Potassium Phosphate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, solution:

Generic: Potassium 4.4 mEq and phosphorus 3 mmol per mL (5 mL) [equivalent to potassium 170 mg and elemental phosphorus 93 mg per mL]

Tablet, Oral:

K-Phos: 500 mg [scored]

Pharmacology

Mechanism of Action

Phosphorus in the form of organic and inorganic phosphate has a variety of important biochemical functions in the body and is involved in many significant metabolic and enzymatic reactions in almost all organs and tissues. It exerts a modifying influence on the steady state of calcium levels, a buffering effect on acid-base equilibrium and a primary role in the renal excretion of hydrogen ion.

Potassium is the major cation of intracellular fluid and is essential for the conduction of nerve impulses in heart, brain, and skeletal muscle; contraction of cardiac, skeletal and smooth muscles; maintenance of normal renal function, acid-base balance, carbohydrate metabolism, and gastric secretion.

Pharmacokinetics/Pharmacodynamics

Absorption

Oral: Well absorbed from upper GI tract

Distribution

Enters cells via active transport from extracellular fluid

Excretion

Primarily urine (>80% to 90% of dose reabsorbed by the kidney); skin and feces (small amounts)

Use: Labeled Indications

Injection: Treatment and prevention of hypophosphatemia; Note: The concomitant amount of potassium must be calculated into the total electrolyte content. For each 1 mmol of phosphate, ~1.5 mEq of potassium will be administered. Therefore, if ordering 30 mmol of potassium phosphate, the patient will receive ~45 mEq of potassium.

Oral: To acidify the urine to lower urinary calcium concentrations; reduce odor and rash caused by ammonia in urine; to increase the antibacterial activity of methenamine

Contraindications

Injection: Hyperphosphatemia, hyperkalemia, hypocalcemia

Oral: Severe renal impairment (<30% of normal function); hyperkalemia, hyperphosphatemia; infected phosphate stones

Dosage and Administration

Dosing: Adult

Acute treatment of hypophosphatemia:

Note: If phosphate repletion is required and a phosphate product is not available at your institution, consider the use of sodium glycerophosphate pentahydrate (Glycophos) as a suitable substitute. Concentration and dosing are different from FDA-approved products; use caution when switching between products. Refer to Sodium Glycerophosphate Pentahydrate monograph.

Caution: The concomitant amount of potassium must be calculated into the total electrolyte content. For each 1 mmol of phosphate, ~1.5 mEq of potassium will be administered. Therefore, if ordering 30 mmol of potassium phosphate, the patient will receive ~45 mEq of potassium. With orders for IV phosphate, there is considerable confusion associated with the use of millimoles (mmol) versus milliequivalents (mEq) to express the phosphate requirement. The most reliable method of ordering IV phosphate is by millimoles, then specifying the potassium or sodium salt. Doses listed as mmol of phosphate.

Repletion of severe hypophosphatemia should be done IV because large doses of oral phosphate may cause diarrhea and intestinal absorption may be unreliable. Reserve intermittent IV infusion for severe depletion situations; may require continuous cardiac monitoring depending on potassium administration rate. Guidelines differ based on degree of illness, need/use of parenteral nutrition, and severity of hypophosphatemia. If potassium >4.0 mEq/L consider phosphate replacement strategy without potassium (eg, sodium phosphates). Patients with severe renal impairment were excluded from phosphate supplement trials. Note: 1 mmol phosphate = 31 mg phosphorus; 1 mg phosphorus = 0.032 mmol phosphate.

General replacement guidelines (Lentz 1978): IV:

Low dose, if serum phosphate losses are recent and uncomplicated: Initial: 0.08 mmol/kg over 6 hours

Intermediate dose, if serum phosphorus level <1 mg/dL (<0.32 mmol/L): Initial: 0.16 mmol/kg per dose over 6 hours

Note: The initial dose may be increased by 25% to 50% if the patient is symptomatic secondary to hypophosphatemia and lowered by 25% to 50% if the patient is hypercalcemic. Do not exceed the maximum dose of 0.24 mmol/kg/dose (or 16.9 mmol for a 70-kg patient).

Critically-ill adult patients receiving concurrent enteral/parenteral nutrition (Brown 2006; Clark 1995): IV: Note: Round doses to the nearest 7.5 mmol for ease of preparation. If administering with phosphate-containing parenteral nutrition, do not exceed 15 mmol/L within parenteral nutrition.

