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Drug overview for KEVEYIS (dichlorphenamide):
Generic name: DICHLORPHENAMIDE (DYE-klor-FEN-a-mide)
Drug class: Carbonic Anhydrase Inhibitors
Therapeutic class: Locomotor System
Dichlorphenamide is a carbonic anhydrase inhibitor that has beneficial effects in the management of periodic paralysis.
No enhanced Uses information available for this drug.
Generic name: DICHLORPHENAMIDE (DYE-klor-FEN-a-mide)
Drug class: Carbonic Anhydrase Inhibitors
Therapeutic class: Locomotor System
Dichlorphenamide is a carbonic anhydrase inhibitor that has beneficial effects in the management of periodic paralysis.
No enhanced Uses information available for this drug.
DRUG IMAGES
KEVEYIS 50 MG TABLET
The following indications for KEVEYIS (dichlorphenamide) have been approved by the FDA:
Indications:
Familial hyperkalemic periodic paralysis
Familial hypokalemic periodic paralysis
Professional Synonyms:
Adynamia episodica hereditaria
Hyperkalemic familial periodic paralysis
Hyperkalemic form of familial periodic paralysis
Hyperkalemic periodic paralysis syndrome
Hyperkalemic periodic paralysis
HyperKPP
Hypokalemic form of familial periodic paralysis
Hypokalemic periodic paralysis
Periodic paralysis I
Periodic paralysis II
Primary hyperkalemic periodic paralysis
Primary hypokalemic periodic paralysis
Indications:
Familial hyperkalemic periodic paralysis
Familial hypokalemic periodic paralysis
Professional Synonyms:
Adynamia episodica hereditaria
Hyperkalemic familial periodic paralysis
Hyperkalemic form of familial periodic paralysis
Hyperkalemic periodic paralysis syndrome
Hyperkalemic periodic paralysis
HyperKPP
Hypokalemic form of familial periodic paralysis
Hypokalemic periodic paralysis
Periodic paralysis I
Periodic paralysis II
Primary hyperkalemic periodic paralysis
Primary hypokalemic periodic paralysis
The following dosing information is available for KEVEYIS (dichlorphenamide):
No enhanced Dosing information available for this drug.
Dichlorphenamide is administered orally.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| KEVEYIS 50 MG TABLET | Maintenance | Adults take 1 tablet (50 mg) by oral route 2 times per day |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| DICHLORPHENAMIDE 50 MG TABLET | Maintenance | Adults take 1 tablet (50 mg) by oral route 2 times per day |
The following drug interaction information is available for KEVEYIS (dichlorphenamide):
There are 2 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Methenamine/Sulfonamides SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Methenamine is hydrolyzed to formaldehyde in acidic urine. Sulfonamides may form an insoluble precipitate with formaldehyde in the urine.(1,2) CLINICAL EFFECTS: The concurrent administration of methenamine and sulfamethizole or sulfathiazole is likely to form a precipitate in the urine.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Methenamine should not be administered to patients receiving sulfonamides.(1-3) DISCUSSION: Methenamine is hydrolyzed to formaldehyde in acidic urine. An in vitro study showed that addition of methenamine and mandelic acid to saturated solutions of sulfamethizole at pH 5.0 and 6.0 produced a precipitate in one hour.(4) |
MB CAPS, ME-NAPHOS-MB-HYO 1, METHENAMINE, METHENAMINE HIPPURATE, METHENAMINE MANDELATE, URELLE, URETRON D-S, URIBEL TABS, URIMAR-T, URNEVA, URO-MP, URO-SP, UROGESIC-BLUE, UROQID-ACID NO.2, URYL |
| Dichlorphenamide/Aspirin (Greater Than 325 mg); Salicylates SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Dichlorphenamide may reduce blood pH, causing a shift of salicylates from plasma into tissues (eg, central nervous system).(1) Alternatively, toxicity may be due to salicylate-induced displacement of dichlorphenamide from its protein binding sites and inhibition of renal tubular secretion. CLINICAL EFFECTS: An increase in the pharmacologic effects of salicylates with possible toxicity may occur. Anorexia, tachypnea, lethargy, and coma have been reported.