Version October 2024
Danicopan, 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. 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 danicopan, unless the risks of delaying therapy with danicopan 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/Precautions for additional guidance on the management of the risk of serious infections caused by encapsulated bacteria. Patients receiving danicopan 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, danicopan is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the VOYDEYA REMS.
Dosage guidance:
Safety: Complete or update vaccination for encapsulated bacteria, specifically S. pneumoniae and N. meningitidis (serogroups A, C, W, Y, and B) according to current Advisory Committee on Immunization Practices (ACIP) recommendations at least 2 weeks prior to danicopan initiation; revaccinate according to current ACIP guidelines. If urgent danicopan treatment is necessary in a patient who is not up to date with S. pneumoniae and N. meningitidis ACIP recommended vaccines against encapsulated bacteria, provide antibacterial prophylaxis and administer the vaccines as soon as possible.
Extravascular hemolysis associated with paroxysmal nocturnal hemoglobinuria: Note: Danicopan is intended as add-on therapy to ravulizumab or eculizumab.
Initial: Oral: 150 mg 3 times a day (Ref).
Dosage adjustment: Oral: May increase dose up to 200 mg 3 times a day if Hb level has not increased by >2 g/dL after 4 weeks of therapy, if a transfusion is required during the previous 4 weeks, or to achieve an appropriate Hb response based on clinical judgement (Ref).
Missed dose: If a dose is missed, it should be administered as soon as remembered unless it is within 3 hours prior to their next dose, in which case the missed dose should be skipped and the next danicopan dose should be administered at the next regularly scheduled time. Do not administer two or more danicopan doses at the same time.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
eGFR ≥30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling.
eGFR <30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling; however, danicopan exposure is increased, although there is no clinically meaningful change in plasma or peak concentrations.
Hepatic impairment prior to treatment initiation:
Mild or moderate hepatic impairment (Child-Turcotte-Pugh class A, B): No dosage adjustment necessary.
Severe hepatic impairment (Child-Turcotte-Pugh class C): Avoid danicopan use (has not been studied).
Acute hepatotoxicity during treatment:
Clinically significant or symptomatic hepatotoxicity: Consider treatment interruption or discontinuation.
Hemolysis (after danicopan discontinuation): If hemolysis occurs following danicopan discontinuation, if appropriate, consider restarting danicopan treatment.
Hyperlipidemia: Initiate cholesterol lowering medication, if indicated.
Infection (suspected): Evaluate immediately if infection is suspected. Promptly treat known infections. Consider danicopan treatment interruption in patients who are undergoing treatment for serious infections.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults in combination with ravulizumab or eculizumab.
>10%:
Endocrine & metabolic: Hypercholesterolemia (including increased LDL cholesterol)
Nervous system: Headache
1% to 10%:
Cardiovascular: Hypertension
Endocrine & metabolic: Increased serum triglycerides
Gastrointestinal: Cholecystitis, pancreatitis, vomiting
Hepatic: Increased serum alanine aminotransferase, increased serum bilirubin
Neuromuscular & skeletal: Limb pain
Miscellaneous: Fever
Frequency not defined:
Hepatic: Increased serum aspartate aminotransferase
Infection: Serious infection
Initiation in patients with unresolved serious infection caused by encapsulated bacteria, including Neisseria meningitidis, Streptococcus pneumoniae, or Haemophilus influenzae type B.
Concerns related to adverse effects:
• Hepatotoxicity: Hepatic enzyme elevations have been observed in danicopan-treated patients. Grades 2 and 3 ALT elevations were observed in patients who received danicopan in the clinical study.
• Hyperlipidemia: Danicopan increases total cholesterol and LDL-cholesterol. Of the danicopan-treated patients who had a normal total cholesterol level at baseline in the clinical study, nearly one-third of patients developed grade 1 hypercholesterolemia and of the small number of patients who had grade 1 hypercholesterolemia at baseline, one case worsened to grade 2 (total cholesterol increase). Of patients in the clinical study with LDL-cholesterol ≤130 mg/dL at baseline, some developed LDL-cholesterol >130 to 160 mg/dL and >160 to 190 mg/dL. Some patients required cholesterol-lowering medications.
• Infection: Complement inhibitors, including danicopan, increase 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. Life-threatening and fatal infections with encapsulated bacteria have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. Note that the Advisory Committee on Immunization Practices recommended administration schedule for patients receiving complement inhibitors differs from the administration schedule in the vaccine prescribing information. Vaccination does not eliminate the risk of serious encapsulated bacterial infections, despite development of antibodies following vaccination; patients receiving danicopan are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Various durations and regimens of antibacterial drug prophylaxis have been considered, but the optimal durations and drug regimens for prophylaxis and their efficacy have not been studied in unvaccinated or vaccinated patients receiving complement inhibitors (including danicopan). Consider the benefits and risks of danicopan treatment (and the benefits and risks of antibacterial prophylaxis) in unvaccinated or vaccinated patients against the known risks for serious infections caused by encapsulated bacteria. Inform patients of the signs/symptoms and instruct them to seek immediate medical care if infection is suspected. Serious infection may become rapidly life-threatening or fatal if not recognized and treated early.
