VA Class:TN400
Citrates (i.e., potassium citrate and citric acid, sodium citrate, sodium citrate and citric acid, tricitrates) are alkalinizing agents.104, 105, 106, 107, 108, 109
Alkalinizing Alternatives to Sodium Bicarbonate
Administration of sodium citrate and other citrate preparations appears to be associated with formation of bicarbonate; therefore, the drugs are used as alkalinizing agents.
Oral citrate solutions, including potassium citrate and citric acid, sodium citrate and citric acid, and tricitrates, are used as alkalinizing agents in conditions where long-term maintenance of an alkaline urine is desirable and in the management of chronic metabolic acidosis associated with conditions such as chronic renal insufficiency or renal tubular acidosis.104, 105, 106, 107, 108, 109, 111
Selection of a specific preparation may in part be determined by the potassium and sodium contents. Preparations containing sodium citrate and citric acid are especially useful when administration of potassium salts is undesirable or contraindicated,105, 109 while those containing potassium citrate and citric acid are used when administration of sodium salts is undesirable or contraindicated.107, 108, 111 Unlike sodium bicarbonate solution, these preparations are generally considered highly palatable and pleasant tasting, and may be particularly useful as an alkalinizing agent in patients who do not tolerate the taste of sodium bicarbonate oral solution.
Potassium citrate and citric acid oral solution and tricitrates oral solution are used as adjuvant therapy to uricosuric agents in gout therapy.106, 107, 108, 111, 112
Sodium citrate has been used to alter cow's milk so that large hard curds are not formed in the stomach of feeding infants†.
Citrate preparations (i.e., potassium citrate and citric acid, sodium citrate, sodium citrate and citric acid, tricitrates) are administered orally.104, 105, 106, 107, 108, 109, 111, 112 Oral citrate solutions should be diluted with adequate amounts of water prior to administration to minimize the risk of GI complications, and followed by additional water after administration;104, 105, 106, 108, 109, 111, 112 palatability may be enhanced by chilling the solution before administration.109 For reconstitution of potassium citrate and citric acid for oral solution in single-dose packets, the contents of one packet should be mixed thoroughly with at least 180 mL of cool water or juice prior to administration and followed by additional water or juice after administration.100, 108 Oral citrate solutions should preferably be taken after meals to avoid the saline laxative effect of the drug.105, 106, 107, 108, 109, 111, 112
Potassium Citrate and Citric Acid
The usual adult dosage of potassium citrate and citric acid solution is 15-30 mL after meals and at bedtime.107, 111 The usual dosage of potassium citrate and citric acid solution in children is 5-15 mL after meals and at bedtime.107, 111 The usual adult 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.100, 108 The single-dose packets of potassium citrate and citric acid for oral solution are not recommended for pediatric use, since dosage for these patients can be more easily regulated with the commercially available oral solution.100, 108 Dosage should be individualized according to the patient's tolerance and response.
The usual adult dosage of sodium citrate as an alkalinizing agent is 1-2 g every 2-4 hours as necessary.
To prevent formation of large curds in the stomach of feeding infants, 100 mg of sodium citrate has been added to each 30 mL of cow's milk.
Sodium Citrate and Citric Acid
The usual adult dosage of sodium citrate and citric acid solution is 10-30 mL,104 diluted in 30-90 mL of water, after meals and at bedtime.104, 105 The usual dosage of sodium citrate and citric acid solution in children 2 years of age or older is 5-15 mL of solution, diluted in 30-90 mL of water, after meals and at bedtime.105, 109 A clinician should be consulted for use of the drug in children younger than 2 years of age.105, 109 Dosage should be individualized according to the patient's tolerance and response.
