Potassium Citrate

×

Overview

What is Potassium Citrate?

Potassium citrate USP is a citrate salt of potassium and has the chemical name 1,2,3-Propanetricarboxylic acid, 2-hydroxy-, tripotassium salt, monohydrate. Its molecular formula is KCHO.HO , and its structural formula is: M.W. 324.41

Potassium citrate USP is a white granular powder that is soluble in water at 154 g/100 ml, almost insoluble in alcohol, and insoluble in organic solvents.

Potassium citrate extended-release tablets USP are supplied as wax matrix tablets, containing 5 mEq (540 mg) potassium citrate or 10 mEq (1080 mg) potassium citrate, for oral administration. In addition, potassium citrate extended-release tablets USP contain the inactive ingredients carnauba wax, magnesium stearate and stearic acid.

What does Potassium Citrate look like?

What are the available doses of Potassium Citrate?

Sorry No records found.

What should I talk to my health care provider before I take Potassium Citrate?

Sorry No records found

How should I use Potassium Citrate?

Potassium citrate extended-release tablets are indicated for the management of renal tubular acidosis (RTA) with calcium stones, hypocitraturic calcium oxalate nephrolithiasis of any etiology, and uric acid lithiasis with or without calcium stones.

Treatment with potassium citrate extended-release tablets should be added to a regimen that limits salt intake (avoidance of foods with high salt content and of added salt at the table) and encourages high fluid intake (urine volume should be at least two liters per day). The objective of treatment with potassium citrate extended-release tablets is to provide potassium citrate in sufficient dosage to restore normal urinary citrate (greater than 320 mg/day and as close to the normal mean of 640 mg/day as possible), and to increase urinary pH to a level of 6.0 to 7.0.

In patients with severe hypocitraturia (urinary citrate of less than 150 mg/day), therapy should be initiated at a dosage of 60 mEq/day (20 mEq three times/day or 15 mEq four times/day with meals or within 30 minutes after meals or bedtime snack). In patients with mild-moderate hypocitraturia (>150 mg/day), potassium citrate extended-release tablets should be initiated at a dosage of 30 mEq/day (10 mEq three times/day with meals). Twenty-four hour urinary citrate and/or urinary pH measurements should be used to determine the adequacy of the initial dosage and to evaluate the effectiveness of any dosage change. In addition, urinary citrate and/or pH should be measured every four months.

Doses of potassium citrate extended-release tablets greater than 100 mEq/day have not been studied and should be avoided.

Serum electrolytes (sodium, potassium, chloride and carbon dioxide), serum creatinine, and complete blood count should be monitored every four months. Treatment should be discontinued if there is hyperkalemia, a significant rise in serum creatinine, or a significant fall in blood hematocrit or hemoglobin.

What interacts with Potassium Citrate?

Potassium citrate extended-release tablets are contraindicated in patients with hyperkalemia (or who have conditions predisposing them to hyperkalemia), as a further rise in serum potassium concentration may produce cardiac arrest. Such conditions include: chronic renal failure, uncontrolled diabetes mellitus, acute dehydration, strenuous physical exercise in unconditioned individuals, adrenal insufficiency, extensive tissue breakdown, or the administration of a potassium-sparing agent (such as triamterene, spironolactone or amiloride).

Potassium citrate extended-release tablets are contraindicated in patients in whom there is cause for arrest or delay in tablet passage through the gastrointestinal tract, such as those suffering from delayed gastric emptying, esophageal compression, intestinal obstruction or stricture or those taking anticholinergic medication. Because of its ulcerogenic potential, potassium citrate extended-release tablets should not be given to patients with peptic ulcer disease.

Potassium citrate extended-release tablets are contraindicated in patients with active urinary tract infection (with either urea-splitting or other organisms, in association with either calcium or struvite stones). The ability of potassium citrate extended-release tablets to increase urinary citrate may be attenuated by bacterial enzymatic degradation of citrate. Moreover, the rise in urinary pH resulting from potassium citrate therapy might promote further bacterial growth.

Potassium citrate extended-release tablets are contraindicated in patients with renal insufficiency (glomerular filtration rate of less than 0.7 ml/kg/min), because of the danger of soft tissue calcification and increased risk for the development of hyperkalemia.

What are the warnings of Potassium Citrate?

Array

HYPERKALEMIA: In patients with impaired mechanisms for excreting potassium, potassium citrate administration can produce hyperkalemia and cardiac arrest. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of potassium citrate in patients with chronic renal failure, or any other condition which impairs potassium excretion such as severe myocardial damage or heart failure, should be avoided.

