Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Keveyis: 50 mg [contains corn starch]
Keveyis: 50 mg [scored; contains corn starch]
Pharmacology
Mechanism of Action
Dichlorphenamide is a carbonic anhydrase inhibitor; the mechanism by which dichlorphenamide exerts its therapeutic effects in patients with periodic paralysis is unknown.
Pharmacokinetics/Pharmacodynamics
Time to Peak
~1.5 to 3 hours.
Half-Life Elimination
Terminal: 32 to 66 hours.
Protein Binding
~88%.
Use: Labeled Indications
Primary periodic paralysis: Treatment of primary hyperkalemic periodic paralysis, primary hypokalemic periodic paralysis, and related variants
Contraindications
Hypersensitivity to dichlorphenamide, other sulfonamides, or any component of the formulation; concomitant use with high-dose aspirin; severe pulmonary disease; hepatic insufficiency
Dosage and Administration
Dosing: Adult
Primary periodic paralysis: Oral: Initial: 50 mg once or twice daily; may increase or decrease dosage at weekly intervals (or more frequently in response to adverse reactions); minimum: 50 mg/day; maximum: 200 mg/day. Evaluate response and need for continued therapy after 2 months of treatment.
Dosing: Geriatric
Refer to adult dosing.
Storage
Store at 20°C to 25°C (68°F to 77°F).
Drug Interactions
Alpha-/Beta-Agonists (Indirect-Acting): Carbonic Anhydrase Inhibitors may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Monitor therapy
Amantadine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Amantadine. Monitor therapy
Amphetamines: Carbonic Anhydrase Inhibitors may decrease the excretion of Amphetamines. Monitor therapy
Amphotericin B: May enhance the hypokalemic effect of Dichlorphenamide. Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May enhance the hypokalemic effect of Dichlorphenamide. Monitor therapy
CarBAMazepine: Carbonic Anhydrase Inhibitors may increase the serum concentration of CarBAMazepine. Monitor therapy
Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of other Carbonic Anhydrase Inhibitors. The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Management: Avoid concurrent use of different carbonic anhydrase inhibitors if possible. Monitor patients closely for the occurrence of kidney stones and with regards to severity of metabolic acidosis. Avoid combination
Diacerein: May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Monitor therapy
Famotidine: Dichlorphenamide may increase the serum concentration of Famotidine. Avoid combination
Flecainide: Carbonic Anhydrase Inhibitors may increase the serum concentration of Flecainide. Monitor therapy
Fosphenytoin-Phenytoin: Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Fosphenytoin-Phenytoin. Specifically, the risk for osteomalacia or rickets may be increased. Monitor therapy
Laxatives: May enhance the hypokalemic effect of Dichlorphenamide. Monitor therapy
Lithium: Carbonic Anhydrase Inhibitors may decrease the serum concentration of Lithium. Monitor therapy
Loop Diuretics: May enhance the hypokalemic effect of Dichlorphenamide. Monitor therapy
Memantine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Memantine. Monitor therapy
MetFORMIN: Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of MetFORMIN. Specifically, the risk of developing lactic acidosis may be increased. Monitor therapy
Methenamine: Carbonic Anhydrase Inhibitors may diminish the therapeutic effect of Methenamine. Management: Consider avoiding this combination. Monitor for decreased therapeutic effects of methenamine if used concomitant with a carbonic anhydrase inhibitor. Consider therapy modification
Methotrexate: Dichlorphenamide may increase the serum concentration of Methotrexate. Avoid combination
OAT1/3 Inhibitors: May increase the serum concentration of Dichlorphenamide. Monitor therapy
Opioid Agonists: May enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Monitor therapy
Oseltamivir: Dichlorphenamide may increase the serum concentration of Oseltamivir. Avoid combination
Penicillins: May enhance the hypokalemic effect of Dichlorphenamide. Monitor therapy
Primidone: Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Primidone. Specifically, osteomalacia and rickets. Carbonic Anhydrase Inhibitors may decrease the serum concentration of Primidone. Monitor therapy
QuiNIDine: Carbonic Anhydrase Inhibitors may decrease the excretion of QuiNIDine. Monitor therapy
Salicylates: May enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Management: Avoid these combinations when possible.Dichlorphenamide use with high-dose aspirin as contraindicated. If another combination is used, monitor patients closely for adverse effects. Tachypnea, anorexia, lethargy, and coma have been reported. Consider therapy modification
Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Consider therapy modification
Theophylline: May enhance the hypokalemic effect of Dichlorphenamide. Monitor therapy
Thiazide and Thiazide-Like Diuretics: May enhance the hypokalemic effect of Dichlorphenamide. Monitor therapy
