Danicopan
FDA Drug Information • Also known as: Voydeya
- Brand Names
- Voydeya
- Drug Class
- Complement Factor D Inhibitor [EPC]
- Route
- ORAL
- Dosage Form
- TABLET, FILM COATED
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA VOYDEYA, a complement inhibitor, increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Neisseria meningitidis , Streptococcus pneumoniae , and Haemophilus influenzae type B [ see Warnings and Precautions (5.1) ]. Life-threatening and fatal infections with encapsulated bacteria have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update vaccination for encapsulated bacteria specifically, Neisseria meningitidis and Streptococcus pneumoniae at least 2 weeks prior to the first dose of VOYDEYA, unless the risks of delaying therapy with VOYDEYA outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria in patients receiving a complement inhibitor. See Warnings and Precautions (5.1) for additional guidance on the management of the risk of serious infections caused by encapsulated bacteria. Patients receiving VOYDEYA are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected. Because of the risk of serious infections caused by encapsulated bacteria, VOYDEYA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the VOYDEYA REMS [see Warnings and Precautions (5.2) ] . WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA See full prescribing information for complete boxed warning. VOYDEYA increases the risk of serious and life-threatening infections, caused by encapsulated bacteria, including Neisseria meningitidis , Streptococcus pneumoniae , and Haemophilus influenzae type B ( 5.1 ). Complete or update vaccination for encapsulated bacteria at least 2 weeks prior to the first dose of VOYDEYA, unless the risks of delaying VOYDEYA outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria in patients receiving a complement inhibitor ( 5.1 ). Patients receiving VOYDEYA are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected ( 5.1 ). VOYDEYA is available only through a restricted program called VOYDEYA REMS ( 5.2 ).
Description
11 DESCRIPTION Danicopan is a small molecule complement Factor D inhibitor. Its chemical name is (2S,4R)-1-{[3-acetyl-5-(2-methylpyrimidin-5-yl)-1H-indazol-1-yl] acetyl}-N-(6-bromopyridin-2-yl)-4-fluoropyrrolidine-2-carboxamide. Its molecular formula is C 26 H 23 BrFN 7 O 3 and its molecular weight is 580.4. Danicopan has the following structural formula: Danicopan is a white/off-white to pale yellow powder. In aqueous solutions, danicopan is considered slightly soluble at pH 1.2 and insoluble from pH 4 to pH 7. Danicopan tablets are available as white to off-white, round, film-coated, immediate release tablets in strengths of 50 mg and 100 mg, intended for oral administration. Each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose acetate succinate, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate. The tablet coating components are polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. Chemical Structure
What Is Danicopan Used For?
1 INDICATIONS AND USAGE VOYDEYA is indicated as add-on therapy to ravulizumab or eculizumab for the treatment of extravascular hemolysis (EVH) in adults with paroxysmal nocturnal hemoglobinuria (PNH). VOYDEYA is a complement factor D inhibitor indicated as add-on therapy to ravulizumab or eculizumab for the treatment of extravascular hemolysis (EVH) in adults with paroxysmal nocturnal hemoglobinuria (PNH) ( 1 ). Limitations of Use VOYDEYA has not been shown to be effective as monotherapy and should only be prescribed as an add-on to ravulizumab or eculizumab. Limitations of Use VOYDEYA has not been shown to be effective as monotherapy and should only be prescribed as an add-on to ravulizumab or eculizumab.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Start 150 mg three times a day orally, with or without food. Depending on clinical response, can increase to 200 mg three times a day. See Full Prescribing Information for instructions on dosage and administration ( 2.1 , 2.2 ). 2.1 Recommended Vaccination and Prophylaxis for Encapsulated Bacterial Infections Vaccinate patients against encapsulated bacteria, including Neisseria meningitidis (serogroups A, C, W, Y, and B) and Streptococcus pneumoniae according to current ACIP recommendations at least 2 weeks prior to initiation of VOYDEYA. If urgent VOYDEYA therapy is indicated in a patient who is not up to date with vaccines for Neisseria meningitidis and Streptococcus pneumoniae according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible [see Warnings and Precautions (5.1) ] . Healthcare professionals who prescribe VOYDEYA must enroll in the VOYDEYA REMS [see Warnings and Precautions (5.2) ] . 2.2 Recommended Dosage Starting Dose: The recommended dosage of VOYDEYA is 150 mg three times a day administered orally. VOYDEYA can be taken with or without food. Dose Adjustment: The dose can be increased to 200 mg three times a day if the patient's hemoglobin (Hgb) level has not increased by greater than 2 g/dL after 4 weeks of therapy, if the patient required a transfusion during the previous 4 weeks, or to achieve an appropriate Hgb response based on clinical judgement. Missed Doses A patient who misses a dose of VOYDEYA should take it as soon as they remember unless it is within 3 hours prior to their next dose, in which case the patient should skip the missed dose and take VOYDEYA at the next regularly scheduled time. Patients should not take two or more doses of VOYDEYA at the same time.
