Framework for using this specialty
Since antibiotic monotherapy is expected to be suitable for the treatment of most odontostomatological infections, the need for a fixed combination of spiramycin-metronidazole should be weighed in view of the possibility of a separate intake of each antibiotic. It is recommended to use the antibiotic treatment with the best risk-benefit ratio as a first-line treatment for odontostomatological infections.
Skin and appendages hypersensitivity
- Allergy reactions, including anaphylactic shock, can occur and are life-threatening (see section Undesirable effects). In these cases, metronidazole should be discontinued and appropriate medical treatment should be initiated.
- Cases of severe skin reactions including Stevens-Johnson syndrome, Lyell’s syndrome, acute generalized exanthematous pustulosis (AGEP) have been reported with spiramycin-metronidazole. Patients should be informed of the signs and symptoms and close skin monitoring should be performed.
- The occurrence of signs or symptoms of Stevens-Johnson syndrome, Lyell’s syndrome (e.g. progressive rash often accompanied by bubbles or lesions of mucous membranes) or AGEP (acute generalized exanthematous pustulosis) (see section Undesirable effects) requires discontinuation of the treatment and contraindicates any further administration of spiramycin or metronidazole alone or in combination.
Central nervous system
- If symptoms suggestive of encephalopathy or cerebellar syndrome appear, the patient's management should be reassessed immediately and treatment with metronidazole should be discontinued.
- Cases of encephalopathy have been reported with metronidazole during post-marketing surveillance. MRI changes associated with encephalopathy have also been observed (see section Undesirable effects). Lesions observed are most frequently located in the cerebellum (particularly in the serrated nucleus) and in the splenium of the corpus callosum. Most cases of encephalopathy and MRI changes are reversible upon discontinuation of treatment. Exceptional cases of fatal outcomes have been reported.
- Watch for signs suggestive of encephalopathy or for worsening in patients with central neurological disease.
- In the event of aseptic meningitis under metronidazole, reintroduction of the treatment is not recommended or must be the subject of an assessment of the benefit-risk ratio in the event of serious infection.
Peripheral nervous system
- Monitor the appearance of signs suggestive of peripheral neuropathies, in particular in the case of prolonged treatment or in patients with severe, chronic or progressive peripheral neurological conditions.
Psychiatric disorders
- Psychotic reactions with possible risky behavior for the patient may occur from the first intake of treatment, especially in the event of a psychiatric history (see section Undesirable effects). The metronidazole must then be discontinued, the doctor is informed and the necessary therapeutic measures taken immediately.
Blood disorders
- In the event of a history of haematological disorders, high-dose treatment and/or prolonged treatment, it is recommended to perform regular blood tests, especially control of the leukocyte formula.
- In case of leukopenia, advisability of continuing treatment depends on the infection severity.
Prolongation of QT interval
There have been reports of QT interval prolongation in patients taking macrolides, including spiramycin.
Caution is advised during treatment with spiramycin in patients with known risk factors for QT prolongation such as:
- an uncorrected electrolyte imbalance (for example, hypokalaemia, hypomagnesemia),
- congenital long QT syndrome,
- cardiac pathologies (for example, heart failure, myocardial infarction, bradycardia),
- concomitant treatment with drugs known to prolong the QT interval (for example, class Ia and class III antiarrhythmics, tricyclic antidepressants, certain antibiotics, certain antipsychotics),
- the elderly, newborns and women may be more sensitive to QT prolongation
- (see sections Posology and Method of administration; Interactions; Undesirable effects; Overdose).
Liver problems
Severe hepatotoxicity/acute hepatic failure, including fatal cases with very rapid onset after initiation of treatment in patients with Cockayne syndrome, have been reported with products containing metronidazole intended for systemic use. In this population, therefore, metronidazole should be used after a careful assessment of the benefit-risk ratio and only if no alternative treatment is available. Liver function tests should be done just before starting treatment, throughout treatment, and after treatment is finished, until liver function is within normal range, or until after the initial values ​​are obtained. If the liver function tests become markedly elevated during treatment, the drug should be discontinued.
Patients with Cockayne syndrome should be instructed to immediately report any symptoms of potential liver damage to their doctor and to stop taking metronidazole.
G6PD deficiency
In patients with G6PD deficiency, cases of acute hemolysis have been reported with spiramycin given by mouth or by injection. Its prescription must therefore be ruled out, and recourse to a therapeutic alternative, if it exists, is strongly recommended.
In the absence of an alternative, the decision must take into account for each patient the danger of hemolysis and the potential benefit expected from the treatment. If the prescription of this medication is necessary, the occurrence of possible hemolysis should be detected.
Drugs interactions
The concomitant use of metronidazole and alcohol is not recommended (see section Interactions).
The concomitant use of metronidazole and busulfan is not recommended (see section Interactions).
The concomitant use of metronidazole and disulfiram is not recommended (see section Interactions).
Interactions with paraclinical examinations
Metronidazole can immobilize treponemes and therefore falsely posit a Nelson test.
Excipients
This medicine contains less than 1 mmol sodium (23 mg) per sachet, that is to say essentially “sodium-free”.
Eurolake ponceau may cause allergic reactions.