MAO inhibitors and beta-adrenergic agonists increase the effects of sympathomimetic amines. Concomitant use of sympathomimetic amines with MAO inhibitors can result in a hypertensive crisis (see CONTRAINDICATIONS). Because MAO inhibitors are long-acting, SEMPREX-D Capsules should not be taken with an MAO inhibitor or for 14 days after stopping use of an MAO inhibitor.
Because of their pseudoephedrine content, SEMPREX-D Capsules may reduce the antihypertensive effects of drugs that interfere with sympathetic activity. Care should be taken in the administration of SEMPREX-D Capsules concomitantly with other sympathomimetic amines because the combined effects on the cardiovascular system may be harmful to the patient
Concomitant administration of SEMPREX-D Capsules with alcohol and other CNS depressants may result in additional reductions in alertness and impairment of CNS performance and should be avoided.
No formal drug interaction studies between SEMPREX-D Capsules and other possibly co-administered drugs have been performed.
There have been no reports of overdosage with Semprex-D Capsules. In the clinical trial program and in international post-marketing experience, there have been two reported overdoses with acrivastine. Doses were 72 mg and 322 mg. Both patients recovered without sequelae. Adverse events included trembling, stridor, loss of consciousness and possible convulsions in the first patient and somnolence in the second.
Since acrivastine and pseudoephedrine have pharmacologically different actions, it is difficult to predict how an individual will respond to overdosage with SEMPREX-D Capsules. However, acute overdosage with SEMPREX-D Capsules may produce clinical signs of either CNS stimulation or depression. Overdosage of sympathomimetics has been associated with the following events: fear, anxiety, tenseness, restlessness, tremor, weakness, pallor, respiratory difficulty, dysuria, insomnia, hallucinations, convulsions, CNS depression, arrhythmias, and cardiovascular collapse with hypotension. Treatment for overdosage with SEMPREX-D Capsules should follow general symptomatic and supportive principles.
In a placebo-controlled, double-blind clinical trial in 18 healthy male subjects, single doses of acrivastine up to 400 mg (50 times the recommended antihistaminic dose) produced only a weak vagolytic effect, manifested as an increase in heart rate, and did not cause cardiac repolarization delays (i.e., increased QTc). Daily doses of acrivastine up to 2400 mg (75 times the recommended antihistamine dose) in an uncontrolled study in 38 cancer patients produced a 15-beats-per-minute increase in mean heart rate and occasional episodes of nausea and vomiting. The effects of acrivastine plus pseudoephedrine at single or multiple doses higher than the recommended daily dose of SEMPREX-D Capsules (i.e., 32 mg acrivastine plus 240 mg pseudoephedrine) on heart rate and cardiac repolarization have not been investigated in clinical trials.
The mean LD50 (single, oral dose) of acrivastine is greater than 4000 mg/kg (23600 mg/m2 or 1000 times the recommended human daily dose) in rats and greater than 1200 mg/kg (3600 mg/m2 or 153 times the recommended human daily dose) in mice. The mean LD50 (single, oral dose) of pseudoephedrine hydrochloride is 2206 mg/kg (13015 mg/m2 or 73 times the recommended human daily dose) in rats and 726 mg/kg (2178 mg/m2 or 12 times the recommended human daily dose) in mice. The toxic and lethal concentrations of acrivastine and pseudoephedrine in human biologic fluids are not known. Based upon pharmacokinetic screening data from clinical trials, the maximum plasma acrivastine concentration after dosing with acrivastine 8 mg was 393 ng/mL and the maximum plasma pseudoephedrine concentration after dosing with pseudoephedrine hydrochloride 60 mg was 1308 ng/mL.
SEMPREX-D Capsules are contraindicated in patients with a known sensitivity to acrivastine, other alkylamine antihistamines (e.g., triprolidine), pseudoephedrine, other sympathomimetic amines (e.g., phenylpropanolamine), or to any other components of the formulation. SEMPREX-D Capsules are contraindicated in patients with severe hypertension or severe coronary artery disease. SEMPREX-D Capsules are contraindicated in patients taking monoamine oxidase (MAO) inhibitors and for 14 days after stopping use of an MAO inhibitor (see Drug Interactions).