Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2017 Publisher: Generics [UK] Limited, t/a Mylan, Station Close, Potters Bar, Hertfordshire, EN6 1TL
Mianserin should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempts 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.
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 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.
As an improvement in the patient’s depression may not occur during the first 2-4 weeks of treatment with mianserin, patients should be closely monitored during this period.
Mianserin has been associated with haematological and hepatic reactions and patients require careful supervision. A full blood count is recommended every 4 weeks during the first 3 months of treatment; subsequent clinical monitoring should continue and treatment should be stopped and a full blood count obtained if fever, sore throat, stomatitis or other signs of infection develop.
Care should always be taken in patients with recent myocardial infarction, heart block or arrhythmia.
Serious cardiotoxic effects appear to be rare at therapeutic dosage, even in patients with pre-existing cardiac disease, recent myocardial infarction or cardiac insufficiency.
Older people are less liable to experience adverse reactions such as agitation, confusion and postural hypotension with mianserin than with tricyclics or bridged tricyclics, but all anti-depressant therapy should be used with caution in this group of patients.
As with tricyclic antidepressants mianserin is known to lower the convulsion threshold and should therefore be used with extreme caution, or avoided if possible, in patients with epilepsy and other pre-disposing factors e.g. brain damage of varying aetiology, concomitant use of neuroleptics, withdrawal from alcohol or drugs with anticonvulsive properties (e.g. benzodiazepines) (see sections 4.5 and 4.8).
When treating patients with diabetes, hepatic or renal insufficiency, normal precautions should be exercised and the dosages of any concurrent therapy kept under review.
Patients with narrow angle glaucoma or symptoms suggestive of prostatic hypertrophy should also be monitored even though anticholinergic side effects are not anticipated with mianserin therapy.
There are indications that mianserin, like other anti-depressants, may precipitate hypomania in susceptible subjects with bipolar affective illness. In such a case treatment with mianserin should be withdrawn.
If surgery is necessary during mianserin therapy the anaesthetist should be informed of the treatment being given.
Care should always be taken in patients with phaeochromocytoma.
Mianserin may potentiate the central nervous depressant action of alcohol, anxiolytics, hypnotics and antipsychotics.
Mianserin should not be started within two weeks of cessation of therapy of Mono Amine Oxidase Inhibitors (MAOIs). MAOIs should not be started until at least 1 to 2 weeks after stopping tricyclic related antidepressants.
Moclobemide should not be started until at least 1 week after stopping mianserin administration.
Phenytoin plasma levels should be monitored in patients treated concurrently with mianserin.
Carbamazepine and phenobarbital accelerate the metabolism of mianserin and can cause reduced plasma concentration.
Mianserin may antagonise the anticonvulsant effect of antiepileptics, barbiturates and primidone by lowering the convulsive threshold (see section 4.4). Caution is advised in patients with epilepsy and other predisposing factors such as brain damage, concomitant use of neuroleptics, withdrawal from alcohol.
There may be increased risk of convulsions when antidepressants are given with atomoxetine.
Interactions with sympathomimetic agents have not been reported, and are unlikely.
Clinical experience has shown that mianserin does not interact with the anti- hypertensives bethanidine, clonidine, guanethidine or propranolol. Nevertheless, the monitoring of blood pressure is recommended for those patients receiving concurrent anti-hypertensive therapy.
There may be an enhanced hypotensive effect if mianserin is taken with diazoxide, hydralazine or nitroprusside.
Concurrent anticoagulant therapy of the coumarin type (eg warfarin) is permissible, but close additional monitoring procedures should be carried out.
Antihistamines and antimuscarinics may have increased antimuscarinic effects if take with mianserin, and antihistamines may have sedative effects.
Mianserin may reduce the effect of sublingual nitrates due to dry mouth. Avoid the concomitant use of mianserin with apraclonidine, brimonidine, sibutramine, or artemether with lumefantrine.
Do not use during pregnancy unless there are compelling reasons. There is no evidence of safety in human pregnancy. Animal studies have not shown hazard.
Mianserin is contraindicated during breast feeding. Breast feeding should be discontinued if treatment with mianserin is considered essential.
The most commonly occurring side effect is drowsiness, particularly during the first few days of treatment. Patients should be warned of the possible hazard in driving or operating machinery. Any drowsiness may be potentiated by alcohol.
The frequency and severity of depression-related symptoms such as blurred vision, dry mouth and constipation do not usually increase during treatment with mianserin; in fact an actual decrease has been observed in many cases.
Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10,000, <1/1000) very rare (<1/10,000) and not known (cannot be estimated from available data).
Not known: Bone marrow depression, usually presenting as granulocytopenia or agranulocytosis has been reported during treatment with mianserin1. Leucopenia and aplastic anaemia.
Not known: Hyponatraemia2
Not known: Suicidal ideation, suicidal behaviour3. Psychotic manifestations, including mania and paranoid delusions, may be exacerbated during antidepressant therapy. Interference with sexual function in adults4, withdrawal symptoms in adults4, withdrawal symptoms (e.g. neuro-muscular irritability) in neonates whose mothers received tricyclic or bridged tricyclic antidepressants during pregnancy4. Hypomania has also been reported at therapeutic dosage and under such circumstances treatment should be withdrawn.
Not known: Dizziness, tremor. Convulsions have also been reported at therapeutic dosage and under such circumstances treatment should be withdrawn.
Not known: Postural hypotension
Not known: Disturbances of liver function. Jaundice, usually mild, has also been reported at therapeutic dosage and under such circumstances treatment should be withdrawn.
Not known: Skin rash, sweating
Not known: Arthralgia, polyarthropathy, arthritis
Not known: Breast disorders (gynaecomastia, nipple tenderness and non- puerperal lactation).
Not known: Oedema
1 These reactions have occurred most commonly after 4-6 weeks and were generally reversible on stopping treatment. A full blood count is recommended every four weeks during the first three months of treatment. In addition, monitoring of the patient’s clinical condition should continue and if a patient develops fever, sore throat, stomatitis or other signs of infection, treatment should be stopped and a full blood count obtained (see section 4.4). These adverse reactions have been observed in all age groups but appear to be more common in the elderly.
2 Usually in the elderly, and possibly due to inappropriate secretion of antidiuretic hormone, hyponatraemia has been associated with all types of antidepressants and should be considered in all patients who develop drowsiness, confusion or convulsions whilst taking an antidepressant.
3 Cases of suicidal ideation and suicidal behaviours have been reported during mianserin therapy or early after treatment discontinuation (see section 4.4).
4 Although not reported with mianserin, these adverse events can occur with tricyclics and bridged tricyclics.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
None stated.
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