(1) PREDISPOSING FACTORS: High doses of salicylates, low body weight. PATIENT MANAGEMENT: The concurrent use of high-dose aspirin or other salicylates with dichlorphenamide is contraindicated. If it is necessary to administer a low-dose salicylate concurrently, use the lowest dose possible or replace it with a non-salicylate anti-inflammatory agent. Monitor salicylate levels and serum bicarbonate concentrations, and monitor the patient for symptoms of toxicity. Adjust the dose as needed.(1) DISCUSSION: An 8-year-old boy with unimpaired renal and hepatic function was found to have developed metabolic acidosis after treatment for glaucoma and joint pain with a combination of aloxiprin 3.6 gram daily and dichlorphenamide 25 mg three times daily. His symptoms resolved after discontinuation of both aloxiprin and dichlorphenamide and did not recur on subsequent therapy with naproxen and dichlorphenamide.(2) A 75-year old woman taking dichlorphenamide 100 mg to 150 mg daily for therapy of glaucoma and high doses of aspirin (975 mg 4 to 5 times daily) for arthritis developed severe acid-base imbalance and salicylate intoxication. The patient did not exhibit ill effects when taking high aspirin doses without dichlorphenamide.(3) |
ACETYL SALICYLIC ACID, ASPIRIN, BALSALAZIDE DISODIUM, BISMUTH SUBSALICYLATE, CHOLINE MAGNESIUM TRISALICYLAT, COLAZAL, DISALCID, MB CAPS, NORGESIC, NORGESIC FORTE, ORPHENADRINE-ASPIRIN-CAFFEINE, ORPHENGESIC FORTE, PHENYL SALICYLATE, SALSALATE, SODIUM SALICYLATE, URELLE, URETRON D-S, URIBEL TABS, URIMAR-T, URNEVA, URO-MP, URO-SP |
There are 4 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Topiramate/Carbonic Anhydrase Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Topiramate is a weak carbonic anhydrase inhibitor and can induce renal bicarbonate loss, resulting in metabolic acidosis. It can also reduce urinary citrate excretion and increase urinary pH, posing a risk for nephrolithiasis. As well, carbonic anhydrase inhibitors can cause decreased sweating and elevated body temperature, predisposing patients to heat-related disorders.(1) CLINICAL EFFECTS: The concurrent use of topiramate with another carbonic anhydrase inhibitor may increase the risk of metabolic acidosis and kidney stone formation.(1) Concurrent use of topiramate with other carbonic anhydrase inhibitors may increase the incidence of oligohidrosis and hyperthermia, especially in pediatric or adolescent patients.(1-2) Overheating and dehydration can lead to brain damage and death. PREDISPOSING FACTORS: Patients with conditions that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhea, and being on a ketogenic diet) may be at increased risk of experiencing adverse effects from concurrent carbonic anhydrase inhibitors.(1) Pediatric and adolescent patients and patients with dehydration may be more likely to experience heat-related disorders.(1) PATIENT MANAGEMENT: The US manufacturer of topiramate states that the concurrent use of topiramate with other carbonic anhydrase inhibitors should be avoided. Patients receiving concurrent therapy should be monitored for the appearance of or worsening of metabolic acidosis, nephrolithiasis, and hyperthermia.(1) Check serum bicarbonate at baseline and periodically during treatment. Monitor for signs and symptoms of metabolic acidosis: hyperventilation, fatigue, anorexia, arrhthymias, stupor. Monitor for signs and symptoms of heat stroke: skin feels very hot with little or no sweating, confusion, muscle cramps, rapid heartbeat, or rapid breathing. Monitor for signs and symptoms of dehydration: dry mouth, urinating less than usual, dark-colored urine, dry skin, feeling tired, dizziness, or irritability. If signs or symptoms of metabolic acidosis, dehydration, oligohidrosis, or elevated body temperature occur, a decreased dose or discontinuation of zonisamide should be considered. DISCUSSION: Topiramate is a weak carbonic anhydrase inhibitor. Carbonic anhydrase inhibitors increase urinary bicarbonate excretion, reduce urinary citrate excretion and increase urinary pH. Concurrent use of topiramate with other carbonic anhydrase inhibitors may increase the risk of metabolic acidosis and kidney stone formation and should therefore be avoided.(1) Case reports of decreased sweating and elevated temperature have been reported, especially in pediatric patients. Some cases resulted in heat stroke that required hospital treatment.(1) |
