What is Dichlorphenamide?
Dichlorphenamide (or diclofenamide) is a carbonic anhydrase inhibitor and sulfonamide that belongs to the meta-disulfamoylbenzene class.
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Dichlorphenamide was first approved for use in the United States in 1958 to treat glaucoma under the trade name Daranide. Following the approval, it was discovered to be effective in treating some cases of therapy-resistant epilepsy. More recently, dichlorphenamide was approved in 2015 in the US under the name Keveyis as an orphan drug to treat primary hypokalemic and hyperkalemic periodic paralysis. Primary hypokalemic and hyperkalemic periodic paralysis is considered to be an inherited condition that results in attacks of muscle weakness or intermittent loss of muscle movement caused by high or low levels of potassium in the blood.
The European Commission granted orphan designation for dichlorphenamide for the treatment of periodic paralysis in 2016.
Dichlorphenamide is a sulfonamide that comprises benzene-1 and 3-disulfonamide, where hydrogens at positions 4 and 5 are substituted by chlorine. Dichlorphenamid is classified as a First Generation Carbonic Anhydrase Inhibitor despite having two sulfate groups.
Dichlorphenamide vs. Acetazolamide
Dichlorphenamide and acetazolamide are both used to treat glaucoma. The primary difference between both drugs is that dichlorphenamide is 30 times more potent.
Dichlorphenamide Mechanism of Action
The pharmacological action associated with dichlorphenamide is its role as a Carbonic Anhydrase Inhibitor. Carbonic Anhydrase Inhibitors are defined as a class of compounds that inhibit carbonic anhydrases, resulting in the secretion of H+ ions by the proximal kidney tubule.
Carbonic anhydrase inhibitors partially suppress the secretion of aqueous humor (inflow), resulting in the reduction of intraocular pressure. Research suggests this occurs through the production of HCO3- ions in the ciliary body by hydration of carbon dioxide. This takes place under the influence of carbonic anhydrase, which is then diffused into the posterior chamber that contains more HCO3- and Na+ ions than the amount plasma. The drop in pressure is then the result of water being attracted to the posterior chamber.
Dichlorphenamide Clinical Trials
Some notable clinical trials testing the use of dichlorphenamide for both primary periodic paralysis and glaucoma include:
Efficacy and Safety of Dichlorphenamide for Primary Periodic Paralysis in Adolescents Compared With Adults: Patients with primary periodic paralysis were enrolled in a double-blind, controlled, crossover study. They were randomized to either dichlorphenamide or placebo for nine weeks with a minimum nine-week between-treatment washout period. Conclusions: Dichlorphenamide was determined to be comparably effective and tolerated among a small number of participants with varying adverse events between groups.
Long-term efficacy and safety of dichlorphenamide for treatment of primary periodic paralysis: Patients with primary periodic paralysis were placed in a double-blind, placebo-controlled study. Participants were randomly assigned to receive dichlorphenamide 50 mg or a placebo twice daily for nine weeks, followed by a 52-week open-label dichlorphenamide treatment phase. The study confirmed long-term dichlorphenamide remains safe and effective for long-term or chronic use with tolerability issues such as paresthesia or cognition-related adverse events manageable in most patients.
Glaucoma treated with Daranide: A Clinical Trial: Clinical trial by Maurice H. Luntz in 1961 to determine the safety and effectiveness of dichlorphenamide for glaucoma.
Recommended doses for primary periodic paralysis are typically 50 mg orally two times a day. The initial prescribed dose may be increased or decreased based on treatment effects on a weekly basis.
The recommended initial dose for a reduction in intraocular pressure is 100–200 mg, followed by 100 mg every 12 hours until the desired response is obtained. Maintenance dosage is typically 25–50 mg, 1–3 times daily.
The maximum recommended dose should not exceed 200 mg orally per day.
The cost of dichlorphenamide has shifted dramatically in the United States in recent years. Historically, the price for a bottle of 100 pills was $50 when the medication was approved for glaucoma. However, following the discovery of more effective glaucoma drugs, the pharmaceutical company Merck discontinued the production of dichlorphenamide.
Sun Pharmaceutical Industries then bought the rights to the drug in 2015 when the US Food and Drug Administration approved it as an orphan drug to treat periodic paralysis. The following year, in 2016, Strongbridge Biopharma acquired Sun Pharmaceutical Industries and raised the price to $150 per tablet.
As a result, dichlorphenamide is sourced outside the United States through wholesale pharmaceutical distributors. Click here to request a quote.
Dichlorphenamide Side Effects
General side effects associated with dichlorphenamide include blurred vision and impaired reaction time. Therefore, it is commonly advised to avoid driving or any high-risk activity while taking this medication.
Emergency medical help should be called in the event of the following reactions:
- Difficult breathing
- Allergic reaction
- Face swelling
- Throat swelling
- Severe and/or abnormal skin reactions
- Sore throat
- Eye irritation or burning
- Blistering skin
- Red and/or purple skin rash
- Peeling skin
- Loss of balance
- Accidental fall
- Worsening of paralysis symptoms
Consult your doctor if you have any of the following symptoms:
- Leg cramps
- Irregular heartbeat
- Chest fluttering
- Increased thirst
- Increased urination
- Numbness and/or tingling
- Muscle weakness and/or limp sensations
- Loss of appetite
- Cognitive issues
- Breathing problems
- Change in sense of taste
The use of dichlorphenamide is contraindicated for individuals with allergies, severe breathing problems, liver disease, individuals who take high doses of aspirin, or those who experience electrolyte imbalances due to low blood levels of potassium and/or/or magnesium.
Dichlorphenamide is strongly discouraged for pregnant and breastfeeding women.
Drugs affected by Dichlorphenamide
Drugs that affect the safety and/or effectiveness of dichlorphenamide include:
- Aspirin (including baby aspirin)
- Antifungal medicines
- Antiviral medicines
Other drugs can affect dichlorphenamide, including prescription medications, over-the-counter drugs, herbal medicines, and vitamins.
Dichlorphenamide (diclofenamide) is a sulfonamide and a carbonic anhydrase inhibitor that belongs to the meta-disulfamoylbenzene class.
Dichlorphenamide was initially approved to treat glaucoma and therapy-resistant epilepsy. The FDA approved the drug in 2015 to treat primary hypokalemic and hyperkalemic periodic paralysis under the name Keveyis.
While dichlorphenamide and acetazolamide are both prescribed to treat glaucoma, dichlorphenamide is considered to be 30 times more potent.
Some side effects include difficulty breathing, allergic reactions, face swelling, throat swelling, severe and/or abnormal skin reactions, fever, sore throat, eye irritation or burning, blistering skin, red and/or purple skin rash, peeling skin, balance issues, and worsening of paralysis symptoms.