Other warnings/precautions:
• Discontinuation in paroxysmal nocturnal hemoglobinuria: Following danicopan discontinuation, signs/symptoms of hemolysis may occur. Signs/symptoms of hemolysis may include a sudden decrease in hemoglobin or fatigue. If danicopan discontinuation is necessary, continue background treatment with ravulizumab or eculizumab or consider alternative therapy if necessary. If hemolysis occurs following danicopan discontinuation, if appropriate, consider restarting danicopan treatment.
• REMS program: Due to the risk of serious infections caused by encapsulated bacteria, danicopan is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the VOYDEYA REMS. REMS information is available at 1-888-765-4747 or at https://www.VoydeyaREMS.com.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Voydeya: 100 mg
Tablet Therapy Pack, Oral:
Voydeya: 50 & 100 MG (180 ea)
No
Tablet Therapy Pack (Voydeya Oral)
50 & 100 mg (per each): $27.54
Tablets (Voydeya Oral)
100 mg (per each): $36.72
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Danicopan is available through certified REMS pharmacies. Access information from the manufacturer may be found at https://alexionaccessnavigator.com/voydeya.
Oral: Administer with or without food. Administer doses at approximately the same times every day.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Voydeya: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218037s000lbl.pdf#page=18
Extravascular hemolysis associated with paroxysmal nocturnal hemoglobinuria: Treatment of extravascular hemolysis, as add-on therapy to ravulizumab or eculizumab, in adults with paroxysmal nocturnal hemoglobinuria.
Limitations of use: Danicopan has not been shown to be effective as monotherapy and should only be prescribed as an add-on to ravulizumab or eculizumab.
Danicopan may be confused with may be confused with avacopan, iptacopan, pegcetacoplan, zilucoplan.
Substrate of P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP/ABCG2, P-glycoprotein/ABCB1
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider therapy modification
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors): Danicopan may increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider therapy modification
CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider therapy modification
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Risk C: Monitor therapy
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Risk C: Monitor therapy
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy
Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Mavorixafor: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Mavorixafor. Risk C: Monitor therapy
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Risk C: Monitor therapy
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider therapy modification
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Risk C: Monitor therapy
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Repotrectinib. Risk X: Avoid combination
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider therapy modification
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy
Rosuvastatin: Danicopan may increase the serum concentration of Rosuvastatin. Management: Limit the rosuvastatin dose to 10 mg once daily if combined with danicopan. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Saquinavir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider therapy modification
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy
Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a P-gp inhibitor. Risk D: Consider therapy modification
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
When administered with a high-fat meal, danicopan AUC and Cmax were ~25% and 93% higher, respectively, compared to the fasted state. The median time to maximum drug concentration were ~3 hours (fed state) and ~2.5 hours (fasted state).
Adverse events were not observed in animal reproduction studies.
It is not known if danicopan is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, including infections with encapsulated bacteria and liver enzyme increases, breastfeeding is not recommended by the manufacturer during therapy and for 3 days after the last danicopan dose.
Assess immunization status prior to treatment. Monitor liver enzymes (at baseline and periodically during treatment). Monitor serum lipid parameters (at baseline and periodically during treatment). Monitor patients for early signs/symptoms of serious infections (evaluate immediately if infection is suspected). Monitor adherence.
Following danicopan discontinuation, closely monitor patients for signs/symptoms of hemolysis for at least 2 weeks after the last dose. Signs/symptoms of hemolysis may include a sudden decrease in hemoglobin or fatigue.
Danicopan is a small molecule complement factor D inhibitor with selective inhibition on the alternative complement pathway (Lee 2023). Danicopan prevents the cleavage of complement factor B into Ba and Bb fragments, which are necessary for formation of the alternative pathway complement component C3 convertase (C3bBb), generation of downstream effectors including C3 fragment opsonization, and the amplification of the terminal pathway. In paroxysmal nocturnal hemoglobinuria, extravascular hemolysis is facilitated by C3 fragment opsonization and its deposition on circulating red blood cells. Danicopan is a proximal inhibitor of the alternative complement pathway and preferentially controls C3 fragment-mediated extravascular hemolysis, while co-administration with ravulizumab or eculizumab is expected to control intravascular hemolysis.
Distribution: Vd: 395 L.
Protein binding: 91.5% to 94.3%.
Metabolism: Extensively metabolized (96%) via oxidation, reduction, and hydrolysis pathways, with amide hydrolysis as the major elimination pathway; CYP-mediated metabolism is minimal.
Half-life elimination: 7.9 hours.
Time to peak: 3.7 hours (150 mg dose).
Excretion: Feces: 69% (~4% as unchanged drug); urine: 25% (<1% as unchanged drug).
Clearance: 63 L/hour.
Kidney function impairment: Following administration of a 200 mg oral dose in subjects with eGFR <30 mL/minute/1.73 m2, the extent of danicopan exposure (AUC0-inf) increased by 52% (compared to subjects with normal kidney function).
Hepatic function impairment: Danicopan Cmax decreased by 27% and AUC0-inf decreased by 8% in subjects with moderate hepatic impairment (Child-Turcotte-Pugh class B).
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