Brand name: Voydeya
Drug class: Complement Inhibitor Agents

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

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

• Obtain baseline liver enzyme levels.

• Assess immunization status prior to initiating danicopan therapy; ensure patient has received recommended vaccines.

Patient Monitoring

• Closely monitor for early signs and symptoms of serious infection; evaluate patient immediately if infection is suspected.

• Monitor liver enzymes periodically during treatment.

• Monitor for signs and symptoms of hemolysis for ≥2 weeks after discontinuation.

• Monitor serum lipid parameters periodically during treatment.

Premedication and Prophylaxis

• Vaccinate patients against encapsulated bacteria, including Neisseria meningitidis(serogroups A, C, W, Y, and B) and Streptococcus pneumoniae according to current Advisory Committee on Immunization Practices (ACIP) recommendations ≥2 weeks prior to treatment initiation. If urgent therapy is indicated in a patient who is not up to date with these vaccines, provide antibacterial drug prophylaxis and administer the vaccines as soon as possible.

REMS

• Because of the risk of serious infections caused by encapsulated bacteria, danicopan is available only through a restricted program called the Voydeya Risk Evaluation and Mitigation Strategy (REMS).

• Danicopan may be prescribed only by clinicians who are enrolled in the Voydeya REMS program. Clinicians must counsel patients regarding the risk of serious infections, provide educational materials, and ensure patients are compliant with vaccinations against encapsulated bacteria and antibacterial drug prophylaxis requirements.

• To obtain additional information or to enroll in the program, clinicians may call 1-888-765-4747 or visit [Web].

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

• Unresolved infection caused by encapsulated bacteria, including Neisseria meningitidis, Streptococcus pneumoniae, or Haemophilus influenzaetype B.

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

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

• Small molecule complement Factor D inhibitor.

• Binds reversibly to complement Factor D and selectively inhibits the alternative pathway (AP) of the complement system.

• Prevents cleavage of complement Factor B into the Ba and Bb fragments, which are required for formation of the AP complement component C3 convertase (C3bBb), generation of downstream effectors including C3 fragment opsonization, and amplification of the terminal pathway.

• Acts proximally in the AP of the complement cascade to control preferentially C3 fragment-mediated extravascular hemolysis; co-administered ravulizumab or eculizumab anticipated to maintain control over membrane attack complex-mediated intravascular hemolysis.

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Medication Guide).

• Advise patients of the risk of serious infections with danicopan therapy. Inform patients of the need to complete or update their vaccinations against encapsulated bacteria ≥2 weeks prior to receiving the first dose of danicopan or receive antibacterial drug prophylaxis if danicopan treatment must be initiated immediately and they have not previously been vaccinated. Inform patients of the requirement to be revaccinated according to Advisory Committee on Immunization Practices (ACIP) recommendations for encapsulated bacteria while on danicopan therapy.

• Inform patients that vaccination may not prevent serious infection and to seek immediate medical attention if the following signs or symptoms of infection occur: fever with or without chills; fever and a rash; fever with chest pain and cough; fever with breathlessness/fast breathing; fever with high heart rate; headache with nausea or vomiting; headache with a fever; headache with a stiff neck or stiff back; confusion; body aches with flu-like symptoms; clammy skin; or eye sensitivity to light.

• Inform patients that they will receive a Patient Safety Card for danicopan that they should carry with them at all times during treatment with danicopan and for 1 week following treatment discontinuation. Inform patients that this card describes symptoms which, if experienced, should prompt them to seek immediate medical evaluation.

• Inform patients that danicopan is available only through a restricted program called Voydeya REMS. Inform patients of the important requirements of the program, including patient counseling and compliance with vaccinations.

• Inform patients with paroxysmal nocturnal hemoglobinuria (PNH) of the importance of taking danicopan as prescribed to minimize the risk of hemolysis.

• Inform patients with PNH that they may develop serious hemolysis if danicopan is discontinued and that they will be monitored by their clinicians for ≥2 weeks following treatment discontinuation.

• Inform patients that elevation in liver enzymes have occurred in patients treated with danicopan, and liver tests will be obtained before and during treatment.

• Inform patients that danicopan may increase cholesterol levels and that monitoring of cholesterol levels will be needed periodically during treatment.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed. Advise women not to breast-feed during treatment with danicopan, and for 3 days after the last dose.

• Inform patients of other important precautionary information.

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.

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