Special Warning : אזהרת שימוש

4.4    Special Warnings and Precautions for use

Special Warnings
Excipient with known effect

This medicinal product contains glucose. It should therefore not be used in patients with glucose-galactose malabsorption syndrome.

Liver failure

Administration of roxithromycin is not recommended in patients with severe liver failure.
In patients with mild to moderate liver failure, roxithromycin should be used with caution.
If it must be administered in these subjects, regular liver function tests are required and if necessary, the dose should be reduced.

Renal ifailure

The amount of active substance and its metabolites eliminated by the renal route is small (10% of the oral dose). No dose adjustment is therefore required in patients with kidney failure.

Elderly subjects

In elderly subjects, the elimination half-life is prolonged. However, after repeated administration of 150 mg every 12 hours, peak plasma concentrations, and the AUC at steady state between two doses of roxithromycindid not differ compared to younger subjects.
No dose adjustment is therefore required in elderly patients.

Co-administration with ergot alkaloids

Severe vasoconstriction (ergotism), potentially leading to peripheral necrosis, has been reported when macrolides are co-admonistered with vasoconstrictive ergot alkaloids.
Before prescribing roxithromycin (see sections 4.3 and 4.5), the physician should make sure that the patient is not receiving treatment with these alkaloids.

Coadministration of roxithromycin with dopaminergic ergot alkaloids is not recommended (see section 4.5).

Serious bullous reactions

Cases of serious bullous skin reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP) have been reported with roxithromycin (see Section 4.8).
If the patient experiences symptoms or signs of AGEP, SJS or TEN (e.g. progressive skin rash often with blisters or mucosal lesions), Rulid treatment should be discontinued.

Precautions for use

Prolongation of the QT interval
Under certain conditions, macrolides, including roxithromycin, have the potential to prolong the QT interval. Roxithromycin should therefore be used with caution in patients with congenital prolonged QT syndrome and proarrhythmic conditions (e.g. uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia), and in patients receiving treatments which may prolong the QT interval such as Class IA and class III 

antiarrhythmic agents and drugs such as astemizole, cisapride or pimozide (see sections       4.5 and 4.8).

Myasthenia

As with other macrolides, roxithromycin may aggravate myasthenia.
Clinical monitoring in long-term treatment

Monitoring of liver function, renal function and blood count is particularly recommended in long-term treatment (e.g. treatment duration exceeding 2 weeks) (See Section 4.8).

Clostridium difficile infection

Cases of Clostridium difficile-associated diarrhea (CDAD) have been reported with the use of almost all antibiotics, including roxithromycin (see Section 4.8). Severity of the disorder can vary from mild diarrhea to life-threatening pseudomembranous enterocolitis.
Antibiotic treatment modifies colon flora, thus leading to an excessive proliferation of C.
difficile.

C. difficile produces A and B toxins which contribute to the development of CDAD. These toxin-producing strains increase morbidity and mortality since these infections may be refractory to the antibiotic treatment and the patient may require a colectomy. The possibility of CDAD should be considered in all patients who develop diarrhea following the use of antibiotics and treatment with roxithromycin should be stopped immediately. It is important that CDAD be considered as a possible diagnosis in patients who have diarrhea during or following antibiotic treatment.

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