EPRONTIA, QSYMIA, QUDEXY XR, TOPAMAX, TOPIRAMATE, TOPIRAMATE ER, TROKENDI XR |
| Methenamine-Sodium Phosphate/Thiazides; Carbonic Anhydrase Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Thiazide diuretics and carbonic anhydrase inhibitors may elevate urinary ph preventing the conversion of methenamine to formaldehyde and mandelic acid.(1) CLINICAL EFFECTS: Concurrent administration may result in alkalinization of the urine causing methenamine to be less effective.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for urinary ph and any worsening symptoms of their infection, including dysuria, flank pain, or fever.(1) DISCUSSION: Administration of thiazide diuretics and carbonic anhydrase inhibitors may result in alkalinization of the urine resulting in therapeutic failure of methenamine. Formaldehyde is released by acid hydrolysis from methenamine resulting in bactericidal concentrations at urinary ph 5.0 to 5.5. Above urinary ph 6.0 there is insufficient quantities of formaldehyde and methenamine released to achieve a therapeutic response.(1) |
UROQID-ACID NO.2 |
| Zonisamide/Carbonic Anhydrase Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Zonisamide is a carbonic anhydrase inhibitor and can induce renal bicarbonate loss, resulting in metabolic acidosis. It can also reduce urinary citrate excretion and increase urinary pH, posing a risk for nephrolithiasis. As well, carbonic anhydrase inhibitors can cause decreased sweating and elevated body temperature, predisposing patients to heat-related disorders. Concurrent use of zonisamide with other carbonic anhydrase inhibitors may result in an additive risk of all these effects.(1-2) CLINICAL EFFECTS: The concurrent use of zonisamide with another carbonic anhydrase inhibitor may increase the risk of metabolic acidosis and kidney stone formation.(1) Concurrent use of zonisamide with other carbonic anhydrase inhibitors may increase the incidence of oligohidrosis and hyperthermia, especially in pediatric or adolescent patients.(1-2) Overheating and dehydration can lead to brain damage and death. PREDISPOSING FACTORS: Patients with conditions that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhea, and being on a ketogenic diet) may be at increased risk of experiencing adverse effects from concurrent carbonic anhydrase inhibitors.(1) Pediatric and adolescent patients and patients with dehydration may be more likely to experience heat-related disorders.(1) PATIENT MANAGEMENT: The UK and US manufacturers of zonisamide state that caution should be used in adults when zonisamide is prescribed with other carbonic anhydrase inhibitors.(1-2) Pediatric and adolescent patients must not take carbonic anhydrase inhibitors concurrently with zonisamide.(1) Check serum bicarbonate at baseline and periodically during treatment. Monitor for signs and symptoms of metabolic acidosis: hyperventilation, fatigue, anorexia, arrhthymias, stupor. Monitor for signs and symptoms of heat stroke: skin feels very hot with little or no sweating, confusion, muscle cramps, rapid heartbeat, or rapid breathing. Monitor for signs and symptoms of dehydration: dry mouth, urinating less than usual, dark-colored urine, dry skin, feeling tired, dizziness, or irritability. If signs or symptoms of metabolic acidosis, dehydration, oligohidrosis, or elevated body temperature occur, a decreased dose or discontinuation of zonisamide should be considered. DISCUSSION: Zonisamide is a carbonic anhydrase inhibitor. Carbonic anhydrase inhibitors increase urinary bicarbonate excretion, reduce urinary citrate excretion and increase urinary pH. Concurrent use of zonisamide with other carbonic anhydrase inhibitors may increase the risk of metabolic acidosis and kidney stone formation and should therefore be avoided.(1) Case reports of decreased sweating and elevated temperature have been reported, especially in pediatric patients. Some cases resulted in heat stroke that required hospital treatment and resulted in death.(1) |
ZONEGRAN, ZONISADE, ZONISAMIDE |