INTERACTION WITH POTASSIUM-SPARING DIURETICS

GASTROINTESTINAL LESIONS

Solid dosage forms of potassium chloride have produced stenotic and/or ulcerative lesions of the small bowel and deaths. These lesions are caused by a high local concentration of potassium ions in the region of the dissolving tablets, which injured the bowel. In addition, perhaps because wax-matrix preparations are not enteric-coated and release some of their potassium content in the stomach, there have been reports of upper gastrointestinal bleeding associated with these products. The frequency of gastrointestinal lesions with wax-matrix potassium chloride products is estimated at one per 100,000 patient-years. Experience with potassium citrate is limited, but a similar frequency of gastrointestinal lesions should be anticipated.

If there is severe vomiting, abdominal pain or gastro-intestinal bleeding, potassium citrate should be discontinued immediately and the possibility of bowel perforation or obstruction investigated.

What are the precautions of Potassium Citrate?

Information For Patients:

Laboratory Tests:

Drug Interactions:

DRUGS THAT SLOW GASTROINTESTINAL TRANSIT TIME (such as anticholinergics) can be expected to increase the gastrointestinal irritation produced by potassium salts. (see section).

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Pregnancy Category C:

Nursing Mothers:

Pediatric Use:

To take each dose without crushing, chewing or sucking the tablet.
To take this medicine only as directed. This is especially important if the patient is also taking both diuretics and digitalis preparations.
To check with physician if there is trouble swallowing tablets or if the tablet seems to stick in the throat.
To check with the doctor at once if tarry stools or other evidence of gastrointestinal bleeding is noticed.

What are the side effects of Potassium Citrate?

Sorry No records found

What should I look out for while using Potassium Citrate?

Potassium citrate extended-release tablets are contraindicated in patients with hyperkalemia (or who have conditions predisposing them to hyperkalemia), as a further rise in serum potassium concentration may produce cardiac arrest. Such conditions include: chronic renal failure, uncontrolled diabetes mellitus, acute dehydration, strenuous physical exercise in unconditioned individuals, adrenal insufficiency, extensive tissue breakdown, or the administration of a potassium-sparing agent (such as triamterene, spironolactone or amiloride).

Potassium citrate extended-release tablets are contraindicated in patients in whom there is cause for arrest or delay in tablet passage through the gastrointestinal tract, such as those suffering from delayed gastric emptying, esophageal compression, intestinal obstruction or stricture or those taking anticholinergic medication. Because of its ulcerogenic potential, potassium citrate extended-release tablets should not be given to patients with peptic ulcer disease.

Potassium citrate extended-release tablets are contraindicated in patients with active urinary tract infection (with either urea-splitting or other organisms, in association with either calcium or struvite stones). The ability of potassium citrate extended-release tablets to increase urinary citrate may be attenuated by bacterial enzymatic degradation of citrate. Moreover, the rise in urinary pH resulting from potassium citrate therapy might promote further bacterial growth.

Potassium citrate extended-release tablets are contraindicated in patients with renal insufficiency (glomerular filtration rate of less than 0.7 ml/kg/min), because of the danger of soft tissue calcification and increased risk for the development of hyperkalemia.

HYPERKALEMIA: In patients with impaired mechanisms for excreting potassium, potassium citrate administration can produce hyperkalemia and cardiac arrest. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of potassium citrate in patients with chronic renal failure, or any other condition which impairs potassium excretion such as severe myocardial damage or heart failure, should be avoided.

INTERACTION WITH POTASSIUM-SPARING DIURETICS

GASTROINTESTINAL LESIONS

Solid dosage forms of potassium chloride have produced stenotic and/or ulcerative lesions of the small bowel and deaths. These lesions are caused by a high local concentration of potassium ions in the region of the dissolving tablets, which injured the bowel. In addition, perhaps because wax-matrix preparations are not enteric-coated and release some of their potassium content in the stomach, there have been reports of upper gastrointestinal bleeding associated with these products. The frequency of gastrointestinal lesions with wax-matrix potassium chloride products is estimated at one per 100,000 patient-years. Experience with potassium citrate is limited, but a similar frequency of gastrointestinal lesions should be anticipated.

If there is severe vomiting, abdominal pain or gastro-intestinal bleeding, potassium citrate should be discontinued immediately and the possibility of bowel perforation or obstruction investigated.

What might happen if I take too much Potassium Citrate?

The administration of potassium salts to persons without predisposing conditions for hyperkalemia (see ) rarely causes serious hyperkalemia at recommended dosages. It is important to recognize that hyperkalemia is usually asymptomatic and may be manifested only by an increased serum potassium concentration and characteristic electrocardiographic changes (peaking of T-wave, loss of P-wave, depression of S-T segment and prolongation of the QT interval). Late manifestations include muscle paralysis and cardiovascular collapse from cardiac arrest.

