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Look Up > Drugs > Amoxapine
Amoxapine
Pronunciation
U.S. Brand Names
Generic Available
Pharmacological Index
Use
Pregnancy Risk Factor
Contraindications
Warnings/Precautions
Adverse Reactions
Overdosage/Toxicology
Drug Interactions
Mechanism of Action
Pharmacodynamics/Kinetics
Usual Dosage
Dietary Considerations
Monitoring Parameters
Reference Range
Test Interactions
Dental Health: Local Anesthetic/Vasoconstrictor Precautions
Dental Health: Effects on Dental Treatment
Patient Information
Nursing Implications
Dosage Forms
References

Pronunciation
(a MOKS a peen)

U.S. Brand Names
Asendin®

Generic Available

Yes


Pharmacological Index

Antidepressant, Tricyclic (Secondary Amine)


Use

Treatment of neurotic or reactive depressive disorder as well as endogenous and psychotic depression; depression accompanied by anxiety or agitation


Pregnancy Risk Factor

C


Contraindications

Hypersensitivity to amoxapine; use of monoamine oxidase inhibitors within past 14 days; recovery from acute myocardial infarction


Warnings/Precautions

May cause sedation, resulting in impaired performance of tasks requiring alertness (ie, operating machinery or driving). Sedative effects may be additive with other CNS depressants and/or ethanol. The degree of sedation is moderate relative to other antidepressants. May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disease. May increase the risks associated with electroconvulsive therapy. This agent should be discontinued, when possible, prior to elective surgery. Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods.

May cause orthostatic hypotension (risk is moderate relative to other antidepressants) - use with caution in patients at risk of hypotension or in patients where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). The degree of anticholinergic blockade produced by this agent is moderate relative to other cyclic antidepressants - use caution in patients with urinary retention, benign prostatic hypertrophy, narrow-angle glaucoma, xerostomia, visual problems, constipation, or history of bowel obstruction.

Use caution in patients with depression, particularly if suicidal risk may be present. Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities). The risk of conduction abnormalities with this agent is moderate relative to other antidepressants. May lower seizure threshold - use caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage, alcoholism, or concurrent therapy with other drugs which lower the seizure threshold. Use with caution in hyperthyroid patients or those receiving thyroid supplementation. Use with caution in patients with hepatic or renal dysfunction and in elderly patients.


Adverse Reactions

>10%:

Central nervous system: Drowsiness

Gastrointestinal: Xerostomia, constipation

1% to 10%:

Central nervous system: Dizziness, headache, confusion, nervousness, restlessness, insomnia, ataxia, excitement, anxiety

Dermatologic: Edema, skin rash

Endocrine: Elevated prolactin levels

Gastrointestinal: Nausea

Neuromuscular & skeletal: Tremor, weakness

Ocular: Blurred vision

Miscellaneous: Diaphoresis

<1%: Hypotension, tachycardia, syncope, hypertension, numbness, incoordination, nasal stuffiness, seizures, neuroleptic malignant syndrome, tardive dyskinesia, extrapyramidal symptoms, photosensitivity, breast enlargement, galactorrhea, SIADH, increased or decreased libido, impotence, menstrual irregularity, painful ejaculation, epigastric distress, vomiting, flatulence, abdominal pain, abnormal taste, diarrhea, testicular edema, urinary retention, delayed micturition, agranulocytosis, leukopenia, elevated liver enzymes, paresthesia, increased intraocular pressure, mydriasis, lacrimation, tinnitus, allergic reactions


Overdosage/Toxicology

Symptoms of overdose include grand mal convulsions, acidosis, coma, renal failure

Following initiation of essential overdose management, toxic symptoms should be treated. Sodium bicarbonate is indicated when QRS interval is >0.10 seconds or QTc >0.42 seconds. Ventricular arrhythmias often respond to phenytoin 15-20 mg/kg (adults) with concurrent systemic alkalinization (sodium bicarbonate 0.5-2 mEq/kg I.V.). Arrhythmias unresponsive to this therapy may respond to lidocaine 1 mg/kg I.V. followed by a titrated infusion. Physostigmine (1-2 mg I.V. slowly for adults or 0.5 mg I.V. slowly for children) may be indicated in reversing cardiac arrhythmias that are due to vagal blockade or for anticholinergic effects, but should only be used as a last measure in life-threatening situations. Seizures usually respond to diazepam I.V. boluses (5-10 mg for adults up to 30 mg or 0.25-0.4 mg/kg/dose for children up to 10 mg/dose). If seizures are unresponsive or recur, phenytoin or phenobarbital may be required.


