Treating with VORANIGO^®

White bearded man drinking a glass of water

A simple, once-daily oral tablet¹

The recommended dose of VORANIGO^® for adults and pediatric patients ≥ 12 years of age depends on the patient’s weight:

Infographic on recommended dose of VORANIGO based on the patient's weight

Pediatric patients may have a higher risk of adverse drug reactions.

Patients should not eat food at least 2 hours before and 1 hour after taking VORANIGO^®.

Infographic depicting the required waiting time between meals and taking VORANIGO.

Tablets are to be swallowed whole with a glass of water and should not be split, crushed, or chewed to ensure the full dose is administered.

Administer VORANIGO^® until radiographic or clinical disease progression or unacceptable toxicity.

Missed dose

If a dose is missed by less than 6 hours, the missed dose should be taken as soon as possible.

If a dose is missed by more than 6 hours, the missed dose should be skipped, and the next dose should be taken at the usual time.

If a dose is vomited, a replacement dose should not be taken. The dose should be taken as usual the following day.

Prior to starting VORANIGO^®

In patients (≥ 12 years) with Grade 2 astrocytoma or oligodendroglioma following surgical intervention, treatment with VORANIGO^® should only be initiated following confirmation of an IDH1 or IDH2 mutation through a validated test.

Infographic of a test tube followed by the VORANIGO logo

Assess complete blood counts and liver laboratory tests, including AST, ALT, GGT, total bilirubin, and ALP, prior to the initiation of VORANIGO^®, every 2 weeks during the first 2 months of treatment, then once monthly for the first 2 years of treatment and as clinically indicated thereafter, with more frequent testing in patients who develop transaminase elevations.
Pregnancy testing is recommended in women of childbearing potential prior to starting treatment with VORANIGO^®.

Contraindications

Hypersensitivity to the active substance or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
Non-medicinal ingredients include:
- Croscarmellose sodium
- Hypromellose
- Lactose monohydrate
- Macrogol
- Magnesium stearate
- Microcrystalline cellulose
- Pharmaceutical ink
- Silicified microcrystalline cellulose
- Sodium lauryl sulfate
- Titanium dioxide

Management of special populations

Elderly

No dosage adjustment is recommended for patients ≥ 65 years of age.

Renal impairment

No dosage adjustment is recommended for patients with renal impairment (CL_cr > 40 mL/min estimated by Cockcroft-Gault).
The pharmacokinetics and safety of VORANIGO^® have not been studied in patients with  CL_cr ≤ 40 mL/min or renal impairment  requiring dialysis.
VORANIGO^® should be used with caution in patients with CL_cr ≤ 40 mL/min or who require dialysis.

Hepatic impairment

No dosage adjustment is recommended for patients with mild or moderate (Child-Pugh Class A or B) hepatic impairment.
The pharmacokinetics and safety of VORANIGO^® have not been studied in patients with severe hepatic impairment (Child-Pugh Class C).
For patients with severe hepatic impairment, monitor for increased adverse reactions.

Pediatric population

The safety and efficacy of VORANIGO^® in  children under 12 years of age have not been established.
Use of VORANIGO^® in pediatric patients 12 years and older is supported by evidence from studies in adults with additional population pharmacokinetic data.
No patients under the age of 18 were treated with VORANIGO^® in the pivotal Phase 3 study (INDIGO) as such no data are available.
Pediatric patients may have a higher risk of adverse drug reactions.

Contraception

Women of childbearing potential should use effective non-hormonal contraception during treatment with VORANIGO^® and for at least  3 months after the last dose. Since the effect of VORANIGO^® on the metabolism and efficacy of systemically acting hormonal contraceptives has not been investigated, barrier methods should be applied as a second form of contraception to avoid pregnancy.
Male patients with female partners of reproductive potential should use effective barrier contraception during treatment with VORANIGO^® and for at least 3 months after the last dose.

Pregnancy

VORANIGO^® is not recommended during pregnancy and in women of childbearing potential not using contraception.
Pregnant women, women of childbearing potential, or male patients with female partners of childbearing potential should be advised on the potential risk to a fetus.

Breastfeeding

Breastfeeding should be discontinued during treatment with VORANIGO^® and for at least  2 months after the last dose.

Fertility

There are no human data on the effect of VORANIGO^® on fertility.
Findings of adverse effects on reproductive organs in both sexes of rats were observed in repeat-dose studies with partial recovery noted. The clinical relevance of these effects is unknown.
Patients who are planning to conceive a child should be advised to seek reproductive counselling before starting treatment.

Monitoring

Infographic depicting the recommended monitoring schedule

In patients with ALT or AST elevations ≤ 3 times the ULN

Weekly monitoring is recommended.

In patients with pre-existing severe hepatic impairment (Child-Pugh Class C)

Treatment with VORANIGO^® may be considered only after careful risk/benefit assessment.
Close monitoring is required.
The use of VORANIGO^® has not been evaluated.

