Acrivastine (1 brand name, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- SEMPREX-D
Indications and Usage
SEMPREX-D Capsules are indicated for relief of symptoms associated with seasonal allergic rhinitis such as sneezing, rhinorrhea, pruritus, lacrimation, and nasal congestion. SEMPREX-D Capsules should be administered when both the antihistaminic activity of acrivastine and the nasal decongestant activity of pseudoephedrine are desired (see CLINICAL PHARMACOLOGY). The efficacy of SEMPREX-D Capsules beyond 14 days of continuous treatment in patients with seasonal allergic rhinitis has not been adequately investigated in clinical trials.SEMPREX-D Capsules have not been adequately studied for effectiveness in relieving the symptoms of the common cold.
Dosage and Administration
The recommended dosage for adults and adolescents 12 years and older is one capsule administered orally, every 4 to 6 hours four times a day.
Contraindications
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).
Adverse Reactions
Information on the incidence of adverse events in clinical investigations conducted in the U.S. was obtained from 33 controlled and 15 uncontrolled clinical studies in which 2499 patients received acrivastine and 2631 patients received acrivastine plus pseudoephedrine hydrochloride for treatment periods ranging from one day to one year. The majority of patients in clinical trials were exposed to acrivastine or acrivastine plus pseudoephedrine for less than 90 days. Acrivastine dosage ranged from 3 to 96 mg/day; 1336 patients received dosages equal to or greater than acrivastine 24 mg/day. Acrivastine plus pseudoephedrine hydrochloride dosages ranged from acrivastine 8 to 48 mg/day plus pseudoephedrine hydrochloride 60 to 240 mg/day. A total of 2335 patients received three or four daily doses of acrivastine 8 mg plus pseudoephedrine hydrochloride 60 mg.In controlled clinical trials, only 12 spontaneously elicited adverse events were reported with frequencies greater than 1% in the acrivastine plus pseudoephedrine hydrochloride treatment group (see table).TABLE 1 ADVERSE EVENTS REPORTED IN CLINICAL TRIALS* (PERCENT OF PATIENTS REPORTING)† Controlled Studies Placebo(N = 1767)Acrivastine(N = 1935)Pseudoephedrine(N = 887)Acrivastine plus Pseudoephedrine(N = 1650) *Includes all events regardless of casual relationship to treatment. †Includes all adverse events with a reported frequency of > 1% for the acrivastine plus pseudoephedrine treatment group.‡SEMPREX-D demonstrates a statistically higher frequency of events than placebo, p ≤ 0.05. CNS Somnolence‡612812 Headache18191919 Dizziness2333 Nervousness‡1243 Insomnia‡1164 MISCELLANEOUS Nausea2332 Dry Mouth‡2357 Asthenia2322 Dyspepsia1122 Pharyngitis2113 Cough Increase1212 Dysmenorrhea1232 The nature and overall frequencies of adverse events from international clinical trials (35 studies involving approximately 1600 patients) were similar to the results obtained in the U.S. studies.Post-marketing clinical experience reports
Drug Interactions
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 patientConcomitant 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.
Overdosage
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