DrugindexOnline^{2nd edition}

Pronouncation: (am-OX-uh-peen)
Class: Tricyclic compound

Trade Names:
Asendin
- Tablets 25 mg
- Tablets 50 mg
- Tablets 100 mg
- Tablets 150 mg

Mechanism of Action

Pharmacology

Inhibits reuptake of norepinephrine and serotonin in CNS.

Pharmacokinetics

Absorption

Rapidly absorbed; t _max is about 90 min.

Distribution

About 90% protein bound.

Metabolism

Extensively metabolized. Major metabolite is 8-hydroxyamoxapine.

Elimination

The t _½ is 8 h. Biologic t _½ of 8-hydroxyamoxapine is 30 h. Metabolites excreted in urine in conjugated form as glucuronides.

Indications and Usage

Relief of symptoms of depression.

Unlabeled Uses

Management of chronic pain associated with migraine, chronic tension headache, diabetic neuropathy, phantom limb pain, tic douloureux, cancer pain, peripheral neuropathy, postherpetic neuralgia, and arthritic pain.

Contraindications

Hypersensitivity to tricyclic antidepressants; not recommended for use during acute recovery phase of MI. Do not use drug concomitantly with MAOIs except under close medical supervision.

Dosage and Administration

Adults

PO Initial dose: 200 to 300 mg/day; may be given in single daily dose at bedtime once effective dosage is established. Divided doses are given for amounts more than 300 mg/day. Hospitalized patients refractory to antidepressant therapy and with no history of seizures may be cautiously titrated to 600 mg/day in divided doses.

Maintenance

Single daily dose of 300 mg or less at bedtime.

Elderly

PO Initially 25 mg twice daily or 3 times daily. If well tolerated, may be increased to 50 mg twice daily or 3 times daily. Some patients may need up to 300 mg/day.

Storage/Stability

Store at room temperature in tightly closed container.

Drug Interactions

Barbiturates, charcoal

May decrease amoxapine blood levels.

Cimetidine, fluoxetine

May increase amoxapine blood levels.

Clonidine

May result in hypertensive crisis.

CNS depressants

Depressant effects may be additive.

MAOIs

May cause serious and possibly fatal hypertensive crisis.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Orthostatic hypotension; hypertension; tachycardia; palpitations; arrhythmias; ECG changes.

CNS

Confusion; hallucinations; delusions; nervousness; restlessness; disturbed concentration; decreased memory; agitation; panic; insomnia; nightmares; mania; exacerbation of psychosis; drowsiness; dizziness; weakness; emotional liability; seizures.

Dermatologic

Rash; pruritus; photosensitivity reaction; dry skin; acne; itching.

EENT

Conjunctivitis; blurred vision; increased intraocular pressure; mydriasis; tinnitus; nasal congestion; peculiar taste in mouth.

GI

Nausea; vomiting; anorexia; GI distress; diarrhea; flatulence; dry mouth; constipation.

Genitourinary

Impotence; sexual dysfunction; nocturia; urinary frequency, retention or hesitancy; urinary tract infection; vaginitis; cystitis.

Hematologic

Bone marrow depression including agranulocytosis; eosinophilia; purpura; thrombocytopenia; leukopenia.

Hepatic

Hepatitis; jaundice.

Metabolic

Elevation or depression of blood glucose levels.

Respiratory

Pharyngitis; rhinitis; sinusitis, cough.

Miscellaneous

Numbness; tremors; menstrual irregularities, dysmenorrhea; breast enlargement in men and women; extrapyramidal symptoms (pseudoparkinsonism, movement disorders, akathisia); tardive dyskinesia. Effects can generally be minimized by starting with low doses and increasing gradually.

Precautions

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Not recommended in children younger than 16 yr of age.

Special Risk Patients

Use with caution in patients with history of seizures, urinary retention, urethral or ureteral spasm, angle-closure glaucoma or increased intraocular pressure, CV disorders, hyperthyroid patients or those patients receiving thyroid medication, hepatic or renal function impairment, schizophrenia, or paranoia.

Neuroleptic malignant syndrome (NMS)

Potentially fatal condition that has been reported with amoxapine. Signs and symptoms include hyperpyrexia, muscle rigidity, altered mental status, irregular pulse, irregular BP, tachycardia, and diaphoresis. Notify health care provider. Discontinue amoxapine and nonessential drugs.

Patients switching from MAOI to amoxapine

Wait 7 to 10 days to prevent hypertensive crisis.

Patient Information

• Explain that full effectiveness of drug may not occur for up to 2 to 3 wk after initiation of drug therapy and that dosage will be tapered slowly before stopping.
• Advise patient that changes in smoking habits can alter drug effectiveness.
• Instruct patient to monitor food intake; weight gain can occur because of increased appetite and craving for sweets.
• Emphasize importance of regular dental care because oral dryness can increase risk for dental caries.
• Instruct patient to report the following symptoms to health care provider: Persistent dry mouth, constipation, urinary retention, fever, sore throat, or muscle rigidity.
• Instruct patient to take sips of water frequently, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs. Suggest patient increase fluids and fiber in diet to alleviate constipation.
• Instruct patient to avoid intake of alcohol or other CNS depressants.
• Caution patient to avoid exposure to sunlight, and to use sunscreen or wear protective clothing to avoid photosensitivity reaction.