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Suicide/suicidal thoughts or clinical worsening: Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.
Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.
Close supervision of patients and in particular those at high risk should accompany drug therapy with antidepressants especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present. With regard to the chance of suicide, in particular at the beginning of treatment, only a limited number of Mirtazapine Tablets should be given to the patient.
Bone marrow depression: Bone marrow depression, which is usually manifested by granulocytopenia or agranulocytosis, has been reported in the users of mirtazapine. This effect is usually seen after 4 to 6 weeks of treatment, but it usually disappears after discontinuation of treatment. Reversible agranulocytosis has also been reported as a rare occurrence in clinical trials with mirtazapine. The attendant doctor should be alert for fever, throat pain, stomatitis and other signs and symptoms suggestive of infection. If these manifestations occur, the treatment should be discontinued and a complete blood count should be taken.
The medicinal product is to be used with caution, and careful monitoring to be applied in patients with: Epilepsy or organic brain syndrome; although clinical experience indicates that epileptic seizures are rare during mirtazapine treatment and should be introduced cautiously in patients who have a history of seizures.
Hepatic impairment: Following a single 15 mg oral dose of mirtazapine, the clearance of mirtazapine was approximately 35% decreased in mild to moderate hepatically impaired patients, compared to subjects with normal hepatic function. The average plasma concentration of mirtazapine was about 55% increased.
Renal impairment: Following a single 15 mg oral dose of mirtazapine, in patients with moderate (creatinine clearance <40 ml/min) and severe (creatinine clearance ≤ 10 ml/min) renal impairment the clearance of mirtazapine was about 30% and 50% decreased respectively, compared to normal subjects. The average plasma concentration of mirtazapine was about 55% and 115% increased respectively. No significant differences were found in patients with mild renal impairment (creatinine clearance <80 ml/min) as compared to the control group.
Heart disease, such as conduction disturbances, angina pectoris or recent myocardial infarction, which requires conventional precautions and caution during concurrent administration of other medicinal products.
Hypotension.
Like with other antidepressants, caution should be exercised when the medicinal product is administered to patients with: micturition disturbances, such as prostatic hyperplasia (although mirtazapine is only slightly anticholinergic).
Acute narrow angle glaucoma and elevated intraocular pressure (during mirtazapine treatment, the risk of these problems is very low because of the low anticholinergic effect of mirtazapine).
Diabetes mellitus: antidepressants may alter glycaemic control. Insulin and/or hypoglycaemic dosage may need to be adjusted and dose monitoring is recommended.
Jaundice: The treatment should be discontinued in the presence of jaundice.
Like in the case of other antidepressants, the following should be considered: An exacerbation of psychotic symptoms may occur when schizophrenia or other psychoses are treated with antidepressants; paranoid thoughts can also be intensified.
When the depressive phase of a bipolar disorder is being treated, a switch to a manic phase may occur. Patients with a history of mania/hypomania should be closely monitored. Mirtazapine should be discontinued in any patient entering a manic phase.
Akathisia/psychomotor restlessness: The use of antidepressants have been associated with the development of akathisia, characterized by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.
Although antidepressants do not cause dependency, abrupt cessation of long-term treatment may cause dizziness, anxiety, agitation, nausea, headache and malaise. As advised in Dosage & Administration, it is recommended to discontinue treatment with mirtazapine gradually.
Elderly patients are often more sensitive, especially to the undesirable effects of antidepressants. In clinical studies of mirtazapine, the reported incidence of undesirable effects has not been any higher in elderly patients than in other age groups. However, experience is still limited.
Hyponatraemia: Hyponatraemia, probably due to inappropriate antidiuretic hormone secretion (SIADH), has been reported very rarely with the use of mirtazapine. Caution should be exercised in patients at risk, such as elderly patients or patients concomitantly treated with medications known to cause hyponatraemia.
Serotonin syndrome: Interaction with serotonergic active substances: serotonin syndrome may occur when selective serotonin reuptake inhibitors (SSRIs) are used concomitantly with other serotonergic active substances (see Interactions). Symptoms of serotonin syndrome may be hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes that include confusion, irritability and extreme agitation progressing to delirium and coma. From post marketing experience it appears that serotonin syndrome occurs very rarely in patients treated with Mirtazapine Tablets alone (see Adverse Reactions).
Lactose: Mirtazapine tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on ability to drive and use machines: Mirtazapine may moderately impair concentration and alertness, especially in the beginning of treatment. This should be considered before engaging in tasks requiring special alertness and concentration, such as driving and operating dangerous machines.
Use in children: Use in children and adolescents under 18 years of age: Mirtazapine 30mg Tablets should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken; the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.
