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Update on Ferring recall of desmopressin nasal sprays

Ferring Pharmaceuticals has issued an update on the global recall in July and August 2020 of its desmopressin nasal sprays, including the 1.5 mg/ml desmopressin acetate formulation used in the treatment of von Willebrand disease (VWD) and mild or moderate hemophilia A (Octostim®, Octim® and Stimate®).

In its notice on February 3, 2021, Ferring stated that it has completed its internal investigation into the causes of out-of-specification test results showing higher concentrations of desmopressin in some vials observed to have lower volumes of solution. This was the result of an issue with the tightness of the seal of the bottle.

Ferring further indicated that to prevent this issue recurrence, it intends to procure, install and qualify a new production line.

Based on the timelines needed to complete these tasks, the company anticipates that it will restart manufacturing the following products in Q2 of 2023, with first deliveries to the market anticipated in the second half of 2023 (depending on the respective health authority approval). This concerns the following products:

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

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

  • Minirin® Nasal Spray (desmopressin 0.1 mg/ml, cold storage formulation)
  • Desmopressin Oral (tablet and oral lyophilizate formulations)
  • Desmopressin Injectable formulations (4 mcg/ml and 15 mcg/ml)

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

Healthcare providers can contact their pharmacies and/or the manufacturers of appropriate alternative desmopressin acetate formulations for information about their availability.

Other alternative therapeutic options (e.g., clotting factor concentrates, tranexamic acid) may be needed, particularly for management of bleeding events and peri-operative care.

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 hemophilia A, including carriers, and many patients with von 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 July and August 2020, including the formulation used in the treatment of mild/moderate hemophilia and VWD (Octostim® and Octim® by Ferring, 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 and 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 in Q2 of 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)1 which 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

  • 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

 1 Srivastava 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-acetate Accessed August 5, 2020.

Source: Update on the Ferring recall of desmopressin products (European Haemophilia Consortium, February 5, 2021)

See also:

WFH Notice: Global recall of Octim®/Octostim® desmopressin nasal spray (1.5 mg/ml) by Ferring Pharmaceuticals (World Federation of Hemophilia, August 4, 2020)