CLASSES
Acidifying Agents
DESCRIPTION
Phosphorus is principal ion in the bone and cartilage
Phosphate supplement used IV to treat hypophosphatemia or prevent hypophosphatemia in patients receiving parenteral nutrition (PN); used orally for urinary acidification
Concomitant potassium content must be taken into consideration when replacing phosphorus; generally used when potassium is less than 4 mg/dL
COMMON BRAND NAMES
K-Phos
HOW SUPPLIED
K-Phos Oral Tab: 500mg
Potassium Phosphate, Dibasic, Potassium Phosphate, Monobasic Intravenous Sol
Potassium Phosphate, Dibasic, Potassium Phosphate, Monobasic/Sodium Phosphate, Dibasic, Sodium Phosphate, Monobasic Intravenous Inj Sol
DOSAGE & INDICATIONS
For the treatment of hypophosphatemia.
NOTE: Serum phosphorus cutoff values represent adult concentrations. Normal serum phosphorus concentrations are higher in children, and thus cutoff values for children will be higher. Hypophosphatemia in children is generally defined as a serum phosphorus concentration less than 4 mg/dL; severe hypophosphatemia is generally defined as serum phosphorus concentrations less than 1 to 1.5 mg/dL. However, there is no consensus definition for degrees of hypophosphatemia in children.
NOTE: Guidelines generally recommend the use of potassium phosphate for potassium serum concentration less than 4 mg/dL and sodium phosphate for potassium serum concentration more than 4 mg/dL. Potassium phosphate is usually appropriate as most conditions associated with hypophosphatemia are also associated with hypokalemia.
For the treatment of moderate hypophosphatemia (i.e., phosphorus serum concentration 1 to 2 mg/dL).
Intravenous dosage
Adults
0.32 to 0.64 mmol/kg/dose (Usual Max: 50 mmol/dose) IV over 2 to 6 hours.
Infants, Children, and Adolescents
Data are very limited in children; doses of 0.08 to 0.16 mmol/kg/dose IV over 6 hours have been recommended. 0.32 to 0.64 mmol/kg/dose IV over 2 to 6 hours based on data in adult patients.
For the treatment of severe hypophosphatemia (i.e., phosphorus serum concentration less than 1 mg/dL).
Intravenous dosage
Adults
0.64 to 1 mmol/kg/dose (Usual Max: 50 mmol/dose) IV over 2 to 6 hours.
Infants, Children, and Adolescents
Data are very limited in children; doses as high as 1 mmol/kg/dose IV over 12 hours have been reported in pediatric patients with DKA and severe hypophosphatemia. 0.64 to 1 mmol/kg/dose IV over 2 to 6 hours based on data in adult patients.
For the treatment of mild hypophosphatemia (i.e., phosphorus serum concentration 2 to 2.5 mg/dL).
Intravenous dosage
Adults
0.16 to 0.32 mmol/kg/dose (Usual Max: 50 mmol/dose) IV over 2 to 6 hours.
Infants, Children, and Adolescents
Data are very limited in children; doses of 0.08 to 0.16 mmol/kg/dose IV over 6 hours have been recommended. 0.16 to 0.32 mmol/kg/dose IV over 2 to 6 hours based on data in adult patients.
For nutritional supplementation to prevent hypophosphatemia in patients receiving parenteral nutrition (PN).
NOTE: Supplementation of phosphate in PN may be limited by physical incompatibility, particularly in neonates who have higher calcium and phosphate requirements.
Intravenous dosage
Adults
20 to 40 mmol/day IV is recommended by guidelines. Titrate dose depending on patient's clinical condition and desired serum concentrations.
Children weighing 50 kg or more and Adolescents
10 to 40 mmol/day IV is recommended by guidelines. Titrate dose depending on patient's clinical condition and desired serum concentrations.
Infants and Children weighing less than 50 kg
0.5 to 2 mmol/kg/day IV is recommended by guidelines. Titrate dose depending on patient's clinical condition and desired serum concentrations.
Neonates
1 to 2 mmol/kg/day IV is recommended by guidelines. Titrate dose depending on patient's clinical condition and desired serum concentrations.
For urinary acidification and to augment the efficacy of methenamine therapy in treating urinary tract infections.
