Consumer medicine information

Rozex Cream

Metronidazole

BRAND INFORMATION

Brand name

Rozex Cream

Active ingredient

Metronidazole

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Rozex Cream.

What is in this leaflet

This leaflet answers some common questions about ROZEX CREAM. Please read this leaflet carefully before you start using the cream. It does not contain all the information available on this medicine.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of using ROZEX CREAM against the benefits it might have for you. If you have any concerns about taking this medicine ask your doctor or pharmacist.

Keep this leaflet with your tube. You may wish to read it again later.

What ROZEX CREAM is used for

ROZEX CREAM is used for the treatment of inflammatory papules and pustules of rosacea. Skin affected by rosacea has one or more of the following features: a redness that looks like a blush; pimples; small knobbly lumps on the nose and / or thin red lines due to enlarged blood vessels.

The active ingredient in ROZEX CREAM is metronidazole which belongs to the class of medicines known as antiprotozoals and antibacterials.

It is not clear how ROZEX CREAM works however it may have antibacterial and anti-inflammatory action.

Preparations that are applied to the skin such as ROZEX CREAM can be used in combination with other oral medications prescribed by your doctor.

Ask your doctor if you have any questions about why ROZEX CREAM has been prescribed for you. Your doctor may have prescribed it for another reason.

Before you use ROZEX CREAM

When you must not use it

  • if you have an allergy to metronidazole or any of the other ingredients listed at the end of this leaflet.
  • if you have or ever have had a blood disorder
  • to treat your child’s skin problem. ROZEX CREAM has not been studied for use in children.
  • if you are pregnant. There are no well-controlled studies of therapy with ROZEX CREAM in pregnant women.

Symptoms of an allergic reaction may include:

  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching, or hives of the skin, especially on the areas of the skin where the cream was applied.

Tell your doctor if you think you have an allergy.

Do not use ROZEX CREAM after the expiry date (EXP) printed on the pack has passed or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your doctor or pharmacist for disposal.

Before you start to use it

Tell your doctor or pharmacist if you are pregnant or plan to become pregnant. With not enough information available on the effect of ROZEX CREAM on pregnant women, ROZEX CREAM is not recommended for use during pregnancy.

Tell your doctor if you are breast-feeding. Your doctor will discuss the risks and benefits of using ROZEX CREAM while breast-feeding.

If you have not told your doctor or pharmacist about any of the above, tell them before you start using ROZEX CREAM.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines you buy without a prescription from a pharmacy, supermarket, or health food shop.

Some medicines and ROZEX CREAM may interfere with each other. Your doctor and pharmacist may have more information on medicines to be careful with while using ROZEX CREAM.

How to use ROZEX CREAM

Things you must do

  • Wash and dry your hands before applying the cream.
  • Apply morning and evening to a dry, clean face.
  • Squeeze a small quantity of ROZEX CREAM onto your fingertips and rub a thin film onto the affected areas.
  • Avoid getting ROZEX CREAM into your eyes.
  • Use a sunscreen when exposure to the sun cannot be avoided.

ROZEX CREAM is only for use on the skin.

Continue to use it even though there may not be an immediate effect. Medicines can take several weeks to show an effect. The average period of treatment is usually three to four months. The recommended duration of treatment should not be exceeded.

While you are taking ROZEX CREAM

Things you must do

  • Tell all doctors and nurses who are treating you that you are using ROZEX CREAM.
  • If you feel that ROZEX CREAM is not helping your condition, tell your doctor or nurse.
  • Tell your doctor if you become pregnant while using ROZEX CREAM.

Things you must not do

  • Do not use cosmetic products that contain alcohol or are abrasive.
  • Do not use medicated soaps. These may have an extra drying or irritant effect.
  • It is not known if ROZEX CREAM can increase the likelihood of skin cancers developing in people who have excessive exposure to sunlight. Therefore you should avoid or minimise exposure of areas treated with ROZEX CREAM to sunlight or other sources of UV light.
  • Unnecessary or prolonged use of ROZEX CREAM should be avoided as the long-term safety is unknown.

Things you can do

  • Apply makeup over ROZEX CREAM.

Things to be careful of

ROZEX CREAM should not come into contact with the eyes or mucous membranes. If accidental contact occurs, rinse thoroughly with water and pat dry.

