amoxapine

Absorption: Well absorbed following oral administration.

Distribution: Widely distributed; enters breast milk.

Protein Binding: 92% bound to plasma proteins.

Metabolism/Excretion: Extensively metabolized by the liver, primarily by the CYP2D6 isoenzyme; the CYP2D6 enzyme system exhibits genetic polymorphism (∼7% of population may be poor metabolizers and may have significantly ↑ amoxapine concentrations and an ↑ risk of adverse effects)..

Half-Life: 8 hr.

Time/Action Profile ⬆ ⬇

(antidepressant effect)

ROUTE	ONSET	PEAK	DURATION
PO	within 1–2 wk	2–6 wk	days–wks

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Angle-closure glaucoma;
Recent MI;
QTc interval prolongation;
Cardiac arrhythmia;
HF.

Use Cautiously in:

Pre-existing cardiovascular disease;
Prostatic hyperplasia (increased susceptibility to urinary retention);
History of seizures (threshold may be lowered);
May ↑ risk of suicide attempt/ideation especially during dose early treatment or dose adjustment;
OB: Safety not established in pregnancy;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Suicide risk, especially at initiation of therapy, may be greater in children and adolescents;
Geri: Appears on Beers list. risk of adverse reactions in older adults, including falls secondary to sedative and anticholinergic effects and orthostatic hypotension. Avoid use in older adults..

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, ARRHYTHMIAS

Derm: photosensitivity, rash

EENT: blurred vision, dry eyes

Endo: gynecomastia, sexual dysfunction

GI: constipation, dry mouth, paralytic ileus

GU: testicular swelling, urinary retention

Hemat: blood dyscrasias

Metab: ↑appetite, weight gain

Neuro: fatigue, sedation, extrapyramidal reactions, NEUROLEPTIC MALIGNANT SYNDROME, tardive dyskinesia

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

Amoxapine is metabolized in the liver by the cytochrome P450 2D6 enzyme, and its action may be affected by drugs that compete for metabolism by this enzyme, including other antidepressants, phenothiazines, carbamazepine, and class 1C antiarrhythmics including propafenone, and flecainide; when these drugs are used concurrently with amoxapine, dosage reduction of one or the other or both may be necessary. Concurrent use of other drugs that inhibit the activity of the enzyme, includingcimetidine, quinidine, amiodarone, and ritonavir may result in ↑ effects of amoxapine.
May cause hypotension, tachycardia, and potentially fatal reactions when used with MAO inhibitors (avoid concurrent use—discontinue 2 wk before starting amoxapine).
Concurrent use with SSRIs may result in ↑ toxicity and should be avoided (fluoxetine should be stopped 5 wk before starting amoxapine).
Concurrent use with clonidine may result in hypertensive crisis and should be avoided.
Concurrent use with levodopa may result in delayed/decreased absorption of levodopa or hypertension.
Blood levels and effects may be ↓ by rifapentine, rifampin, and rifabutin.
Cimetidine, fluoxetine, phenothiazines, or oral contraceptives↑ levels and may cause toxicity.
Increased risk of extrapyramidal reactions with other drugs causing extrapyramidal reactions (phenothiazines).

Route/Dosage ⬆ ⬇

PO (Adults ): 50 mg 2–3 times daily, increase to 100 mg 2–3 times daily by end of 1 wk (not to exceed 300 mg daily in outpatients, 600 mg daily in divided doses in hospitalized patients). Once optimal dose is achieved, may be given as a single bedtime dose; no single dose to exceed 300 mg.
PO Geriatric Patients ): 25 mg 2–3 times daily, may be increased to 50 mg 2–3 times daily (not >300 mg/day).

Availability ⬆ ⬇

(Generic available)

Tablets: 25 mg; 50 mg; 100 mg; 150 mg

Assessment ⬆ ⬇

Monitor mental status (orientation, mood, behavior) frequently. Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient.
Monitor BP and pulse before and during initial therapy. Notify physician or other health care professional of decreases in BP (10–20 mmHg) or sudden increase in pulse rate. Patients taking high doses or with a history of cardiovascular disease should have ECG monitored before and periodically during therapy.
Observe for onset of extrapyramidal side effects (akathisia: restlessness; dystonia: muscle spasms and twisting motions; pseudoparkinsonism: mask facies, rigidity, tremors, drooling, shuffling gait, dysphagia, pill-rolling motions of hands). Dose reduction or discontinuation may be necessary. Trihexyphenidyl or diphenhydramine may be used to control these symptoms.
Monitor for tardive dyskinesia (lip smacking or puckering, puffing of cheeks, rhythmic chewing or worm-like movement of tongue and mouth, uncontrolled movements of extremities). Notify health care professional immediately if these symptoms occur; they may be irreversible.
Monitor for development of neuroleptic malignant syndrome(fever, respiratory distress, tachycardia, convulsions, diaphoresis, hypertension or hypotension, pallor, tiredness, severe muscle stiffness, loss of bladder control). Notify health care professional immediately if these symptoms occur.
Assess for sexual dysfunction.

Lab Test Considerations:

May cause ↑ serum prolactin levels.
- Monitor CBC and differential during chronic therapy. May rarely cause bone marrow suppression.
- In chronic therapy, periodically monitor hepatic and renal function. Serum glucose may be ↑ or ↓.

Implementation ⬆ ⬇

Dose increases should be made at bedtime because of sedation. Dose titration is a slow process; may take wks to mos. May give entire dose (if <300 mg) at bedtime, when dose is stabilized.
Taper amoxapine to avoid withdrawal effects.
PO: Administer medication with or immediately after a meal to minimize gastric irritation.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed. Abrupt discontinuation may cause nausea, headache, and malaise.
Inform patient of the possibility of extrapyramidal symptoms and tardive dyskinesia. Instruct patient to report these symptoms immediately.
May cause drowsiness and blurred vision. Caution patient to avoid driving and other activities requiring alertness until response to drug is known.
Orthostatic hypotension, sedation, and confusion are common during early therapy, especially in geriatric patients. Protect patient from falls and advise patient to make position changes slowly.
Refer patient to nutritional or weight management program as appropriate.
Advise patient to avoid alcohol or other CNS depressant drugs during and for 3–7 days after therapy.
Instruct patient to notify health care professional if dry mouth or constipation persists or if urinary retention, uncontrolled movements, or rigidity occur. Sugarless candy or gum may diminish dry mouth, and an increase in fluid intake or bulk may prevent constipation. If these symptoms persist, dosage reduction or discontinuation may be necessary. Consult health care professional if dry mouth persists for more than 2 wk.
Advise patient to inform health care professional if breast enlargement or sexual dysfunction occurs.
Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Inform patient to monitor dietary intake. Increased appetite may lead to undesired weight gain.
Advise patient to notify health care professional of medication regimen before treatment or surgery.
Therapy for depression is usually prolonged. Emphasize the importance of follow-up exams to monitor effectiveness and side effects and to improve coping skills.
Treatment is not a cure since symptoms can recur after discontinuation of medication.
Pedi: Caution parents/guardians of teenagers or children taking this medication about possible increase in suicide risk. Teach parents how to assess for suicidal thoughts and to report concerns immediately.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