iNova

What it is

Tetrabenazine SUN (tetrabenazine) is supplied as tablets containing 25 mg of tetrabenazine. The tablets are yellow, circular, flat faced with beveled edge and uncoated, debossed with "179" on one side and scored on the other side. Tetrabenazine is a synthetic derivative of benzylquinolizine that causes depletion of dopamine and other monoamines in the central nervous system. It is an inhibitor of monoamine transportation into pre-synaptic neuronal vesicles, by inhibition of VMAT2 (vesicular monoamine transporter 2), which is principally located in the central nervous system.

Approved indications

— Control of chorea — Control of hemiballismus — Control of tardive dyskinesia — Control of buccolingual dyskinesia — Treatment of certain dystonic syndromes

Dosing overview

For adults, an initial dosage of 25 mg twice a day is recommended, which can be increased by 25 mg a day every 3 or 4 days until the desired therapeutic effect is achieved, or until 200 mg/day is given, or unwanted side effects intervene. In children, 12.5 mg twice a day has been used as an initial dose with increments of 12.5 mg every 3 to 4 days until the desired therapeutic effect is obtained, or an upper limit of 3 mg/kg/day is reached, or unwanted side effects intervene. Dosage may need to be reduced in patients with impaired renal or hepatic function or in elderly patients.

Key safety warnings

Tetrabenazine may cause depression or worsen pre-existing depression, and cases of suicidal ideation and behaviour have been reported in patients taking the product. Particular caution should be exercised in treating patients with a history of depression or prior suicide attempts or ideation. If depression or suicidal ideation occurs it should be controlled by reducing the dose and/or initiating antidepressant therapy. If depression or suicidal ideation is profound, or persists, discontinuation of tetrabenazine and initiation of antidepressant therapy should be considered. 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 is a rare complication of tetrabenazine therapy, most often occurring early in treatment or in response to changes in dose. The main symptoms of this condition are mental changes, rigidity, hyperthermia, autonomic dysfunction and elevated creatinine phosphokinase levels. If Neuroleptic Malignant Syndrome is suspected tetrabenazine should be withdrawn immediately and appropriate treatment initiated. Tetrabenazine causes a small increase of about 8 msec in the corrected QT interval, and in slow metabolisers this increase may be greater at 30 msec. Tetrabenazine should be used with caution with other drugs known to prolong QTc and in patients with congenital long QT syndromes and a history of cardiac arrhythmias. Dysphagia and choking attacks with a possibly consequent bronchopneumonia appear to be the only acutely dangerous adverse effects of tetrabenazine reported so far. If these occur, therapy should be discontinued.

Contraindications

Tetrabenazine should not be given closer than one day before or in combination with levodopa or reserpine as it blocks the action of these drugs, particularly the central action. Tetrabenazine should not be administered to persons with a known sensitivity to tetrabenazine or to any of the excipients. Tetrabenazine should not be given to patients with Parkinsonism or depression, as it may worsen these conditions. It should not be administered within two weeks of treatment with a monoamine oxidase inhibitor (MAOI). Tetrabenazine is contraindicated during breast-feeding.

PBS listing

The 25 mg tablet is listed on the PBS with 2 items under a streamlined restriction, with an ex-manufacturer price of A$179.49.

Regulatory history

Tetrabenazine SUN was first registered on the ARTG on 23 August 1991. The current product information was first approved on 28 November 2022.