Altargo - patient leaflet, side effects, dosage

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Single plasma samples were obtained from 516 adult and paediatric patients who received topical treatment with retapamulin 10 mg/g ointment twice daily for 5 days for the treatment of secondarily infected traumatic lesions. Sampling occurred pre-dose for adult subjects on days 3 or 4, and between 0–12 hours after the last application for paediatric subjects on days 3 or 4. The majority of samples (89%) were below the lower limit of quantitation (0.5 ng/ml). Of the samples that had measurable concentrations 90% had retapamulin concentrations less than 2.5 ng/ml. The maximum measured plasma concentration of retapamulin was 10.7 ng/ml in adults and 18.5 ng/ml in paediatric patients (aged 2–17 years).

Patients aged from 2 months to 24 months

Single plasma samples were obtained approximately 4–8 hours after the first application on days 3 or 4 from patients aged from 2 months to 2 years with impetigo or with secondarily infected traumatic lesions or dermatoses (note that retapamulin is not indicated for use in secondarily infected dermatoses). Retapamulin concentrations were measurable in 46% (36/79) of samples (range 0.52 to 177.3 ng/ml) but the majority of these samples (27/36; 75%) contained < 5.0 ng/ml.

Among the children aged from 9 months to 2 years plasma concentrations of retapamulin were measurable in 32% (16/50) of samples. A single retapamulin concentration (95.1 ng/ml) exceeded the highest concentration observed in patients aged 2–17 years (18.5 ng/ml). This plasma concentration was observed in a child with a secondary infected dermatosis, for which retapamulin is not indicated for use.

Retapamulin is not recommended for use in children aged less than 9 months. In children aged from 2 months to 9 months plasma concentrations of retapamulin were measurable in 69% (20/29) of samples. Four plasma retapamulin concentrations (26.9, 80.3, 174.3, and 177.3 ng/ml) exceeded the highest concentration observed in patients aged 2–17 years (18.5 ng/ml).

Distribution

Due to the very low systemic exposures, tissue distribution of retapamulin has not been investigated in humans.

In vitro , retapamulin was shown to be a P-glycoprotein (Pgp) substrate and inhibitor.

However, the maximum individual systemic exposure in humans following topical application of 10 mg/g ointment on 200 cm2 of abraded skin (Cmax= 22 ng/ml; AUC(0–24) = 238 ng.h/ml) was 660-fold lower than the retapamulin IC50 for Pgp inhibition.

Retapamulin is approximately 94% bound to human plasma proteins.

Biotransformation

The in vitro oxidative metabolism of retapamulin in human liver microsomes was primarily mediated by CYP3A4 with minor contributions from CYP2C8 and CYP2D6 (see section 4.5).

Elimination

Retapamulin elimination in humans has not been investigated.

Special populations

No pharmacokinetic data are available in patients with renal or hepatic impairment. However, due to the low systemic plasma levels that have been observed, no safety problems are foreseen.

• 5.3 Preclinical safety data

Repeated-dose toxicity

In 14-day (50, 150 or 450 mg/kg) oral toxicity studies in rats there was evidence of adaptive hepatic and thyroid changes. Neither of these findings is of clinical relevance.

In monkeys dosed orally (50, 150 or 450 mg/kg) for 14 days there was dose-related emesis.

Carcinogenesis, mutagenesis, reproductive toxicity

Long-term studies in animals to evaluate carcinogenic potential have not been conducted with retapamulin.

There was no evidence of genotoxicity when evaluated in vitro for gene mutation and/or chromosomal effects in the mouse lymphoma cell assay, in cultured human peripheral blood lymphocytes, or when evaluated in vivo for chromosomal effects in a rat micronucleus test.

There was no evidence of impaired fertility in male or female rats at oral doses of 50, 150, or 450 mg/kg/day, resulting in exposure margins of up to 5-times the highest human estimated exposure (topical application to 200 cm2 abraded skin: AUC 238 ng.h/ml).

In an embryotoxicity study in rats, developmental toxicity (decreased fetal body weight and delayed skeletal ossification) and maternal toxicity were observed at oral doses of > 150 mg/kg/day (Corresponding to > 3 times the human estimated exposure (see above). There were no treatment-related malformations in rats.

Retapamulin was given as a continuous intravenous infusion to pregnant rabbits from day 7 to day 19 of gestation. Maternal toxicity was demonstrated at dosages of > 7.2 mg/kg/day corresponding to > 8 times the estimated human exposure (see above). There was no treatment-related effect on embryofetal development.

No studies to evaluate effects of retapamulin on pre-/postnatal development were performed. However, there were no systemic effects on juvenile rats with topical application of retapamulin ointment.

• 6. PHARMACEUTICAL PARTICULARS

  • 6.1 List of excipients

White soft paraffin

Butylated hydroxytoluene (E321)

• 6.2 Incompati­bilities

Not applicable

• 6.3 Shelf life

Unopened tube and sachet: 2 years.

In-use tube: 7 days.

• 6.4 Special precautions for storage

Do not store above 25°C.

• 6.5 Nature and contents of container

0.5 g aluminium foil sachet. Carton of 12 sachets.

5 g, 10 g and 15 g aluminium tubes with a plastic screw cap. Carton of 1 tube.

Not all pack sizes may be marketed.

• 6.6 Special precautions for disposal

Any remaining ointment at the end of treatment should be discarded.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

• 7. MARKETING AUTHORISATION HOLDER

Glaxo Group Ltd

980 Great West Road

BrentfordMiddlesex TW8 9GS

United Kingdom

• 8. MARKETING AUTHORISATION NUMBER(S )

EU/1/07/390/001

EU/1/07/390/002

EU/1/07/390/003

EU/1/07/390/004

• 9. DATE OF FIRST AUTHORISATION/RE­NEWAL OF THE AUTHORISATION

Date of first authorisation: 24 May 2007

Date of latest renewal: 20 April 2012

• 10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines Agency: /.

