BOXED WARNING
Anemia, bleeding, bone marrow suppression, herpes infection, immunosuppression, infection, leukopenia, neutropenia, radiation therapy, requires an experienced clinician, thrombocytopenia, varicella, viral infection
Hematologic toxicity (e.g., anemia, neutropenia, leukopenia, and thrombocytopenia) has been reported with mechlorethamine therapy. This drug requires an experienced clinician knowledgeable in the use of cancer chemotherapy. Infection and bleeding may occur as a result of bone marrow suppression. Intravenous (IV) mechlorethamine should be used cautiously in patients receiving other myelosuppressive therapy (e.g., radiation therapy). Monitor hematologic parameters (e.g., complete blood count panel) frequently during therapy. Bone morrow function should be recovered prior to administering IV mechlorethamine and/or radiation therapy. Use of IV mechlorethamine is contraindicated in patients who have an infectious disease. Immunosuppression has been reported with IV mechlorethamine therapy and bacterial, fungal, or viral infection (e.g., varicella, herpes infection) may occur. Herpes zoster infection may occur during or be precipitated by mechlorethamine treatment. Discontinue therapy in patients with herpes zoster infection.
Extravasation
Extravasation resulting in severe tissue damage (e.g., inflammation, induration, or sloughing of tissue) has been reported with mechlorethamine therapy. If extravasation or signs of drug leakage occur, promptly treat with sterile isotonic sodium thiosulfate (1/6 molar) and apply an ice compress for 6 to 12 hours. For a 1/6 molar solution of sodium thiosulfate, use 4.14 g of sodium thiosulfate per 100 mL of Sterile Water for Injection or 2.64 g of anhydrous sodium thiosulfate per 100 mL. Alternatively, dilute 4 mL of 10% sodium thiosulfate injection with 6 mL of Sterile Water for Injection.
Accidental exposure, ocular exposure
Mechlorethamine is highly toxic and the powder, solution must be handled and administered with care; all injectable forms contain a boxed warning against accidental exposure. Review and diligently follow special handling procedures before and during mechlorethamine handling because of the toxic properties of the drug such as corrosivity, carcinogenicity, mutagenicity, and teratogenicity. Appropriate protective equipment should be worn to avoid accidental exposure to mechlorethamine during preparation, handling, and administration. Avoid exposure to the eyes, avoid inhalation of dust or vapors, and avoid accidental contact with the skin or mucous membranes. Contaminated clothing should be destroyed. To clean gloves, tubing, surfaces, etc., after contact with mechlorethamine, soak in aqueous solution containing equal parts sodium thiosulfate 5% and sodium bicarbonate 5% for 45 minutes. Any unused solution and vials should be neutralized by mixing with an equal volume of sodium thiosulfate/sodium bicarbonate solution prior to disposal. Accidental skin contact with parenteral mechlorethamine should be treated with thorough rinsing of the area with water for at least 15 minutes, while removing contaminated clothing and shoes, followed by rinsing with 2% sodium thiosulfate solution. Medical attention should be sought immediately. Ocular exposure to mechlorethamine in any formulation causes pain, burns, inflammation, photophobia, and blurred vision. Blindness and severe irreversible anterior eye injury may occur. The topical gel does not contain a boxed warning regarding accidental exposure, but should only be applied to the skin, and several warnings regarding proper application and need for care in handling during administration apply. If accidental eye contact occurs to mechlorethamine topical gel or other dosage forms, rinse the exposed eye(s) with copious amounts of water, normal saline, or a balanced salt solution for at least 15 minutes; promptly seek emergency care, which should include consult of an ophthalmologist. If oral mucous membrane exposure occurs with topical mechlorethamine gel use, immediately rinse the area for at least 15 minutes with water and promptly seek medical attention. Individuals other than the patient should avoid direct skin contact with mechlorethamine gel due to the risks of secondary exposure including dermatitis, mucosal injury, and secondary cancers.
New primary malignancy
The risk of a new primary malignancy is increased with the use of alkylating agents such as mechlorethamine, particularly when alkylating agents are used in combination with other antineoplastic agents or radiation therapy. Thymic lymphomas, pulmonary adenomas, and squamous cell tumors have been observed in the animal studies. Additionally, non-melanoma skin cancer has been reported in patients who received mechlorethamine topical gel. Some non-melanoma skin cancers occurred in patients who had received prior therapies known to cause non-melanoma skin cancer. Monitor patients for non-melanoma skin cancers during and after treatment with mechlorethamine topical gel.
Pregnancy
Mechlorethamine may cause fetal harm when administered during pregnancy based on its mechanism of action, data from animal studies, genotoxicity findings, and case reports in humans. Females of reproductive potential should avoid pregnancy during mechlorethamine therapy. Congenital malformations have been reported in newborns following systemic mechlorethamine use in pregnant women; however, there have been no reports of these malformations with mechlorethamine topical gel based on limited data in pregnant women. Pregnant patients should be apprised of the potential hazard to the fetus. Fetal malformations including fetal death and growth retardation occurred in animals after a single subcutaneous 1 mg/kg dose.
