PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Agents for Leishmaniasis and/or Trypanosomiasis
    Respiratory Antifungals

    DEA CLASS

    Rx

    DESCRIPTION

    Oral inhalation/IM/IV antifungal agent
    Used for Pneumocystis jiroveci (Pneumocystis carinii) pneumonia treatment and prophylaxis 
    Parenteral administration is associated with several major ADRs

    COMMON BRAND NAMES

    NebuPent, Pentam

    HOW SUPPLIED

    NebuPent/Pentamidine/Pentamidine Isethionate Respiratory (Inhalation) Pwd F/Recon: 300mg
    Pentam/Pentamidine/Pentamidine Isethionate Intramuscular Inj Pwd F/Sol: 300mg
    Pentam/Pentamidine/Pentamidine Isethionate Intravenous Inj Pwd F/Sol: 300mg

    DOSAGE & INDICATIONS

    For the treatment of Pneumocystis pneumonia (PCP).
    For the treatment of PCP in HIV-infected patients.
    Intravenous or Intramuscular dosage
    Adults

    4 mg/kg/dose IV or IM once daily for 21 days as alternative therapy for moderate to severe infection then chronic suppressive therapy. May reduce dose to 3 mg/kg in the event of toxicities.

    Adolescents

    4 mg/kg/dose IV or IM once daily for 21 days as alternative therapy for moderate to severe infection then chronic suppressive therapy. May reduce dose to 3 mg/kg in the event of toxicities.

    Infants and Children 4 months to 12 years

    4 mg/kg/dose IV or IM once daily for 21 days as alternative therapy if intolerant to sulfamethoxazole; trimethoprim or clinical failure then chronic suppressive therapy.

    For the treatment of PCP in solid organ transplant recipients.
    Intravenous or Intramuscular dosage
    Adults

    4 mg/kg/dose IV or IM once daily for 14 to 21 days as alternative therapy. May reduce dose 2 to 3 mg/kg in the event of toxicities.

    Infants, Children, and Adolescents 4 months to 17 years

    4 mg/kg/dose IV or IM once daily for 14 to 21 days as alternative therapy. May reduce dose 2 to 3 mg/kg in the event of toxicities.

    For the treatment of PCP in patients with hematological malignancies, cancer, or autoimmune/inflammatory disease.
    Intravenous or Intramuscular dosage
    Adults

    4 mg/kg/dose IV or IM once daily for 14 to 21 days as alternative therapy.

    Infants, Children, and Adolescents 4 months to 17 years

    4 mg/kg/dose IV or IM once daily for 14 to 21 days as alternative therapy.

    For pneumocystis pneumonia (PCP) prophylaxis.
    For primary PCP prophylaxis in HIV-infected patients.
    Nebulized dosage
    Adults

    300 mg nebulized every 4 weeks as alternative therapy. Recommended for patients with CD4 count less than 200 cells/mm3, CD4 less than 14%, or CD4 count of 200 to 250 cells/mm3 if antiretroviral therapy (ART) initiation must be delayed and if CD4 count monitoring every 3 months is not possible. May discontinue if the CD4 count is 200 cells/mm3 or more for more than 3 months in response to ART or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit.

    Adolescents 17 years

    300 mg nebulized every 4 weeks as alternative therapy. Recommended for patients with CD4 count less than 200 cells/mm3, CD4 less than 14%, or CD4 count of 200 to 250 cells/mm3 if antiretroviral therapy (ART) initiation must be delayed and if CD4 count monitoring every 3 months is not possible. May discontinue if the CD4 count is 200 cells/mm3 or more for more than 3 months in response to ART or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit.

    Adolescents 13 to 16 years†

    300 mg nebulized every 4 weeks as alternative therapy. Recommended for patients with CD4 count less than 200 cells/mm3, CD4 less than 14%, or CD4 count of 200 to 250 cells/mm3 if antiretroviral therapy (ART) initiation must be delayed and if CD4 count monitoring every 3 months is not possible. May discontinue if the CD4 count is 200 cells/mm3 or more for more than 3 months in response to ART or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit.

    Children 6 to 12 years†

    300 mg nebulized every 4 weeks as alternative therapy. Recommended for patients with CD4 count less than 200 cells/mm3 or CD4 less than 15%. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 200 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 200 cells/mm3 or CD4 is less than 15%.

    Children 5 years†

    300 mg nebulized every 4 weeks as alternative therapy. Recommended for patients with CD4 count less than 500 cells/mm3 or CD4 less than 15%. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 500 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 500 cells/mm3 or CD4 is less than 15%.

    For secondary PCP prophylaxis (i.e., long-term suppressive therapy) in HIV-infected patients.
    Nebulized dosage
    Adults

    300 mg nebulized every 4 weeks as alternative therapy. May discontinue if the CD4 count is more than 200 cells/mm3 for more than 3 months in response to antiretroviral therapy (ART) or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit. If PCP is diagnosed or recurs at a CD4 count of more than 200 cells/mm3, lifelong prophylaxis is necessary.

    Adolescents 17 years

    300 mg nebulized every 4 weeks as alternative therapy. May discontinue if the CD4 count is more than 200 cells/mm3 for more than 3 months in response to antiretroviral therapy (ART) or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit. If PCP is diagnosed or recurs at a CD4 count of more than 200 cells/mm3, lifelong prophylaxis is necessary.

    Adolescents 13 to 16 years†

    300 mg nebulized every 4 weeks as alternative therapy. May discontinue if the CD4 count is more than 200 cells/mm3 for more than 3 months in response to antiretroviral therapy (ART) or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit. If PCP is diagnosed or recurs at a CD4 count of more than 200 cells/mm3, lifelong prophylaxis is necessary.

    Children 6 to 12 years†

    300 mg nebulized every 4 weeks as alternative therapy. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 200 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 200 cells/mm3 or CD4 is less than 15%.

    Children 5 years†

    300 mg nebulized every 4 weeks as alternative therapy. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 500 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 500 cells/mm3 or CD4 is less than 15%.

    For primary PCP prophylaxis in hematopoietic stem cell transplant (HSCT) recipients†.
    Nebulized dosage
    Adults

    300 mg nebulized every 3 to 4 weeks starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT as alternative therapy. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.

    Adolescents

    300 mg nebulized every 3 to 4 weeks starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT as alternative therapy. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.

    Children 6 to 12 years

    300 mg nebulized every 4 weeks starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT as alternative therapy. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.

    Children 1 to 5 years

    9 mg/kg/dose nebulized every 4 weeks starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT as alternative therapy. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.

    Intravenous dosage
    Infants and Children 4 months to 12 years

    4 mg/kg/dose IV every 2 to 4 weeks starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT as alternative therapy. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.

    For PCP prophylaxis in solid organ transplant recipients†.
    Nebulized dosage
    Adults

    300 mg nebulized every 3 to 4 weeks for 3 to 6 months after kidney transplant, for at least 6 to 12 months after other transplants, as well as for at least 6 weeks during and after antirejection therapy in kidney transplant recipients, as alternative therapy. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.

    Children and Adolescents

    300 mg nebulized every 3 to 4 weeks for 3 to 6 months after kidney transplant, for at least 6 to 12 months after other transplants, as well as for at least 6 weeks during and after antirejection therapy in kidney transplant recipients, as alternative therapy. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.

    For primary PCP prophylaxis in patients with cancer-related immunosuppression and hematological malignancies†.
    Nebulized dosage
    Adults

    300 mg nebulized every 4 weeks as alternative therapy. Recommended for patients receiving alemtuzumab, fludarabine/cyclophosphamide/rituximab, corticosteroids at doses equivalent to more than 20 mg/day of prednisone for 4 weeks, nucleoside or purine analogs, radiotherapy for brain tumors/metastasis plus high-dose steroids as well as for patients with acute lymphoblastic leukemia (ALL) and lymphoma treated with R-CHOP14 or escalated BEACOPP. Duration of prophylaxis for ALL is from induction to the end of maintenance. Prophylaxis for alemtuzumab-associated treatment and fludarabine/cyclophosphamide/rituximab treatment is suggested for at least 6 months after treatment completion.

    Children and Adolescents 6 to 17 years

    300 mg nebulized every 4 weeks as alternative therapy. Recommended for patients receiving alemtuzumab or corticosteroids at doses equivalent to more than 0.4 mg/kg/day or 16 mg/day of prednisone for 1 month or more as well as patients with acute lymphoblastic leukemia (ALL), severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome (WAS), X-linked agammaglobulinemia, human leukocyte antigen (HLA) II combined immunodeficiency, acute myeloid leukemia (AML), and solid tumors. Duration of prophylaxis for ALL is from induction to the end of maintenance. Patients receiving corticosteroids or with SCID, WAS, X-linked agammaglobulinemia, or HLA II combined immunodeficiency require lifelong prophylaxis or until restoration of the underlying defect. Prophylaxis is recommended for patients with AML and solid tumors for the duration of chemotherapy.  