Sodium citrate and citric acid may be used as a buffer to maintain an approximate pH in various extemporaneous formulations. Addition of the following concentration of the drugs should generally produce a solution buffered to the approximate pH listed:
pH | Citric Acid Monohydrate g/L | Sodium Citrate Dihydrate g/L |
|---|---|---|
2.5 | 64.4 | 7.8 |
3.0 | 57.4 | 17.6 |
3.5 | 47.6 | 31.4 |
4.0 | 40.6 | 41.2 |
4.5 | 30.8 | 54.9 |
5.0 | 19.6 | 70.6 |
5.5 | 9.8 | 84.3 |
6.0 | 4.2 | 92.1 |
6.5 | 1.8 | 95.6 |
Adapted from Schumacher GE. Buffer formulations. Am J Hosp Pharm . 1966; 23:628-9.
The usual adult dosage of tricitrates solution is 15-30 mL diluted in water 4 times daily, after meals and at bedtime.106, 112 The usual dosage of tricitrates solution in children is 5-15 mL 4 times daily, after meals and at bedtime.106, 112 Dosage should be individualized according to the patient's tolerance and response.
Oral citrate preparations generally are well tolerated when given in the usual dosages to patients with normal renal function and urine output.104, 105, 108, 109 Excessive doses of sodium-containing formulations may cause metabolic alkalosis, especially in patients with renal dysfunction or hypocalcemia.105, 109 Large doses also may cause tetany or depression of the heart associated with decreasing ionized calcium concentrations. Large doses of potassium-containing formulations may cause hyperkalemia and alkalosis, particularly in patients with impaired renal function.108, 111 Listlessness, weakness, mental confusion, and paresthesia of the extremities may be associated with hyperkalemia.108, 111, 112 Oral citrate preparations may have a saline laxative effect when administered orally.
Precautions and Contraindications
To avoid complications, the clinical condition of the patient should be evaluated and laboratory determinations (e.g., serum electrolytes, acid-base balance) obtained periodically during therapy with oral citrate preparations, especially in patients with renal disorders.104, 105, 108, 109 Patients with renal impairment are at risk of developing hypernatremia or alkalosis in the presence of hypocalcemia.104, 105
Sodium-containing citrate preparations should be used with caution in patients with low urine output unless the patient is closely supervised during therapy.105, 109, 112 Citrate preparations containing sodium should be used with extreme caution in patients with congestive heart failure, hypertension, renal dysfunction, peripheral or pulmonary edema, or toxemia of pregnancy.105, 109, 112 Citrate preparations containing potassium should be used with extreme caution in patients in whom excessive potassium may have a deleterious effect.
Sodium citrate and citric acid oral solution (Cytra-2, Bicitra®) is contraindicated in patients receiving a sodium-restricted diet and in those with severe renal impairment.105, 109 Tricitrates oral solution is contraindicated in patients with severe renal impairment with azotemia or oliguria, untreated Addison's disease, or severe myocardial damage.112 Sodium citrate and citric acid (Oracit®) is contraindicated in patients with severe renal impairment, oliguria or azotemia, untreated Addison's disease, adynamia episodica hereditaria, acute dehydration, heat cramps, anuria, severe myocardial damage, and hyperkalemia.104 Potassium citrate and citric acid oral solution and potassium citrate and citric acid for oral solution are also contraindicated in patients with adynamia episodica hereditaria, acute dehydration, heat cramps, anuria, severe myocardial damage, or hyperkalemia (from any cause).108, 111
Controlled studies to date in pregnant women receiving potassium citrate have not shown a risk to the fetus in the first trimester of pregnancy and there is no evidence of risk in subsequent trimesters.110
It is not known whether potassium citrate is distributed into milk.110 Because potassium freely distributes into and out of milk, use of potassium citrate by a nursing woman with normal plasma potassium concentrations should have no adverse effect on the nursing infant; milk potassium concentrations may be increased in hyperkalemic women.110
