|
|
Look
Up > Drugs > Astemizole
(Discontinued by manufacturer
6/18/99) |
Astemizole
(Discontinued by manufacturer 6/18/99) |
| |
|
Pronunciation |
|
(a
STEM mi
zole) |
|
|
U.S. Brand
Names |
|
Hismanal® |
|
|
Generic
Available |
|
No |
|
|
Pharmacological Index |
|
Antihistamine |
|
|
Use |
|
Perennial and seasonal allergic rhinitis and other allergic symptoms
including urticaria |
|
|
Pregnancy Risk
Factor |
|
C |
|
|
Contraindications |
|
Hypersensitivity to astemizole or any component; concurrent use of
erythromycin, quinine, ketoconazole, itraconazole, clarithromycin,
troleandomycin, mibefradil dihydrochloride, or in patients with significant
hepatic dysfunction |
|
|
Warnings/Precautions |
|
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. |
|
|
Adverse
Reactions |
|
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
|
|
|
Overdosage/Toxicology |
|
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.
|
|
|
Drug
Interactions |
|
CYP3A3/4 enzyme substrate |
|
|
Mechanism of
Action |
|
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 |
|
|
Pharmacodynamics/Kinetics |
|
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
|
|
|
Usual Dosage |
|
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 |
|
|
Dietary
Considerations |
|
Should be taken on an empty stomach; do not take with grapefruit
juice |
|
|
Mental Health: Effects
on Mental Status |
|
May cause drowsiness or nervousness; rare reports of
depression |
|
|
Mental Health:
Effects on Psychiatric
Treatment |
|
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 |
|
|
Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
|
No information available to require special precautions |
|
|
Dental Health:
Effects on Dental Treatment |
|
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 |
|
|
Patient
Information |
|
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. |
|
|
Nursing
Implications |
|
Raise bed rails at night; may need assistance with ambulation; administer on
an empty stomach |
|
|
Dosage Forms |
|
Tablet: 10 mg |
|
|
References |
|
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.
|
|
Copyright © 1978-2000 Lexi-Comp Inc. All Rights Reserved
| |