    Intravenous dosage
    Infants, Children, and Adolescents 4 months to 17 years

    4 mg/kg/dose IV every 4 weeks as alternative therapy. Recommended for patients receiving alemtuzumab or corticosteroids at doses equivalent to more than 0.4 mg/kg/day or 16 mg/day of prednisone for 1 month or more as well as patients with acute lymphoblastic leukemia (ALL), severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome (WAS), X-linked agammaglobulinemia, human leukocyte antigen (HLA) II combined immunodeficiency, acute myeloid leukemia (AML), and solid tumors. Duration of prophylaxis for ALL is from induction to the end of maintenance. Patients receiving corticosteroids or with SCID, WAS, X-linked agammaglobulinemia, or HLA II combined immunodeficiency require lifelong prophylaxis or until restoration of the underlying defect. Prophylaxis is recommended for patients with AML and solid tumors for the duration of chemotherapy.

    For the treatment of leishmaniasis†.
    For the treatment of cutaneous leischmaniasis†.
    Intravenous or Intramuscular dosage
    Adults

    3 to 4 mg/kg/dose IV or IM every other day for 3 or 4 doses. Alternatively for L. (V.) panamensis/guyanensis, 2 mg/kg/dose IV or IM every other day for 7 doses.[63762]

    Infants 4 months and older, Children, and Adolescents

    3 to 4 mg/kg/dose IV or IM every other day for 3 or 4 doses. Alternatively for L. (V.) panamensis/guyanensis, 2 mg/kg/dose IV or IM every other day for 7 doses.[63762]

    For the treatment of mucosal leishmaniasis†.
    Intravenous or Intramuscular dosage
    Adults

    2 to 4 mg/kg/dose IV or IM every other day or 3 times weekly for 15 or more doses as a lesser alternative.

    Infants 4 months and older, Children, and Adolescents

    2 to 4 mg/kg/dose IV or IM every other day or 3 times weekly for 15 or more doses as a lesser alternative.

    For the treatment of visceral leishmaniasis†.
    Intravenous or Intramuscular dosage
    Adults

    4 mg/kg/dose IV or IM every other day or 3 times weekly for 15 to 30 doses as second-line therapy due to toxicity and lower efficacy.[63762]

    Infants 4 months and older, Children, and Adolescents

    4 mg/kg/dose IV or IM every other day or 3 times weekly for 15 to 30 doses as second-line therapy due to toxicity and lower efficacy.[63762]

    For the treatment of African trypanosomiasis (sleeping sickness)† due to Trypanosoma brucei gambiense without CNS involvement (first stage or hemolymphatic stage).
    Intramuscular or Intravenous dosage
    Adults

    4 mg/kg/dose IM or IV once daily for 7 to 10 days.

    Infants 4 months and older, Children, and Adolescents

    4 mg/kg/dose IM or IV once daily for 7 to 10 days.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    4 mg/kg IM or IV daily; 300 mg nebulized once every 4 weeks.

    Geriatric

    4 mg/kg IM or IV daily; 300 mg nebulized once every 4 weeks.

    Adolescents

    >= 17 years: 4 mg/kg IM or IV daily; 300 mg nebulized once every 4 weeks.
    < 17 years: 4 mg/kg IM or IV daily; safety and efficacy of nebulized solution not established, but 300 mg nebulized  once every 4 weeks has been recommended.

    Children

    >= 5 years: 4 mg/kg IM or IV daily; safety and efficacy of nebulized solution not established, but 300 mg nebulized  once every 4 weeks has been recommended..
    < 5 years: 4 mg/kg IM or IV daily; safety and efficacy of nebulized solution not established.

    Infants

    > 4 months: 4 mg/kg IM or IV daily; safety and efficacy of nebulized solution not established. 
    <= 4 months: Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    No dosage adjustment is recommended. However, pentamidine should be used with caution in patients with renal dysfunction due to its nephrotoxic potential.

    ADMINISTRATION

    Injectable Administration

    Administer by intravenous infusion or deep intramuscular injection, however; intramuscular injection is painful and has been associated with sterile abscess formation at the injection site.
    The FDA-labeled administration instructions caution against the use of sodium chloride for the initial vial reconstitution due to the potential for precipitation.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Infusion:
    Rapid IV administration can cause hypotension.
    Reconstitute 300 mg vial for parenteral use with 3—5 ml of sterile water for injection or D5W to give IV solutions of concentrations 100—60 mg/ml. Withdraw the appropriate dose and dilute in 50—250 ml of D5W.
    In a stability study, pentamidine was prepared as a 1 or 2 mg/ml admixture using 100 ml of normal saline and was stored at room temperature in PVC bags. At 48 hours, there was no visual precipitation and the admixture retained > 90% of the initial concentration. Once the admixture was infused through PVC administration sets, there was a 10% loss of initial concentration which may be due to adsorption to the set.
    A two week drug binding study in elastomeric infusion devices included pentamidine diluted in both D5W and normal saline. Admixtures were stored at 35 degrees C with constant gentle agitation. At the end of the two week period, there was minimal drug loss indicating no binding to the elastomeric reservoir.
    With patient in the supine position, infuse slowly IV over 60—120 minutes. Monitor blood pressure following the dose until stable.

    Intramuscular Administration

    Reconstitute 300 mg vial for parenteral use with 3 ml of sterile water for injection to give an IV solution of concentration 100 mg/ml.
    Withdraw the desired dose and inject deeply into a large muscle mass. Aspirate prior to injection to avoid injection into a blood vessel. Discard unused portion of reconstituted solution.

    Inhalation Administration

    Administer the solution via nebulization using the Respirgard II jet nebulizer.
    Nebulizer flow rate should be 5—7 L/minute from 40—50 PSO oxygen or air source. Treatments last 30—45 minutes.
    Solution for inhalation:
    Use sterile water for injection only. Sodium chloride injection can cause precipitation.
    Reconstitute 300 mg for inhalation with 6 ml of sterile water for injection.

    STORAGE

    NebuPent:
    - Product should not be stored at room temperature for more than 48 hours
    - Protect from light
    - Store unreconstituted product at 68 to 77 degrees F
    Pentam:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store reconstituted product in accordance with package insert instructions

    CONTRAINDICATIONS / PRECAUTIONS

    Hypotension

    Intramuscular or rapid intravenous administration of pentamidine is associated with hypotension, which can occur following the initial dose. Patients should be in a supine position. Blood pressure should be monitored frequently until it stabilizes. Pentamidine for inhalation can also cause hypotension. Prolonged therapy with pentamidine has been associated with dysrhythmias (see Adverse Reactions). Equipment for airway maintenance and other supportive measures should be readily available.

    Apheresis, AV block, bradycardia, cardiac arrhythmias, cardiac disease, cardiomyopathy, celiac disease, females, fever, geriatric, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)

    Systemically administered pentamidine can cause cardiac arrhythmias, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), as well as other cardiac side effects. Systemically adminstered pentamidine is considered to be associated with a well-established risk for QT prolongation and TdP. Extremely limited evidence in case reports suggest inhaled pentamidine may be associated with possible TdP; however, systemic absorption of inhaled pentamidine is limited. Patients who have cardiac disease or arrhythmias should be monitored closely, and ECGs should be administered during and after parenteral pentamidine therapy. Use systemically administered pentamidine with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

    Diabetes mellitus, hyperglycemia, hypoglycemia, pancreatitis

    Pentamidine is toxic to pancreatic cells. Patients receiving intravenous pentamidine can become acutely hypoglycemic immediately following the infusion. Patients with diabetes mellitus, patients with preexisting pancreatitis, or those with hypoglycemia or hyperglycemia should receive pentamidine with caution. Patients should be monitored for hypoglycemia for 4 to 6 hours following administration of pentamidine via any route.

    Anemia, bone marrow suppression, radiation therapy

    Patients with a history of bleeding disorders, anemia, or bone marrow suppression should receive intravenous pentamidine with caution, since it can cause thrombocytopenia, leukopenia, and/or anemia. Risk-benefit should be considered in patients who have had previous radiation therapy or cytotoxic therapy.

    Intramuscular injections

    Although pentamidine can be administered via intramuscular injection, caution should be used when administering intramuscular injections to patients receiving pentamidine. IM injections may cause bleeding, bruising, or hematomas due to thrombocytopenia secondary to pentamidine-induced bone marrow suppression.

    Dental disease, dental work

    Pentamidine should be used with caution in patients with dental disease. Pentamidine can cause myelosuppression and there may be an increased risk of infection. Dental work should be performed prior to initiating pentamidine therapy or deferred until blood counts return to normal. Patients should be instructed on proper oral hygiene.

    Dehydration, renal disease

    Parenteral pentamidine can cause azotemia or acute renal insufficiency (see Adverse Reactions). It should be used with caution in patients with preexisting renal disease. Nephrotoxicity can be worsened by dehydration, so patients should be well hydrated before therapy.

    Hepatic disease

    Pentamidine can cause elevations in AST, ALT, bilirubin, and/or alkaline phosphatase. Patients with preexisting hepatic disease may be especially vulnerable to the effects of this medication.

    Asthma

    Asthmatic patients can experience bronchospasm when taking aerosolized pentamidine. Caution should be used in patients with asthma. Pretreatment with a bronchodilator may reduce the risk of bronchospasm.

