FABHALTA™ NSS - Oman
FABHALTA™ NSS - Oman
Regulatory Affairs
FABHALTA™ (iptacopan)
200 mg Hard capsules
National Succinct Statement (NSS)
Version 1.4
Effective date: 25-Feb-2025
Safety Label Change (SLC) N/A – No changes compared to previous version
Tracking number:
Document status: Final
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FABHALTA™
Important note: Before prescribing, consult full prescribing information: US: https://www.fda.gov/
Disclaimer: This link will contain the most updated product information approved by the reference country.
Presentation:
Hard capsules containing 200mg of iptacopan (as iptacopan hydrochloride monohydrate)
Indications:
Paroxysmal Nocturnal Hemoglobinuria
FABHALTA is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH).
Immunoglobulin A Nephropathy
FABHALTA is indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to- creatinine ratio (UPCR) ≥1.5 g/g.
This indication is approved under accelerated approval based on reduction of proteinuria. It has not been established whether FABHALTA slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial.
Complement 3 Glomerulopathy
FABHALTA is indicated for the treatment of adults with complement 3 glomerulopathy (C3G), to reduce proteinuria.
Dosage and administration:
Recommended Vaccination and Prophylaxis for Encapsulated Bacterial Infections
Vaccinate patients against encapsulated bacteria, including Streptococcus pneumoniae and Neisseria meningitidis (serogroups A, C, W, Y and B), according to current ACIP recommendations at least 2 weeks prior to initiation of FABHALTA.
If urgent FABHALTA therapy is indicated in a patient who is not up to date with vaccines for Streptococcus pneumoniae and Neisseria meningitidis according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible.
Recommended Dosage
The recommended dosage of FABHALTA is 200 mg orally twice daily without regard to food. Swallow capsules whole. Do not open, break, or chew capsules.
If a dose or doses are missed, advise the patient to take one dose of FABHALTA as soon as possible (even if it is soon before the next scheduled dose) and then to resume the regular dosing schedule.
PNH Patients Switching From Anti-C5 (eculizumab, ravulizumab) to FABHALTA
To reduce the potential risk of hemolysis with abrupt discontinuation of other PNH therapies:
For patients switching from eculizumab, initiate FABHALTA no later than 1 week after the last dose of eculizumab.
For patients switching from ravulizumab, initiate FABHALTA no later than 6 weeks after the last dose of ravulizumab.
There is no available information regarding the timeframe for initiation of FABHALTA after other PNH therapies.
Contraindications:
♦ Hypersensitivity to iptacopan or to any of the excipients. ♦ For initiation in patients with unresolved serious infection caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae type B.
Warnings and precautions:
Serious infections caused by encapsulated bacteria:
♦ Complement inhibitors such as Fabhalta may predispose individuals to serious, life- threatening, or fatal infections. ♦ To reduce the risk of infection, patients must be vaccinated against encapsulated bacteria, including Neisseria meningitidis and Streptococcus pneumoniae. It is recommended to vaccinate against Haemophilus influenzae type B if available. ♦ Vaccines should be administered at least 2 weeks prior to administration of the first dose of Fabhalta. ♦ If Fabhalta must be initiated prior to vaccination, administer the vaccine as soon as possible after the first dose of Fabhalta and provide patients with antibacterial drug prophylaxis until 2 weeks after vaccination. ♦ If necessary, patients may be revaccinated. ♦ Patients should be informed of and monitored for early signs and symptoms of serious bacterial infection. ♦ Immediately evaluate and treat patients if a bacterial infection is suspected.
Monitoring PNH Manifestations after Discontinuation of Fabhalta:
♦ Monitor patients for at least two weeks for signs and symptoms of hemolysis. ♦ Signs and symptoms include elevated lactate dehydrogenase (LDH) levels, along with sudden decrease in hemoglobin or PNH clone size, fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events (including thrombosis), dysphagia, or erectile dysfunction. ♦ Consider alternative therapy if discontinuation of Fabhalta is necessary. ♦ Consider restarting Fabhalta if hemolysis occurs.
Hyperlipidemia
FABHALTA may increase total cholesterol, LDL-cholesterol, and serum triglycerides.
Of the 54 FABHALTA-treated patients who had a normal total cholesterol level at baseline in APPLY-PNH, 43% developed Grade 1 hypercholesterolemia during the randomized treatment period. One FABHALTA- treated patient in APPLY-PNH experienced increased total cholesterol that worsened to Grade 2 from Grade 1 at baseline.