Oral dosage
Adults
2 tablets (1,000 mg; 7.5 mmol of phosphorus) PO four times daily with meals and at bedtime.
MAXIMUM DOSAGE
Adults
8 tablets/day PO. Specific maximum dosage information is not available for IV use; however, single maximum doses of 1 mmol/kg/dose IV (Usual Max: 50 mmol/dose) have been used; individualize dosage based on indication, phosphate serum concentrations, and other clinical parameters.
Geriatric
8 tablets/day PO. Specific maximum dosage information is not available for IV use; however, single maximum doses of 1 mmol/kg/dose IV (Usual Max: 50 mmol/dose) have been used; individualize dosage based on indication, phosphate serum concentrations, and other clinical parameters.
Adolescents
Safety and efficacy of oral formulation have not been established. Specific maximum dosage information is not available for IV use; however, single maximum doses of 1 mmol/kg/dose IV (Usual Adult Max: 50 mmol/dose) have been used; individualize dosage based on indication, phosphate serum concentrations, and other clinical parameters.
Children
Safety and efficacy of oral formulation have not been established. Specific maximum dosage information is not available for IV use; however, single maximum doses of 1 mmol/kg/dose IV (Usual Adult Max: 50 mmol/dose) have been used; individualize dosage based on indication, phosphate serum concentrations, and other clinical parameters.
Infants
Safety and efficacy of oral formulation have not been established. Specific maximum dosage information is not available for IV use; however, single maximum doses of 1 mmol/kg/dose IV have been used; individualize dosage based on indication, phosphate serum concentrations, and other clinical parameters.
Neonates
Safety and efficacy of oral formulation have not been established. Specific maximum dosage information is not available for IV use; individualize dosage based on indication, phosphate serum concentrations, and other clinical parameters.
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
Specific guidelines for dosage adjustments in renal impairment are not available; but dosage adjustments are necessary. In end-stage renal disease (ESRD), phosphorous levels are often elevated, leading to the need for phosphate-binding versus phosphate replacement.
ADMINISTRATION
Oral Administration
Oral Solid Formulations
Dissolve tablets in 180 to 240 mL of water. Let tablets soak in the water for 2 to 5 minutes or more, and stir. If any particles remain, they may be crushed and stirred vigorously to aid in dissolution.
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Check IV compatibility prior to admixing or infusing with other drugs or solutions; phosphate salts may precipitate when mixed with calcium salts under selected circumstances. Precipitation in the admixture is dependent primarily on the concentration of calcium and phosphate in the solution, the pH and temperature of the solution, however, other factors such as amino acid concentration and the presence of other additives must also be observed.
Intravenous Administration
Dilution
Potassium phosphate injection MUST be diluted prior to administration. Injection of concentrated potassium solution has been instantaneously fatal.
Dilute in sufficient volume of a compatible IV infusion solution (i.e., 100 to 500 mL of 5% Dextrose Injection or 0.9% NaCl Injection). Potassium phosphate dilution should follow similar dilution guidelines for potassium chloride.
Peripheral line: Potassium infusion via a peripheral vein may cause burning pain and phlebitis at the infusion site. Usual recommended maximum concentration for potassium for peripheral line is 100 mEq/L (68 mmol/L potassium phosphate); however, concentrations up to 200 mEq/L (136 mmol/L potassium phosphate) have been safely administered via peripheral lines in adults. For pediatric patients, data are limited; the usual recommended maximum concentration for peripheral line ranges from 40 to 100 mEq/L (68 mmol/L potassium phosphate); however, concentrations up to 200 mEq/L (136 mmol/L potassium phosphate) have been safely administered via peripheral lines.
Central line: Higher concentrations of 300 to 400 mEq/L must be administered via central line. Concentrations up to 400 mEq/L (272 mmol/L potassium phosphate) have been safely administered via central lines in adults. For pediatric patients, data are limited; the usual recommended maximum concentration for central line ranges from 80 to 200 mEq/L (136 mmol/L potassium phosphate); however, concentrations up to 400 mEq/L (272 mmol/L potassium phosphate) may be administered via central line.
Intravenous infusion
Maximum concentrations and recommended infusion rates may differ according to institution and patient care setting; potassium injections should NEVER be administered by IV push.
