European Haemophilia Consortium (EHC) (2024)

The European Haemophilia Consortium (EHC) would like to update its February 2021 statement concerning the international recall of all Ferring Pharmaceutical Limited nasal sprays containing desmopressin, including Octim®, Octostim®, Desmospray®, DDAVP Spray® and Stimate®.

On 31 May 2022, Ferring Pharmaceuticals Limited informed the EHC that the above products would not be back onto the European market until mid-2024, at the earliest.

The EHC, on behalf of its members, responded to the company and outlined the frustration and disappointment of the community in the lack of availability of safe and efficacious home treatment options. The EHC stressed that although alternatives exist they cannot be used at home by patients and this results in absences from work and school and an adverse impact on patients’ health due to the delays in managing bleeds. The EHC strongly encouraged the company to make any effort necessary to bring these products back on the market sooner.

Ferring explained that this delay is due to procuring, installing and qualifying a new production line for the manufacturing of Minirin® (desmopressin) Nasal Spray 0.1 mg/ml room temperature stable (RTS) formulation and Octostim® (desmopressin) Nasal Spray 1.5 mg/ml. At the earliest, the company estimates that these changes, together with changes to the product package material, will result in product deliveries in the second half of 2024.

This concerns the following products:

• Minirin® (desmopressin) Nasal Spray 0.1 mg/ml room temperature stable (RTS) formulation
• Octostim® (desmopressin) Nasal Spray 1.5 mg/ml
• DDAVP® (desmopressin acetate, 10 mcg/0.1 mL)
• Stimate® (desmopressin acetate, 1.5 mg/1 mL) Nasal Spray
• Generic Desmopressin Acetate (10 mcg/0.1mL) Nasal Spray

Ferring continues to manufacture the following desmopressin products, whose availability varies by market:

• Minirin® (desmopressin) Nasal Spray 0.1 mg/ml Cold Storage Formulation
• Desmopressin Oral (tablet and oral lyophilizate) formulations
• Desmopressin Injectable formulations

In addition, other dosage forms of desmopressin acetate are available from other manufacturers.

Healthcare providers can contact their pharmacies and/or the manufacturers of these dosage forms for information about these alternatives’ availability.

Background

• Desmopressin (1-deamino-8-D-arginine vasopressin, also known as DDAVP) is a synthetic analogue of vasopressin that boosts plasma levels of factor VIII and von Willebrand factor¹
• Desmopressin may be the treatment of choice for patients with mild or moderate haemophilia A, including carriers, and many patients withvon Willebrand disease (VWD), particularly those with type 1 VWD¹
• Though desmopressin may be given subcutaneously, it is primarily administered by intravenous infusion or nasal spray¹
• Ferring Pharmaceuticals initiated a worldwide precautionary recall of its desmopressin nasal sprays in mid-July 2020, including the formulation used in the treatment of mild/moderate haemophilia and VWD (Octostim®, Octim®, Stimate® by CSL Behring, and other brand names worldwide)
• The withdrawn formulations contained higher than specified concentrations of desmopressin
• Recall announcements were issued around the world from July 10 to August 5 by different parties: Ferring Pharmaceuticals, national regulatory authorities, ministries of health, and distributors
• The recall level (i.e., pharmacy or patient-level) and formulations were withdrawn at the national level vary according to local regulatory decisions and requirements
• Although the majority of countries have issued pharmacy-level recalls, patients may consider returning the unused product to the pharmacy after consulting their treatment centres
• Ferring completed its internal investigation and identified the cause of the issue in relation to the tightness of bottle seals
• Ferring announced a complete overhaul of its production line with planned resuming of manufacturing of desmopressin products to Q2/2023 and supply to the market in the second half of 2023, at the earliest

Risks

• Potential health consequences of exposure to an increased amount of desmopressin include water retention, hypotension, and hyponatremia (low sodium concentration in the blood),¹which in some extreme cases could lead to a seizure, coma, and death²
• No reports of adverse events that have been linked to the use of out-of-specification batches are known at this time

Availability of alternative options

• Ferring announced a complete overhaul of its production line with planned resuming of manufacturing of desmopressin products to Q2/2023 and supply to the market in the second half of 2023, at the earliest
• Pending manufacture restart, injectable (intravenous or subcutaneous) formulations of desmopressin (4 micrograms/mL and 15 micrograms/mL) are available and should be considered as alternative options for affected patients
• Patient/caregiver education and training on administration of subcutaneous or intravenous treatment is recommended as needed
• Coordination with healthcare providers is recommended for all patients affected by the recall to discuss alternative therapeutic options (e.g., clotting factor concentrates, tranexamic acid, or alternative forms of desmopressin) that may be needed, particularly for the management of bleeding events and perioperative care
• In collaboration with healthcare providers and national authorities, NMOs are advised to update their communities on the situation in their countries
• Healthcare providers are asked to look into alternative products with their local pharmacists to ensure patients continue to access desmopressin-based treatments

¹Srivastava A, Santagostino E, Dougall A, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition.Haemophilia. 2020:26(Suppl 6):1-158.http://doi.org/10.1111/hae.14046

²U.S. Food and Drug Administration.Ferring US Issues Voluntary Nationwide Recall of DDAVP^®Nasal Spray 10 mcg/0.1mL, Desmopressin Acetate Nasal Spray 10 mcg/0.1mL, STIMATE^®Nasal Spray 1.5 mg/mL Due to Superpotency. FDA website. Silver Spring, MD: U.S. Food and Drug Administration.http://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/ferring-us-issues-voluntary-nationwide-recall-ddavpr-nasal-spray-10-mcg01ml-desmopressin-acetateAccessed August 5, 2020.