dichlorphenamide (Rx)

Brand and Other Names:Keveyis
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

tablet

  • 50mg

Periodic Paralysis

Indicated for primary hyperkalemic periodic paralysis, primary hypokalemic periodic paralysis, and related variants

50 mg PO qDay or q12hr initially; increase or decrease at weekly intervals according to individual response; not to exceed 200 mg/day

Evaluate response after 2 months of treatment to decide drug should be continued

Dosing Considerations

Obtain baseline and periodic measurements of serum potassium and sodium bicarbonate

Safety and efficacy not established

Periodic Paralysis

Indicated for primary hyperkalemic periodic paralysis, primary hypokalemic periodic paralysis, and related variants

50 mg PO qDay or q12hr initially; increase or decrease at weekly intervals according to individual response; not to exceed 200 mg/day

Evaluate response after 2 months of treatment to decide whether drug should be continued

Use lowest effective dose possible, owing to risk increased risk of falls

Dosing Considerations

Obtain baseline and periodic measurements of serum potassium and sodium bicarbonate

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Interactions

Interaction Checker

and dichlorphenamide

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    No Interactions Found
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    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Adverse Effects

            >10%

            Paresthesia (44%)

            Cognitive disorder (14%)

            Dysgeusia (14%)

            Confusional state (11%)

            1-10%

            Headache (8%)

            Hypoesthesia (8%)

            Lethargy (8%)

            Fatigue (8%)

            Muscle spasms (8%)

            Rash (8%)

            Dizziness (6%)

            Diarrhea (6%)

            Nausea (6%)

            Malaise (6%)

            Decreased weight (6%)

            Arthralgia (6%)

            Muscle twitching (6%)

            Dyspnea (6%)

            Pharyngolaryngeal pain (6%)

            Pruritus (6%)

            Postmarketing Reports

            Amnesia

            Cardiac failure

            Convulsion

            Fetal death

            Hallucination

            Nephrolithiasis

            Pancytopenia

            Psychotic disorder

            Renal tubular necrosis

            Stupor

            Syncope

            Tremor

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            Warnings

            Contraindications

            Hypersensitivity to dichlorphenamide or other sulfonamides

            Coadministration with high-dose aspirin

            Severe pulmonary disease, limiting compensation to metabolic acidosis caused by dichlorphenamide

            Hepatic insufficiency; dichlorphenamide may aggravate hepatic encephalopathy

            Cautions

            Fatalities associated with sulfonamides reported; hypersensitivity, anaphylaxis, and idiosyncratic reactions reported and may include Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias; pulmonary symptoms may occur in isolation or as part of a systemic reaction; discontinue at first sign of rash

            Dichlorphenamide increases potassium excretion and may cause hypokalemiareported; monitor potassium levels periodically; risk is greater when used with conditions associated with hypokalemia (eg, adrenocortical insufficiency, hyperchloremic metabolic acidosis, respiratory acidosis) and in patients receiving other drugs that may cause hypokalemia; if hypokalemia develops or persists, consider dose reduction or discontinuation of drug, and correct serum potassium

            Can cause hyperchloremic nonanion gap metabolic acidosis; coadministration with other drugs that cause metabolic acidosis may increase the severity; measure bicarbonate at baseline and then periodically; if metabolic acidosis develops or persists, consider reducing dose or discontinuing the drug

            Increased risk of falls; risk is greater in elderly patients and with higher doses

            Drug interaction overview

            • Aspirin and other salicylates
              • Carbonic anhydrase inhibitors, including dichlorphenamide, can cause metabolic acidosis, which may increase salicylate toxicity
              • Contraindicated with high-dose aspirin owing to risk of anorexia, tachypnea, lethargy, and coma
              • Monitor carefully if coadministered with low-dose aspirin
            • OAT1 substrates
              • Dichlorphenamide is an inhibitor of OAT1 transporters in vitro
              • Coadministration may increase plasma exposure of OAT1 substrates
              • Use with sensitive OAT1 substrates (methotrexate, famotidine, oseltamivir) is not recommended
            • OAT1/3 inhibitors
              • Dichlorphenamide is a substrate of human transporters OAT1 and OAT3
              • Monitor for signs of dichlorphenamide toxicity if coadministered with OAT1 or OAT3 inhibitors
            • Drug-induced hypokalemia
              • Hypokalemia risk increases if coadministered with other drugs that decrease serum potassium (eg, loop diuretics, thiazide diuretics, laxatives, antifungals, penicillin, theophylline)
            • Drug-induced metabolic acidosis
              • Coadministration with other drugs that cause metabolic acidosis may increase acidosis severity
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            Pregnancy & Lactation

            Pregnancy

            Data are not available on the developmental risk associated with the use in pregnant women

            Animal studies

            • Dichlorphenamide was teratogenic when administered orally to pregnant rats; fetal limb reduction defects observed at 17 x MRHD

            Clinical considerations

            • Treatment can cause metabolic acidosis
            • Effect of dichlorphenamide-induced metabolic acidosis has not been studied in pregnancy; however, metabolic acidosis in pregnancy (due to other causes) can cause decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the fetus’ ability to tolerate labor
            • Monitor pregnant women for metabolic acidosis and treat as in the nonpregnant state
            • Monitor newborns of mothers treated with dichlorphenamide for metabolic acidosis because of possible occurrence of transient metabolic acidosis following birth
            • Labor or delivery
              • Although the effect on labor and delivery in humans has not been established, the development of dichlorphenamide-induced metabolic acidosis in the mother and/or in the fetus might affect the fetus’ ability to tolerate labor

            Lactation

            Unknown if distributed in human breast milk

            Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Carbonic anhydrase inhibitor, but the exact mechanism by which dichlorphenamide is able to treat periodic paralysis is unknown

            Dichlorphenamide helps to normalize blood-potassium levels by decreasing levels

            Absorption

            Peak plasma time: 1.5-3 hr

            Steady-state achieved: Within 10 days of twice-daily dosing

            Distribution

            Protein bound: 88%

            Metabolism

            Not a substrate of CYP isoenzymes

            Elimination

            Half-life: 32-66 hr

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            Administration

            Oral Administration

            May take with or without food

            Storage

            Store at controlled room temperature of 20-25ºC (68-77ºF)

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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.