Lucidorda Dordaviprone 125mg Capsules 10's

Dordaviprone is an oral targeted anticancer medicine used for certain patients with diffuse midline glioma (DMG), an aggressive type of brain tumor.

Dordaviprone is a novel oral targeted therapy for adults and children ≥1 year with H3 K27M-mutant diffuse midline glioma that has progressed following prior therapy.

It is specifically indicated for adult and pediatric patients—1 year of age and older whose tumor:

• Is a diffuse midline glioma
• Contains the H3 K27M mutation
• Has progressed following prior therapy.

The medicine is unusual because it is administered once weekly, rather than daily. The major safety considerations are QTc prolongation, serious hypersensitivity, and embryo-fetal toxicity, together with clinically important CYP3A4 drug interactions.

The FDA approval was granted through the accelerated approval pathway, based on overall response rate and duration of response. Continued approval may depend on confirmation of clinical benefit.

H3 K27M-mutant diffuse midline glioma.

Dordaviprone is indicated for:

• Adults and children ≥1 year of age with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.
• The H3 K27M mutation should be identified from a tumor specimen.

Important limitation:

Dordaviprone is not a general treatment for all brain tumors. Its approved indication is specifically linked to H3 K27M-mutant diffuse midline glioma.

Dordaviprone has a distinctive mechanism of action.

• It acts as a protease activator of mitochondrial caseinolytic protease P (ClpP) and also inhibits the dopamine D2 receptor.
• H3 K27M-mutant diffuse midline gliomas are associated with loss of normal H3 K27 trimethylation, an important epigenetic modification.

In simple terms:

H3 K27M mutation → abnormal epigenetic regulation → tumor-cell survival and growth

Dordaviprone → ClpP activation / altered mitochondrial and cellular signaling → cellular stress and apoptosis → inhibition of tumor growth

Adult dosage

The recommended adult dose is:

• 625 mg orally once weekly
• The entire prescribed dose is taken once per week on the same day each week.
• Because the available capsule strength is 125 mg, an adult 625 mg dose corresponds to:
• 5 × 125-mg capsules once weekly.

Do not change the number of capsules unless instructed by the treating physician.

Take on an empty stomach

At least 1 hour before food OR at least 3 hours after food.

Pediatric dosage

It depends on body weight

Body weight - Recommended dose 10 to <12.5 kg - 125 mg once weekly 12.5 to <27.5 kg - 250 mg once weekly 27.5 to <42.5 kg - 375 mg once weekly 42.5 to <52.5 kg - 500 mg once weekly ≥52.5 kg - 625 mg once weekly

If the patient cannot swallow the capsule

The capsule can be opened, and its contents mixed with approximately 15–30 mL of:

• Water
• Apple juice
• Lemonade
• Sports drink

The prepared liquid should be administered within 2 hours of preparation.

Missed dose

If a dose is missed:

• Within 2 days: take the missed dose as soon as possible.
• More than 2 days late: skip the missed dose and take the next dose on the regularly scheduled day.

If vomiting occurs

• Do not take another dose.
• Take the next dose at the regularly scheduled time.

Common:

The safety profile of dordaviprone is still being characterized because it is a relatively new medicine.

Reported adverse reactions include:

• Fatigue
• Nausea
• Headache
• Dizziness
• Decreased appetite
• Vomiting
• Constipation
• Diarrhea
• Increased liver enzymes
• Electrolyte abnormalities

The frequency and severity can vary considerably between adult and pediatric patients.

Serious:

QTc interval prolongation

Severe QT prolongation can potentially lead to dangerous cardiac arrhythmias.

Patients should promptly report:

• Fainting
• Severe dizziness
• Palpitations
• Rapid or irregular heartbeat
• Seizure-like episodes

ECG and electrolyte monitoring are recommended before starting treatment and periodically during therapy as clinically indicated.

Serious hypersensitivity

Serious hypersensitivity reactions, including anaphylaxis, can occur.

Symptoms may include:

• Difficulty breathing
• Facial or throat swelling
• Hives
• Severe rash
• Sudden dizziness or collapse

Clinically significant hypersensitivity requires immediate medical management, and serious hypersensitivity requires permanent discontinuation of Dordaviprone.

Embryo-fetal toxicity

• Dordaviprone may cause fetal harm.
• Women who can become pregnant should use effective contraception during treatment and for the recommended period following the last dose.

Dordaviprone is metabolized by CYP3A4, making CYP3A4-related interactions clinically important.

CYP3A4 inhibitors

• Strong and moderate CYP3A4 inhibitors can increase dordaviprone exposure and potentially increase toxicity.
• Therefore, concomitant use requires careful medical management and may require dose modification.

CYP3A4 inducers

Strong and moderate CYP3A4 inducers should generally be avoided because they can decrease dordaviprone exposure and potentially reduce its antitumor activity.

Patients should inform their physician about:

• Antibiotics
• Antifungals
• Antiepileptic medicines
• Antiviral medicines
• Herbal supplements
• OTC medicines

before starting any new treatment.

• Store Dordaviprone at 20°C–25°C (68°F–77°F)
• At room temperature
• In the original container
• In a child-resistant container
• Out of reach of children.

Do not use capsules that are expired, broken, or damaged.

For patients receiving dordaviprone:

• Take it once weekly, not once daily.
• Take it on the same day every week.
• Take the entire prescribed dose at the same time.
• Take it on an empty stomach.
• Do not change the dose without your oncologist's instruction.
• If vomiting occurs, do not repeat the dose.
• Inform your doctor about every prescription, OTC medicine, and supplement.
• Avoid medicines that can significantly affect CYP3A4 unless specifically approved by your physician.
• Tell your doctor if you have a history of heart-rhythm problems or long-QT syndrome.
• Attend scheduled ECG and electrolyte monitoring.
• Report palpitations, fainting, or severe dizziness immediately.
• Report any signs of a serious allergic reaction immediately.
• Women of reproductive potential should use effective contraception.
• Do not breastfeed during treatment and for the recommended period after treatment.
• Do not stop treatment without consulting the treating oncologist.