Special Warning : אזהרת שימוש

4.4. Special warnings and precautions for use
Hypersensitivity / Skin and appendages
Allergic reactions, including anaphylactic shock, can occur and be life-threatening (see section 4.8). In this case, treatment with metronidazole must be discontinued and appropriate medical treatment initiated.
If, at the start of treatment, patients experience generalised erythema with fever and pustules, acute generalised exanthematous pustulosis should be suspected (see section 4.8). If this occurs, treatment must be discontinued and any further administration of metronidazole alone or in combination with other agents is contraindicated.
Severe skin reactions have been reported with metronidazole, such as Stevens-Johnson syndrome, toxic epidermal necrolysis (or Lyell's syndrome), and acute generalised exanthematous pustulosis (AGEP). Patients must be informed of the signs and symptoms of these conditions and the skin should be closely monitored.
If any signs or symptoms of Stevens-Johnson syndrome, toxic epidermal necrolysis (e.g., progressive skin rash often with blisters or mucosal lesions) or AGEP (generalised erythema with fever and pustules) (see section 4.8) occur, treatment must be discontinued and any further administration of metronidazole alone or in combination with other agents is contraindicated.
Central nervous system
If symptoms suggestiveof encephalopathy or cerebellar syndrome occur (for example, ataxia, dysarthria, gait disturbance, nystagmus, tremor, vertigo, confusion, convulsions, peripheral sensory neuropathy, headache (see section 4.8)), the patient’s treatment must be immediately reassessed, and therapy with metronidazole treatment must be discontinued.
Cases of encephalopathy have been reported as part of post-marketing surveillance of the drug. Cases of MRI changes associated with encephalopathy have also been observed (see section 4.8). Damage is most often located in the cerebellum (particularly in the dentate nucleus) and in the splenium of the corpus callosum. Most cases of encephalopathy and MRI changes are reversible on treatment discontinuation. Very rare cases of fatal outcome have been reported.
Patients should be monitored for warning signs of encephalopathy, and exacerbation of symptoms in patients with CNS disorders. If aseptic meningitis occurs during treatment, rechallenge with metronidazole is not recommended, and      an assessment of the benefit/risk ratio should be done for patients with serious infection.
Peripheral nervous system
Patients should be monitored for warning signs of peripheral neuropathy, particularly in long-term treatment or in patients with severe, chronic or progressive peripheral neurological disorders.
Psychiatric disorders
From administration of the first doses, patients may experience psychotic reactions, including self- endangering behaviour, particularly if they have a history of psychiatric disorders (see section 4.8). If this happens, metronidazole must be discontinued, the physician informed, and appropriate therapeutic measures instituted immediately.
Haematological effects
In patients who have a history of haematological disorders or who are receiving high-dose and/or long- term treatment, regular blood tests, and particularly leukocyte counts, should be performed.
In patients with leukopenia, continued treatment will depend on how serious the infection is.
Excipient with known effect
Wheat starch (containing gluten)
This medicine contains trace amounts of gluten (from wheat starch) and is therefore unlikely to cause problems for patients with coeliac disease.
One tablet contains no more 8.215 micrograms of gluten.
Patients with an allergy to wheat (different from coeliac disease) should not take this medicinal product (see section 4.3).


Paediatric population
Tablets are contraindicated in children under 6 years of age because of the risk of pulmonary aspiration. Other presentations of metronidazole-based medicinal products are available for young children.
Interaction with other medicinal products
Concomitant use of metronidazole and alcohol is not recommended (see section 4.5).
Concomitant use of metronidazole and busulfan is not recommended (see section 4.5).
Concomitant use of metronidazole and disulfiram is not recommended (see section 4.5).
Interference with paraclinical examinations and laboratory tests
Metronidazole may immobilise treponemes, and thus lead to false positive results for the Nelson test.

Metronidazole may interfere with certain types of blood tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH], triglycerides, glucose), which may lead to a false negative or an abnormally low result. These analytical methods are based on a decrease in ultraviolet absorbance, which occurs when hydrogenated nicotinamide adenine dinucleotide (NADH) is oxidised to nicotinamide adenine dinucleotide (NAD). This interference is due to the similarity of the absorption peaks of NADH (340 nm) and metronidazole (322 nm) at pH 7.
Patients with Cockayne SyndromeCases of severe hepatotoxicity/acute liver failure of very rapid onset after treatment initiation, including cases with fatal outcome, have occurred in patients with Cockayne syndrome who were administered medicinal products containing metronidazole intended for systemic use. In this population, metronidazole must therefore be used after thorough evaluation of the benefit/risk ratio and only if no alternative treatment is available. Liver function tests must be performed just before treatment initiation, during treatment and after treatment discontinuation, until liver function values are within the normal range, or until baseline values are reached. If the liver function test values markedly increase during treatment, the medicinal product should be discontinued.
Patients with Cockayne syndrome must be instructed to immediately report any symptoms of potential liver damage to their doctor and to stop taking metronidazole.

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