    Children, infants, neonates

    The safety and efficacy of pentamidine solution for injection has not been established for neonates and infants 4 months or younger. The solution for injection is approved for use in pediatric patients older than 4 months of age. The safety and the efficacy of pentamidine nebulized solution has not been established in neonates, infants, children, and adolescents 16 years of age or younger.

    Pregnancy

    There are no adequate and well-controlled studies of pentamidine in human pregnancy, and its ability to cause fetal harm or affect reproductive capacity is unknown. A literature report indicated that intravenously administered pentamidine in pregnant rats at 4 mg/kg/day was embryolethal; teratogenicity was not observed in this study. It is unknown whether pentamidine administered via the aerosolized route crosses the placenta at clinically significant concentrations. Pentamidine isethionate should not be given to a pregnant woman unless the potential benefits are judged to outweigh the unknown risks.
     

    Breast-feeding

    Data are limited regarding use of pentamidine during breast-feeding and its' excretion into human breast milk is unknown. According to the manufacturer, because of the potential for serious adverse events in a nursing infant, a decision should be made to either discontinue breast-feeding or discontinue use of the drug. Additionally, pentamidine may be used to treat infections in patients with HIV and the Centers for Disease Control and Prevention (CDC) recommends that in the US, HIV-infected mothers not breast-feed their infants to avoid the risk of postnatal transmission of HIV. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    ADVERSE REACTIONS

    Severe

    bronchospasm / Rapid / 0-15.0
    azotemia / Delayed / 8.5-8.5
    renal failure (unspecified) / Delayed / 0-1.0
    SIADH / Delayed / 0-1.0
    hyperkalemia / Delayed / 0-1.0
    ventricular tachycardia / Early / 0-1.0
    vasculitis / Delayed / 0-1.0
    torsade de pointes / Rapid / 0-1.0
    stroke / Early / 0-1.0
    tissue necrosis / Early / 0-1.0
    anaphylactoid reactions / Rapid / 0-1.0
    Stevens-Johnson syndrome / Delayed / 0-1.0
    pancreatitis / Delayed / 0-1.0
    diabetic ketoacidosis / Delayed / 0-1.0
    pancytopenia / Delayed / 0-1.0
    peptic ulcer / Delayed / 0-1.0
    seizures / Delayed / 0-1.0
    cyanosis / Early / 0-1.0
    laryngospasm / Rapid / 0-1.0
    eosinophilic pneumonia / Delayed / 0-1.0
    pneumothorax / Early / 0-1.0
    angioedema / Rapid / 0-1.0
    hearing loss / Delayed / 0-1.0

    Moderate

    dyspnea / Early / 0-48.3
    wheezing / Rapid / 1.0-32.4
    leukopenia / Delayed / 10.4-10.4
    elevated hepatic enzymes / Delayed / 8.7-8.7
    hypoglycemia / Early / 0-5.9
    hypotension / Rapid / 0-5.0
    anemia / Delayed / 1.0-5.0
    chest pain (unspecified) / Early / 1.0-5.0
    candidiasis / Delayed / 0-5.0
    thrombocytopenia / Delayed / 0-2.6
    confusion / Early / 1.7-1.7
    hallucinations / Early / 0-1.7
    hematuria / Delayed / 0-1.0
    urinary incontinence / Early / 0-1.0
    flank pain / Delayed / 0-1.0
    hypomagnesemia / Delayed / 0-1.0
    hypocalcemia / Delayed / 0-1.0
    peripheral vasodilation / Rapid / 0-1.0
    palpitations / Early / 0-1.0
    sinus tachycardia / Rapid / 0-1.0
    phlebitis / Rapid / 0-1.0
    skin ulcer / Delayed / 0-1.0
    erythema / Early / 0-1.0
    diabetes mellitus / Delayed / 0-1.0
    hyperglycemia / Delayed / 0-1.0
    eosinophilia / Delayed / 0-1.0
    neutropenia / Delayed / 0-1.0
    prolonged bleeding time / Delayed / 0-1.0
    splenomegaly / Delayed / 0-1.0
    gastritis / Delayed / 0-1.0
    constipation / Delayed / 0-1.0
    esophagitis / Delayed / 0-1.0
    colitis / Delayed / 0-1.0
    oral ulceration / Delayed / 0-1.0
    melena / Delayed / 0-1.0
    memory impairment / Delayed / 0-1.0
    depression / Delayed / 0-1.0
    peripheral neuropathy / Delayed / 0-1.0
    pneumonitis / Delayed / 0-1.0
    hemoptysis / Delayed / 0-1.0
    tachypnea / Early / 0-1.0
    hepatomegaly / Delayed / 0-1.0
    hepatitis / Delayed / 0-1.0
    peripheral edema / Delayed / 0-1.0
    meningitis / Delayed / 0-1.0
    gout / Delayed / 0-1.0
    blepharitis / Early / 0-1.0
    conjunctivitis / Delayed / 0-1.0
    blurred vision / Early / 0-1.0
    hyperchloremic acidosis / Delayed / Incidence not known
    hypertension / Early / Incidence not known
    sialadenitis / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known

    Mild

    fatigue / Early / 65.7-65.7
    cough / Delayed / 38.0-62.7
    fever / Early / 0-51.0
    dizziness / Early / 0-45.1
    injection site reaction / Rapid / 0-11.1
    anorexia / Delayed / 5.9-5.9
    nausea / Early / 1.0-5.9
    diarrhea / Early / 0-5.0
    headache / Early / 0-5.0
    night sweats / Early / 0-5.0
    infection / Delayed / 0-5.0
    influenza / Delayed / 1.0-5.0
    pharyngitis / Delayed / 0-5.0
    sinusitis / Delayed / 1.0-5.0
    rash / Early / 3.3-3.3
    dysgeusia / Early / 1.7-1.7
    syncope / Early / 0-1.0
    xerosis / Delayed / 0-1.0
    pruritus / Rapid / 0-1.0
    urticaria / Rapid / 0-1.0
    hypersalivation / Early / 0-1.0
    gingivitis / Delayed / 0-1.0
    xerostomia / Early / 0-1.0
    abdominal pain / Early / 0-1.0
    dyspepsia / Early / 0-1.0
    vomiting / Early / 0-1.0
    hypoesthesia / Delayed / 0-1.0
    drowsiness / Early / 0-1.0
    tremor / Early / 0-1.0
    vertigo / Early / 0-1.0
    emotional lability / Early / 0-1.0
    paranoia / Early / 0-1.0
    insomnia / Early / 0-1.0
    paresthesias / Delayed / 0-1.0
    anxiety / Delayed / 0-1.0
    hyperventilation / Early / 0-1.0
    nasal congestion / Early / 0-1.0
    rhinitis / Early / 0-1.0
    laryngitis / Delayed / 0-1.0
    chills / Rapid / 0-1.0
    lethargy / Early / 0-1.0
    arthralgia / Delayed / 0-1.0
    myalgia / Early / 0-1.0
    ocular pain / Early / 0-1.0

