Document: spc-doc_PL 44673-0156 change

• spc-doc_PL 00030-0212
• spc-doc_PL 44673-0156

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Voltarol Pain-eze Emulgel®

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Diethylammonium-{-o-[2,6-dichlorophenyl)-amino]-phenyl}-acetate.

100g of Voltarol Pain-eze Emulgel contains 1.16g of the active substance diclofenac diethylammonium, which corresponds to 1g diclofenac sodium.

For excipients, see section 6.1

3 PHARMACEUTICAL FORM

Gel for topical administration.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the local symptomatic relief of pain and inflammation in:

•    Soft-tissue injuries: trauma of the tendons, ligaments, muscles and joints,

•    e.g. due to sprains, strains, bruises and backache (sports injuries)

•    localised forms of soft tissue rheumatism: tendonitis (e.g. tennis elbow), bursitis, shoulder-hand syndrome and periarthropathy.

4.2 Posology and method of administration

Adults and children aged 14 years and over: Voltarol Pain-eze Emulgel should be rubbed gently into the skin. Depending on the size of the affected site to be treated 2-4g (a circular shaped mass approximately 2.0-2.5 cm in diameter) should be applied 3-4 times a day. After application, the hands should be washed unless they are the site being treated.

A period of at least 4 hours should be left between applications. The dose should not be applied more than 4 times in a 24 hour period.

If symptoms persist after 7 days or get worse at any time, medical advice should be sought.

Not to be used for more than 7 days unless recommended by a doctor.

Use in the elderly: The usual adult dosage may be used.

Children and adolescents: There are insufficient data on efficacy and safety available for the children and adolescents below 14 years of age (see also contraindications section 4.3). In children aged 14 years and over, if this product is required for more than 7 days for pain relief or if the symptoms worsen the patient/parents of the adolescent is/are advised to consult a doctor.

4.3 Contraindications

Patients with or without chronic asthma in whom attacks of asthma, urticaria or acute rhinitis are precipitated by acetylsalicylic acid (aspirin) or other nonsteroidal anti-inflammatory agents (NSAIDs).

Hypersensitivity to diclofenac, acetylsalicylic acid, other non-steroidal antiinflammatory drugs or any of the excipients.

Third trimester of pregnancy.

Concomitant use of oral NSAID's.

Voltarol Pain-eze Emulgel should not be co-administered with other products containing diclofenac.

The use in children and adolescents aged less than 14 years is contraindicated.

4.4 Special warnings and precautions for use

The possibility of systemic adverse events from application of Voltarol Pain-eze Emulgel cannot be excluded if the preparation is used on large areas of skin and over a prolonged period (see the product information on systemic forms of diclofenac).

Voltarol Pain-eze Emulgel should be applied only to intact, non-diseased skin and not to skin wounds or open injuries. It should not be allowed to come into contact with the eyes or mucous membranes, and should not be ingested.

Discontinue the treatment if a skin rash develops after applying the product.

Patients with a history of, or active, peptic ulceration. Some possibility of gastro-intestinal bleeding in those with a significant history of this condition has been reported in isolated cases.

Like other drugs that inhibit prostaglandin synthetase activity, diclofenac and other NSAIDs can precipitate bronchospasm if administered to patients suffering from or with a previous history of asthma or allergic disease.

Voltarol Pain-eze Emulgel contains propylene glycol which may cause mild localised skin irritation in some people.

Voltarol Pain-eze Emulgel can be used with non-occlusive bandages but should not be used with an airtight occlusive dressing.

4.5 Interaction with other medicinal products and other forms of interaction

Since systemic absorption of diclofenac from a topical application of Voltarol Pain-eze Emulgel is very low such interactions are very unlikely. There are no known interactions with Voltarol Pain-eze Emulgel but for a list of interactions known with oral diclofenac the Summary of Product Characteristics for oral dosage forms should be consulted.

