Rulid

/ Sanofi

Adults: 300 mg per day, i.e. 1 x 150 mg tablet in the morning and evening,
preferably before meals.
Treatment duration: Treatment duration for throat infections is 10 days.

Treatment of infections caused by microorganisms sensitive to roxithromycin, e.g, ENT, bronchopulmonary, genital and skin manifestations.

Hypersensitivity to macrolides or to any of the excipients.
Coadministration with:
vasoconstrictive ergot alkaloids: dihydroergotamine, ergotamine.
Colchicine.
Concomitant use with drugs that may cause ventricular arrhythmias (torsades de pointes, prolonged QT interval) is contraindicated. Such drugs include for example terfenadine, astemizole, cisapride or pimozide.
Women breast-feeding an infant who is treated with cisapride.

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 insufficiency: The amount of active substance and its metabolites eliminated by the urinary route are small (10% of the oral dose). There is therefore no need to adjust dosage in patients with kidney failure.
Elderly subjects: The elimination half-life is longer in elderly subjects. However, after repeated administration of 150 mg every 12 hours, peak plasma concentrations, area under the curve and steady state in the interval between 2 roxithromycin doses are no different to those found in young subjects.
It is therefore not necessary to adjust the dose in elderly subjects.
Duration of treatment: In young animals, bone growth plate abnormalities were observed at doses at least 10 times higher than therapeutic doses. It is therefore recommended to limit dosage to 5-8 mg/kg/day for a period not exceeding 10 days.
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, the physician should make sure that the patient is not receiving treatment with these alkaloids.
Coadministration of roxithromycin with colchicine or dopaminergic ergot alkaloids is not recommended.
Severe bullous reactions: Cases of severe bullous skin reactions such as Stevens Johnson syndrome or toxic epidermal necrolysis have been reported with roxithromycin. If symptoms or signs of SJS or TEN (e.g. progressive skin rash often with blisters or mucosal lesions) are present, Rulid treatment should be discontinued.
Prolongation of the QT interval: In certain conditions, macrolides, including roxithromycin, have the potential to prolong the QT interval. Therefore, roxithromycin should 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 III antiarrhythmic agents and drugs such as astemizole, cisapride or pimozide.
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).
Clostridium difficile infection: Cases of Clostridium difficile-associated diarrhea (CDAD) have been reported with the use of almost all antibiotics, including roxithromycin. 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.

Common: Headache, dizziness, nausea, vomiting, gastric pain, diarrhea , rash.
See prescribing information for full details

Contraindicated combinations
Colchicine: Potentiation of colchicine-induced adverse effects, which may be fatal.
Cisapride: Increased risk of ventricular arrhythmias, especially torsades de pointes.
Ergotamine/Dihydroergotamine: Ergotism, potentially leading to peripheral necrosis (decreased hepatic elimination of ergotamine and inhibition of hepatic elimination of dihydroergotamine).
Concomitant use of roxithromycin and ergotamine or hidydroergotamine, may cause perfusion disturbances, especially in the fingers and toes.
Inadvisable combinations
Dopaminergic ergot alkaloids (bromocriptine, cabergoline, lisuride,
pergolide): Increased plasma concentrations of the dopaminergic agent with possible increased in activity or occurrence of symptoms of overdose.
Terfenadine: Certain macrolides are capable of a pharmacokinetic interactions with terfenadine leading to increased serum concentrations of terfenadine. This may result in severe ventricular arrhythmias, typically torsade de pointes. Although such a reaction has not been demonstrated with roxithromycin and studies in a limited number of healthy volunteers have not shown any pharmacokinetic interaction or relevant ECG changes, the association of roxithromycin and terfenadine is not recommended.
Astemizole and Pimozide: Other drugs, such as astemizole or pimozide, which are metabolized by hepatic CYP3A isozyme have been associated with QT interval prolongation and/or cardiac arrhythmias (typically torsades de pointe) as a result of increase in their serum level subsequent to interaction with significant inhibitors of this isozyme, including some macrolide antibacterials. Although roxithromycin has no or limited ability to complex CYP3A and therefore to inhibit the metabolism of other drugs processed by this isozyme, a potential for clinical interaction of roxithromycin with the above mentioned drugs cannot be either ascertained or ruled out in confidence; therefore, association of roxithromycin with such drugs is not recommended.
Class IA and III antiarrhytmic agents: Roxithromycin, like other macrolides, should be used with caution in patients receiving Class IA and III antiarrhythmic agents.
Combinations requiring precautions for use
Drugs likely to induce torsades de pointes: (amiodarone, amisulpride, arsenic compounds, bepridil, chlorpromazine, citalopram, cyamemazine, diphemanil, disopyramide, dofetilide, dolasetron, domperidone, dronedarone, droperidol, erythromycin, escitalopram, flupentixol, fluphenazine, halofantrine, haloperidol, hydroquinidine, ibutilide, levofloxacin, levomepromazine, lumefantrine, mequitazine, methadone, mizolastine, moxifloxacin, pentamidine, pimozide, pipamperone, pipotiazine, prucalopride, quinidine, sertindole, sotalol, spiramycin, sulpiride, sultopride, tiapride, toremifene, vandetanib, vincamine, zuclopenthixol).
This serious cardiac rhythm disorder can be caused by a number of antiarrhythmic and non-antiarrhythmic drugs. Hypokalemia (especially induced by potassium-depleting agents) is a promoting factor, as is bradycardia (especially induced by bradycardiainducing agents) or pre-existing congenital or acquired QT interval prolongation. The medicinal products which cause this adverse effect include class la and III antiarrhythmic agents, and certain neuroleptics. Other agents not belonging to these classes are also involved.
Increased risk of ventricular arrhythmias, especially torsades de pointes.
When co-administering these agents, clinical and ECG monitoring are required.
Bradycardia-inducing agents: Increased risk of ventricular arrhythmias, especially torsades de pointes. Clinical and ECG monitoring required.
Vitamin K antagonists (acenocoumarol, fluindione, phenindione, warfarin): Increased vitamin K antagonist effect and increased risk of hemorrhage. INR should be monitored more frequently. Dose adjustment of the vitamin K antagonist during treatment with the macrolide and after treatment discontinuation may be necessary.

Pregnancy: As a precaution, roxithromycin should preferably not be used during pregnancy.
Although there is no evidence of teratogenic or fetotoxic effects from animal studies at doses higher than 200 mg/kg/day or 40 times the therapeutic dosage in humans, the clinical data are insufficient.
Lactation: Most macrolides have been found to be excreted in breast milk, at concentrations equal to or higher than plasma concentrations. However, the amounts ingested by the breastfed newborn are low compared to pediatric doses. The highest risk for the infant is intestinal flora imbalance. Breast-feeding during treatment is therefore possible. If the breast-fed infant develops gastro-intestinal disorders (intestinal candidiasis, diarrhea), breast-feeding must be stopped (or treatment with the drug discontinued).
If the breast-fed newborn or infant is being treated with cisapride, use of macrolides in the mother is contraindicated as a precaution due to the potential risk of interaction in the infant (torsades de pointes).

In case of overdosage: gastric lavage and symptomatic treatment: there is no specific antidote.

Storage: Do not store above 25°C.