CONTRAINDICATIONS / PRECAUTIONS
General Information
Hypersensitivity reactions have been reported with IV and topical mechlorethamine therapy. Use is contraindicated in patients with a previous or known history of severe hypersensitivity reaction (e.g., anaphylaxis) to mechlorethamine.
Anemia, bleeding, bone marrow suppression, herpes infection, immunosuppression, infection, leukopenia, neutropenia, radiation therapy, requires an experienced clinician, thrombocytopenia, varicella, viral infection
Hematologic toxicity (e.g., anemia, neutropenia, leukopenia, and thrombocytopenia) has been reported with mechlorethamine therapy. This drug requires an experienced clinician knowledgeable in the use of cancer chemotherapy. Infection and bleeding may occur as a result of bone marrow suppression. Intravenous (IV) mechlorethamine should be used cautiously in patients receiving other myelosuppressive therapy (e.g., radiation therapy). Monitor hematologic parameters (e.g., complete blood count panel) frequently during therapy. Bone morrow function should be recovered prior to administering IV mechlorethamine and/or radiation therapy. Use of IV mechlorethamine is contraindicated in patients who have an infectious disease. Immunosuppression has been reported with IV mechlorethamine therapy and bacterial, fungal, or viral infection (e.g., varicella, herpes infection) may occur. Herpes zoster infection may occur during or be precipitated by mechlorethamine treatment. Discontinue therapy in patients with herpes zoster infection.
Dental disease, dental work
Myelosuppressive effects of mechlorethamine can increase the risk of infection or bleeding; therefore, dental work should be delayed until blood counts have returned to normal. Patients, especially those with dental disease, should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks.
Extravasation
Extravasation resulting in severe tissue damage (e.g., inflammation, induration, or sloughing of tissue) has been reported with mechlorethamine therapy. If extravasation or signs of drug leakage occur, promptly treat with sterile isotonic sodium thiosulfate (1/6 molar) and apply an ice compress for 6 to 12 hours. For a 1/6 molar solution of sodium thiosulfate, use 4.14 g of sodium thiosulfate per 100 mL of Sterile Water for Injection or 2.64 g of anhydrous sodium thiosulfate per 100 mL. Alternatively, dilute 4 mL of 10% sodium thiosulfate injection with 6 mL of Sterile Water for Injection.
Accidental exposure, ocular exposure
Mechlorethamine is highly toxic and the powder, solution must be handled and administered with care; all injectable forms contain a boxed warning against accidental exposure. Review and diligently follow special handling procedures before and during mechlorethamine handling because of the toxic properties of the drug such as corrosivity, carcinogenicity, mutagenicity, and teratogenicity. Appropriate protective equipment should be worn to avoid accidental exposure to mechlorethamine during preparation, handling, and administration. Avoid exposure to the eyes, avoid inhalation of dust or vapors, and avoid accidental contact with the skin or mucous membranes. Contaminated clothing should be destroyed. To clean gloves, tubing, surfaces, etc., after contact with mechlorethamine, soak in aqueous solution containing equal parts sodium thiosulfate 5% and sodium bicarbonate 5% for 45 minutes. Any unused solution and vials should be neutralized by mixing with an equal volume of sodium thiosulfate/sodium bicarbonate solution prior to disposal. Accidental skin contact with parenteral mechlorethamine should be treated with thorough rinsing of the area with water for at least 15 minutes, while removing contaminated clothing and shoes, followed by rinsing with 2% sodium thiosulfate solution. Medical attention should be sought immediately. Ocular exposure to mechlorethamine in any formulation causes pain, burns, inflammation, photophobia, and blurred vision. Blindness and severe irreversible anterior eye injury may occur. The topical gel does not contain a boxed warning regarding accidental exposure, but should only be applied to the skin, and several warnings regarding proper application and need for care in handling during administration apply. If accidental eye contact occurs to mechlorethamine topical gel or other dosage forms, rinse the exposed eye(s) with copious amounts of water, normal saline, or a balanced salt solution for at least 15 minutes; promptly seek emergency care, which should include consult of an ophthalmologist. If oral mucous membrane exposure occurs with topical mechlorethamine gel use, immediately rinse the area for at least 15 minutes with water and promptly seek medical attention. Individuals other than the patient should avoid direct skin contact with mechlorethamine gel due to the risks of secondary exposure including dermatitis, mucosal injury, and secondary cancers.
Hyperuricemia, tumor lysis syndrome (TLS)
Hyperuricemia may occur with IV mechlorethamine use. Take measures to prevent tumor lysis syndrome (TLS) and hyperuricemia (e.g., fluids) prior to starting mechlorethamine, especially in patients with highly chemosensitive disease (e.g., lymphoma).
