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XENAZINE is a brand name for Tetrabenazine. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Movement disorders associated with organic central nervous system conditions, e.g. Huntington’s chorea, hemiballismus and senile chorea. Tetrabenazine is also indicated for the treatment of moderate to severe tardive dyskinesia, which is disabling and/or socially embarrassing. The condition should be persistent…
Verbatim from this product's MHRA label. Tap a section to expand.
Adults The tablets are for oral administration. Organic Central Nervous System Movement Disorders Dosing of tetrabenazine involves careful titration of therapy to determine an individualised dose for each patient. When first prescribed, tetrabenazine therapy should be titrated slowly over several weeks to allow the identification of a dose for chronic use that reduces chorea and is well tolerated.
Dosage and administration are variable and only a guide is given. 5 mg to 25 mg per day and should be titrated up slowly every 4 to 7 days to allow identification of a dose that is efficacious and well tolerated. After titration is initiated, the total daily dose should be given in two to three divided doses.
Titration can be up to 200 mg per day or dose-limiting adverse events, whichever happens first. If the adverse event does not resolve, after dose reduction, consideration should be given to withdrawing tetrabenazine treatment. If there is no improvement at the maximum dose in seven days, it is unlikely that the compound will be of benefit to the patient, either by increasing the dose or by extending the duration of treatment.
Discontinuation of Treatment with Tetrabenazine Discontinuation of tetrabenazine is associated with the return of chorea (without significant worsening compared to baseline). Other adverse reactions to sudden treatment withdrawal are possible but unlikely and generally mild.
Resumption of Treatment Following treatment interruption of greater than 5 days or a treatment interruption occurring due to a change in the patient’s medical condition or concomitant medications, tetrabenazine therapy should be retitrated when resumed.
5 mg per day. If adverse events such as akathisia, restlessness, parkinsonism, depression, insomnia, anxiety, or intolerable sedation occur, titration should be stopped and the dose should be reduced. 5 mg a day subsequently titrated according to response.
Medication should be discontinued if there is no clear benefit or if the side- effects cannot be tolerated. For any indication, if adverse events such as akathisia, restlessness, parkinsonism, depression, insomnia, anxiety, or intolerable sedation occur, titration should be stopped and the dose should be reduced.
The Elderly No specific studies have been performed in the elderly. Paediatric Population The safety and efficacy of tetrabenazine in children have not been established. Other information Hepatic Insufficiency A study in hepatically impaired subjects has shown that there is a markedly decreased metabolism of tetrabenazine to its metabolites with a higher mean Cmax in hepatically impaired subjects in comparison with healthy subjects.
). At least 14 days should elapse between the discontinuation of a MAOI and initiation of treatment with tetrabenazine. Concomitant Use of Neuroleptic Drugs Adverse reactions associated with tetrabenazine, such as QTc prolongation, NMS, and extrapyramidal disorders, may be exaggerated by concomitant use of dopamine antagonists.
) and patients should be monitored clinically for the development of parkinsonism. Antihypertensive Drugs and Beta-Blockers The concurrent use of tetrabenazine with anti-hypertensive drugs and beta-blockers may increase the risk of orthostatic hypotension.
Interaction with CNS Depressants The possibility of additive sedative effects should be considered when tetrabenazine is used in conjunction with CNS depressants (including alcohol, neuroleptics, hypnotics, and opioids). Patients Taking CYP2D6 Inhibitors In vitro and in vivo studies indicate that the tetrabenazine metabolites α-HTBZ and β- HTBZ are substrates for CYP2D6.
The effect of CYP2D6 inhibition on the pharmacokinetics of tetrabenazine and its metabolites was studied in 25 healthy subjects following a single 50 mg dose of tetrabenazine given after 10 days of administration of the strong CYP2D6 inhibitor paroxetine 20 mg daily.
