Dichlorphenamide
FDA Drug Information • Also known as: Dichlorphenamide, Keveyis, Ormalvi
- Brand Names
- Dichlorphenamide, Keveyis, Ormalvi
- Drug Class
- Carbonic Anhydrase Inhibitor [EPC]
- Route
- ORAL
- Dosage Form
- TABLET
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Dichlorphenamide tablets USP contain dichlorphenamide, an oral carbonic anhydrase inhibitor. Dichlorphenamide USP, a dichlorinated benzenedisulfonamide, is known chemically as 4, 5– dichloro- 1,3-benzenedisulfonamide. Its empirical formula is C 6 H 6 Cl 2 N 2 O 4 S 2 and its structural formula is: Dichlorphenamide USP is a white or practically white crystalline powder with a molecular weight of 305.16. It is soluble in 10% w/v sodium hydroxide solution, sparingly soluble in 10% w/v sodium carbonate solution and very slightly to practically insoluble in water. Dichlorphenamide tablets USP are supplied as tablets, for oral administration, each containing 50 mg dichlorphenamide USP. Inactive ingredients are colloidal silicon dioxide, lactose monohydrate, magnesium stearate and pregelatinized starch. diclorophenamide-Label.jpg
What Is Dichlorphenamide Used For?
1 INDICATIONS AND USAGE Dichlorphenamide tablets are indicated for the treatment of primary hyperkalemic periodic paralysis, primary hypokalemic periodic paralysis, and related variants. Dichlorphenamide tablets are an oral carbonic anhydrase inhibitor indicated for the treatment of primary hyperkalemic periodic paralysis, primary hypokalemic periodic paralysis, and related variants ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in labeling: Hypersensitivity and Other Life-Threatening Reactions [see Warnings and Precautions ( 5.1 )] Hypokalemia [see Warnings and Precautions ( 5.3 )] Metabolic Acidosis [see Warnings and Precautions ( 5.4 )] Falls [ see Warnings and Precautions ( 5.5 )] Most common adverse reactions (incidence at least 10% and greater than placebo) include paresthesias, cognitive disorder, dysgeusia, and confusional state ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc. at 1-844-874-7464, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In a 9-week randomized controlled trial in adults with hyperkalemic or hypokalemic periodic paralysis (Study 1), the most common adverse reactions in patients treated with dichlorphenamide, with rates greater than placebo, were paresthesia, cognitive disorder, dysgeusia, and confusional state. The mean dose of dichlorphenamide was 94 mg/day in patients with hypokalemic periodic paralysis and 82 mg/day in patients with hyperkalemic periodic paralysis. Table 1 lists the incidence of adverse reactions that occurred in ≥ 5% of patients treated with dichlorphenamide and more commonly than in patients treated with placebo in Study 1. Table 1: Adverse Reactions in Patients Treated with dichlorphenamide with Incidence > 5% and more common than in Patients Treated with Placebo in Study 1 * Cognitive disorder combined cases with the preferred terms of cognitive disorder, disturbance in attention, and mental impairment. diclorophenamide-Table 1.jpg 6.2 Postmarketing Experience Adverse reactions have been identified during postapproval use of dichlorphenamide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following are adverse reactions which have been reported during postapproval use of dichlorphenamide and were serious or are not reported in the previous section of labeling [see Clinical Trials Experience ( 6.1 ) ]: amnesia, cardiac failure, condition aggravated, convulsion, hallucination, nephrolithiasis, pancytopenia, psychotic disorder, renal tubular necrosis, stupor, syncope, tremor.