    DRUG INTERACTIONS

    Abarelix: (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include abarelix. The effect of abarelix on the QT interval may be due to androgen deprivation or other variables. Patients with a baseline QTc value > 450 msec may not be appropriate candidates for abarelix receipt. Prescribers need to weigh the potential benefits and risks of abarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval.
    Acetohexamide: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Alfuzosin: (Major) Pentamidine has been associated with QT prolongation and torsade de pointes. Drugs with a possible risk for QT prolongation include alfuzosin. Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval; use caution in co-administration.
    Alogliptin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Alogliptin; Metformin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine. (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Alogliptin; Pioglitazone: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Alpha-glucosidase Inhibitors: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Monitor for needed adjustments in diabetes treatments.
    Amikacin: (Major) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, such as systemic aminoglycosides. Renal function and aminoglycoside concentratons should be closely monitored.
    Aminoglycosides: (Major) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, such as systemic aminoglycosides. Renal function and aminoglycoside concentratons should be closely monitored.
    Amiodarone: (Major) The concomitant use of amiodarone and pentamidine should only be done after careful assessment of risks versus benefits. If possible, avoid coadministration. Pentamidine has been associated with QT prolongation. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with pentamidine. Amisulpride causes dose- and concentration- dependent QT prolongation. Systemic pentamidine has been associated with QT prolongation.
    Amlodipine; Celecoxib: (Major) Avoid concurrent or sequential use of pentamidine with celecoxib. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable. Celecoxib may enhance the exposure and toxicity of pentamidine. Celecoxib is a CYP2D6 inhibitor, and pentamidine is a CYP2D6 substrate.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with clarithromycin include intravenous pentamidine.
    Amphotericin B cholesteryl sulfate complex (ABCD): (Moderate) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with pentamidine. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B lipid complex (ABLC): (Moderate) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with pentamidine. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B liposomal (LAmB): (Moderate) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with pentamidine. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B: (Moderate) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with pentamidine. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include pentamidine.
    Apomorphine: (Major) Use apomorphine and pentamidine together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Systemic pentamidine has been associated with QT prolongation.
    Aripiprazole: (Major) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Systemic pentamidine has been associated with QT prolongation. Aripiprazole should be used cautiously and with close monitoring with pentamidine.
    Arsenic Trioxide: (Major) If possible, drugs that are known to prolong the QT interval, like pentamidine, should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Pentamidine-induced hypokalemia or hypomagnesemia can also potentiate the cardiac toxicity of arsenic trioxide.
    Artemether; Lumefantrine: (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include artemether; lumefantrine. Consider ECG monitoring if pentamidine must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine.is an inhibitor and pentamidine is a substrate of the CYP2D6 isoenzyme; therefore, coadministration may lead to increased pentamidine concentrations and drug toxicity.
    Asenapine: (Major) Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents with a possible risk for QT prolongation whenever possible. Pentamidine has been associated with QT prolongation and should be used cautiously with other agents that may have this effect.
    Atazanavir; Cobicistat: (Moderate) The plasma concentrations of pentamidine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as nephrotoxicity or electrolyte disorders, is recommended during coadministration. Cobicistat is a CYP2D6 inhibitor, while pentamidine is a CYP2D6 substrate.
    Atomoxetine: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with atomoxetine include pentamidine.
    Azithromycin: (Major) Avoid coadministration of azithromycin with pentamidine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Systemic pentamidine has been associated with QT prolongation.
    Bacitracin: (Moderate) Additive nephrotoxicity may occur. Both bacitracin and pentamidine may cause a decline in renal function. Bacitracin renal toxicity may occur when the drug is systemically administered or given via topical administration over large surface areas or in prolonged topical use (e.g., severe burns). When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as intravenous pentamidine. Monitor renal function closely.
    Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with pentamidine. Both drugs have been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
    Bepridil: (Contraindicated) According to the manufacturer, bepridil is contraindicated for use with drugs that prolong the QT interval, such as pentamidine. Bepridil inhibits the cardiac conduction system and has Class I antiarrhythmic properties; the drug is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and systemic pentamidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and systemic pentamidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Bleomycin: (Moderate) Previous or concurrent treatment with nephrotoxic agents, like pentamidine, may result in decreased bleomycin clearance if renal function has been impaired. Monitor for signs/symptoms of bleomycin toxicity (e.g., pulmonary toxicity) in patients with concomittant or prior history of systemic pentamidine therapy.
    Bumetanide: (Moderate) Drugs that are associated with hypokalemia and/or hypomagnesemia such as loop diuretics should be used with caution in patients also receiving pentamidine. Since pentamidine may cause QT prolongation independently of electrolyte imbalances, the risk for cardiac arrhythmias is potentiated by the concomitant use of agents associated with electrolyte loss. .
    Bupivacaine; Meloxicam: (Major) Avoid concurrent or sequential use of pentamidine with meloxicam. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Buprenorphine: (Major) Buprenorphine should be used cautiously and with close monitoring with pentamidine. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval, such as pentamidine. If these drugs are used together, consider the potential for additive effects on the QT interval.
    Buprenorphine; Naloxone: (Major) Buprenorphine should be used cautiously and with close monitoring with pentamidine. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval, such as pentamidine. If these drugs are used together, consider the potential for additive effects on the QT interval.
    Cabotegravir; Rilpivirine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with pentamidine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Pentamidine has also been associated with QT prolongation.
    Canagliflozin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Canagliflozin; Metformin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Celecoxib: (Major) Avoid concurrent or sequential use of pentamidine with celecoxib. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable. Celecoxib may enhance the exposure and toxicity of pentamidine. Celecoxib is a CYP2D6 inhibitor, and pentamidine is a CYP2D6 substrate.
    Celecoxib; Tramadol: (Major) Avoid concurrent or sequential use of pentamidine with celecoxib. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable. Celecoxib may enhance the exposure and toxicity of pentamidine. Celecoxib is a CYP2D6 inhibitor, and pentamidine is a CYP2D6 substrate.
    Ceritinib: (Major) Avoid coadministration of ceritinib with systemic pentamidine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Systemic pentamidine has been associated with QT prolongation.
    Chloroquine: (Major) Avoid coadministration of chloroquine with pentamidine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Systemic pentamidine has also been associated with QT prolongation.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Avoid concurrent or sequential use of pentamidine with ibuprofen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Chlorpromazine: (Major) Phenothiazines may cause QT prolongation. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and torsade de pointes (TdP); case reports have included patients receiving therapeutic doses of chlorpromazine. Drugs with a possible risk for QT prolongation and TdP that should be used with caution with chlorpromazine include pentamidine. Pentamidine has been associated with QT prolongation.
    Chlorpropamide: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Cidofovir: (Contraindicated) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, including cidofovir. The combination use of IV pentamidine and cidofovir is contraindicated. Pentamidine should be discontinued at least 7 days prior to beginning cidofovir.
    Ciprofloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering pentamidine with ciprofloxacin. Pentamidine has been associated with QT prolongation, and ciprofloxacin is associated with a possible risk for QT prolongation and TdP.
    Cisapride: (Contraindicated) Pentamidine has been associated with QT prolongation. Because of the potential for torsades de pointes (TdP), use of cisapride with pentamidine is contraindicated.
    Cisplatin: (Major) Avoid the concomitant or sequential use of intravenous pentamidine with cisplatin if possible due to the risk of additive nephrotoxicity. Cisplatin can cause nephrotoxicity. Nephrotoxic events (increased creatinine, impaired renal function, azotemia, and renal failure) are common with the parenteral administration of pentamidine.
    Citalopram: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with citalopram include intravenous pentamidine, which has been associated with QT prolongation.
    Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with clarithromycin include intravenous pentamidine.
    Clindamycin: (Moderate) Concomitant use of pentamidine and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
    Clofarabine: (Major) Avoid the concomitant use of clofarabine and pentamidine if possible; coadministration may result in additive nephrotoxicity. Monitor patients closely for signs of renal toxicity if concomitant use is required.
    Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with pentamidine. QT prolongation and torsade de pointes have been reported in patients receiving clofazimine in combination with QT prolonging medications. Systemic pentamidine has been associated with QT prolongation.
    Clozapine: (Major) Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with clozapine include pentamidine.
    Cobicistat: (Moderate) The plasma concentrations of pentamidine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as nephrotoxicity or electrolyte disorders, is recommended during coadministration. Cobicistat is a CYP2D6 inhibitor, while pentamidine is a CYP2D6 substrate.
    Codeine; Phenylephrine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include pentamidine.
    Codeine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include pentamidine.
    Crizotinib: (Major) Avoid coadministration of crizotinib with systemic pentamidine due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Systemic pentamidine has also been associated with QT prolongation.
    Cyclosporine: (Moderate) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, including cyclosporine.
    Dapagliflozin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Dapagliflozin; Metformin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Dapagliflozin; Saxagliptin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine. (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Darunavir: (Moderate) The plasma concentrations of pentamidine may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as nephrotoxicity or electrolyte disorders, is recommended during coadministration. Darunavir is a CYP2D6 inhibitor, while pentamidine is a CYP2D6 substrate.
    Darunavir; Cobicistat: (Moderate) The plasma concentrations of pentamidine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as nephrotoxicity or electrolyte disorders, is recommended during coadministration. Cobicistat is a CYP2D6 inhibitor, while pentamidine is a CYP2D6 substrate. (Moderate) The plasma concentrations of pentamidine may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as nephrotoxicity or electrolyte disorders, is recommended during coadministration. Darunavir is a CYP2D6 inhibitor, while pentamidine is a CYP2D6 substrate.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) The plasma concentrations of pentamidine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as nephrotoxicity or electrolyte disorders, is recommended during coadministration. Cobicistat is a CYP2D6 inhibitor, while pentamidine is a CYP2D6 substrate. (Moderate) The plasma concentrations of pentamidine may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as nephrotoxicity or electrolyte disorders, is recommended during coadministration. Darunavir is a CYP2D6 inhibitor, while pentamidine is a CYP2D6 substrate.
    Dasatinib: (Major) Pentamidine has been associated with serious cardiac arrhythmias including QT prolongation, and is considered to have an established risk of torsade de pointes. The drug should be used cautiously in patients receiving agents which may cause QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval).
    Degarelix: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Systemic pentamidine has been associated with QT prolongation. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
    Deutetrabenazine: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and pentamidine. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Systemic pentamidine has been associated with QT prolongation.
    Dextromethorphan; Quinidine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include systemic pentamidine.
    Diclofenac: (Major) Avoid concurrent or sequential use of pentamidine with diclofenac. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Diclofenac; Misoprostol: (Major) Avoid concurrent or sequential use of pentamidine with diclofenac. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Diflunisal: (Major) Avoid concurrent or sequential use of pentamidine with diflunisal. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Diphenhydramine; Ibuprofen: (Major) Avoid concurrent or sequential use of pentamidine with ibuprofen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Diphenhydramine; Naproxen: (Major) Avoid concurrent or sequential use of pentamidine with naproxen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Disopyramide: (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include disopyramide. Additive effects on the QT interval are possible.
    Dofetilide: (Major) Coadministration of dofetilide and pentamidine is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of Systemic pentamidine has been associated with QT prolongation.
    Dolasetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dolasetron and pentamidine should be used together cautiously. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Systemic pentamidine has also been associated with QT prolongation. Concurrent use may increase the risk of QT prolongation.
    Dolutegravir; Rilpivirine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with pentamidine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Pentamidine has also been associated with QT prolongation.
    Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include pentamidine.
    Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include pentamidine.
    Dronedarone: (Contraindicated) Concomitant use of dronedarone and pentamidine is contraindicated. Pentamidine has been associated with QT prolongation. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include pentamidine.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) L-methylfolate and pentamidine should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with pentamidine. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Efavirenz: (Major) Although data are limited, coadministration of efavirenz and pentamidine may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of both drugs
    Efavirenz; Emtricitabine; Tenofovir: (Major) Although data are limited, coadministration of efavirenz and pentamidine may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of both drugs
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Although data are limited, coadministration of efavirenz and pentamidine may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of both drugs
    Eliglustat: (Major) Coadministration of systemic pentamidine and eliglustat may result in increased concentrations of pentamidine and, theoretically, an increased risk of QT prolongation. If coadministration is necessary, use caution and monitor closely. Systemic pentamidine has been associated with QT prolongation. In addition, data from healthy volunteers has shown that pentamidine metabolism is mediated in part by CYP2D6. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of pentamidine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as nephrotoxicity or electrolyte disorders, is recommended during coadministration. Cobicistat is a CYP2D6 inhibitor, while pentamidine is a CYP2D6 substrate.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of pentamidine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as nephrotoxicity or electrolyte disorders, is recommended during coadministration. Cobicistat is a CYP2D6 inhibitor, while pentamidine is a CYP2D6 substrate.
    Empagliflozin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Empagliflozin; Linagliptin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Monitor for needed adjustments in diabetes treatments. (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Empagliflozin; Linagliptin; Metformin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Monitor for needed adjustments in diabetes treatments. (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Empagliflozin; Metformin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with pentamidine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Pentamidine has also been associated with QT prolongation.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with pentamidine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Pentamidine has also been associated with QT prolongation.
    Encorafenib: (Major) Avoid coadministration of encorafenib and pentamidine due to the potential for additive QT prolongation. If unavoidable, monitor ECGs and electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Systemic pentamidine has been associated with QT prolongation.
    Enflurane: (Major) Pentamidine has been associated with serious cardiac arrhythmias including QT prolongation, and is considered to have an established risk of torsades de pointes. The drug should be used cautiously, if at all, in patients receiving agents which may cause QT prolongation or torsade de pointes including halogenated anesthetics such as enflurane.
    Entrectinib: (Major) Avoid coadministration of entrectinib with pentamidine due to the risk of QT prolongation. Both entrectinib and systemic pentamidine have been associated with QT prolongation.
    Eribulin: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with eribulin include pentamidine.
    Ertugliflozin; Metformin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Ertugliflozin; Sitagliptin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Erythromycin: (Major) Pentamidine has been associated with serious cardiac arrhythmias including QT prolongation. The drug should be used cautiously, if at all, in patients receiving agents which may cause QT prolongation or torsade de pointes (TdP). Erythromycin administration is associated with QT prolongation and torsade de pointes (TdP).
    Erythromycin; Sulfisoxazole: (Major) Pentamidine has been associated with serious cardiac arrhythmias including QT prolongation. The drug should be used cautiously, if at all, in patients receiving agents which may cause QT prolongation or torsade de pointes (TdP). Erythromycin administration is associated with QT prolongation and torsade de pointes (TdP).
    Escitalopram: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as pentamidine, should be done with caution and close monitoring.
    Ethacrynic Acid: (Moderate) Drugs that are associated with hypokalemia and/or hypomagnesemia such as loop diuretics should be used with caution in patients also receiving pentamidine. Since pentamidine may cause QT prolongation independently of electrolyte imbalances, the risk for cardiac arrhythmias is potentiated by the concomitant use of agents associated with electrolyte loss. .
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) L-methylfolate and pentamidine should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with pentamidine. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Etodolac: (Major) Avoid concurrent or sequential use of pentamidine with etodolac. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Ezogabine: (Major) Ezogabine has been associated with QT prolongation. The manufacturer of ezogabine recommends caution during concurrent use of medications known to increase the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with ezogabine include pentamidine.
    Famotidine; Ibuprofen: (Major) Avoid concurrent or sequential use of pentamidine with ibuprofen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Fenoprofen: (Major) Avoid concurrent or sequential use of pentamidine with fenoprofen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Fingolimod: (Major) Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsades de pointes (TdP). Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with fingolimod include pentamidine.
    Flecainide: (Major) Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for torsade de pointes (TdP) has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Intravenous pentamidine has been associated with QT prolongation and may induce electrolyte abnormalities that may increase the risk of proarrhythmia. Monitoring of the ECG may be advisable with coadministration.
    Fluconazole: (Major) Intravenous pentamidine has been associated with QT prolongation and should be used with caution in combination with fluconazole. Fluconazole has been associated with QT prolongation and rare cases of torsades de pointes (TdP).
    Fluoxetine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include pentamidine.
    Fluphenazine: (Minor) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation should be used cautiously with pentamidine. Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Flurbiprofen: (Major) Avoid concurrent or sequential use of pentamidine with flurbiprofen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Fluvoxamine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and pentamidine. Systemic pentamidine has been associated with QT prolongation. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as pentamidine. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Systemic pentamidine has also been associated with QT prolongation. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment. Also, concomitant use of foscarnet and IV pentamidine can cause significant hypocalcemia, hypomagnesemia, and nephrotoxicity. Both agents are associated with a risk for nephrotoxicity. One fatality has been reported from severe hypocalcemia following this combination. Electrolyte imbalances can precipitate seizures or cardiac dysfunction during therapy with foscarnet.
    Fostemsavir: (Major) Avoid coadministration of systemic pentamidine with fostemsavir due to increased risk of QT prolongation. Systemic pentamidine has been associated with QT prolongation. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
    Furosemide: (Moderate) Drugs that are associated with hypokalemia and/or hypomagnesemia such as loop diuretics should be used with caution in patients also receiving pentamidine. Since pentamidine may cause QT prolongation independently of electrolyte imbalances, the risk for cardiac arrhythmias is potentiated by the concomitant use of agents associated with electrolyte loss. .
    Gallium Ga 68 Dotatate: (Major) Avoid use of mannitol and pentamidine, if possible. Concomitant administration of nephrotoxic drugs, such as pentamidine, increases the risk of renal failure after administration of mannitol.
    Gallium: (Contraindicated) Concurrent use of gallium nitrate with other potentially nephrotoxic drugs, including pentamidine, may increase the risk for developing severe renal insufficiency. If use of pentamidine is indicated, gallium nitrate administration should be discontinued, and hydration for several days after administration of pentamidine is recommended. Serum creatinine concentrations and urine output should be closely monitored during and subsequent to this period. Gallium nitrate should be discontinued if the serum creatinine concentration exceeds 2.5 mg/dl.
    Ganciclovir: (Moderate) Use ganciclovir with pentamidine only if the potential benefits are judged to outweigh the risks. Concurrent use of agents that inhibit rapidly dividing cell populations (i.e., bone marrow, spermatogonia, germinal layers of the skin, gastrointestinal mucosa) with ganciclovir should be done cautiously, in order to avoid additive toxicity. Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, including ganciclovir.
    Gemifloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering pentamidine with gemifloxacin. Pentamidine has been associated with QT prolongation. Gemifloxacin may also prolong the QT interval in some patients, with the maximal change in the QTc interval occurring approximately 5 to 10 hours following oral administration. The likelihood of QTc prolongation may increase with increasing dose of gemifloxacin; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Major) Use gemtuzumab ozogamicin and pentamidine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Systemic pentamidine has also been associated with QT prolongation.
    Gentamicin: (Major) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, such as systemic aminoglycosides. Renal function and aminoglycoside concentratons should be closely monitored.
    Gilteritinib: (Major) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and pentamidine is necessary. Gilteritinib and systemic pentamidine have both been associated with QT prolongation.
    Glasdegib: (Major) Avoid coadministration of glasdegib with pentamidine due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Systemic pentamidine has been associated with QT prolongation.
    Glimepiride: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Glimepiride; Rosiglitazone: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Glipizide: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Glipizide; Metformin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Glyburide: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Glyburide; Metformin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Goserelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving pentamidine. Systemic pentamidine has been associated with QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval.
    Granisetron: (Major) Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences. Pentamidine has been associated with QT prolongation.
    Halofantrine: (Contraindicated) Halofantrine is considered to have a well-established risk for QT prolongation and torsades de pointes and should be avoided in patients receiving drugs which may induce QT prolongation including pentamidine.
    Haloperidol: (Major) QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval, including pentamidine.
    Halothane: (Major) Pentamidine has been associated with serious cardiac arrhythmias including QT prolongation, and is considered to have an established risk of torsades de pointes. The drug should be used cautiously, if at all, in patients receiving agents which may cause QT prolongation or torsade de pointes including halogenated anesthetics such as halothane.
    Histrelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving pentamidine. Systemic pentamidine has been associated with QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval.
    Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like pentamidine. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
    Hydrocodone; Ibuprofen: (Major) Avoid concurrent or sequential use of pentamidine with ibuprofen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Hydroxychloroquine: (Major) Avoid coadministration of pentamidine and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Systemic pentamidine has been associated with QT prolongation.
    Hydroxyzine: (Major) Caution is recommended if hydroxyzine is administered with pentamidine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Systemic pentamidine has been associated with QT prolongation.
    Ibuprofen: (Major) Avoid concurrent or sequential use of pentamidine with ibuprofen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Ibuprofen; Oxycodone: (Major) Avoid concurrent or sequential use of pentamidine with ibuprofen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Ibuprofen; Pseudoephedrine: (Major) Avoid concurrent or sequential use of pentamidine with ibuprofen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Ibutilide: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as pentamidine. Pentamidine has been associated with QT prolongation.
    Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as pentamidine.
    Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like pentamidine. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
    Incretin Mimetics: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Indomethacin: (Major) Avoid concurrent or sequential use of pentamidine with indomethacin. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Inotersen: (Moderate) Use caution with concomitant use of inotersen and pentamidine due to the risk of glomerulonephritis and nephrotoxicity.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with pentamidine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Systemic pentamidine has also been associated with QT prolongation.
    Insulins: (Moderate) Monitor patients receiving insulin closely for changes in glycemic control during the use of pentamidine; dosage adjustments of insulin may be necessary. Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed hyperglycemia with prolonged pentamidine therapy.
    Isoflurane: (Major) Pentamidine has been associated with serious cardiac arrhythmias including QT prolongation, and is considered to have an established risk of torsades de pointes. The drug should be used cautiously, if at all, in patients receiving agents which may cause QT prolongation or torsade de pointes including halogenated anesthetics such as isoflurane.
