VORANIGO is administered orally as a once-daily tablet1
The recommended dosage of VORANIGO:
Adult patients- 40 mg orally once daily until disease progression or unacceptable toxicity
- Patients weighing ≥40 kg, take 40 mg orally once daily
- Patients weighing <40 kg, take 20 mg orally once daily
Continue VORANIGO until disease progression or unacceptable toxicity.
Take VORANIGO tablets at about the same time each day. If a dose is missed by less than 6 hours, take the missed dose as soon as possible within 6 hours. If a dose is missed by more than 6 hours, skip the missed dose, and take the next dose at the usual time.
If vomiting occurs after taking a dose, do not take a replacement dose, and take the next dose at the scheduled time on the following day.
Monitoring and dose modifications
Initial assessment and continued monitoring for treatment with VORANIGO.
Before initiating VORANIGO1:
- Evaluate blood chemistry and liver laboratory tests
- Verify pregnancy status in females of reproductive potential
During treatment with VORANIGO1:
- Monitor liver laboratory tests (AST, ALT, GGT, total bilirubin, and alkaline phosphatase) prior to the start of VORANIGO, every 2 weeks during the first 2 months of treatment and then monthly for the first 2 years of treatment, and as clinically indicated, with more frequent testing in patients who develop transaminase elevations
- Reduce the dose, withhold, or permanently discontinue VORANIGO based on severity
Pregnancy and fertility considerations1:
- Based on animal embryo-fetal toxicity studies, VORANIGO can cause fetal harm when administered to pregnant women
- Based on findings in animals, VORANIGO may impair fertility in females and males of reproductive potential. The effects on female and male fertility were not reversible in rats
- Advise females of reproductive potential to use effective nonhormonal contraception during treatment with VORANIGO and for 3 months after the last dose. VORANIGO can render some hormonal contraceptives ineffective
- Advise male patients with female partners of reproductive potential to use effective contraception during treatment with VORANIGO and for 3 months after the last dose
- Because of the potential for adverse reactions in breastfed children from VORANIGO, advise women not to breastfeed during treatment with VORANIGO and for 2 months after the last dose
The VORANIGO USPI does not include recommendations for electrocardiogram monitoring before or during treatment.1
Recommended VORANIGO dosage reductions for adverse reactions (ARs)1
| Dose reduction | Recommended dose and schedule |
|---|---|
| Adult patients and pediatric patients 12 years and older weighing at least 40 kg | |
| First | 20 mg once daily |
| Second | 10 mg once daily |
| Pediatric patients 12 years and older weighing less than 40 kg | |
| First | 10 mg once daily |
| Permanently discontinue VORANIGO in patients unable to tolerate 10 mg once daily | |
Adjustments to monitoring and dosing due to ARs
Additional blood counts, including liver laboratory tests, and dose modifications are recommended for increases in ALT, AST, and total bilirubin.1
Recommended dosage modifications and management for ARs1
Hepatotoxicity (Elevation of ALT or AST)
| Adverse reaction |
|
|||||||||||
| Hepatotoxicity (Elevation of ALT or AST) |
|
|||||||||||
| Other ARs |
|
|||||||||||
| Severitya | Management and dosage modifications |
|---|---|
| Grade 1 ALT or AST increase >ULN to 3 x ULN without concurrent total bilirubin >2 x ULN |
Continue VORANIGO at current dose Monitor liver laboratory tests weekly until recovery to <Grade 1 |
| Grade 2 ALT or AST >3 to 5 x ULN without concurrent total bilirubin >2 x ULN |
First occurrence: Withhold VORANIGO until recovery to ≤Grade 1 or baseline
Recurrence: Withhold VORANIGO until recovery to ≤Grade 1 or baseline, and resume VORANIGO at reduced dose
See dosage reduction info
|
| Grade 3 ALT or AST >5 to 20 x ULN without concurrent total bilirubin >2 x ULN |
First occurrence: Withhold VORANIGO until recovery to ≤Grade 1 or baseline
Recurrence: Permanently discontinue VORANIGO
|
| Grade 2 or 3 ALT or AST >3 to 20 x ULN with concurrent total bilirubin >2 x ULN |
First occurrence: Withhold VORANIGO until recovery to ≤Grade 1 or baseline
Recurrence: Permanently discontinue VORANIGO
|
| Grade 4 Any ALT or AST >20 x ULN |
Permanently discontinue VORANIGO |
| Severitya | Management and dosage modifications |
|---|---|
| Grade 3 |
First occurrence: Withhold VORANIGO until recovery to ≤Grade 1 or baseline
Recurrence: Permanently discontinue VORANIGO
|
| Grade 4 | Permanently discontinue VORANIGO |
aARs graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Dosing changes to VORANIGO in INDIGO
The median duration of exposure to VORANIGO was 12.7 months (range: 1 to 30 months).1
| Duration of exposure to VORANIGO | Number of patients |
|---|---|
| ≥6 months | 153 (92%) |
| ≥1 year | 89 (53%) |
Dosage interruptions and discontinuations in patients treated with VORANIGO in the INDIGO trial.
Dosage interruptions1
- Dosage interruptions of VORANIGO due to an AR occurred in 30% of patients
- ARs which required dose interruption in ≥5% of patients included ALT increased (14%), COVID-19 (9%), and AST increased (6%)
Dose reductions1
- Dose reductions of VORANIGO due to an AR occurred in 11% of patients
- ARs which required dose reduction in ≥5% of patients included ALT increased (8%)
Discontinuations1
- Permanent discontinuation of VORANIGO due to an AR occurred in 3.6% of patients
- ARs which resulted in permanent discontinuation of VORANIGO in ≥2% of patients included ALT increased (3%)
Find VORANIGO access and patient support materials
ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal.
Reference: 1. Voranigo. Package insert. Servier Pharmaceuticals LLC; 2024.
