Dordaviprone(LuciDorda)

Dordaviprone is an oral antineoplastic agent that acts as a protease activator of mitochondrial caseinolytic protease P (ClpP) and also inhibits dopamine D2 receptors.

Lucius-related Certificates

Drug Testing Report

Drug Approval Certificate

Target

Dordaviprone is a protease activator of mitochondrial caseinolytic protease P (ClpP) and also inhibits dopamine D2 receptors.

Dosage and Administration

Select patients based on the presence of H3 K27M mutation in tumor specimens. There is currently no FDA-approved test to detect this mutation.

Before initiating dordaviprone and during treatment, monitor ECGs and electrolytes as clinically indicated.

Administer on an empty stomach, at least 1 hour before or 3 hours after a meal. Administer orally once weekly, preferably on the same day and at the same time each week. The recommended adult dose is a fixed dose once weekly. Pediatric patients are dosed by weight tier; higher body weight corresponds to a higher dose. The recommended dose for children with very low body weight has not been established.

Swallow capsules whole. If patients cannot swallow whole, the capsule may be opened and the contents mixed with an appropriate amount of liquid and taken orally. After mixing, administer within the specified time; otherwise discard and prepare a new mixture. Continue until disease progression or unacceptable toxicity.

If vomiting occurs after dosing, do not take an additional dose; take the next dose as scheduled. If a dose is missed, take it as soon as possible within the allowed time window; if the allowed time has passed, skip that dose and take the next dose as scheduled.

For adverse reactions, interrupt dosing, reduce the dose, or permanently discontinue based on severity. Avoid concomitant use with strong or moderate CYP3A4 inhibitors; if unavoidable, adjust the dose as recommended. Avoid concomitant use with strong or moderate CYP3A4 inducers. Avoid concomitant use with drugs known to prolong the QTc interval; if unavoidable, administer separately.

Use in Specific Populations

Pregnancy

Based on animal studies and its mechanism of action, dordaviprone can cause fetal harm. Use in pregnant women may pose a risk to the fetus; advise pregnant women of the potential risk.

Lactation

There are no data on the presence of dordaviprone and its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise not to breastfeed during treatment and for a period after the last dose.

Females and Males of Reproductive Potential: Confirm pregnancy status in females of reproductive potential before initiating treatment. Females of reproductive potential should use effective contraception during treatment and for a period after the last dose. Male patients with female partners of reproductive potential should also use effective contraception during treatment and for a period after the last dose.

Fertility

Based on its mechanism of action, dordaviprone may impair fertility in males and females.

Pediatric Use

The safety and effectiveness of dordaviprone have been established in pediatric patients 1 year of age and older for the treatment of H3 K27M-mutant diffuse midline glioma. The safety and effectiveness in children under 1 year of age have not been established. The recommended dose for children with very low body weight has not been determined.

Geriatric Use

Clinical studies did not include a sufficient number of geriatric patients to determine whether they respond differently from younger patients.

Hepatic and Renal Impairment

Severe renal impairment and moderate hepatic impairment may increase dordaviprone exposure. The effect of severe hepatic impairment is unknown. No clinically significant pharmacokinetic differences have been observed for mild hepatic impairment, age, sex, race, etc.

Adverse Reactions

Hypersensitivity reactions: Dordaviprone can cause severe hypersensitivity reactions. Symptoms may include rash, urticaria, fever, hypotension, wheezing, and facial or throat swelling. For clinically significant hypersensitivity or anaphylaxis, immediately interrupt dosing and provide appropriate medical management. Depending on severity, temporary interruption or permanent discontinuation may be required.

QTc interval prolongation: Dordaviprone can cause concentration-dependent QTc interval prolongation, increasing the risk of ventricular tachyarrhythmias or sudden death. Monitor ECGs and electrolytes before initiating and during treatment. Interrupt or reduce the dose for QT prolongation; permanently discontinue for signs of life-threatening arrhythmia.

Embryo-fetal toxicity: Can cause fetal harm; advise patients of the risk and use contraception.

Common adverse reactions: fatigue, headache, vomiting, nausea, musculoskeletal pain.

Common laboratory abnormalities: lymphopenia, decreased calcium, increased alanine aminotransferase.

Other clinically important adverse reactions: peripheral neuropathy, seizure, diarrhea, tremor, venous thromboembolic events.

Serious adverse reactions: include hydrocephalus, vomiting, headache, seizure, muscle weakness, etc. Fatal adverse reactions include cardiac arrest, intracranial hemorrhage, encephalopathy, etc.

Daily Precautions

Patients and caregivers should read the FDA-approved patient information and Instructions for Use, and reread each time they receive a refill, to obtain possible new information.

If symptoms of an allergic reaction occur, such as rash, urticaria, fever, dizziness or fainting, wheezing or difficulty breathing, facial or throat swelling, immediately stop the drug and seek emergency medical help.

If cardiac-related symptoms occur, such as dizziness, fainting, palpitations, etc., seek medical attention immediately. Check ECGs and electrolytes before and during treatment as needed.

Tell healthcare providers about all medications being used, including prescription drugs, over-the-counter drugs, vitamins, and herbal products. Do not start or stop any medication on your own. Dordaviprone may interact with other drugs.

Take on an empty stomach once weekly on the same day and at the same time as prescribed. Swallow whole; if unable to swallow whole, mix the capsule contents with liquid according to the Instructions for Use and take, ensuring no drug residue remains. Do not take an additional dose after vomiting; handle missed doses as prescribed.

Females and male patients of reproductive potential should use effective contraception. Do not breastfeed during treatment and for a period after the last dose. If concerned about fertility, consult a doctor.

Store the drug at room temperature, with a child-resistant cap, and keep out of reach of children.