KEVEYIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KEVEYIS (KEVEYIS).
Keveyis (dichlorphenamide) is a carbonic anhydrase inhibitor. It reduces the frequency of attacks in primary hyperkalemic periodic paralysis by decreasing intracellular pH, which stabilizes muscle cell membranes and reduces potassium efflux from muscle cells.
| Metabolism | Dichlorphenamide is metabolized primarily in the liver via glucuronidation and sulfation. The major metabolic pathways involve conjugation with glucuronic acid and sulfate. The drug is excreted mainly in the urine as metabolites and unchanged drug. |
| Excretion | Primarily renal: unchanged drug accounts for ~82% of dose in urine; fecal excretion <5%; minor hepatic metabolism. |
| Half-life | Terminal elimination half-life: 15–20 hours following a single oral dose; at steady state, half-life 42–80 hours (mean ~60 h) due to dose-dependent kinetics. |
| Protein binding | 99% bound to serum proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 3.5–5.8 L/kg, indicating extensive extravascular distribution and binding to peripheral tissues. |
| Bioavailability | Oral bioavailability ~70–80% under fed conditions; food increases absorption and reduces variability. |
| Onset of Action | Oral: clinical reduction in attack frequency noted within 1–2 weeks; time to maximal preventive effect 3–4 weeks. |
| Duration of Action | Sustained reduction in paroxysmal non-kinesigenic dyskinesia (PNKD) attacks while on continuous therapy; effect wanes upon discontinuation over weeks. |
| Molecular Weight | 168.2 |
50 mg orally twice daily with food; may increase to 100 mg twice daily after 2 weeks if needed.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-59 mL/min: 50 mg once daily; eGFR 15-29 mL/min: 50 mg every other day; eGFR <15 mL/min or dialysis: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 50%; Class C: avoid use. |
| Pediatric use | Not approved for pediatric use; no established dosing. |
| Geriatric use | Start at 50 mg twice daily; monitor renal function; caution due to age-related renal decline. |
| 1st trimester | No human data; animal studies show developmental toxicity at doses >30 mg/kg/day; avoid use unless benefit outweighs risk. |
| 2nd trimester | No human data; animal studies show delayed ossification at high doses; use only if clearly needed. |
| 3rd trimester | No human data; potential risk of neonatal hypoglycemia or electrolyte disturbances; use with caution. |
Clinical note
Comprehensive clinical and safety monograph for KEVEYIS (KEVEYIS).
| Placental transfer | Not studied in humans; molecular weight (168.2 Da) and chemical properties suggest likely placental transfer; animal studies confirm fetal exposure. |
| Breastfeeding | No data on excretion in human milk; due to potential for serious adverse reactions in nursing infants (e.g., hypokalemia), breastfeeding is not recommended during treatment and for at least 2 days after last dose. |
■ FDA Black Box Warning
WARNING: CARDIAC ARRHYTHMIAS AND DEATH HAVE BEEN REPORTED WITH THE USE OF KEVEYIS. Keveyis can cause hypokalemia, which may predispose patients to serious cardiac arrhythmias. Electrolyte levels should be monitored before and during therapy.
| Serious Effects |
Hypersensitivity to dichlorphenamide or any componentConcomitant use with high-dose aspirin (≥325 mg/day) or other carbonic anhydrase inhibitors
| Precautions | Hypokalemia: Monitor serum potassium regularly; supplement if needed., Cardiac arrhythmias: Risk increases with hypokalemia; obtain baseline ECG and monitor., Renal stones: Increased risk due to reduced urinary citrate excretion., Sulfonamide allergy: Cross-sensitivity may occur., Hepatic impairment: Use with caution., Renal impairment: Contraindicated in severe renal disease., Pregnancy: Based on animal data, may cause fetal harm. |
| Food/Dietary | Avoid high-potassium foods if potassium levels are elevated; otherwise no specific dietary restrictions. Consistent carbohydrate intake may help prevent attacks. Limit alcohol as it can precipitate weakness. Ketogenic diet may increase risk of metabolic acidosis. |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | No human data available; in animal studies, no teratogenic effects observed at doses up to 10 times the human equivalent dose. Risk cannot be ruled out. |
| Fetal Monitoring | Monitor renal function and electrolytes (potassium, bicarbonate) during pregnancy. |
| Fertility Effects | No human fertility data; animal studies show no impairment at clinically relevant doses. |
| Clinical Pearls | KEVEYIS (dichlorphenamide) is a carbonic anhydrase inhibitor used for primary periodic paralysis. Monitor serum potassium closely; hypokalemia can precipitate paralytic attacks. Use with caution in patients with history of sulfonamide allergy due to cross-sensitivity. Not for acute attacks; it is prophylactic therapy. Renal stones are a known adverse effect due to reduced urinary citrate excretion. |
| Patient Advice | Take KEVEYIS exactly as prescribed, usually twice daily with food to reduce gastrointestinal upset. · Do not stop suddenly; taper under medical supervision to avoid rebound attacks. · Stay well hydrated to reduce risk of kidney stones. · Report any signs of allergic reaction (rash, hives, difficulty breathing) immediately. · Avoid potassium-depleting diuretics and corticosteroids; discuss all medications with your doctor. · Monitor for symptoms of hypokalemia (muscle weakness, cramps, fatigue) and report them. |