Indications:

Roxithromycin is indicated for the treatment of the following types of mild to moderately severe infections caused by or likely to be caused by susceptible micro-organisms: • upper respiratory tract infection - acute pharyngitis, tonsillitis and sinusitis • dental infections • lower respiratory tract infection - acute bronchitis; acute exacerbations of chronic bronchitis and community acquired pneumonia • skin and skin structure infections • non-gonococcal urethritis.

Contraindications:

known hypersensitivity to macrolides, including erythromycin • severely impaired hepatic function • concomitant therapy with vasoconstrictive ergot alkaloids

Adverse reactions:

Gastrointestinal. Nausea, vomiting, epigastric pain, diarrhoea (very rarely containing blood), anorexia, flatulence. In clinical studies, the incidence of gastrointestinal events was higher with the 300 mg once daily dosage regimen than with 150 mg twice daily. Hypersensitivity. Urticaria, rash, pruritus, angioedema. Rarely, serious allergic reactions may occur, e.g. asthma, bronchospasm, anaphylactic like reactions, purpura, glottic oedema, generalised oedema, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome. Hepatic. Moderate increases in serum transaminases (AST and ALT) and/or alkaline phosphatase levels have been observed and are somewhat more likely to occur in the elderly (> 65 years). Acute cholestatic hepatitis and acute hepatocellular injury are rarely reported. Other. Headache, dizziness, paraesthesia, tinnitus, malaise, moniliasis (candidiasis), pancreatitis, disorders of taste and/or smell.

Interactions:

Roxithromycin has a much lower affinity for cytochrome P450 than erythromycin, and consequently has fewer interactions. Interactions may be observed, however, with drugs that bind to alpha-1-acid glycoprotein, e.g. disopyramide. Roxithromycin does not appear to interact with oral contraceptives, prednisolone, carbamazepine, ranitidine or antacids. Theophylline. A study in normal subjects concurrently administered roxithromycin and theophylline has shown some increase in the plasma concentration of the latter. While a change in dosage is usually not required, patients with high levels of theophylline at commencement of treatment should have levels monitored. Ergot alkaloids. Reactions of ergotism with possible peripheral necrosis have been reported after concomitant therapy of macrolides with vasoconstrictive ergot alkaloids, particularly ergotamine and dihydroergotamine. Because a clinical interaction with roxithromycin cannot be excluded, administration of roxithromycin to patients taking ergot alkaloids is contraindicated. Disopyramide. An in vitro study has shown that roxithromycin can displace protein bound disopyramide; such an effect in vivo could result in increased serum levels of disopyramide. Consequently, ECG and, if possible, disopyramide serum levels should be monitored. Terfenadine. Some macrolide antibiotics (e.g. erythromycin) may increase serum levels of terfenadine. This can result in severe cardiovascular adverse events, including QT prolongation, torsades de pointes and other ventricular arrhythmias. Such a reaction has not been documented with roxithromycin, which has a much lower affinity for cytochrome P450 than erythromycin. However, in the absence of a systematic interaction study, concomitant administration of roxithromycin and terfenadine is not recommended. Astemizole, cisapride, pimozide. Other drugs, such as astemizole, cisapride or pimozide, which are metabolised by the hepatic isozyme CYP3A4, have been associated with QT interval prolongation and/or cardiac arrhythmias (typically torsades de pointes) as a result of an 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 CYP3A4 and hence 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. Thus, concomitant administration of roxithromycin and such drugs is not recommended. Warfarin. While no interaction was observed in volunteer studies, roxithromycin appears to interact with warfarin. Increases in prothrombin time (international normalised ratio (INR)) have been reported in patients treated concomitantly with roxithromycin and warfarin or the related vitamin K antagonist phenprocoumon, and severe bleeding episodes have occurred as a consequence. Digoxin and other cardiac glycosides. A study in healthy volunteers has shown that roxithromycin may increase the absorption of digoxin. This effect, common to other macrolides, may very rarely result in cardiac glycoside toxicity. This may be manifested by symptoms such as nausea, vomiting, diarrhoea, headache or dizziness. Cardiac glycoside toxicity may also elicit heart conduction and/or rhythm disorders. Consequently, in patients treated with roxithromycin and digoxin or another cardiac glycoside, ECG and, if possible, the serum level of the cardiac glycoside should be monitored. This is mandatory if symptoms suggesting cardiac glycoside overdosage have occurred. Midazolam. Roxithromycin, like other macrolides, may increase the area under the midazolam concentration-time curve and the midazolam half-life. Thus, the effects of midazolam may be enhanced and prolonged in patients treated with roxithromycin. There is no conclusive evidence for an interaction between roxithromycin and triazolam. Cyclosporin. A slight increase in plasma concentrations of cyclosporin A has been observed. This does not generally necessitate altering the usual dosage.

Warnings:

Hepatic impairment. Monitor liver function. Prolonged treatment increases risk of hepatotoxicity. History of arrhythmias.Use in pregnancy (Category B1) Use in lactation Small amounts of roxithromycin are excreted in the breast milk. Breastfeeding or treatment of the mother should be discontinued as necessary. No dosage adjustment is required in elderly patients.

Form:

SOLUTION FOR INJECTION