Update on the Recall of Desmopressin Nasal Sprays
The European Haemophilia Consortium (EHC) would like to provide an update on its November 2020 statement on the international recall of all Ferring Pharmaceutical Limited nasal sprays containing desmopressin, including Octim®, Octostim®, Desmospray®, DDAVP Spray® and Stimate®.
In February 2021, Ferring informed both the World Federation of Hemophilia (WFH) and the EHC that it had completed its internal investigation into the causes of its higher than the specified concentration of desmopressin. This was the result of an issue in the tightness of the seal of the bottle.
The company further indicated that to prevent this issue recurrence, it intended 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:
- 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 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 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
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-acetateAccessed August 5, 2020.
Jim is aged 66 and has Haemophilia A with a high titer inhibitor which he developed at age 14.
Maria Elisa Mancuso (MD, PhD) is a Haematologist and works as a Senior Haematology Consultant at the Center for Thrombosis and Haemorrhagic Diseases of IRCCS Humanitas Research Hospital in Rozzano, Milan, Italy. She is Adjunct Clinical Professor at Humanitas University. She obtained a post-degree in Clinical and Experimental Haematology and a PhD in Clinical Methodology. She is involved in clinical research and has published several original articles in peer-reviewed journals a The Lancet, Blood, Journal of Thrombosis and Haemostasis, Haematologica, Thrombosis and Haemostasis, British Journal of Haematology and Haemophilia. She is reviewer for several peer-reviewed journals and member of the Editorial Board of JTH. She is a member of several scientific societies (ISTH, WFH, ASH, EAHAD, SISET, AICE) and was a medical member of the Inhibitor Working Group of the European Hemophilia Consortium. She is co-chair of the ADVANCE Study Group. She has acted also as co-chair of the Scientific and Standardization Subcommittee of ISTH on FVIII, FIX and rare bleeding disorders. She has been involved as principal and co-investigator in several clinical trials, and she takes care of both children and adults with hemophilia and other congenital bleeding disorders with a specific scientific interest in novel therapies, prophylaxis, inhibitors, and chronic hepatitis C.
As a patient with factor II deficiency, the diagnostic and treatment of rare bleeding disorders is a matter dear to my heart. My motivation to participate in the work of the ERIN committee is to improve both diagnostic and treatment for patients with rare bleeding disorders across Europe.
Economist and financial expert by profession, executive coach and trainer by passion and haemophilia advocate by every drop of my blood through my son (who has severe haemophilia A with inhibitors). Bringing a good decade of practical experience from the corporate insurance world, laser focus, growth mindset and resilience from my own experience, offering you anything I can just do, in hope that together we can make life more fulfilled for those impacted by bleeding disorders.
Amy Owen-Wyard is a Registered Mental Health Nurse. With experience working with children, young people, their families and adults with severe and enduring mental health conditions. Amy was also involved in a service improvement to provide a holistic care approach for those in general hospitals to support both their mental and physical health, whilst sharing her expertise and knowledge in mental health with the wider multidisciplinary team.
