Rozamet^® (Cream) Instructions for Use

Marketing Authorization Holder

Jadran-Galenski Laboratorij, D.D. (Croatia)

Contact Information

JADRAN-GALENSKI LABORATORIJ d.d. (Croatia)

ATC Code

D06BX01 (Metronidazole)

Active Substance

Metronidazole (Rec.INN registered by WHO)

Dosage Form

Rozamet®

Cream for external use 1%: tube 25 g

Dosage Form, Packaging, and Composition

Cream for external use homogeneous, white in color, odorless.

Excipients: glycerol, liquid paraffin, emulsifier Lanette SX [cetearyl alcohol, sodium lauryl sulfate, purified water], propylene glycol, methylparahydroxybenzoate, propylparahydroxybenzoate, purified water.

25 g – aluminum tubes* (1) – cardboard packs.

* coated with protective varnish on the inside and outside, with a sealed protective membrane opening and a plastic cap equipped with a conical device for piercing the protective membrane.

Clinical-Pharmacological Group

Antiprotozoal drug with antibacterial activity for external use

Pharmacotherapeutic Group

Antibiotics and antimicrobial agents used in dermatology; antimicrobial agents for topical use; other antimicrobial agents

Pharmacological Action

Mechanism of action and pharmacodynamic effects

Metronidazole is a nitroimidazole derivative. It has antimicrobial and antiprotozoal activity against gram-negative aerobic and anaerobic microorganisms and protozoa.

Metronidazole is particularly effective for topical application against papulopustular inflammatory elements of rosacea. The mechanism of action also appears to include an anti-inflammatory effect.

Pharmacokinetics

The C_max of metronidazole in blood plasma after topical application of 1 g of Rozamet^® cream to the facial skin averages 32.9 ng/ml (range 14.8-54.4 ng/ml) and is reached within 6-24 hours.

The C_max of metronidazole in blood plasma after topical application does not exceed 0.5% of the average C_max of metronidazole in blood plasma after oral administration of 250 mg of metronidazole in tablet form.

With topical application, the concentration of metronidazole at the site of cream application is significantly higher than in the blood plasma.

Protein binding is insignificant. The lowest concentration of metronidazole is determined in adipose tissue. It is excreted by the kidneys unchanged and in the form of metabolites.

Indications

Adults

• Treatment of rosacea.

ICD codes

Dosage Regimen

Adults

Rozamet^® cream is applied in a thin layer to previously cleansed affected skin areas 2 times/day, in the morning and in the evening, avoiding contact with the eyes, lips, and nasal mucous membranes.

The average duration of treatment is 3-4 months. However, in the presence of clear signs of therapy effectiveness, the attending physician may consider continuing treatment for an additional 3-4 months, depending on the severity of the patient’s condition. In the absence of clear clinical improvement, treatment should be discontinued.

Children

The safety and efficacy of Rozamet^® in children aged 0 to 18 years have not been established to date. Data are not available.

Method of administration

The medicinal product is for external use only. Before applying the cream, the affected skin area should be washed with warm water or a mild detergent that does not cause skin irritation. After applying the cream, the use of cosmetic products that do not have comedogenic and astringent properties is possible.

Adverse Reactions

The adverse events listed below are presented according to the affected organs and organ systems and frequency of occurrence. Frequency is defined as follows

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after drug registration to ensure continuous monitoring of the benefit-risk balance of the drug. Healthcare professionals are encouraged to report any suspected adverse drug reactions through the national adverse reaction reporting system of the member states of the Eurasian Economic Union.

Contraindications

• Hypersensitivity to metronidazole and other components of the drug;
• Children under 18 years of age.

Use in Pregnancy and Lactation

Pregnancy

There are no data on clinical experience with the topical use of metronidazole in pregnant women. When taken orally, Metronidazole crosses the placental barrier and rapidly enters the fetal bloodstream. No signs of fetal toxicity were observed after oral administration of metronidazole to rats or mice.

Nevertheless, since animal reproduction toxicity studies do not always predict the human response, and since carcinogenic properties of metronidazole were demonstrated in rodents after oral administration, the drug during pregnancy should be used only if the expected benefit to the mother outweighs the potential risk to the fetus after consultation with a doctor.

Breastfeeding period

After oral administration, Metronidazole passes into breast milk in concentrations similar to those found in blood plasma. Although after topical application of metronidazole in breastfeeding women its concentration in blood plasma is significantly lower than after oral administration, the decision to discontinue breastfeeding or discontinue the drug should be made taking into account the assessment of the importance of the drug for the mother and the risk to the child after consultation with a doctor.

Pediatric Use

Rozamet^® is not recommended for use in children under 18 years of age due to the lack of data on the safety and efficacy of metronidazole use in patients of this age category.

Geriatric Use

No dose adjustment is required for elderly patients.

Special Precautions

If signs of skin irritation appear due to the use of Rozamet^® cream, the frequency of its application should be reduced, its use should be temporarily suspended, or the drug should be discontinued and a doctor should be consulted.

Avoid getting the cream into the eyes and on mucous membranes. In case of accidental contact, rinse thoroughly with warm water.

During treatment, exposure to UV radiation (direct sunlight, tanning beds, sunlamps) should be avoided. Under the influence of UV radiation, Metronidazole is converted into an inactive metabolite, so its effectiveness is significantly reduced.

Excessive and prolonged use of the drug should be avoided.

Metronidazole is a nitroimidazole derivative; it should be used with caution in patients with blood disorders, including in the medical history.

Excipients

The medicinal product Rozamet^® contains cetearyl alcohol, which may cause local skin reactions (e.g., contact dermatitis).

The drug contains propylene glycol, which may cause skin irritation.

The medicinal product Rozamet^® contains methylparahydroxybenzoate and propylparahydroxybenzoate, which may cause allergic reactions (including delayed ones).

Effect on ability to drive vehicles and operate machinery

The drug does not have a negative effect on the ability to perform potentially hazardous activities requiring increased concentration and speed of psychomotor reactions (driving vehicles, working with moving machinery, work of a dispatcher and operator) based on the pharmacodynamic profile and clinical experience of use.

Overdose

To date, no cases of overdose with topical use of the drug have been reported. When the drug is used in accordance with the instructions for use, overdose is unlikely.

Drug Interactions

No cases of interaction with other medicinal products have been reported with the use of Rozamet^® cream. Interaction with systemic drugs is unlikely due to the low absorption of metronidazole after topical application.

Nevertheless, a disulfiram-like reaction is observed in a small number of patients with simultaneous oral use of metronidazole and ethanol.

The warning to exercise caution when using metronidazole concomitantly with warfarin or other indirect anticoagulants due to a possible increase in prothrombin time applies only to orally administered metronidazole.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 2 years. Do not use after the expiration date.

The shelf life of the drug after first opening is 2 months.

Dispensing Status

The drug is available without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.