Mirtazapine Side Effects

Brand Names: Remeron SolTab, Remeron

Please note - some side effects for Mirtazapine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Mirtazapine - for the Consumer

Mirtazapine

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Mirtazapine:

Abnormal dreams; abnormal thinking; constipation; dizziness; drowsiness; dry mouth; flu symptoms; increased appetite; weakness; weight gain.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); decreased ability to fight infection (fever, chills, sore throat); mental or mood changes; mouth sores; thoughts of hurting yourself; tremors; worsening of depression.

Mirtazapine Orally Disintegrating Tablets

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Mirtazapine Orally Disintegrating Tablets:

Abnormal dreams; abnormal thinking; constipation; dizziness; drowsiness; dry mouth; flu symptoms; increased appetite; weakness; weight gain.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); decreased ability to fight infection (fever, chills, sore throat); mental or mood changes; mouth sores; seizures; swelling of the legs and feet; thoughts of hurting yourself; tremors; worsening of depression.

Mirtazapine Side Effects - for the Professional

Mirtazapine

Associated with Discontinuation of Treatment

Approximately 16% of the 453 patients who received Mirtazapine in U.S. 6-week controlled clinical trials discontinued treatment due to an adverse experience, compared to 7% of the 361 placebo-treated patients in those studies. The most common events (~1 %) associated with discontinuation and considered to be drug related (i.e., those events associated with dropout at a rate at least twice that of placebo) included:

Commonly Observed Adverse Events in U.S. Controlled Clinical Trials

The most commonly observed adverse events associated with the use of Mirtazapine tablets (incidence of 5% or greater) and not observed at an equivalent incidence among placebo-treated patients (Mirtazapine incidence at least twice that for placebo) were:

Adverse Events Occurring at an Incidence of 1% or More Among Mirtazapine Treated Patients

The table that follows enumerates adverse events that occurred at an incidence of 1% or more, and were more frequent than in the placebo group, among Mirtazapine-treated patients who participated in short-term U.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 one episode of an event at some time during their treatment. Reported adverse events were classified using a standard COSTART-based dictionary terminology.

The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other investigations involving different treatments, uses and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the side effect incidence rate in the population studied.

ECG Changes

The electrocardiograms for 338 patients who received Mirtazapine and 261 patients who received placebo in 6-week, placebo-controlled trials were analyzed. Prolongation of QTc ≥500 msec was not observed among Mirtazapine-treated patients; mean change in QTc was +1.6 msec for Mirtazapine and -3.1 msec for placebo. Mirtazapine was associated with a mean increase in heart rate of 3.4 bpm, compared to 0.8 bpm for placebo. The clinical significance of these changes is unknown.

Other Adverse Events Observed During the Premarketing Evaluation of Mirtazapine

During its premarketing assessment, multiple doses of Mirtazapine were administered to 2,796 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 2,796 patients exposed to multiple doses of Mirtazapine who experienced an event of the type cited on at least one occasion while receiving Mirtazapine. All reported events are included except those already listed in the previous table, 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 one 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 the previous table appear in this listing. Events of major clinical importance are also described in theWARNINGS andPRECAUTIONS sections.

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.

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, stupor, dementia, diplopia, drug dependence, paralysis, grand mal convulsion, hypotonia, myoclonus, psychotic depression, withdrawal 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.

Other Adverse Events Observed During Postmarketing Evaluation of Mirtazapine

Adverse events reported since market introduction, which were temporally (but not necessarily causally) related to Mirtazapine therapy, include four cases of the ventricular arrhythmia torsades de pointes. In three of the four cases, however, concomitant drugs were implicated. All patients recovered.

