Citrate Salts, Citric Acid, Citric Acid Monohydrate, Potassium Citrate, Potassium Citrate Monohydrate, Sodium Citrate, Sodium Citrate and Citric Acid, Sodium Citrate Dihydrate

Class: Alkalinizing Agents
VA Class: TN400
CAS Number: 77-92-9
Brands: Bicitra, Cytra-2, Cytra-3, Cytra-K, Oracit

Introduction

Alkalinizing agents.104 105 106 107 108 109 a

Uses for Citrate Salts, Citric Acid, Citric Acid Monohydrate, Potassium Citrate, Potassium Citrate Monohydrate, Sodium Citrate, Sodium Citrate and Citric Acid, Sodium Citrate Dihydrate

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

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).104 106 107 108 109 111 112 a

Chronic Metabolic Acidosis

Citrates are used for management of chronic metabolic acidosis associated with conditions such as chronic renal insufficiency or renal tubular acidosis.104 105 106 107 108 109 111 114 a

Adjuvant in Gout Therapy

Citrates are used as adjuvants to uricosuric agents in gout therapy.108 111 112

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.a

Gastric Acid Neutralization

Some citrate salts (e.g., sodium citrate and citric acid) also used for buffering and neutralizing gastric hydrochloric acid.105 109

Compounding Uses

Sodium citrate and citric acid may be used as a buffer to maintain an approximate pH in various extemporaneous formulations.a (See Compatibility under Stability.)

Citrate Salts, Citric Acid, Citric Acid Monohydrate, Potassium Citrate, Potassium Citrate Monohydrate, Sodium Citrate, Sodium Citrate and Citric Acid, Sodium Citrate Dihydrate Dosage and Administration

General

  • Selection of a specific preparation may in part be determined by potassium and sodium content.a

  • Unlike sodium bicarbonate solution, citrate solutions generally are considered highly palatable and pleasant tasting, and may be particularly useful as alkalinizing agents in patients who do not tolerate the taste of sodium bicarbonate oral solution.105 106 107 108 109 111 112 a

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;104 105 106 108 109 111 112 a enhance palatability by chilling the solution before administration.109 a

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.100 108

Administer oral citrate solutions after meals to avoid the saline laxative effect of the drugs as well as upset stomach.105 106 107 108 109 111 112 a

Shake oral solutions well before use, unless otherwise directed.105 106 107

Reconstitution

Reconstitute 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.100 108

Dosage

Pediatric Patients

General Pediatric Dosage
Potassium Citrate and Citric Acid
Oral

Usually, 5–15 mL of solution, diluted with 1/2 glass of water, after meals and at bedtime.107 111

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.108 Individualize dosage according to the patient’s tolerance and response.a

Sodium Citrate and Citric Acid
Oral

Children ≥2 years of age: Usually, 5–15 mL of solution, diluted in 30–90 mL of water, after meals and at bedtime;105 109 individualize dosage according to patient’s tolerance and response.a Consult a clinician for use in children <2 years of age.105 109

Tricitrates
Oral

Usually, 5–15 mL 4 times daily, after meals and at bedtime;106 112 individualize dosage according to patient’s tolerance and response.a

Prevention of Milk Curdling
Sodium Citrate
Oral

Prevention 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.a

Adults

General Adult Dosage
Potassium Citrate and Citric Acid
Oral

Usually, 15–30 mL of solution, diluted with 1 glass of water, after meals and at bedtime.107 111 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.108 Individualize dosage according to patient’s tolerance and response.a

Sodium Citrate
Oral

Usually, 1–2 g every 2–4 hours as necessary for alkalinization effect.a

Sodium Citrate and Citric Acid
Oral

Usually, 10–30 mL of solution,104 diluted in 30–90 mL of water, after meals and at bedtime.104 105 Individualize dosage according to patient’s tolerance and response.a

Tricitrates
Oral

Usually, 15–30 mL of solution diluted in water 4 times daily, after meals and at bedtime.106 112 Individualize dosage according to the patient’s tolerance and response.a

Gastric Acid Neutralization
Sodium Citrate and Citric Acid
Oral

15 mL of solution, diluted in 15 mL of water, taken as a single dose.105

Cautions for Citrate Salts, Citric Acid, Citric Acid Monohydrate, Potassium Citrate, Potassium Citrate Monohydrate, Sodium Citrate, Sodium Citrate and Citric Acid, Sodium Citrate Dihydrate