Concomitant use of citrate preparations and aluminum-containing antacids may increase GI absorption of aluminum.113, 114, 115 In patients with chronic kidney disease who require aluminum-containing phosphate binders, concomitant use of citrate preparations should be avoided because of the risk of aluminum absorption and potential toxicity with concomitant use.105, 109, 112, 114 Sodium bicarbonate may be an alternative to citrates if aluminum-containing phosphate binders are required.113, 115
The potential for toxicity exists in patients receiving cardiac glycosides concomitantly with citrate preparations.108, 111, 112
Drugs Affecting the Renin-Angiotensin-Aldosterone System
Concomitant use of potassium-containing citrate preparations with an angiotensin converting-enzyme (ACE) inhibitor or mineralocorticoid (aldosterone) receptor antagonist (e.g., eplerenone, spironolactone) may increase serum potassium concentrations and increase the risk of hyperkalemia and associated toxicity.108, 111, 112, 116
Drugs Increasing Serum Potassium Concentrations
Concomitant administration of potassium-containing citrate preparations with potassium-sparing diuretics (e.g., amiloride, triamterene) or potassium-containing agents may increase serum potassium concentrations and increase the risk of hyperkalemia and associated toxicity.108, 111, 112, 116
Drugs with pH-dependent Urinary Excretion
Alkalinization of the urine with citrates may enhance urinary excretion and decrease therapeutic and toxic effects of salicylates.116 (For further information on the effects of alkalinizing agents on salicylate pharmacokinetics, see Drug Interactions: Acidifying and Alkalinizing Agents and also see Pharmacokinetics: Elimination, in the Salicylates General Statement 28:08.04.24.) Alkalinization of the urine with citrates also may enhance urinary excretion of chlorpropamide and lithium.116
Alkalinization of the urine with citrates may decrease urinary excretion of amphetamines, pseudoephedrine, and quinidine and increase serum concentrations of these drugs.116 Dosage reduction of pseudoephedrine may be necessary.116 Concomitant use of amphetamines and citrates should be avoided, especially in patients with amphetamine overdosage, since toxicity will be prolonged.116 If citrate therapy is initiated or discontinued in a patient receiving a stable quinidine dosage regimen, ECGs and serum quinidine concentrations should be monitored.116
Citrates (i.e., potassium citrate and citric acid, sodium citrate, sodium citrate and citric acid, tricitrates) are alkalinizing agents.105, 108, 109, 111 Metabolism of these drugs appears to be associated with formation of bicarbonate.105, 108, 109, 111 Citrates are extensively metabolized, and less than 5% of an oral dose is excreted in urine unchanged.104, 105 108, 109
Sodium citrate has anticoagulant activity. Sodium citrate prevents the clotting of blood by forming an undissociated calcium citrate complex, making calcium unavailable to the clotting mechanism. Anticoagulant sodium citrate solution, when added to blood, prevents the clotting of blood and the crenation or swelling of cells. The sterile solution is used as an anticoagulant for banked blood for transfusion and to prepare citrated human plasma and blood for fractionation.
Sodium citrate prevents the curdling of milk by rennin, and has been used for this purpose to alter cow's milk so that large hard curds are not formed in the stomach of feeding infants.
Citrates (i.e., potassium citrate and citric acid, sodium citrate, sodium citrate and citric acid, tricitrates) are alkalinizing agents.
Citric acid occurs as colorless, translucent crystals or as a white, granular to fine, crystalline powder. The drug is odorless or practically odorless and has a strongly acidic taste. Citric acid may occur as the anhydrous form or may contain 1 molecule of water; concentration is expressed in terms of anhydrous citric acid. Citric acid is very soluble in water and freely soluble in alcohol.
Potassium citrate occurs as transparent crystals or as a white, granular powder. The drug is odorless and has a cooling, saline taste. Potassium citrate may occur as the anhydrous form or may contain 1 molecule of water; concentration is expressed in terms of anhydrous potassium citrate. The drug is freely soluble in water and almost insoluble in alcohol.
