Tetrabenazine Other names: Tetrabenzaine

Tetrabenazine should be used with caution in combination with other drugs known to prolong QTc and in patients with congenital long QT syndromes and a history of cardiac arrythmias.

The possibility of additive sedative effects should be considered when tetrabenazine is used in conjunction with CNS depressants (including alcohol, neuroleptics, hypnotics, and opioids).

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 C_max and an approximately 3-fold increase in AUC for α-HTBZ in subjects given paroxetine prior to tetrabenazine compared to tetrabenazine given alone. For β-HTBZ, C_max and AUC were increased 2.4- 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. The effect of moderate or weak CYP2D6 inhibitors such as duloxetine, terbinafine, amiodarone, or sertraline has not been evaluated.

The use of tetrabenazine in patients with renal insufficiency has not been studied.

The concurrent use of tetrabenazine with anti-hypertensive drugs and beta-blockers may increase the risk of orthostatic hypotension.

Adverse reactions associated with tetrabenazine, such as QTc prolongation, NMS, and extrapyramidal disorders, may be exaggerated by concomitant use of dopamine antagonists. There is a potential for significant dopamine depletion when administering tetrabenazine concomitantly with neuroleptic agents (e.g., haloperidol, chlorpromazine, metoclopramide, etc.) and patients should be monitored clinically for the development of parkinsonism.

In animal studies with tetrabenazine there was no evidence of effect on pregnancy or in utero survival. Female cycle lengths were increased and a delay in fertility was seen.

Tetrabenazine inhibits the action of levodopa and thereby attenuates its effect.

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.

Tetrabenazine may cause depression or worsen pre-existing depression. Particular caution should be exercised in treating patients with a history of depression or prior suicide attempts or ideation.

There are no adequate and well controlled studies for the use of tetrabenazine in pregnant women. Studies in animals have shown reproductive toxicity. 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.

It is unknown whether tetrabenazine or its metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. Tetrabenazine is contraindicated during breast-feeding.

Fertility

In animal studies with tetrabenazine there was no evidence of effect on pregnancy or in utero survival. Female cycle lengths were increased and a delay in fertility was seen.

Patients should be advised that tetrabenazine may cause somnolence and therefore may modify their performance at skilled tasks (driving ability, operation of machinery, etc.) to a varying degree, depending on dose and individual susceptibility.