Fabhalta Iptacopan Hydrochloride Capsules

1. Indications and Usage
Paroxysmal Nocturnal Hemoglobinuria (PNH):
Treatment of adult patients with PNH.
IgA Nephropathy (IgAN):
Treatment to reduce proteinuria and slow the decline in estimated glomerular filtration rate (eGFR) in adults at risk of rapid disease progression.
C3 Glomerulopathy (C3G):
Treatment of adults with C3G, including C3 glomerulonephritis and dense deposit disease.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY.
Recommended Dosage:
Standard Dose: 200 mg taken orally twice daily.
Administration:
Swallow capsules whole; do not open, crush, or chew.
Can be taken with or without food.
Missed Dose: If a dose is missed, take it as soon as remembered unless it is close to the next scheduled dose. Do not double the dose to make up for a missed one.
Special Populations:
Renal Impairment: Not recommended for patients with severe renal impairment (eGFR <30 mL/min/1.73 m²).
Hepatic Impairment: Not recommended for patients with severe hepatic impairment (Child-Pugh C).
3. Mechanism of Action
Complement Factor B Inhibition:
Iptacopan is a small molecule that binds directly and reversibly to Complement Factor B.
Pathway Modulation:
By inhibiting Factor B, iptacopan prevents the formation of the alternative pathway C3 convertase, thereby reducing downstream effector generation and terminal complement amplification.
Dual Control in PNH:
It controls both intravascular hemolysis (mediated by Membrane Attack Complex) and extravascular hemolysis (mediated by C3b opsonization) by acting proximally in the complement cascade.
4. Safety and Warnings
Serious Infections (Boxed Warning):
Iptacopan increases the risk of serious or fatal infections caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b.
Vaccination Requirements:
Patients must be vaccinated against encapsulated bacteria according to current clinical guidelines prior to initiating treatment.
Contraindications:
Active serious infection caused by encapsulated bacteria.
History of hypersensitivity to iptacopan or any excipients.
Monitoring:
Monitor for signs and symptoms of hemolysis if treatment is discontinued. Close monitoring is required for at least 2 weeks after stopping therapy in PNH patients.
5. Adverse Reactions
Most Common (PNH):
Headache, nasopharyngitis, diarrhea, abdominal pain, nausea, bacterial infections, viral infections, rash, and decreased platelet count.
Most Common (IgA Nephropathy):
Upper respiratory tract infections, dyslipidemia, and abdominal pain.
Most Common (C3G):
Nasopharyngitis and viral infections.
Laboratory Abnormalities:
Decreased platelet count, increased cholesterol/lipids, and elevated liver enzymes have been observed.
6. Drug Interactions
CYP2C8 Substrates/Inducers/Inhibitors:
Iptacopan is metabolized primarily by CYP2C8.
Strong CYP2C8 Inducers (e.g., Rifampin): May significantly decrease iptacopan exposure, leading to reduced efficacy. Avoid concomitant use or monitor closely.
Strong CYP2C8 Inhibitors (e.g., Gemfibrozil): May increase iptacopan exposure, increasing the risk of adverse reactions. Avoid concomitant use or consider dose reduction.
Oral Contraceptives:
Interaction has not been fully established; additional non-hormonal contraception is recommended for women of childbearing potential.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Iptacopan hydrochloride.
Available Strength: 200 mg capsules.
Appearance:
Light yellow opaque hard gelatin capsule, printed with “LNP200” on the body and “NVR” on the cap.
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).
Keep in the original package to protect from moisture.