DICLOFENAC TEVA CLASSICS 1 % Gel T/100g

Diclofenac diethylamine ................................................................................................................... 1,16 g

Quantity corresponding to diclofenac sodium ................................................................................... 1,00 g

For 100 g of gel.

Excipient with known effect: each gram of gel contains 50 mg of propylene glycol.

In adults (from 15 years of age):

• Short-term local treatment for minor trauma: sprain, contusion;

• Adjunctive local treatment of pain of muscular and tendinous-ligamentous origin;

• Symptomatic treatment of painful flare-ups of osteoarthritis, after at least one medical opinion.

Dosage

Reserved for adults (from 15 years of age).

The dosage depends on the indication. The occurrence of undesirable effects can be minimised by using the lowest possible dose for the shortest treatment duration necessary to relieve symptoms (see section Warnings and precautions).

Minor trauma: sprain, contusion

1 local application, 2 to 3 times a day, for a maximum duration of 4 days. If the pain persists beyond this, a doctor must be consulted.

On medical advice, the maximum duration of treatment is 7 days.

The dose administered at each application must not exceed 2,5 g of gel (i.e. approximately 6 cm of gel).

Pain of muscular and tendinous-ligamentous origin

As adjunctive treatment: 1 local application, 3 to 4 times a day, for a maximum duration of 7 days. If the pain persists beyond this, a doctor must be consulted.

On medical advice, the maximum duration of treatment is 14 days.

The dose administered at each application must not exceed 2,5 g of gel (i.e. approximately 6 cm of gel).

Painful flare-ups of osteoarthritis

Only after at least one medical opinion.

1 local application, 3 to 4 times a day, for a duration of 7 days. Treatment may be continued, if necessary, for a maximum duration of 14 days. If the pain persists beyond this, a doctor must be consulted.

The dose administered at each application must not exceed 4 g of gel (i.e. approximately 10 cm of gel).

Special populations

Paediatric population

DICLOFENAC TEVA CLASSICS is contraindicated in children under 15 years of age (see section Contraindications).

Elderly patients

This medicine should be used with caution in elderly people who are more prone to adverse effects (see sections Warnings and precautions and Adverse effects).

Method of administration

Topical use.

Work the gel in with a gentle, prolonged massage over the painful or inflamed area.

After application:

• Hands must be wiped with absorbent paper (for example), then washed (except in case of a flare-up of digital osteoarthritis, see section Warnings and precautions). The absorbent paper must be thrown in the bin after use.

• Patients must wait for DICLOFENAC TEVA CLASSICS to dry before taking a shower or bath.

• Hypersensitivity to the active substance or to any of the excipients listed in section Composition.

• Pregnancy, from the beginning of the 6th months (beyond 24 weeks of amenorrhoea) (see section Fertility, pregnancy and breastfeeding).

• Damaged skin, whatever the lesion: weeping dermatoses, eczema, infected lesion, burn or wound.

• History of asthma, angioedema, urticaria or acute rhinitis triggered by diclofenac or a substance with a similar activity such as acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs).

• In children and adolescents under 15 years of age.

Special warnings

Do not apply to mucous membranes, nor to the eyes.

The appearance of a skin rash after application requires immediate discontinuation of treatment.

Special precautions for use

Wearing gloves by the physiotherapist, in case of intensive use, is recommended.

Due to the low systemic absorption during normal use of the gel, the drug interactions reported for diclofenac per os are unlikely.

Pregnancy

There is no clinical data on the use of diclofenac during pregnancy. Even though the systemic exposure to diclofenac achieved after topical administration is lower compared to that observed following oral administration, the risk of possible harmful effects on the embryo or foetus is not known.

Inhibition of prostaglandin synthesis by NSAIDs may affect the course of pregnancy and/or the development of the embryo or foetus.

Risks associated with use during the 1st trimester

Data from epidemiological studies suggest an increased risk of miscarriage, cardiac malformations and gastroschisis after treatment with a prostaglandin synthesis inhibitor in early pregnancy.

The absolute risk of cardiovascular malformation increased from less than 1% in the general population to approximately 1,5% in individuals exposed to NSAIDs. The risk appears to increase with dose and duration of treatment. In animals, administration of a prostaglandin synthesis inhibitor has been shown to cause increased pre- and post-implantation loss and an increase in embryo-foetal lethality. In addition, an increased incidence of certain malformations, including cardiovascular, has been reported in animals given a prostaglandin synthesis inhibitor during the organogenesis period of gestation.

Risks associated with use from the 12th gestational age (weeks of amenorrhea) and until birth:

From the 12th week of amenorrhoea and until birth, all NSAIDs, through inhibition of prostaglandin synthesis, may expose the foetus to functional renal impairment:

• in utero which may be observed from 12 weeks of amenorrhea (onset of fetal diuresis): oligohydramnios (most often reversible upon discontinuation of treatment), or even anhydramnios, particularly in the case of prolonged exposure.

• at birth, renal insufficiency (reversible or not) may persist, particularly in cases of late and prolonged exposure (with a risk of delayed severe hyperkalaemia).

Risks associated with use beyond the 24th weeks of amenorrhea and until birth:

Beyond the 24th week of amenorrhoea, NSAIDs may expose the foetus to cardiopulmonary toxicity (premature closure of the ductus arteriosus and pulmonary arterial hypertension). Constriction of the ductus arteriosus may occur from the beginning of the 6th month (beyond the 24th week of amenorrhea) and may lead to fetal or neonatal right heart failure or even intrauterine fetal death. This risk is all the greater the closer the intake is to term (lower reversibility). This effect exists even for a single intake.