Drug Interactions

CYP1A2, 2C9, 2C19, 2D6, and 3A3/4 enzyme substrate

Amoxapine inhibits the antihypertensive response to bethanidine, clonidine, debrisoquin, guanadrel, guanethidine, guanabenz, guanfacine; monitor BP; consider alternate antihypertensive agent

Abrupt discontinuation of clonidine may cause hypertensive crisis, amoxapine may enhance the response

Use with altretamine may cause orthostatic hypertension

Amoxapine may be additive with or may potentiate the action of other CNS depressants (sedatives, hypnotics, or ethanol)

With MAO inhibitors, hyperpyrexia, hypertension, tachycardia, confusion, seizures, and deaths have been reported (serotonin syndrome); this combination should be avoided

Amoxapine may increase the prothrombin time in patients stabilized on warfarin

Cimetidine and methylphenidate may decrease the metabolism of amoxapine; additive anticholinergic effects seen with other anticholinergic agents

The SSRIs, to varying degrees, inhibit the metabolism of TCAs and clinical toxicity may result

Use of lithium with a TCA may increase the risk for neurotoxicity

Phenothiazines may increase concentration of some TCAs and TCAs may increase concentration of phenothiazines; monitor for altered clinical response

TCAs may enhance the hypoglycemic effects of tolazamide, chlorpropamide, or insulin; monitor for changes in blood glucose levels

Cholestyramine and colestipol may bind TCAs and reduce their absorption; monitor for altered response

TCAs may enhance the effect of amphetamines; monitor for adverse CV effects

Verapamil and diltiazem appear to decrease the metabolism of imipramine and potentially other TCAs; monitor for increased TCA concentrations. The pressor response to I.V. epinephrine, norepinephrine, and phenylephrine may be enhanced in patients receiving TCAs; this combination is best avoided.

Grapefruit juice,amprenavir, indinavir, ritonavir may inhibit the metabolism of clomipramine and potentially other TCAs; monitor for altered effects; a decrease in TCA dosage may be required

Quinidine may inhibit the metabolism of TCAs; monitor for altered effect

Combined use of anticholinergics with TCAs may produce additive anticholinergic effects; combined use of beta-agonists with TCAs may predispose patients to cardiac arrhythmias


Mechanism of Action

Reduces the reuptake of serotonin and norepinephrine. The metabolite, 7-OH-amoxapine has significant dopamine receptor blocking activity similar to haloperidol.


Pharmacodynamics/Kinetics

Onset of antidepressant effect: Usually occurs after 1-2 weeks

Absorption: Oral: Rapidly and well absorbed

Distribution: Vd: 0.9-1.2 L/kg; distributes into breast milk

Protein binding: 80%

Metabolism: Extensive in the liver

Half-life: Parent drug: 11-16 hours; Active metabolite (8-hydroxy): Adults: 30 hours

Time to peak serum concentration: Within 1-2 hours

Elimination: Excretion of metabolites and parent compound in urine


Usual Dosage

Once symptoms are controlled, decrease gradually to lowest effective dose. Maintenance dose is usually given at bedtime to reduce daytime sedation. Oral:

Adolescents: Initial: 25-50 mg/day; increase gradually to 100 mg/day; may administer as divided doses or as a single dose at bedtime

Adults: Initial: 25 mg 2-3 times/day, if tolerated, dosage may be increased to 100 mg 2-3 times/day; may be given in a single bedtime dose when dosage <300 mg/day

Elderly: Initial: 25 mg at bedtime increased by 25 mg weekly for outpatients and every 3 days for inpatients if tolerated; usual dose: 50-150 mg/day, but doses up to 300 mg may be necessary

Maximum daily dose:

