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Danicopan (Monograph)

Brand name: Voydeya
Drug class: Complement Inhibitor Agents

Medically reviewed by Drugs.com on Nov 10, 2024. Written by ASHP.

Warning

Risk Evaluation and Mitigation Strategy (REMS):

FDA approved a REMS for danicopan to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of danicopan and consists of elements to assure safe use and implementation system. See the FDA REMS page ([Web]) for specific information.

Warning

    Serious Infections Caused By Encapsulated Bacteria
  • Risk of serious infections, especially those caused by encapsulated bacteria, including Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type B. Infections may quickly become life-threatening or fatal if not recognized and treated early.

  • Complete or update vaccination for encapsulated bacteria at least 2 weeks prior to the first dose of danicopan, unless risks of delaying therapy outweigh 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.

  • Patients receiving danicopan are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor for early signs and symptoms of serious infections; evaluate immediately if infection is suspected.

  • Because of risk of serious infections, danicopan is available only through a Risk Evaluation and Mitigation Strategy (REMS) program.

Introduction

Small molecule complement factor D inhibitor.

Uses for Danicopan

Paroxysmal Nocturnal Hemoglobinuria

Add-on therapy to ravulizumab or eculizumab for treatment of extravascular hemolysis in adults with paroxysmal nocturnal hemoglobinuria (PNH); designated an orphan drug by FDA for this use. Should only be prescribed as add-on therapy to ravulizumab or eculizumab; has not been shown to be effective as monotherapy.

Options for PNH management include supportive care (e.g., iron supplementation, RBC transfusion, antibiotics for bacterial infection, anticoagulation, corticosteroids), allogeneic bone marrow transplantation, and/or terminal complement inhibitors (e.g., ravulizumab, eculizumab); choice of therapy is based on PNH classification and symptom severity.

Danicopan Dosage and Administration

General

Pretreatment Screening

Patient Monitoring

Premedication and Prophylaxis

REMS

Administration

Oral Administration

Available as tablets containing 50 mg or 100 mg of danicopan.

Administer orally with or without food.

If a dose is missed, administer as soon as it is remembered unless it is within 3 hours of next scheduled dose, in which case skip the missed dose and take next dose at regularly scheduled time. Do not administer 2 or more doses at the same time.

Dosage

Adults

Paroxysmal Nocturnal Hemoglobinuria
Oral

Recommended starting dosage: 150 mg 3 times daily.

Dosage can be increased to 200 mg 3 times daily if hemoglobin level has not increased by >2 g/dL after 4 weeks of treatment, if patient required a transfusion during the previous 4 weeks, or to achieve an appropriate hemoglobin response based on clinical judgement.

Special Populations

Hepatic Impairment

No dosage adjustment required in mild to moderate hepatic impairment (Child-Pugh class A and B).

Avoid use in severe hepatic impairment.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time.

Cautions for Danicopan

Contraindications

Warnings/Precautions

Warnings

Serious Infections Caused by Encapsulated Bacteria

Risk of serious, life-threatening, or fatal infections caused by encapsulated bacteria including Neisseria meningitidis (caused by any subgroup, including non-groupable strains), Streptococcus pneumoniae, or Haemophilus influenzaetype B. (See Boxed Warning.) Infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors.

Complete or update vaccinations against encapsulated bacteria, specifically Neisseria meningitidis and Streptococcus pneumoniae ≥2 weeks prior to the first dose of danicopan, according to current Advisory Committee on Immunization Practices (ACIP) recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering duration of danicopan therapy.

If urgent danicopan therapy indicated in a patient not up to date with vaccines against encapsulated bacteria, provide antibacterial drug prophylaxis and administer these vaccines as soon as possible. Because optimal duration and drug regimen for prophylaxis has not been studied in unvaccinated or vaccinated patients, weigh benefits and risks of danicopan treatment and antibacterial drug prophylaxis against risks for serious infections caused by encapsulated bacteria.

Vaccination does not eliminate risk of serious encapsulated bacterial infections.

Closely monitor patients for early signs and symptoms of serious infection. Evaluate patients immediately if infection suspected.

Inform patients of signs and symptoms of infection; instruct patients to seek immediate medical care if these occur. Promptly treat known infections.

Consider interruption of danicopan in patients undergoing treatment for serious infections.

Because of risk of serious infections caused by encapsulated bacteria, danicopan is available only through a REMS program. (See REMS under Dosage and Administration.)

Other Warnings and Precautions

Hepatic Enzyme Increases

Hepatic enzyme elevations observed.

Assess liver enzymes prior to starting danicopan and periodically during treatment. Consider treatment interruption or discontinuation if clinically important elevations occur or patient is symptomatic.

Monitoring of PNH Manifestations After Treatment Discontinuation

After danicopan discontinuation, closely monitor patients for ≥2 weeks after the last dose for signs and symptoms of hemolysis. Signs and symptoms may include sudden decrease in hemoglobin or fatigue.

If danicopan discontinuation required, continue background treatment with ravulizumab or eculizumab or consider alternative therapy if necessary.

