BCG Apogepha 100 mg - Beipackzettel, Nebenwirkungen, Wirkung, Anwendungsgebiete

MAH: APOGEPHA Arzneimittel GmbH; RMP vs. 0.3; Data Lock point: 30 November 2021; Final sign off: 23 November 2021

This is a summary of the risk management plan (RMP) for BCG Apogepha 50/100 mg. The RMP details important risks of BCG Apogepha 50/100 mg, how these risks can be minimised, and how more information will be obtained about risks and uncertainties (missing information) of BCG Apogepha 50/100 mg.

BCG Apogepha 50/100 mg summary of product characteristics (SmPC) and its package leaflet give essential information to healthcare professionals and patients on how BCG Apogepha 50/100 mg should be used.

Important new concerns or changes to the current version will be included in updates.

• I. The medicine and what it is used for

BCG Apogepha 50 mg/100mg:

Treatment of superficial, epithelial non-invasive urothelial carcinomas (carcinoma urotheliale Ta, Tis, T1).

BCG Apogepha 50/100 mg contains live attenuated Bacillus Calmette-Guerin, Brazilian BCG Moreau substrain, as the active substance and is administered intravesically in the urinary bladder.

• II. Risks associated with the medicine and activities to minimise or further characterise the risks

Important risks of BCG Apogepha 50/100 mg, together with measures to minimise such risks and the proposed studies for learning more about BCG Apogepha 50/100 mg risks, are outlined below.

Measures to minimise the risks identified for the medicinal product BCG Apogepha 50/100 mg can be:

• Specific information, such as warnings, precautions, interactions, advice during pregnancy and lactation, clinical measures or advice on correct use are included in the package leaflet (section 2 and 3) and SmPC (section 4.1 to 4.9) addressed to patients and healthcare professionals;
• Important advice on the medicine’s pac­kaging, such as warnings, advice on correct use, correct storage or disposal are pointed out on the outer carton;
• The authorised pack size – the amount of medicine in a pack is chosen so to ensure that the medicine is used correctly;
• The medicine’s legal status — BCG Apogepha 50/100 mg is supplied to the patient with prescription only. Its use is restricted to physicians experienced in this therapy with strict indication.

Together, these measures constitute routine risk minimisation measures.

In the case of BCG Apogepha 50/100 mg, these measures are supplemented with additional risk minimisation measures mentioned under relevant important risks, below.

In addition to these measures, information about adverse reactions is collected continuously and regularly analysed, so that immediate action can be taken as necessary. These measures constitute routine pharmacovigilance activities.

• II.A List of important risks and missing information

Important risks of BCG Apogepha 50/100 mg are risks that need special risk management activities to further investigate or minimise the risk, so that the medicinal product can be safely administered.

Important risks can be regarded as identified or potential. Identified risks are concerns for which there is sufficient proof of a link with the use of BCG Apogepha 50/100 mg.

Potential risks are concerns for which an association with the use of this medicine is possible based on available data, but this association has not been established yet and needs further evaluation.

Missing information refers to information on the safety of the medicinal product that is currently missing and needs to be collected (e.g. on the long-term use of the medicine).

Table II.A: Summary of important risks and missing information

Summary of safety concerns
Important identified risks	Severe systemic BCG infection / reaction, incl.: – BCG sepsis, granulomatous pulmonary or hepatic reactions – Abscesses (e.g., skin, renal, psoas), infected aneurysms, BCG infection of implants and surrounding tissue (e.g., aortic graft infection, cardiac defibrillator, hip or knee arthroplasty) – Reiter’s syndrome – Chorioretinitis, conjunctivitis, uveitis – Haemophagocytic syndrome Missing or delayed diagnosis of severe systemic BCG infection / reaction Bladder contracture Oligospermia, azoospermia
Important potential risks	None
Missing information	None

• II.B Summary of important risks

Tables II.B: Summary of important risks

Important identified risk: Severe systemic BCG infection / reaction , incl.: – BCG sepsis, granulomatous pulmonary or hepatic reactions – Abscesses (e.g., skin, renal, psoas), infected aneurysms, BCG infection of implants and surrounding tissue (e. g. aortic graft infection, cardiac defibrillator, hip or knee arthroplasty) – Reiter’s syndrome – Chorioretinitis, conjunctivitis, uveitis – Haemophagocytic syndrome
Evidence for linking the risk to the medicine	SmPC; Published data
Risk factors and risk groups	Traumatic catheterisation or instillations given too early after transurethral resection; underlying immunosuppression; advanced age; poor general status; HLA-B27 positivity
Risk minimisation measures	Routine risk minimisation measures: SmPC section 4.2, 4.4 and 4.8 PL section 2 and 4 Prescription medicine only Additional risk minimisation measures: None

Important identified risk: Missing or delayed diagnosis of severe systemic BCG infection / reaction
Evidence for linking the risk to the medicine	SmPC; Published data
Risk factors and risk groups	Long latency period between BCG exposure and systemic BCG infection and non-specific symptoms of the disease. In elderly or debilitated patients correct and early diagnosis is particularly important to avoid fatal consequences

Risk minimisation measures

Routine risk minimisation measures: SmPC section 4.4 and 4.8. PL section 4 Prescription medicine only Additional risk minimisation measures: Patient Alert Card

Important identified risk: Bladder contracture
Evidence for linking the risk to the medicine	SmPC; Published data
Risk factors and risk groups	BCG induced bladder contracture appears to be associated with multiple transurethral resections and maintenance instillations. The risk of bladder contracture may increase in patients with low bladder capacity.
Risk minimisation measures	Routine risk minimisation measures: SmPC section 4.4 and 4.8. PL section 4 Prescription medicine only Additional risk minimisation measures: None

Important identified risk: Oligospermia, azoospermia
Evidence for linking the risk to the medicine	SmPC; Published data
Risk factors and risk groups	Young male patients
Risk minimisation measures	Routine risk minimisation measures: SmPC section 4.6 and 4.8. PL section 4 Prescription medicine only Additional risk minimisation measures: None

II.C Post-authorisation development plan

II.C.1 Studies which are conditions of the marketing authorisation

Not applicable, since there are no studies which are conditions of the marketing authorisation or specific obligation of BCG Apogepha 50/100 mg.

II.C.2 Other studies in post-authorisation development plan

Not applicable, since there are no studies required for BCG Apogepha 50/100 mg.