Fabhalta^® (Capsules) Instructions for Use

Marketing Authorization Holder

Novartis Pharma AG (Switzerland)

Manufactured By

Novartis Pharma Productions GmbH (Germany)

Packaging and Quality Control Release

NOVARTIS PHARMACEUTICAL MANUFACTURING, LLC (Slovenia)

ATC Code

L04AJ08 (Iptacopan)

Active Substance

Iptacopan (Rec.INN registered by WHO)

Dosage Form

Fabhalta®

Capsules 200 mg: 56 pcs.

Dosage Form, Packaging, and Composition

Capsules are hard, size No. 0, opaque, light yellow in color; the body is marked in black ink with “LNP200”, the cap is marked in black ink with “NVR”; capsule contents: powder from white or almost white to light violet-pink in color.

Excipients:
capsule shell gelatin, titanium dioxide (E171), iron oxide yellow (E172), iron oxide red (E172);
printing ink shellac (E904), iron oxide black (E172), propylene glycol (E1520), strong ammonia solution (E527), potassium hydroxide (E525).

14 pcs. – blisters (4) – cardboard packs.

Clinical-Pharmacological Group

Immunosuppressive drug

Pharmacotherapeutic Group

Immunosuppressants; complement inhibitors

Pharmacological Action

An inhibitor of the proximal part of the complement cascade, which targets factor B (FB) with selective inhibition of the alternative pathway of complement activation without affecting the lectin and classical pathways. Inhibition of factor B suppresses the activity of the alternative pathway C3 convertase and the subsequent formation of C5 convertase.

In paroxysmal nocturnal hemoglobinuria, intravascular hemolysis is mediated by membrane attack complex (MAC) reactions, whereas extravascular hemolysis is associated with C3 opsonization. Iptacopan acts on the proximal component of the alternative pathway of the complement cascade, blocking both C3-mediated extravascular hemolysis and terminal complement cascade-mediated intravascular hemolysis.

Pharmacokinetics

Following oral administration of iptacopan, C_max in plasma is reached in approximately 2 hours. When administered according to the recommended regimen of 200 mg twice daily, steady state is reached in approximately 5 days with minimal accumulation (1.4-fold). Iptacopan is characterized by concentration-dependent binding to plasma proteins due to targeted binding with factor B in the systemic circulation. At clinically significant plasma concentrations, the binding of iptacopan to plasma proteins in vitro ranged from 75% to 93%. After administration of iptacopan 200 mg twice daily, the apparent V_d at steady state was approximately 288 L. Approximately 50% of the dose is metabolized by oxidation.

The metabolism of iptacopan involves N- and O-dealkylation, oxidation, and dehydrogenation, occurring primarily via the CYP2C8 isoenzyme (98%) and to a lesser extent via the CYP2D6 isoenzyme (2%). Glucuronidation (UGT1A1, UGT1A3, UGT1A8) is a secondary metabolic pathway. In plasma, Iptacopan was the main component, accounting for 83% of the AUC_{0-48 h}. The only metabolites detected in plasma in minor amounts were two acyl glucuronides, accounting for 8% and 5% of the AUC_{0-48 h}, respectively. The metabolites of iptacopan are not considered pharmacologically active.

In a human study after a single oral dose of [¹⁴C]-iptacopan 100 mg, the mean total excretion of radioactive substances (iptacopan and metabolites) was 71.5% in feces and 24.8% in urine, giving a total mean excretion of >96% of the dose. Specifically, 17.9% of the dose was excreted in urine as unchanged iptacopan, and 16.8% in feces. The T_1/2 of iptacopan at steady state is approximately 25 hours after administration of iptacopan 200 mg twice daily.

Indications

As monotherapy for adults: paroxysmal nocturnal hemoglobinuria (PNH) with hemolytic anemia.

ICD codes

Dosage Regimen

Orally.

The recommended dose is 200 mg twice daily.

Paroxysmal nocturnal hemoglobinuria (PNH) is a disease that requires long-term treatment. Discontinuation of iptacopan treatment without clinical indications is not recommended.

