Acrivastine and pseudoephedrine

Acrivastine and pseudoephedrine: Drug information
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(For additional information see “Acrivastine and pseudoephedrine: Patient drug information”)

Brand Names: U.S. Semprex®-D
Pharmacologic Category Alkylamine Derivative; Alpha/Beta Agonist; Decongestant; Histamine H1; Antagonist Histamine H1 Antagonist, Second Generation
Dosing: Adult Rhinitis, nasal congestion, allergic symptoms: Oral: One capsule every 4-6 hours (maximum: 4 doses/24 hours); treatment for >14 days has not been evaluated
Dosing: Pediatric Children ≥12 years: Refer to adult dosing.
Dosing: Geriatric Refer to adult dosing.
Dosing: Renal Impairment Avoid use in patients with Clcr ≤48 mL/minute.
Dosing: Hepatic Impairment There are no dosage adjustments recommended in manufacturer’s labeling.
Dosage Forms: U.S. Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule:

Semprex®-D: Acrivastine 8 mg and pseudoephedrine hydrochloride 60 mg

Generic Equivalent Available: U.S. No
Use Relief of symptoms associated with seasonal allergic rhinitis
Adverse Reactions Significant Also refer to Pseudoephedrine monograph.
>10%: Central nervous system: Headache (19%), somnolence (12%)

1% to 10%:

Central nervous system: Insomnia (4%), dizziness (3%), nervousness (3%)

Endocrine & metabolic: Dysmenorrhea (2%)

Gastrointestinal: Xerostomia (7%), dyspepsia (2%), nausea (2%)

Respiratory: Pharyngitis (3%), cough (2%)

Postmarketing and/or case reports: Anaphylaxis, angioedema, bronchospasm, erythema multiforme

Contraindications Hypersensitivity to pseudoephedrine, acrivastine (or other alkylamine antihistamines), or any component of the formulation; use with or within 14 days of MAO inhibitors; severe hypertension, severe coronary artery disease
Warnings/Precautions
Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease (including hypertension and ischemic heart disease); contraindicated with severe disease.

• Diabetes: Use with caution in patients with diabetes mellitus.

• Increased intraocular pressure/glaucoma: Use with caution in patients with increased intraocular pressure or glaucoma.

• Prostatic hyperplasia/urinary obstruction: Use with caution in patients with prostatic hyperplasia and/or GU obstruction.

• Pyloroduodenal obstruction: Use with caution in patients with pyloroduodenal obstruction (including stenotic peptic ulcer).

• Renal impairment: Use with caution in patients with renal impairment; avoid use in patients with Clcr ≤48 mL/minute.

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.

Special populations:

• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects.

Drug Interactions
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Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy

Antacids: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Aluminum Hydroxide. Risk C: Monitor therapy

Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Levocabastine (Nasal); Paliperidone. Risk C: Monitor therapy

Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Benzylpenicilloyl Polylysine: Antihistamines may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. A histamine skin test may be used to assess persistent antihistaminic effects. Risk D: Consider therapy modification

Benzylpenicilloyl Polylysine: Alpha-/Beta-Agonists may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Consider use of a histamine skin test as a positive control to assess a patient’s ability to mount a wheal and flare response. Risk D: Consider therapy modification

Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy

Bromocriptine: Alpha-/Beta-Agonists may enhance the adverse/toxic effect of Bromocriptine. Including increased blood pressure, ventricular arrhythmias, and seizure. Risk C: Monitor therapy

Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Carbonic Anhydrase Inhibitors: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Brinzolamide; Dorzolamide. Risk C: Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

FentaNYL: Alpha-/Beta-Agonists (Indirect-Acting) may decrease the serum concentration of FentaNYL. Specifically, fentanyl nasal spray serum concentrations may decrease and onset of effect may be delayed. Risk C: Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination

MAO Inhibitors: May enhance the hypertensive effect of Alpha-/Beta-Agonists (Indirect-Acting). Risk X: Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. Risk D: Consider therapy modification

Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy

Ethanol/Nutrition/Herb Interactions Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Pregnancy Risk Factor B (show table)
Pregnancy Implications Teratogenic effects were not observed in animal reproduction studies with this combination; therefore, the manufacturer classifies acrivastine/pseudoephedrine as pregnancy category B. The use of antihistamines for the treatment of rhinitis during pregnancy is generally considered to be safe at recommended doses. Information related to the use of acrivastine during pregnancy is limited; therefore, other agents are preferred. Also refer to the Pseudoephedrine monograph for additional information.
Lactation Pseudoephedrine enters breast milk/not recommended
Breast-Feeding Considerations It is not known if acrivastine is excreted into breast milk. According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy with this combination product should take into account the risk of exposure to the infant and the benefits of treatment to the mother. Pseudoephedrine is excreted into breast milk; refer to the Pseudoephedrine monograph for additional information.
Pricing: U.S. (www.drugstore.com)
Capsules (Semprex-D)

8-60 mg (30): $76.27

International Brand Names Duact (DK, FI)
Mechanism of Action Refer to Pseudoephedrine; acrivastine is an analogue of triprolidine and it is considered to be relatively less sedating than traditional antihistamines; believed to involve competitive blockade of H1-receptor sites resulting in the inability of histamine to combine with its receptor sites and exert its usual effects on target cells
Pharmacodynamics/Kinetics
Pseudoephedrine: See Pseudoephedrine.

Acrivastine:

Absorption: Rapidly absorbed

Distribution: ~0.5-0.8 L/kg

Protein binding: ~50% primarily to albumin

Metabolism: Minimally hepatic

Half-life elimination: ~2-4 hours

Acrivastine propionic acid metabolite (active): ~4 hours

Time to peak: ~1.1 hours

Excretion: Urine (84%); feces (13%)

REFERENCES
Brogden RN and McTavish D, “Acrivastine: A Review of Its Pharmacological Properties and Therapeutic Efficacy in Allergic Rhinitis, Urticaria, and Related Disorders,” Drugs, 1991, 41(6):927-40. [PubMed 1715267]
Levien TL and Baker DE, “Reviews of Acrivastine and Midotrine,” Hosp Pharm, 1995, 30(3):229-35.