Avoid conditions known to make rosacea worse such as hot, spicy foods, alcohol, extremes of temperature, and excessive exposure to sunlight.

Use ROZEX CREAM less frequently if your face becomes hot, red, itchy, or swollen.

Do not exceed the recommended duration of treatment.

Stop using ROZEX CREAM and see your doctor if the problem persists.

If you forget to use it

If you forget to apply ROZEX CREAM use it again as directed, as soon as you remember.

Do not apply a double dose to make up for forgotten individual doses.

If you have trouble remembering to use your medicine, ask your pharmacist for some hints.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well whilst you are using ROZEX CREAM.

All medicines can have side effects. Sometimes they are serious, but most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • dry skin
  • superficial reddening of skin
  • severe itching of the skin
  • skin discomfort (burning, dryness, pain of skin/stinging)
  • skin irritation
  • worsening of rosacea
  • hyperpigmentation and other pigmentation disorders

These are more common side effects of ROZEX CREAM.

Tell your doctor or pharmacist if you notice any of the following:

  • contact dermatitis
  • reduced sense of touch or sensation
  • tingling or pricking sensation (‘pins and needles’)
  • numbness in the extremities
  • dysgeusia (metallic taste)
  • seborrhoea (red, itchy rash and white scales)
  • sunburn
  • skin infection
  • hives
  • gastritis
  • bronchitis
  • stuffy, runny nose
  • skin exfoliation
  • swelling face
  • nausea
  • excess watery fluid collection on the face or eyelids

These are uncommon side effects of ROZEX CREAM.

Tell your doctor or pharmacist if you notice any of the following:

  • hypothyroidism
  • Bursitis (inflammation or irritation of the bursa)
  • Myalgia (muscle pain)
  • osteoporosis
  • conjunctivitis
  • abscess

These are rare side effects of ROZEX GEL.

Other side effects not listed above may occur in some patients. Tell your doctor or pharmacist if you notice any side effects not mentioned in this leaflet.

If any of the side effects become serious or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

In case of accidental swallowing

Immediately telephone your doctor or Poisons Information Centre for advice on telephone 13 11 26 if in Australia or 0800 POISON or 0800 764 766 if in New Zealand.

After using ROZEX CREAM

If you have queries about any aspect of your medicine or any questions regarding the information in this leaflet, discuss them with your doctor or pharmacist.

Storage

Keep the medicine in a cool dry place where the temperature stays below 25°C.

Do not store it, or any other medicine, in a bathroom, near a sink, or on a window sill.

Do not leave it in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop using ROZEX CREAM or it has passed its expiry date, ask your pharmacist what to do with any that is left over. Return any unused medicine to your pharmacist.

Product Description

What it looks like

ROZEX CREAM is a smooth white cream in a plastic tube with a screw cap containing 3g, 5g, 15g, 30g and 50g of cream.

Not all pack sizes may be available.

Ingredients

Each gram of ROZEX CREAM contains 7.5 mg/g of metronidazole as the active ingredient.

It also contains the following inactive ingredients:

  • benzyl alcohol,
  • isopropyl palmitate,
  • glycerol,
  • sorbitol,
  • emulsifying wax,
  • lactic acid or sodium hydroxide,
  • purified water.

Sponsor / Distributor

Galderma Australia Pty Ltd
Level 18, 1 Denison Street
North Sydney, NSW 2060
Telephone 1800 800 765

Distributed in New Zealand by:

Healthcare Logistics’
58 Richard Pearce Drive
Airport Oaks
Auckland
Telephone 0800 174 104

Made in France

Australian Registration Number: AUST R 72393

® Registered Trademark

This leaflet was updated in August 2023.

Published by MIMS May 2024

BRAND INFORMATION

Brand name

Rozex Cream

Active ingredient

Metronidazole

Schedule

S4

 

1 Name of Medicine

Metronidazole.

2 Qualitative and Quantitative Composition

Rozex Cream contains 0.75% w/w metronidazole as the active ingredient in an oil-in-water cream base.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

White to beige shiny cream.

4 Clinical Particulars

4.1 Therapeutic Indications

Rozex Cream is indicated for the treatment of inflammatory papules and pustules of rosacea.