Of the 34 FABHALTA-treated patients who had a normal cholesterol level at baseline in APPOINT-PNH, 24% developed Grade 1 hypercholesterolemia during the core treatment period.
Of the 60 FABHALTA-treated patients who had LDL-cholesterol ≤ 130 mg/dL at baseline in APPLY-PNH, 17% developed LDL-cholesterol > 130-160 mg/dL, 8% developed LDL- cholesterol > 160-190 mg/dL, and 7% developed LDL-cholesterol > 190 mg/dL during the randomized treatment period. Of the 36 FABHALTA- treated patients who had LDL- cholesterol ≤ 130 mg/dL at baseline in APPOINT-PNH, 11% developed LDL-
cholesterol > 130-160 mg/dL and 3% developed LDL-cholesterol > 160-190 mg/dL.
Of the 52 patients with normal triglyceride levels at baseline in APPLY-PNH, 23% developed Grade 1 elevated triglycerides during the randomized treatment period. Three FABHALTA- treated patients in APPLY-PNH experienced an increase in triglycerides from Grade 1 to Grade 2.
Of the 37 FABHALTA-treated patients who had a normal triglyceride level at baseline in APPOINT-PNH, 27% developed Grade 1 elevated triglycerides in the core treatment period.
Of the 102 FABHALTA-treated patients in APPLY-PNH and APPOINT-PNH, two patients required cholesterol-lowering medications.
Monitor serum lipid parameters periodically during treatment with FABHALTA and initiate cholesterol- lowering medication, if indicated.
Pregnancy, lactation, females and males of reproductive potential
Pregnancy: Animal reproduction studies have not shown risk of increased fetal abnormalities. There are risks to the mother and fetus associated with untreated PNH and C3G. May consider use in pregnant women or women planning to become pregnant following an assessment of the risks and benefits.
Lactation: There are no data on the presence of iptacopan or its metabolites in either human or animal milk, the effects on the breastfed child or on milk production. Since many medicinal products are secreted into human milk, and because of the potential for serious adverse reactions in a breastfed child, breastfeeding should be discontinued during treatment and for 5 days after the final dose.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Paroxysmal Nocturnal Hemoglobinuria (PNH)
The data described below reflects the exposure in adults with PNH who received FABHALTA (n = 62) or anti- C5 treatment (US-approved and non-US-approved eculizumab product or US-approved and non-US-approved ravulizumab product, n = 35) in APPLY-PNH [NCT04558918] and adults who received FABHALTA (n = 40) in APPOINT-PNH [NCT04820530] at the recommended dosing regimen for 24 weeks. In APPLY-PNH, serious adverse reactions were reported in 2 (3%) patients with PNH receiving FABHALTA. Serious adverse reactions included pyelonephritis, urinary tract infection and COVID-19. In APPOINT-PNH, serious adverse reactions were reported in 2 (5%) patients with PNH receiving FABHALTA. Serious adverse reactions included COVID-19 and bacterial pneumonia. The most common adverse reactions (≥ 10%) with FABHALTA were headache, nasopharyngitis, diarrhea, abdominal pain, bacterial infection, viral infection, nausea, and rash.
Table 1 describes the adverse reactions that occurred in > 5% of patients treated with FABHALTA in the APPLY-PNH or APPOINT-PNH studies.
Table 1: Adverse Reactions Reported in > 5% of Patients Treated with FABHALTA in APPLY-PNH or APPOINT-PNH Studies (24-Week Treatment Period)
Adverse reactions | APPLY-PNH | APPOINT-PNH | |
| FABHALTA (N = 62) n (%) | Anti-C5 (Eculizumab or Ravulizumab) (N = 35) n (%) | FABHALTA (N = 40) n (%) |
Headachea | 12 (19) | 1 (3) | 11 (28) |
Nasopharyngitisb | 10 (16) | 6 (17) | 6 (15) |
Diarrhea | 9 (15) | 2 (6) | 3 (8) |
Abdominal paina | 9 (15) | 1 (3) | 3 (8) |
Bacterial infectionc | 7 (11) | 4 (11) | 2 (5) |
Nausea | 6 (10) | 1 (3) | 2 (5) |
Viral infectiond | 6 (10) | 11 (31) | 7 (18) |
Arthralgia | 5 (8) | 1 (3) | 0 |
Thrombocytopeniaa | 4 (6) | 0 | 0 |
Dizziness | 4 (6) | 0 | 1 (3) |
Systemic hypertensiona | 4 (6) | 0 | 0 |
Lipid disordere | 4 (6) | 0 | 3 (8) |
Rashf | 2 (3) | 0 | 4 (10) |
aIncludes similar terms. bNasopharyngitis contains: rhinitis allergic, upper respiratory tract infection, pharyngitis, rhinitis. cBacterial infection contains: pyelonephritis, urinary tract infection, bronchitis bacterial, bronchitis haemophilus, cholecystitis, folliculitis, cellulitis, arthritis bacterial, sepsis, klebsiella infection, staphylococcal infection, Pseudomonas infection, hordeolum, pneumonia bacterial. dViral infection contains: COVID-19, herpes zoster, oral herpes, nasal herpes, influenza A virus test positive, influenza. eLipid disorder contains: dyslipidemia, blood cholesterol increased, low density lipoprotein increased, hypercholesterolemia, blood triglycerides increased, hyperlipidemia. fRash contains: dermatitis allergic, acne, erythema multiforme, rash maculo-papular, rash erythematous. | |||
Clinically relevant adverse reactions reported in less than or equal to 5% of patients includes urticaria in one patient (3%) in APPOINT-PNH.