Potassium Citrate and Citric Acid for Oral Solution
Potassium citrate and citric acid for oral solution contains potassium citrate and citric acid in a sugar-free base.100 Each single-dose packet contains 3300 mg of potassium citrate monohydrate and 1002 mg of citric acid monohydrate and when reconstituted as directed, each single-dose packet provides 2 mEq of potassium, which is equivalent to 2 mEq of bicarbonate.100 Each packet of potassium citrate and citric acid for oral solution is equivalent to 15 mL of the potassium citrate and citric acid oral solution.100
Potassium Citrate and Citric Acid Oral Solution
Potassium citrate and citric acid oral solution is a solution of potassium citrate and citric acid in a suitable aqueous medium. Each 100 mL of potassium citrate and citric acid oral solution contains 7.55-8.35 g of potassium, 12.18-13.46 g of citrate (equivalent to 20.9-23.1 g of potassium citrate monohydrate), and 6.34-7.02 g of citric acid monohydrate. Each mL of potassium citrate and citric acid oral solution contains about 2 mEq of potassium and provides approximately 2 mEq of bicarbonate. Potassium citrate and citric acid oral solution has a pH of 4.9-5.4.
Sodium citrate occurs as colorless crystals or as a white, crystalline powder. Sodium citrate may occur as the anhydrous form or may contain 2 molecules of hydration; concentration is expressed in terms of anhydrous sodium citrate. The hydrous form of the drug is freely soluble in water, very soluble in boiling water, and insoluble in alcohol.
Sodium Citrate and Citric Acid Oral Solution
Sodium citrate and citric acid oral solution is a solution of sodium citrate and citric acid in a suitable aqueous medium and occurs as a clear solution having the color of any added preservative or flavoring agent. Each 100 mL of sodium citrate and citric acid oral solution contains 2.23-2.46 g of sodium, 6.11-6.75 g of citrate (equivalent to 9.5-10.5 g of sodium citrate dihydrate), and 6.34-7.02 g of citric acid monohydrate. Each mL of sodium citrate and citric acid oral solution contains about 1 mEq of sodium and provides approximately 1 mEq of bicarbonate. Sodium citrate and citric acid oral solution has a pH of 4-4.4.
Tricitrates oral solution is a solution of citric acid, potassium citrate, and sodium citrate in a suitable aqueous medium. Each 100 mL of tricitrates oral solution contains 6.34-7.02 g of citric acid monohydrate, 12.20-13.48 g of citrate as potassium citrate and sodium citrate, 3.78-4.18 g of potassium (equivalent to 10.45-11.55 g of potassium citrate monohydrate), and 2.23-2.46 g of sodium (equivalent to 9.5-10.5 g of sodium citrate dihydrate. Each mL of tricitrates oral solution contains about 1 mEq each of potassium and sodium and provides approximately 2 mEq of bicarbonate. Tricitrates oral solution has a pH of 4.9-5.4.
The hydrous form of citric acid is efflorescent in dry air.
Potassium citrate is deliquescent when exposed to moist air.
Potassium Citrate and Citric Acid for Oral Solution
Potassium citrate and citric acid for oral solution should be protected from excessive heat and freezing.100, 108
Potassium Citrate and Citric Acid Oral Solution
Potassium citrate and citric acid oral solution should be stored in tight, light-resistant container at 20-25°C and protected from excessive heat and freezing.107, 111
Sodium Citrate and Citric Acid Oral Solution
Sodium citrate and citric acid oral solution generally should be stored in tight containers and protected from freezing or excessive heat.104, 105, 109 The manufacturer's labeling should be consulted for specific storage recommendations.