• A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer responsible for batch release

Glaxo Operations UK Ltd. (trdg as Glaxo Wellcome Operations)

Harmire Road

Barnard Castle

Durham, DL12 8DT

United Kingdom

• B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

• C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETI AUTHORISATION

  
  

• Periodic Safety Update Reports

The marketing authorisation holder shall submit periodic safety update reports for this product in accordance with the requirements set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH R

EFFECTIVE USE OF THE MEDICINAL PRODUCT

Risk Management Plan (RMP)

The MAH shall perform the required ph agreed RMP presented in Module 1.8.2. updates of the RMP.

An updated RMP should be submitted:

• At the request of the European Medicines Agency;
• Whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached.

If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the same time.

0.5 g SACHET

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Altargo 10 mg/g ointment

Retapamulin

Cutaneous use.

2. What you need to know before you use Altargo

Other medicines and Altargo

Do not apply other ointments, creams or lotions to the area being treated with Altargo unless specifically instructed to do so by your doctor.

Tell your doctor if you are using, have recently used or might use any other medicines. If the patient is a child less than two years old it is especially important that you tell your doctor about any other medicines that the child is being given, including medicines bought without a prescription. It is possible that using Altargo in children who are taking certain medicines (such as some medicines to treat fungal infections) could result in blood concentrations of Altargo that are higher than This might lead to side effects. Your doctor will decide if Altargo can be used for a child age than 2 years old who is taking other medicines.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask

your doctor or pharmacist for advice before using this medicine. Your doctor will decide if this treatment is right for you.

Driving and using machines

Altargo is not expected to affect your ability to drive or use machi

Altargo contains butylated hydroxytoluene (E321)

3. How to use Altargo

It may cause local skin reactions (e.g. contact derm , or irritation of the eyes and mucous membranes.

Always use this medicine exactly you are not sure.

ually put on the infected skin twice a day for five days.

After applying your ointment, you may cover the treated area with a sterile bandage or gauze dressing, unless your doctor has told you to leave it uncovered.

Keep using Altargo for as long as your doctor advises.

Altargo is for use on the skin only. It must not be put in the eyes, on the mouth or lips, inside the nose or inside the female genital area. If the ointment accidentally gets on to these areas, wash the area water and consult your doctor if you experience discomfort. If you accidentally use Altargo e your nose you could have a nose bleed.

Wash your hands before and after applying the ointment.

If you use more Altargo than you should

Carefully wipe off the extra ointment.

If you forget to use Altargo

Apply the ointment as soon as you remember, and apply the next dose at the usual time.

If you accidentally swallow Altargo

Contact your doctor or pharmacist for advice.

If you stop using Altargo

If you stop using Altargo too soon, the bacteria may start to grow again and your infection may come back. Do not stop using this medicine before talking to your doctor or pharmacist.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Conditions to look out for

Severe skin reactions or allergies (frequency not known)

If you develop a severe skin reaction or an allergy: (e.g. severe itching or severe rash, swelling of the face, lips, or tongue):

• stop using Altargo
• carefully wipe off the ointment
• contact your doctor or pharmacist immediately.

The following side effects have occurred on the skin where Altargo has been applied:

Common side effects (may affect up to 1 in 10 people):

• – skin irritation

Uncommon side effects (may affect up to 1 in 100 people):

• – pain, itching, redness or rash (contact dermatitis)

5. How to store Altargo

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after ‘EXP’. The expiry date refers to the last day of that month.

Do not store above 25°C.

Discard open tubes 7 days after opening, even if they are not empty. They should not be kept for future use.

Do not throw away any medicines via household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other informationWhat Altargo containsThe active substance is retapamulin. Each gram of ointment contains 10 milligrams of retapamulin.The other ingredients are white soft paraffin and butylated hydroxytoluene preservative.or 15 grams of ointment,

What Altargo looks like and contents of the pack

Altargo is a smooth, off-white ointment.

It is supplied in an aluminium tube with a plastic cap, containing eith or in an aluminium foil sachet containing 0.5 g of ointment.

Pack of 1 tube.

Pack of 12 sachets.

Not all pack sizes may be marketed in your country

Marketing Authorisation Holder and Manufacturer

M^nuf Manufacturer

Glaxo Operations UK, Ltd, (trading as Glaxo

Wellcome Operations)

Harmire Road

Barnard Castle

County Durham DL12 8DT

Ísland

Vistor hf.

Simi: + 354 535 7000

Italia

GlaxoSmithKline S.p.A.

Tel: + 39 (0)45 9218 111

Kvnpog

GlaxoSmithKline Cyprus Ltd

Tql: + 357 22 39 70 00

Latvija

GlaxoSmithKline Latvia SIA Tel: + 371 67312687

Lietuva

GlaxoSmithKline Lietuva UAB

Tel: + 370 5 264 90 00

This leaflet was last revised in

Slovenská republika

GlaxoSmithKline Slovakia s. r. o.

Tel: + 421 (0)2 48 26 11 11

Suomi/Finland

GlaxoSmithKline Oy

Puh/Tel: + 358 (0)10 30 30 30

Sverige

GlaxoSmithKline AB

Tel: + 46 (0)8 638 93 00

United Kingdom

GlaxoSmithKline UK

Tel: + 44 (0)800 221441

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Detailed information on this medicine is available on the European Medicines Agency web site:

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