Tetrabenazine (tetrabenazine)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Tetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is a monoamine-depleting agent; the drug reversibly inhibits uptake of monoamines (e.g., dopamine, serotonin, norepinephrine, histamine) into synaptic vesicles and depletes monoamine stores.
Tetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is a monoamine-depleting agent. The drug reversibly inhibits uptake of monoamines (e.g., dopamine, norepinephrine, serotonin, histamine) into synaptic vesicles and depletes monoamine stores from nerve terminals.
Patients with Huntington's disease appear to exhibit oversensitivity to dopamine stimulation, resulting in choreic movements. Although the precise mechanism of tetrabenazine's antichorea effects has not been established, it appears to be related to the drug's ability to reversibly and selectively inhibit VMAT2 in the CNS, thereby decreasing the uptake of monoamines into synaptic vesicles and depleting monoamine stores from nerve terminals. In contrast, reserpine binds to both VMAT type 1 (VMAT1), which is expressed primarily in peripheral tissues (e.g., adrenal medulla, enterochromaffin cells), and VMAT2; because reserpine binds irreversibly to the transporter protein, monoamine depletion is long lasting.
Tetrabenazine and its metabolites preferentially deplete dopamine; the dose of tetrabenazine required to deplete norepinephrine or serotonin is approximately fivefold higher than that required to deplete dopamine. The preferential depletion of dopamine in the striatum is thought to contribute to the drug's antichorea effects. Tetrabenazine exhibits weak in vitro binding affinity for dopamine type 2 (D2) receptors.
The drug does not possess binding affinity for gamma-aminobutyric acid (GABA), glutamate, glycine, histamine, or norepinephrine receptors or ion channels.
The duration of tetrabenazine's action reportedly ranges from 16 to 24 hours. Following oral administration, tetrabenazine is rapidly and extensively metabolized in the liver, primarily by carbonyl reductase, to form 2 major active metabolites (alpha- and beta-dihydrotetrabenazine (HTBZ)), which are subsequently metabolized primarily by cytochrome P-450 (CYP) isoenzyme 2D6 to form 9-desmethyl-alpha-dihydrotetrabenazine (a minor metabolite) and 9-desmethyl-beta-dihydrotetrabenazine (a major metabolite). Plasma concentrations of the parent drug are generally undetectable.
Peak plasma concentrations of alpha-HTBZ and beta-HTBZ occur 1-1.5 hours following oral administration of the drug; administration with food has no effect on peak plasma concentrations or area under the plasma concentration-time curve (AUC) of these metabolites. The drug and alpha-HTBZ distribute rapidly into the CNS, with the highest and lowest concentrations occurring in the striatum and cortex, respectively. At least 19 metabolites of the drug have been identified.
Approximately 75% of an oral dose of tetrabenazine is eliminated in urine as metabolites, and fecal excretion accounts for 7-16% of the dose.
USES: Tetrabenazine is used to decrease the uncontrollable movements (chorea) caused by Huntington's disease. However, it is not a cure for the disease. Reducing the chorea will help you take part in more of your normal daily activities.
This medication is thought to work by decreasing the amount of certain natural substances in the brain (monoamines such as dopamine, serotonin, and norepinephrine), which are involved with nerve and muscle function. Tetrabenazine belongs to a class of drugs called monoamine depletors.
Generic name: tetrabenazine
Pronunciation: (TE-tra-BEN-a-zeen)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Tetrabenazine
Indications
The following indications are listed for Tetrabenazine:
- Chorea Associated With Huntington's Disease
Dosing
No dosing information is available for this tab.
Tetrabenazine tablets are administered orally without regard to food. If a dose of tetrabenazine is missed, the prescribed dose should be taken at the next scheduled time; an additional dose should not be administered to replace the missed dose.
Store tetrabenazine tablets at 25degreesC; excursions permitted between 15-30degreesC.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Tetrabenazine and its alpha-dihydrotetrabenazine (alpha-HTBZ), beta-dihydrotetrabenazine (beta-HTBZ), and 9-desmethyl-beta-dihydrotetrabenazine (DHTBZ) metabolites do not substantially inhibit cytochrome P-450 (CYP) isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A, nor do they substantially induce CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, or 3A4 in vitro. Neither tetrabenazine nor its alpha-HTBZ, beta-HTBZ, or 9-desmethyl-beta-DHTBZ metabolites are likely to be substrates or inhibitors of P-glycoprotein (P-gp) at clinically relevant concentrations in vivo.
Tetrabenazine's active metabolites alpha-HTBZ and beta-HTBZ are substrates of CYP2D6.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Patients who are actively suicidal or patients with untreated or inadequately treated depression.
Hepatic impairment.
Concomitant therapy with a monoamine oxidase (MAO) inhibitor. At least 14 days should elapse between discontinuance of an MAO inhibitor and initiation of tetrabenazine.
Concomitant therapy with reserpine. At least 20 days should elapse between discontinuance of reserpine and initiation of tetrabenazine therapy.
Concomitant therapy with deutetrabenazine or valbenazine.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in >=5%of patients with Huntington's chorea receiving tetrabenazine and at an incidence greater than that reported with placebo include sedation or somnolence, insomnia, fatigue, depression, anxiety, irritability, balance difficulties, extrapyramidal adverse effects (e.g., akathisia, bradykinesia, parkinsonism, hypertonia), nausea, vomiting, ecchymosis, falls, laceration of the head, and upper respiratory tract infection.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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The manufacturer states that safety and efficacy of tetrabenazine have not been established in pediatric patients.
Although controlled clinical trials have not been conducted to date, tetrabenazine has been effective in a limited number of pediatric patients with hyperkinetic movement disorders, including Tourette syndrome+ and severe chorea+. Limited experience suggests that the drug may have a similar adverse effect profile in pediatric patients as in adults, possibly with fewer parkinsonian adverse effects.
May cause fetal harm based on animal studies. There are no adequate and well-controlled studies of tetrabenazine in pregnant women. Reproduction studies in animals revealed no clear effects on embryofetal development when tetrabenazine was administered orally during the period of organogenesis at dosages up to 3 and 12 times the maximum recommended human dosage in rats and rabbits, respectively. However, when the drug was administered to rats during pregnancy and lactation, increased stillbirths, reduced pup survival, and delayed pup maturation were observed. Rats dosed orally with tetrabenazine do not produce 9-desmethyl-beta-dihydrotetrabenazine (DHTBZ), a major human metabolite of the drug. Oral administration of 9-desmethyl-beta-DHTBZ to rats at clinically relevant doses during the period of organogenesis or throughout pregnancy and lactation increased embryofetal and offspring postnatal mortality, decreased growth, and produced neurobehavioral and reproductive impairment in offspring. Maternal toxicity was also observed.
It is not known whether tetrabenazine or its metabolites distribute into milk; one study suggests that the drug does distribute into human milk. The effects of tetrabenazine on breastfed infants or on the production of milk are unknown. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for tetrabenazine and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.
The manufacturer provides no specific dosage recommendations for tetrabenazine in geriatric patients.
Pharmacokinetics of tetrabenazine and its principal metabolites have not been evaluated in geriatric individuals.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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