Tricitrates oral solution should be stored in tight container at 20-25°C and protected from excessive heat and freezing.106, 112
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | For solution | Potassium Citrate Monohydrate 3300 mg and Citric Acid Monohydrate 1002 mg per packet | Cytra-K Crystals | Cypress |
Solution | Potassium Citrate Monohydrate 1100 mg/5 mL and Citric Acid Monohydrate 334 mg/5 mL* | Cytra-K | Cypress | |
Potassium Citrate Monohydrate and Citric Acid Monohydrate Solution |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Bulk | Powder |
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Solution (Shohl's Solution) | Hydrous Sodium Citrate 490 mg/5 mL and Citric Acid 640 mg/5 mL | Oracit® | Carolina Medical |
Sodium Citrate Dihydrate 500 mg (321.5 mg of citrate) per 5 mL and Citric Acid Monohydrate 334 mg/5 mL | Bicitra® | Ortho-McNeil | ||
Cytra-2 | Cypress |
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Solution | Citric Acid Monohydrate 334 mg/5 mL, Potassium Citrate Monohydrate 550 mg/5 mL, and Sodium Citrate Dihydrate 500 mg (321.5 mg of citrate) per 5 mL* | Citric Acid Monohydrate, Potassium Citrate Monohydrate, and Sodium Citrate Dihydrate Solution | |
Cytra-3 Syrup | Cypress |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
100. Alza Pharmaceuticals. Polycitra®-K (potassium citrate and citric acid for oral solution) crystals prescribing information. Mountain View, CA; Feb 2000. From the Alza website ([Web])
101. Alza Pharmaceuticals. Polycitra®-K (potassium citrate and citric acid) oral solution prescribing information. Mountain View, CA; Apr 1998. From the Alza website ([Web])
102. Alza Pharmaceuticals. Bicitra® (potassium citrate and citric acid) oral solution prescribing information. Mountain View, CA; Apr 1998. From the Alza website ([Web])
103. Alza Pharmaceuticals. Polycitra®-LC and syrup (tricitrates) oral solution prescribing information. Mountain View, CA; Apr 1998. From the Alza website ([Web])
104. Carolina Medical Products. ORACIT® oral citrate (Shohl';s) solution prescribing information. Farmville, NC; 1986 May.
105. Cypress Pharmaceuticals. Cytra-2®(sodium citrate and citric acid) oral solution prescribing information.Madison, MS; 2006 Mar.
106. Cypress Pharmaceuticals. Cytra-3® (potassium citrate, sodium citrate, and citric acid) oral syrup prescribing information.Madison, MS; 1998 Jul.
107. Cypress Pharmaceuticals. Cytra-K Oral Solution (potassium citrate and citric acid) prescribing information. Madison, MS; 1998 Jun.
108. Cypress Pharmaceuticals. Cytra-K Crystals (potassium citrate and citric acid for oral solution) prescribing information. Madison, MS; 1997 Dec .
109. Ortho-McNeil Pharmaceutical. Bicitra® (sodium citrate and citric acid) oral solution prescribing information. Raritan, NJ; 2005 Mar.
110. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. Lippincott Williams & Wilkins: Philadelphia, PA; 2008.
111. Pai Pharmaceutical Associates. Potassium citrate and citric acid oral solution prescribing information. Greenville, SC; 2000 Jun.
112. Pai Pharmaceutical Associates. Potassium citrate, sodium citrate, and citric acid oral solution prescribing information. Greenville, SC; 1999 Dec.
113. Rudy D, Sica DA, Comstock T et al. Aluminum-citrate interaction in end-stage renal disease. Int J Artif Organs . 1991; 14:625-9. [PubMed 1748529]
114. KDOQI, National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. Am J Kidney Dis . 2005; 46(4 Suppl 1):S1-21. Available at [Web]. Accessed 2008 Jun 13.
115. Walker JA, Sherman RA, Cody RP. The effect of oral bases on enteral aluminum absorption. Arch Intern Med . 1990; 150:2037-9. [PubMed 2171446]
116. Tatro DS, ed. Drug interaction facts. St. Louis: Wolters Kluwer Health; 2008 (Apr):202he, 313b, 470, 579, 580, 608, 620b, 672, 684a.