FABHALTA Hard capsule Ref.[110453] Active ingredients: Iptacopan

Serious infections caused by encapsulated bacteria

The use of complement inhibitors, such as iptacopan, may predispose individuals to serious, lifethreatening or fatal infections caused by encapsulated bacteria. To reduce the risk of infection, all patients must be vaccinated against encapsulated bacteria, including Neisseria meningitidis and Streptococcus pneumoniae. It is recommended to vaccinate patients against Haemophilus influenzae type B if vaccine is available. Healthcare professionals should refer to local vaccination guideline recommendations.

Vaccines should be administered at least 2 weeks prior to administration of the first dose of iptacopan. If treatment must be initiated prior to vaccination, patients should be vaccinated as soon as possible and provided with antibacterial prophylaxis until 2 weeks after vaccine administration.

If necessary, patients may be revaccinated in accordance with local vaccination guideline recommendations.

Vaccination reduces, but does not eliminate, the risk of serious infection. Serious infection may rapidly become life-threatening or fatal if not recognised and treated early. Patients should be informed of and monitored for early signs and symptoms of serious infection. Patients should be immediately evaluated and treated if infection is suspected. The use of iptacopan during treatment of serious infection may be considered following an assessment of the risks and benefits (see section 4.8).

PNH laboratory monitoring

Patients with PNH receiving iptacopan should be monitored regularly for signs and symptoms of haemolysis, including measuring lactate dehydrogenase (LDH) levels.

Monitoring of PNH manifestations after treatment discontinuation

If treatment must be discontinued, patients should be closely monitored for signs and symptoms of haemolysis for at least 2 weeks after the last dose. These signs and symptoms include, but are not limited to, elevated LDH levels along with sudden decrease in haemoglobin or PNH clone size, fatigue, haemoglobinuria, abdominal pain, dyspnoea, dysphagia, erectile dysfunction, or major adverse vascular events (MAVEs), including venous or arterial thrombosis. If treatment discontinuation is necessary, alternative therapy should be considered.

If haemolysis occurs after discontinuation of iptacopan, restarting treatment should be considered.

Co-administration with other medicinal products

Concomitant use of iptacopan with strong inducers of CYP2C8, UGT1A1, PgP, BCRP and OATP1B1/3 has not been studied clinically; therefore, concomitant use is not recommended due to the potential for reduced efficacy of iptacopan (see section 4.5). If an alternative concomitant medicinal product cannot be identified, patients should be monitored for potential signs and symptoms of haemolysis.

Educational materials

All physicians who intend to prescribe FABHALTA must ensure they have received and are familiar with the physician educational materials. Physicians must explain and discuss the benefits and risks of FABHALTA therapy with the patient and provide them with the patient information pack. The patient should be instructed to seek prompt medical care if they experience any sign or symptom of serious infection or serious haemolysis following treatment discontinuation.

Effects of other medicinal products on iptacopan

Strong inducers of CYP2C8, UGT1A1, PgP, BCRP and OATP1B1/3

Although concomitant administration of iptacopan with strong inducers of CYP2C8, UGT1A1, PgP, BCRP and OATP1B1/3, such as rifampicin, has not been studied clinically, concomitant use with iptacopan is not recommended due to the potential for reduced efficacy of iptacopan (see section 4.4).

Effects of iptacopan on other medicinal products

CYP3A4 substrates

In vitro data showed iptacopan has potential for induction of CYP3A4 and may decrease the exposure of sensitive CYP3A4 substrates. The concomitant use of iptacopan and sensitive CYP3A4 substrates has not been studied clinically. Caution should be exercised if co-administration of iptacopan with sensitive CYP3A4 substrates is required, especially for those with a narrow therapeutic index (e.g. carbamazepine, ciclosporin, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus).

