Product information for ACTILYSE 20 mg :
In 2022, Boehringer implemented an improved manufacturing process for the active ingredient alteplase which made it free of gentamicin. As a result of this change, the previously included warning on hypersensitivity to gentamicin has been removed from the Product Information of Actilyse®.
BI is still producing Actilyse® vials containing traces of gentamicin for other countries. So as part of broader efforts to tackle global supply constraints of Lytics medicines, the Medicines & Healthcare products Regulatory Agency issued an exemption allowing production of specific batches of Actilyse® 20 mg with potential traces of gentamicin. These batches will be supplied to the United Kingdom alongside vials free of gentamicin.
Summary of Product Characteristics (SmPC): Actilyse® powder and solvent for solution for injection and infusion 20 mg
The following batch of Actilyse 20 mg (supplied with an additional sticker on the outer packaging), have been made available in the UK that have been manufactured using a previous manufacturing process that could result in trace residues of gentamicin being present in the product.
| Actilyse® 20 mg drug product batch | Expiry date |
|---|---|
| 205197 | 31.10.2025 |
The table below highlights the additional warnings that apply specifically to the presence of gentamicin in this batch compared to the information contained in the currently published SmPC that applies to all other batches of Actilyse 10 mg, 20 mg and 50 mg.
The other information in the current SmPC (see link below) remains valid for all other batches of product.
| Named batch of Actilyse® 20 mg | Current published SmPC dated 05/2023: All other batches of Actilyse® 10 mg, 20 mg, 50 mg | |
|---|---|---|
Section 4.3 Contraindications | Generally, in all indications Actilyse should not be administered to patients with known hypersensitivity to the active substance alteplase, gentamicin (a trace residue from the manufacturing process) or to any of the excipients listed in section 6.1. | Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. |
Section 4.4 Special Warnings and precautions for use | Hypersensitivity Immune-mediated hypersensitivity reactions associated with the administration of Actilyse can be caused by the active substance alteplase, gentamicin (a trace residue from the manufacturing process), or any of the excipients. No sustained antibody formation to the recombinant human tissue-type plasminogen activator molecule has been observed after treatment. There is no systematic experience with re-administration of Actilyse. Angio-oedema represents the most common hypersensitivity reaction reported with Actilyse. This risk may be enhanced in the indication acute ischaemic stroke and/or by concomitant treatment with ACE inhibitors (see section 4.5). Patients treated for any authorised indication should be monitored for angio‑oedema during and for up to 24h after infusion. If a severe hypersensitivity reaction (e.g. angio-oedema) occurs, the infusion should be discontinued and appropriate treatment promptly initiated. This may include intubation. | Hypersensitivity Immune-mediated hypersensitivity reactions associated with the administration of Actilyse can be caused by the active substance alteplase or any of the excipients. No sustained antibody formation to the recombinant human tissue-type plasminogen activator molecule has been observed after treatment. There is no systematic experience with re-administration of Actilyse. Angio-oedema represents the most common hypersensitivity reaction reported with Actilyse. This risk may be enhanced in the indication acute ischaemic stroke and/or by concomitant treatment with ACE inhibitors (see section 4.5). Patients treated for any authorised indication should be monitored for angio‑oedema during and for up to 24h after infusion. If a severe hypersensitivity reaction (e.g. angio-oedema) occurs, the infusion should be discontinued and appropriate treatment promptly initiated. This may include intubation. |
The corresponding patient information leaflet and information letter for hospitals and HCPs are available for download here.
Reporting adverse events
Adverse events should be reported. Reporting form and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Boehringer Ingelheim Drug Safety on 0800 328 1627 (freephone).