AHFS Class:

• First Generation Antihistamines 4:04

Generic Name(s):

• Clemastine Fumarate

Associated Monographs

• Antihistamines General Statement

Clemastine is an ethanolamine-derivative, first generation antihistamine.

Administration

Clemastine fumarate is administered orally.

Dosage

Dosage of clemastine fumarate should be individualized according to the patient's response and tolerance.

Allergic Rhinitis

For the symptomatic treatment of allergic rhinitis in adults and children 12 years of age and older, the usual initial dosage of clemastine fumarate is 1.34 mg every 12 hours; this is the maximum daily dosage recommended for self-medication . When used under the direction of a clinician in this age group, dosage may be increased as necessary, but should not exceed 8.04 mg daily.

For the symptomatic treatment of allergic rhinitis in children 6 to younger than 12 years of age, clemastine fumarate should be used as directed by a clinician. The usual initial dosage of clemastine fumarate is 0.67 mg twice daily; since single doses of up to 3.02 mg have been well tolerated by this age group, dosage may be increased as necessary, but should not exceed 4.02 mg daily.

Allergic Urticaria and Angioedema

For the symptomatic treatment of mild allergic urticaria and angioedema in adults and children 12 years of age and older, clemastine fumarate should be used only at the 2. 68-mg dosage level. The usual dosage in these patients is 2.68 mg 1-3 times daily; dosage should not exceed 8.04 mg daily. For the symptomatic treatment of mild allergic urticaria and angioedema in children 6 to younger than 12 years of age, the usual initial dosage of clemastine fumarate is 1.34 mg twice daily; dosage may be increased as necessary, but should not exceed 4.02 mg daily.

Common Cold

For the temporary relief of rhinorrhea or sneezing associated with the common cold in adults and children 12 years of age and older, the usual dosage of clemastine fumarate for self-medication is 1.34 mg every 12 hours, not to exceed 2.68 mg daily unless otherwise directed by a clinician.

Clemastine fumarate shares the toxic potentials of other antihistamines, and the usual precautions of antihistamine therapy should be observed. (See Cautions in the Antihistamines General Statement 4:00.)

Pediatric Precautions

Like other antihistamines, clemastine fumarate should not be used in premature or full-term neonates. (See Cautions: CNS Effects and Pediatric Precautions, in the Antihistamines General Statement 4:00.) Safety and efficacy of clemastine fumarate tablets in children younger than 12 years of age have not been established. Safety and efficacy of clemastine fumarate oral solution in children younger than 6 years of age have not been established.

Overdosage and toxicity (including death) have been reported in children younger than 2 years of age receiving nonprescription (over-the-counter, OTC) preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection. There is limited evidence of efficacy for these preparations in this age group, and appropriate dosages (i.e., approved by the US Food and Drug Administration [FDA]) for the symptomatic treatment of cold and cough have not been established. Therefore, FDA stated that nonprescription cough and cold preparations should not be used in children younger than 2 years of a the agency continues to assess safety and efficacy of these preparations in older children. Meanwhile, because children 2-3 years of age also are at increased risk of overdosage and toxicity, some manufacturers of oral nonprescription cough and cold preparations agreed to voluntarily revise the product labeling to state that such preparations should not be used in children younger than 4 years of age. FDA recommends that parents and caregivers adhere to the dosage instructions and warnings on the product labeling that accompanies the preparation if administering to children and consult with their clinician about any concerns. Clinicians should ask caregivers about use of nonprescription cough and cold preparations to avoid overdosage. For additional information on precautions associated with the use of cough and cold preparations in pediatric patients, see Cautions: Pediatric Precautions in the Antihistamines General Statement 4:00.

Geriatric Precautions

Geriatric patients (60 years of age and older) may be particularly susceptible to dizziness, sedation, and hypotension.

Mutagenicity and Carcinogenicity

The mutagenic potential of clemastine fumarate has not been determined. There was no evidence of carcinogenesis in rats receiving clemastine fumarate at an oral dosage of 84 mg/kg (about 500 times the usual human adult dosage) for 2 years or in mice receiving 206 mg/kg (about 1300 times the usual human adult dosage) for 85 weeks.

Pregnancy, Fertility, and Lactation

Pregnancy

Reproduction studies in rats and rabbits using oral clemastine fumarate dosages up to 312 and 188 times the usual human adult dosage, respectively, have not revealed evidence of harm to the fetus. There are no adequate and controlled studies to date using clemastine fumarate in pregnant women, and the drug should be used during pregnancy only when clearly needed.

Fertility

Oral dosages of clemastine fumarate 312 times the usual human adult dosage have decreased mating ability in male rats, but dosages 156 times the usual human adult dosage had no effect on mating.

Lactation

Clemastine is distributed into milk. (See Pharmacokinetics: Distribution.) Drowsiness, irritability, refusal to feed, and high-pitched cry occurred in one breast-fed infant (10 weeks of age) of a woman who received 2.68 mg of clemastine fumarate daily for 3 days. Because of the potential for serious adverse reactions to clemastine in nursing infants, some manufacturers recommend discontinuance of nursing or the drug; however, the American Academy of Pediatrics (AAP) states that the drug may be used with caution during breast-feeding.

Pharmacokinetics

Absorption

Clemastine fumarate is rapidly and almost completely absorbed from the GI tract. Peak plasma concentrations of the drug are attained within 2-5 hours after a single oral dose. Following oral administration of clemastine fumarate, the antihistaminic effect of the drug (as measured by suppression of the wheal response induced by intradermal injection of histamine) is maximal within 5-7 hours and persists for 10-12 and, in some individuals, up to 24 hours.

Distribution

Distribution of clemastine into human body fluids and tissues has not been fully characterized, but the drug has been shown to distribute into milk. Following oral administration of 2.68 mg of clemastine fumarate daily for 3 days in one nursing woman, a milk clemastine concentration of about 5-10 mcg/mL occurred 20 hours after the last dose of the drug and was about 25-50% of the simultaneous maternal plasma drug concentration; clemastine was undetectable in milk 6 days after discontinuance of the drug.

Elimination

The exact metabolic fate of clemastine is not clearly established, but the drug appears to be extensively metabolized. Clemastine and its metabolites are eliminated principally in urine.

Chemistry and Stability

Chemistry

Clemastine is an ethanolamine-derivative antihistamine. Clemastine fumarate occurs as a colorless to faintly yellow, odorless, crystalline powder and is very slightly soluble in water and sparingly soluble in alcohol. Clemastine fumarate oral solution has a pH of approximately 6.2. Each 1.34 mg of clemastine fumarate is approximately equivalent to 1 mg of clemastine.

Stability

Clemastine fumarate oral solution and tablets should be stored in tight, light-resistant containers at 20-25°C.

Additional Information

For further information on chemistry, pharmacology, pharmacokinetics, uses, cautions, acute toxicity, drug interactions, laboratory test interferences, and dosage and administration of clemastine fumarate, see the Antihistamines General Statement 4:00.

Please see the general statement for a list of references.