| Dextroamphetamine Transdermal/Urinary Alkalinizers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Urinary alkalinizers decrease the renal elimination of dextroamphetamine.(1) CLINICAL EFFECTS: Concurrent use of dextroamphetamine and urinary alkalinizers may result in increased dextroamphetamine levels and side effects. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of dextroamphetamine with urinary alkalinizing agents should be avoided.(1) DISCUSSION: Concurrent use of alkalinizing agents with dextroamphetamine decreases the renal elimination of dextroamphetamine. Co-administration of these should be avoided because of the potential of increased actions of dextroamphetamine.(1) |
XELSTRYM |
There are 7 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Sympathomimetics/Urinary Alkalinizers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Unionized sympathomimetic amines will be reabsorbed into systemic circulation from the distal tubules of the kidneys. CLINICAL EFFECTS: Enhanced sympathomimetic activity and increased risk of sympathomimetic toxicity. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Watch patient for enhanced sympathomimetic side effects when urinary alkalinizers are concomitantly used. A lower dose of certain sympathomimetics may be required. DISCUSSION: Signs and symptoms of sympathomimetic toxicity include euphoria, confusion, delirium, hallucinations and nervousness. |
AKOVAZ, BENZPHETAMINE HCL, EMERPHED, EPHEDRINE HCL, EPHEDRINE SULFATE, EPHEDRINE SULFATE-0.9% NACL, EPHEDRINE SULFATE-NACL, LISDEXAMFETAMINE DIMESYLATE, MIDODRINE HCL, REZIPRES, VYVANSE |
| Lithium/Carbonic Anhydrase Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Carbonic anhydrase inhibitors may increase the renal excretion of lithium, either by alkalinization of the urine or by impairing the proximal tubular reabsorption of lithium. CLINICAL EFFECTS: Concurrent use of a carbonic anhydrase inhibitor may result in decreased levels and clinical effectiveness of lithium. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Lithium levels should be monitored in patients receiving concurrent therapy or if the carbonic anhydrase inhibitor is withdrawn from concurrent therapy. The dose of lithium may need to be adjusted. DISCUSSION: One study involving six subjects showed that the concurrent use of a single dose of both lithium carbonate and acetazolamide caused a 27% to 31% increase in the urinary excretion of lithium.(1) Acetazolamide has been used in combination with other agents to treat lithium toxicity.(2) |
LITHIUM CARBONATE, LITHIUM CARBONATE ER, LITHIUM CITRATE, LITHIUM CITRATE TETRAHYDRATE, LITHOBID |
| Brinzolamide/Carbonic Anhydrase Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Brinzolamide and other carbonic anhydrase inhibitors cause a decrease in aqueous humor secretion by slowing the formation of bicarbonate ions with a subsequent reduction of sodium and fluid transport which results in a reduction of intraocular pressure.(1) CLINICAL EFFECTS: If brinzolamide is given with other carbonic anhydrase inhibitors it may cause electrolyte disturbances, because brinzolamide can be absorbed systemically.(1) PREDISPOSING FACTORS: Patients with conditions that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhea, and being on a ketogenic diet) may be at increased risk of experiencing adverse effects from concurrent carbonic anhydrase inhibitors. PATIENT MANAGEMENT: It is not recommended to use brinzolamide with systemic carbonic anhydrase inhibitors. DISCUSSION: Although no human data is available, electrolyte imbalance, development of an acidotic state, and possible nervous system effects may occur following oral administration of brinzolamide and another carbonic anhydrase inhibitor.(1) |
AZOPT, BRINZOLAMIDE, SIMBRINZA |
