Tetrabenazine

(BAN, rINN)
Tetrabenazine Chemical formula
Synonyms: Ro-1-9569; Tetrabenatsiini; Tetrabenazin; Tetrabenazina; Tétrabénazine; Tetrabenazinum. 1,3,4,6,7,11b-Hexahydro-3-isobutyl9,10-dimethoxybenzo-[a]quinolizin-2-one.
Cyrillic synonym: Тетрабеназин.

💊 Chemical information

Chemical formula: C19H27NO3 = 317.4.
CAS — 58-46-8.
ATC — N07XX06.
ATC Vet — QN07XX06.

💊 Adverse Effects

Drowsiness is the most frequent adverse effect of tetrabenazine. Orthostatic hypotension, symptoms of extrapyramidal dysfunction, gastrointestinal disturbances, and depression may also occur. Neuroleptic malignant syndrome and parkinsonism have been reported rarely. Overdosage has produced sedation, sweating, hypotension, and hypothermia.

Effects on mental function.

Depression is well documented as an adverse effect of tetrabenazine, and occurs in about 15% of patients; it has been reported to respond to reboxetine.1 Florid psychiatric symptoms such as panic attacks and obsessive-compulsive symptoms may be precipitated or exacerbated by tetrabenazine.2
1. Schreiber W, et al. Reversal of tetrabenazine induced depression by selective noradrenaline (norepinephrine) reuptake inhibition. J Neurol Neurosurg Psychiatry 1999; 67: 550
2. Bruneau MA, et al. Catastrophic reactions induced by tetrabenazine. Can J Psychiatry 2002; 47: 683.

Extrapyramidal disorders.

Dysphagia and choking were associated with tetrabenazine in the treatment of Huntington’s chorea.1 Fatal pneumonia, probably as a consequence of aspiration, had also been reported.
1. Snaith RP, Warren H de B. Treatment of Huntington’s chorea with tetrabenazine. Lancet 1974; i: 413–14.

Overdosage.

A patient who swallowed about 1 g (40 tablets) of tetrabenazine became drowsy 2 hours later and marked sweating occurred.1 Her state of consciousness improved after 24 hours and she talked rationally and gained full control of micturition after 72 hours.
1. Kidd DW, McLellan DL. Self-poisoning with tetrabenazine. Br J Clin Pract 1972; 26: 179–80.

💊 Precautions

Tetrabenazine may exacerbate the symptoms of parkinsonism. It may cause drowsiness; affected patients should not drive or operate machinery.

💊 Interactions

Tetrabenazine has been reported to block the action of reserpine. It may also diminish the effects of levodopa and exacerbate the symptoms of parkinsonism. Use of tetrabenazine immediately after a course of an MAOI may lead to confusion, restlessness, and disorientation; tetrabenazine should not be given with, or within 14 days of stopping, such therapy.

💊 Pharmacokinetics

Absorption of tetrabenazine is poor and erratic after oral doses. It appears to be extensively metabolised by first-pass metabolism. Its major metabolite, hydroxytetrabenazine, which is formed by reduction, is reported to be as active as the parent compound. It is excreted in the urine mainly in the form of metabolites.

💊 Uses and Administration

Tetrabenazine is used in the management of movement disorders including chorea, ballism, dystonias, tardive dyskinesia, and similar symptoms of CNS dysfunction. For the treatment of chorea, ballism, and other organic CNS movement disorders, a starting oral dose of 25 mg three times daily has been recommended; the BNF considers a dose of 12.5 mg twice daily (or 12.5 mg daily in the elderly) more appropriate initially, which is less likely to cause excessive sedation. The dose may be gradually increased by 25 mg daily every 3 or 4 days according to response up to a maximum of 200 mg daily. If the patient does not respond within 7 days of receiving the maximum dose further treatment with tetrabenazine is unlikely to be of benefit. For moderate to severe tardive dyskinesia, a dose of 12.5 mg daily is recommended initially, subsequently titrated according to response.

Extrapyramidal disorders.

In a long-term study1 of the use of tetrabenazine in 400 patients with movement disorders, the best responses seemed to be in tardive dyskinesia, tardive dystonia, and Huntington’s disease but benefit was also obtained in some patients with idiopathic dystonia, segmental myoclonus, and Tourette’s syndrome. Others have commented that in severe dystonia unresponsive to other drugs a combination of tetrabenazine with trihexyphenidyl and pimozide is sometimes effective.2Tetrabenazine significantly reduced chorea in ambulatory patients with Huntington’s disease in a small 12-week randomised placebo-controlled study.3 It was well tolerated, although there was a significant increase in reports of drowsiness and insomnia, which generally resolved with adjustment of doses.
1. Jankovic J, Beach J. Long-term effects of tetrabenazine in hyperkinetic movement disorders. Neurology 1997; 48: 358–62
2. Marsden CD, Quinn NP. The dystonias. BMJ 1990; 300: 139–44
3. Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology 2006; 66: 366–72.

💊 Preparations

Proprietary Preparations

Canad.: Nitoman; Denm.: Nitoman; Fr.: Xenazine; India: Revocon; Irl.: Nitoman; Israel: Xenazine; NZ: Xenazine; Port.: Nitoman; Revocon; UK: Xenazine.
Published May 08, 2019.