Concurrent use of aspirin or other NSAIDs may result in an increased incidence of adverse reactions.

4.6 Fertility, Pregnancy and lactation Pregnancy

The systemic concentration of diclofenac is lower after topical administration, compared to oral formulations. With reference to experience from treatment with NSAIDs with systemic uptake, the following is recommended:

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/fetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5 %. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-fetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, diclofenac should not be given unless clearly necessary. If diclofenac is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the fetus to:

-    cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

-    renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;

The mother and the neonate, at the end of pregnancy, to:

-    possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.

-    inhibition of uterine contractions resulting in delayed or prolonged labour.

Lactation

Like other NSAIDs, diclofenac passes into breast milk in small amounts. However, at therapeutic doses of Voltarol Pain-eze Emulgel no effects on the suckling child are anticipated. Because of a lack of controlled studies in lactating women, the product should only be used during lactation under advice from a healthcare professional. Under this circumstance, Voltarol Pain-eze Emulgel should not be applied on the breasts of nursing mothers, nor elsewhere on large areas of skin or for a prolonged period of time (see section 4.4).

4.7 Effects on ability to drive and use machines

Cutaneous application of Topical diclofenac has no influence on the ability to drive and use machines.

4.8 Undesirable effects

Adverse reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: very common (> 1/10); common (> 1/100, < 1/10); uncommon (> 1/1,000, < 1/100); rare (> 1/10,000, < 1/1,000); very rare (< 1/10,000), Not known: cannot be estimated from the available data.

Table 1

Immune system disorder
Very rare	Hypersensitivity (including urticaria), angioneurotic oedema
Infections and infestations
Very rare	Rash pustular
Respiratory, thoracic and mediastinal disorders
Very rare	Asthma
Skin and subcutaneous tissue disorders
Common	Rash, eczema, erythema, dermatitis (including dermatitis contact), pruritus
Rare	Dermatitis bullous
Very rare	Photosensitivity reaction

General: Systemic absorption of Voltarol Pain-eze Emulgel is low compared with plasma levels obtained following administration of oral forms of Voltarol and the likelihood of systemic side-effects occurring with topical diclofenac is small compared with the frequency of side-effects associated with oral diclofenac.

However, where Voltarol Pain-eze Emulgel is applied to a relatively large area of skin and over a prolonged period, the possibility of systemic side-effects cannot be completely excluded. If such usage is envisaged, the data sheet on Voltarol oral dosage forms should be consulted.

4.9 Overdose

Signs and symptoms

The low systemic absorption of topical diclofenac renders overdose very unlikely. However, undesirable effects similar to those observed following an overdose of Diclofenac tablets can be expected if Topical diclofenac is inadvertently ingested (1 tube of 100 g contains the equivalent of 1000 mg diclofenac sodium).

In the event of accidental ingestion, resulting in significant systemic adverse effects, general therapeutic measures normally adopted to treat poisoning with non-steroidal anti-inflammatory medicines should be used. Gastric decontamination and the use of activated charcoal should be considered, especially within a short time of ingestion.

Treatment

Management of overdosage with NSAIDs essentially consists of supportive and symptomatic measures. There is no typical clinical picture resulting from diclofenac overdosage. Supportive and symptomatic treatment should be given for complications such as hypotension, renal failure, convulsions, gastro-intestinal irritation, and respiratory depression; specific therapies such as forced diuresis, dialysis or haemoperfusion are probably of no help in eliminating NSAIDs due to their high rate of protein binding and extensive metabolism.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Topical products for joint and muscular pain, anti

inflammatory preparations, non-steroids for topical use (ATC code M02A A15)

Diclofenac is a non-steroidal anti-inflammatory (NSAID)with pronounced analgesic, anti-inflammatory and antipyretic properties. Inhibition of prostaglandin synthesis is the primary mechanism of action of diclofenac.

