No

Antihistamine

Perennial and seasonal allergic rhinitis and other allergic symptoms including urticaria

C

Hypersensitivity to astemizole or any component; concurrent use of erythromycin, quinine, ketoconazole, itraconazole, clarithromycin, troleandomycin, mibefradil dihydrochloride, or in patients with significant hepatic dysfunction

Use with caution in patients receiving drugs which prolong QRS or rare cases of severe cardiovascular events (cardiac arrest, arrhythmias) have been reported. Safety and efficacy in children <12 years of age have not been established. Discontinue therapy immediately with signs of cardiotoxicity including syncope.

The recommended daily dose of astemizole should not be exceeded. Astemizole should not be used on an "as needed" (ie, prn) basis for immediate relief of symptoms. Patients should be advised that astemizole should not be taken with grapefruit juice because of the potential for grapefruit to influence the metabolism of astemizole.

1% to 10%:

Central nervous system: Drowsiness, headache, fatigue, nervousness, dizziness

Gastrointestinal: Appetite increase, weight gain, nausea, diarrhea, abdominal pain, xerostomia

Neuromuscular & skeletal: Arthralgia

Respiratory: Pharyngitis

<1%: Palpitations, edema, depression, angioedema, photosensitivity, rash, hepatitis, myalgia, paresthesia, bronchospasm, epistaxis, thickening of mucous

Symptoms of overdose include sedation, apnea, diminished mental alertness, ventricular tachycardia, torsade de pointes

There is not a specific treatment for an antihistamine overdose, however most of its clinical toxicity is due to anticholinergic effects. Anticholinesterase inhibitors including physostigmine, neostigmine, pyridostigmine and edrophonium may be useful for the overdose with severe life-threatening symptoms. Physostigmine 1-2 mg (0.5 mg or 0.02 mg/kg for children) I.V., slowly may be given to reverse the anticholinergic effects. Cases of ventricular arrhythmias following dosages >200 mg have been reported, however, overdoses of up to 500 mg have been reported without ill effect. Patients should be carefully observed with EKG monitoring in cases of suspected overdose. Magnesium may be helpful for torsade de pointes or a lidocaine bolus followed by a titrated infusion.

CYP3A3/4 enzyme substrate

Competes with histamine for H₁-receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract; binds to lung receptors significantly greater than it binds to cerebellar receptors, resulting in a reduced sedative potential

Onset of action: <24 hours, but may take 2-3 days

Peak effect: 9-12 days

Duration: Long-acting, with steady-state plasma levels seen within 4-8 weeks following initiation of chronic therapy

Distribution: Nonsedating action reportedly due to the drug's low lipid solubility and poor penetration through the blood-brain barrier

Protein binding: 97%

Metabolism: Undergoes exclusive first-pass metabolism

Half-life: 20 hours

Time to peak serum concentration: Oral: Long-acting, with steady-state plasma levels of parent compound and metabolites seen within 4-8 weeks following initiation of chronic therapy; peak plasma levels appear in 1-4 hours following administration

Elimination: By metabolism in the liver to active and inactive metabolites, which are thereby excreted in feces and to a lesser degree in urine

Oral:

<6 years: 0.2 mg/kg/day

6-12 years: 5 mg/day (not to exceed 10 mg daily)

Children >12 years and Adults: 10-30 mg/day; administer 30 mg on first day, 20 mg on second day, then 10 mg/day in a single dose

Should be taken on an empty stomach; do not take with grapefruit juice

May cause drowsiness or nervousness; rare reports of depression

Concurrent use with psychotropics may produce additive sedation; contraindicated with nefazodone; use caution with the SSRIs; may inhibit astemizole's metabolism resulting in elevated serum levels and risk of cardiotoxicity

No information available to require special precautions

Up to 10% of patients taking astemizole may have significant dry mouth which will disappear with cessation of drug therapy; no erythromycin products or antifungals (ketoconazole, itraconazole) should be given since cardiotoxicities could occur

Notify prescriber if taking any cardiac medication. Take as directed; do not exceed recommended dose. Take on an empty stomach (1 hour before or 2 hours after meals). Avoid use of other depressants, alcohol, or sleep-inducing medications unless approved by prescriber. You may experience drowsiness or dizziness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); dry nasal membranes (use of humidifier may help); or dry mouth, abdominal pain, or nausea (frequent small meals, frequent mouth care, chewing gum, or sucking hard candy may help). Report persistent sedation, depression, or agitation; difficulty breathing or expectorating (thick secretions); tremors or loss of coordination; lack of improvement or worsening or condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Raise bed rails at night; may need assistance with ambulation; administer on an empty stomach

Tablet: 10 mg

Cunliffe NA, Barnes AJ, and Dunbar EM, "Stevens-Johnson Syndrome Following Astemizole Therapy," Postgrad Med J, 1995, 71(836):383.

Gudi R, Krishnamurthy M, and Pachter BR, "Astemizole in the Treatment of Granulocyte Colony Stimulating Factor-Induced Bone Pain," Ann Intern Med, 1995, 123(3):236-7.

Hoppu K, Tikanoja T, Tapanainen P, et al, "Accidental Astemizole Overdose in Young Children," Lancet, 1991, 338(8766):538-40.

Krstenansky PM and Cluxton RJ Jr, "Astemizole: A Long Acting Nonsedating Antihistamine," Drug Intell Clin Pharm, 1987, 21(12):947-53.

Richards DM, Brogden RN, Heel RC, et al, "Astemizole: A Review of Its Pharmacodynamic Properties and Therapeutic Efficacy," Drugs, 1984, 28(1):38-61.

Rook A, Adlakha A, Verma-Ansil B, et al, "Torsade de Pointes Ventricular Tachycardia Associated With Overdose of Astemizole," Mayo Clin Proc, 1994, 69:589-93.

"Safety of Terfenadine and Astemizole," Med Lett Drugs Ther, 1992, 34(863):9-10.

Simons FE, Kesselman MS, and Giddins NG, "Astemizole-Induced Torsade de Pointes," Lancet, 1988, 2(8611):624.

Snook J, Boothman-Burrell D, Watkins J, et al, "Torsade de Pointes Ventricular Tachycardia Associated With Astemizole Overdose," Br J Clin Pract, 1988, 42(6):257-9.

Wiley JF 2d and Gelber ML, "Cardiotoxic Effects of Astemizole Overdose in Children," J Pediatr, 1992, 120(5):799-802.

Yaffe SJ and Aranda JV, Pediatric Pharmacology: Therapeutic Principles in Practice, Philadelphia PA: WB Saunders Co, 1992.