| Dorzolamide/Carbonic Anhydrase Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Dorzolamide and other carbonic anhydrase inhibitors cause a decrease in aqueous humor secretion by slowing the formation of bicarbonate ions with a subsequent reduction of sodium and fluid transport which results in a reduction of intraocular pressure.(1) CLINICAL EFFECTS: If dorzolamide is given with other carbonic anhydrase inhibitors it may cause electrolyte disturbances, because dorzolamide can be absorbed systemically.(1) PREDISPOSING FACTORS: Patients with conditions that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhea, and being on a ketogenic diet) may be at increased risk of experiencing adverse effects from concurrent carbonic anhydrase inhibitors. PATIENT MANAGEMENT: The manufacturer of dorzolamide states that concurrent use with oral carbonic anhydrase inhibitors is not recommended.(1) DISCUSSION: Although no human data is available, electrolyte imbalance, development of an acidotic state, and possible nervous system effects may occur following administration of dorzolamide and oral carbonic anhydrase inhibitors.(1) |
BRIMONIDINE-DORZOLAMIDE, COSOPT, COSOPT PF, DORZOLAMIDE, DORZOLAMIDE HCL, DORZOLAMIDE-TIMOLOL, TIMOLOL-BRIMONI-DORZOL-BIMATOP, TIMOLOL-BRIMONIDIN-DORZOLAMIDE, TIMOLOL-DORZOLAMIDE-BIMATOPRST |
| Memantine; Amantadine/Urinary Alkalinizers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Memantine and amantadine elimination is impaired by urinary alkalinization.(1,2) CLINICAL EFFECTS: Potentiation of memantine or amantadine effects may be observed. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor patient for adverse reactions such as dizziness, headache, or confusion if a urinary alkalinizer is required. The memantine or amantadine dose may need to be adjusted when a urinary alkalinizer is started or stopped.(1,2) DISCUSSION: The clearance of memantine was reduced by about 80% under alkaline urine conditions at pH 8. Urine alkalinization may lead to an accumulation of memantine with a possible increase in adverse effects. Urine pH is also altered by diet and clinical state of the patient (e.g., renal tubular acidosis or severe infections of the urinary tract). Hence, memantine should be used with caution under these conditions.(1) A study in rats showed that concomitant administration of sodium bicarbonate with amantadine caused a decrease in amantadine renal clearance (1.16 vs. 0.76). Amantadine's area-under-the-curve (AUC) was increased approximately 78%.(3) A study in 12 healthy subjects showed that plasma concentrations of memantine are dependent on urine pH. Alkaline urine pH caused a 79% reduction in renal clearance.(4) |
AMANTADINE, AMANTADINE HCL, GOCOVRI, MEMANTINE HCL, MEMANTINE HCL ER, MEMANTINE HCL-DONEPEZIL HCL ER, NAMENDA, NAMENDA XR, NAMZARIC, OSMOLEX ER |
| Metformin/Carbonic Anhydrase Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Carbonic anhydrase inhibitors increase bicarbonate excretion which may cause metabolic acidosis.(1) High systemic concentrations of metformin may result in lactic acidosis.(2,3) Topiramate, a mild carbonic anhydrase inhibitor, may also increase systemic exposure to metformin.(1) CLINICAL EFFECTS: Carbonic anhydrase inhibitors may increase the risk for metformin associated lactic acidosis.(1-3) Untreated lactic acidosis may be fatal. Symptoms of lactic acidosis include malaise, myalgias, respiratory distress, low blood pH, increased anion gap and elevated blood lactate.(2) Carbonic anhydrase inhibitors linked to this monograph are acetazolamide, dichlorphenamide, methazolamide, sulthiame, topiramate, and zonisamide. PREDISPOSING FACTORS: Risk factors for metformin associated lactic acidosis include renal impairment,sepsis, dehydration, excessive alcohol intake, acute or chronic metabolic acidosis, hepatic insufficiency, acute heart failure, metformin plasma levels > 5 micrograms/mL, and conditions which may lead to tissue hypoxia. Geriatric patients may also be at higher risk due to slower metformin clearance and increased half-life in this population. The risk for metabolic acidosis is higher with increased doses of either agent. PATIENT MANAGEMENT: For patients receiving concurrent therapy, monitor renal function and assure that patient does not have risk factors for metformin associated lactic acidosis. Discontinue metformin when risk factors are present. If both drugs are given, monitor renal function and for signs and symptoms of metformin toxicity (lactic acidosis) such as malaise, myalgias, respiratory distress, increasing somnolence, and respiratory distress. Laboratory results which may signal lactic acidosis include: low pH, an increased anion gap, and increased lactate to pyruvate ratio. Manufacturer recommendations: the manufacturer of metformin recommends caution with concomitant use of carbonic anhydrase inhibitors due to an increased risk for metformin associated lactic acidosis.