INGREZZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INGREZZA (INGREZZA).
Vesicular monoamine transporter 2 (VMAT2) inhibitor; reduces presynaptic dopamine release.
| Metabolism | Primarily metabolized by CYP2D6; also metabolized by CYP3A4, CYP1A2, and other pathways. |
| Excretion | Approximately 60% renal (as unchanged drug and metabolites) and 30% fecal. |
| Half-life | Terminal elimination half-life of deutetrabenazine is 9-10 hours; clinical context: supports twice-daily dosing. |
| Protein binding | Deutetrabenazine and its active metabolites are 60-68% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution: approximately 5.5 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral bioavailability: approximately 80%. |
| Onset of Action | Oral: clinical effect observed within 4-8 weeks; maximum effect may take longer. |
| Duration of Action | Duration of action: approximately 12 hours; clinical note: doses administered twice daily maintain therapeutic levels. |
80 mg orally once daily; may titrate from 40 mg once daily for 7 days to reduce nausea.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment recommended for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), not recommended due to lack of data. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): No adjustment. Moderate to severe (Child-Pugh B or C): Not recommended due to limited data. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; clinical studies included patients aged ≥65 years with no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INGREZZA (INGREZZA).
| Breastfeeding | It is not known whether valbenazine or its metabolites are excreted in human milk. In nursing rats, valbenazine was detected in milk, with a milk-to-plasma ratio of approximately 3.2. Because of the potential for serious adverse reactions in nursing infants, including sedation and extrapyramidal symptoms, advise patients that breastfeeding is not recommended during treatment with INGREZZA. |
| Teratogenic Risk | INGREZZA (valbenazine) is classified as Pregnancy Category C. In animal studies, valbenazine was not teratogenic at exposures up to 8 times the human therapeutic dose. However, at doses producing maternal toxicity, there was evidence of developmental delay (reduced fetal body weight) in rats and rabbits, and increased fetal malformations (skull, vertebrae) in rabbits. The risk to human fetuses is unknown; it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution in first trimester due to lack of data. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to valbenazine or any component","Concurrent use with monoamine oxidase inhibitors (MAOIs) due to potential serotonin syndrome"]
| Precautions | ["May cause depression and suicidal thoughts/behaviors in patients with Huntington's disease","Can cause QT prolongation; monitor ECG","May cause akathisia, restlessness, and parkinsonism","Risk of sedation/somnolence","Avoid use with strong CYP2D6 inhibitors or inducers","Dose adjustment required with moderate/strong CYP3A4 inhibitors"] |
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| Fetal Monitoring | No specific monitoring requirements are established. However, given the potential for extrapyramidal symptoms and sedation, monitor infants for any adverse effects if exposure occurs during pregnancy or lactation. Routine prenatal care and fetal ultrasound are recommended to assess for developmental abnormalities. |
| Fertility Effects | In animal studies, valbenazine had no significant effects on male or female fertility at doses up to 8 times the human therapeutic dose. In humans, no fertility studies have been conducted. There is potential for hormonal effects due to dopamine antagonism, which could theoretically affect prolactin and menstrual cycle regulation, but no specific data are available. |