Description of Select Adverse Reactions (graded per NCI CTCAE Version 4.03 unless noted otherwise)
Platelet Count Decreased
Of the 37 FABHALTA-treated patients who had normal platelet counts at baseline in APPLY-PNH, 43% experienced any Grade thrombocytopenia during the randomized treatment period. Three FABHALTA-treated patients in APPLY-PNH experienced decreased platelets that worsened to Grade ≥ 3 from baseline (one patient with normal platelets that worsened to Grade 4, one patient with baseline Grade 1 that worsened to Grade 4, and one patient with baseline Grade 3 that worsened to Grade 4).
Immunoglobulin A Nephropathy (IgAN)
The safety of FABHALTA was evaluated in APPLAUSE-IgAN, a randomized placebo- controlled, double-blind clinical study in adults with IgAN (eGFR ≥ 20 mL /min/1.73 m2 at baseline).
The data below reflect FABHALTA exposure in 235 patients with IgAN (eGFR ≥ 20 mL/min/1.73 m2 at baseline) with a median duration of 43 weeks (up to 104 weeks) in APPLAUSE-IgAN. Table 2 describes the adverse reactions that occurred in ≥ 3 % of patients treated with FABHALTA and were ≥ 2% higher in frequency than placebo. All of these adverse reactions were mild or moderate in severity.
Table 2: Adverse Reactions Reported in ≥ 3% of Adult Patients with IgAN (eGFR ≥ 20 mL /min/1.73 m2) Treated with FABHALTA and ≥ 2% Higher in Frequency Than Placebo in APPLAUSE-IgAN
Adverse reaction | FABHALTA (N = 235) n (%) | Placebo (N = 235) n (%) |
Upper respiratory tract infection | 20 (9) | F16 (7) |
Lipid disorder1 | 15 (6) | 10 (4) |
Abdominal pain1 | 15 (6) | 5 (2) |
Nausea | 8 (3) | 2 (1) |
Dizziness | 7 (3) | 2 (1) |
1 Includes similar terms. | ||
Complement 3 Glomerulopathy (C3G)
The safety of FABHALTA was evaluated in APPEAR-C3G, a randomized, placebo- controlled, double-blind trial in adult patients with native kidney C3G. No new adverse reactions were identified during the 6-month placebo-controlled period of APPEAR-C3G, in which 38 patients were treated with FABHALTA and 36 patients were treated with placebo. The most common adverse reactions that occurred in ≥ 10% of patients treated with FABHALTA and were ≥ 5% higher in frequency than placebo were nasopharyngitis (11% in FABHALTA, 3% placebo) and viral infections (29% in FABHALTA, 22% placebo), mainly respiratory infections. One patient (3%) on FABHALTA and none on placebo had a serious adverse reaction of pneumonia and bacteremia secondary to an encapsulated organism (S. pneumoniae).
Interactions:
CYP2C8 Inducers
Concomitant use of CYP2C8 inducers (e.g., rifampin) may decrease iptacopan exposure, which may result in loss of or reduced efficacy of FABHALTA. Monitor the clinical response and discontinue use of the CYP2C8 inducer if loss of efficacy of FABHALTA is evident.
Strong CYP2C8 Inhibitors
Concomitant use of strong CYP2C8 inhibitors (e.g., gemfibrozil) may increase iptacopan exposure, which may result in an increased risk for adverse reactions with FABHALTA. Coadministration with a strong CYP2C8 inhibitor is not recommended.
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Leaflet revision date: March 2025.
NSS version number: 1.4
Leaflet presentation: R02