Version May 2024
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]
Generic: 50 mg
Yes
Tablets (Dichlorphenamide Oral)
50 mg (per each): $340.10
Tablets (Keveyis Oral)
50 mg (per each): $397.63
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpha-/Beta-Agonists (Indirect-Acting): Carbonic Anhydrase Inhibitors may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Risk C: Monitor therapy
Amantadine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Amantadine. Risk C: Monitor therapy
Amphetamines: Carbonic Anhydrase Inhibitors may decrease the excretion of Amphetamines. Risk C: Monitor therapy
Amphotericin B: May enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May enhance the hypokalemic effect of Dichlorphenamide. Risk C: 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. Risk X: Avoid combination
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Diacerein: May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Risk C: Monitor therapy
Famotidine: Dichlorphenamide may increase the serum concentration of Famotidine. Risk X: Avoid combination
Fexinidazole: May increase the 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 the excretion of Flecainide. Risk C: 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. Risk C: Monitor therapy
Laxatives: May enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Leflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Lithium: Carbonic Anhydrase Inhibitors may decrease the serum concentration of Lithium. Risk C: Monitor therapy
Loop Diuretics: May enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Memantine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Memantine. Risk C: Monitor therapy
MetFORMIN: Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of MetFORMIN. Specifically, the risk of developing lactic acidosis may be increased. Risk C: Monitor therapy
Methenamine: Carbonic Anhydrase Inhibitors may diminish the therapeutic effect 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 the serum concentration of Methotrexate. Risk X: Avoid combination
Nitisinone: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
OAT1/3 Inhibitors: May increase the serum concentration of Dichlorphenamide. Risk C: Monitor therapy
Opioid Agonists: May enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapy
Oseltamivir: Dichlorphenamide may increase the serum concentration of Oseltamivir. Risk X: Avoid combination
Penicillins: May enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Polyethylene Glycol-Electrolyte Solution: Diuretics may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy
Pretomanid: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: 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. Risk D: Consider therapy modification
Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy
Taurursodiol: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk X: Avoid combination
Teriflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Theophylline: May enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Thiazide and Thiazide-Like Diuretics: May enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Vaborbactam: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
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.
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