For: Tardive Dyskinesia
Ingrezza (valbenazine) is a novel, highly-selective VMAT2 inhibitor for the treatment of tardive dyskinesia.
INGREZZA- valbenazine capsule
Neurocrine Biosciences, Inc.
1 INDICATIONS AND USAGE
INGREZZA is indicated for the treatment of adults with tardive dyskinesia [see Clinical Studies ( 14) ] .
2 DOSAGE AND ADMINISTRATION
2.1 Dosing and Administration Information
The initial dose for INGREZZA 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 INGREZZA orally with or without food [see Clinical Pharmacology ( 12.3) ] .
2.2 Dosage Recommendations for Patients with Hepatic Impairment
The recommended dose for patients with moderate or severe hepatic impairment (Child-Pugh score 7 to 15) is INGREZZA 40 mg once daily [see Use in Specific Populations ( 8.7), Clinical Pharmacology ( 12.3)].
2.3 Dosage Recommendations for Known CYP2D6 Poor Metabolizers
Consider reducing INGREZZA dose based on tolerability for known CYP2D6 poor metabolizers [see Use in Specific Populations ( 8.6), Clinical Pharmacology ( 12.3)].
2.4 Dosage Recommendations for Concomitant Use with Strong CYP3A4 Inducers and Strong CYP3A4 or CYP2D6 Inhibitors
Coadministration with Strong CYP3A4 Inducers
Concomitant use of strong CYP3A4 inducers with INGREZZA is not recommended [ see Drug Interactions ( 7.1) ].
Coadministration with Strong CYP3A4 In hibito rs
Reduce INGREZZA dose to 40 mg once daily when INGREZZA is coadministered with a strong CYP3A4 inhibitor [see Drug Interactions ( 7.1)].
Coadministration with Strong CYP 2D6 In hibito rs
Consider reducing INGREZZA dose based on tolerability when INGREZZA is coadministered with a strong CYP2D6 inhibitor [see Drug Interactions ( 7.1)].
3 DOSAGE FORMS AND STRENGTHS
INGREZZA is available as 40 mg capsules. The white opaque body and purple cap capsule is printed with 'VBZ" and '40" in black ink.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Somnolence
INGREZZA can cause somnolence. Patients should not perform activities requiring mental alertness such as operating a motor vehicle or operating hazardous machinery until they know how they will be affected by INGREZZA [see Adverse Reactions ( 6.1)].
DESCRIPTION
INGREZZA contains valbenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, present as valbenazine tosylate salt, with the chemical name, L-Valine, (2R,3R ,11bR)-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H -benzo[a ]quinolizin-2-yl ester, 4-methylbenzenesulfonate (1:2). Valbenazine tosylate is slightly soluble in water. Its molecular formula is C38 H54 N2 O10 S2 , and its molecular weight is
762.97 g/mol (ditosylate salt) with the following structure:
The following chemical structure of INGREZZA contains valbenazine, a selective vesicular monoamine transporter 2 inhibitor, present as valbenazine tosylate salt, with the chemical name, L-Valine, (2R,3R,11bR)-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-yl ester, 4-methylbenzenesulfonate (1:2). Valbenazine tosylate is slightly soluble in water. Its molecular formula is C38H54N2O10S2, and its molecular weight is 762.97 g/mol (ditosylate salt).
The molecular formula of valbenazine free base is C24 H38 N2 O4 and its molecular weight is 418.57.
INGREZZA capsules are intended for oral administration only. Each capsule contains 73 mg of valbenazine tosylate, which is equivalent to 40 mg of valbenazine free base. It also contains the following inactive ingredients: mannitol, partially pregelatinized starch, fumed silica, and magnesium stearate. The capsule shell contains gelatin, candurin silver fine, FD&C Red#40, and FD&C Blue#1.
12 CLINICAL PHARMACOLOGY
Figure 1: Effects of Hepatic Impairment on Valbenazine PharmacokineticsFigure 2: Effects of Strong CYP3A4 Inducers and Inhibitors on Valbenazine PharmacokineticsFigure 3: Effects of Valbenazine on Pharmacokinetics of Other Drugs
12.1 Mechanism of Action
The mechanism of action of valbenazine in the treatment of tardive dyskinesia is unknown, but is thought to be mediated through the reversible inhibition of vesicular monoamine transporter 2 (VMAT2), a transporter that regulates monoamine uptake from the cytoplasm to the synaptic vesicle for storage and release.