Mirtazapine Tablets

Associated with Discontinuation of Treatment

Approximately 16 percent of the 453 patients who received Mirtazapine in U.S. 6-week controlled clinical trials discontinued treatment due to an adverse experience, compared to 7 percent of the 361 placebo-treated patients in those studies. The most common events (≥1%) associated with discontinuation and considered to be drug related (i.e., those events associated with dropout at a rate at least twice that of placebo) included:

Commonly Observed Adverse Events in U.S. Controlled Clinical Trials

The most commonly observed adverse events associated with the use of Mirtazapine tablets (incidence of 5% or greater) and not observed at an equivalent incidence among placebo-treated patients (Mirtazapine incidence at least twice that for placebo) were:

Adverse Events Occurring at an Incidence of 1% or More Among Mirtazapine Treated Patients

The table that follows enumerates adverse events that occurred at an incidence of 1% or more, and were more frequent than in the placebo group, among Mirtazapine-treated patients who participated in short-term U.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 one episode of an event at some time during their treatment. Reported adverse events were classified using a standard COSTART-based dictionary terminology.

The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other investigations involving different treatments, uses and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the side effect incidence rate in the population studied.

ECG Changes

The electrocardiograms for 338 patients who received Mirtazapine and 261 patients who received placebo in 6-week, placebo-controlled trials were analyzed. Prolongation in QTc ≥ 500 msec was not observed among Mirtazapine-treated patients; mean change in QTc was +1.6 msec for Mirtazapine and -3.1 msec for placebo. Mirtazapine was associated with a mean increase in heart rate of 3.4 bpm, compared to 0.8 bpm for placebo. The clinical significance of these changes is unknown.

Other Adverse Events Observed During the Premarketing Evaluation of Mirtazapine

During its premarketing assessment, multiple doses of Mirtazapine were administered to 2,796 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 2,796 patients exposed to multiple doses of Mirtazapine who experienced an event of the type cited on at least one occasion while receiving Mirtazapine. All reported events are included except those already listed in the previous table, 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 one 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 the previous table appear in this listing. Events of major clinical importance are also described in the WARNINGS and PRECAUTIONS sections.

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.

Musculoskeletal System:frequent: myasthenia, arthralgia; infrequent: arthritis, tenosynovitis; rare: pathologic fracture, osteoporosis fracture, bone pain, myositis, tendon rupture, arthosis, bursitis.

Nervous System:frequent: hypesthesia, apathy, depression, hypokinesia, vertigo, twitching, agitation, anxiety, amnesia, hyperkinesia, paresthesia; infrequent: ataxia, delirium, delusions, depersonalization, dyskinesia, extrapyramidial syndrome, libido increased, coordination abnormal, dysarthria, hallucinations, manic reaction, neurosis, dystonia, hostility, reflexes increased, emotional lability, euphoria, paranoid reaction; rare: aphasia, nystagmus, akathisia, stupor, dementia, diplopia, drug dependence, paralysis, grand mal convulsion, hypotonia, myoclonus, psychotic depression, withdrawal 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.

Other Adverse Events Observed During Postmarketing Evaluation of Mirtazapine

Adverse events reported since market introduction, which were temporally (but not necessarily causally) related to Mirtazapine therapy, include four cases of the ventricular arrhythmia torsades de pointes. In three of the four cases, however, concomitant drugs were implicated. All patients recovered.

Side Effects by Body System

Nervous system

Although the exact incidence has not been reported, paresthesia appears to be a relatively common side effect of mirtazapine. Patients typically experience paresthesia in the extremities or generalized in the body. However, several cases of oral paresthesia associated with the orally disintegrating tablet have been reported. Patients have described a sensation of swelling in the mouth, numbness, and anesthesia. The symptoms occur shortly after ingestion and resolve after a few hours.

Nearly all selective serotonin reuptake inhibitors, mixed serotonin/norepinephrine reuptake inhibitors, and tricyclic antidepressants cause sleep abnormalities to some extent. These antidepressants have marked dose-dependent effects on rapid eye movement (REM) sleep, causing reductions in the overall amount of REM sleep over the night and delays the first entry into REM sleep (increased REM sleep onset latency (ROL)), both in healthy subjects and depressed patients. The antidepressants that increase serotonin function appear to have the greatest effect on REM sleep. The reduction in REM sleep is greatest early in treatment, but gradually returns towards baseline during long-term therapy; however, ROL remains long. Following discontinuation of therapy the amount of REM sleep tends to rebound. Some of these drugs (i.e., bupropion, mirtazapine, nefazodone, trazodone, trimipramine) appear to have a modest or minimal effect on REM sleep.