There was approximately 30% increase in Cmax and an approximately 3-fold increase in AUC for α-HTBZ in subjects given paroxetine prior to tetrabenazine compared to tetrabenazine given alone. 4- and 9- fold, respectively, in subjects given paroxetine prior to tetrabenazine given alone.
The elimination half-life of α-HTBZ and β-HTBZ was approximately 14 hours when tetrabenazine was given with paroxetine. Caution should be used when adding a strong CYP2D6 inhibitor (such as fluoxetine, paroxetine or quinidine) to a patient already receiving a stable dose of tetrabenazine and a reduction in the dose of tetrabenazine should be considered.
In the treatment of chorea, the dose of tetrabenazine should be titrated to determine the most appropriate dose for each patient. When first prescribed, tetrabenazine therapy should be titrated slowly over several weeks to allow the identification of a dose that both reduces chorea and is well tolerated.
If the adverse effect does not resolve or decrease, consideration should be given to discontinuing tetrabenazine. 2). 5). 5). Tardive Dyskinesia Pre-synaptic dopamine depletion could theoretically lead to supersensitivity to dopamine. Tetrabenazine is a central monoamine depleting agent which can cause extrapyramidal symptoms and theoretically cause tardive dyskinesia in humans.
There have been cases of tardive dyskinesia with tetrabenzine reported in the literature and in post-marketing; therefore, physicians should be aware of the possible risk. If signs and symptoms of tardive dyskinesia appear in a patient treated with tetrabenazine, drug discontinuation should be considered.
Depression/Suicidality Tetrabenazine may cause depression or worsen pre-existing depression. 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.
Patients should be closely monitored for the emergence of such adverse events, and patients and their caregivers should be informed of the risks and instructed to report any concerns to their doctor immediately. If depression or suicidal ideation occurs, it may be controlled by reducing the dose of tetrabenazine 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. 8). Anger and Aggression There is a potential risk of anger and aggressive behavior occurring or worsening in patients taking tetrabenazine with a history of depression or other psychiatric illnesses.
8). • With impaired hepatic function • With parkinsonism and hypokinetic-rigid syndrome (parkinsonism).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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The elimination half life of tetrabenazine and its metabolites in subjects with hepatic impairment was also prolonged. Increased exposure to other circulating metabolites and the contribution of tetrabenazine or those metabolites to safety and efficacy are unknown.
2). Renal Insufficiency The use of tetrabenazine in patients with renal insufficiency has not been studied.
The effect of moderate or weak CYP2D6 inhibitors such as duloxetine, terbinafine, amiodarone, or sertraline has not been evaluated.
Other Cytochrome P450 inhibitors:
Based on in vitro studies, a clinically significant interaction between tetrabenazine and other P450 inhibitors (other than CYP2D6 inhibitors) is not likely. , quinidine, procainamide, amiodarone, sotalol). Digoxin Digoxin is a substrate for P-glycoprotein.
A study in healthy volunteers showed that tetrabenazine (25 mg twice daily for 3 days) did not affect the bioavailability of digoxin, suggesting that at this dose, tetrabenazine does not affect P-glycoprotein in the intestinal tract.
In vitro studies also do not suggest that tetrabenazine or its metabolites are P-glycoprotein inhibitors. Paediatric Population Interaction studies have only been performed in adults. 6 Fertility, Pregnancy and lactation Pregnancy There are no adequate and well controlled studies for the use of tetrabenazine in pregnant women.
3). The potential risk for humans is unknown. Tetrabenazine is not recommended during pregnancy and in women of childbearing potential not using contraception. The effect of tetrabenazine on labour and delivery in humans is unknown. Lactation It is unknown whether tetrabenazine or its metabolites are excreted in human milk.
A risk to the suckling child cannot be excluded. 3). Fertility In animal studies with tetrabenazine there was no evidence of effect on pregnancy or in utero survival. 3). ) to a varying degree, depending on dose and individual susceptibility.