Drug Interactions
7 DRUG INTERACTIONS Aspirin: anorexia, tachypnea, lethargy, and coma have been reported with concomitant use of dichlorphenamide and high-dose aspirin. The concomitant use of dichlorphenamide tablets and high-dose aspirin is contraindicated. Dichlorphenamide tablets should be used with caution in patients receiving lower doses of aspirin ( 4 , 5.2 , 7.1 ) 7.1 Aspirin and Other Salicylates Carbonic anhydrase inhibitors, including dichlorphenamide, can cause metabolic acidosis [see Warnings and Precautions ( 5.2 , 5.4 )] , which can increase the risk of salicylate toxicity. Anorexia, tachypnea, lethargy, and coma have been reported with concomitant use of dichlorphenamide and high-dose aspirin. Therefore, concomitant use of dichlorphenamide and high-dose aspirin is contraindicated. Patients with concomitant use of dichlorphenamide and low-dose aspirin should be carefully monitored [see Contraindications ( 4 ) and Warnings and Precautions ( 5.2 )]. 7.2 Drugs that are Substrates of Organic Anion Transporter1 (OAT1) In vitro , dichlorphenamide is an inhibitor of OAT1 transporters. The concomitant administration of dichlorphenamide may increase the plasma exposures of OAT1 substrates. Use of dichlorphenamide with drugs that are sensitive to OAT1 inhibition (e.g., methotrexate, famotidine, oseltamivir) is not recommended [see Clinical Pharmacology ( 12.3 )]. 7.3 Drugs that Cause Hypokalemia The risk of hypokalemia is greater with coadministration of dichlorphenamide and other drugs that can cause hypokalemia (e.g., loop diuretics, thiazide diuretics, laxatives, antifungals, penicillins, and theophylline) [see Warnings and Precautions ( 5.3 )]. 7.4 Drugs that Cause Metabolic Acidosis Coadministration of dichlorphenamide and other drugs that can cause metabolic acidosis may increase the severity of the acidosis [see Warnings and Precautions ( 5.4 )]. 7.5 Drugs that are Inhibitors of OAT1 or OAT3 An in vitro transporter study indicated that dichlorphenamide is a substrate of human transporters OAT1 and OAT3 [see Clinical Pharmacology ( 12.3 )] . Therefore, signs of dichlorphenamide toxicity should be monitored when administered with OAT1 or OAT3 inhibitors.
Contraindications
4 CONTRAINDICATIONS Dichlorphenamide is contraindicated in the following circumstances: Hypersensitivity to dichlorphenamide or other sulfonamides [see Warnings and Precautions ( 5.1 )] Concomitant use of dichlorphenamide and high dose aspirin [see Warnings and Precautions ( 5.2 ) and Drug Interactions ( 7.1 )] Severe pulmonary disease, limiting compensation to metabolic acidosis caused by dichlorphenamide [see Warnings and Precautions ( 5.4 )] Hepatic insufficiency: dichlorphenamide may aggravate hepatic encephalopathy. Hepatic insufficiency ( 4 ) Severe pulmonary obstruction ( 4 ) Hypersensitivity to dichlorphenamide or other sulfonamides ( 4 ) Concomitant use with high dose aspirin ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of dichlorphenamide in pregnant women. A no-effect dose has not been established. Dichlorphenamide was teratogenic when administered orally to pregnant rats. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4%, and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal adverse reactions Dichlorphenamide treatment can cause metabolic acidosis [see Warnings and Precautions ( 5.4 )] . The 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. Pregnant patients should be monitored for metabolic acidosis and treated as in the nonpregnant state. Newborns of mothers treated with dichlorphenamide should be monitored for metabolic acidosis because of possible occurrence of transient metabolic acidosis following birth. Labor or Delivery Although the effect of dichlorphenamide 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. Data Animal Data Teratogenic effects (fetal limb reduction defects) were reported following oral administration of dichlorphenamide to pregnant rats during organogenesis at 350 mg/kg, or 17 times the maximum recommended human dose (200 mg/day) on a body surface area (mg/m 2 ) basis. A no-effect dose for adverse effects on embryofetal development has not been established.
Overdosage
10 OVERDOSAGE Symptoms of overdosage or toxicity may include drowsiness, anorexia, nausea, vomiting, dizziness, ataxia, tremor, and tinnitus. In the event of overdosage, induce emesis or perform gastric lavage. The electrolyte disturbances most likely to be encountered from overdosage are hypokalemia and hyperchloremic metabolic acidosis.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Each dichlorphenamide tablet USP, 50 mg is white colored flat round tablet with beveled edge, scored on one side and engraved with "C" above and "43" below on other side. They are supplied as follows: Bottles of 100.............................................NDC 16571-242-01 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.