Pharmacology
Tetrabenazine has a low and erratic bioavailability. It is extensively metabolised by first-pass metabolism. Little to no unchanged tetrabenazine can be detected in the urine. The major metabolite, hydroxytetrabenazine, is formed by reduction. Following i.v. administration of radiolabelled tetrabenazine to humans, the radioactivity decreased to minimal levels within 10 hours and could not be detected 3 days later. Forty percent (40%) of total activity was found in the urine within 24 hours and 2.5% in the feces. Fifty four percent (54%) of the total activity was excreted after 48 hours.
Indications
Nitoman (tetrabenazine) has been found useful in the treatment of hyperkinetic movement disorders such as Huntington's chorea, Hemiballismus, Senile Chorea, Tic and Gille's de la Tourette Syndrome and Tardive Dyskinesia.
Tetrabenazine is not indicated for the treatment of levodopa-induced dyskinetic/choreiform movements (see Warnings).
Tetrabenazine should only be used by (or in consultation with) physicians who are experienced in the treatment of hyperkinetic movement disorders.
Precautions
Levodopa: Tetrabenazine exacerbates Parkinsonian symptoms, and thereby attenuates the effect of levodopa (see Warnings).
Antidepressants and Monoamine Oxidase Inhibitors (MAOIs): Central excitation and possibly hypertension have occurred when tetrabenazine was added to existing therapy with desipramine or MAOIs.
There is no information on the safety and efficacy of antidepressant drugs, including MAOIs, in the treatment of tetrabenazine-induced depression (see Contraindications).
Neuroleptic Agents: There is a potential for severe manifestations of dopamine deficiency, when administering Nitoman concomitantly with neuroleptic agents (e.g., haloperidol, chlorpromazine, metoclopramide, etc.). Neuroleptic malignant syndrome has been observed in isolated cases.
Tetrabenazine may cause drowsiness and orthostatic hypotension. Therefore caution is recommended when driving, operating machinery, or performing other skilled tasks until the effect of Nitoman is known.
Limited information indicates that Nitoman is excreted in milk, therefore it should be avoided in breast-feeding mothers.
Animal reproductive studies have not been performed with Nitoman. There is no information on the safety of the drug in human pregnancy. However, tetrabenazine has been used for many years and no cases of malformation have been reported.
Supplied
Each round, yellowish-buff tablet, with CL25 imprinted across one face and a single break bar on the other, contains: tetrabenazine 25 mg. Nonmedicinal ingredients: iron oxide, lactose, magnesium stearate, starch maize white and talc. Bottles of 112. Store in well-closed containers. Store at 15 to 30°C.
Contraindications
Nitoman (tetrabenazine) is contraindicated in patients with a known hypersensitivity to the drug or to any of the components of the formulation.
Nitoman is contraindicated in patients with a current episode or a history of clinical depression (see Warnings).
Nitoman should not be administered together with a monoamine oxidase inhibitor (MAOI). At least 14 days should elapse between the discontinuation of an MAOI and initiation of treatment with Nitoman, as well as between the discontinuation of Nitoman and the initiation of treatment with an MAOI (see Precautions, Drug Interactions).
Warnings
Depression: Nitoman may cause depression. Recognition of depression may be difficult because this condition may often be disguised by somatic complaints. The drug should be stopped immediately at the first signs or symptoms of depression. The depression can be profound, and the possibility of suicide should be kept in mind until the depression clears. There is no information on the safety or efficacy of antidepressant drug treatment in Nitoman-induced depression.
Parkinsonism: Nitoman can induce symptoms of Parkinsonism, which are seen more frequently in the elderly and at relatively low doses. Nitoman dosage should be adjusted as tolerated and needed. Levodopa-induced dyskinetic/choreiform movements should be treated by reducing the dose of levodopa, and not by giving Nitoman, since the latter exacerbates Parkinsonian symptoms.
Adverse Effects
The most commonly observed adverse reactions with Nitoman (tetrabenazine) include, in decreasing order of frequency and observed during clinical use of the drug: signs and symptoms of Parkinsonism; drowsiness, fatigue, weakness; depression; anxiety, nervousness; insomnia; restlessness, akathisia; drooling; irritability, agitation; nausea, vomiting, epigastric pain; confusion, disorientation; hypotension; dizziness.
Although Nitoman has been in clinical use for a number of years, controlled clinical trials with the drug are limited.
Overdose
Signs and symptoms of overdosage may include drowsiness, sweating, hypotension and hypothermia.
Treatment is symptomatic.
Dosage
No adequately controlled clinical studies have been performed in children. Limited clinical experience suggests that treatment should be started at approximately half the adult dose, and titrated slowly and carefully according to tolerance and individual response.
An initial starting dose of 12.5 mg 2 to 3 times a day is recommended. This can be increased by 12.5 mg a day every 3 to 5 days until the maximal tolerated and effective dose is reached for the individual, and may have to be up/down titrated depending on individual tolerance. In most cases the maximal tolerated dose will be 25 mg t.i.d. In very rare cases, a 200 mg dose has been reached (the maximum recommended dose in some publications).
If there is no improvement at the maximal tolerated dose in 7 days, it is unlikely that Nitoman will be of benefit to the patient, either by increasing the dose or by extending the duration of treatment.
Geriatrics and Debilitated Patients: No adequately controlled clinical studies have been performed in the elderly and/or debilitated patients. Clinical experience suggests that a reduced initial and maintenance dose should be used. Parkinsonian-like adverse reactions are relatively common in these patients and may be dose-limiting.