At the end of pregnancy, the mother and the newborn may present:

• prolongation of bleeding time due to an anti-aggregating action, which may occur even after administration of very low doses of the medicine;

• inhibition of uterine contractions resulting in delayed term or prolonged labour.

As a consequence :

Unless absolutely necessary, this medicine must not be prescribed to a woman who is planning a pregnancy or during the first 5 months of pregnancy (first 24 weeks of amenorrhea). If this medicine is administered to a woman wishing to become pregnant or who is pregnant for less than 6 months, the dose should be as low as possible and the duration of treatment as short as possible. Prolonged use is strongly discouraged.

From the beginning of the 6th months (beyond 24 weeks of amenorrhea): any intake of this medicine, even a single one, is contraindicated. Accidental intake from this date onwards warrants cardiac and renal monitoring, fetal and/or neonatal, depending on the gestational age at exposure. The duration of this monitoring should be adapted to the elimination half-life of the molecule.

Breast-feeding

NSAIDs pass into breast milk, so this medicine is not recommended for women who are breastfeeding.

In case of breastfeeding, this medicine must under no circumstances be applied to the breast.

Fertility

Like all NSAIDs, use of this medicinal product may temporarily impair female fertility by affecting ovulation; it is therefore not recommended in women wishing to conceive. In women having difficulty conceiving or undergoing fertility investigations, discontinuation of treatment should be considered.

Adverse effects are classified by decreasing frequency, according to the following conventions: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000), frequency not known: cannot be estimated from the available data. Within each frequency group, adverse effects are presented in order of decreasing seriousness.

* The occurrence of asthma attacks may be linked in some subjects to an allergy to aspirin or an NSAID. In this case, this medicine is contraindicated.

Other systemic effects of NSAIDs: these depend on the transdermal passage of the active ingredient and therefore on the quantity of gel applied, the surface area treated, the degree of skin integrity, the duration of treatment and whether or not an occlusive dressing is used (digestive and renal effects).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Centres of Pharmacovigilance - Website: https://signalement.social-sante.gouv.fr/.

In case of overdose, wipe off excess gel with absorbent paper then rinse thoroughly with water.

In case of accidental or deliberate ingestion, effects similar to those observed in oral diclofenac overdose and resulting in adverse effects may occur. The therapeutic measures required are those generally adopted in cases of NSAID poisoning. The recommendations to follow will be those indicated by the regional Poison Control Centre, depending on the quantities ingested and the characteristics of the patient.

Pharmacotherapeutic class: NON-STEROIDAL ANTI-INFLAMMATORY DRUG FOR TOPICAL USE, ATC code: M02AA15.

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), derived from phenylacetic acid of the arylcarboxylic acid group, with analgesic, anti-inflammatory and antipyretic properties.

As with all NSAIDs, the exact mechanism of action of diclofenac is not fully elucidated but is essentially based on inhibition of prostaglandin biosynthesis, substances playing a major role in the genesis of inflammation, pain and fever, through inhibition of the two cyclooxygenases (COX-1 and COX-2).

In gel form, it has local anti-inflammatory and analgesic activity.

Applied locally in gel form, diclofenac is absorbed through the skin.

Absorption

The quantity of diclofenac absorbed through the skin is proportional to the treated surface area and depends both on the total dose applied and on the degree of skin hydration.

The systemic passage of the gel, compared with that of oral forms of diclofenac in healthy volunteers, is of the order of 6%, as estimated from its urinary excretion and that of its hydroxylated metabolites, after single administration. An occlusion of 10 hours leads to a threefold increase in the amount of diclofenac absorbed.

The systemic passage of the gel, compared with that of oral forms of diclofenac in healthy volunteers, is of the order of 13,9% after repeated administration.

The concentrations measured in synovial fluid, as well as in synovial tissue, are 40 times higher than plasma concentrations.

Distribution

Diclofenac concentrations were measured in plasma, synovial tissue and synovial fluid after local application of the gel to the joints of the hand and knee. Maximum plasma concentrations are about 100 times lower than those measured after oral administration of the same amount of diclofenac. 99,7% of diclofenac is bound to serum proteins, mainly albumin (99,4%).

Diclofenac accumulates in the skin, which acts as a reservoir from which the drug is released in a sustained manner into the underlying tissues. From there, diclofenac is distributed and persists preferentially in deep inflamed tissues, such as the joint, where it is found at concentrations up to 20 times that measured in plasma.

Biotransformation

The biotransformation of diclofenac involves in part glucuronoconjugation of the intact molecule, but essentially single and multiple hydroxylation of several phenolic metabolites, the majority of which are converted into glucuronide conjugates. Two of the phenolic metabolites are biologically active, but to a lesser extent compared with diclofenac.

Elimination

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

Characteristics in patients

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

Acute toxicity, repeated-dose toxicity, genotoxicity and carcinogenicity studies revealed no risk associated with the use of diclofenac at therapeutic doses in humans. No teratogenic potential of diclofenac was detected in mice, rats or rabbits. Diclofenac had no effect on fertility in rats; the prenatal, perinatal and postnatal development of the offspring was not affected.

Studies have shown that diclofenac diethylamine 1,16 g/100 g in gel form is well tolerated. No phototoxic potential was observed in mice and guinea pigs with diclofenac diethylamine 1,16 g/100 g in gel form, and the latter does not cause skin sensitisation in guinea pig tests.

3 years.

No special precautions for storage.

No special requirements.

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