    Itraconazole: (Major) Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with itraconazole include pentamidine.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with pentamidine due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Systemic pentamidine has been associated with QT prolongation.
    Kanamycin: (Major) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, such as systemic aminoglycosides. Renal function and aminoglycoside concentratons should be closely monitored.
    Ketoconazole: (Major) Ketoconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ketoconazole include pentamidine.
    Ketoprofen: (Major) Avoid concurrent or sequential use of pentamidine with ketoprofen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Ketorolac: (Major) Avoid concurrent or sequential use of pentamidine with ketorolac. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with clarithromycin include intravenous pentamidine.
    Lansoprazole; Naproxen: (Major) Avoid concurrent or sequential use of pentamidine with naproxen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Lapatinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of lapatinib with systemic pentamidine is necessary; correct electrolyte abnormalities prior to treatment. Systemic pentamidine has been associated with QT prolongation. Lapatinib has also been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib.
    Lefamulin: (Major) Avoid coadministration of lefamulin with pentamidine as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Systemic pentamidine has been associated with QT prolongation.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with pentamidine due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Systemic pentamidine has also been associated with QT prolongation.
    Leuprolide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving pentamidine. Systemic pentamidine has been associated with QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval.
    Leuprolide; Norethindrone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving pentamidine. Systemic pentamidine has been associated with QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval.
    Levofloxacin: (Major) Concurrent use of pentamidine and levofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Additionally, rare cases of TdP have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. Pentamidine has also been associated with QT prolongation.
    Levoketoconazole: (Major) Ketoconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ketoconazole include pentamidine.
    Levomefolate: (Minor) L-methylfolate and pentamidine should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with pentamidine. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Levomethadyl: (Contraindicated) Levomethadyl is associated with an established risk of QT prolongation and/or torsades de pointes and is contraindicated in combination with other agents that may prolong the QT interval, such as pentamidine.
    Linagliptin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Monitor for needed adjustments in diabetes treatments.
    Linagliptin; Metformin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Monitor for needed adjustments in diabetes treatments. (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Lithium: (Major) Lithium should be used cautiously and with close monitoring with pentamidine. Lithium and systemic pentamidone have both been associated with QT prolongation.
    Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with pentamidine due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Systemic pentamidine has been associated with QT prolongation.
    Loop diuretics: (Moderate) Drugs that are associated with hypokalemia and/or hypomagnesemia such as loop diuretics should be used with caution in patients also receiving pentamidine. Since pentamidine may cause QT prolongation independently of electrolyte imbalances, the risk for cardiac arrhythmias is potentiated by the concomitant use of agents associated with electrolyte loss. .
    Loperamide: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like pentamidine, should be used cautiously and with close monitoring with loperamide.
    Loperamide; Simethicone: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like pentamidine, should be used cautiously and with close monitoring with loperamide.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with systemic pentamidine due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Systemic pentamidine and lopinavir have been associated with QT prolongation.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as pentamidine. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Systemic pentamidine has been associated with QT prolongation.
    Mannitol: (Major) Avoid use of mannitol and pentamidine, if possible. Concomitant administration of nephrotoxic drugs, such as pentamidine, increases the risk of renal failure after administration of mannitol.
    Maprotiline: (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include maprotiline. Maprotiline may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP have been described with maprotiline, but rarely occur at normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
    Meclofenamate Sodium: (Major) Avoid concurrent or sequential use of pentamidine with meclofenamate. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Mefenamic Acid: (Major) Avoid concurrent or sequential use of pentamidine with mefenamic acid. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Mefloquine: (Major) Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval, such as pentamidine. Intravenous pentamidine has been associated with QT prolongation and this risk may be increased with other drugs that might prolong the QT interval.
    Meloxicam: (Major) Avoid concurrent or sequential use of pentamidine with meloxicam. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Meperidine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include pentamidine.
    Mesoridazine: (Contraindicated) Both mesoridazine and pentamidine have been associated with QT prolongation. Mesoridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Mesoridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, including pentamidine.
    Metformin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Metformin; Repaglinide: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine. (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Metformin; Rosiglitazone: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Metformin; Saxagliptin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine. (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Metformin; Sitagliptin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Methadone: (Major) Pentamidine has been associated with QT prolongation. Methadone may inhibit cardiac potassium channels and may prolong the QT interval. The need to coadminister methadone or pentamidine with drugs known to prolong the QT interval should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is considered to be associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
    Metronidazole: (Major) Concomitant use of metronidazole and systemic pentamidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Midostaurin: (Major) The concomitant use of midostaurin and pentamidine may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Systemically adminstered pentamidine is considered to be associated with a well-established risk for QT prolongation and torsade de pointes (TdP). Extremely limited evidence in case reports suggest inhaled pentamidine may be associated with possible TdP; however, systemic absorption of inhaled pentamidine is limited.
    Mifepristone: (Major) Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously and with close monitoring with mifepristone include pentamidine. Systemic pentamidine is associated with QT prolongation.
    Mirabegron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as systemic pentamidine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
    Mirtazapine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and pentamidine. Coadminister with caution. Systemic pentamidine has been associated with QT prolongation. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation.
    Mobocertinib: (Major) Concomitant use of mobocertinib and systemic pentamidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Moxifloxacin: (Major) Concurrent use of pentamidine and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Pentamidine has been associated with QT prolongation. Moxifloxacin has also been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
    Nabumetone: (Major) Avoid concurrent or sequential use of pentamidine with nabumetone. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Naproxen: (Major) Avoid concurrent or sequential use of pentamidine with naproxen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Naproxen; Esomeprazole: (Major) Avoid concurrent or sequential use of pentamidine with naproxen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Naproxen; Pseudoephedrine: (Major) Avoid concurrent or sequential use of pentamidine with naproxen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Nateglinide: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib and pentamidine; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Systemic pentamidine has been associated with QT prolongation.
    Norfloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering pentamidine with norfloxacin. Pentamidine has been associated with QT prolongation. Quinolones have also been associated with QT prolongation and TdP. For norfloxacin specifically, extremely rare cases of TdP were reported during post-marketing surveillance. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Octreotide: (Major) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with octreotide include pentamidine. Intravenous pentamidine is associated with a risk of QT prolongation.
    Ofloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering pentamidine with ofloxacin. Pentamidine has been associated with QT prolongation. Some quinolones, including ofloxacin, have also been associated with QT prolongation. Additionally, post-marketing surveillance for ofloxacin has identified very rare cases of TdP.
    Olanzapine: (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Olanzapine; Fluoxetine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include pentamidine. (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Olanzapine; Samidorphan: (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Ondansetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), ondansetron and pentamidine should be used together cautiously. Ondansetron has been associated with QT prolongation and post-marketing reports of torsade de pointes (TdP). Among 42 patients receiving a 4 mg bolus dose of intravenous ondansetron for the treatment of postoperative nausea and vomiting, the mean maximal QTc interval prolongation was 20 +/- 13 msec at the third minute after antiemetic administration (p < 0.0001). If ondansetron and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended. Pentamidine has been associated with QT prolongation.
    Oritavancin: (Moderate) Pentamidine is metabolized by CYP2D6; oritavancin is a weak CYP2D6 inducer. Plasma concentrations and efficacy of pentamidine may be reduced if these drugs are administered concurrently.
    Osilodrostat: (Major) Monitor ECGs in patients receiving osilodrostat with pentamidine. Osilodrostat is associated with dose-dependent QT prolongation. Systemic pentamidine has been associated with QT prolongation.
    Osimertinib: (Major) Avoid coadministration of pentamidine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Systemic pentamidine has also been associated with QT prolongation.
    Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of pentamidine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Systemic pentamidine has been associated with QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
    Oxaprozin: (Major) Avoid concurrent or sequential use of pentamidine with oxaprozin. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Ozanimod: (Major) In general, do not initiate ozanimod in patients taking pentamidine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Systemic pentamidine has been associated with QT prolongation.
    Pacritinib: (Major) Concomitant use of pacritinib and systemic pentamidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Systemic pentamidine has been associated with QT prolongation. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
    Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include pentamidine.
    Paromomycin: (Major) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, such as systemic aminoglycosides. Renal function and aminoglycoside concentratons should be closely monitored.
    Paroxetine: (Moderate) Pentamidine is a substrate of CYP2D6 and paroxetine is a potent inhibitor of CYP2D6. Because pentamidine is a CYP2D6 substrate and has a possible risk of QT prolongation and torsade de pointes, concurrent use of a potent CYP2D6 inhibitor such as paroxetine may increase the risk of such events.
    Pasireotide: (Major) Cautious use of pasireotide and pentamidine is needed, as coadministration may have additive effects on the prolongation of the QT interval.
    Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include pentamidine.
    Peginterferon Alfa-2b: (Moderate) Monitor for adverse effects associated with increased exposure to pentamidine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while pentamidine is partially metabolized by the CYP2D6 isoenzyme.
    Perphenazine: (Minor) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include perphenazine.
    Perphenazine; Amitriptyline: (Minor) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include perphenazine.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval. Systemic pentamidine has been associated with QT prolongation. Coadministration may increase the risk for QT prolongation.
    Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of pentamidine with pimozide is contraindicated.
    Pioglitazone; Glimepiride: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Pioglitazone; Metformin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Piroxicam: (Major) Avoid concurrent or sequential use of pentamidine with piroxicam. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Pitolisant: (Major) Avoid coadministration of pitolisant with pentamidine as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Systemic pentamidine has been associated with QT prolongation.
    Plazomicin: (Major) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, such as systemic aminoglycosides. Renal function and aminoglycoside concentratons should be closely monitored.
    Ponesimod: (Major) In general, do not initiate ponesimod in patients taking pentamidine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Systemic pentamidine has been associated with QT prolongation
    Posaconazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering posaconazole with pentamidine. Both posaconazole and pentamidine have been associated with QT prolongation, while posaconazole has also been associated with rare cases of TdP.
    Pramlintide: (Moderate) Pentamidine can be harmful to pancreatic cells, which may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include pentamidine.
    Procainamide: (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include procainamide. Additive effects on the QT interval are possible.
    Prochlorperazine: (Minor) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include prochlorperazine.
    Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include pentamidine.