CYP2C8 substrates

In vitro data showed iptacopan has potential for time-dependent inhibition of CYP2C8 and may increase the exposure of sensitive CYP2C8 substrates, such as repaglinide, dasabuvir or paclitaxel. The concomitant use of iptacopan and sensitive CYP2C8 substrates has not been studied clinically. Caution should be exercised if co-administration of iptacopan with sensitive CYP2C8 substrates is required.

Pregnancy

There are no or limited amount of data from the use of iptacopan in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity at exposures between 2- and 8-fold the human exposure at the maximum recommended human dose (MRHD) (see section 5.3).

PNH in pregnancy is associated with adverse maternal outcomes, including worsening cytopenias, thrombotic events, infections, bleeding, miscarriages and increased maternal mortality, as well as adverse foetal outcomes, including foetal death and premature delivery.

The use of iptacopan in pregnant women or women planning to become pregnant may only be considered following a careful assessment of the risk and benefits, if necessary.

Breast-feeding

It is unknown whether iptacopan is excreted in human milk. There are no data on the effects of iptacopan on the breast-fed newborn/infant or on milk production.

A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from FABHALTA therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility

There are no data on the effect of iptacopan on human fertility. Available non-clinical data do not suggest an effect of iptacopan treatment on fertility (see section 5.3).

FABHALTA has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most commonly reported adverse reactions were upper respiratory tract infection (18.9%), headache (18.3%) and diarrhoea (11.0%). The most commonly reported serious adverse reaction was urinary tract infection (1.2%).

Tabulated list of adverse reactions

Table 1 shows the adverse reactions observed in the clinical studies with iptacopan in patients with PNH. Adverse reactions are listed by MedDRA system organ class (SOC) and frequency, using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000) or very rare (<1/10 000).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1. Adverse reactions:

¹ Upper respiratory tract infection includes preferred terms influenza, nasopharyngitis, pharyngitis, rhinitis, sinusitis, and upper respiratory tract infection.
² Urinary tract infection includes preferred terms urinary tract infection and cystitis escherichia.
³ Bronchitis includes preferred terms bronchitis, bronchitis haemophilus and bronchitis bacterial.
⁴ Headache includes preferred terms headache and head discomfort.
⁵ Abdominal pain includes preferred terms abdominal pain, abdominal pain upper, abdominal tenderness and abdominal discomfort.

Description of selected adverse reactions

Platelet count decreased

Decrease in platelet count events was reported in 12/164 (7%) patients with PNH. Of these, 5 patients had events of mild severity, 5 had moderate events and 2 had severe events. Patients with severe events had concurrent anti-platelet antibodies or idiopathic bone marrow aplasia with pre-existing thrombocytopenia. The events started within the first 2 months of iptacopan treatment in 7/12 patients, and after a longer exposure (111 to 951 days) in 5/12 patients. At the cut-off date, 7 (58%) patients had recovered or events were resolving and iptacopan treatment was continued throughout in all patients.

Infections

In PNH clinical studies 1/164 (0.6%) PNH patients reported serious bacterial pneumonia while receiving treatment with iptacopan; the patient had been vaccinated against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type B and recovered following treatment with antibiotics while continuing treatment with iptacopan.

Blood cholesterol and blood pressure increases

In patients treated with iptacopan 200 mg twice a day in PNH clinical studies, mean increases from baseline of approximately 0.7 mmol/l were seen at month 6 for total cholesterol and LDL-cholesterol. The mean values remained within the normal ranges. Increases in blood pressure, particularly diastolic blood pressure (DBP), were observed (mean increase 4.7 mmHg at month 6). The mean DBP did not exceed 80 mmHg. Total cholesterol, LDL-C and DBP increases correlated with increases in haemoglobin (improvement in anaemia) in patients with PNH (see section 5.1).

Heart rate decrease

In patients treated with iptacopan 200 mg twice a day in PNH clinical studies, a mean decrease in heart rate of approximately 5 bpm was seen at month 6 (mean of 68 bpm).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Not applicable.