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Serious Infections Caused by Encapsulated Bacteria [see Warnings and Precautions (5.1) ] Hepatic Enzyme Increases [see Warnings and Precautions (5.3) ] Hyperlipidemia [see Warnings and Precautions (5.4) ] Most frequent adverse reaction (incidence ≥10%) was headache ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Alexion Pharmaceuticals, Inc. at 1-844-259-6783 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of VOYDEYA was evaluated in 86 adults with PNH in Study ALXN2040-PNH-301 [see Clinical Studies (14) ] . Study ALXN2040-PNH-301 enrolled adults with PNH with clinically significant EVH who had been treated with a stable dose of ravulizumab or eculizumab for at least the previous 6 months. Patients were randomly assigned 2:1 to receive double-blind VOYDEYA 150 mg (n=57) or placebo (n=29) orally three times a day in addition to ravulizumab or eculizumab for 12 weeks. Patients received either US-approved or non-US-approved ravulizumab or eculizumab in the trial. Among patients who were randomized to receive VOYDEYA, 84% were exposed for at least 12 weeks. Serious adverse reactions were reported in 5% of patients who received VOYDEYA and included pancreatitis, cholecystitis, and blood bilirubin increased. No specific serious adverse reaction was reported in more than 1 patient treated with VOYDEYA. Permanent discontinuation of VOYDEYA due to an adverse reaction occurred in 5% of patients and included 1 patient with blood bilirubin increase and pancreatitis, 1 patient with hepatic enzyme increased, and 1 patient with ALT increased and aspartate aminotransferase increased. Dosage reduction due to an adverse reaction occurred in 1 patient and the adverse reaction was COVID-19. Among the 57 patients treated with VOYDEYA in Study ALXN2040-PNH-301, the most common adverse reaction (≥10%) was headache. Table 1 describes adverse reactions reported in ≥5% of patients treated with VOYDEYA and greater than placebo in the randomized, controlled period of Study ALXN2040-PNH-301. Table 1 Adverse Reactions Reported in ≥5% of VOYDEYA-Treated Patients with PNH and Greater than Placebo Adverse Reactions Common Toxicity Criteria Adverse Events (CTCAE) VOYDEYA (with ravulizumab or eculizumab) N = 57 Placebo (ravulizumab or eculizumab only) N = 29 n (%) n (%) Headache 6 (11) 3 (10) Vomiting Represents a composite of multiple, related adverse reactions 4 (7) 0 (0) Pyrexia 4 (7) 0 (0) Alanine aminotransferase increased 3 (5) 1 (3) Hypertension 3 (5) 1 (3) Pain in extremity 3 (5) 0 (0) Clinically relevant adverse reactions in <5% of patients include increased serum triglycerides.
