Nirogacestat

Nirogacestat is a prescription medication indicated for progressing desmoid tumors in adults who require systemic treatment

• Nirogacestat is available under the following different brand names: Ogsiveo

Common side effects of Nirogacestat include:

• diarrhea
• ovarian toxicity
• rash
• nausea
• fatigue
• stomatitis
• headache
• abdominal pain
• cough
• alopecia
• upper respiratory tract infection 
• dyspnea

Serious side effects of Nirogacestat include:

• liver problems
• ovarian toxicity 
• new non-melanoma skin cancers
• electrolyte abnormalities 

Rare side effects of Nirogacestat include:

• none 

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

• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheadedness, or passing out;
• 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.

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 the FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 50 mg

Desmoid Tumors

Adult dosage

• 150 mg orally two times a day
• Continue until disease progression or 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.

• Nirogacestat has severe interactions with no other drugs
• Nirogacestat has serious interactions with at least 109 other drugs
• Nirogacestat has moderate interactions with no other drugs
• Nirogacestat 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 Nirogacestat?”

Long-Term Effects

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

Cautions

• Diarrhea, sometimes severe, reported; monitor, and manage with antidiarrheal medication; modify dose as recommended
• ALT or AST elevations occurred; monitor liver function tests regularly and modify dose as recommended
• New non-melanoma skin cancers may occur; perform dermatologic evaluations before initiating and routinely during treatment
• Electrolyte abnormalities reported; monitor phosphate and potassium levels regularly supplement as necessary and modify dose as recommended
• Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to pregnant females
• Ovarian toxicity
  • May impair women’s reproductive function and fertility
  • Impact on fertility may be dependent on the duration of therapy and gonadal function at the time of treatment
  • Long-term effects on fertility have not been established
  • Advise patients on potential risks for ovarian toxicity before initiating
  • Monitor for changes in menstrual cycle regularity or the development of symptoms of estrogen deficiency, including hot flashes, night sweats, and vaginal dryness
• Drug interaction overview
  • CYP3A4 substrate
    • Inhibits of CYP3A4 and CYP2C19 substrates
    • Strong or moderate CYP3A4 inhibitors
    • Avoid coadministration
    • Avoid eating or drinking grapefruit products, Seville oranges, and starfruit during treatment
  • Strong or moderate CYP3A inhibitors increase nirogacestat exposure and increase the risk of toxicities
  • Strong or moderate CYP3A4 inducers
    • Avoid coadministration
    • Strong or moderate CYP3A inducers decrease nirogacestat exposure and efficacy
  • Gastric acid-reducing agents
    • Avoid coadministration with proton pump inhibitors and H2 blockers
    • May administer 2 hours before or 2 hours after antacids
  • Sensitive CYP3A4 substrates
    • Avoid coadministration with CYP3A substrates where minimal concentration changes may lead to serious adverse reactions
    • Nirogacestat increases the exposure of CYP3A substrates and increases the risk of adverse reactions related to these substrates
  • Sensitive CYP2C19 substrates
    • Avoid coadministration with CYP2C19 substrates where minimal concentration changes may lead to serious adverse reactions
    • Nirogacestat increases exposure to CYP2C19 substrates and increases the risk of adverse reactions related to these substrates

Pregnancy and Lactation

• Based on findings from animal studies and their mechanism of action, fetal harm or loss of pregnancy may occur when administered to pregnant females
• Verify the pregnancy status of females of reproductive potential before initiating
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for 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 findings in animal studies, female and male fertility may be impaired
  • Nirogacestat interfered with folliculogenesis and spermatogenesis in nonclinical studies resulting in changes that included ovarian atrophy
• Lactation
  • There are no data on the presence of nirogacestat or its metabolites in human milk or the effects of nirogacestat on breastfed children or milk production
  • Advise women not to breastfeed during treatment and for 1 week after the last dose