Amoxapine | Asendin
ASENDIN / Amoxapine is indicated for the relief of symptoms of depression in patients with neurotic or reactive depressive disorders as well as endogenous and psychotic depressions. It is indicated for depression accompanied by anxiety or agitation.
Effective dosage of amoxapine may vary from one patient to another. Usual effective dosage is 200 to 300 mg daily. Three weeks constitutes an adequate period of trial providing dosage has reached 300 mg daily (or lower level of tolerance) for at least two weeks. If no response is seen at 300 mg, dosage may be increased, depending upon tolerance, up to 400 mg daily. Hospitalized patients who have been refractory to antidepressant therapy and who have no history of convulsive seizures may have dosage raised cautiously up to 600 mg daily in divided doses. Amoxapine may be given in a single daily dose, not to exceed 300 mg, preferably at bedtime. If the total daily dosage exceeds 300 mg, it should be given in divided doses.
- Initial Dosage for Adults: Usual starting dosage is 50 mg two or three times daily. Depending upon tolerance, dosage may be increased to 100 mg two or three times daily by the end of the first week. (Initial dosage of 300 mg daily may be given, but notable sedation may occur in some patients during the first few days of therapy at this level.) Increases above 300 mg daily should be made only if 300 mg daily has been ineffective during a trial period of at least two weeks. When effective dosage is established, the drug may be given in a single dose (not to exceed 300 mg) at bedtime.
- Elderly Patients: In general, lower dosages are recommended for these patients. Recommended starting dosage of amoxapine is 25 mg two or three times daily. If no intolerance is observed, dosage may be increased by the end of the first week to 50 mg two or three times daily. Although 100 to 150 mg daily may be adequate for many elderly patients, some may require higher dosage. Careful increases up to 300 mg daily are indicated in such cases. Once an effective dosage is established, amoxapine may conveniently be given in a single bedtime dose, not to exceed 300 mg.
- Maintenance: Recommended maintenance dosage of amoxapine is the lowest dose that will maintain remission. If symptoms reappear, dosage should be increased to the earlier level until they are controlled. For maintenance therapy at dosages of 300 mg or less, a single dose at bedtime is recommended.
—–INDICATIONS AND USAGE—–
- See description above.
—–DOSAGE AND ADMINISTRATION—–
- See description above.
—–CONTRAINDICATIONS—–
- Amoxapine is contraindicated in patients who have shown prior hypersensitivity to dibenzoxazepine compounds. It should not be given concomitantly with monoamine oxidase inhibitors. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressants and monoamine oxidase inhibitors simultaneously. When it is desired to replace a monoamine oxidase inhibitor with amoxapine, a minimum of 14 days should be allowed to elapse after the former is discontinued. Amoxapine should then be initiated cautiously with gradual increase in dosage until optimum response is achieved. The drug is not recommended for use during the acute recovery phase following myocardial infarction.
—–WARNINGS—–
- Clinical Worsening and Suicide Risk: Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of shortterm placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.
The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications.
—–PRECAUTIONS—–
- General: In prescribing the drug it should be borne in mind that the possibility of suicide is inherent in any severe depression, and persists until a significant remission occurs; the drug should be dispensed in the smallest suitable amount. Manic depressive patients may experience a shift to the manic phase. Schizophrenic patients may develop increased symptoms of psychosis; patients with paranoid symptomatology may have an exaggeration of such symptoms. This may require reduction of dosage or the addition of a major tranquilizer to the therapeutic regimen. Antidepressant drugs can cause skin rashes and/or “drug fever” in susceptible individuals. These allergic reactions may, in rare cases, be severe. They are more likely to occur during the first few days of treatment, but may also occur later. Amoxapine should be discontinued if rash and/or fever develop. Amoxapine possesses a degree of dopamine-blocking activity which may cause extrapyramidal symptoms in <1% of patients. Rarely, symptoms indicative of tardive dyskinesia have been reported.
- Information for Patients Given the likelihood that some patients exposed chronically to neuroleptics will develop tardive dyskinesia, it is advised that all patients in whom chronic use is contemplated be given, if possible, full information about this risk. The decision to inform patients and/or their guardians must obviously take into account the clinical circumstances and the competency of the patient to understand the information provided.
Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with amoxapine and should counsel them in its appropriate use. A patient Medication Guide about “Antidepressant Medicines, Depression and other Serious Mental Illness, and Suicidal Thoughts or Actions” is available for amoxapine. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.
Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking amoxapine. Patients should be advised that taking amoxapine can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle-closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle-closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible.
—–ADVERSE REACTIONS—–
- Adverse reactions reported in controlled studies in the United States are categorized with respect to incidence below. Following this is a listing of reactions known to occur with other antidepressant drugs of this class.
- Incidence Greater Than 1%: The most frequent types of adverse reactions occurring with amoxapine in controlled clinical trials were sedative and anticholinergic: these included drowsiness (14%), dry mouth (14%), constipation (12%), and blurred vision (7%). Less frequently reported reactions are:
- CNS and Neuromuscular: anxiety, insomnia, restlessness, nervousness, palpitations, tremors, confusion, excitement, nightmares, ataxia, alterations in EEG patterns.
- Allergic: edema, skin rash.
- Endocrine: elevation of prolactin levels.
- Gastrointestinal: nausea.
- Other: dizziness, headache, fatigue, weakness, excessive appetite, increased perspiration.
- Incidence Less Than 1%
- Anticholinergic: disturbances of accommodation, mydriasis, delayed micturition, urinary retention, nasal stuffiness.
- Cardiovascular: hypotension, hypertension, syncope, tachycardia.
- Allergic: drug fever, urticaria, photosensitization, pruritus, vasculitis, hepatitis.
- CNS and Neuromuscular: tingling, paresthesias of the extremities, tinnitus, disorientation, seizures, hypomania, numbness, incoordination, disturbed concentration, hyperthermia, extrapyramidal symptoms, including, tardive dyskinesia. Neuroleptic malignant syndrome has been reported. (See WARNINGS.) Hematologic: leukopenia, agranulocytosis.
- Gastrointestinal: epigastric distress, vomiting, flatulence, abdominal pain, peculiar taste, diarrhea.
- Endocrine: increased or decreased libido, impotence, menstrual irregularity, breast enlargement and galactorrhea in the female, syndrome of inappropriate antidiuretic hormone secretion.
- Other: lacrimation, weight gain or loss, altered liver function, painful ejaculation.
- Drug Relationship Unknown: The following reactions have been reported rarely, and occurred under uncontrolled circumstances where a drug relationship was difficult to assess. These observations are listed to serve as alerting information to physicians.
- Anticholinergic: paralytic ileus.
- Cardiovascular: atrial arrhythmias (including atrial fibrillation), myocardial infarction, stroke, heart block.
- CNS and Neuromuscular: hallucinations. Hematologic: thrombocytopenia, eosinophilia, purpura, petechiae.
- Gastrointestinal: parotid swelling.
- Endocrine: change in blood glucose levels.
- Other: pancreatitis, hepatitis, jaundice, urinary frequency, testicular swelling, anorexia, alopecia.
- Additional Adverse Reactions: The following reactions have been reported with other antidepressant drugs.
- Anticholinergic: sublingual adenitis, dilation of the urinary tract.
- CNS and Neuromuscular : delusions. Gastrointestinal: stomatitis, black tongue.
- Endocrine: gynecomastia.