INGREZZA SPRINKLE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INGREZZA SPRINKLE (INGREZZA SPRINKLE).
INGREZZA SPRINKLE contains valbenazine, a selective VMAT2 inhibitor that reduces the release of dopamine into the synaptic cleft, thereby decreasing dopaminergic neurotransmission in the striatum. The exact mechanism for the treatment of tardive dyskinesia is unknown but is thought to involve modulation of dopamine signaling.
| Metabolism | Primarily metabolized by esterase-mediated hydrolysis to the active metabolite, NBI-98782. Subsequent metabolism of NBI-98782 involves CYP3A4/5 and CYP2D6, with minor contributions from other CYP enzymes and hydrolysis. Valbenazine is also a substrate of P-glycoprotein (P-gp). |
| Excretion | 60% renal (as unchanged drug and metabolites), 40% fecal (as metabolites). |
| Half-life | 17-20 hours; steady state reached in approximately 5 days. |
| Protein binding | 99% bound to human serum albumin. |
| Volume of Distribution | 1.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | 95% (oral capsule), with food decreasing peak concentration but not extent of absorption. |
| Onset of Action | 1 week for initial effect; maximal effect 2-4 weeks. |
| Duration of Action | 6-8 hours for motor symptom control; once-daily dosing provides continuous coverage. |
Initial dose: 40 mg orally once daily (as 1 capsule of INGREZZA SPRINKLE 40 mg or 4 capsules of 10 mg). After 1 week, increase to target dose of 80 mg orally once daily (as 2 capsules of 40 mg or 8 capsules of 10 mg). Capsules may be swallowed whole or opened and sprinkled onto soft food.
| Dosage form | CAPSULE |
| Renal impairment | No adjustment recommended for mild to moderate renal impairment. For severe renal impairment (eGFR <30 mL/min/1.73 m2) or end-stage renal disease (ESRD), reduce dose to 40 mg once daily. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): No adjustment. Moderate or severe hepatic impairment (Child-Pugh B or C): Not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment required; however, clinical studies included limited numbers of patients ≥65 years old, and no overall differences in safety or efficacy were observed. Monitor for increased somnolence or dizziness. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INGREZZA SPRINKLE (INGREZZA SPRINKLE).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or effects on milk production. Valbenazine and its active metabolite are present in animal milk. Due to potential for serious adverse reactions (e.g., sedation, extrapyramidal symptoms) in breastfed infants, breastfeeding is not recommended during treatment. M/P ratio not available. |
| Teratogenic Risk | Valbenazine is a VMAT2 inhibitor. No adequate and well-controlled studies in pregnant women. In animal studies, fetal developmental toxicity (including decreased fetal body weight and delayed ossification) occurred at maternal toxic doses. Based on mechanism of action, there is potential risk for fetal harm, especially in the first trimester when dopamine regulation is critical for embryonic development. Use only if benefit outweighs risk. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concomitant use with monoamine oxidase inhibitors (MAOIs) or use within 14 days of MAOI therapy due to increased risk of serotonin syndrome."]
| Precautions | ["Somnolence and sedation: may impair ability to drive or operate machinery.","QT prolongation: avoid use with other drugs that prolong QT interval, in patients with congenital long QT syndrome, or with electrolyte abnormalities.","Pregnancy: may cause fetal harm based on animal data; advise pregnant women of potential risk.","Lactation: advise not to breastfeed during treatment and for 5 days after last dose.","Patients with bipolar disorder: may unmask or exacerbate depression, mania, or hypomania.","Hepatic impairment: not recommended in patients with moderate to severe hepatic impairment (Child-Pugh B or C).","Renal impairment: dosage adjustment recommended for severe renal impairment."] |
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| Fetal Monitoring | Monitor for maternal adverse effects including increased heart rate, QT prolongation, and somnolence. Fetal monitoring via periodic ultrasound for growth and development if exposure during pregnancy. Consider fetal echocardiogram due to risk of QT prolongation. |
| Fertility Effects | No human data. In animal studies, no effects on fertility were observed at clinically relevant doses. However, based on mechanism, potential for alteration in prolactin levels which may affect reproductive function. |