    Promethazine; Dextromethorphan: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include pentamidine.
    Promethazine; Phenylephrine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include pentamidine.
    Propafenone: (Major) Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with propafenone include pentamidine. Pentamidine has been associated with QT prolongation and may also cause electrolyte disturbances, such as hypokalemia, hypomagnesemia, and hypocalcemia which may increase the risk for cardiac arrhythmia. Monitor heart rate and serum electrolytes closely.
    Quetiapine: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with quetiapine include pentamidine. Pentamidine has been associated with QT prolongation.
    Quinidine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include systemic pentamidine.
    Quinine: (Major) Concurrent use of quinine and pentamidine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Pentamidine has also been associated with QT prolongation. In addition, concentrations of pentamidine may be increased with concomitant use of quinine. Pentamidine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
    Ranolazine: (Major) Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the tmax of the maximum dosage (1000 mg PO twice daily). However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. In addition, ranolazine and/or metabolites are moderate inhibitors of CYP2D6 isoenzymes. Based on drug interaction studies with metoprolol, a CYP2D6 substrate, ranolazine may theoretically increase plasma concentrations of CYP2D6 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. The manufacturer for ranolazine suggests that lower doses of CYP2D6 substrates may be required during ranolazine treatment. Drugs that are CYP2D6 substrates that also have a possible risk for QT prolongation and TdP that should be used cautiously with ranolazine include pentamidine.
    Relugolix: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Systemic pentamidine has also been associated with QT prolongation.
    Relugolix; Estradiol; Norethindrone acetate: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Systemic pentamidine has also been associated with QT prolongation.
    Repaglinide: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Ribociclib: (Major) Avoid coadministration of ribociclib with pentamidine due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Systemic pentamidine has also been associated with QT prolongation. Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with pentamidine due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Systemic pentamidine has also been associated with QT prolongation. Concomitant use may increase the risk for QT prolongation.
    Rilpivirine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with pentamidine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Pentamidine has also been associated with QT prolongation.
    Risperidone: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include pentamidine.
    Rolapitant: (Major) Use caution if pentamidine and rolapitant are used concurrently, and monitor for pentamidine-related adverse effects. Pentamidine is a CYP2D6 substrate and rolapitant is a moderate CYP2D6 inhibitor; the inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration. Exposure to another CYP2D6 substrate, following a single dose of rolapitant increased about 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in the CYP2D6 substrate concentrations, the last time point measured.
    Romidepsin: (Major) Romidepsin has been reported to prolong the QT interval. Pentamidine has been associated with QT prolongation. If romidepsin must be coadministered with another drug that prolongs the QT interval, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
    Saquinavir: (Contraindicated) The concurrent use of systemic pentamidine and saquinavir boosted with ritonavir is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Saquinavir boosted with ritonavir causes dose-dependent QT and PR prolongation; avoid use with other drugs that may prolong the QT or PR interval, such as pentamidine.
    Saxagliptin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with pentamidine is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Systemic pentamidine has been associated with QT prolongation.
    Sertraline: (Major) Use caution and monitor patients for QT prolongation when administering pentamidine with sertraline. Systemic pentamidine has been associated with QT prolongation. QTc prolongation and torsade de pointes (TdP) have been reported during postmarketing use of sertraline; most cases had confounding risk factors. The risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Sevoflurane: (Major) Pentamidine has been associated with serious cardiac arrhythmias including QT prolongation, and is considered to have an established risk of torsades de pointes. The drug should be used cautiously, if at all, in patients receiving agents which may cause QT prolongation or torsade de pointes including halogenated anesthetics such as sevoflurane.
    Simvastatin; Sitagliptin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving pentamidine due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Systemic pentamidine has been associated with QT prolongation.
    Sitagliptin: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Solifenacin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering solifenacin with pentamidine. Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined. Pentamidine has also been associated with QT prolongation.
    Sorafenib: (Major) Avoid coadministration of sorafenib with systemic pentamidine due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib is associated with QTc prolongation. Systemic pentamidine has also been associated with QT prolongation.
    Sotalol: (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP), such as sotalol, should be used cautiously with pentamidine. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Streptomycin: (Major) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, such as systemic aminoglycosides. Renal function and aminoglycoside concentratons should be closely monitored.
    Sulfonylureas: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Sulindac: (Major) Avoid concurrent or sequential use of pentamidine with sulindac. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Sumatriptan; Naproxen: (Major) Avoid concurrent or sequential use of pentamidine with naproxen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Sunitinib: (Major) Monitor patients for QT prolongation if coadministration of pentamidine with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Systemic pentamidine has also been associated with QT prolongation.
    Tacrolimus: (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include tacrolimus. Tacrolimus has been associated with a possible risk for QT prolongation.
    Tamoxifen: (Major) Caution is advised with the concomitant use of tamoxifen and pentamidine due to an increased risk of QT prolongation. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have been described when tamoxifen is used at lower doses. Systemic pentamidine has also been associated with QT prolongation.
    Telavancin: (Major) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs such as intravenous pentamidine may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance. In addition, both telavancin and pentamidine have been associated with QT prolongation. Caution is recommended when prescribing these drugs together.
    Telithromycin: (Major) Telithromycin has the potential to prolong the QT interval and should be used cautiously in combination with other drugs that may also prolong the QT interval, including pentamidine. Pentamidine has been associated with QT prolongation.
    Terfenadine: (Contraindicated) Use of these drugs together is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Terfenadine is associated with a well-established risk for QT prolongation and TdP. Terfenadine should not be used with other drugs with an established risk for QT prolongation. Systemic pentamidine has been associated with serious cardiac arrhythmias including QT prolongation, and is considered to have an established risk ofTdP. Rare cases of QT prolongation have been reported with inhaled pentamidine.
    Tetrabenazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as pentamidine.
    Thiazide diuretics: (Moderate) Drugs that are associated with hypokalemia and/or hypomagnesemia such as thiazide diuretics should be used with caution in patients also receiving pentamidine. Since pentamidine may cause QT prolongation independently of electrolyte imbalances, the risk for cardiac arrhythmias is potentiated by the concomitant use of agents associated with electrolyte loss. Closely monitor serum electrolytes during pentamidine therapy.
    Thiazolidinediones: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Thioridazine: (Contraindicated) Both thioridazine and pentamidine have been associated with QT prolongation. Thioridazine is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, including pentamidine.
    Tobramycin: (Major) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, such as systemic aminoglycosides. Renal function and aminoglycoside concentratons should be closely monitored.
    Tolazamide: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Tolbutamide: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Tolmetin: (Major) Avoid concurrent or sequential use of pentamidine with tolmetin. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable.
    Tolterodine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering tolterodine with pentamidine. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Pentamidine has also been associated with QT prolongation.
    Toremifene: (Major) Avoid coadministration of systemic pentamidine with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Systemic administration of pentamidine has also been associated with QT prolongation.
    Torsemide: (Moderate) Drugs that are associated with hypokalemia and/or hypomagnesemia such as loop diuretics should be used with caution in patients also receiving pentamidine. Since pentamidine may cause QT prolongation independently of electrolyte imbalances, the risk for cardiac arrhythmias is potentiated by the concomitant use of agents associated with electrolyte loss. .
    Trazodone: (Major) Pentamidine has been associated with QT prolongation and should be avoided in combination with trazodone. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of torsade de pointes (TdP). Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval.
    Triclabendazole: (Major) Monitor ECGs in patients receiving triclabendazole with pentamidine. Transient prolongation of the mean QTc interval was noted on the ECG recordings in dogs administered triclabendazole. Systemic pentamidine has been associated with QT prolongation.
    Trifluoperazine: (Minor) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include trifluoperazine. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Triptorelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving pentamidine. Systemic pentamidine has been associated with QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval.
    Valganciclovir: (Moderate) Use valganciclovir with pentamidine only if the potential benefits are judged to outweigh the risks. Concurrent use of agents that inhibit rapidly dividing cell populations (i.e., bone marrow, spermatogonia, germinal layers of the skin, gastrointestinal mucosa) with valganciclovir should be done cautiously, in order to avoid additive toxicity. Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, including valganciclovir.
    Vancomycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as systemic pentamidine, can lead to additive nephrotoxicity. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations.
    Vandetanib: (Major) Avoid coadministration of vandetanib with pentamidine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Systemic pentamidine has also been associated with QT prolongation.
    Vardenafil: (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include vardenafil. Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produce an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). When vardenafil was given with prescriptive doses of another agent known to prolong the QT interval, an additive effect on the QT interval was observed.
    Vasopressin, ADH: (Moderate) Monitor hemodynamics and adjust the dose of vasopressin as needed when used concomitantly with drugs suspected of causing syndrome of inappropriate antidiuretic hormone (SIADH), such as pentamidine. Use together may increase the pressor and antidiuretic effects of vasopressin.
    Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. If vemurafenib and another drug that is associated with a possible risk for QT prolongation and torsade de pointes (TdP) must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Pentamidine has been associated with QT prolongation. Pentamidine is a CYP2D6 substrate and vemurafenib is a weak CYP2D6 inhibitor; therefore, increased pentamidine concentrations may occur.
    Venlafaxine: (Major) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with pentamidine include venlafaxine. Venlafaxine administration is associated with a possible risk of QT prolongation; torsades de pointes (TdP) has reported with post-marketing use.
    Voclosporin: (Major) Use caution if pentamidine is coadministered with voclosporin due to the risk of additive QT prolongation. Concomitant use may also result in additive nephrotoxicity; monitor for renal toxicity if concomitant use is required. Systemic pentamidine has been associated with QT prolongation. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
    Voriconazole: (Major) Voriconazole has been associated with QT prolongation and rare cases of torsades de pointes. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with voriconazole include pentamidine. Pentamidine has been associated with QT prolongation. Also, voriconazole is an inhibitor of the CYP 2C19 isoenzyme and interactions are possible with agents that are substrates of this enzyme, such as pentamidine; increased plasma levels of pentamidine may occur.
    Vorinostat: (Major) Vorinostat therapy is associated with a risk of QT prolongation. Vorinostat should be used with caution if given with other agents that may prolong the QT interval including pentamidine.
    Zalcitabine, ddC: (Major) Treatment with zalcitabine should be temporarily suspended when systemic pentamidine. Coadministration of intravenous pentamidine and zalcitabine was possibly associated with one death due to fulminant pancreatitis; both drugs are associated with pancreatitis when used alone. Intravenous pentamidine is required to treat Pneumocystis carinii pneumonia, treatment with zalcitabine should be temporarily suspended.
    Ziprasidone: (Contraindicated) Concomitant use of ziprasidone and pentamidine is contraindicated by the manufacturer of ziprasidone due to the potential for additive QT prolongation and torsade de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors. Systemic pentamidine has been associated with QT prolongation.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies of pentamidine in human pregnancy, and its ability to cause fetal harm or affect reproductive capacity is unknown. A literature report indicated that intravenously administered pentamidine in pregnant rats at 4 mg/kg/day was embryolethal; teratogenicity was not observed in this study. It is unknown whether pentamidine administered via the aerosolized route crosses the placenta at clinically significant concentrations. Pentamidine isethionate should not be given to a pregnant woman unless the potential benefits are judged to outweigh the unknown risks.
     

