Лист-звернення до медичних та фармацевтичних працівників.

Metamizole: risk of drug-induced liver damage.

February 2021

Dear medical and pharmaceutical professionals,

Teva Ukraine LLC, as the holder of registration certificates for medicinal products containing metamizole sodium – Spazmalgon®, tablets and Sedalgin Plus, tablets, in agreement with the European Medicines Agency (EMA) and the State Enterprise “State Expert Center of the Ministry of Health of Ukraine” informs you about the risk of drug-induced liver damage.

Resume:

• Cases of drug-induced liver injury (DIE) have been reported following the use of metamizole.
• Advise patients about:
• early symptoms indicating drug-induced liver damage,
• Discontinue use of metamizole if such symptoms occur and seek medical attention for evaluation and monitoring of liver function;
• Metamizole should not be re-administered to patients with a history of liver injury during metamizole treatment, for whom no other cause of liver injury has been identified.

The sections "Special instructions for use" and "Adverse reactions" of the instructions for medical use of medicines containing metamizole will be updated accordingly.

Causes of the security problem

Metamizole is a non-opioid pyrazolone derivative with potent analgesic, antipyretic, and weak anti-inflammatory properties.

Metamizole is also available in fixed combination preparations such as:

• metamizole sodium + pitofenone hydrochloride + fenpiverinium bromide, intended for adults and children over 15 years of age for symptomatic treatment of mild to moderate pain syndrome in spasms of smooth muscles of internal organs: renal colic and inflammatory diseases of the urinary tract, accompanied by pain and dysuric disorders; stomach and intestinal spasms, hepatic colic, biliary dyskinesia; spastic dysmenorrhea; and
• metamizole sodium + caffeine + thiamine hydrochloride, intended for adults and children over 12 years of age for symptomatic treatment of pain syndrome in migraine, tension headache; inflammatory and degenerative diseases of the musculoskeletal system; postoperative conditions; diseases of the peripheral nervous system (radiculitis, plexitis, neuritis, neuralgia, polyneuritis, polyneuropathies); dysmenorrhea.

Recently discovered new information on liver damage prompted a comprehensive review of the data related to the potential of metamizole to cause MUP. During the review, EMA's Pharmacovigilance Risk Assessment Committee (PRAC) considered information from all available sources, including adverse drug reaction reports and studies published in the scientific literature.

Liver damage has been reported to be predominantly hepatocellular in nature and to occur within days to months of initiation of treatment. Signs and symptoms have included elevated serum liver enzymes with or without jaundice, often in the context of other drug hypersensitivity reactions (e.g. skin rash, blood dyscrasias, fever and eosinophilia) or accompanied by signs of autoimmune hepatitis. In some patients, liver damage has recurred with repeated administration of metamizole.

The mechanism of liver damage caused by metamizole is not clearly understood, but available data indicate an immunoallergic mechanism.

Overall, drug-induced liver injury can progress to potentially serious consequences, such as acute liver failure requiring liver transplantation.

Based on almost 100 years of marketing experience with metamizole and the duration of its effect on patients, cases of liver damage due to the use of metamizole are considered to be very rare, but the exact frequency of this adverse reaction cannot be determined.

Early detection of potential liver injury due to metamizole is important. Patients should be instructed to watch closely for symptoms of potential liver injury and encouraged to discontinue metamizole and seek medical attention if such symptoms develop. Healthcare professionals are advised to assess and monitor liver function in patients with signs and symptoms suggestive of any liver injury.

Re-administration of metamizole-containing medicinal products is not recommended in the event of a previous case of liver injury that occurred during metamizole treatment, for which no other cause of liver injury has been identified.

REPORTING OF SIDE EFFECTS

Please report any suspected adverse reactions to the State Enterprise "State Expert Center of the Ministry of Health of Ukraine" by phone at 044 202 17 00 or via the link https://aisf.dec.gov.ua/ .

If you have information about the occurrence of an adverse reaction or lack of effectiveness when using a Teva drug, please contact the company's Pharmacovigilance Department by phone at +38050-462-17-67 or by email at Safety.Ukraine@teva.ua . 

If you have any questions or need additional information or medical clarifications regarding Teva drugs, you can contact the company's Support Center by phone at 0-800-502-284 , or the Medical Department by email at medinfo@teva.ua .