Voltarol Pain-eze Emulgel is an anti-inflammatory and analgesic preparation designed for topical application. In inflammation and pain of traumatic or rheumatic origin, Voltarol Pain-eze Emulgel relieves pain, decreases swelling, and shortens the time to return to normal function. Due to an aqueous-alcoholic base the gel also exerts a soothing and cooling effect.

5.2 Pharmacokinetic properties Absorption

The quantity of diclofenac absorbed through the skin is proportional to the size of the treated area, and depends on both the total dose applied and the degree of skin hydration. Absorption amounts to about 6 % of the applied dose of diclofenac after topical application of 2.5 g Voltarol Pain-eze Emulgel on 500 cm² skin, determined by reference to the total renal elimination, compared with Voltarol tablets. A 10-hour occlusion leads to a three-fold increase in the amount of diclofenac absorbed.

Distribution

Diclofenac concentrations have been measured from plasma, synovial tissue and synovial fluid after topical administration of Voltarol Pain-eze Emulgel to hand and knee joints. Maximum plasma concentrations are approximately 100 times lower than after oral administration of the same quantity of diclofenac. 99.7 % of diclofenac is bound to serum proteins, mainly albumin (99.4 %).

Diclofenac accumulates in the skin which acts as reservoir from where there is a sustained release of drug into underlying tissues. From there, diclofenac preferentially distributes and persists in deep inflamed tissues, such as the joint, where it is found in concentrations up to 20 times higher than in plasma.

Biotransformation

Biotransformation of diclofenac involves partly glucuronidation of the intact molecule, but mainly single and multiple hydroxylation resulting in several phenolic metabolites, most of which are converted to glucuronide conjugates. Two of the phenolic metabolites are biologically active, however, to a much smaller extent than diclofenac.

Elimination

The total systemic clearance of diclofenac from plasma is 263 ± 56 ml/min. The terminal plasma half-life is 1-2 hours. Four of the metabolites, including the two active ones, also have short plasma half-lives of 1-3 hours. One metabolite, 3'-hydroxy-4'-methoxy-diclofenac, has a longer half-life but is virtually inactive. Diclofenac and its metabolites are excreted mainly in the urine.

Characteristics in patients

No accumulation of diclofenac and its metabolites is to be expected in patients suffering from renal impairment. In patients with chronic hepatitis or non-decompensated cirrhosis, the kinetics and metabolism of diclofenac are the same as in patients without liver disease.

5.3 Preclinical safety data

Preclinical data from acute and repeated dose toxicity studies, as well as from genotoxicity, mutagenicity, and carcinogenicity studies with diclofenac revealed no specific hazard for humans at the intended therapeutic doses. There was no evidence that diclofenac had a teratogenic potential in mice, rats or rabbits. Diclofenac had no influence on the fertility of parent animals in

rats. The prenatal, perinatal and postnatal development of the offspring was not affected.

Voltarol Pain-eze Emulgel was well tolerated in a variety of studies. There was no potential for phototoxicity and diclofenac-containing gel caused no skin sensitisation.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Diethylamine, carbomers, cetomacrogol, cocoyl capryloccaprate, isopropyl alcohol, liquid paraffin, perfume creme 45 (containing benzyl benzoate), propylene glycol, purified water.

6.2 Incompatibilities

None stated.

6.3 Shelf life

Three years.

6.4 Special precautions for storage

Do not store above 30°C.

Voltarol Pain-eze Emulgel should be kept out of reach and sight of children.

6.5 Nature and contents of container

Sealed aluminium tubes with protective inner coating, closed with a polypropylene screw cap.

Packaging available in packs of 10g, 30g, 40g and 50g.

Aluminium laminated tube (low density polyethylene /aluminium/high density polyethylene (internal layer)) fitted with a high density polyethylene shoulder and closed by a moulded seal. The tube is closed with a polypropylene screw cap, incorporating a moulded feature used to insert, twist and remove the seal before first use.