Dordaviprone

Dordaviprone is a prescription medicine for the treatment of diffuse midline glioma harboring an H3 K27M mutation in adults and children aged 1 year and older with progressive disease following prior therapy. 

• Dordaviprone is available under the following different brand names: Modeyso

Common side effects of Dordaviprone include:

• tiredness 
• nausea 
• vomiting
• headache 
• muscle, joint, and bone pain
• decreased white blood cells
• decreased red blood cells
• decreased calcium
• increased liver enzymes

Serious side effects of Dordaviprone include:

• symptoms of allergic reactions may include rash, dizziness, hives, wheezing or trouble breathing, fever, swelling of the face or throat 
• symptoms of QTc interval prolongation may include feeling lightheaded or faint, heart palpitations, dizziness, shortness of breath, fast heartbeat

Rare side effects of Dordaviprone 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

Oral Capsule

• 125 mg

Glioma

Adult Dosage

• 625 mg orally once weekly until disease progression or unacceptable toxicity

Pediatric Dosage

• Children weighing less than 10 kg: Recommended dose not established
• Children weighing 10 kg to less than 12.5 kg: 125 mg orally once weekly
• Children weighing 12.5 kg to less than 27.5 kg: 250 mg orally once weekly
• Children weighing 27.5 kg to less than 42.5 kg: 375 mg orally once weekly
• Children weighing 42.5 kg to less than 52.5 kg: 500 mg orally once weekly
• Children weighing 52.5 kg and more: 625 mg orally once weekly
• Continue therapy until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your doctor has directed you to use this medication, 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, healthcare provider, or pharmacist first.

Drug interaction overview

• Dordaviprone is a moderately sensitive CYP3A4 substrate
• Strong or moderate CYP3A4 inhibitors
• Avoid concomitant use
  • If concomitant use is unavoidable, reduce dordaviprone dosage in adults and pediatric patients weighing 52.5 kg and more.
• Coadministration may increase dordaviprone exposure, which may increase the risk of adverse reactions (eg, QT prolongation)
• Strong or moderate CYP3A4 inducers
• Avoid concomitant use
  • Coadministration may decrease dordaviprone exposure, which may reduce its efficacy
• Other QT prolonging drugs
  • Avoid concomitant use
  • If concomitant use is unavoidable, separate administration of dordaviprone and a QT-prolonging product
  • Coadministration with other products known to prolong the QT interval may increase the risk of QTc-associated arrhythmias

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• Hypersensitivity
  • Can cause severe hypersensitivity reactions
  • Signs and symptoms may include rash, hives, fever, low blood pressure, wheezing, or swelling of face or throat
  • If hypersensitivity or anaphylaxis occurs, hold or permanently discontinue therapy, based on the severity
  • Initiate appropriate medical treatment and supportive care
• QTc interval prolongation
  • Concentration-dependent QTc interval prolongation reported; may increase risk for ventricular tachyarrhythmias (eg, TdP) or sudden death
  • Evaluate ECGs and electrolytes before starting and periodically during therapy as clinically indicated
  • Increase ECG and electrolyte monitoring frequency in patients
  • Taking other products with known potential to prolong the QT interval
• Taking strong or moderate CYP3A4 inhibitors
  • With congenital long QT syndrome or existing QTc prolongation
  • With a history of ventricular arrhythmias, electrolyte abnormalities, or heart failure
  • If QT prolongation occurs, hold, reduce dosage, or permanently discontinue, based on severity
• Embryo-fetal toxicity
  • May cause fetal harm when administered during pregnancy
  • Advise pregnant patients and females of reproductive potential of potential fetal risk
  • Effective contraception is recommended during and after therapy in females of reproductive potential and male patients with female partners of reproductive potential

Pregnancy and Lactation

Pregnancy

• May cause fetal harm when administered during pregnancy, based on findings from animal studies and its mechanism of action
• There are no available data on use in pregnant patients to inform drug-associated risk
• Advise pregnant patients of potential fetal risk
• Verify pregnancy status before starting therapy in females of reproductive potential

Contraception requirements

• Females of reproductive potential and male patients with female partners of reproductive potential should use effective contraception during therapy and for 1 month after last dose

Infertility

• May impair fertility in female and male patients, based on its mechanism of action (dopamine D2-receptor inhibition and mitochondrial function alterations)

Lactation

• No data on the presence of dordaviprone or its metabolites in human milk or its effects on breastfed children or milk production
• Due to the potential for serious adverse reactions in breastfed children, avoid breastfeeding during therapy and for 1 week after the last dose