Nervous system side effects including somnolence (56%), headache (12%), dizziness (7% to 12%), insomnia (8%), abnormal dreams (4%), abnormal thinking (3%), confusion (2%), tremor (2%), sleep abnormalities, and paresthesia have been reported. Activation of mania and seizures have occurred rarely. One case of seizures, one case of akathisia, and one patient with a transient ischemic attack have also been reported.

Gastrointestinal

Gastrointestinal side effects including dry mouth (25%), increased appetite (17%), and constipation (13%) have been reported. Other reported gastrointestinal adverse effects have included diarrhea (9%), nausea (4%), vomiting, anorexia, cholecystitis, glossitis, and colitis. One case of subclinical pancreatitis has also been reported.

Metabolic

Metabolic side effects have been reported. Nonfasting triglyceride increases to greater than 20% above the normal upper limits have been reported in 15% of patients receiving mirtazapine in clinical trials. Weight gain has been reported in 12% of patients. Less frequently reported were peripheral edema (2%), thirst, and weight loss. In one small study, mirtazapine appeared to improve glucose tolerance by reducing cortisol secretion.

Musculoskeletal

Musculoskeletal side effects including myalgia, arthralgia (2.4%), and myasthenia have been reported in less than 2% of patients receiving mirtazapine.

Numerous cases of mirtazapine- induced arthralgia have been reported. Symptoms tend to appear within 2 to 22 days of starting mirtazapine and resolve shortly after discontinuation of treatment.

Hepatic

Hepatic side effects including liver function test abnormalities (primarily ALT (SGPT) elevations greater than three times normal concentrations) have been reported in 2% of patients receiving mirtazapine. Patients typically did not develop signs or symptoms of hepatic dysfunction

A case of mirtazapine- associated, dose-dependent asymptomatic elevation of liver enzymes has been reported. In this patient, elevated liver enzymes were discovered 3 months after starting mirtazapine (30 mg/day) and following a dose reduction (15 mg/day) liver enzymes decreased, but remained above normal. Liver enzymes returned to normal 2 months after discontinuation of mirtazapine.

Respiratory

Respiratory side effects including dyspnea (1%) have been reported.

Cardiovascular

Cardiovascular side effects including hypertension, vasodilation, angina pectoris, bradycardia, and ventricular extrasystoles have been reported infrequently.

Tachycardia, palpitation, chest pain, and postural hypotension were reported by at least 1% of patients in clinical trials, however, the incidence was less than that of placebo. ECG changes were also noted in 3% of patients. The incidence was similar to that of placebo and the changes were not considered clinically significant.

Hematologic

Coagulopathy (i.e., ecchymosis) developed in a patient three days after initiating mirtazapine therapy (30 mg/day). Following discontinuation of mirtazapine, prothrombin time, activated partial thromboplastin time, and international normalized ratio returned to normal and symptoms of ecchymosis disappeared.

Hematologic and lymphatic side effects such as lymphadenopathy, leukopenia, anemia, petechiae, thrombocytopenia, lymphocytosis, and pancytopenia have been reported but are uncommon. Agranulocytosis occurred in two patients and neutropenia in one patient during premarketing clinical trials. One case of coagulopathy has been reported.

Dermatologic

Dermatologic side effects including pruritus, rash, acne, dry skin, and alopecia have been reported infrequently.

General

General side effects have included asthenia (8%), flu syndrome (5%), and back pain (2%).

Ocular

Ocular side effects including eye pain, abnormality of accommodation, conjunctivitis, lacrimation, and glaucoma have been reported infrequently. A case of palinopsia has also been recorded.

Genitourinary

Genitourinary side effects including urinary frequency (2%), urinary tract infection, kidney calculus, cystitis, urinary incontinence, vaginitis, hematuria, impotence, and polyuria have been reported.

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