amoxapine

amoxapine /amox·a·pine/ (ah-mok´sah-pen) a tricyclic antidepressant of the dibenzoxazepine class.

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amoxapine (mok´spēn),

n brand name: Asendin;
drug class: tricyclic antidepressant;
action: inhibits both norepinephrine and serotonin (5-HT) uptake in brain;
uses: depression.

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amoxapine

a tricyclic antidepressant, similar to amitriptyline, used in the treatment of psychogenic dermatoses in dogs and cats.

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amoxapine

Pharmacologic class: Tricyclic compound

Therapeutic class: Antidepressant

Pregnancy risk category C

FDA Boxed Warning

• Drug may increase risk of suicidal thinking and behavior in children and adolescents with major depressive disorder and other psychiatric disorders. Risk must be balanced with clinical need, as depression itself increases suicide risk. With patient of any age, observe closely for clinical worsening, suicidality, and unusual behavior changes when therapy begins. Advise family to observe patient closely and communicate with prescriber as needed.
• Drug isn't approved for use in pediatric patients.

Action

Unclear. Inhibits reuptake of norepinephrine or serotonin at presynaptic neuron, thereby increasing levels of these neurotransmitters in brain. Also has sedative, anticholinergic, and mild peripheral vasodilatory properties.

Availability

Tablets: 25 mg, 50 mg, 100 mg, 150 mg

⊘Indications and dosages

➣ Depression accompanied by anxiety or agitation

Adults: Initially, 50 mg P.O. two or three times daily, increased to 100 mg two or three times daily by end of first week. If starting dosage (up to 300 mg/day) is tolerated but ineffective for at least 2 weeks, dosage may be increased. For outpatients, maximum suggested dosage is 400 mg/day; for hospitalized patients, 600 mg/day.

Dosage adjustment

• Elderly patients

Off-label uses

• Analgesic adjunct for phantom limb pain or chronic pain

Contraindications

• Hypersensitivity to drug or other tricyclic antidepressants (TCAs)
• MAO inhibitor use within past 14 days
• Patients younger than age 16

Precautions

Use cautiously in:
• renal or hepatic impairment, prostatic hypertrophy, hyperthyroidism, angle-closure glaucoma, bipolar disorder, schizophrenia
• elderly patients
• pregnant or breastfeeding patients.

Administration

☞ Don't give drug if patient has taken MAO inhibitors within past 14 days.
• If desired, give daily dose up to 300 mg at bedtime.
• If patient is scheduled for surgery, discuss need for dosage tapering with prescriber.

Route	Onset	Peak	Duration
P.O.	Unknown	2-4 hr	2-4 wk

Adverse reactions

CNS: agitation, restlessness, fatigue, panic, anxiety, dizziness, drowsiness, difficulty articulating words, excitement, hypomania, psychosis exacerbation, extrapyramidal effects, tardive dyskinesia, poor coordination, hallucinations, headache, insomnia, nightmares, numbness, paresthesia, peripheral neuropathy, weakness, neuroleptic malignant syndrome, seizures, coma, suicidal behavior or ideation (especially in children and adolescents)

CV: ECG changes, hypertension, orthostatic hypotension, arrhythmias, heart block, myocardial infarction, tachycardia

EENT: blurred vision, dry eyes, mydriasis, abnormal visual accommodation, increased intraocular pressure, tinnitus

GI: nausea, vomiting, constipation, anorexia, epigastric pain, dry mouth, paralytic ileus

GU: urine retention, delayed voiding, urinary tract dilation, gynecomastia

Hematologic: agranulocytosis, thrombocytopenia, thrombocytopenic purpura, leukopenia

Metabolic: changes in blood glucose level

Skin: photosensitivity rash, urticaria, flushing, diaphoresis

Other: increased appetite, weight gain, high fever, edema, hypersensitivity reactions

Interactions

Drug-drug. Adrenergics, anticholinergics, anticholinergic-like drugs: increased anticholinergic effects

Amiodarone, cimetidine, quinidine, ritonavir: increased amoxapine effects

Barbiturates: reduced amoxapine blood level, increased CNS and respiratory effects

Clonidine: hypertensive crisis

CNS depressants (including antihistamines, opioids, sedative-hypnotics): increased CNS depression

Drugs metabolized by CYP450 2D6 (such as other antidepressants, carbamazepine, class IC antiarrhythmics, phenothiazines): decreased amoxapine clearance, possible toxicity

Guanethidine: antagonism of antihypertensive action

Levodopa: delayed or decreased levodopa absorption, hypertension

MAO inhibitors: hypotension, tachycardia, extreme excitation, fever, hyperpyrexia, seizures

Rifabutin, rifampin, rifapentine: decreased amoxapine blood level and effects

Selective serotonin reuptake inhibitors: increased toxicity

Sympathomimetics: increased pressor effects of direct-acting sympathomimetics (epinephrine, norepinephrine), possibly causing arrhythmias; decreased pressor effects of indirect-acting sympathomimetics (ephedrine, metaraminol)

Valproic acid: increased valproic acid blood level, greater risk of adverse reactions

Drug-diagnostic tests. Eosinophils, liver function tests: increased values

Glucose, granulocytes, platelets, white blood cells: increased or decreased values

Drug-herbs. Evening primrose: lower seizure threshold, increased risk of seizures

Drug-behaviors. Alcohol use: increased CNS sedation

Smoking: increased metabolism and altered drug effects

Sun exposure: increased risk of photosensitivity reactions

Patient monitoring

☞ Watch for signs and symptoms of neuroleptic malignant syndrome (high fever, rapid pulse and breathing, profuse sweating).
• Monitor patient for signs and symptoms of psychosis. If these occur, consult prescriber.
• Evaluate patient for development of tardive dyskinesia (involuntary movements of face, arms, legs, and trunk).
• Assess for changes in mood and mental status.
• Check blood pressure for orthostatic hypertension.
☞ Watch for signs and symptoms of depression, and assess for suicidal ideation.
• Monitor CBC with white cell differential, glucose level, and kidney and liver function test results.

Patient teaching

☞ Tell patient to contact prescriber immediately if he develops high fever, rapid pulse and breathing, profuse sweating, changes in mental status, or involuntary movements.
☞ Instruct patient to promptly report severe mood changes or suicidal thoughts.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• Tell patient that stopping drug suddenly can cause withdrawal symptoms.
• Advise patient to rise slowly and carefully to avoid dizziness.
• Caution patient that drug may cause serious interactions with many common drugs. Instruct him to tell all prescribers that he's taking this drug.
• Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.
• Tell patient he'll undergo frequent blood testing during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.

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amoxapine Neuropharmacology A tricyclic antidepressant Adverse effects Tardive dyskinesia, sedation, postural hypotension, cholinergic effects—eg dry mouth, blurred vision, constipation, urinary retention, weight gain, neuroleptic malignant syndrome, cardiovascular effects—EKG, slow AV conduction; withdrawal symptoms accompany abrupt withdrawal