Tovorafenib Dosage

Medically reviewed by Drugs.com. Last updated on Jun 6, 2024.

Applies to the following strengths: 100 mg; 25 mg/mL

Usual Adult Dose for Malignant Glioma

The recommended dose based on BSA is 380 mg/m2 orally once a week

Recommended immediate release tablet dosage based on BSA:
BSA 0.30 to 0.89 m2: Administer oral suspension once a week.
BSA 0.90 to 1.12 m2: 400 mg orally once a week
BSA 1.13 to 1.39 m2: 500 mg orally once a week
BSA 1.40 m2 or greater: 600 mg orally once a week

Recommended oral suspension dosage based on BSA:
BSA 0.30 to 0.35 m2: 125 mg orally once a week
BSA 0.36 to 0.42 m2: 150 mg orally once a week
BSA 0.43 to 0.48 m2: 175 mg orally once a week
BSA 0.49 to 0.54 m2: 200 mg orally once a week
BSA 0.55 to 0.63 m2: 225 mg orally once a week
BSA 0.64 to 0.77 m2: 275 mg orally once a week
BSA 0.78 to 0.83 m2: 300 mg orally once a week
BSA 0.84 to 0.89 m2: 350 mg orally once a week
BSA 0.90 to 1.05 m2: 375 mg orally once a week
BSA 1.06 to 1.25 m2: 450 mg orally once a week
BSA 1.26 to 1.39 m2: 525 mg orally once a week
BSA 1.40 m2 or greater: 600 mg orally once a week

Maximum dose: 600 mg orally once a week
Duration of therapy: Until disease progression or intolerable toxicity.

Comments:

Before starting treatment, confirm the presence of BRAF fusion or rearrangement, or BRAF V600 mutation.
The recommended dosage for patients with BSA less than 0.3 m2 has not been established.

Use: For the treatment of patients with relapsed or refractory low-grade glioma harboring a BRAF fusion or rearrangement, or BRAF V600 mutation

Usual Pediatric Dose for Malignant Glioma

6 months or older:
The recommended dose based on BSA is 380 mg/m2 orally once a week

Recommended immediate release tablet dosage based on BSA:
BSA 0.30 to 0.89 m2: Administer oral suspension once a week.
BSA 0.90 to 1.12 m2: 400 mg orally once a week
BSA 1.13 to 1.39 m2: 500 mg orally once a week
BSA 1.40 m2 or greater: 600 mg orally once a week

Recommended oral suspension dosage based on BSA:
BSA 0.30 to 0.35 m2: 125 mg orally once a week
BSA 0.36 to 0.42 m2: 150 mg orally once a week
BSA 0.43 to 0.48 m2: 175 mg orally once a week
BSA 0.49 to 0.54 m2: 200 mg orally once a week
BSA 0.55 to 0.63 m2: 225 mg orally once a week
BSA 0.64 to 0.77 m2: 275 mg orally once a week
BSA 0.78 to 0.83 m2: 300 mg orally once a week
BSA 0.84 to 0.89 m2: 350 mg orally once a week
BSA 0.90 to 1.05 m2: 375 mg orally once a week
BSA 1.06 to 1.25 m2: 450 mg orally once a week
BSA 1.26 to 1.39 m2: 525 mg orally once a week
BSA 1.40 m2 or greater: 600 mg orally once a week

Maximum dose: 600 mg orally once a week
Duration of therapy: Until disease progression or intolerable toxicity.

Comments:

Before starting treatment, confirm the presence of BRAF fusion or rearrangement, or BRAF V600 mutation.
The recommended dosage for patients with BSA less than 0.3 m2 has not been established.

Use: For the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation

Renal Dose Adjustments

Mild to Moderate Renal Dysfunction (estimated GFR [eGFR] 30 mL/min or more): No adjustment recommended
Severe Renal Dysfunction (eGFR less than 30 mL/min): Unknown

Liver Dose Adjustments

Mild liver dysfunction: No adjustment recommended
Moderate to Severe liver dysfunction: Unknown

Dose Adjustments

Recommended Dosage Reductions for Adverse Reactions:
Immediate release tablets:

BSA 0.30 to 1.12 m2: Administer the oral suspension once a week.
BSA 1.13 to 1.39 m2:
First Dosage Reduction: 400 mg orally once a week
Second Dosage Reduction: Administer oral suspension once a week.
BSA 1.40 m2 or greater:
First Dosage Reduction: 500 mg orally once a week
Second Dosage Reduction: 400 mg orally once a week

Oral Suspension:

