Health Canada has released a new drug safety information/alert to raise awareness to health care professionals and public about the below safety concern which recently made safety labelling changes for the product monograph. –Health Product Info Watch – May 2020. The safety concern discussed below in brief.
Hypofibrinogenaemia associated with Tigecycline use:
Tigecycline is a tetracycline derivative antibiotic used in the treatment of various bacterial infections which included complicated Intra-abdominal Infections, skin infections and community-acquired pneumonia. This drug has orphan designation for the treatment of Acute Myeloid Leukemia. The safety profile for this drug in pediatric population is not established. The brand name of this drug is Tygacil marketed by Pfizer. It was developed in response to the growing rate of antibiotic resistant bacteria and gained fast-track approval by the US-FDA (approved on 17‑Jun‑2005).
Hypofibrinogenaemia is a condition of abnormally low level of fibrinogen (0.2 and 0.8 grams per liter) which can cause mild to severe bleeding.
Health Canada received case reports pertaining to adverse reaction hypofibrinogenaemia which is added as a new safety concern to the Health Canada’s Product monograph of Tigecycline. The risk of hypofibrinogenaemia and recommendations on monitoring of blood coagulation parameters have been included in the Warnings and Precautions and Adverse Reactions (Post Marketing Adverse Reactions) sections of the Canadian product monograph for Tigecycline.
Case reports in FAERS:
In US-FDA’s FAERS (FDA Adverse Event Reporting System), there are total 47 adverse event reports pertaining to association of hypofibrinogenaemia with tigecycline use. These case reports were being received since 2011. In the year 2015, highest number of case reports for tigecycline‑hypofibrinogenaemia combination were found. All the 47 case reports with this adverse reaction are considered as serious with two fatal cases and all cases were received from health care professional(s) as reporter.
47 cases distribution:
By Product name: Generic (Tigecycline) – 40; Brand (Tygacil) – 7
By Gender: Male (29); Female (16); Not specified (2)
By Age group: Adult (4); Elder (18); Not specified (25)
Case reports in VigiBase:
In the global drug safety database-VigiBase (Maintained by WHO-UMC), the total number of case reports with this Drug-ADR combination of Tigecycline-Hypofibrinogenaemia are 21 which were received originated from different countries (member countries for the international drug safety monitoring).
Advice to Health care professionals:
The Warnings and Precautions and Adverse Reactions sections of the Canadian product monograph for Tygacil has updated with the risk of hypofibrinogenemia.
Physicians should monitor for blood coagulation parameters, including blood fibrinogen prior to treatment initiation with tigecycline and regularly while on treatment.
Every medicine has its own benefits and risks (known & unknown). The medicine is prescribed to patient considering the positive benefit risk (known) profile with respect to individual patient (considering ongoing concurrent illness/disease). If any unanticipated adverse events (both expected and unexpected) are experienced by patient. It is advisable to report the same to health regulatory bodies of that nation.
Health care professionals and consumers are advised to voluntarily report these new safety observations to Canada’s post-market surveillance program by submitting the voluntary reporting form online under drug health products.
For more information on other product safety updates- Product monograph brand safety updates