Danicopan

Danicopan is a prescription medication indicated for paroxysmal nocturnal hemoglobinuria (PNH) in patients who experience clinically significant extravascular hemolysis (EVH), as an add-on to complement component-5 (C5) inhibitor therapy (eg, eculizumab, ravulizumab).

• Danicopan is available under the following different brand names: Voydeya.

Common side effects of Danicopan include:

• headache

Serious side effects of Danicopan include:

• increased liver enzyme levels
• increased cholesterol

Rare side effects of Danicopan 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 dosage

Tablet

• 50 mg
• 100 mg

Paroxysmal nocturnal hemoglobinuria

Adult dosage

• 150 mg orally three times a day initially
• Increase to 200 mg three times a day if hemoglobin (Hgb) level has not increased by more than 2 g/dL after 4 weeks, if a patient required a transfusion during those 4 weeks, or to achieve an appropriate Hgb response based on clinical judgment

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.

• Danicopan has severe interactions with no other drugs
• Danicopan has serious interactions with no other drugs
• Danicopan has moderate interactions with no other drugs
• Danicopan 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

• Unresolved serious infection caused by encapsulated bacteria, including Neisseria meningitidis, Streptococcus pneumoniae, or Haemophilus influenzae type B

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• Serious infections caused by encapsulated bacteria
• Complement inhibitors increase a patient’s susceptibility to serious, life-threatening, or fatal infections caused by encapsulated bacteria including N meningitidis (caused by any serogroup, including non-groupable strains), S pneumoniae, and H influenzae type B
• Initiation of Danicopan is contraindicated in patients with unresolved serious infections caused by encapsulated bacteria
• Life-threatening and fatal infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors
• ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in vaccine prescribing information; if urgent therapy is indicated in a patient who is not up to date with vaccines against encapsulated bacteria according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible
• The benefits and risks of treatment with this drug, as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against known risks for serious infections caused by encapsulated bacteria
• Vaccination does not eliminate the risk of serious encapsulated bacterial infections, despite the development of antibodies following vaccination; closely monitor patients for early signs and symptoms of serious infection and evaluate patients immediately if an infection is suspected; inform patients of these signs and symptoms and instruct patients to seek immediate medical care if these signs and symptoms occur
• Complete or update vaccination against encapsulated bacteria, specifically N meningitidis and S pneumoniae, at least 2 weeks before initiating
• Revaccinate according to ACIP guidelines during the duration of treatment
• Promptly treat known infections; serious infection may rapidly become life-threatening or fatal if not recognized and treated early; consider interruption of Danicopan in patients who are undergoing treatment for serious infections
• Increased liver enzymes
  • Liver enzyme elevations observed
  • Assess liver enzyme test results before initiating and periodically during treatment
  • Consider treatment interruption or discontinuation if elevations are clinically significant or if the patient becomes symptomatic
  • Not studied in patients with severe hepatic impairment
  • Monitor PNH manifestations after discontinuing
  • After discontinuing, closely monitor patients for more than 2 weeks after the last dose for signs and symptoms of hemolysis
  • If discontinuation of Danicopan is necessary, continue background treatment with ravulizumab or eculizumab or consider alternative therapy if necessary
  • Signs and symptoms of hemolysis may include a sudden decrease in hemoglobin or fatigue
  • If hemolysis occurs after, consider restarting Danicopan if appropriate
• Hyperlipidemia
  • Increases total cholesterol and LDL-cholesterol
  • Some patients required cholesterol-lowering medications
  • Monitor serum lipids periodically during treatment and initiate cholesterol-lowering medication, if indicated
• Drug interaction overview
• Inhibits BCRP and P-gp
• BCRP substrates
  • Monitor, and consider a dose reduction of the BCRP substrate
  • Danicopan increases plasma concentrations of BCRP substrates; consider a dose reduction of BCRP substrate according to its prescribing information
  • Significantly increases rosuvastatin exposure; do not exceed rosuvastatin dose of 10 mg/day if coadministered
• P-gp substrates
  • Monitor, and consider dose reduction of P-gp substrate
  • Danicopan increases plasma concentrations of P-gp substrates; consider a dose reduction of P-gp substrates where minimal concentration changes may lead to serious adverse reactions

Pregnancy and Lactation

• Data are not available regarding use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
• Clinical considerations
  • There are risks to the mother and fetus associated with untreated PNH in pregnancy
  • Use of Danicopan in pregnant women or women planning to become pregnant may be considered following an assessment of the risks and benefits
  • PNH in pregnancy is associated with adverse maternal outcomes, including worsening cytopenias, thrombotic events, infections, bleeding, miscarriages, and increased maternal mortality, and adverse fetal outcomes, including fetal death and premature delivery
• Lactation
  • There are no data on the presence of Danicopan in human milk, its effects on breastfed children, or its effect on milk production
  • Danicopan is present in animal milk; when a drug is present in animal milk, it is likely to be present in human milk
  • Because of the potential for serious adverse reactions in breastfed children, including serious infections with encapsulated bacteria and liver enzyme increases, advise patients not to breastfeed during treatment and for 3 days after the last dose