4.2 Dose and Method of Administration

Rozex Cream should be applied in a thin layer to the affected areas of the skin twice daily, morning and evening. Areas to be treated should be washed with a mild cleanser before application. Patients may use non-comedogenic and non-astringent cosmetics after application of Rozex Cream. The dosage does not need to be adjusted for elderly patients. Safety and effectiveness in paediatric patients have not been established. Rozex is not recommended for use in children.
The average period of treatment is three to four months. The recommended duration of treatment should not be exceeded. If a clear benefit has been demonstrated continued therapy for a further three to four months period may be considered by the prescribing physician depending upon the severity of the condition. Clinical experience with Rozex Cream over prolonged periods is limited at present. Patients should be monitored to ensure that clinical benefit continues and that no local or systemic events occur. In the absence of a clear clinical improvement therapy should be stopped.
Rozex should not be used in or close to the eyes.
The use of a sunscreen is recommended when exposure to sunlight cannot be avoided.

4.3 Contraindications

Rozex Cream is contraindicated in individuals with a history of hypersensitivity to metronidazole or other ingredients of the formulation.

4.4 Special Warnings and Precautions for Use

Rozex has been reported to irritate the eyes (watering), therefore contact with the eyes should be avoided, as well as with mucous membranes. If a reaction suggesting local irritation occurs, patients should be directed to use the medication less frequently, discontinue use temporarily or discontinue use until further instructions.
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 nitroimidazole compound and should be used with care in patients with evidence or a history of blood dyscrasia.
Patients should be advised to avoid or minimise exposure of areas treated with topical metronidazole to sunlight or other sources of UV light (see Section 5.3 Preclinical Safety Data, Genotoxicity, Carcinogenicity; Section 4.6 Fertility, Pregnancy and Lactation, Effects on fertility). Unnecessary or prolonged use of this medication should be avoided as the long-term safety of topical metronidazole is unknown.

Use in the elderly.

No data available.

Paediatric use.

Rozex Cream has not been studied in children. Rosacea is a skin disorder which principally affects adults.
Rozex Cream is not recommended for use in children due to a lack of data on safety and efficacy.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Interaction with systemic medication is unlikely because absorption of metronidazole following cutaneous application of Rozex Cream is low. Nevertheless it should be mentioned that a disulfiram-like reaction has been reported in a small number of patients taking oral metronidazole and alcohol concomitantly. Oral metronidazole has also been reported to potentiate the effect of warfarin and other coumarin anticoagulants resulting in a prolongation of prothrombin time. However the effect of topical metronidazole on prothrombin is not known.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Oral metronidazole caused hypospermatogenesis, infertility and abnormal spermatozoa in mice and rats with a NOEL in rats being about 200 times the estimated human metronidazole dose contained in the Rozex Cream, based on body surface area.
(Category B2)
The potential adverse effects of Rozex Cream on pregnancy have not been determined however oral metronidazole is known to cross the placental barrier and enter the foetal circulation rapidly. There is no conclusive evidence of fetotoxicity or teratogenicity in animal studies with metronidazole nor has clinical experience to date with the use of metronidazole in pregnant women revealed evidence of a fetotoxic or teratogenic effect of the drug. Because there are no well controlled studies of therapy with Rozex Cream in pregnant women, Rozex Cream should not be used during pregnancy.
 After oral administration metronidazole is excreted in breast milk in concentrations similar to those found in the plasma. Metronidazole blood levels from topical application are significantly lower than those achieved after oral metronidazole. A decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

(See Table 1.)
The total number of adverse effects occurred in less than 3% of patients. Of the eleven patients who discontinued a study prematurely because of a dermatological adverse event, 2.5% were in the cream treatment group and 6.7% in the gel treatment group.

Postmarketing experience.

The following nonserious adverse experiences have been reported since Rozex Cream was first marketed in 1995: contact dermatitis/ allergic reaction; skin exfoliation, swelling face, local irritation, erythema, pruritus, burning, dryness, tightness, discomfort, rash, hyperpigmentation, pigmentation disorders, hypertrichosis, facial oedema, eyelid oedema, treatment failure (worsening of rosacea), watery eyes, metallic taste, tingling or numbness in the extremities, nausea, other (zoster lesion, pustules on the nose and vesicular bullous eruptions). The causal relationship with topical metronidazole has not been unequivocally established for these adverse experiences.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

There is no human experience with overdosage of Rozex Cream.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Metronidazole is an antiprotozoal (trichomoniasis, amoebiasis, giardiasis) and anaerobic antibacterial agent. However, the mechanisms by which Rozex acts in reducing inflammatory lesions of rosacea are unknown.

