Amoxapine

Pregnancy Category C.

Studies performed in mice, rats, and rabbits have demonstrated no evidence of teratogenic effect due to amoxapine. Embryotoxicity was seen in rats and rabbits given oral doses approximating the human dose. Fetotoxic effects (intrauterine death, stillbirth, decreased birth weight) were seen in animals studied at oral doses 3-10 times the human dose. Decreased postnatal survival (between days 0-4) was demonstrated in the offspring of rats at 5-10 times the human dose. There are no adequate and well-controlled studies in pregnant women. Amoxapine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Amoxapine, like many other systemic drugs, is excreted in human milk. Because effects of the drug on infants are unknown, caution should be exercised when amoxapine is administered to nursing women.

In a 21-month toxicity study at three dose levels in rats, pancreatic islet cell hyperplasia occurred with slightly increased incidence at doses 5-10 times the human dose. Pancreatic adenocarcinoma was detected in low incidence in the mid-dose group only, and may possibly have resulted from endocrinemediated organ hyperfunction. The significance of these findings to man is not known.

Treatment of male rats with 5-10 times the human dose resulted in a slight decrease in the number of fertile matings. Female rats receiving oral doses within the therapeutic range displayed a reversible increase in estrous cycle length.

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.

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.

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.