Entrectinib

Entrectinib is a prescription medication used to treat the symptoms of Non-Small Cell Lung Cancer and Neurotrophic Tyrosine Receptor Kinase Gene Fusion Solid Tumors. 

• Entrectinib is available under the following different brand names: Rozlytrek

Common side effects of Entrectinib include:

• Changes in mental status,
• Vision changes,
• Nausea,
• Vomiting,
• Diarrhea,
• Constipation,
• Fever,
• Cough,
• Dizziness,
• Tiredness,
• Weight gain,
• Swelling,
• Muscle or joint pain,
• Trouble breathing, and
• Changes in the sense of taste or touch

Serious side effects of Entrectinib include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Bone pain,
• Problems moving,
• Fast or pounding heartbeats,
• Fluttering in the chest,
• Shortness of breath,
• Sudden dizziness,
• Nausea,
• Vomiting,
• Loss of appetite,
• Right side upper stomach pain,
• Swelling in the lower legs,
• Rapid weight gain,
• Cough,
• Wheezing,
• Trouble breathing while laying down,
• Confusion,
• Hallucinations,
• Problems with memory or concentration,
• Dizziness,
• Mood changes,
• Trouble sleeping,
• Blurred vision,
• Double vision,
• Increased sensitivity to light,
• Seeing flashes of light, and
• "Floaters" in the vision

Rare side effects of Entrectinib 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 dosage

Capsule

• 100 mg
• 200 mg

Non-small Cell Lung Cancer

Adult dosage

• 600 mg orally once a day
• Continue until disease progression or unacceptable toxicity

Neurotrophic Tyrosine Receptor Kinase Gene Fusion Solid Tumors

Adult dosage

• 600 mg orally once a day
• Continue until disease progression or unacceptable toxicity

Pediatric dosage

• Children below 12 years: Safety and efficacy not established
• Children above 12 years
• Recommended dosage is based on body surface area (BSA)
• 0.91-1.1 m2: 400 mg orally once a day
• 1.11-1.5 m2: 500 mg orally once a day
• Above 1.5 m2: 600 mg orally once a day

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.

• Entrectinib has severe interactions with the following drug
  • lefamulin
• Entrectinib has serious interactions with at least 198 other drugs.
• Entrectinib has moderate interactions with at least 37 other drugs.
• Entrectinib 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 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 Entrectinib?”

Long-Term Effects

See “What Are Side Effects Associated with Using Entrectinib?”

Cautions

• Increase of fractures reported; promptly evaluate patients with signs or symptoms (.g, pain, changes in mobility, deformity) of fractures
• Increased liver transaminase reported; monitor liver tests every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated
• Hyperuricemia was reported, as well as elevated uric acid levels; assess serum uric acid levels before initiation and periodically during treatment
• Vision disorders have occurred, including blurred vision, photophobia, diplopia, visual impairment, photopsia, cataract, and vitreous floaters
• Based on literature reports in humans with congenital mutations leading to changes in TRK signaling, findings from animal studies, and its mechanism of action, fetal harm may occur when administered to a pregnant woman
• QT prolongation
  • QT prolongation reported; patients with at least 1 post-baseline ECG assessment experienced prolonged QT interval of above 60 ms after starting treatment
  • Assess QT interval and electrolytes at baseline and periodically during treatment
  • Adjust monitoring frequency based on risk factors such as congestive heart failure (CHF), electrolyte abnormalities, or concomitant medications known to prolong the QTc interval
• CNS adverse reactions
  • CNS adverse reactions reported, including cognitive impairment, mood disorders, dizziness, and sleep disturbances
  • Advise patients and caregivers of these risks
  • Instruct patients not to drive or operate hazardous machinery if experiencing CNS adverse reactions
• Congestive heart failure
  • CHF occurred in clinical trials
  • Among patients with CHF, the median time to onset was 2 months
  • Myocarditis in the absence of CHF was also documented
  • Assess left ventricular ejection fraction before initiation in patients with symptoms or known risk factors for CHF
  • Monitor for clinical signs and symptoms of CHF, including shortness of breath and edema
  • For patients with myocarditis, with or without a decreased ejection fraction, MRI or cardiac biopsy may be required to make the diagnosis
• Drug interaction overview
  • Entrectinib is a CYP3A4 substrate
  • Moderate and strong CYP3A inhibitors
  • Coadministration with a strong or moderate CYP3A inhibitor increases entrectinib plasma concentrations, which could increase the frequency or severity of adverse reactions
  • Avoid coadministration
  • If coadministration is unavoidable, reduce the dose
  • Grapefruit products are CYP3A4 inhibitors; avoid these products during treatment
  • Moderate and strong CYP3A inducers
  • Coadministration with a strong or moderate CYP3A inducer decreases entrectinib plasma concentrations, which may reduce entrectinib efficacy
  • Avoid coadministration
  • Drugs that prolong QT interval
  • QTc interval prolongation can occur
  • Avoid coadministration with other products with a known potential to prolong QT interval

Pregnancy and Lactation

• Based on literature reports in humans with congenital mutations leading to changes in TRK signaling, findings from animal studies, and its mechanism of action, fetal harm may occur when administered to a pregnant woman
• No data available on use in pregnant women
• Verify the pregnancy status of females of reproductive potential before initiating treatment
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for at least 5 weeks following the final dose
  • Males with female partners of reproductive potential: Use effective contraception during treatment and for 3 months following the final dose
• Lactation
  • There are no data on the presence of entrectinib or its metabolites in human milk or their effects on either the breastfed child or on milk production
  • Owing to the potential adverse reactions in breastfed children from entrectinib, advise a lactating woman to discontinue breastfeeding during treatment and for 7 days after the final dose