ROVAMYCIN Film-coated tablet Ref.[8592] Active ingredients: Spiramycin

QT interval prolongation

Cases of QT interval prolongation have been reported in patients taking macrolides, including spiramycin.

Caution should be exercised when using spiramycin, in patients with known risk factors for prolongation of the QT interval such as:

• uncorrected electrolyte imbalance (e.g. hypokalemia, hypomagnesemia).
• congenital long QT syndrome.
• cardiac disease (e.g. heart failure, myocardial infarction, bradycardia).
• concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, some anti-infectives, some antipsychotics).

Elderly patients, neonates and women may be more sensitive to QTc-prolonging effect. (See Sections 4.2 Posology and Method of Administration, 4.5 Interactions, 4.8 Undesirable Effects, 4.9 Overdose).

Severe cutaneous adverse reactions (SCARs)

Cases of severe cutaneous adverse reactions including Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been reported with the use of spiramycin. Patients should be advised of the signs and symptoms and monitored closely for skin reactions. If symptoms or signs of SJS, TEN (e.g. progressive skin rash often with blisters or mucosal lesions) or AGEP are present, spiramycin treatment should be discontinued. (See Section 4.8 Undesirable effects).

If, at the start of treatment, patients experience generalized erythema and pustules, accompanied by fever, acute generalized exanthematous pustulosis should be suspected (see Section 4.8 Undesirable effects); if such a reaction occurs, treatment must be discontinued and any further administration of spiramycin alone or in combination is contraindicated.

Since the active substance is not excreted via the kidney, there is no need to adjust dosage in patients with renal failure.

Very rare cases of hemolytic anemia have been reported in patients with glucose-6-phosphatedehydrogenase deficiency. Spriamycin is therefore not recommended for such patients.

Interactions requiring precautions for use

Levodopa (associated with carbidopa)

Inhibition of carbidopa absorption with decreased plasma concentrations of levodopa. Clinical monitoring and possible adjustment of levodopa dosage, if required.

Drugs known to prolong QT interval

Spiramycin, like other macrolides, should be used with caution in patients receiving drugs known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, some antiinfectives, some antipsychotics) (See Section 4.4 Warnings and Precautions for use).

Specific problems with INR imbalance

Many cases of increased activity in oral anticoagulants have been reported for patients taking antibiotics. The marked severity of the infection or inflammation, patient age and general health status appear to be risk factors. Under these circumstances, it is difficult to distinguish between the effect of the infection and its treatment in the onset of INR imbalance. However, certain classes of antibiotics are more involved; particularly fluoroquinolones, macrolides, cyclines, cotrimoxazole and certain cephalosporins.

Pregnancy

Spiramycin can be used during pregnancy if necessary. Extensive use of spiramycin during pregnancy has shown no evidence of malformation or fetotoxicity to date.

Lactation

Spiramycin is excreted into breast milk. Gastrointestinal disorders in neonates have been reported. Consequently, breast-feeding is not recommended to women taking spiramycin.

Not relevant.

Gastrointestinal system:

Gastralgia, nausea, vomiting, diarrhea and, very rarely, pseudo-membranous colitis.

Skin and appendages:

• Rash, urticaria, pruritis.
• Very rarely angioedema, anaphylactic shock.
• Isolated cases of vasculitis, including Henoch-Schonlein purpura.
• Very rarely, acute generalized exanthematous pustulosis (see Section 4.4 Warnings and Precautions for use).
• Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN).

Central and peripheral nervous system:

• Occasional cases of transient paresthesia.
• Transient dysgeusia

Liver effects:

• Very rarely abnormal results to liver function tests.
• Unknown frequency mixed or more rarely cytolytic cholestatic hepatitis have been reported.

Hematological effect:

• Very rarely hemolytic anemia (see Section 4.4. Warnings and Precautions for use).
• Unknown frequency: leukopenia, neutropenia.

Cardiac disorder:

Electrocardiogram QT prolonged, ventricular arrhythmia, ventricular tachycardia, torsade de pointes, which may result in cardiac arrest. (See Section 4.4 Warnings and Precautions for use).