(2) The manufacturer of topiramate notes that topiramate can frequently cause metabolic acidosis and that metformin should not be used in patients with metabolic acidosis.(1) DISCUSSION: A literature search for lactic acidosis due solely to the combination of metformin and carbonic anhydrase inhibitors or topiramate did not reveal any case reports of symptomatic metabolic acidosis due to this combination. Never-the-less, since carbonic anhydrase inhibitors act by inhibiting the reabsorption of bicarbonate in the renal tubule, some lowering of systemic bicarbonate and pH is common and supports the plausibility of this interaction. In addition, a pharmacokinetic interaction has been described with topiramate. A study in healthy volunteers evaluated the effect of topiramate 100 mg every 12 hours on the kinetics of metformin 500 mg every 12 hours. Mean metformin exposure (area-under-curve or AUC) was increased 25%.(1) |
ACTOPLUS MET, ALOGLIPTIN-METFORMIN, DAPAGLIFLOZIN-METFORMIN ER, GLIPIZIDE-METFORMIN, GLYBURIDE-METFORMIN HCL, INVOKAMET, INVOKAMET XR, JANUMET, JANUMET XR, JENTADUETO, JENTADUETO XR, KAZANO, METFORMIN ER GASTRIC, METFORMIN ER OSMOTIC, METFORMIN HCL, METFORMIN HCL ER, PIOGLITAZONE-METFORMIN, RIOMET, SAXAGLIPTIN-METFORMIN ER, SEGLUROMET, SITAGLIPTIN-METFORMIN, SYNJARDY, SYNJARDY XR, TRIJARDY XR, XIGDUO XR, ZITUVIMET, ZITUVIMET XR |
| Dichlorphenamide/Aspirin (Less Than or Equal To 325 mg) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Carbonic anhydrase inhibitors (eg, acetazolamide) may reduce blood pH, causing a shift of salicylates from plasma into tissues (eg, central nervous system).(1) Alternatively, toxicity may be due to salicylate-induced displacement of the carbonic anhydrase inhibitor from its protein binding sites and inhibition of renal tubular secretion. CLINICAL EFFECTS: An increase in the pharmacologic effects of salicylates with possible toxicity may occur. Anorexia, tachypnea, lethargy, and coma have been reported.(1) PREDISPOSING FACTORS: High doses of salicylates, low body weight. PATIENT MANAGEMENT: The concurrent use of high-dose aspirin or other salicylates with dichlorphenamide is contraindicated. If it is necessary to administer a low-dose salicylate concurrently, use the lowest dose possible or replace it with a non-salicylate anti-inflammatory agent. Monitor salicylate levels and serum bicarbonate concentrations, and monitor the patient for symptoms of toxicity. Adjust the dose as needed.(1) DISCUSSION: An 8-year-old boy with unimpaired renal and hepatic function was found to have developed metabolic acidosis after treatment for glaucoma and joint pain with a combination of aloxiprin 3.6 gram daily and dichlorphenamide 25 mg three times daily. His symptoms resolved after discontinuation of both aloxiprin and dichlorphenamide and did not recur on subsequent therapy with naproxen and dichlorphenamide.(2) A 75-year old woman taking dichlorphenamide 100 mg to 150 mg daily for therapy of glaucoma and high doses of aspirin (975 mg 4 to 5 times daily) for arthritis developed severe acid-base imbalance and salicylate intoxication. The patient did not exhibit ill effects when taking high aspirin doses without dichlorphenamide.(3) |
ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, ASPIRIN-DIPYRIDAMOLE ER, BUTALBITAL-ASPIRIN-CAFFEINE, CARISOPRODOL-ASPIRIN, CARISOPRODOL-ASPIRIN-CODEINE, DURLAZA, YOSPRALA |
The following contraindication information is available for KEVEYIS (dichlorphenamide):
Drug contraindication overview.
Hypersensitivity to dichlorphenamide or other sulfonamides. Concomitant use of high-dose aspirin. (See Concomitant Use with Aspirin under Cautions: Warnings/Precautions, and also see Drug Interactions: Aspirin.) Severe pulmonary disease that limits compensation to dichlorphenamide-induced metabolic acidosis.