If hemolysis occurs after discontinuation, consider restarting danicopan if appropriate.

Hyperlipidemia

Increases in total cholesterol and LDL cholesterol observed.

Monitor serum lipid parameters periodically during treatment; initiate cholesterol-lowering medication, if needed.

Specific Populations

Pregnancy

No data available in pregnant individuals to evaluate for drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to 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 risks and benefits.

Lactation

No data on presence of danicopan in human milk, effects on breast-fed children, or effects on milk production. Excreted into animal milk.

Because of potential for serious adverse reactions in breast-fed children, advise patients not to breast-feed during treatment and for 3 days after the last dose.

Pediatric Use

Safety and effectiveness not established.

Geriatric Use

Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger adults.

Hepatic Impairment

Danicopan peak plasma concentration and AUC decreased by 27 and 8%, respectively, in patients with moderate hepatic impairment (Child-Pugh class B).

Not evaluated in severe hepatic impairment (Child-Pugh class C); avoid use.

Renal Impairment

Following oral administration in patients with severe renal impairment (eGFR <30 mL/minute per 1.73 m2), danicopan AUC increased by 52%; no clinically important change in peak plasma drug concentration or time to peak plasma concentration observed.

Common Adverse Effects

Most frequently reported adverse effect (≥10%): headache.

Drug Interactions

P-glycoprotein (P-gp) substrate. Not a substrate of breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, or OATP1B3.

Not an inducer of CYP1A2, CYP2B6, or CYP2C9. Non-CYP based metabolism is primary clearance pathway for danicopan; minimal contribution of CYP metabolism in human hepatocytes suggestive of very low likelihood of CYP-based drug interactions with danicopan.

Inhibitor of BCRP and P-gp. Does not inhibit transporters OATP1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 2, or multidrug and toxin extrusion (MATE) 1 and MATE2-K.

Drugs Affecting or Affected by Transport Systems

BCRP Substrates

Concomitant use increases plasma concentrations of BCRP substrate, which may increase risk for adverse reactions associated with the substrate.

If used concomitantly, monitor more frequently for adverse reactions associated with BCRP substrate. Consider dosage reduction of BCRP substrate in accordance with its prescribing information.

P-gp Substrates

Concomitant use may increase plasma concentration of P-gp substrate.

Dosage adjustment may be necessary for P-gp substrates where minimal concentration changes may lead to serious adverse reactions.

Specific Drugs

Drug

Interaction

Comments

Antacids (calcium carbonate, aluminum/magnesium hydroxide/simethicone)

No clinically important interaction

Bupropion

No clinically important interaction

Fexofenadine (P-gp substrate)

Danicopan dosed to steady state increased fexofenadine peak plasma concentration and AUC by 1.4-fold and 1.6-fold, respectively

Dosage adjustment may be necessary for P-gp substrates where minimal concentration changes may lead to serious adverse reactions

Midazolam

No clinically important interaction

Mycophenolic acid

No clinically important interaction

Omeprazole (proton pump inhibitor)

No clinically important interaction

Rosuvastatin( BCRP substrate)

Danicopan increased rosuvastatin peak plasma concentration and AUC by 3.3-fold and 2.2-fold, respectively

Do not exceed rosuvastatin dosage of 10 mg once daily when used concomitantly

Tacrolimus (P-gp substrate)

Danicopan dosed to steady state increased tacrolimus peak plasma concentration and AUC by 1.1-fold and 1.5-fold, respectively

Dosage adjustment may be necessary for P-gp substrates where minimal concentration changes may lead to serious adverse reactions

Warfarin

No clinically important interaction

Danicopan Pharmacokinetics

Absorption

Bioavailability

Exposures at steady state generally increase in a dose-proportional manner from 150 mg 3 times daily to 200 mg 3 times daily.

Systemic exposure reaches steady state in approximately 2 days. Approximately 2-fold accumulation expected at steady state following 3 times daily dosing compared to a single dose.

Median time to peak plasma concentration: 3.7 hours.

Food

Administration with high-fat meal increased AUC and peak plasma concentration by approximately 25 and 93%, respectively, compared to fasted state.

Median time to peak plasma concentration in fed or fasted state was 3 or 2.5 hours, respectively.

Distribution

Extent

Mainly distributed in plasma.

Unknown if distributed into human milk.

Plasma Protein Binding

91.5–94.3%

Elimination

Metabolism

Extensively metabolized (96%) via oxidation, reduction, and hydrolysis pathways, with amide hydrolysis being the major pathway.

Elimination Route

Fecal: 69% (3.57% as unchanged drug).

Urine: 25% (0.48% as unchanged drug).

Half-life

7.9 hours.

Special Populations

Age (16.9–82 years), sex, or race does not appear to have clinically important effects on danicopan pharmacokinetics.

Stability

Storage

Oral

Tablets, Film-Coated

20–25°C; excursions permitted to 15–30°C.

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Danicopan

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

50 mg

Voydeya

Alexion Pharmaceuticals

100 mg

Voydeya

Alexion Pharmaceuticals

AHFS DI Essentials™. © Copyright 2025, Selected Revisions November 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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