Treatment measures for hyperkalemia include the following: (1) elimination of potassium-rich foods, medications containing potassium, and of potassium-sparing diuretics, (2) intravenous administration of 300-500 ml/hr of 10% dextrose solution containing 10-20 units of insulin/1000 ml, (3) correction of acidosis, if present, with intravenous sodium bicarbonate, and (4) use of exchange resins, hemodialysis or peritoneal dialysis.

In treating hyperkalemia, it should be recalled that in patients who have been stabilized on digitalis, too rapid a lowering of the serum potassium concentration can produce digitalis toxicity.

How should I store and handle Potassium Citrate?

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146 PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146 PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146 PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146 PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146 PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146 PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146 PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146 PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146 PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146 PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146 PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146 PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146 PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146 PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146 PROVIGIL (modafinil) Tablets100 mg:NDC 54868-4492-1 - Bottles of 10NDC 54868-4492-0 - Bottles of 30200 mg:NDC 54868-4897-1 - Bottles of 10NDC 54868-4897-0 - Bottles of 30Store at 20° - 25° C (68° - 77° F). Manufactured for:Cephalon, Inc.Frazer, PA 19355U.S. Patent Nos. RE37,516 / 4,927,855© Cephalon, Inc., 2008. All rights reservedMarch 2008PROV-011Repackaging and Relabeling by:Physicians Total Care, Inc.Tulsa, OK 74146

×

Clinical Information

Chemical Structure

No Image found

Clinical Pharmacology

When potassium citrate is given orally, the metabolism of absorbed citrate produces an alkaline load. The induced alkaline load in turn increases urinary pH and raises urinary citrate by augmenting citrate clearance without measurably altering ultrafilterable serum citrate. Thus, potassium citrate therapy appears to increase urinary citrate principally by modifying the renal handling of citrate, rather than by increasing the filtered load of citrate. The increased filtered load of citrate may play some role, however, as in small comparisons of oral citrate and oral bicarbonate, citrate had a greater effect on urinary citrate.

In addition to raising urinary pH and citrate, potassium citrate increases urinary potassium by approximately the amount contained in the medication. In some patients, potassium citrate causes a transient reduction in urinary calcium.

The changes induced by potassium citrate produce a urine that is less conducive to the crystallization of stone-forming salts (calcium oxalate, calcium phosphate and uric acid). Increased citrate in the urine, by complexing with calcium, decreases calcium ion activity and thus the saturation of calcium oxalate. Citrate also inhibits the spontaneous nucleation of calcium oxalate and calcium phosphate (brushite).

The increase in urinary pH also decreases calcium ion activity by increasing calcium complexation to dissociated anions. The rise in urinary pH also increases the ionization of uric acid to more soluble urate ion.

Potassium citrate therapy does not alter the urinary saturation of calcium phosphate, since the effect of increased citrate complexation of calcium is opposed by the rise in pH-dependent dissociation of phosphate. Calcium phosphate stones are more stable in alkaline urine.

In the setting of normal renal function, the rise in urinary citrate following a single dose begins by the first hour and lasts for 12 hours. With multiple doses the rise in citrate excretion reaches its peak by the third day and averts the normally wide circadian fluctuation in urinary citrate, thus maintaining urinary citrate at a higher, more constant level throughout the day. When the treatment is withdrawn, urinary citrate begins to decline toward the pre-treatment level on the first day.

The rise in citrate excretion is directly dependent on the potassium citrate dosage. Following long-term treatment, potassium citrate at a dosage of 60 mEq/day raises urinary citrate by approximately 400 mg/day and increases urinary pH by approximately 0.7 units.

In patients with severe renal tubular acidosis or chronic diarrheal syndrome where urinary citrate may be very low (<100 mg/day), potassium citrate may be relatively ineffective in raising urinary citrate. A higher dose of potassium citrate may therefore be required to produce a satisfactory citraturic response. In patients with renal tubular acidosis in whom urinary pH may be high, potassium citrate produces a relatively small rise in urinary pH.

Non-Clinical Toxicology

Potassium citrate extended-release tablets are contraindicated in patients with hyperkalemia (or who have conditions predisposing them to hyperkalemia), as a further rise in serum potassium concentration may produce cardiac arrest. Such conditions include: chronic renal failure, uncontrolled diabetes mellitus, acute dehydration, strenuous physical exercise in unconditioned individuals, adrenal insufficiency, extensive tissue breakdown, or the administration of a potassium-sparing agent (such as triamterene, spironolactone or amiloride).