Adults: Infuse over 2 to 6 hours. Usual infusion rates are 7.5 to 15 mmol/hour (11 to 22 mEq/hour potassium). Rates as high as 20 mmol/hour (29 mEq/hour potassium) have been safely used in adult ICU patients.
Pediatrics: Data are limited; infusion rates of 6 to 12 hours have been used. The usual infusion rate based on potassium content is 0.17 to 0.34 mmol/kg/hour (0.25 to 0.5 mEq/kg/hour).
General guidelines for potassium administration recommend a central line for higher infusion rates to minimize infusion-related burning and phlebitis and continuous cardiac monitoring to monitor for signs of hyperkalemia.
Parenteral Nutrition (PN) Preparation
Parenteral nutrition admixtures containing calcium phosphate precipitates have resulted in embolic deaths when infused.
Generally, phosphate should be added first to the PN admixture, and calcium should be added to the end of the compounding sequence to take advantage of the maximum volume of PN formulation.
STORAGE
Generic:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Discard unused portion. Do not store for later use.
- Store at controlled room temperature (between 68 and 77 degrees F)
K-Phos:
- Store at controlled room temperature (between 68 and 77 degrees F)
CONTRAINDICATIONS / PRECAUTIONS
Hyperkalemia, renal failure, renal impairment
Potassium phosphate is contraindicated in diseases where hyperkalemia may be present, including patients with renal failure or severe renal impairment (CrCl less than 30% of normal). Careful monitoring of renal function may be required at periodic intervals during phosphate therapy.
Nephrolithiasis
Oral potassium phosphate is contraindicated in patients who have a phosphate nephrolithiasis infection (i.e., infected phosphate stones). Patients with kidney stones may pass old stones when phosphate therapy is started and should be warned of this possibility.
Dehydration, hyperphosphatemia, hypocalcemia
Potassium phosphate is contraindicated in diseases where hyperphosphatemia or hypocalcemia may be present. High serum phosphate concentrations may increase the incidence of extraskeletal calcification. Caution should be exercised when considering use in patients with acute dehydration. Since this product contains potassium, it should be used with caution if potassium restriction is desired. Careful monitoring of serum calcium, phosphorus, and potassium may be required at periodic intervals during phosphate therapy.
Cardiac disease
Due to the possibility of developing hyperkalemia and subsequent cardiac arrest, potassium phosphate should be used cautiously in patients with cardiac disease. Use particular caution when administering to a digitalized patient.
Burns
Due to the possibility of developing hyperkalemia and subsequent cardiac arrest, potassium phosphate should be used cautiously in patients with extensive tissue breakdown (e.g., severe burns).
Adrenal insufficiency, hypoparathyroidism, muscle channelopathy, pancreatitis
Use caution when considering potassium phosphate in patients who have severe adrenal insufficiency (Addison's disease), myotonia congenita (muscle channelopathy), hypoparathyroidism, or acute pancreatitis.
Osteomalacia
Potassium phosphate should be administered cautiously to patients who have osteomalacia (rickets), which may be associated with hyperphosphatemia and/or hypocalcemia. While rickets may benefit from some phosphate therapy, high serum phosphate concentrations may increase the incidence of extra-skeletal calcification.
Pregnancy
Animal reproduction studies have not been conducted with potassium phosphate. It is unknown if potassium phosphate can cause fetal harm when administered during pregnancy or can affect reproduction capacity. Potassium phosphate should only be used during pregnancy if clearly needed.
Breast-feeding
Maternal phosphorous intake during lactation appears to have no significant effect on phosphorus concentrations normally found in human milk. There appears to be no apparent ill effect of maternal supplementation, when required, on the infant during breast-feeding.
