14) ] Most common adverse reactions (≥5% or greater and twice placebo) were somnolence, increased appetite, weight gain, and dizziness. gov/medwatch. 1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below are from clinical trials in which mirtazapine was administered to 2796 patients in phase 2 and 3 clinical studies. The trials consisted of double-blind controlled and open-label studies, inpatient and outpatient studies, fixed dose, and titration studies.
S. 6-week placebo-controlled clinical trials discontinued treatment due to an adverse reaction, compared to 7% of the 361 placebo-treated patients in those studies. The most common reactions leading to discontinuation (≥1% and at a rate at least twice that of placebo) are included in Table 2.
5% 0% Common Adverse Reactions The most common adverse reactions (≥5% and twice placebo) associated with the use of mirtazapine are listed in Table 3. S. S. placebo-controlled trials in which patients were dosed in a range of 5 to 60 mg/day.
This table shows the percentage of patients in each group who had at least 1 episode of an adverse reaction at some time during their treatment. S. Clinical Studies of Mirtazapine in Patients with MDD Mirtazapine (n=453) Placebo (n=361) Body as a Whole Asthenia 8% 5% Flu Syndrome 5% 3% Back Pain 2% 1% Digestive System Dry Mouth 25% 15% Increased Appetite 17% 2% Constipation 13% 7% Metabolic and Nutritional Disorders Weight Gain 12% 2% Peripheral Edema 2% 1% Edema 1% 0% Musculoskeletal System Myalgia 2% 1% Nervous System Somnolence 54% 18% Dizziness 7% 3% Abnormal Dreams 4% 1% Thinking Abnormal 3% 1% Tremor 2% 1% Confusion 2% 0% Respiratory System Dyspnea 1% 0% Urogenital System Urinary Frequency 2% 1% ECG Changes The electrocardiograms for 338 patients who received mirtazapine and 261 patients who received placebo in 6-week, placebo-controlled trials were analyzed.
8 bpm for placebo. The clinical significance of these changes is unknown. Other Adverse Reactions Observed During the Premarketing Evaluation of Mirtazapine The following list does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general or excessively specific so as to be uninformative, 4) which were not considered to have significant clinical implications, or 5) which occurred at a rate equal to or less than placebo.
Adverse reactions are categorized by body system according to the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare adverse reactions are those occurring in fewer than 1/1000 patients.
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 : goiter, hypothyroidism. Hemic and Lymphatic System : rare : lymphadenopathy, leukopenia, petechia, anemia, thrombocytopenia, lymphocytosis, pancytopenia. Metabolic and Nutritional Disorders: frequent : thirst; infrequent : 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, angle-closure 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.
2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of mirtazapine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
, galactorrhea and gynecomastia) Musculoskeletal and connective tissue disorders : increased creatine kinase blood levels and rhabdomyolysis Psychiatric disorders : somnambulism (ambulation and other complex behaviors out of bed) Skin and subcutaneous tissue disorders : severe skin reactions, including Stevens-Johnson syndrome, bullous dermatitis, erythema multiforme and toxic epidermal necrolysis