pseudoephedrine/desloratadine (Rx)

>10%

Desloratadine

• Fever (12%)
• Irritability (12%)
• Headache (12%)
• Diarrhea (15-21%)
• Cough (11%)
• Upper respiratory tract infection (11-21%)

1-10%

Desloratadine

• Pharyngitis (4.1%)
• Dry mouth (3%)
• Myalgia (2.1%)
• Emotional lability (3%)
• Erythema (3%)
• Macopapular rash (3%)
• Dizziness (4%)
• Fatigue (2.1%)
• Somnolence (2.1%)
• Urinary tract infection (4%)
• Dyspepsia (3%)
• Insomnia (5%)
• Dysmenorrhea (2.1%)

Frequency Not Defined

Pseudoephedrine

• CNS (tremor, restlessness, etc)
• Insomnia
• Arrhythmia
• Hypotension
• Tachycardia
• Fatigue
• Rash
• Urticaria
• Anorexia
• Xerostomia
• Dysuria
• Polyuria
• Nausea
• Vomiting
• Ischemic colitis

Postmarketing Reports

Hypersensitivity reactions (eg, rash, edema, dyspnea, anaphylaxis)

CNS: Headache, somnolence, dizziness

Cardiovascular: Tachycardia

Neurologic: Movement disorders (including dystonia, tics, and extrapyramidal symptoms), seizures

Hepatic: Elevated liver enzymes and bilirubin, hepatitis (rare)

Skin reactions: Generalized exanthematous pustulosis, increased appetite

Contraindications

Hypersensitivity; adverse reaction to sympathomimetics

Severe HTN, severe coronary artery disease

Concurrent MAO inhibitors, or within 2 wk of discontinuance of MAO inhibitors

Hepatic impairment

Urinary retention

Narrow-angle glaucoma

Clarinex-D 12 hr: also renal impairment

Cautions

Caution in renal impairment, HTN, diabetes mellitus, ischemic heart disease, increase IOP, hyperthyroidism, BPH

Concomitant antihistamines or decongestants (generally avoid)

Seizures and tachycardia reported

Pregnancy

The limited available data in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage; there are no adequate and well-controlled studies in pregnant women

The majority of studies examining use of pseudoephedrine in pregnancy did not find an association with increased risk of congenital anomalies; a few case-control studies conducted reported potential associations with isolated congenital disorders; however, methodological limitations of these studies made the interpretation of results unreliable

Reproductive potential

• There are no data available on human infertility associated with desloratadine, pseudoephedrine, or combination; there are no animal fertility studies with combination or pseudoephedrine alone
• Female: There were no clinically relevant effects of desloratadine on female fertility in rats
• Male: A male specific decrease in fertility occurred at an oral desloratadine dose of ≥12 mg/kg in rats (approximately 65 times the RHD); male fertility was unaffected at a desloratadine dose of 3 mg/kg (approximately 10 times the RHD)

Animal data

• Data on animal reproduction studies conducted with combination of desloratadine and pseudoephedrine or pseudoephedrine alone are also limited
• Desloratadine given during organogenesis to pregnant rats was not teratogenic at approximately 320 times that at recommended human daily oral dose (RHD) of 5 mg/day
• Desloratadine given during organogenesis to pregnant rabbits was not teratogenic at AUC-based exposures of desloratadine approximately 230 times that at RHD
• Desloratadine given to pregnant rats during organogenesis through lactation resulted in reduced body weight and slow righting reflex of F1 pups at exposures of desloratadine and its metabolite approximately 70 times or greater than that at the RHD

Lactation

Desloratadine and pseudoephedrine both pass into breast milk; there are no sufficient data on effects of desloratadine on breastfed infant or effects of desloratadine on milk production

Pseudoephedrine has been reported to decrease milk production and to cause irritability in breastfed infants; the decision should be made whether to discontinue nursing or to discontinue drug, taking into account developmental and health benefits of breastfeeding, the nursing mother’s clinical need, and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Pseudoephedrine: Sympathomimetic; exerts decongestant action on nasal mucosa; stimulates the alpha-adrenergic receptors causing bronchodilation and vasoconstriction

Desloratadine: Selective histamine-1 receptor antagonist; inhibits histamine release from mast cells

Protein Binding

Desloratadine: 82-87%

Excretion

Pseudoephedrine: Urine

Desloratadine: Urine

Peak Plasma Time

Pseudoephedrine: 6-9 hr

Desloratadine: 4-7 hr

Peak Plasma Concentration

Pseudoephedrine: 363 ng/mL

Desloratadine: 1.09 ng/mL

AUC

Pseudoephedrine: 4,588 ng·hr/mL

Desloratadine: 31.6 ng·hr/mL

Metabolism

Pseudoephedrine: <1% metabolized in liver

Desloratadine: major metabolite of loratadine; extensively metabolized by glucuronidation to active metabolite 3-hydroxydesloratadine

Half-Life

Pseudoephedrine: 3-6 hr (urine pH 5); 9-16 hr (urine pH 8)

Desloratadine: 27 hr