Special Warning : אזהרת שימוש

4.4       Special warnings and precautions for use
Hypersensitivity/skin and appendices
Allergic reactions, including anaphylactic shock, can occur and may be life-threatening (see section 4.8).
In these cases, metronidazole should be discontinued and appropriate medical treatment should be implemented.
The onset of a pyrexial generalised erythema associated with pustules at the beginning of treatment should lead to the suspicion of acute generalised exanthematous pustulosis (see section 4.8); this requires therapy cessation and contraindicates any new administration of metronidazole, alone or combined.
Cases of severe skin reaction including Stevens-Johnson syndrome, Lyell’s Syndrome and acute generalised exanthematous pustulosis (AGEP) have been reported with metronidazole. Patients must be informed of the signs and symptoms and the skin should be closely monitored.
The occurrence of signs or symptoms of Stevens-Johnson syndrome, Lyell’s Syndrome (e.g., progressive rash often with blisters or mucous membrane injuries) or AGEP (pyrexial generalised erythema with pustules) (see section 4.8) requires therapy cessation and contraindicates any new administration of metronidazole, alone or combined.
Central nervous system
If symptoms suggestive of 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 management must be immediately reassessed, and the metronidazole treatment must be discontinued.
Cases of encephalopathy have been reported during post-marketing monitoring of this medicine. Cases of MRI changes associated with encephalopathy have also been observed (see section 4.8). The observed lesions are localised more frequently in the cerebellum (particularly in the dentate nucleus) and in the splenium of the corpus callosum. Most encephalopathy cases and MRI changes are reversible upon treatment discontinuation. Rare cases with fatal outcomes have been reported.
Signs suggestive of encephalopathy or deterioration in patients with central neurological conditions should be monitored.
In the event of aseptic meningitis while being treated with metronidazole, reinitiating treatment is not recommended or must be subject to an assessment of the benefit/risk ratio in the case of a severe infection.
Peripheral nervous system
Signs suggestive of peripheral neuropathy, especially in the case of prolonged treatment or in patients with severe, chronic or progressive peripheral neurological conditions, should be monitored.
Psychiatric disorders
Psychotic reactions with possible risky behaviour for the patient can occur starting from the first doses of the treatment, particularly in patients with psychiatric history (see section 4.8). Metronidazole should therefore be discontinued, the doctor informed and the necessary therapeutic measures taken immediately.
Blood disorders
In the case of history of haematological disorders, with a high-dose treatment and/or prolonged treatment, it is recommended to perform regular blood tests, especially differential white blood cell count.
In the case of leucopoenia, treatment continuation depends on the severity of the infection.
Hepatotoxicity in patients with Cockayne Syndrome
Cases of severe hepatotoxicity/acute hepatic failure, including cases resulting in a fatal outcome with a very fast onset after initiation of the treatment in patients with Cockayne syndrome, have been reported with products containing metronidazole for systemic use. In this population, metronidazole should not be used unless the benefit is considered to outweigh the risk and no alternative treatment is available.
Hepatic function tests must be performed before the start of treatment, throughout the treatment and after the end of treatment, until the hepatic function is within a normal range or until the initial values are obtained. If the hepatic function tests become significantly increased during the treatment, the medicinal product should be discontinued.
Patients with Cockayne syndrome should be advised to immediately report all symptoms of potential hepatic lesions to their doctor and to stop taking metronidazole (see section 4.8).
Excipient with known effect
This medicinal product contains sucrose. Its use is not recommended in patients with fructose intolerance, glucose-galactose malabsorption syndrome or sucrase-isomaltase deficiency.
This medicinal product contains 3 g of sucrose per measuring spoon, which should be taken into account in the daily allowance in the case of a low-sugar diet or diabetes.
This medicinal product contains 1% by vol of ethanol (alcohol), i.e., up to 40 mg of alcohol per measuring-spoon which is equivalent to 12 ml of beer, 5 ml of wine per dose. The use of this medicinal product is dangerous in alcoholic subjects and must be taken into account in pregnant or breast-feeding women, children and high-risk groups, such as those with liver failure or epilepsy.
This medicinal product contains less than 1 mmol (23 mg) of sodium per dose; that is, it is essentially “sodium-free”.
This medicinal product contains “parahydroxybenzoate” and may cause allergic reactions (possibly delayed reactions).
Interaction with other medicinal products
The concomitant use of metronidazole and alcohol is not recommended (see section 4.5).
The concomitant use of metronidazole and busulfan is not recommended (see section 4.5).
The 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 Nelson test results.
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.

Effects on Driving

4.7       Effects on ability to drive and use machines
It is necessary to warn patients about the potential risk of vertigo, confusion, hallucinations, seizures, or vision disorders and advise them not to drive or use machines if this type of disorder occurs.