Tovorafenib

Tovorafenib is a prescription medication indicated for relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation.

• Tovorafenib is available under the following different brand names: Ojemda.

Common side effects of Tovorafenib include:

• rash
• fever
• hair color changes 
• dry skin
• tiredness 
• constipation
• viral infection 
• nausea
• vomiting 
• acne
• headache 
• upper respiratory tract infection

Serious side effects of Tovorafenib include:

• bleeding problems include headache, dizziness or feeling weak, coughing up blood or blood clots, vomiting blood or vomit that looks like “coffee grounds”, red or black stools that look like tar
• skin reactions, including sensitivity to sunlight (photosensitivity) include rash, peeling, redness, or irritation, bumps or tiny papules, blisters, acne
• liver problems include yellowing of the skin or eyes, tiredness, dark or brown (tea-colored) urine, bruising, nausea or vomiting, bleeding, loss of appetite, pain in the upper right stomach area

Rare side effects of Tovorafenib include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablet

• 100 mg

Oral suspension

• 25 mg/mL after reconstitution (300mg/12mL per bottle)

Glioma

Adult and pediatric dosage

• 380 mg/m2 orally every week with or without food
• Not to exceed 600 mg/week
• Continue once weekly dosing until disease progression or intolerable toxicity
• Pediatric dosage
  • 380 mg/m2 orally every week with or without food
  • Not to exceed 600 mg/week
  • Continue once weekly dosing until disease progression or intolerable toxicity
• Dosing for BSA below 0.3 m2: Not established

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Tovorafenib has severe interactions with no other drugs
• Tovorafenib has serious interactions with no other drugs
• Tovorafenib has moderate interactions with no other drugs
• Tovorafenib has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Tovorafenib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Tovorafenib?”

Cautions

• Hemorrhage
  • Hemorrhage, including major hemorrhage defined as symptomatic bleeding in a critical area or organ, can occur
  • Advise patients and caregivers of hemorrhage risk during treatment
  • Monitor for signs and symptoms of hemorrhage and evaluate as clinically indicated
  • Withhold and resume at a reduced dose upon improvement, or permanently discontinue based on severity
• Skin toxicity including photosensitivity
  • Rash, including maculopapular rash and photosensitivity, reported
  • Monitor for new or worsening skin reactions
  • Consider dermatologic consultation and initiate supportive care as clinically indicated
  • Withhold, reduce dose, or permanently discontinue based on severity
  • Advise patients to use precautionary measures against ultraviolet exposure (eg, sunscreen, sunglasses, and/or protective clothing) during treatment
• Hepatotoxicity
  • Can cause hepatotoxicity
  • Monitor liver function tests, including ALT, AST, and bilirubin, before initiating, 1 month after initiation, and then every 3 Months thereafter and as clinically indicated
  • Withhold and resume at same or reduced dose upon improvement, or permanently discontinue based on the severity
• Effect on growth
  • Can cause reductions in growth velocity
  • Growth velocity recovered after interruption of treatment
  • Routinely monitor patient growth during treatment
• Embryofetal toxicity
  • Based on findings from animal studies and its mechanism of action, Tovorafenib may cause fetal harm when administered to pregnant women
  • Advise pregnant women and females of reproductive potential of potential fetal risk
• NF1-associated tumors
  • Based on nonclinical data in neurofibromatosis type 1 (NF1) models without BRAF alterations, Tovorafenib may promote tumor growth in patients with NF1 tumors
  • Confirm evidence of a BRAF alteration before treatment initiation
• Drug interaction overview
  • Substrate of CYP2C8 (major)
  • Inhibitor of CYP3A4 (moderate)
  • Strong or moderate CYP2C8 inhibitors
    • Avoid
      • Coadministration may increase the systemic exposure to Tovorafenib and increase the risk of adverse effects
  • Strong or moderate CYP2C8 inducers
    • Avoid
      • Coadministration may decrease systemic exposure to Tovorafenib and reduce efficacy
  • Sensitive CYP3A4 substrates
    • Avoid
      • Avoid coadministration with certain CYP3A substrates where minimal concentration changes may lead to serious therapeutic failures
      • If coadministration is unavoidable, monitor for loss of efficacy unless otherwise recommended in the Prescribing Information for CYP3A substrates
• Hormonal contraceptives
  • Avoid
    • If coadministration is unavoidable, use additional effective nonhormonal contraception during coadministration for 28 days after discontinuing Tovorafenib
    • Coadministration with hormonal contraceptives (CYP3A substrate) may decrease progestin and ethinyl estradiol exposure, which may lead to contraceptive failure and/or an increase in breakthrough bleeding

Pregnancy and Lactation

• Based on findings from animal studies and its mechanism of action, Tovorafenib can cause fetal harm when administered to pregnant women
• There are no available data on use in pregnant women
• Advise pregnant females of potential risk
• Verify pregnancy status in females of reproductive potential before initiating
• Contraception
  • Females of reproductive potential
    • Use effective non-hormonal contraception during treatment and for 28 days after the last dose
    • Tovorafenib can render hormonal contraceptives ineffective
  • Males
    • Advise male patients with female partners of reproductive potential to use effective nonhormonal contraception during treatment and for 2 weeks after the last dose
• Infertility
  • Based on findings in animals, may impact fertility in men and women of reproductive potential
  • Effects on men's fertility were reversible
  • Effects on women's fertility were not reversible
• Lactation
  • Data are not available regarding on presence of Tovorafenib or its metabolites in human milk, its effects on breastfed children, or on milk production
  • Due to the potential for serious adverse reactions in breastfed children, advise lactating women not to breastfeed during treatment and for 2 weeks following the last dose