Version May 2024
Iptacopan, a complement inhibitor, increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, 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 at least 2 weeks prior to the first dose of iptacopan, unless the risks of delaying therapy with iptacopan 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.
Patients receiving iptacopan 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, iptacopan is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the FABHALTA REMS.
Dosage guidance:
Safety: Vaccinate against encapsulated bacteria, including S. pneumoniae, N. meningitidis (serogroups A, C, W, Y, and B), and H. influenzae type B according to current Advisory Committee on Immunization Practices (ACIP) recommendations at least 2 weeks prior to iptacopan initiation; revaccinate according to current ACIP guidelines. If urgent iptacopan treatment is necessary in a patient who is not up to date with S. pneumoniae, N. meningitidis, and H. influenzae type B vaccines according to ACIP recommendations, provide antibacterial prophylaxis and administer the vaccines as soon as possible.
Paroxysmal nocturnal hemoglobinuria: Oral: 200 mg twice daily (Ref).
Conversion from C5 inhibitors:
Conversion from eculizumab: When converting from eculizumab to iptacopan, initiate iptacopan no later than 1 week following the last eculizumab dose.
Conversion from ravulizumab: When converting from ravulizumab to iptacopan, initiate iptacopan no later than 6 weeks following the last ravulizumab dose.
Missed dose: If a dose or doses are missed, administer one iptacopan dose as soon as possible (even if it is soon before the next scheduled dose) and then resume the regular dosing schedule.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Kidney function estimated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <30 mL/minute/1.73 m2 without hemodialysis: Use is not recommended.
eGFR <30 mL/minute/1.73 m2 with hemodialysis: Use is not recommended.
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): Use is not recommended.
Hemolysis (after iptacopan discontinuation): If hemolysis occurs following iptacopan discontinuation, consider restarting iptacopan (if appropriate) or initiating another paroxysmal nocturnal hemoglobinuria (PNH) treatment.
Hyperlipidemia: Initiate cholesterol-lowering medications if indicated.
Infection: Evaluate immediately if an infection is suspected. Promptly treat known infections. Consider iptacopan 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.
>10%:
Gastrointestinal: Abdominal pain (8% to 15%), diarrhea (8% to 15%)
Infection: Bacterial infection (5% to 11%, including bacterial pneumonia, pyelonephritis, urinary tract infection), viral infection (10% to 18%)
Nervous system: Headache (19% to 28%)
Respiratory: Nasopharyngitis (15% to 16%)
1% to 10%:
Cardiovascular: Hypertension (6%)
Dermatologic: Skin rash (3% to 10%), urticaria (3%)
Endocrine & metabolic: Dyslipidemia (6% to 8%, including hypercholesterolemia, increased LDL cholesterol, increased serum triglycerides)
Gastrointestinal: Nausea (5% to 10%)
Hematologic & oncologic: Thrombocytopenia (6%)
Nervous system: Dizziness (3% to 6%)
Neuromuscular & skeletal: Arthralgia (8%)
Frequency not defined: Infection: Serious infection
Serious hypersensitivity to iptacopan or any component of the formulation; initiation in patients with unresolved serious infection caused by encapsulated bacteria, including S. pneumoniae, N. meningitidis, or H. influenza type B.
Concerns related to adverse effects:
• Hyperlipidemia: Iptacopan increases total cholesterol, LDL-cholesterol, and serum triglycerides. Among 2 studies, one-fourth to one-half of iptacopan-treated patients with normal total cholesterol level at baseline developed grade 1 hypercholesterolemia during the treatment period. One patient experienced increased total cholesterol that worsened from grade 1 (at baseline) to grade 2. Among patients in the studies with baseline LDL-cholesterol ≤130 mg/dL, 11% to 17% developed LDL-cholesterol >130 to 160 mg/dL, 3% to 8% developed LDL-cholesterol >160 to 190 mg/dL, and 7% developed LDL-cholesterol >190 mg/dL during the treatment period. Among patients in the studies with normal baseline triglyceride levels approximately one-fourth of patients developed grade 1 elevated triglycerides during the treatment period. Three patients experienced an increase in triglycerides from grade 1 to grade 2. Some patients required cholesterol-lowering medications.
• Infection: Complement inhibitors, including iptacopan, increase the susceptibility to serious, life-threatening, or fatal infections caused by encapsulated bacteria, including S. pneumoniae, N. meningitidis (caused by any serogroup, including non-groupable strains), 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 (ACIP) recommended administration schedule in patients receiving complement inhibitors differs from the administration schedule in the vaccine prescribing information. The optimal prophylactic antibacterial drug regimens and durations and their efficacy have not been studied in unvaccinated or vaccinated patients receiving complement inhibitors (including iptacopan). Consider the benefits and risks of iptacopan treatment (and the benefits and risks of antibacterial drug prophylaxis) in unvaccinated or vaccinated patients versus the known risks for serious infections caused by encapsulated bacteria. Vaccination does not eliminate the risk of serious encapsulated bacterial infections, despite development of antibodies following vaccination. Inform patients of 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 iptacopan discontinuation, signs/symptoms of hemolysis may occur. Signs/symptoms include elevated lactate dehydrogenase (LDH) levels along with a sudden decrease in hemoglobin or paroxysmal nocturnal hemoglobinuria (PNH) clone size, fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events (eg, thrombosis, stroke, and myocardial infarction), dysphagia, or erectile dysfunction. If iptacopan discontinuation is necessary, consider alternative PNH therapy.
