KEVEYIS Tablet Ref.[10013] Active ingredients: Diclofenamide

5.1 Hypersensitivity / Anaphylaxis / Idiosyncratic Reactions

Fatalities associated with the administration of sulfonamides have occurred due to adverse reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias. Pulmonary involvement can occur in isolation or as part of a systemic reaction.

KEVEYIS should be discontinued at the first appearance of skin rash or any sign of immune-mediated or idiosyncratic adverse reaction.

5.2 Concomitant Use of Aspirin

Anorexia, tachypnea, lethargy, and coma have been reported with concomitant use of dichlorphenamide and high-dose aspirin. The concomitant use of KEVEYIS and high dose aspirin is contraindicated. KEVEYIS should be used with caution in patients receiving low dose aspirin.

5.3 Hypokalemia

KEVEYIS increases potassium excretion and can cause hypokalemia. The risk of hypokalemia is greater when KEVEYIS is used in patients with conditions associated with hypokalemia (e.g., adrenocortical insufficiency, hyperchloremic metabolic acidosis, or respiratory acidosis), and in patients receiving other drugs that may cause hypokalemia (e.g., loop diuretics, thiazide diuretics, laxatives, antifungals, penicillin, and theophylline).

Baseline and periodic measurement of serum potassium during KEVEYIS treatment are recommended.

If hypokalemia develops or persists, consideration should be given to reducing the dose or discontinuing KEVEYIS.

5.4 Metabolic Acidosis

KEVEYIS can cause hyperchloremic non-anion gap metabolic acidosis. Concomitant use of KEVEYIS with other drugs that cause metabolic acidosis may increase the severity of metabolic acidosis.

Baseline and periodic measurement of serum bicarbonate during KEVEYIS treatment are recommended.

If metabolic acidosis develops or persists, consideration should be given to reducing the dose or discontinuing KEVEYIS.

5.5 Falls

KEVEYIS increases the risk of falls. The risk of falls is greater in the elderly and with higher doses of KEVEYIS. Consider dose reduction or discontinuation of KEVEYIS in patients who experience falls while treated with KEVEYIS.

The following serious adverse reactions are described elsewhere in labeling:

• Hypersensitivity / Anaphylaxis / Idiosyncratic 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)]

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 KEVEYIS, with rates greater than placebo, were paresthesia, cognitive disorder, dysgeusia, and confusional state. The mean dose of KEVEYIS 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 KEVEYIS and more commonly than in patients treated with placebo in Study 1.

Table 1. Adverse Reactions in Patients Treated with KEVEYIS 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.

The following 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 for dichlorphenamide that were serious adverse events or are not reported in the previous section of labeling [see Clinical Trials Experience (6.1)]: amnesia, cardiac failure, condition aggravated, convulsion, fetal death, hallucination, nephrolithiasis, pancytopenia, psychotic disorder, renal tubular necrosis, stupor, syncope, tremor.

7.1 Aspirin and Salicylates

KEVEYIS may cause an elevation in salicylate levels in patients receiving aspirin. Anorexia, tachypnea, lethargy, and coma have been reported with concomitant use of dichlorphenamide and high-dose aspirin.

Concomitant use of KEVEYIS and high dose aspirin is contraindicated. KEVEYIS should be used with caution in patients receiving low dose aspirin [see Contraindications (4) and Warnings and Precautions (5.2)].

Pregnancy Category C.

There are no adequate and well-controlled studies in pregnant women. 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/m²) basis. A no-effect dose has not been established. KEVEYIS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether dichlorphenamide is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when dichlorphenamide is administered to a nursing woman.

Safety and effectiveness in pediatric patients have not been established.

The risk of falls and of metabolic acidosis are greater in elderly patients.