FABHALTA Dosage & Rx Info | Uses, Side Effects

Fabhalta Generic Name & Formulations

Legal Class

General Description

Iptacopan 200mg; caps.

Pharmacological Class

Complement inhibitor.

How Supplied

Caps—60

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

Manufacturer

Novartis Pharmaceuticals Corp

Generic Availability

Mechanism of Action

Iptacopan binds to Factor B of the alternative complement pathway and regulates the cleavage of C3, generation of downstream effectors, and the amplification of the terminal pathway. Iptacopan acts proximally in the alternative pathway of the complement cascade to control both C3b-mediated extravascular hemolysis and terminal complement-mediated intravascular hemolysis.

Fabhalta Indications

Indications

Paroxysmal nocturnal hemoglobinuria (PNH).

Fabhalta Dosage and Administration

Prior to Treatment Evaluations

Vaccinate patients against encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis (serogroups A, C, W, Y and B), and Haemophilus influenzae type B, according to current ACIP recommendations at least 2 weeks prior to initiation.

If urgent Fabhalta therapy is indicated in a patient who is not up to date with vaccines for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible.

Adult

Swallow whole. 200mg twice daily. Switching from eculizumab: initiate iptacopan no later than 1 week after the last dose of eculizumab. Switching from ravulizumab: initiate iptacopan no later than 6 weeks after the last dose of raviluzumab.

Children

Not established.

Fabhalta Contraindications

Contraindications

Unresolved serious infection caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae type B.

Fabhalta Boxed Warnings

Boxed Warning

Serious infections caused by encapsulated bacteria.

Fabhalta Warnings/Precautions

Warnings/Precautions

Increased risk of serious infections caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B. Complete or update vaccination against encapsulated bacteria at least 2 weeks prior to treatment. Give antibacterial prophylaxis if iptacopan must be initiated immediately and vaccines against encapsulated bacteria are not up-to-date. Monitor closely for signs of serious infections; evaluate immediately if infection is suspected. Consider interrupting iptacopan if undergoing treatment for serious infections. Monitor for hemolysis for at least 2 weeks after the last dose; if occurs, consider restarting iptacopan. Monitor serum lipid parameters periodically during therapy; initiate cholesterol-lowering medication if needed. Severe renal impairment (eGFR <30mL/min/1.73m²) with or without hemodialysis or severe hepatic impairment: not recommended. Pregnancy. Nursing mothers: not recommended (during and for 5 days after the last dose).

Pregnancy Considerations

Risk Summary

Insufficient data is available from clinical trials on the use of Fabhalta in pregnant women to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk: PNH during pregnancy is associated with adverse maternal outcomes.

Nursing Mother Considerations

Risk Summary

No data on the presence of iptacopan or its metabolite in either human or animal milk, the effects on the breastfed child or on milk production.
Discontinue breastfeeding during treatment and for 5 days after the last dose.

Pediatric Considerations

Safety and efficacay in pediatric patients with PNH have not been established.

Renal Impairment Considerations

Fabhalta is not recommended for use in patient with severe renal impairment (eGFR <30 mL/min/1.73m²) with or without hemodialysis.

No dose adjustment is required in patients with mild or moderate renal impairment.

Hepatic Impairment Considerations

Fabhalta is not recommended for use in patients with severe hepatic impairment.

No dose adjustement is required in patients with mild or moderate hepatic impairment.

REMS

YES

Fabhalta Pharmacokinetics

Absorption

Peak plasma concentrations reached ~2 hours post dose. Steady state is achieved in ~5 days.

Distribution

Apparent volume of distribution: ~288 L. Plasma protein bound: 75–93%.

Metabolism

N-dealkylation, O-deethylation, oxidation, and dehydrogenation, mostly driven by CYP2C8 (98%) with a small contribution from CYP2D6 (2%).

Elimination

Fecal (71.5%), renal (28.4%). Half-life: ~25 hours. Clearance: 7.96 L/h.

Fabhalta Interactions

Interactions

Antagonized by CYP2C8 inducers (eg, rifampin); monitor and discontinue CYP2C8 inducer if loss of efficacy for iptacopan is evident. Potentiated by strong CYP2C8 inhibitors (eg, gemfibrozil): not recommended.

Fabhalta Adverse Reactions

Adverse Reactions

Headache, nasopharyngitis, diarrhea, abdominal pain, bacterial infection, viral infection, nausea, rash; serious infections, hyperlipidemia.

Fabhalta Clinical Trials

Clinical Trials

The approval was based on data from the open-label, active comparator-controlled phase 3 APPLY-PNH trial (ClinicalTrials.gov Identifier: NCT04558918), which evaluated the efficacy and safety of iptacopan in 97 adults with PNH presenting with residual anemia despite treatment with anti-complement 5 (C5) treatment (eculizumab or ravulizumab) for at least 6 months prior to randomization.

Study participants were randomly assigned 8:5 to switch to iptacopan 200mg orally twice daily (n=62) or to continue anti-C5 treatment (n=35) throughout the duration of the 24-week randomized controlled period. The coprimary endpoints were the proportion of patients with sustained increase in hemoglobin levels from baseline of at least 2g/dL and sustained hemoglobin levels of at least 12g/dL, in the absence of red blood cell transfusions.

Findings showed that 82.3% of patients in the iptacopan arm demonstrated a sustained increase of hemoglobin levels from baseline of at least 2g/dL in the absence of transfusions compared with none of the patients in the anti-C5 arm (difference, 81.5%; P <.0001); 77.5% of complement inhibitor-naïve patients who received iptacopan met this outcome. Moreover, 67.7% of patients in the iptacopan arm achieved sustained hemoglobin levels of at least 12g/dL in the absence of transfusions vs 0% in the anti-C5 arm (difference, 66.6%; P <.0001).

Results for secondary endpoints included the following for iptacopan vs anti-C5, respectively:

Transfusion avoidance rates: 95.2% vs 45.7% (difference, 49.5%; P <.0001).
Hemoglobin change from baseline: 3.6g/dL vs -0.1g/dL (difference, 3.7; P <.0001).
Absolute reticulocyte count change from baseline (10⁹/L): -116 vs 0 (difference, -116; P <.0001).

Fabhalta Note

Notes

Available only through a restricted Fabhalta REMS program. To enroll or for more information call (833) 993-2242 or visit www.Fabhalta-REMS.com.

Fabhalta Patient Counseling

Patient Counseling

Serious Infections Caused by Encapsulated Bacteria

Risk of serious infection. Advise patients to complete or update their vaccinations against encapsulated bacteria at least 2 weeks prior to receiving the first dose of Fabhalta or receive antibacterial drug prophylaxis if Fabhalta treatment must be initiated immediately and they have not been previously vaccinated.
Advise patients to revaccinate according to current ACIP recommendations for encapsultated bacterial during therapy.
Advise patients to carry their Patient Safety Card for Fabhalta at all times during and for 2 weeks after treatment. The card describes symptoms, which if occurs, should prompt the patient to seek immediate medical evaluation.

Fabhalta REMS

Fabhalta is available only through a retricted program called Fabhalta REMS.

Discontinuation

Advise the risk of serious hemolysis due to PNH if Fabhalta is discontinued. Health care providers should monitor patients for at least 2 weeks after discontinuations of Fabhalta.
Patients should keep the Patient Safety Card with them for 2 weeks after discontinuing Fabhalta after the last dose. Increased risk for serious infection for a few weeks after the last dose.

Hyperlipidemia

Advise patients that their cholesterol and triglycerides may increase and should be monitored periodically during treatment.

Cost Savings Program

Novartis Patient Support

Fabhalta

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