Drug Interactions
7 DRUG INTERACTIONS BCRP substrates: Monitor patients more frequently for adverse reactions and consider dose reduction of the BCRP substrate drug. For rosuvastatin, the dose should not exceed 10 mg once daily ( 7.1 ). P-gp substrates: Dose adjustment might be necessary for P-gp substrates where minimal concentration changes may lead to serious adverse reactions ( 7.2 ). 7.1 BCRP Substrates Danicopan is a Breast Cancer Resistance Protein (BCRP) inhibitor. Concomitant use of VOYDEYA with a BCRP substrate increases the plasma concentrations of the BCRP substrate [see Clinical Pharmacology (12.3) ] , which may increase the risk for adverse reactions associated with the BCRP substrate. If used together, monitor patients more frequently for adverse reactions associated with the BCRP substrate, and consider dose reduction of the BCRP substrate according to its prescribing information. Rosuvastatin Danicopan significantly increased rosuvastatin exposure. The dose of rosuvastatin should not exceed 10 mg once daily when concomitantly used with VOYDEYA [see Clinical Pharmacology (12.3) ] . 7.2 P-gp Substrates Danicopan is an inhibitor of P-glycoprotein (P-gp). Concomitant administration of VOYDEYA with a P-gp substrate may increase the plasma concentration of the P-gp substrate. Dose adjustment might be necessary for P-gp substrates where minimal concentration changes may lead to serious adverse reactions [see Clinical Pharmacology (12.3) ] .
Contraindications
4 CONTRAINDICATIONS VOYDEYA is contraindicated for initiation in patients with unresolved serious infection caused by encapsulated bacteria, including Neisseria meningitidis , Streptococcus pneumoniae , or Haemophilus influenzae type B [see Warnings and Precautions (5.1) ] . Initiation in patients with unresolved serious infection caused by encapsulated bacteria ( 4 ).
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no available data on VOYDEYA use in pregnant individuals to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with untreated PNH in pregnancy (see Clinical Considerations ) . The use of VOYDEYA in pregnant women or women planning to become pregnant may be considered following an assessment of the risks and benefits. In animal reproduction studies, oral administration of danicopan to pregnant New Zealand White (NZW) rabbits and Wistar Hans (WH) rats during organogenesis at exposures 18 or 25-times, respectively, above the human exposure at the maximum recommended human dose (MRHD) of 200 mg three times a day (based on AUC) resulted in no adverse developmental effects (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Fetal/Neonatal Risk 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. Data Animal Data There were no effects on early embryonic development and fetal development in NZW rabbits (where danicopan is pharmacodynamically active) up to a mean maternal systemic exposure 18-times the exposure at the MRHD (based on AUC) or during post-natal development up to a mean maternal systemic exposure 9-times the exposure at the MRHD (based on AUC). In WH rats (where danicopan lacks pharmacodynamic activity), there were no effects on...
Overdosage
10 OVERDOSAGE Serum ALT elevations occurred after treatment cessation without a taper in 2 healthy subjects who received danicopan 500 mg and 800 mg twice a day. These abnormal ALT findings were transient, with no evidence of hepatic function abnormality and resolved spontaneously. In case of overdose, elevations in liver enzymes may occur. General supportive measures are recommended. It is not known if VOYDEYA can be removed by dialysis.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING VOYDEYA (danicopan) tablets are available in the doses and packages listed in Table 4. Table 4 VOYDEYA Tablet Presentations Dose Tablet Strength Film-Coated Tablet Markings Tablet Color/Shape Pack Size NDC Code Each carton contains two high density polyethylene bottles with desiccant and child resistant seal, with 180 tablets per carton: 150 mg 50 mg Debossed on one side with "DCN 50" White to off-white, round film-coated tablets One bottle with 90 × 50 mg per tablet (25682-040-90) One bottle with 90 × 100 mg per tablet (25682-043-90) 25682-046-92 100 mg Debossed on one side with "DCN 100" 200 mg 100 mg Debossed on one side with "DCN 100" White to off-white, round film-coated tablets Two bottles with 90 tablets per bottle: 90 × 100 mg per tablet (25682-043-90) 25682-043-92 Each carton contains four 7-day blister cards with 168 tablets per carton: 150 mg 50 mg Debossed on one side with "DCN 50" White to off-white, round film-coated tablets Four blister cards with 42 tablets per card: 21 × 50 mg per tablet and 21 × 100 mg per tablet (25682-049-42) 25682-049-04 100 mg Debossed on one side with "DCN 100" 200 mg 100 mg Debossed on one side with "DCN 100" White to off-white, round film-coated tablets Four blister cards with 42 tablets per card: 42 × 100 mg per tablet (25682-043-42) 25682-043-04 Store and dispense in the original container at 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP controlled room temperature].
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.