FLAGYL

They derive from the antiparasitic and antibacterial activity of metronidazole and its pharmacokinetic characteristics. They take into account both the clinical studies conducted on this medicine and its place within the range of anti-infective products currently available.

They are limited to infections caused by germs defined as sensitive:

· amoebiasis,

· urogenital trichomoniasis,

· non-specific vaginitis,

· giardiasis,

· curative treatment of medico-surgical infections caused by sensitive anaerobic germs,

· transition from curative injectable treatments for infections caused by sensitive anaerobic germs.

Official recommendations regarding the appropriate use of antibacterials should be taken into account.

Pregnancy

Animal studies have not demonstrated any teratogenic effect. In the absence of a teratogenic effect in animals, a malformative effect in the human species is not expected. Indeed, to date, substances responsible for malformations in the human species have proven to be teratogenic in animals during well-conducted studies on two species.

In clinical practice, the analysis of a high number of exposed pregnancies has apparently revealed no particular malformative or foetotoxic effect of metronidazole. However, only epidemiological studies would allow for verifying the absence of risk. Consequently, metronidazole may be prescribed during pregnancy if necessary.

Breastfeeding

As metronidazole passes into breast milk, avoid administration of this medicine during breastfeeding.

Patients should be warned of the potential risk of dizziness, confusion, hallucinations, convulsions or visual disturbances and be advised not to drive vehicles or operate machinery if such disturbances occur.

Hematological and lymphatic system disorders

· Neutropenia, agranulocytosis, thrombocytopenia.

Cardiac disorders

· Unspecified frequency: cases of QT interval prolongation have been reported, particularly when metronidazole is administered with medicines that may prolong the QT interval.

Psychiatric disorders

· Hallucinations,

· psychotic reactions with paranoia and/or delirium which may be accompanied in isolation by suicidal ideas or acts (see section 4.4),

· depressive mood.

Nervous system disorders

· Peripheral sensory neuropathies,

· headache,

· dizziness,

· confusion,

· convulsions,

· encephalopathy which may be associated with MRI changes generally reversible on discontinuation of treatment. Exceptional cases of fatal evolution have been reported (see section 4.4),

· subacute cerebellar syndrome (ataxia, dysarthria, gait disturbances, nystagmus, tremors) (see section 4.4),

· aseptic meningitis (see section 4.4),

· unspecified frequency: posterior reversible encephalopathy syndrome (PRES)*

* the adverse effect is only applicable to systemic formulations.

Eye disorders

· Transient visual disturbances such as blurred vision, diplopia, myopia, decreased visual acuity, change in color vision,

· optic neuropathies/neuritis.

Gastrointestinal disorders

· Benign digestive disorders (epigastric pain, nausea, vomiting, diarrhoea),

· glossitis with sensation of dry mouth, stomatitis, taste disorders, anorexia,

· reversible pancreatitis on discontinuation of treatment,

· discoloration or change in appearance of the tongue (mycosis).

Hepatobiliary disorders

· Elevations of liver enzymes (ALAT, ASAT, alkaline phosphatases), very rare cases of acute liver injury of a cytolytic nature (sometimes icteric), cholestatic or mixed. Isolated cases of hepatocellular insufficiency which may require liver transplantation have been reported.

· Cases of severe and irreversible hepatotoxicity/acute liver failure, including cases of fatal outcome with very rapid onset after initiation of systemic use of metronidazole, have been reported in patients with Cockayne syndrome (see section 4.4).

Skin and subcutaneous tissue disorders

· Flushing, pruritus, skin rash sometimes febrile,

· urticaria, angioedema, anaphylactic shock (see section 4.4),

· very rare cases of acute generalized exanthematous pustulosis (see section 4.4),

· Lyell syndrome,

· Stevens-Johnson syndrome,

· fixed pigment erythema.

Miscellaneous

· Appearance of a reddish-brown discoloration of urine due to the presence of water-soluble pigments from the metabolism of the product.

Reporting of suspected adverse effects

Reporting suspected adverse effects after medicinal product authorization is important. It allows for continuous monitoring of the benefit/risk ratio of the medicinal product. Healthcare professionals report any suspected adverse effect via the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr/ .