How to Dose Valbenazine
Start valbenazine at 40 mg once daily, then increase to the recommended dose of 80 mg once daily after one week for tardive dyskinesia, or titrate by 20 mg increments every two weeks for Huntington's disease chorea. 1
Standard Dosing Algorithm
For Tardive Dyskinesia
- Week 1: 40 mg once daily
- Week 2 onwards: 80 mg once daily (recommended dose)
- Alternative maintenance doses of 40 mg or 60 mg once daily may be considered based on individual response and tolerability 1
For Chorea Associated with Huntington's Disease
- Week 1-2: 40 mg once daily
- Week 3-4: 60 mg once daily
- Week 5 onwards: 80 mg once daily (recommended dose)
- Doses of 40 mg or 60 mg once daily may be considered depending on response and tolerability 1
Administration Details
- Can be taken with or without food 1
- INGREZZA capsules may be swallowed whole
- INGREZZA SPRINKLE may be opened and sprinkled over soft food (avoid milk or drinking water), or swallowed whole with water
- Do not crush or chew 1
Dose Adjustments for Specific Populations
Hepatic Impairment
Reduce dose to 40 mg once daily for moderate or severe hepatic impairment (Child-Pugh score 7-15). 1 Patients with moderate to severe hepatic impairment have significantly higher exposure to both valbenazine and its active metabolite compared to those with normal hepatic function 1.
CYP2D6 Poor Metabolizers
Reduce dose to 40 mg once daily for known CYP2D6 poor metabolizers. 1 These patients have increased exposure to valbenazine's active metabolite, which may increase the risk of exposure-related adverse reactions 1.
Renal Impairment
No dose adjustment required for any degree of renal impairment, including end-stage renal disease 1. The drug is primarily eliminated via biliary and fecal routes with less than 1% recovered in urine 1.
Geriatric Patients
No dose adjustment required for elderly patients. Clinical trials showed similar safety and effectiveness in patients 65 years and older compared to younger patients 1.
Drug Interaction Dose Modifications
Strong CYP2D6 Inhibitors
Reduce valbenazine dose when co-administered with strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine). 1 These medications increase exposure to the active metabolite, potentially increasing adverse reaction risk.
Strong CYP3A4 Inducers
Concomitant use with strong CYP3A4 inducers is not recommended (e.g., rifampin, carbamazepine, phenytoin, St. John's wort). 1 These agents decrease exposure to both valbenazine and its active metabolite, potentially reducing efficacy.
Digoxin Co-administration
Monitor digoxin concentrations closely when co-administering with valbenazine due to P-glycoprotein inhibition. Digoxin dose adjustment may be necessary 1.
Clinical Efficacy Data
The 80 mg dose demonstrated robust efficacy in phase 3 trials, with a mean reduction in AIMS dyskinesia score of -3.2 compared to -0.1 for placebo at week 6 2. The 40 mg dose showed intermediate efficacy with a reduction of -1.9 2. The 60 mg dose, approved through model-informed drug development, showed predicted efficacy between the 40 mg and 80 mg doses 3.
Response rates (≥50% reduction in AIMS dyskinesia score) were 40.0% for 80 mg versus 8.7% for placebo, yielding a number needed to treat of 4 4.
Safety Considerations
- Most common adverse event meeting the ≥5% threshold and ≥2 times placebo rate was somnolence/sedation/fatigue (10.9% vs 4.2% placebo), with a number needed to harm of 15 4
- Discontinuation due to adverse events was low (2.9% vs 1.6% placebo) 4
- QT prolongation: Valbenazine can prolong the QT interval, though mean changes were minimal (2.1 ms for 80 mg vs 1.2 ms for placebo) 5
- No clinically significant cardiovascular effects on blood pressure or heart rate 5
- Psychiatric status remained stable during treatment 2
Special Warnings
Pregnancy and Lactation
- Animal studies showed increased stillbirths and postnatal mortality at doses less than the maximum recommended human dose 1
- Advise women not to breastfeed during treatment and for 5 days after the final dose 1
Contraception
Some formulations (e.g., cariprazine mentioned in general context) may require effective contraception in females of childbearing age, though this is not specifically stated in valbenazine labeling 6.