8 Undesirable effects System/organ categories Reactions Very common (>1/10) Common (<1/10 but >1/100) Uncommon (<1/100 but (>1/1,000) Rare (<1/1,000 but (>1/10,000) Very rare (<1/10,0000 ) Unknown Blood & lymphatic system disorders Leukopaenia, Neutropenia Immune Hypersensitivi system disorders ty Metabolism and nutrition orders Decreased appetite Dehydration Increased appetite Psychiatric disorders Depression, Anxiety, Restlessness, Confusion Irritability, Obsessive- compulsive disorder, Agitation Aggression, Anger, Suicidal ideation, Suicidal attempt, Nervousness, Sleep disorder Nervous system disorders Sedation/ Somnolence/ Drowsiness, Extrapyramida l event, Insomnia, Akathisia Parkinsonism (may include balancing pro- blems), Gait imbalance/ balance difficulty, Bradykinesia, Dystonia, Lethargy, Dizziness, Dysarthria, Headache Neuroleptic Malignant Syndrome, Ataxia, Tremor, Excess salivation Memory loss Eye disorders Blepharospas m Oculogyric crisis, Photophobia Cardiac disorders Palpitations Vascular disorders Hypertension Postural hypotension, Hypertensive crisis Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection Pneumonia, Dyspnoea, Bronchitis Cough, Pneumonia aspiration Gastro- intestinal disorders Nausea Diarrhoea, Vomiting, Constipation Dysphagia Dry mouth Heptaobiliary disorders Increased ALT, Increased AST Skin & subcutaneous tissue disorders Hyperhidrosis, Rash, Pruitus, Urticaria Renal and urinary Dysuria Urinary tract infection disorders Reproductive system and breast disorders Irregular menstrual cycle/amenorr hea/menstrual disorders General disorders […]
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. Dysphagia Dysphagia is a component of Huntington’s disease.
However, drugs that reduce dopaminergic transmission have been associated with esophageal dysmotility and dysphagia. Dysphagia may be associated with aspiration pheumonia. In clinical trials, some of the cases of dysphagia were associated with aspiration pneumonia.
Whether these events were related to treatment is unknown. Neuroleptic Malignant Syndrome A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with tetrabenazine and other drugs that reduce dopaminergic transmission.
Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria, rhabdomyolysis, and acute renal failure.
The management of NMS should include (1) immediate discontinuation of tetrabenazine and other drugs not essential to concurrent therapy; (2) intensive symptomatic treatment and medical monitoring; and (3) treatment of any concomitant serious medical problems for which specific treatments are available.
There is no general agreement about specific pharmacological treatment regimens for NMS. If the patient requires treatment with tetrabenazine after recovery from NMS, the potential reintroduction of therapy should be carefully considered.
The patient should be carefully monitored, since recurrences of NMS have been reported. QTc Prolongation Tetrabenazine causes a small increase (up to 8 msec) in the corrected QT interval. 5). Cardiac Disease Tetrabenazine has not been evaluated in patients with a recent history of myocardial infarction or unstable heart disease.
Akathisia, Restlessness, and Agitation Patients taking tetrabenazine should be monitored for the presence of akathisia. Patients taking tetrabenazine should also be monitored for signs and symptoms of restlessness and agitation, as these may be indicators of developing akathisia.
If a patient develops akathisia, the tetrabenazine dose should be reduced; however, some patients may require discontinuation of therapy. Orthostatic Hypotension Tetrabenazine can induce postural dizziness and syncope. Patients who are vulnerable to hypotension should be closely monitored in the initial stages of therapy.
Hyperprolactinemia Tetrabenazine elevates serum prolactin concentrations in humans. Following administration of 25 mg to healthy volunteers, peak plasma prolactin levels increased 4- to 5-fold. Tissue culture experiments indicate that approximately one third of human breast cancers are prolactin-dependent in vitro, a factor of potential importance if tetrabenazine is being considered for a patient with previously detected breast cancer.
Although amenorrhea, […]