Clinical trials.

One multicentre randomised, double-blind, placebo-controlled clinical study was conducted to evaluate Rozex Cream for the treatment of rosacea. All the patients included in the trial had moderate to severe (stage 2) rosacea. The prescribed therapy was applied daily for 12 weeks with follow up at weeks 3, 6, 9 and 12. The results are tabulated in Table 2.
There were no significant differences between the treatment groups in the reduction of erythema or telangiectasis. For a subgroup within the Rozex Cream group who had dry skin there was a significant reduction in erythema (59.6% vs 30.4%, p=0.05).
In another randomised single-blind multicentre study (n=100) in which the gel and cream formulations were compared, there were no significant differences in lesion counts or global assessment of improvement at weeks 4, 8 and 12. All patients recruited to the study had moderate to severe stage 2 rosacea. The percent reduction in mean lesion count from baseline to week 12 was 61.3% (MZ cream) vs 63.5% (MZ gel), p= n.s.

5.2 Pharmacokinetic Properties

Absorption.

Following a single topical 1 gram application of Rozex Cream to the face of twelve normal human subjects, a mean maximum serum metronidazole concentration of 32.9 nanogram.mL-1 was reported (range: 14.8 to 54.4 nanogram.mL-1). This is less than 0.5% of the mean maximum metronidazole concentration reported in the same subjects administered a single oral 250 mg tablet of metronidazole (mean Cmax = 7248 nanogram.mL-1, range: 4270 to 13,970 nanogram.mL-1). The Tlag and Tmax for metronidazole after topical administration of the cream formulation were significantly (p < 0.05) prolonged when compared with oral administration. In comparison to the oral tablet the mean Tmax for the topical formulation occurred 7.0 hours later (95% confidence interval: 2.7 to 11.3 hours).

Distribution.

The extent of exposure (area under the curve (AUC)) from a 1 gram application of metronidazole administered topically was 1.2% of the AUC of a single oral 250 mg metronidazole dose (mean = 912.7 nanogram.hr mL-1 and approximately 67,207 nanogram.hr mL-1 and respectively).

Metabolism.

The hydroxymetabolite (2-hydroxymethylmetronidazole) Cmax after the 250 mg oral dose ranged from 626 to 1788 nanogram.mL-1 and peaked between 4 and 12 hours. Following topical application of Rozex Cream the hydroxymetabolite serum concentrations were below the quantifiable limit of the assay (< 9.6 nanogram.mL-1) at the majority of time points. The hydroxymetabolite Cmax after topical administration of the cream ranged from below the quantifiable limit to 17.6 nanogram.mL-1.

5.3 Preclinical Safety Data

Genotoxicity.

Metronidazole has shown evidence of mutagenic activity in several bacterial systems. In addition, a dose response increase in the frequency of micronuclei was observed in mice after intraperitoneal injection and an increase in chromosome aberrations has been found in human lymphocyte cultures. The benefit/risk ratio should therefore be carefully assessed in each case particularly in relation to the severity of the disease and the age of the patient.

Carcinogenicity.

Animal studies with oral metronidazole showed increased incidences of tumour in the lung, liver, testes, reticulum, mammary gland, and pituitary gland in certain rodent species. Evidence of photocarcinogenicity of metronidazole has also been reported in mice. Although there is no evidence to date of a carcinogenic effect in humans it is prudent to avoid unnecessary and prolonged use of Rozex Cream and to avoid or to minimise exposure of sites treated with Rozex Cream to the sun.

6 Pharmaceutical Particulars

6.1 List of Excipients

Benzyl alcohol, isopropyl palmitate, glycerol, sorbitol 70% (non-crystallising), emulsifying wax, lactic acid or sodium hydroxide solutions to adjust pH and purified water.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Do not refrigerate.

6.5 Nature and Contents of Container

3 g, 5 g, 15 g, 30 g and 50 g tubes. Not all pack sizes may be marketed.
AUST R 72393.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical name: 2-methyl-5-nitroimidazole-1-ethanol.

Chemical structure.


Molecular formula: C6H9N3O3.
Molecular weight: 171.16.

CAS number.

443-48-1.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes