Other Adverse Events Observed During the Premarketing Evaluation of Mirtazapine
During its premarketing assessment, multiple doses of mirtazapine tablets were administered to 2796 patients in clinical studies. The conditions and duration of exposure to mirtazapine varied greatly, and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, fixed-dose and titration studies. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories.
In the tabulations that follow, reported adverse events were classified using a standard COSTART-based dictionary terminology. The frequencies presented, therefore, represent the proportion of the 2796 patients exposed to multiple doses of mirtazapine who experienced an event of the type cited on at least 1 occasion while receiving mirtazapine. All reported events are included except those already listed in Table 4, those adverse experiences subsumed under COSTART terms that are either overly general or excessively specific so as to be uninformative, and those events for which a drug cause was very remote.
It is important to emphasize that, although the events reported occurred during treatment with mirtazapine, they were not necessarily caused by it.
Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on 1 or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. Only those events not already listed in Table 4 appear in this listing. Events of major clinical importance are also described in the WARNINGS
Body as a Whole: frequent:
malaise, abdominal pain, abdominal syndrome acute; infrequent:
chills, fever, face edema, ulcer, photosensitivity reaction, neck rigidity, neck pain, abdomen enlarged; rare:
cellulitis, chest pain substernal.
Cardiovascular System: frequent:
hypertension, vasodilatation; infrequent:
angina pectoris, myocardial infarction, bradycardia, ventricular extrasystoles, syncope, migraine, hypotension; rare:
atrial arrhythmia, bigeminy, vascular headache, pulmonary embolus, cerebral ischemia, cardiomegaly, phlebitis, left heart failure.
Digestive System: frequent:
vomiting, anorexia; infrequent:
eructation, glossitis, cholecystitis, nausea and vomiting, gum hemorrhage, stomatitis, colitis, liver function tests abnormal; rare:
tongue discoloration, ulcerative stomatitis, salivary gland enlargement, increased salivation, intestinal obstruction, pancreatitis, aphthous stomatitis, cirrhosis of liver, gastritis, gastroenteritis, oral moniliasis, tongue edema.
Endocrine System: rare:
Hemic and Lymphatic System: rare:
lymphadenopathy, leukopenia, petechia, anemia, thrombocytopenia, lymphocytosis, pancytopenia.
Metabolic and Nutritional Disorders: frequent:
dehydration, weight loss; rare:
gout, SGOT increased, healing abnormal, acid phosphatase increased, SGPT increased, diabetes mellitus, hyponatremia.
Musculoskeletal System: frequent:
myasthenia, arthralgia; infrequent:
arthritis, tenosynovitis; rare:
pathologic fracture, osteoporosis fracture, bone pain, myositis, tendon rupture, arthrosis, bursitis.
Nervous System: frequent:
hypesthesia, apathy, depression, hypokinesia, vertigo, twitching, agitation, anxiety, amnesia, hyperkinesia, paresthesia; infrequent:
ataxia, delirium, delusions, depersonalization, dyskinesia, extrapyramidal syndrome, libido increased, coordination abnormal, dysarthria, hallucinations, manic reaction, neurosis, dystonia, hostility, reflexes increased, emotional lability, euphoria, paranoid reaction; rare:
aphasia, nystagmus, akathisia (psychomotor restlessness), stupor, dementia, diplopia, drug dependence, paralysis, grand mal convulsion, hypotonia, myoclonus, psychotic depression, withdrawal syndrome, serotonin syndrome.
Respiratory System: frequent:
cough increased, sinusitis; infrequent:
epistaxis, bronchitis, asthma, pneumonia; rare:
asphyxia, laryngitis, pneumothorax, hiccup.
Skin and Appendages: frequent:
pruritus, rash; infrequent:
acne, exfoliative dermatitis, dry skin, herpes simplex, alopecia; rare:
urticaria, herpes zoster, skin hypertrophy, seborrhea, skin ulcer.
Special Senses: infrequent:
eye pain, abnormality of accommodation, conjunctivitis, deafness, keratoconjunctivitis, lacrimation disorder, glaucoma, hyperacusis, ear pain; rare:
blepharitis, partial transitory deafness, otitis media, taste loss, parosmia.
Urogenital System: frequent:
urinary tract infection; infrequent:
kidney calculus, cystitis, dysuria, urinary incontinence, urinary retention, vaginitis, hematuria, breast pain, amenorrhea, dysmenorrhea, leukorrhea, impotence; rare:
polyuria, urethritis, metrorrhagia, menorrhagia, abnormal ejaculation, breast engorgement, breast enlargement, urinary urgency.