When switching from other PNH drug therapy to iptacopan treatment, the dosing interval and mechanism of action of the previously used drugs should be taken into account.

Adverse Reactions

Infections and infestations very common – upper respiratory tract infection; common – urinary tract infection, bronchitis; uncommon – bacterial pneumonia.

Blood and lymphatic system disorders common – thrombocytopenia.

Nervous system disorders very common – headache, dizziness.

Gastrointestinal disorders very common – diarrhea; common – abdominal pain, nausea.

Skin and subcutaneous tissue disorders uncommon – urticaria.

Musculoskeletal and connective tissue disorders common – arthralgia.

Contraindications

Hypersensitivity to iptacopan; lack of vaccination against Neisseria meningitidis and Streptococcus pneumoniae, except when the risk of delaying iptacopan treatment outweighs the risk of developing an infection caused by these encapsulated bacteria; initiation of therapy in patients with an unresolved serious infection caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae type b.

Use in Pregnancy and Lactation

There are insufficient data on the use of iptacopan in pregnant women to determine the associated risks of major birth defects, miscarriage, and other adverse maternal or fetal outcomes. Lack of treatment for PNH during pregnancy is associated with risks to the mother and fetus. The use of iptacopan in pregnant women or women planning pregnancy may be considered after a risk-benefit assessment.

It is currently unknown whether Iptacopan passes into breast milk after oral administration. There are no data on the effects of iptacopan on the breastfed child or on milk production.

The benefits of breastfeeding for child development and health should be weighed against the mother’s need for iptacopan and any potential adverse effects (including serious infections caused by encapsulated bacteria) in the breastfed child due to the use of iptacopan or the mother’s underlying condition.

Use in Hepatic Impairment

Dosage adjustment in patients with hepatic impairment is not required.

Use in Renal Impairment

Dosage adjustment in patients with mild or moderate renal impairment is not required. Data on the use of iptacopan in patients with severe renal impairment or on hemodialysis are not available. Renal excretion is not a major route of elimination for iptacopan and its metabolites.

Pediatric Use

The safety and efficacy of iptacopan in children and adolescents under 18 years of age have not been established. No data are available.

Geriatric Use

Dosage adjustment in patients aged 65 years and older is not required.

Special Precautions

Healthcare professionals should inform patients with PNH about the importance of adhering to the dosing regimen to minimize the risk of hemolysis.

To reduce the risk of infections, all patients should be vaccinated against encapsulated bacteria, including Neisseria meningitidis and Streptococcus pneumoniae. Vaccination against Haemophilus influenzae type b is recommended if available. Vaccination should be completed at least 2 weeks before the first dose of iptacopan. If iptacopan treatment must be initiated before vaccination, the patient should be vaccinated as soon as possible. In this case, a prophylactic course of antibacterial therapy for up to 2 weeks is required after vaccination. Patients may be revaccinated as necessary in accordance with local vaccination guidelines.

Vaccination reduces, but does not completely eliminate, the risk of serious infections. A serious infection can quickly become life-threatening or fatal if not recognized and treated early. Patients should be informed about the early signs and symptoms of serious infections and monitored for the development of serious infections. If an infection is suspected, the patient should be immediately examined and given appropriate treatment. The use of iptacopan during treatment of a serious infection may be considered after a risk-benefit assessment.

After discontinuation of iptacopan therapy, the patient should be closely monitored for signs and symptoms of hemolysis for at least 2 weeks after the last dose. Such signs include: increased LDH activity accompanied by a sudden decrease in hemoglobin concentration or a decrease in PNH clone size, fatigue, hemoglobinuria, abdominal pain, dyspnea, dysphagia, erectile dysfunction, and major adverse vascular events (MAVE), including thrombosis. If discontinuation of iptacopan treatment is necessary, alternative treatment options should be considered.

If hemolysis occurs after discontinuation of iptacopan treatment, resumption of treatment should be considered.

The maximum duration of continuous use of iptacopan in conducted clinical studies can be up to 4 years.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.