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Pronunciation |
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(a
MOKS a
peen) |
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U.S. Brand
Names |
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Asendin® |
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Generic
Available |
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Yes |
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Pharmacological Index |
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Antidepressant, Tricyclic (Secondary Amine) |
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Use |
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Treatment of neurotic or reactive depressive disorder as well as endogenous
and psychotic depression; depression accompanied by anxiety or
agitation |
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Pregnancy Risk
Factor |
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C |
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Contraindications |
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Hypersensitivity to amoxapine; use of monoamine oxidase inhibitors within
past 14 days; recovery from acute myocardial infarction |
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Warnings/Precautions |
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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. |
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Adverse
Reactions |
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>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 |
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Overdosage/Toxicology |
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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. |
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Drug
Interactions |
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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 |
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Mechanism of
Action |
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Reduces the reuptake of serotonin and norepinephrine. The metabolite,
7-OH-amoxapine has significant dopamine receptor blocking activity similar to
haloperidol. |
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Pharmacodynamics/Kinetics |
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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
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Usual Dosage |
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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 |
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Dietary
Considerations |
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Alcohol: Avoid use |
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Monitoring
Parameters |
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Monitor blood pressure and pulse rate prior to and during initial therapy
evaluate mental status; monitor weight |
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Reference Range |
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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) |
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Test
Interactions |
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glucose |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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Use with caution; epinephrine, norepinephrine and levonordefrin have been
shown to have an increased pressor response in combination with
TCAs |
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Dental Health:
Effects on Dental Treatment |
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>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 |
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Patient
Information |
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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. |
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Nursing
Implications |
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May increase appetite and possibly a craving for sweets; recognize signs of
neuroleptic malignant syndrome and tardive dyskinesia |
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Dosage Forms |
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Tablet: 25 mg, 50 mg, 100 mg, 150 mg |
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References |
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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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