MOTETIS Tablet Ref.[8566] Active ingredients: Tetrabenazine

Tardive Dyskinesia

The condition should be persistent despite withdrawal of antipsychotic therapy, or in cases where withdrawal of antipsychotic medication is not a realistic option; also, where the condition persists despite reduction in dosage of antipsychotic medication or switching to atypical antipsychotic medication.

Depression

Tetrabenazine may cause depression or worsen pre-existing depression. If depression occurs, it may be controlled by reducing the dose of tetrabenazine and/or initiating antidepressant therapy. If depression is profound, or persists, discontinuation of tetrabenazine and initiation of antidepressant therapy should be considered. MAOI antidepressants should not be used until at least two weeks have elapsed since the last tetrabenazine dose to avoid a potentially serious drug interaction.

Parkinsonism

Tetrabenazine can induce parkinsonism and exacerbate pre-existing symptoms of Parkinson’s Disease. The tetrabenazine dose should be adjusted as clinically indicated to minimise this side effect.

Neuroleptic malignant syndrome

Neuroleptic Malignant Syndrome is a rare complication of tetrabenazine therapy. Neuroleptic Malignant Syndrome most often occurs early in treatment or in response to changes in dose. The main symptoms of this condition are mental changes, rigidity, hyperthermia, autonomic dysfunction (sweating and fluctuations in blood pressure) and elevated creatinine phosphokinase levels. If Neuroleptic Malignant syndrome is suspected tetrabenazine should be withdrawn immediately and appropriate treatment initiated. Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose absorption should not take this medicine.

Cardiac effects

Tetrabenazine causes a small increase (up to 8 msec) in the corrected QT interval. Tetrabenazine should be used with caution in combination with other drugs known to prolong QTc and in patients with congenital long QT syndromes and a history of cardiac arrhythmias.

Levodopa should be administered with caution in the presence of tetrabenazine.

Tetrabenazine should not be administered in the presence of MAOIs because of the risk of possible severe adverse effects.

Tetrabenazine should not be used concomitantly with reserpine.

The possibility of additive sedative effects should be considered when tetrabenazine is used in conjunction with CNS depressants (including alcohol, neuroleptics, hypnotics and opioids).

There is a potential for significant dopamine depletion when administering tetrabenazine concomitantly with neuroleptic agents (e.g. haloperidol, chlorpromazine, metoclopramide, etc.) and patients should be monitored clinically for the development of Parkinsonism.

Neuroleptic malignant syndrome has been observed in isolated cases.

The concurrent use of tetrabenazine with anti-hypertensive drugs and beta-blockers may increase the risk of orthostatic hypotension.

Inhibitors of CYP2D6 (e.g. fluoxetine, paroxetine, terbinafine, moclobemide and quinidine) may result in increased plasma concentrations of the active metabolite dihydrotetrabenazine, and they should only be combined with caution. A reduction of the tetrabenazine dose may be necessary.

Tetrabenazine should be used with caution with drugs known to prolong QTc including antipsychotic medications (e.g. chlorpromazine, thioridazine), antibiotics (e.g. gatifloxacin, moxifloxacin) and Class IA and III antiarrythmic medications (e.g. quinidine, procainamide, amiodarone, sotalol).

Pregnancy

Category B2.

There is inadequate evidence of safety of the drug in human pregnancy and no evidence from animal work, but it has been in wide use for many years without apparent ill consequence.

Breast-feeding

Tetrabenazine should be avoided in breast-feeding mothers.

Patients should be advised that tetrabenazine may cause drowsiness and therefore may modify their performance at skilled tasks (driving ability, operation of machinery, etc.) to a varying degree, depending on dose and individual susceptibility.

Adverse effects are usually mild with little hypotensive action and few digestive disorders. The main unwanted effect reported to date has been drowsiness, which occurs with higher doses. If depression occurs, it can be controlled by reducing the dose or by giving antidepressant drugs such as the monoamine oxidase inhibitors. However, tetrabenazine should not be given immediately after a course of any of the monoamine oxidase inhibitors as such treatment may lead to a state of restlessness, disorientation and confusion. In man, a Parkinsonian-like syndrome has been reported on rare occasions, usually in doses above 200 mg per day, but this disappears on reducing the dose.

Neuroleptic malignant syndrome (NMS) associated with the use of tetrabenazine has been reported rarely. This may occur soon after initiation of therapy, following an increase in dosage or after prolonged treatment. The clinical features usually include hyperthermia, severe extrapyramidal symptoms including muscular rigidity, autonomic dysfunction and altered levels of consciousness. Skeletal muscle damage may occur. If NMS is suspected tetrabenazine should be withdrawn and appropriate supportive therapy instituted; treatment with dantrolene and bromocriptine may be effective.

Other potential adverse effects are listed below. Effects are generally reversible once the treatment is stopped.

Body system: Reaction*

Blood and lymphatic systems disorders: Leucopenia (<1/10,000)

Psychiatric disorders: Depression (>1/10), Agitation (<1/10 and >1/100), Confusion (<1/10 and >1/100), Anxiety (<1/10 and >1/100), Insomnia (<1/10 and >1/100), Disorientation nervousness, Restlessness sleep disorders

Nervous system disorders: Drowsiness (>1/10), Parkinsonism (>1/10) (may include Balance impaired, Trembling, Drooling), Neuroleptic malignant syndrome (<1/10,000) Ataxia, Akathisia, Dystonia, Memory impairment, Dizziness

Eye disorders: Oculogyric crisis (<1/10,000), Photophobia (<1/10,000)

Cardiac disorders: Bradycardia

Vascular disorders: Postural hypotension

Gastrointestinal system disorders: Dysphagia, Nausea, Vomiting, Epigastric pain, Diarrhoea, Constipation, Dry mouth

Skin and subcutaneous tissue disorders: Sweating

Reproductive system and breast disorders: Menstrual irregularity

General disorders and administration site conditions: Fatigue, weakness, hypotherima

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected reactions https://nzphvc.otago.ac.nz/reporting/