patients may require discontinuation of therapy.
Orthostatic Hypotension
Tetrabenazine may induce postural hypotension at therapeutic doses. This should be considered in patients who may be vulnerable to hypotension or its effects. Monitoring of vital signs on standing should be considered in patients who are vulnerable to hypotension.
Hyperprolactinemia
Tetrabenazine elevates serum prolactin concentrations in humans. Following administration of 25 mg to healthy volunteers, maximum 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, galactorrhoea, gynecomastia and impotence can be caused by elevated serum concentrations, the clinical significance of elevated serum prolactin concentrations for most patients is unknown.
Chronic increase in serum prolactin levels (although not eva luated in the tetrabenazine development program) has been associated with low levels of estrogen and increased risk of osteoporosis. If there is a clinical suspicion of symptomatic hyperprolactinaemia, appropriate laboratory testing should be done and consideration should be given to discontinuation of tetrabenazine.
Binding to Melanin-Containing Tissues
Since tetrabenazine or its metabolites bind to melanin-containing tissues, it could accumulate in these tissues over time. This raises the possibility that tetrabenazine may cause toxicity in these tissues after extended use. The clinical relevance of tetrabenazine's binding to melanin-containing tissues is unknown.
Although there are no specific recommendations for periodic ophthalmic monitoring, prescribers should be aware of the possibility of ophthalmologic effects after long term exposure.
Hepatic Insufficiency
Tetrabenazine should be used with caution in patients with hepatic impairment (see section 4.2).
Drug-Disease Interactions
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Tetrabenazine should not be used concomitantly with reserpine, MAO inhibitors.
Levodopa should be administered with caution in the presence of Tetrabenazine.
Concomitant use with tricyclic antidepressants, alcohol, opioids, beta blocking agents, antihypertensive drugs, hypnotics and neuroleptics is not recommended.
No interaction studies with tetrabenazine have been performed in vivo, and metabolising enzymes are partly unknown. In vitro studies indicate that tetrabenazine may be a CYP2D6 inhibitor and therefore cause increased plasma concentrations of medicinal products metabolised by CYP2D6.
In vitro and in vivo studies indicate that the tetrabenazine metabolites α-DTBZ and β-DTBZ are substrates for CYP2D6. Inhibitors of CYP2D6 (e.g. fluoxetine, paroxetine, terbinafine, moclobemide and quinidine) may result in increased plasma concentrations of α-HTBZ and β-HTBZ,, why they should only be combined with caution. A reduction of the tetrabenazine dose may be necessary.
Tetrabenazine should be used with caution with drugs known to prolong QTc including antipsychotic medications (e.g |