Inpatient: 600 mg

Outpatient: 400 mg


Dietary Considerations

Alcohol: Avoid use


Monitoring Parameters

Monitor blood pressure and pulse rate prior to and during initial therapy evaluate mental status; monitor weight


Reference Range

Therapeutic: Amoxapine: 20-100 ng/mL (SI: 64-319 nmol/L); 8-OH amoxapine: 150-400 ng/mL (SI: 478-1275 nmol/L); both: 200-500 ng/mL (SI: 637-1594 nmol/L)


Test Interactions

glucose


Dental Health: Local Anesthetic/Vasoconstrictor Precautions

Use with caution; epinephrine, norepinephrine and levonordefrin have been shown to have an increased pressor response in combination with TCAs


Dental Health: Effects on Dental Treatment

>10% of patients experience dry mouth; long-term treatment with TCAs such as amoxapine increases the risk of caries by reducing salivation and salivary buffer capacity


Patient Information

Take exactly as directed (do not increase dose or frequency). Full effect may not occur for 3-5 weeks; may cause physical and/or psychological dependence. Do not use excessive alcohol or other prescription or OTC medications (especially pain medications, sedatives, antihistamines, or hypnotics) without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience drowsiness, lightheadedness, impaired coordination, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea, vomiting, increased appetite, or dry mouth (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help); or altered sexual drive or ability (reversible). Report persistent CNS effects (confusion, restlessness, anxiety, insomnia, excitation, headache, dizziness, fatigue, impaired coordination); muscle cramping, weakness, tremors, or rigidity; visual disturbances; excessive GI symptoms (cramping, constipation, vomiting); or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.


Nursing Implications

May increase appetite and possibly a craving for sweets; recognize signs of neuroleptic malignant syndrome and tardive dyskinesia


Dosage Forms

Tablet: 25 mg, 50 mg, 100 mg, 150 mg


References

Boakes AJ, Laurence DR, Teoh PC, et al, "Interactions Between Sympathomimetic Amines and Antidepressant Agents in Man," Br Med J, 1973, 1(849):311-5.

Crome P and Ali C, "Clinical Features and Management of Self-Poisoning With Newer Antidepressants," Med Toxicol Adverse Drug Exp, 1986, 1(6):411-20.

Glassman AH and Preud'homme XA, "Review of the Cardiovascular Effects of Heterocyclic Antidepressants," J Clin Psychiatry, 1993, 54(Suppl):16-22.

Larochelle P, Hamet P, and Enjalbert M, "Responses to Tyramine and Norepinephrine After Imipramine and Trazodone," Clin Pharmacol Ther, 1979, 26(1):24-30.

Leonard BE, "Safety of Amoxapine," Lancet, 1989, 2(8666):808.

Litovitz TC and Troutman WG, "Amoxapine Overdose. Seizures and Fatalities," JAMA, 1983, 250(8):1069-71.

Mancias P, Kramer L, and Butler IJ, "Amoxapine Overdose in a Young Man: A Transient Mitochondrial Abnormality?" Pharmacotherapy, 1995, 15(4):528-32.

Merigian KS, Browning RG, and Leeper KV, "Successful Treatment of Amoxapine-Induced Refractory Status Epilepticus With Propofol (Diprivan®)," Acad Emerg Med, 1995, 2(2):128-33.

Mitchell JR, "Guanethidine and Related Agents. III Antagonism by Drugs Which Inhibit the Norepinephrine Pump in Man," J Clin Invest, 1970, 49(8):1596-604.

Rundegren J, van Dijken J, Mörnstad H, et al, "Oral Conditions in Patients Receiving Long-Term Treatment With Cyclic Antidepressant Drugs," Swed Dent J, 1985, 9(2):55-64.

Schatzberg AF. "Recent Developments in the Acute Somatic Treatment of Major Depression," J Clin Psychiatry, 1992, 53(Suppl):20-5.

Svedmyr N, "The Influence of a Tricyclic Antidepressive Agent (Protriptyline) on Some of the Circulatory Effects of Noradrenaline and Adrenalin® in Man," Life Sci, 1968, 7(1):77-84.

Tasset JJ and Pesce AJ, "Amoxapine in Human Overdose," J Anal Toxicol, 1984, 8(3):124-8.


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