BSA 0.30 to 0.35 m2:
First Dosage Reduction: 100 mg orally once a week
Second Dosage Reduction: 75 mg orally once a week
BSA 0.36 to 0.42 m2:
First Dosage Reduction: 125 mg orally once a week
Second Dosage Reduction: 100 mg orally once a week
BSA 0.43 to 0.48 m2:
First Dosage Reduction: 150 mg orally once a week
Second Dosage Reduction: 125 mg orally once a week
BSA 0.49 to 0.54 m2:
First Dosage Reduction: 175 mg orally once a week
Second Dosage Reduction: 150 mg orally once a week
BSA 0.55 to 0.63 m2:
First Dosage Reduction: 200 mg orally once a week
Second Dosage Reduction: 150 mg orally once a week
BSA 0.64 to 0.77 m2:
First Dosage Reduction: 225 mg orally once a week
Second Dosage Reduction: 200 mg orally once a week
BSA 0.78 to 0.83 m2:
First Dosage Reduction: 250 mg orally once a week
Second Dosage Reduction: 200 mg orally once a week
BSA 0.84 to 0.89 m2:
First Dosage Reduction: 300 mg orally once a week
Second Dosage Reduction: 250 mg orally once a week
BSA 0.90 to 1.05 m2:
First Dosage Reduction: 325 mg orally once a week
Second Dosage Reduction: 275 mg orally once a week
BSA 1.06 to 1.25 m2:
First Dosage Reduction: 375 mg orally once a week
Second Dosage Reduction: 325 mg orally once a week
BSA 1.26 to 1.39 m2:
First Dosage Reduction: 450 mg orally once a week
Second Dosage Reduction: 375 mg orally once a week
BSA 1.40 m2 or greater:
First Dosage Reduction: 500 mg orally once a week
Second Dosage Reduction: 400 mg orally once a week

Recommended Dosage Modifications for Adverse Reactions:
Hemorrhage:

Intolerable grade 2 or any grade 3 hemorrhage:
Withhold treatment with this drug.
If improved to grade 0 to 1, resume at lower dosage.
If not improved, consider permanent discontinuation of this drug.
First occurrence of any grade 4 hemorrhage:
Withhold treatment with this drug.
If improved to grade 0 to 1, resume at lower dosage or permanently discontinue this drug.
If recurrent grade 4 hemorrhage occurs, permanently discontinue this drug.

Skin Toxicity including Photosensitivity:

Intolerable grade 2 to 4 skin toxicity:
Withhold treatment with this drug.
If improved to grade 0 to 1, resume at lower dosage.
If not improved, consider permanent discontinuation of this drug.

Hepatotoxicity:

Grade 3 AST or ALT or grade 3 bilirubin:
Withhold treatment with this drug.
If improved to grade 2 or baseline resume as follows:
If laboratory abnormality resolves within 8 days, resume this drug at the same dose.
If laboratory abnormality does not resolve within 8 days, resume this drug at lower dose.
First occurrence of any grade 4 adverse reactions:
Withhold treatment with this drug.
If improved to grade 0 to 1, resume at lower dosage or permanently discontinue this drug.
If recurrent grade 4 adverse reactions occur, permanently discontinue this drug.

Other Adverse Reactions:

Intolerable grade 2 or any grade 3 adverse reactions:
Withhold treatment with this drug.
If improved to grade 0 to 1, resume at lower dosage.
If not improved, consider permanent discontinuation of this drug.
First occurrence of any grade 4 adverse reactions:
Withhold treatment with this drug.
If improved to grade 0 to 1, resume at lower dosage or permanently discontinue this drug.
If recurrent grade 4 adverse reactions occur, permanently discontinue this drug.

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 6 months.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

Before starting treatment, evaluate liver function tests, including ALT, AST, and bilirubin.
Administer the drug at a regularly scheduled time once a week, with or without food.
If a dose is missed by 3 days or less, take it immediately and take the next dose on its regularly scheduled day.
If a dose is missed by more than 3 days, skip it, and take the next dose on its regularly scheduled day.
If vomiting happens shortly after taking a dose, repeat that dose.
Swallow tablets whole with water. Do not chew, cut, or crush.
Administer the oral suspension using the supplied oral dosing syringe or feeding tube (minimum 12 French).
Suspension must be used immediately after reconstitution.
If the oral suspension is not administered within 15 minutes of preparation, it should be discarded.

Storage requirements:

Store at 20C to 25C (68F to 77F). Excursions are permitted between 15C to 30C (59F to 86F).

Reconstitution techniques:

Reconstitute the powder with 14 mL of room temperature water.
After reconstitution, each milliliter of oral suspension contains 25 milligrams of this drug.
Product foaming after reconstitution reduces the deliverable volume.
Each bottle delivers 300 mg of this drug in 12 mL.
For doses greater than 300 mg, reconstitute two bottles to achieve the dose.

General:

This indication is approved under accelerated approval based on response rate and duration. Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
The US FDA approved test for the detection of BRAF fusion or rearrangement, or BRAF V600 mutation in relapsed or refractory pediatric low-grade glioma is not currently available.

Monitoring:
Hematologic: Hemorrhage
Hepatic: Liver function (prior to and during therapy)
Other: Growth velocity

Patient advice:

Read the US FDA-approved patient labeling (Patient Information and Instructions for Use).
This drug can cause hemorrhage, contact your healthcare provider if signs or symptoms of bleeding occur.
This drug can cause skin toxicities, contact your healthcare provider if you experience worsening or intolerable rash.
This drug can cause photosensitivity, limit direct ultraviolet exposure during treatment by using precautionary measures like sunscreen, sunglasses, and protective clothing.
This drug can cause liver toxicity, contact your healthcare provider if signs or symptoms of liver dysfunction occur. Serum liver tests (ALT, AST, and bilirubin) should be done on a regular basis during treatment.
Patient growth will be monitored during treatment with this drug since it may reduce growth velocity.
Breastfeeding is not recommended during treatment and for 2 weeks after the last dose.
This drug has the potential to impair fertility in both males and females with reproductive potential.
Patients should contact their healthcare provider if they have a known or suspected pregnancy during treatment since this drug has the potential to cause fetal harm.