Version August 2025
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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Use is contraindicated.
Refer to adult dosing. Use with caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Dysgeusia (14%)
Nervous system: Cognitive dysfunction (14%; including decreased mental acuity, disturbance in attention), confusion (11%), paresthesia (44%)
1% to 10%:
Dermatologic: Pruritus (6%), skin rash (8%)
Endocrine & metabolic: Weight loss (6%)
Gastrointestinal: Diarrhea (6%), nausea (6%)
Nervous system: Dizziness (6%), fatigue (8%), headache (8%), hypoesthesia (8%), lethargy (8%), malaise (6%)
Neuromuscular & skeletal: Arthralgia (6%), muscle spasm (8%), muscle twitching (6%)
Respiratory: Dyspnea (6%), pharyngolaryngeal pain (6%)
Postmarketing:
Cardiovascular: Heart failure, syncope
Gastrointestinal: Abdominal cramps (Ciafaloni 2019), anorexia (Ciafaloni 2019)
Hematologic & oncologic: Pancytopenia
Nervous system: Amnesia, asthenia (Ciafaloni 2019), ataxia (Ilyas 1991), hallucination, numbness (Ciafaloni 2019), psychosis, seizure, stupor, tremor
Renal: Flank pain (Ciafaloni 2019), nephrolithiasis (Sansone 2021), renal tubular necrosis
Hypersensitivity to dichlorphenamide, other sulfonamides, or any component of the formulation; concomitant use with high-dose aspirin; severe pulmonary disease; hepatic insufficiency
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
Special populations:
• Older adult: Use with caution in elderly patients; the risk of falls and metabolic acidosis is increased in this population.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Keveyis: 50 mg [scored]
Keveyis: 50 mg [contains corn starch]
Ormalvi: 50 mg
Generic: 50 mg
Yes
Tablets (Dichlorphenamide Oral)
50 mg (per each): $340.10
Tablets (Keveyis Oral)
50 mg (per each): $456.00
Tablets (Ormalvi Oral)
50 mg (per each): $456.00
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Primary periodic paralysis: Treatment of primary hyperkalemic periodic paralysis, primary hypokalemic periodic paralysis, and related variants
Substrate of OAT1/3;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Amantadine: Carbonic Anhydrase Inhibitors may increase serum concentration of Amantadine. Risk C: Monitor
Amphetamines: Carbonic Anhydrase Inhibitors may decrease excretion of Amphetamines. Risk C: Monitor
Amphotericin B: May increase hypokalemic effects of Dichlorphenamide. Risk C: Monitor
Antifungal Agents (Azole Derivatives, Systemic): May increase hypokalemic effects of Dichlorphenamide. Risk C: Monitor
Carbonic Anhydrase Inhibitors: May increase adverse/toxic effects of 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. Risk X: Avoid
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
Diacerein: May increase therapeutic effects of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Risk C: Monitor
EPINEPHrine (Systemic): Diuretics may increase arrhythmogenic effects of EPINEPHrine (Systemic). Diuretics may decrease vasopressor effects of EPINEPHrine (Systemic). Risk C: Monitor
Famotidine: Dichlorphenamide may increase serum concentration of Famotidine. Risk X: Avoid
Fexinidazole: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Management: Avoid use of fexinidazole with OAT1/3 substrates when possible. If combined, monitor for increased OAT1/3 substrate toxicities. Risk D: Consider Therapy Modification
Flecainide: Carbonic Anhydrase Inhibitors may decrease excretion of Flecainide. Risk C: Monitor
Isocarboxazid: May increase hypotensive effects of Diuretics. Risk X: Avoid
Laxatives: May increase hypokalemic effects of Dichlorphenamide. Risk C: Monitor
Leflunomide: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
Lithium: Carbonic Anhydrase Inhibitors may decrease serum concentration of Lithium. Risk C: Monitor
Loop Diuretics: May increase hypokalemic effects of Dichlorphenamide. Risk C: Monitor
Memantine: Carbonic Anhydrase Inhibitors may increase serum concentration of Memantine. Risk C: Monitor
MetFORMIN: Carbonic Anhydrase Inhibitors may increase adverse/toxic effects of MetFORMIN. Specifically, the risk of developing lactic acidosis may be increased. Risk C: Monitor
Methenamine: Carbonic Anhydrase Inhibitors may decrease therapeutic effects of Methenamine. Management: Consider avoiding the concomitant use of medications that alkalinize the urine, such as carbonic anhydrase inhibitors, and methenamine. Monitor for decreased therapeutic effects of methenamine if used concomitant with a carbonic anhydrase inhibitor. Risk D: Consider Therapy Modification
Methotrexate: Dichlorphenamide may increase serum concentration of Methotrexate. Risk X: Avoid
Nitisinone: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
OAT1/3 Inhibitors: May increase serum concentration of Dichlorphenamide. Risk C: Monitor
Opioid Agonists: May increase adverse/toxic effects of Diuretics. Opioid Agonists may decrease therapeutic effects of Diuretics. Risk C: Monitor
Oseltamivir: Dichlorphenamide may increase serum concentration of Oseltamivir. Risk X: Avoid
Penicillins: May increase hypokalemic effects of Dichlorphenamide. Risk C: Monitor
Piperacillin: May increase hypokalemic effects of Diuretics. Risk C: Monitor
Polyethylene Glycol-Electrolyte Solution: Diuretics may increase nephrotoxic effects of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor
Pretomanid: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
Salicylates: May increase adverse/toxic effects 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. Risk D: Consider Therapy Modification
Sodium Phosphates: Diuretics may increase nephrotoxic effects of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor
Taurursodiol: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk X: Avoid
Teriflunomide: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
Theophylline: May increase hypokalemic effects of Dichlorphenamide. Risk C: Monitor
Thiazide and Thiazide-Like Diuretics: May increase hypokalemic effects of Dichlorphenamide. Risk C: Monitor
Vaborbactam: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
Vadadustat: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
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.
It is not known if dichlorphenamide is present in breast milk.
According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Evaluate response after 2 months of treatment. Monitor serum potassium and serum sodium bicarbonate at baseline and periodically throughout treatment.
Dichlorphenamide is a carbonic anhydrase inhibitor; the mechanism by which dichlorphenamide exerts its therapeutic effects in patients with periodic paralysis is unknown.
Protein binding: ~88%.
Half-life elimination: Terminal: 32 to 66 hours.
Time to peak: ~1.5 to 3 hours.