Please consult the VORANIGO^® Product Monograph for complete information on monitoring.

Drug-drug interactions

Moderate and strong CYP1A2 inhibitors

(e.g. ciprofloxacin, fluvoxamine)

Co-administration of VORANIGO^® with moderate or strong CYP1A2 inhibitors may increase VORANIGO^® plasma concentration.

Avoid concomitant use of VORANIGO^® with a moderate and strong CYP1A2 inhibitor. If concomitant use cannot be avoided, monitor for increased adverse reactions and modify the dosage as recommended.

Moderate CYP1A2 inducers

(e.g. phenytoin, rifampicin)

Co-administration of VORANIGO^® with moderate CYP1A2 inducers and smoking tobacco may decrease VORANIGO^® plasma concentration.

Avoid concomitant use of VORANIGO^® with moderate CYP1A2 inducers and smoking tobacco.

CYP substrates with narrow therapeutic index

(e.g. alfentanil, carbamazepine, cyclosporine, everolimus, fentanyl, ifosfamide, pimozide, quinidine, sirolimus, tacrolimus, tamoxifen)

Co-administration of VORANIGO^® with CYP2C19 or CYP3A4 substrates may decrease their plasma concentrations and therapeutic effects.

Avoid concomitant use of VORANIGO^® with CYP2C19 or CYP3A4 substrates where minimal concentration changes may lead to  reduced efficacy.

Hormonal contraceptives

Co-administration of VORANIGO^® may decrease concentrations of hormonal contraceptives which may lead to contraception failure.

Concomitant use of a barrier method of contraception is recommended during the treatment and for at least 3 months after the last dose.

Management of ARs and dose modifications

Hepatotoxicity¹

Severity*	Management and dose modifications
Grade 1
ALT or AST increase > ULN to 3 X ULN without concurrent T-Bil > 2 X ULN	Continue VORANIGO® at current dose Monitor liver laboratory tests weekly until recovery to < Grade 1
Grade 2
ALT or AST > 3–5 X ULN without concurrent T-Bil > 2 X ULN	1^st occurence
	Withhold VORANIGO® until recovery  to ≤ Grade 1 or baseline Recovery in ≤ 28 days: resume VORANIGO® at the same dose Recovery in > 28 days: resume VORANIGO® at reduced dose (see table below)
	Recurrence
	Withhold VORANIGO® until recovery to ≤ Grade 1 or baseline, and resume VORANIGO® at reduced dose (see table below)
Grade 3
ALT or AST > 5–20 X ULN without concurrent T-Bil > 2 X ULN	1^st occurrence
	Withhold VORANIGO^® until recovery to ≤ Grade 1 or baseline Recovery in ≤ 28 days: resume VORANIGO^® at reduced dose (see table below) Not recovered in ≤ 28 days: permanently discontinue VORANIGO^®
	Recurrence
	Permanently discontinue VORANIGO^®
Grade 2 or 3
Any ALT or AST > 3–20 X ULN with concurrent T-Bil > 2 X ULN	1^st occurrence
	Withhold VORANIGO® until recovery to ≤ Grade 1 or baseline Resume VORANIGO® at reduced dose (see table below)
	Recurrence
	Permanently discontinue VORANIGO®
Grade 4
Any ALT or AST > 20 X ULN	Permanently discontinue VORANIGO®

Other ARs¹

Grade 3
	1^st occurrence
	Withhold VORANIGO® until recovery  to ≤ Grade 1 or baseline Resume VORANIGO® at reduced dose (see table below)
	Recurrence
	Permanently discontinue VORANIGO®
Grade 4
	Permanently discontinue VORANIGO®

Recommended dose reductions for VORANIGO^®

Dose level	Dose and schedule	Number and strength of tablets
Patients ≥ 12 years of age weighing ≥ 40 kg
Starting dose	40 mg once daily	One 40 mg tablet / once daily
First dose reduction	20 mg once daily	Two 10 mg tablets / once daily
Second dose reduction	10 mg once daily	One 10 mg tablet / once daily
Patients ≥ 12 years of age weighing < 40 kg
Starting dose	20 mg once daily	Two 10 mg tablets / once daily
First dose reduction	10 mg once daily	One 10 mg tablet / once daily
Permanently discontinue VORANIGO® in patients unable to tolerate 10 mg once daily.

Please consult the VORANIGO^® Product Monograph for complete information on monitoring.

VORANIGO^®  resources

VORANIGO^® information leaflet

An overview of VORANIGO^® in the treatment of IDH1/2-mutant glioma, including efficacy and safety data, as well as dosing and administration information.

Download

AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: gamma-glutamyl transferase; ALP: alkaline phosphatase; CL_cr: creatinine clearance; AR: adverse reaction; ULN: upper limit of normal; T-Bil: total bilirubin; CYP: cytochrome P450
*Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

References:

VORANIGO^® Product Monograph. Servier Canada. August 27, 2024.
Data on File. INDIGO clinical trial participant.

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Treating with VORANIGO®