Tardivex Capsule

Treatment of adults with Tardive Dyskinesia.

Valbenazine and its active metabolites bind to and inhibit vesicular monoamine transporter 2 (VMAT2) with high selectivity with no significant binding to VMAT1. This prevents the reuptake and storage of monoamine neurotransmitters noradrenaline, dopamine, and serotonin in synaptic vesicles making them vulnerable to metabolism by cytosolic enzymes. The presynaptic release of monoamine neurotransmitters is decreased due to the lack of vesicles with packaged neurotransmitters ready for release into the synapse. Neither valbenazine nor its active metabolite exhibits significant off-target binding at dopamine, serotonin, or adrenaline receptors.

The initial dose is 40 mg once daily. After one week, increase the dose to the recommended dose of 80 mg once daily. Continuation of 40 mg once daily may be considered for some patients. Administer it orally with or without food.

Concomitant use of Tardivex with MAOIs may increase the concentration of monoamine neurotransmitters in synapses, potentially leading to an increased risk of adverse reactions such as serotonin syndrome, or attenuated treatment effect of Tardivex. Avoid concomi-tant use of Tardivex with MAOIs. Concomitant use of Tardivex with strong CYP3A4 inhibitors increased the exposure (Cmax and AUC) to valbenazine and its active metabolite compared with the use of valbenazine alone. Reduce the dose when valbenazine is co-administered with a strong CYP3A4 inhibitor. Consider reducing the dose based on tolerability when valbenazine is coadministered with a strong CYP2D6 inhibitor. Concomitant use of strong CYP3A4 inducers with valbenazine is not recommended. Digoxin concentrations should be monitored when co-administering valbenazine with digoxin. Increased digoxin exposure may increase the risk of exposure related adverse reactions.

Somnolence, QT Prolongation

The limited available data on Valbenazine use in pregnant women are insufficient to inform a drug-associated risk. A woman should not breastfeed during treatment with valbenazine and for 5 days after the final dose.

Tardivex can cause somnolence. May impair the patient's ability to drive or operate hazardous machinery. Tardivex may prolong the QT interval. For patients who are CYP2D6-poor metabolizers or are taking a strong CYP2D6 inhibitor, dose reduction may be necessary. Avoid use in patients with congenital long QT syndrome or with arrhyth­mias associated with a prolonged QT interval. No dosage adjustment is necessary for patients with mild to moderate renal impairment. Use is not recommended in patients with severe renal impairment.

The clinical trials involving valbenazine do not provide information regarding symptoms with overdose. No specific antidotes for valbenazine are known. In managing overdose, provide supportive care, including close medical supervision and monitoring, and consider the possibility of multiple drug involvement.

Store below 25°C, in a cool & dry place. Keep away from light. Keep all the medicines out of the reach of children.