Pralsetinib

Pralsetinib is a prescription medication used for the treatment of Non-Small Cell Lung Cancer, Medullary Thyroid Cancer, and Thyroid Cancer. 

• Pralsetinib is available under the following different brand names: Gavreto.

Common side effects of Pralsetinib include:

• High blood pressure, 
• Low blood cell counts or other abnormal laboratory tests, 
• Muscle or joint pain, 
• Tiredness, and
• Constipation

Serious side effects of Pralsetinib include:

• Hives, 
• Difficulty breathing, 
• Swelling of the face, lips, tongue, or throat, 
• Fever, 
• Chills, 
• New or worsening cough, 
• Shortness of breath,
• Chest pain, 
• Severe headache, 
• Dizziness, 
• Confusion, 
• Trouble speaking, 
• Any wound that will not heal, 
• Unusual bleeding (bruising, nosebleeds, bleeding gums, abnormal vaginal bleeding, any bleeding that will not stop), 
• Weakness, 
• Drowsiness, 
• Pink or brown urine, 
• Bloody or tarry stools, 
• Coughing up blood, 
• Vomit that looks like coffee grounds, 
• Tiredness, 
• Sore throat, 
• Mouth sores, 
• Skin sores, 
• Pale skin, 
• Cold hands and feet, 
• Lightheadedness, 
• Nausea, 
• Vomiting, 
• Loss of appetite, 
• Stomach pain (upper right side), and
• Yellowing of the skin or eyes (jaundice)

Rare side effects of Pralsetinib 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

• 100 mg

Non-Small Cell Lung Cancer

Adult dosage

• 400 mg orally once a day on an empty stomach
• Continue until disease progression or until unacceptable toxicity.

Medullary Thyroid Cancer

Adult dosage

400 mg orally once a day

• Continue until disease progression or until unacceptable toxicity.

Pediatric dosage

• Children under 12 years: Safety and efficacy not established.
• Children aged 12 years and above
  • 400 mg orally once a day
  • Continue until disease progression or until unacceptable toxicity.

Thyroid Cancer

Adult dosage

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

Pediatric dosage

• Children below 12 years: Safety and efficacy not established.
• Children aged 12 years and above
  • 400 mg orally once 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.

• Pralsetinib has severe interactions with no other drugs.
• Pralsetinib has serious interactions with at least 52 other drugs.
• Pralsetinib has moderate interactions with the following drugs:
  • berotralstat
  • lonafarnib
• Pralsetinib 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, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• Severe, life-threatening, and fatal ILD/pneumonitis can occur; monitor for pulmonary symptoms indicative of ILD/pneumonitis.
• Serious hepatic adverse reactions reported; monitor AST/ALT before initiation, every 2 weeks during the first 2 months, and then monthly thereafter and as clinically indicated.
• May cause serious, including fatal, hemorrhagic events.
• Based on findings from animal studies and its mechanism of action, may cause fetal harm when administered to pregnant females
• Tumor lysis syndrome reported in MTC-treated patients; patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration; closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated.
• Hypertension
  • Hypertension occurred; treatment-emergent hypertension was mostly managed with antihypertensive therapy.
  • Do not initiate uncontrolled hypertension.
  • Optimize blood pressure (BP) before initiation.
  • Monitor BP after 1 week, then at least monthly thereafter and as clinically indicated.
  • Initiate or adjust antihypertensive therapy as needed.
• Impaired wound healing
  • Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway.
  • May have the potential to adversely affect wound healing.
  • Withhold for at least 5 days before elective surgery.
  • Do not administer for at least 2 weeks following major surgery and until adequate wound healing.
  • Safety of resumption after resolution of wound healing complications has not been established.
• Drug interaction overview
• Pralsetinib is a CYP3A4 and P-gp substrate.
• Strong CYP3A4 inhibitors
  • Avoid coadministration.
  • Strong CYP3A inhibitors increase exposure and risk of toxicities to pralsetinib.
• Combined P-gp and strong CYP3A inhibitors
  • Avoid coadministration; if unable to avoid it, decrease the pralsetinib dose
  • Combined P-gp and strong CYP3A inhibitors increase plasma concentrations and the effects of pralsetinib.
• Strong CYP3A4 inducers
  • Avoid coadministration; if unable to avoid it, increase the pralsetinib dose
  • Strong CYP3A inducers decrease exposure to pralsetinib.

Pregnancy and Lactation

• Based on animal studies and its mechanism of action, fetal harm may occur when administered to pregnant females
• No data available on use in pregnant females to inform a drug-associated risk.
• Verify the pregnancy status of females of reproductive potential before initiation.
• Contraception
  • Females of reproductive potential: Use effective nonhormonal contraception during treatment and for 2 weeks after the final dose; pralsetinib may render hormonal contraceptives ineffective.
  • Males with female partners of reproductive potential: Use effective contraception during treatment and for 1 week after the final dose.
• Infertility
  • Based on histopathological findings in male and female rats and a dedicated fertility study, fertility may be impaired
• Lactation
  • There are no data on the presence of pralsetinib or its metabolites in human milk, its effects on breastfed children, or milk production.
  • Advise females not to breastfeed during treatment and for 1 week after the final dose.