    Data are limited regarding use of pentamidine during breast-feeding and its' excretion into human breast milk is unknown. According to the manufacturer, because of the potential for serious adverse events in a nursing infant, a decision should be made to either discontinue breast-feeding or discontinue use of the drug. Additionally, pentamidine may be used to treat infections in patients with HIV and the Centers for Disease Control and Prevention (CDC) recommends that in the US, HIV-infected mothers not breast-feed their infants to avoid the risk of postnatal transmission of HIV. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: Pentamidine's mechanism of action is not clearly known and can vary, depending on the organism being treated. Pentamidine may interfere with the incorporation of nucleotides into both DNA and RNA. It also may inhibit oxidative phosphorylation and the biosynthesis of DNA, RNA, proteins, and phospholipids. Finally, pentamidine may have folate-antagonist actions, since other agents that are effective against Pneumocystis (e.g., TMP-SMX, pyrimethamine, and trimetrexate) are also folate antagonists.

    PHARMACOKINETICS

    Pentamidine is poorly absorbed from the gastrointestinal tract and must be given parenterally or by inhalation to be effective.
     
    Biotransformation of pentamidine in humans is unknown. At least six metabolites have been identified in rats. Elimination of systemic drug is primarily renal, and half-life is increased in patients with renal dysfunction. Half-lives vary, depending on the route of administration. The terminal half-life is 2—4 weeks. Urinary excretion may persist for up to 8 weeks after discontinuation. Multiple dosing may result in drug accumulation, even in patients with normal renal function. No information on fecal excretion in humans is available.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A5, CYP2D6, CYP2C19, CYP1A1, CYP4A11
    Previous data suggest that pentamidine was metabolized by the CYP2C19 isoenzyme; however, this has not been confirmed. In vitro data suggest that the CYP1A1, 3A5, and 4A11 isoenzymes may contribute to the metabolism of pentamidine, but data from healthy volunteers show that the CYP1A1 and 2D6 are the mediating enzymes in humans. Drug interactions with pentamidine are not well studied. Because of this, clinicians should be cautious of using concurrent drugs that have similar toxicities.

    Intravenous Route

    After a single 4 mg/kg IV dose of pentamidine, peak plasma pentamidine concentrations are 0.6 mcg/mL after completion of the IV infusion. Peak steady-state concentrations after repeated doses of 3 mg/kg/day reach 0.5 mcg/ml.
     
    Parenteral doses of pentamidine are widely distributed into body tissues and fluids. Highest concentrations are found in the liver, followed by the kidneys, adrenals, spleen, lungs, and pancreas. Additional accumulation in lung tissue may not occur beyond the first week of IV therapy. Pentamidine is thought to have poor CNS penetration. Pentamidine is detected in brain tissue approximately 30 days after the start of therapy. Steady-state volume of distribution is 3—32 L/kg. Protein binding is approximately 69%.
     
    Over 24 hours, 2.5% of the IV dose is excreted in the urine. Half-lives vary, depending on the route of administration. The half-life of intravenous pentamidine is approximately 6.5 hours.

    Intramuscular Route

    After a single 4 mg/kg IM dose of pentamidine, peak plasma pentamidine concentrations are 0.2 mcg/mL 40 minutes after the IM dose. Peak steady-state concentrations after repeated doses of 3 mg/kg/day reach 0.5 mcg/ml.
     
    Parenteral doses of pentamidine are widely distributed into body tissues and fluids. Highest concentrations are found in the liver, followed by the kidneys, adrenals, spleen, lungs, and pancreas. Additional accumulation in lung tissue may not occur beyond the first week of IM therapy. Pentamidine is thought to have poor CNS penetration. Pentamidine is detected in brain tissue approximately 30 days after the start of therapy. Steady-state volume of distribution is 3—32 L/kg. Protein binding is approximately 69%.
     
    Over 24 hours, 4—17% of the IM dose is excreted in the urine. Half-lives vary, depending on the route of administration. The half-life of intramuscular pentamidine ranges from 9.1—13.2 hours.

    Inhalation Route

    Systemic absorption of inhaled pentamidine is minimal. After a nebulized dose of 4 mg/kg, serum pentamidine concentrations average less than 20 ng/ml.
     
    Distribution of inhaled pentamidine is variable. Distribution of the drug in the lungs is more uniform when the patient is in the supine position during inhalation. Similar to other drug therapy delivered via nebulization, the type of nebulizer used has a significant impact on particle size and nebulization efficiency, which, in turn, affects drug deposition. Aerosolized pentamidine produces concentrations in the lungs that are 10—100 times that produced by the same dose of IV pentamidine; however, distribution throughout the lung is not uniform.
     
    There is no information available on the elimination of nebulized pentamidine.