SEMPREX-D Capsules should be used with caution in patients with hypertension, diabetes mellitus, ischemic heart disease, increased intraocular pressure, hyperthyroidism, prostatic hypertrophy, stenosing peptic ulcer, or pyloroduodenal obstruction. Overdose of sympathomimetic amines may produce CNS stimulation with convulsions or cardiovascular collapse with accompanying hypotension. The elderly are more likely to have adverse reactions to sympathomimetic amines.

General

Acrivastine is sedating in some patients. In controlled clinical trials, somnolence (i.e., drowsiness, sedation, sleepiness) was more common with SEMPREX-D Capsules (by an average of 6%) than with placebo (see ADVERSE REACTIONS).

Patients should be advised to assess their individual responses to SEMPREX-D Capsules before engaging in any activity requiring mental alertness, such as driving a motor vehicle or operating machinery. Concurrent use of SEMPREX-D Capsules with alcohol or other CNS depressants may cause additional reductions in alertness and impairment of CNS performance and should be avoided (see DRUG INTERACTIONS).

Use in Patients with Diminished Renal Function

Acrivastine and pseudoephedrine are excreted primarily through the kidney. Both compounds therefore accumulate in patients with impaired renal function. Due to the differential effects of renal failure on the serum half-life and clearance of acrivastine and pseudoephedrine, use of SEMPREX-D Capsules, a fixed combination product, in patients with renal impairment (creatinine clearance = 48 mL/min) is not recommended (see OVERDOSAGE and CLINICAL PHARMACOLOGY).

Use in the Elderly (Approximately 60 Years or Older)

Elderly patients who participated in clinical trials did not differ in effectiveness or adverse effects from younger patients. Antihistamines, however, as a pharmaceutical class, are more likely to cause dizziness, sedation, bladder- neck obstruction, and hypotension in elderly patients. The elderly are also more likely to have adverse reactions to sympathomimetics such as pseudoephedrine (see CLINICAL PHARMACOLOGY and

WARNINGS

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Carcinogenicity studies with the combination of acrivastine and pseudoephedrine have not been performed. Oral doses of acrivastine alone at levels up to 40 mg/kg/day (236 mg/m²/day or 10 times the recommended human daily dose) for 20 to 22 months in rats and up to 250 mg/kg/day (750 mg/m²/day or 32 times the recommended human daily dose) for 20 to 24 months in mice revealed no evidence of carcinogenic potential. No evidence of mutagenicity (with or without metabolic activation) was observed in the Ames Salmonella mutagenicity assay or in the L5178Y/ tk+/- mouse lymphoma assay. In an in vitro cytogenetic study performed in cultured human lymphocytes, acrivastine induced structural chrornosomal abnormalities in the absence of metabolic activation, but not in its presence. In an in vivo cytogenetic study in rats given single oral doses of acrivastine up to 1000 mg/kg (5900 mg/m² or 249 times the recommended human daily dose) there were no structural chromosomal alterations.

Reproduction- fertility studies in rats given acrivastine alone at levels up to 200 mg/kg/day (1180 mg/m²/day or 50 times the recommended human daily dose) had no effect on male or female fertility. Similarly, no effect on fertility was seen in male rats given acrivastine 20 mg/kg/day and pseudoephedrine 100 mg/kg/day (118 and 590 mg/m²/day or 5 and 3 times the recommended human daily doses, respectively) or in female rats given acrivastine 4 mg/kg/day and pseudoephedrine 20 mg/kg/day (23.6 and 118 mg/m²/day or 1 and 0.7 times the recommended human daily doses, respectively).

Pregnancy

Nonteratogenic Effects: In a perinatal-postnatal study in rats, acrivastine given alone at levels up to 500 mg/kg/day (2950 mg/m²/day or 124 times the recommended human daily dose) was associated with maternal and neonatal mortality at the maximum dose level. Neonatal survival was decreased in rats given a combination of acrivastine 20 mg/kg/day and pseudoephedrine 100 mg/kg/day (118 and 590 mg/m²/day or 5 and 3 times the human dose, respectively).

Nursing Mothers

It is not known whether acrivastine is excreted in human milk; pseudoephedrine is excreted in human milk. SEMPREX-D Capsules should only be used in nursing mothers when the potential benefit justifies the potential risks to the nursing infant.

Pediatric Use

Safety and effectiveness of SEMPREX- D Capsules in children under the age of 12 years have not been established.

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