Hepatic insufficiency. (See Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)
Hypersensitivity to dichlorphenamide or other sulfonamides. Concomitant use of high-dose aspirin. (See Concomitant Use with Aspirin under Cautions: Warnings/Precautions, and also see Drug Interactions: Aspirin.) Severe pulmonary disease that limits compensation to dichlorphenamide-induced metabolic acidosis.
Hepatic insufficiency. (See Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)
There are 6 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Hepatic cirrhosis |
| Hyperchloremic acidosis |
| Hypokalemia |
| Hyponatremia |
| Primary adrenocortical insufficiency |
| Renal tubular acidosis |
There are 4 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Blood dyscrasias |
| Disease of liver |
| Recurrent calcium renal calculi |
| Respiratory acidosis |
There are 4 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Gout |
| Kidney disease with reduction in glomerular filtration rate (GFr) |
| Type 1 diabetes mellitus |
| Type 2 diabetes mellitus |
The following adverse reaction information is available for KEVEYIS (dichlorphenamide):
Adverse reaction overview.
Adverse effects reported in 5% or more of patients receiving dichlorphenamide for periodic paralysis and at a higher incidence than that reported with placebo include paresthesia, cognitive disorder, dysgeusia, confusional state, headache, hypoesthesia, lethargy, fatigue, muscle spasms, rash, dizziness, diarrhea, nausea, malaise, weight loss, arthralgia, muscle twitching, dyspnea, pharyngolaryngeal pain, and pruritus.
Adverse effects reported in 5% or more of patients receiving dichlorphenamide for periodic paralysis and at a higher incidence than that reported with placebo include paresthesia, cognitive disorder, dysgeusia, confusional state, headache, hypoesthesia, lethargy, fatigue, muscle spasms, rash, dizziness, diarrhea, nausea, malaise, weight loss, arthralgia, muscle twitching, dyspnea, pharyngolaryngeal pain, and pruritus.
There are 30 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. |
Crystalluria Depression Nephrotoxicity Pruritus of skin Skin rash |
| Rare/Very Rare |
|---|
|
Accidental fall Agranulocytosis Allergic dermatitis Anaphylaxis Aplastic anemia Blood dyscrasias Drug fever Drug-induced psychosis Dyskinesia Heart failure Hepatic necrosis Hypokalemia Kidney stone Metabolic acidosis Muscle weakness Myopia Pancytopenia Renal tubular necrosis Seizure disorder Stevens-johnson syndrome Stupor Toxic epidermal necrolysis Tremor Unsteady gait Urticaria |
There are 29 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Acute cognitive impairment Anorexia Dysgeusia Fatigue Head sensation disturbance Increased urinary frequency Malaise Paresthesia Weight loss |
Arthralgia Diarrhea Dizziness Drowsy Dyspnea Headache disorder Hypoesthesia Lethargy Muscle fasciculation Muscle spasm Nausea Sore throat |
| Rare/Very Rare |
|---|
|
Constipation Hallucinations Irritability Memory impairment Nervousness Parosmia Syncope Vomiting |
The following precautions are available for KEVEYIS (dichlorphenamide):
Safety and efficacy of dichlorphenamide have not been established in pediatric patients.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Category C. (See Users Guide.) There are no adequate and well-controlled studies of dichlorphenamide in pregnant women; teratogenic effects have been observed in animals. The drug should be used during pregnancy only if the potential benefits justify the potential risks to the fetus.
It is not known whether dichlorphenamide is distributed into milk. Because many drugs are distributed into human milk, caution is advised if dichlorphenamide is used in nursing women.
Adverse effects such as risk of falls and metabolic acidosis appear to be greater in geriatric patients.
The following prioritized warning is available for KEVEYIS (dichlorphenamide):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for KEVEYIS (dichlorphenamide)'s list of indications:
| Familial hyperkalemic periodic paralysis | |
| G72.3 | Periodic paralysis |
| Familial hypokalemic periodic paralysis | |
| G72.3 | Periodic paralysis |
Formulary Reference Tool