Trientine: Carbonic Anhydrase Inhibitor Diuretics may decrease the serum concentration of Trientine. Monitor therapy
Adverse Reactions
>10%:
Central nervous system: Paresthesia (44%), cognitive dysfunction (14%), confusion (11%)
Gastrointestinal: Dysgeusia (14%)
1% to 10%:
Central nervous system: Fatigue (8%), headache (8%), hypoesthesia (8%), lethargy (8%), dizziness (6%), malaise (6%)
Dermatologic: Skin rash (8%), pruritus (6%)
Endocrine & metabolic: Weight loss (6%)
Gastrointestinal: Diarrhea (6%), nausea (6%)
Neuromuscular & skeletal: Muscle spasm (8%), arthralgia (6%), muscle twitching (6%)
Respiratory: Dyspnea (6%), pharyngolaryngeal pain (6%)
Frequency not defined: Central nervous system: Difficulty thinking, disturbance in attention
Postmarketing: Amnesia, cardiac failure, hallucination, increased severity of condition, nephrolithiasis, pancytopenia, psychosis, renal tubular necrosis, seizure, stupor, syncope, tremor
Warnings/Precautions
Concerns related to adverse effects:
- CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
- Fall risk: Use of dichlorphenamide increases the risk of falls, especially in elderly patients and patients receiving high doses. Consider dose reduction or discontinuation in patients who experience falls.
- Hypokalemia: Dichlorphenamide increases potassium excretion and may cause hypokalemia; risk is increased in patients with a history of conditions associated with hypokalemia (eg, adrenocortical excess, renal tubular acidosis type 1 and 2) and coadministration with medications associated with hypokalemia (eg, loop diuretics, thiazide diuretics, laxative, antifungals, penicillin, theophylline). Monitor serum potassium at baseline and periodically throughout treatment; discontinue use or reduce the dose if hypokalemia develops or persists and correct potassium levels.
- Metabolic acidosis: Hyperchloremia nonanion gap metabolic acidosis may occur; concomitant use of medications associated with metabolic acidosis may increase the severity of acidosis. Concomitant use in patients with respiratory acidosis (eg, advanced lung diseases) may lead to respiratory decompensation. Monitor serum sodium bicarbonate at baseline and periodically throughout treatment; discontinue use or reduce the dose if metabolic acidosis develops or persists.
- Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, 2 antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or, at the very least, this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/toxic epidermal necrolysis), some clinicians choose to avoid exposure to these classes. Discontinue use at the first appearance of skin rash or any sign of immune-mediated or other life-threatening adverse reaction.
Disease-related concerns:
- Hepatic impairment: Use is contraindicated in patients with hepatic impairment.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
- Salicylate toxicity: Concomitant use of high-dose aspirin and dichlorphenamide is contraindicated due to increased risk of salicylate toxicity; anorexia, coma, lethargy, and tachypnea have been reported. Closely monitor patients using low-dose aspirin.
Special populations:
- Elderly: Use with caution in the elderly; the risk of falls and metabolic acidosis is increased in this population.
Monitoring Parameters
Evaluate response after 2 months of treatment. Monitor serum potassium and serum sodium bicarbonate at baseline and periodically throughout treatment.
Pregnancy
Pregnancy Considerations
Some symptoms of primary hyperkalemic periodic paralysis may be worsened by pregnancy (Charles 2013). Information related to potassium management of primary periodic paralysis in pregnancy is limited (Levitt 2014).
Maternal treatment with dichlorphenamide may cause metabolic acidosis. Although the effect of dichlorphenamide-induced metabolic acidosis has not been studied in pregnancy, 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. Newborns should be monitored for possible transient metabolic acidosis and treated appropriately.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience change in taste, headache, loss of strength and energy, dizziness, diarrhea, nausea, weight loss, joint pain, or throat pain. Have patient report immediately to prescriber signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), signs of acidosis (confusion, fast breathing, fast heartbeat, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy), burning or numbness feeling, confusion, difficulty focusing, shortness of breath, or signs of a severe sulfonamide reaction (rash; red, swollen, blistered, or peeling skin; red or irritated eyes; mouth, throat, nose, or eye sores; fever, chills, or sore throat; cough that is new or worse; loss of strength and energy; any bruising or bleeding; or signs of liver problems like dark urine, fatigue, lack of appetite, nausea or abdominal pain, light-colored stools, vomiting, or yellow skin) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.