Contraindications

  • Potassium citrate and citric acid (oral solution and for oral solution [Cytra-K Crystals]): Manufacturer states that preparation is contraindicated in severe renal impairment with oliguria or azotemia, untreated Addison’s disease, adynamia episodica hereditaria, acute dehydration, heat cramps, anuria, severe myocardial damage, or hyperkalemia (from any cause).108 111

  • Sodium citrate and citric acid oral solution (Bicitra, Cytra-2): Manufacturers state that preparations are contraindicated in patients requiring sodium-restricted diet and those with severe renal impairment.105 109

  • Sodium citrate and citric acid (Oracit): Manufacturer states that preparation is contraindicated in severe renal impairment, oliguria or azotemia, untreated Addison’s disease, adynamia episodica hereditaria, acute dehydration, heat cramp, anuria, severe myocardial damage, and hyperkalemia.104

  • Tricitrates oral solution (e.g., Cytra-3): Manufacturer states that preparation is contraindicated in severe renal impairment with oliguria and azotemia, untreated Addison’s disease, and severe myocardial damage.112 a

Warnings/Precautions

Warnings

Electrolyte and Acid-Base Disturbances

Potassium-containing formulations: Large doses may cause hyperkalemia and alkalosis, especially in patients with renal impairment.108 111 Listlessness, weakness, mental confusion, and tingling of the extremities may be associated with hyperkalemia.108 111 112

Sodium-containing formulations: Excessive doses may cause metabolic alkalosis, especially in patients with hypocalcemia or renal impairment.105 109 a Possible tetany or depression of the heart associated with decreased ionized calcium concentrations may occur with large doses.a

General Precautions

Concomitant Disease

Sodium-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.105 109 112

Potassium-containing formulations: Use with extreme caution in patients in whom excessive potassium may cause deleterious effects.a

Adequate Patient Evaluation and Monitoring

Evaluate patient’s clinical condition and monitor serum electrolyte concentrations and acid-base balance periodically, especially in patients with renal impairment, to avoid complications.104 105 108 109 a

Laxative Effects

Possible saline laxative effects; dilute citrate solution with water and administer after meals to minimize this effect.104 105 108 a

Specific Populations

Pregnancy

Potassium citrate: Category A.110

Lactation

Not known whether potassium citrate is distributed into milk.110 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.110

Renal Impairment

Use citrates with caution in patients with renal impairment.105 109 112 Monitor serum electrolyte concentrations and acid-base balance to avoid complications (see Warnings/Precautions under Cautions).104 105 108 109 111 112 a Manufacturers state that citrates are contraindicated in patients with severe renal impairment (see Contraindications under Cautions).104 105 108 109 111 112 a

Common Adverse Effects

Generally well tolerated at recommended dosages in patients with normal renal function and urine output.104 105 108 109 a (See Warnings under Cautions.)

Interactions for Citrate Salts, Citric Acid, Citric Acid Monohydrate, Potassium Citrate, Potassium Citrate Monohydrate, Sodium Citrate, Sodium Citrate and Citric Acid, Sodium Citrate Dihydrate

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Potential for hyperkalemia and toxicity with citrate preparations containing potassium108 111 112 116

Amphetamines

Urinary alkalinization may decrease renal elimination of amphetamines116

Avoid concomitant use, especially in amphetamine overdosage116

Antacids (aluminum-containing)

Increased GI absorption of aluminum;113 114 115 risk of aluminum toxicity in patients with chronic kidney disease receiving citrates and aluminum-containing drugs114

Avoid concomitant use in patients with chronic kidney disease;105 109 112 sodium bicarbonate may be an alternative if aluminum-containing phosphate binders required113 115

Cardiac glycosides

Potential for toxicity108 111 112

Chlorpropamide

Urinary alkalinization may increase renal elimination of chlorpropamide116

Diuretics, potassium-sparing

Potential for hyperkalemia and toxicity with citrate preparations containing potassium108 111 112 116

Eplerenone

Potential for hyperkalemia and toxicity with citrate preparations containing potassium116

Lithium

Urinary alkalinization may increase renal lithium clearance116

Potassium-containing drugs

Potential for hyperkalemia and toxicity with citrate preparations containing potassium108 112 116

Pseudoephedrine

Urinary alkalinization may decrease elimination of pseudoephedrine116

Pseudoephedrine dosage reduction may be needed116

Quinidine

Urinary alkalinization may decrease elimination of quinidine116

Monitor ECGs and serum quinidine concentrations if citrate therapy is initiated or discontinued in a patient receiving a stable quinidine dosage116