• REMS program: Due to the risk of serious infections, iptacopan is available only via a restricted REMS program (Fabhalta REMS). REMS information is available at 1-833-99FABHA or at http://www.FABHALTA-REMS.com.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Fabhalta: 200 mg
No
Capsules (Fabhalta Oral)
200 mg (per each): $904.11
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.
Iptacopan is available through certified REMS pharmacies. Examples from the manufacturer may be found at https://www.fabhalta-rems.com/#Main.
Oral: Administer without regard to food. Swallow whole; do not open, break, or chew capsules.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Fabhalta: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/218276s000lbl.pdf#page=16
Paroxysmal nocturnal hemoglobinuria: Treatment of paroxysmal nocturnal hemoglobinuria (PNH) in adults.
Fabhalta may be confused with Fabrazyme.
Iptacopan may be confused with avacopan, pegcetacoplan, zilucoplan.
Substrate of CYP2C8 (major), CYP2D6 (minor), UGT1A1, UGT1A3, UGT1A8; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
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 Lexicomp 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
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
BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. 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
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
CYP2C8 Inducers (Moderate): May decrease the serum concentration of Iptacopan. Risk C: Monitor therapy
CYP2C8 Inhibitors (Strong): May increase the serum concentration of Iptacopan. Risk X: Avoid combination
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
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
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
Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C8 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C8 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor therapy
Mitapivat: May decrease the serum concentration of UGT1A1 Substrates. 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
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
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
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
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
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
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
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
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Adverse events were not observed in animal reproduction studies conducted in doses 4 to 6 times the maximum recommended human dose (based on AUC).
It is not known if iptacopan is present in breast milk.
Breastfeeding is not recommended by the manufacturer during therapy and for 5 days after the last dose of iptacopan.
Assess immunization status prior to treatment. Monitor serum lipid parameters at baseline and periodically during treatment. Consider monitoring baseline lactate dehydrogenase (LDH). Monitor closely for early signs/symptoms of serious infection and evaluate immediately if an infection is suspected. Following iptacopan discontinuation, closely monitor patients for signs/symptoms of hemolysis for at least 2 weeks after the last dose; signs/symptoms include elevated LDH levels along with a sudden decrease in hemoglobin or paroxysmal nocturnal hemoglobinuria (PNH) clone size, fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events (eg, thrombosis, stroke, and myocardial infarction), dysphagia, or erectile dysfunction. Monitor adherence.
Iptacopan is a small-molecule complement factor B inhibitor. Iptacopan binds to factor B of the alternative complement pathway and regulates C3 cleavage, generating downstream effectors, and amplifying the terminal pathway. In paroxysmal nocturnal hemoglobinuria (PNH), intravascular hemolysis (IVH) is mediated by the downstream membrane attack complex (MAC), while extravascular hemolysis (EVH) is facilitated by C3b opsonization. Iptacopan acts proximally in the alternative complement cascade pathway to control both C3b-mediated EVH and terminal complement-mediated IVH.
Onset: Inhibition of alternative pathway biomarkers, in vitro alternative pathway assay and plasma Bb, began ~2 hours after a single initial dose (in healthy volunteers).
Distribution: Vdss: ~288 L.
Protein binding: 75% to 93%.
Metabolism: ~50% of the dose is attributed to oxidative pathways, including N-dealkylation, O-deethylation, oxidation, and dehydrogenation, predominantly via CYP2C8 (98%), with a minor contribution via CYP2D6 (2%). Iptacopan undergoes phase 2 metabolism through glucuronidation via UGT1A1, UGT1A3, and UGT1A8. Iptacopan accounts for 83% of the drug-related species with 2 minor inactive acyl glucuronide metabolites (8% and 5%) detected in plasma.
Half-life elimination: ~25 hours (at steady state).
Time to peak: ~2 hours.
Excretion: Feces (71.5%; 16.8% as parent drug); Urine (24.8%; 17.9% as parent drug).
Clearance: 7.96 L/hour (at steady state).
Hepatic function impairment: Unbound iptacopan AUCinf was increased by 1.5-, 1.6-, and 3.7-fold in patients with mild (Child-Turcotte-Pugh class A), moderate (Child-Turcotte-Pugh class B), and severe (Child-Turcotte-Pugh class C) hepatic impairment, respectively (compared to subjects with normal hepatic function).
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