Low dose, serum phosphorus level 2.3 to 3 mg/dL (0.74 to 0.96 mmol/L): 0.16 to 0.32 mmol/kg over 4 to 6 hours

Intermediate dose, serum phosphorus level 1.6 to 2.2 mg/dL (0.51 to 0.71 mmol/L): 0.32 to 0.64 mmol/kg over 4 to 6 hours

High dose, serum phosphorus <1.5 mg/dL (<0.5 mmol/L): 0.64 to 1 mmol/kg over 8 to 12 hours

Obesity: May use adjusted body weight for patients weighing >130% of ideal body weight (and BMI<40 kg/m²) by using [IBW + 0.25 (actual body weight - IBW)].

Parenteral nutrition: IV: 10 to 15 mmol/1,000 kcal (Hicks, 2001) or 20 to 40 mmol/24 hours (Mirtallo 2004 [ASPEN guidelines])

Urine acidification: Oral: 1,000 mg 4 times daily

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: If phosphate repletion is required and a phosphate product is not available at your institution, consider the use of sodium glycerophosphate pentahydrate (Glycophos) as a suitable substitute. Concentration and dosing are different from FDA approved products; use caution when switching between products. Refer to sodium glycerophosphate pentahydrate monograph.

Caution: The concomitant amount of potassium must be calculated into the total electrolyte content. Each 1 mmol of phosphate provides ~1.5 mEq of potassium. With orders for IV phosphate, there is considerable confusion associated with the use of millimoles (mmol) versus milliequivalents (mEq) to express the phosphate requirement. The most reliable method of ordering IV phosphate is by millimoles, then specifying the potassium or sodium salt. Intravenous doses provided are as mmol of phosphate.

Phosphorus - Recommended Daily Allowance (RDA) and Estimated Average Requirement (EAR):

1 to 6 months: EAR: 3.2 mmol/day (adequate intake).

7 to 12 months: EAR: 8.9 mmol/day (adequate intake).

1 to 3 years:

RDA: 14.8 mmol/day.

EAR: 12.3 mmol/day.

4 to 8 years:

RDA: 16.1 mmol/day.

EAR: 13.1 mmol/day.

9 to 18 years:

RDA: 40.3 mmol/day.

EAR: 34 mmol/day.

19 to 30 years:

RDA: 22.6 mmol/day.

EAR: 18.7 mmol/day.

Hypophosphatemia, acute treatment: Hypophosphatemia does not necessarily equate with phosphate depletion. Hypophosphatemia may occur in the presence of low, normal, or high total body phosphate and conversely, phosphate depletion may exist with normal, low, or elevated levels of serum phosphate (Gaasbeek 2005). Repletion of severe hypophosphatemia should be done IV because large doses of oral phosphate may cause diarrhea and intestinal absorption may be unreliable. It is difficult to provide concrete guidelines for the treatment of severe hypophosphatemia because the extent of total body deficits and response to therapy are difficult to predict. Aggressive doses of phosphate may result in a transient serum elevation followed by redistribution into intracellular compartments or bone tissue. Guidelines differ based on degree of illness, need/use of TPN, and severity of hypophosphatemia. If hyperkalemia exists, consider phosphate replacement strategy without potassium (eg, sodium phosphates). Various regimens for replacement of phosphate in adults have been studied. The regimens below have only been studied in adult patients; however, many institutions have used them in children safely and successfully (ASPEN [Corkins 2015]). Patients with severe renal impairment were excluded from phosphate supplement adult trials. Note: 1 mmol phosphate = 31 mg phosphorus; 1 mg phosphorus = 0.032 mmol phosphate.

IV doses may be incorporated into the patient's maintenance IV fluids; intermittent IV infusion should be reserved for severe depletion situations; requires continuous cardiac monitoring. Note: Doses listed as mmol of phosphate.

Children and Adolescents: Note: There are no prospective studies of parenteral phosphate replacement in children. The following weight-based guidelines for adult dosing may be cautiously employed in pediatric patients (ASPEN [Corkins 2015]). Guidelines differ based on degree of illness, use of TPN, and severity of hypophosphatemia.

General replacement guidelines (Lentz 1978): Note: The initial dose may be increased by 25% to 50% if the patient is symptomatic secondary to hypophosphatemia and lowered by 25% to 50% if the patient is hypercalcemic.

