Citrates
Drug class: Antineoplastic Agents
Usage of Citrates
Preparations containing sodium citrate and citric acid are especially useful when administration of potassium salts is undesirable or contraindicated, while those containing potassium citrate and citric acid are used when administration of sodium salts is undesirable or contraindicated.
Alkalinization of Urine
Citrates are used for alkalinization of urine (as alternatives to sodium bicarbonate) in conditions where long-term maintenance of an alkaline urine is desirable (e.g., management of uric acid and cystine calculi of the urinary tract).
Chronic Metabolic Acidosis
Citrates are used for management of chronic metabolic acidosis associated with conditions such as chronic renal insufficiency or renal tubular acidosis.
Adjuvant in Gout Therapy
Citrates are used as adjuvants to uricosuric agents in gout therapy.
Prevention of Milk Curdling
Sodium citrate has been used to alter cow’s milk so that large hard curds are not formed in the stomach of feeding infants† [off-label].
Gastric Acid Neutralization
Some citrate salts (e.g., sodium citrate and citric acid) also used for buffering and neutralizing gastric hydrochloric acid.
Compounding Uses
Sodium citrate and citric acid may be used as a buffer to maintain an approximate pH in various extemporaneous formulations. (See Compatibility under Stability.)
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How to use Citrates
General
Administration
Oral Administration
Dilute oral citrate solutions with adequate amounts of water prior to administration to minimize the risk of GI complications, and follow with additional water after administration; enhance palatability by chilling the solution before administration.
Reconstitute contents of single-dose packets containing potassium citrate and citric acid for oral solution with cool water or juice prior to administration; give additional water or juice after administration.
Administer oral citrate solutions after meals to avoid the saline laxative effect of the drugs as well as upset stomach.
Shake oral solutions well before use, unless otherwise directed.
ReconstitutionReconstitute contents of single-dose packets containing potassium citrate and citric acid for oral solution with at least 180 mL of cool water or juice prior to administration.
Dosage
Pediatric Patients
General Pediatric Dosage Potassium Citrate and Citric Acid OralUsually, 5–15 mL of solution, diluted with 1/2 glass of water, after meals and at bedtime.
Do not use single-dose packets of potassium citrate and citric acid for oral solution in pediatric patients, since dosage for these patients can be more easily regulated with the commercially available oral solution. Individualize dosage according to the patient’s tolerance and response.
Sodium Citrate and Citric Acid OralChildren ≥2 years of age: Usually, 5–15 mL of solution, diluted in 30–90 mL of water, after meals and at bedtime; individualize dosage according to patient’s tolerance and response. Consult a clinician for use in children <2 years of age.
Tricitrates OralUsually, 5–15 mL 4 times daily, after meals and at bedtime; individualize dosage according to patient’s tolerance and response.
Prevention of Milk Curdling Sodium Citrate OralPrevention of the formation of large curds in the stomach of feeding infants: Add 100 mg of sodium citrate to each 30 mL of cow’s milk.
Adults
General Adult Dosage Potassium Citrate and Citric Acid OralUsually, 15–30 mL of solution, diluted with 1 glass of water, after meals and at bedtime. The usual dosage of potassium citrate and citric acid for oral solution is one single-dose packet (containing 3300 mg of potassium citrate monohydrate and 1002 mg of citric acid monohydrate), reconstituted as directed 4 times daily, after meals and at bedtime. Individualize dosage according to patient’s tolerance and response.
Sodium Citrate OralUsually, 1–2 g every 2–4 hours as necessary for alkalinization effect.
Sodium Citrate and Citric Acid OralUsually, 10–30 mL of solution, diluted in 30–90 mL of water, after meals and at bedtime. Individualize dosage according to patient’s tolerance and response.
Tricitrates OralUsually, 15–30 mL of solution diluted in water 4 times daily, after meals and at bedtime. Individualize dosage according to the patient’s tolerance and response.
Gastric Acid Neutralization Sodium Citrate and Citric Acid Oral15 mL of solution, diluted in 15 mL of water, taken as a single dose.
Warnings
Contraindications
Warnings/Precautions
Warnings
Electrolyte and Acid-Base DisturbancesPotassium-containing formulations: Large doses may cause hyperkalemia and alkalosis, especially in patients with renal impairment. Listlessness, weakness, mental confusion, and tingling of the extremities may be associated with hyperkalemia.
Sodium-containing formulations: Excessive doses may cause metabolic alkalosis, especially in patients with hypocalcemia or renal impairment. Possible tetany or depression of the heart associated with decreased ionized calcium concentrations may occur with large doses.
General Precautions
Concomitant DiseaseSodium-containing formulations: Use with extreme caution in patients with low urine output (unless patient is closely supervised), CHF, hypertension, renal dysfunction, peripheral or pulmonary edema, or toxemia of pregnancy.
Potassium-containing formulations: Use with extreme caution in patients in whom excessive potassium may cause deleterious effects.
Adequate Patient Evaluation and MonitoringEvaluate patient’s clinical condition and monitor serum electrolyte concentrations and acid-base balance periodically, especially in patients with renal impairment, to avoid complications.
Laxative EffectsPossible saline laxative effects; dilute citrate solution with water and administer after meals to minimize this effect.
Specific Populations
PregnancyPotassium citrate: Category A.
LactationNot known whether potassium citrate is distributed into milk. Because potassium freely distributes into and out of milk, use of potassium citrate by nursing woman with normal plasma potassium concentrations should have no adverse effect on nursing infant; milk potassium concentrations may be increased in hyperkalemic women.
Renal ImpairmentUse citrates with caution in patients with renal impairment. Monitor serum electrolyte concentrations and acid-base balance to avoid complications (see Warnings/Precautions under Cautions). Manufacturers state that citrates are contraindicated in patients with severe renal impairment (see Contraindications under Cautions).
Common Adverse Effects
Generally well tolerated at recommended dosages in patients with normal renal function and urine output. (See Warnings under Cautions.)
What other drugs will affect Citrates
Specific Drugs
Drug
Interaction
Comments
ACE inhibitors
Potential for hyperkalemia and toxicity with citrate preparations containing potassium
Amphetamines
Urinary alkalinization may decrease renal elimination of amphetamines
Avoid concomitant use, especially in amphetamine overdosage
Antacids (aluminum-containing)
Increased GI absorption of aluminum; risk of aluminum toxicity in patients with chronic kidney disease receiving citrates and aluminum-containing drugs
Avoid concomitant use in patients with chronic kidney disease; sodium bicarbonate may be an alternative if aluminum-containing phosphate binders required
Cardiac glycosides
Potential for toxicity
Chlorpropamide
Urinary alkalinization may increase renal elimination of chlorpropamide
Diuretics, potassium-sparing
Potential for hyperkalemia and toxicity with citrate preparations containing potassium
Eplerenone
Potential for hyperkalemia and toxicity with citrate preparations containing potassium
Lithium
Urinary alkalinization may increase renal lithium clearance
Potassium-containing drugs
Potential for hyperkalemia and toxicity with citrate preparations containing potassium
Pseudoephedrine
Urinary alkalinization may decrease elimination of pseudoephedrine
Pseudoephedrine dosage reduction may be needed
Quinidine
Urinary alkalinization may decrease elimination of quinidine
Monitor ECGs and serum quinidine concentrations if citrate therapy is initiated or discontinued in a patient receiving a stable quinidine dosage
Salicylates
Urinary alkalinization may increase renal elimination of salicylates; possible decreased therapeutic and toxic effects of salicylates
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