Potassium citrate extended-release tablets are contraindicated in patients in whom there is cause for arrest or delay in tablet passage through the gastrointestinal tract, such as those suffering from delayed gastric emptying, esophageal compression, intestinal obstruction or stricture or those taking anticholinergic medication. Because of its ulcerogenic potential, potassium citrate extended-release tablets should not be given to patients with peptic ulcer disease.

Potassium citrate extended-release tablets are contraindicated in patients with active urinary tract infection (with either urea-splitting or other organisms, in association with either calcium or struvite stones). The ability of potassium citrate extended-release tablets to increase urinary citrate may be attenuated by bacterial enzymatic degradation of citrate. Moreover, the rise in urinary pH resulting from potassium citrate therapy might promote further bacterial growth.

Potassium citrate extended-release tablets are contraindicated in patients with renal insufficiency (glomerular filtration rate of less than 0.7 ml/kg/min), because of the danger of soft tissue calcification and increased risk for the development of hyperkalemia.

HYPERKALEMIA: In patients with impaired mechanisms for excreting potassium, potassium citrate administration can produce hyperkalemia and cardiac arrest. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of potassium citrate in patients with chronic renal failure, or any other condition which impairs potassium excretion such as severe myocardial damage or heart failure, should be avoided.

INTERACTION WITH POTASSIUM-SPARING DIURETICS

GASTROINTESTINAL LESIONS

Solid dosage forms of potassium chloride have produced stenotic and/or ulcerative lesions of the small bowel and deaths. These lesions are caused by a high local concentration of potassium ions in the region of the dissolving tablets, which injured the bowel. In addition, perhaps because wax-matrix preparations are not enteric-coated and release some of their potassium content in the stomach, there have been reports of upper gastrointestinal bleeding associated with these products. The frequency of gastrointestinal lesions with wax-matrix potassium chloride products is estimated at one per 100,000 patient-years. Experience with potassium citrate is limited, but a similar frequency of gastrointestinal lesions should be anticipated.

If there is severe vomiting, abdominal pain or gastro-intestinal bleeding, potassium citrate should be discontinued immediately and the possibility of bowel perforation or obstruction investigated.

CNS Active Drugs

Methylphenidate

In a single-dose study in healthy volunteers, simultaneous administration of modafinil (200 mg) with methylphenidate (40 mg) did not cause any significant alterations in the pharmacokinetics of either drug. However, the absorption of PROVIGIL may be delayed by approximately one hour when coadministered with methylphenidate.

In a multiple-dose, steady-state study in healthy volunteers, modafinil was administered once daily at 200 mg/day for 7 days followed by 400 mg/day for 21 days. Administration of methylphenidate (20 mg/day) during days 22-28 of modafinil treatment 8 hours after the daily dose of modafinil did not cause any significant alterations in the pharmacokinetics of modafinil.

Dextroamphetamine

In a single dose study in healthy volunteers, simultaneous administration of modafinil (200 mg) with dextroamphetamine (10 mg) did not cause any significant alterations in the pharmacokinetics of either drug. However, the absorption of PROVIGIL may be delayed by approximately one hour when coadministered with dextroamphetamine.

In a multiple-dose, steady-state study in healthy volunteers, modafinil was administered once daily at 200 mg/day for 7 days followed by 400 mg/day for 21 days. Administration of dextroamphetamine (20 mg/day) during days 22-28 of modafinil treatment 7 hours after the daily dose of modafinil did not cause any significant alterations in the pharmacokinetics of modafinil.

Clomipramine

The coadministration of a single dose of clomipramine (50 mg) on the first of three days of treatment with modafinil (200 mg/day) in healthy volunteers did not show an effect on the pharmacokinetics of either drug. However, one incident of increased levels of clomipramine and its active metabolite desmethylclomipramine has been reported in a patient with narcolepsy during treatment with modafinil.

Triazolam

In the drug interaction study between PROVIGIL and ethinyl estradiol (EE), on the same days as those for the plasma sampling for EE pharmacokinetics, a single dose of triazolam (0.125 mg) was also administered. Mean C and AUC of triazolam were decreased by 42% and 59%, respectively, and its elimination half-life was decreased by approximately an hour after the modafinil treatment.

Monoamine Oxidase (MAO) Inhibitors

Interaction studies with monoamine oxidase inhibitors have not been performed. Therefore, caution should be used when concomitantly administering MAO inhibitors and modafinil.

Other Drugs

Warfarin

There were no significant changes in the pharmacokinetic profiles of R- and S-warfarin in healthy subjects given a single dose of racemic warfarin (5 mg) following chronic administration of modafinil (200 mg/day for 7 days followed by 400 mg/day for 27 days) relative to the profiles in subjects given placebo. However, more frequent monitoring of prothrombin times/INR is advisable whenever PROVIGIL is coadministered with warfarin (See )

Ethinyl Estradiol

Administration of modafinil to female volunteers once daily at 200 mg/day for 7 days followed by 400 mg/day for 21 days resulted in a mean 11% decrease in C and 18% decrease in AUC of ethinyl estradiol (EE; 0.035 mg; administered orally with norgestimate). There was no apparent change in the elimination rate of ethinyl estradiol.

Cyclosporine

One case of an interaction between modafinil and cyclosporine, a substrate of CYP3A4, has been reported in a 41 year old woman who had undergone an organ transplant. After one month of administration of 200 mg/day of modafinil, cyclosporine blood levels were decreased by 50%. The interaction was postulated to be due to the increased metabolism of cyclosporine, since no other factor expected to affect the disposition of the drug had changed. Dosage adjustment for cyclosporine may be needed.

Potential Interactions with Drugs That Inhibit, Induce, or are Metabolized by Cytochrome P-450 Isoenzymes and Other Hepatic Enzymes

In in vitro studies using primary human hepatocyte cultures, modafinil was shown to slightly induce CYP1A2, CYP2B6 and CYP3A4 in a concentration-dependent manner. Although induction results based on in vitro experiments are not necessarily predictive of response in vivo, caution needs to be exercised when PROVIGIL is coadministered with drugs that depend on these three enzymes for their clearance. Specifically, lower blood levels of such drugs could result (See Other Drugs, above).

The exposure of human hepatocytes to modafinil in vitro produced an apparent concentration-related suppression of expression of CYP2C9 activity suggesting that there is a potential for a metabolic interaction between modafinil and the substrates of this enzyme (e.g., S-warfarin and phenytoin). In a subsequent clinical study in healthy volunteers, chronic modafinil treatment did not show a significant effect on the single-dose pharmacokinetics of warfarin when compared to placebo (see ).

In vitro studies using human liver microsomes showed that modafinil reversibly inhibited CYP2C19 at pharmacologically relevant concentrations of modafinil. CYP2C19 is also reversibly inhibited, with similar potency, by a circulating metabolite, modafinil sulfone. Although the maximum plasma concentrations of modafinil sulfone are much lower than those of parent modafinil, the combined effect of both compounds could produce sustained partial inhibition of the enzyme. Drugs that are largely eliminated via CYP2C19 metabolism, such as diazepam, propranolol, phenytoin (also via CYP2C9) or S-mephenytoin may have prolonged elimination upon coadministration with PROVIGIL and may require dosage reduction and monitoring for toxicity.

Tricyclic antidepressants

CYP2C19 also provides an ancillary pathway for the metabolism of certain tricyclic antidepressants (e.g., clomipramine and desipramine) that are primarily metabolized by CYP2D6. In tricyclic-treated patients deficient in CYP2D6 (i.e., those who are poor metabolizers of debrisoquine; 7-10% of the Caucasian population; similar or lower in other populations), the amount of metabolism by CYP2C19 may be substantially increased. PROVIGIL may cause elevation of the levels of the tricyclics in this subset of patients. Physicians should be aware that a reduction in the dose of tricyclic agents might be needed in these patients.

In addition, due to the partial involvement of CYP3A4 in the metabolic elimination of modafinil, coadministration of potent inducers of CYP3A4 (e.g., carbamazepine, phenobarbital, rifampin) or inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole) could alter the plasma levels of modafinil.

Information For Patients:

Laboratory Tests:

Drug Interactions:

DRUGS THAT SLOW GASTROINTESTINAL TRANSIT TIME (such as anticholinergics) can be expected to increase the gastrointestinal irritation produced by potassium salts. (see section).

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Pregnancy Category C:

Nursing Mothers:

Pediatric Use:

Some patients may develop minor gastrointestinal complaints during potassium citrate therapy, such as abdominal discomfort, vomiting, diarrhea, loose bowel movements or nausea. These symptoms are due to the irritation of the gastrointestinal tract, and may be alleviated by taking the dose with meals or snack, or by reducing the dosage. Patients may find intact matrices in feces. (see also ,

×

Reference

This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"

While we update our database periodically, we cannot guarantee it is always updated to the latest version.

×

Review

×

Professional

Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72

×

Tips

×

Interactions

A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).

Disclaimer: