Larotrectinib

Larotrectinib is a prescription medication used for the treatment of solid tumors. 

• Larotrectinib is available under the following different brand names: Vitrakvi.

Common side effects of Larotrectinib include:

• Nausea,
• Vomiting,
• Diarrhea,
• Constipation,
• Cough,
• Dizziness,
• Tiredness, and
• Abnormal liver function tests

Serious side effects of Larotrectinib include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Severe or ongoing stomach pain,
• Vomiting,
• Diarrhea,
• Confusion,
• Memory problems,
• Severe dizziness,
• Problems with speech or coordination,
• Numbness, tingling, or burning pain in the hands or feet,
• Fever,
• Flu symptoms,
• Sore throat,
• Cough,
• Sores or ulcers in the mouth or on the skin,
• Unusual tiredness,
• Lightheadedness,
• Shortness of breath,
• Pale skin,
• Cold hands and feet,
• Pain, warmth, redness, or swelling under the skin,
• Loss of appetite,
• Stomach pain (upper right side),
• Nausea,
• Vomiting,
• Dark urine,
• Clay-colored stools, and
• Yellowing of the skin or eyes (jaundice)

Rare side effects of Larotrectinib 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, loss of coordination, feeling 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

Capsule

• 25 mg
• 100 mg

Oral solution

• 20 mg/mL

Solid Tumors

Adult dosage

• 100 mg orally two times a day
• Continue until disease progression or until unacceptable toxicity.

Pediatric dosage

• Body surface area (BSA) below 1 m2: 100 mg/m2 orally two times a day  
• BSA above1 m2: 100 mg orally two times a day
• Continue until disease progression or until unacceptable toxicity.

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.

• Larotrectinib has severe interactions with the following drug:
  • lonafarnib
• Larotrectinib has serious interactions with at least 80 other drugs.
• Larotrectinib has moderate interactions with at least 68 other drugs. 
• Larotrectinib has minor interactions with at least 252 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 your products. 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, or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• Increased transaminases of any grade occurred; median time to onset of increased AST/ALT was 2 months; monitor liver tests every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated; withhold or permanently discontinue based on severity; if withheld, modify dosage when resumed
• Can cause fetal harm.
  • Skeletal fractures reported; promptly evaluate patients with signs or symptoms of potential fracture (e.g., pain, changes in mobility, deformity); no data are available on effects on healing of known fractures or risk of future fractures
• CNS effects
  • CNS adverse reactions (e. g., dizziness, cognitive impairment, mood disorders, sleep disturbances)
  • Cognitive impairment included memory impairment, confused state, disturbance in attention, delirium, and cognitive disorders; median onset time: 5.6 months (range: 2 days to 41 months)
  • Mood disorders included anxiety, depression, agitation, and irritability; median onset time: 3.9 months (range: 1 day to 40.5 months)
  • Consult on the risks; advise patients not to drive or operate hazardous machinery if experiencing neurologic adverse reactions.
  • Withhold or permanently discontinue based on the severity.
  • If withheld, modify dosage when resumed.
• Drug interaction overview
  • Major CYP3A4 substrate; also, a P-gp and BCRP substrate
    • Moderately inhibits CYP3A4.
  • Strong CYP3A4 inhibitors
    • Avoid coadministration, including grapefruit or grapefruit juice.
    • Strong CYP3A4 inhibitors may increase larotrectinib plasma concentrations and potentially result in a higher incidence of adverse reactions.
    • If unavoidable, modify the dose as recommended.
  • Strong CYP3A4 inducers
    • Avoid coadministration.
    • Strong CYP3A4 inducers may decrease larotrectinib plasma concentrations, which may decrease efficacy.
    • If unavoidable, modify the dose as recommended.
  • Sensitive CYP3A4 substrates
  • Avoid coadministration.
    • Larotrectinib may increase plasma concentrations of sensitive CYP3A4 substrates, which may increase the incidence and/or severity of adverse reactions.
    • If unavoidable, monitor for increased adverse reactions of drugs that are sensitive to CYP3A4 substrates.

Pregnancy and Lactation

• Based on literature reports, findings from animal studies, and its mechanism of action, embryofoetal harm may occur when administered to pregnant females
• There are no available data on use in pregnant females.
• Verify pregnancy status in females of reproductive potential before initiation.
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for at least 1 week after the last dose.
  • Males with female partners of reproductive potential: Use effective contraception during treatment and for 1 week after the last dose.
• Infertility
  • Based on histopathological findings in reproductive tracts of female rats in a 1-month repeated-dose study, fertility may be reduced
• Lactation
  • There are no data on the presence of Larotrectinib or its metabolites in human milk and its effects on breastfed children or milk production
  • Advise females not to breastfeed during treatment and for 1 week after the final dose.