Low dose: 0.08 mmol/kg over 6 hours; use if losses are recent and uncomplicated.

Intermediate dose: 0.16 to 0.24 mmol/kg over 4 to 6 hours; use if serum phosphorus level 0.5 to 1 mg/dL (0.16 to 0.32 mmol/L).

High dose: 0.36 mmol/kg over 6 hours; use if serum phosphorus <0.5 mg/dL (<0.16 mmol/L).

Patients receiving TPN (Clark 1995):

Low dose: 0.16 mmol/kg over 4 to 6 hours; use if serum phosphorus level 2.3 to 3 mg/dL (0.73 to 0.96 mmol/L).

Intermediate dose: 0.32 mmol/kg over 4 to 6 hours; use if serum phosphorus level 1.6 to 2.2 mg/dL (0.51 to 0.72 mmol/L).

High dose: 0.64 mmol/kg over 8 to 12 hours; use if serum phosphorus <1.5 mg/dL (<0.5 mmol/L).

Critically ill adult trauma patients receiving TPN (Brown 2006):

Low dose: 0.32 mmol/kg over 4 to 6 hours; use if serum phosphorus level 2.3 to 3 mg/dL (0.73 to 0.96 mmol/L).

Intermediate dose: 0.64 mmol/kg over 4 to 6 hours; use if serum phosphorus level 1.6 to 2.2 mg/dL (0.51 to 0.72 mmol/L).

High dose: 1 mmol/kg over 8 to 12 hours; use if serum phosphorus <1.5 mg/dL (<0.5 mmol/L).

Alternative method in critically ill patients (Kingston 1985):

Low dose: 0.25 mmol/kg over 4 hours; use if serum phosphorus level 0.5 to 1 mg/dL (0.16 to 0.32 mmol/L).

Moderate dose: 0.5 mmol/kg over 4 hours; use if serum phosphorus level <0.5 mg/dL (<0.16 mmol/L).

Parenteral nutrition, maintenance phosphorus requirement (ASPEN [Mirtallo 2004]):

Infants and Children ≤50 kg: IV: 0.5 to 2 mmol/kg/day of phosphorus as an additive to parenteral nutrition solution.

Children >50 kg and Adolescents: IV: 10 to 40 mmol/day of phosphorus as an additive to parenteral nutrition solution.

Dosing: Obesity

Refer to indication-specific dosing for obesity-related information (may not be available for all indications).

Reconstitution

In general, the dose, concentration of infusion, and rate of administration may be dependent on patient condition and specific institution policy. Intermittent infusion doses of potassium phosphate are typically prepared in 100 to 250 mL of NS or D₅W (usual phosphate concentration range: 0.15 to 0.6 mmol/mL) (Charron 2003; Rosen 1995). Suggested maximum concentrations:

Central line administration: 26.8 mmoL potassium phosphate/100 mL (40 mEq potassium/100 mL)

Peripheral line administration: 6.7 mmoL potassium phosphate/100 mL (10 mEq potassium/100 mL)

Observe the vial for the presence of translucent visible particles. Do not use vial if particles are present. Dilute in a compatible IV fluid.

Administration

IV: Injection must be diluted in appropriate IV solution and volume prior to administration. In general, the dose, concentration of infusion, and rate of administration may be dependent on patient condition/indication and specific institution policy. Must consider administration precautions for phosphate and potassium when prescribing.

For patients with severe symptomatic hypophosphatemia (ie, <1.5 mg/dL), may administer at rates up to 15 mmol phosphate/hour (this rate will deliver potassium at 22.5 mEq/hour) (Charron 2003). In patients with renal dysfunction and/or less severe hypophosphatemia, slower administration rates (eg, over 4 to 6 hours) or oral repletion is recommended. Potassium infusion rates >10 mEq/hour should be administered via central line (minimizes burning and phlebitis). ECG monitoring is recommended for potassium infusions >10 mEq/hour.

Vesicant/irritant (may depend on concentration); ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave needle/cannula in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote; remove needle/cannula; apply dry cold compresses (Hurst 2004; Reynolds 2014); elevate extremity.

Hyaluronidase: Intradermal or SubQ: Inject a total of 1 to 1.7 mL (15 units/mL) as five separate 0.2 to 0.3 mL injections (using a 25-gauge needle) into area of extravasation at the leading edge in a clockwise manner (MacCara 1983; Reynolds 2014; Zenk 1981).

Oral: Administer at mealtime and at bedtime. Dissolve tablets in 6 to 8 oz of water prior to administration to avoid GI injury. For best results, soak tablets in water for at least 2 to 5 minutes and stir. If any tablet particles remain undissolved, crush and stir vigorously to speed dissolution.

Storage

Injection: Store intact vials at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).

Oral: Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

Aliskiren: Potassium Salts may enhance the hyperkalemic effect of Aliskiren. Monitor therapy

Alpha-/Beta-Agonists (Indirect-Acting): Urinary Acidifying Agents may decrease the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Monitor therapy

Amantadine: Urinary Acidifying Agents may decrease the serum concentration of Amantadine. Monitor therapy

Amphetamines: Urinary Acidifying Agents may decrease the serum concentration of Amphetamines. Monitor therapy

Angiotensin II Receptor Blockers: Potassium Salts may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Potassium Salts may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy

Antacids: May decrease the serum concentration of Potassium Phosphate. Management: Consider separating administration of antacids and oral potassium phosphate by at least 2 hours to decrease risk of a significant interaction. Consider therapy modification

Burosumab: Phosphate Supplements may enhance the adverse/toxic effect of Burosumab. Avoid combination

Calcium Salts: May decrease the absorption of Phosphate Supplements. Management: This applies only to oral phosphate and calcium administration. Administering oral phosphate supplements as far apart from the administration of an oral calcium salt as possible may be able to minimize the significance of the interaction. Consider therapy modification

ChlorproPAMIDE: Urinary Acidifying Agents may increase the serum concentration of ChlorproPAMIDE. Monitor therapy

Drospirenone: Potassium Salts may enhance the hyperkalemic effect of Drospirenone. Monitor therapy

Eplerenone: May enhance the hyperkalemic effect of Potassium Salts. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Consider therapy modification

Erdafitinib: Serum Phosphate Level-Altering Agents may diminish the therapeutic effect of Erdafitinib. Management: Avoid coadministration of serum phosphate level-altering agents with erdafitinib before initial dose increase period based on serum phosphate levels (Days 14 to 21). Consider therapy modification

Heparin: May enhance the hyperkalemic effect of Potassium Salts. Monitor therapy

Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Potassium Salts. Monitor therapy

Iron Preparations: May decrease the absorption of Phosphate Supplements. Management: Administer oral phosphate supplements as far apart from the administration of an oral iron preparation as possible to minimize the significance of this interaction. Exceptions: Ferric Carboxymaltose; Ferric Derisomaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification

Magnesium Salts: May decrease the serum concentration of Phosphate Supplements. Management: Administer oral phosphate supplements as far apart from the administration of an oral magnesium salt as possible to minimize the significance of this interaction. Consider therapy modification

Mecamylamine: Urinary Acidifying Agents may decrease the serum concentration of Mecamylamine. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Phosphate Supplements. Management: Administer oral phosphate supplements as far apart from the administration of an iron-containing oral multivitamin as possible to minimize the significance of this interaction. Consider therapy modification

Nicorandil: May enhance the hyperkalemic effect of Potassium Salts. Monitor therapy

Potassium-Sparing Diuretics: Potassium Salts may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Consider therapy modification

Salicylates: Potassium Phosphate may increase the serum concentration of Salicylates. Monitor therapy

Sucralfate: May decrease the absorption of Phosphate Supplements. Management: This applies only to oral phosphate administration. Administering oral phosphate supplements at least 2 hours before sucralfate may reduce the significance of the interaction. Consider therapy modification

Adverse Reactions

Frequency not defined.

Cardiovascular: Bradycardia, cardiac arrhythmia, chest pain, ECG changes, edema, heart block, hypotension, localized phlebitis

Central nervous system: Confusion, lethargy, paralysis, paresthesia

Endocrine & metabolic: Hyperkalemia

Gastrointestinal: Diarrhea, nausea, stomach pain, vomiting

Genitourinary: Decreased urine output

Neuromuscular & skeletal: Tetany (with large doses of phosphate), weakness

Renal: Acute renal failure

Respiratory: Dyspnea

Warnings/Precautions

Concerns related to adverse effects:

• Extravasation: Vesicant/irritant (may depend on concentration); ensure proper catheter or needle position prior to and during infusion. Avoid extravasation.
• Hyperkalemia: Close monitoring of serum potassium concentrations is needed to avoid hyperkalemia; severe hyperkalemia may lead to muscle weakness/paralysis and cardiac conduction abnormalities (eg, heart block, ventricular arrhythmias, asystole).
• Laxative effect: A mild laxative effect may occur with oral use within the first few days of therapy; if the laxative effect persists to a self-limiting degree, consider reducing the dose or discontinue use until diarrhea improves.