Inflammation, skin disease
Dermatitis has been commonly reported with mechlorethamine topical gel use. Monitor patients for redness, swelling, inflammation, itchiness, blisters, ulceration, and secondary skin infections. Applying mechlorethamine topical gel to the face, genitalia, anus, and intertriginous skin increase the risk of dermatitis. Therapy interruption and application frequency reduction is necessary in patients who develop skin disease such as skin ulceration, blistering, or moderate to severe or severe dermatitis.
Suppurative inflammation
Intravenous mechlorethamine should not be used in patients with foci of acute or chronic suppurative inflammation because the drug can cause the rapid development of amyloidosis.
New primary malignancy
The risk of a new primary malignancy is increased with the use of alkylating agents such as mechlorethamine, particularly when alkylating agents are used in combination with other antineoplastic agents or radiation therapy. Thymic lymphomas, pulmonary adenomas, and squamous cell tumors have been observed in the animal studies. Additionally, non-melanoma skin cancer has been reported in patients who received mechlorethamine topical gel. Some non-melanoma skin cancers occurred in patients who had received prior therapies known to cause non-melanoma skin cancer. Monitor patients for non-melanoma skin cancers during and after treatment with mechlorethamine topical gel.
Children, infants, neonates
The safety and efficacy of mechlorethamine topical gel have not been established in adolescents, children, infants, and neonates. There has been limited experience in using IV mechlorethamine (e.g., MOPP regimen for Hodgkin lymphoma) in pediatric patients; the safety and efficacy of IV mechlorethamine have not been established in well controlled trials in this patient population.
Pregnancy
Mechlorethamine may cause fetal harm when administered during pregnancy based on its mechanism of action, data from animal studies, genotoxicity findings, and case reports in humans. Females of reproductive potential should avoid pregnancy during mechlorethamine therapy. Congenital malformations have been reported in newborns following systemic mechlorethamine use in pregnant women; however, there have been no reports of these malformations with mechlorethamine topical gel based on limited data in pregnant women. Pregnant patients should be apprised of the potential hazard to the fetus. Fetal malformations including fetal death and growth retardation occurred in animals after a single subcutaneous 1 mg/kg dose.
Contraception requirements, infertility, male-mediated teratogenicity, reproductive risk
Counsel patients about the reproductive risk and contraception requirements during mechlorethamine treatment. Advise females of reproductive potential to use effective contraception including a barrier method (i.e., condoms) during treatment. Due to male-mediated teratogenicity, advise males with female partners of reproductive potential to use effective contraception including a barrier method during treatment. Patients who become pregnant while receiving mechlorethamine should be apprised of the potential hazard to the fetus. Infertility or impaired fertility may occur in females or males based on data from animal studies using systemic mechlorethamine. It is not known if the effect on fertility is reversible.
Breast-feeding
Advise patients that breast-feeding is not recommended during mechlorethamine treatment due to the potential for serious adverse reactions in the breastfed child. There are no data on the presence of mechlorethamine or its metabolites in human milk, the effects on the breast-fed child, or the effects on milk production.
DRUG INTERACTIONS
Acetaminophen; Ibuprofen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Aldesleukin, IL-2: (Moderate) The safety and efficacy of aldesleukin, IL 2 in combination with any antineoplastic agents have not been established. Hypersensitivity reactions have been reported in patients receiving combination regimens containing sequential high dose aldesleukin, IL 2 and dacarbazine. Aldesleukin, IL 2 can decrease dacarbazine serum concentrations by increasing the volume of distribution of dacarbazine by 36 percent via an unknown mechanism.
Amlodipine; Celecoxib: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Bupivacaine; Meloxicam: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Celecoxib: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Celecoxib; Tramadol: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Diclofenac: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diclofenac; Misoprostol: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diflunisal: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Diphenhydramine; Ibuprofen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diphenhydramine; Naproxen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Echinacea: (Major) Echinacea possesses immunostimulatory activity and may theoretically reduce the response to drugs that alter immune system activity like antineoplastic drugs. Although documentation is lacking, coadministration of echinacea with immunosuppressants is not recommended by some resources.
Etodolac: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
Fenoprofen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Flucytosine: (Minor) Flucytosine can cause significant hematologic toxicity. It should be used cautiously with all antineoplastic agents, especially those that cause bone marrow depression.
Flurbiprofen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Hydrocodone; Ibuprofen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Famotidine: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Oxycodone: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Pseudoephedrine: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Indomethacin: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ketoprofen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ketorolac: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Lansoprazole; Naproxen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Meclofenamate Sodium: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Mefenamic Acid: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Meloxicam: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Nabumetone: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Esomeprazole: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Pseudoephedrine: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Nonsteroidal antiinflammatory drugs: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Oxaprozin: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
Piroxicam: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Sulindac: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Sumatriptan; Naproxen: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Tolmetin: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Valdecoxib: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.