ADVERSE REACTIONS
Severe
muscle paralysis / Delayed / Incidence not known
seizures / Delayed / Incidence not known
AV block / Early / Incidence not known
hyperkalemia / Delayed / Incidence not known
cardiac arrest / Early / Incidence not known
aluminum toxicity / Delayed / Incidence not known
Moderate
hypocalcemia / Delayed / Incidence not known
hypertension / Early / Incidence not known
dyspnea / Early / Incidence not known
hyperphosphatemia / Delayed / Incidence not known
confusion / Early / Incidence not known
tetany / Early / Incidence not known
hypotension / Rapid / Incidence not known
phlebitis / Rapid / Incidence not known
osteomalacia / Delayed / Incidence not known
bone pain / Delayed / Incidence not known
Mild
tremor / Early / Incidence not known
weakness / Early / Incidence not known
muscle cramps / Delayed / Incidence not known
paresthesias / Delayed / Incidence not known
injection site reaction / Rapid / Incidence not known
abdominal pain / Early / Incidence not known
diarrhea / Early / Incidence not known
nausea / Early / Incidence not known
vomiting / Early / Incidence not known
arthralgia / Delayed / Incidence not known
DRUG INTERACTIONS
Monograph content under development
PREGNANCY AND LACTATION
Pregnancy
Animal reproduction studies have not been conducted with potassium phosphate. It is unknown if potassium phosphate can cause fetal harm when administered during pregnancy or can affect reproduction capacity. Potassium phosphate should only be used during pregnancy if clearly needed.
Maternal phosphorous intake during lactation appears to have no significant effect on phosphorus concentrations normally found in human milk. There appears to be no apparent ill effect of maternal supplementation, when required, on the infant during breast-feeding.
MECHANISM OF ACTION
Phosphorus homeostasis
Phosphorus has numerous functions in the human body. In addition to its well-known role as a structural component of teeth and bone, phosphorus also serves as a buffer in intracellular and renal tubular fluids, and is an essential element of nucleic acids, phospholipid cell membranes, and phosphoproteins. Phospholipids present in cell membranes serve as regulators of solute transport into and out of cells. Phosphoproteins are required for mitochondrial function. Other functions of phosphorus include regulation of the intermediary metabolism of carbohydrates, fats, and proteins; regulation of enzymatic reactions including glycolysis, ammoniagenesis, 1-hydroxylation of 25-hydroxyvitamin D; and regulation of the oxygen-carrying capacity of hemoglobin.
Phosphorus is present in high-energy adenosine triphosphate (ATP) bonds, which fuel a variety of physiological processes, including muscle contractions, neurologic function, and electrolyte transport, as well as other important biochemical reactions. Intracellular inorganic phosphate serves as the phosphorus source from which ATP is resynthesized. The prime determinant of intracellular inorganic phosphate is extracellular inorganic phosphate.
The relationship between phosphorus and calcium is a reciprocal one and is regulated partially by parathyroid hormone. Parathyroid hormone decreases the reabsorption of phosphate by the kidney, thereby lowering phosphate levels. The hormone stimulates an increase in calcium levels by increasing bone resorption, gut calcium absorption, and reabsorption of calcium in renal tubules. When serum phosphorus levels are high, serum calcium levels are generally low, and vice versa.
Potassium homeostasis
Potassium is the primary intracellular cation. It plays a major role in muscle and nerve cell electrodynamics. Its concentration inside the cell (roughly 150 to 160 mEq/L) is 25 to 35 times greater than extracellular concentrations.
Urinary acidification
Phosphates are excreted at the distal renal tubule where hydrogen ion is exchanged for sodium ion causing a decrease in urine pH.
PHARMACOKINETICS
Potassium phosphate is administered intravenously or orally. The primary route of phosphate excretion is renal. More than 80% of an administered dose is excreted by the kidneys. Fecal excretion accounts for the remainder. Normal plasma concentrations of phosphorus are between 2.5 and 4.5 mg/dL in adults. In pediatric patients, normal plasma concentrations of phosphorus are higher than adults due to the demands of physical growth and vary by age.
Neonates: 4.8 to 8.2 mg/dL
Children 1 to 3 years: 3.8 to 6.5 mg/dL
Children 4 to 11 years: 3.7 to 5.6 mg/dL
Children and Adolescents 12 to 15 years: 2.9 to 5.4 mg/dL
Adolescents 16 years and older: 2.7 to 4.7 mg/dL
Oral Route
Following oral administration, phosphate is absorbed via an active, energy-dependent process. In general, in adults, about two thirds of orally administered phosphate is absorbed from the bowel. Due to the formation of insoluble complexes, foods or drugs containing large amounts of calcium or aluminum decrease the amount of phosphate absorbed. The absorption of phosphate is most favorable when phosphate and calcium are administered in equal amounts (as in milk). Phosphate absorption is also stimulated by vitamin D.