Disease-related concerns:

• Acid/base disorders: Use with caution in patients with acid/base alterations; changes in serum potassium concentrations can occur during acid/base correction, monitor closely.
• Adrenal insufficiency: Use with caution in patients with adrenal insufficiency (eg, Addison disease); adrenal insufficiency requires close monitoring of serum potassium and phosphorus concentrations to avoid hyperkalemia and/or hyperphosphatemia.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease (eg, heart failure, cardiac arrhythmias); patients may be more susceptible to life-threatening cardiac effects associated with hyper/hypokalemia.
• Dehydration: Use with caution in patients with acute dehydration.
• Myotonia congenita: Use with caution in patients with myotonia congenita.
• Pancreatitis: Use with caution in patients with acute pancreatitis.
• Parathyroid disease: Use with caution in patients with hypoparathyroidism.
• Renal calculi: Patients with renal calculi may pass preformed stones when phosphate therapy is initiated.
• Renal impairment: Use with caution in patients with renal impairment; renal impairment requires close monitoring of serum potassium and phosphorus concentrations to avoid hyperkalemia and/or hyperphosphatemia. Oral tablets are contraindicated in patients with severe renal impairment.
• Rickets: Use with caution in patients with rickets; may increase the risk of extraskeletal calcification.
• Tissue breakdown: Use with caution in patients with extensive tissue breakdown (eg, severe burns).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Aluminum: The parenteral product may contain aluminum; toxic aluminum concentrations may be seen with high doses, prolonged use, or renal dysfunction. Premature neonates are at higher risk due to immature renal function and aluminum intake from other parenteral sources. Parenteral aluminum exposure of >4 to 5 mcg/kg/day is associated with CNS and bone toxicity; tissue loading may occur at lower doses (Federal Register 2002). See manufacturer's labeling.
• Oral administration: Tablets should be dissolved completely in water prior to administration to avoid GI injury due to administration of a concentrated potassium salt preparation.
• Parenteral administration: Use extreme caution when administering potassium phosphate parenterally; evaluate patient's renal function, cardiac and fluid status, and any factors contributing to altered potassium concentrations (eg, acidosis, alkalosis) prior to therapy. Closely monitor potassium and phosphate concentrations and response to therapy. Parenteral potassium may cause pain and phlebitis, requiring a decrease in infusion rate or potassium concentration.

Other warnings/precautions:

• Calcium/phosphate compatibility: Admixture of phosphate and calcium in IV fluids can result in calcium phosphate precipitation.

Monitoring Parameters

IV: Serum potassium, calcium, phosphorus, magnesium (to facilitate potassium repletion); cardiac monitor (if intermittent infusion or potassium infusion rates >0.5 mEq/kg/hour in children or >10 mEq/hour in adults); to assess adequate replacement, repeat serum potassium and phosphorus levels 2 to 4 hours after dose; renal function

Oral: Serum potassium, phosphorus, and calcium; renal function; serum salicylate concentration (in patients taking concomitant salicylates)

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. Phosphorus requirements are the same in pregnant and nonpregnant women (IOM 1997). Although this product is not used for potassium supplementation, adverse events have not been observed following use of potassium supplements in healthy women with normal pregnancies. Use caution in pregnant women with other medical conditions (eg, preeclampsia; may be more likely to develop hyperkalemia) (IOM 2004).

Patient Education

What is this drug used for?

Injection:

• It is used to treat or prevent low phosphate levels.

Tablets:

• It is used to lower the urine's pH.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Abdominal pain
• Nausea
• Vomiting

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• High potassium like abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, or numbness or tingling feeling.
• Low calcium like muscle cramps or spasms, numbness and tingling, or seizures.
• Severe diarrhea
• Bone pain
• Joint pain
• Feeling of heaviness in arms or legs
• Paralysis
• Chest pain
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

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