Topical treatment of rosacea.

Official recommendations on the proper use of anti-bacterial agents should be taken into account.

Apply a thin layer of gel to the affected areas of the skin twice daily, morning and evening after washing with mild soap. Patients should wash their hands after applying Rozex. They should use non-comedogenic and non-astringent cosmetics. It is not necessary to adjust dosage in elderly people.

Rozex is not recommended in children due to lack of safety and efficacy data.

The usual duration of treatment is 3 to 4 months.

The recommended duration of treatment should not be exceeded. However, if a clear benefit has been demonstrated, continued therapy for a further three- to four-month period may be considered by the prescribing physician depending on the severity of the rosacea.

In clinical studies, topical metronidazole therapy for rosacea has been continued for up to 2 years.

In the absence of a clear clinical improvement, therapy should be stopped.

- Warning: Avoid contact with the eyes. If contact with the eyes occurs the gel should be washed out carefully with water.

- Precautions: The following statements take into account the possibility that metronidazole may be absorbed after topical application. However there is no evidence of any significant systemic concentrations of metronidazole following topical applications. Peripheral neuropathy has been reported in association with prolonged use of oral metronidazole. The elimination half-life of metronidazole remains unchanged in the presence of renal failure. Such patients, however, retain the metabolite of metronidazole. The clinical significance of this is not known at present. However in patients undergoing haemodialysis, metronidazole and its metabolites are efficiently removed.

The UV exposure (sunbathing, solarium, sunlamp) should be avoided during the therapy with metronidazole.

Metronidazole transforms into inactive metabolite due to UV exposure, therefore its efficacy decreases significantly. Phototoxic side-effects haven’t been reported in clinical trials in relation to metronidazole.

Metronidazole is a nitro imidazole and should be used with caution in patients with an evidence of, or history of blood dyscrasia.

Patients are advised not to take alcohol during systemic metronidazole therapy because of the possibility of a disulfiram-like reaction.

Some potentiation of anti-coagulant therapy has been reported when metronidazole has been used with the warfarin type oral anticoagulants.

Patients receiving phenobarbitone metabolise metronidazole at a much faster rate than normal, reducing the half-life to 3 hours.

Pregnancy

Animal studies have not revealed any teratogenic effects of metronidazole.

The analysis of a high number of exposed pregnancies showed no particular malformative or foetotoxic effect of metronidazole.

Rozex can therefore be used during pregnancy if necessary.

Breast-feeding

After oral administration, metronidazole is excreted in breast milk in concentrations similar to those found in the plasma. However, metronidazole blood levels from topical administration of Rozex are significantly lower than those achieved after oral administration (serum concentration from topical administration is less than 1% of that from oral administration) (see section 5.2). The administration of Rozex in mothers who are breast-feeding may therefore be considered.

Considering the pharmacodynamic profile of Rozex and clinical experience, Rozex should have no influence on the ability to drive and use machines.

Adverse reactions are classified by System Organ Class and frequency, using the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to <1/1000), very rare (< 1/10000), unknown frequency (cannot be estimated from the available data).

Reporting of suspected adverse reactions

Saudi Arabia:

The National Pharmacovigilance Centre (NPC):

- SFDA Call Centre: 19999

- Email: npc.drug@sfda.gov.sa

Website: https//ade.sfda.gov.sa/

Other GCC States:

- Please contact the relevant competent authority.

No data exists regarding overdose in humans. Acute oral toxicity studies with a topical gel formulation containing 0.75% metronidazole in rats have shown no toxic action with doses of up to 5 g of finished product per kilogram body weight, the highest dose used. This dose is equivalent to the oral intake of 12 tubes of 30 g of Rozex for an adult weighing 72 kg, and 2 tubes of Cream for a child weighing 12 kg.

Pharmacotherapeutic class:CHEMOTHERAPEUTICS FOR EXTERNAL USE, ATC Code: D06BX01

Metronidazole is an antiparasitic and antibacterial agent which is active against a wide range of pathogenic microorganisms. Metronidazole is particularly effective against the papulopustular inflammatory component of the disease.

Its mechanism of action seems likely to involve an anti-inflammatory effect.

ANTIMICROBIAL ACTIVITY SPECTRUM

The breakpoints separating susceptible (S) strains from intermediate (I) sensitivity strains, and the latter from resistant (R) strains are:

S £ 4 mg/l and R > 4 mg/l

The prevalence of acquired resistance may vary geographically and over time for selected species. Local information on resistance is therefore desirable, particularly when treating severe infections. These data can only provide an indication of the likelihood of a given bacterial strain being susceptible to this antibiotic.

Where variability in the prevalence of resistance in France is known for a bacterial species, it is shown in the table below:

Note: this spectrum is for systemic forms of metronidazole.With topical dosage forms, the in situ drug concentrations achieved are significantly higher than plasma concentrations.Some uncertainties remain with regard to the kinetics of in situ concentrations on local physicochemical conditions which may alter the activity of the antibiotic and in situ product stability.

After application of 1 g Rozex 0.75% Gel to the faces of 12 healthy subjects, the reported mean serum concentration of metronidazole was 32.9 ng/ml (14.8–54.4 ng/ml). This result is less than 1% of the mean serum concentration found in healthy subjects after administration of 250 mg of oral metronidazole (mean Cmax = 7245 ng/ml: 4270–13970 ng/ml). Peak concentrations were observed 0.25–4 hr after oral administration of metronidazole and 6–24 hr after cutaneous application of Rozex 0.75% Gel.

Earlier onset of UV-induced skin tumours was observed in nude mice treated with metronidazole intraperitoneally.

Propylene glycol(E1520), Carbomer 940, disodium edetate, methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216), sodium hydroxide(for pH adjustment), purified water.

Not applicable.

Store at room temperature.

Do not store above 30C.

15 g, 30 g or 50 g in varnished aluminium tubes.

Not all pack sizes may be marketed.

No special requirements.