Salicylates

Urinary alkalinization may increase renal elimination of salicylates; possible decreased therapeutic and toxic effects of salicylates116

Citrate Salts, Citric Acid, Citric Acid Monohydrate, Potassium Citrate, Potassium Citrate Monohydrate, Sodium Citrate, Sodium Citrate and Citric Acid, Sodium Citrate Dihydrate Pharmacokinetics

Distribution

Extent

Not known whether potassium citrate is distributed into milk.110

Elimination

Metabolism

Metabolism of citrates appears to be associated with bicarbonate formation. 105 108 109 111 a

Elimination Route

Citrates are excreted in urine, mainly as metabolites; <5% of an oral dose is excreted in the urine unchanged.104 105 108 109 a

Stability

Storage

Oral

Solution

Potassium citrate and citric acid oral solutions (e.g., Cytra-K): Tight, light-resistant containers at 20–25°C; protect from excessive heat or freezing.107 111

Potassium citrate and citric acid for oral solution (Cytra-K Crystals): Protect from excessive heat or freezing.108

Sodium citrate and citric acid oral solution (Oracit): Well-closed containers at 15–30°C.104

Sodium citrate and citric acid oral solution (Cytra-2): Tight, light-resistant containers at 20–25°C; protect from freezing.105

Sodium citrate and citric acid oral solution (Bicitra): Tight containers; protect from freezing or excessive heat.109

Tricitrates oral solution (e.g., Cytra-3): Tight, light-resistant containers at 20–25°C; protect from excessive heat or freezing.106 112

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Oral

Solution

May use sodium citrate and citric acid as a buffer to maintain an approximate pH in various extemporaneous formulations.a In general, the addition of the following concentration of the drugs should produce a solution buffered to the approximate pH listed:

Adapted from Schumacher GE. Buffer formulations. Am J Hosp Pharm. 1966; 23:628-9.

Citrate Buffer

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

Actions

  • Potassium citrate is absorbed and then appears to be metabolized to potassium bicarbonate, resulting in systemic alkalinization.108 111

  • Sodium citrate is absorbed and then appears to be metabolized to sodium bicarbonate, resulting in systemic alkalinization.105 109

  • Sodium citrate has anticoagulant activity;a prevents the clotting of blood by forming an undissociated calcium citrate complex, making calcium unavailable to the clotting mechanism. a Anticoagulant sodium citrate solution, when added to blood, prevents the clotting of blood and the crenation or swelling of cells.a Sterile solution is used as an anticoagulant for banked blood for transfusion and to prepare citrated human plasma and blood for fractionation.a

  • Sodium citrate prevents the curdling of milk by rennin; has been used to alter cow’s milk so that large hard curds are not formed in the stomach of feeding infants.a

Advice to Patients

  • Importance of following instructions for dosage preparation, including reconstitution and/or dilution recommendations.104 105 106 107 108 109 (See Oral Administration under Dosage and Administration.)

  • Importance of taking drugs only as prescribed, unless otherwise instructed by a clinician.105 106 107 109 111

  • Importance of taking doses after meals to avoid saline laxative effect.104 105 106 107 108 109 111 112

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.104 105 106 107 108 109

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.105 106 107 108 109

  • Importance of informing patients of other important precautionary information.104 105 106 107 108 109 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Potassium Citrate and Citric Acid

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

Sodium Citrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder

Sodium Citrate and Citric Acid

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/5 mL and Citric Acid Monohydrate 334 mg/5 mL

Bicitra

Ortho-McNeil

Cytra-2

Cypress

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Tricitrates

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/5 mL*

Cytra-3 Syrup

Cypress

Citric Acid Monohydrate, Potassium Citrate Monohydrate, and Sodium Citrate Dihydrate Solution

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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 ()

101. Alza Pharmaceuticals. Polycitra-K (potassium citrate and citric acid) oral solution prescribing information. Mountain View, CA; Apr 1998. From the Alza website ()

102. Alza Pharmaceuticals. Bicitra (potassium citrate and citric acid) oral solution prescribing information. Mountain View, CA; Apr 1998. From the Alza website ()

103. Alza Pharmaceuticals. Polycitra-LC and syrup (tricitrates) oral solution prescribing information. Mountain View, CA; Apr 1998. From the Alza website ()

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 . 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.

a. AHFS Drug Information 2008. McEvoy GK, ed. Citrate Salts. Bethesda, MD: American Society of Health-System Pharmacists; 2008: 2710-11.

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