DICLOFENAC ZENTIVA 1 % Gel T/50g

Gel.

Diclofenac sodium....................................................................................................................................... 1,00 g

As diclofenac diethylamine................................................................................................1,16 g

For 100 g.

Excipient with known effect: propylene glycol.

Excipients:

In adults (from 15 years of age):

• Short-term local treatment in case of minor trauma: sprain (strain), contusion;

• Adjunctive local treatment of pain of muscular and tendino-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 (strain), 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 ZENTIVA 1 %, gel 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). Absorbent paper must be disposed of in the bin after use and not in the toilet to prevent the product from entering the wastewater system.

• If too much gel is applied, the excess must be wiped off with absorbent paper.

• Before dressing or applying a non-occlusive bandage, the gel should be left to dry on the skin for a few minutes.

• If patients need to shower or take a bath, they must apply the product afterwards.

This medicine is contraindicated in the following cases:

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

• Pregnancy, from the beginning of the 6th month (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 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.

This medicine contains propylene glycol (50 mg/g of gel) and may cause skin irritation.

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, drug interactions reported for oral diclofenac are unlikely.

Pregnancy

There are no clinical data on the use of DICLOFENAC ZENTIVA 1 %, gel during pregnancy. Even though systemic exposure to DICLOFENAC ZENTIVA 1 %, gel following topical administration is lower compared with that observed after oral administration, the risk of possible harmful effects on the embryo or foetus is not known.

During the first 5 months of pregnancy, DICLOFENAC ZENTIVA 1 %, gel must not be used unless absolutely necessary. If used, the dose should be the lowest and the duration of treatment as short as possible.

From the beginning of the 6th month of pregnancy (24 weeks of amenorrhea), systemic use of prostaglandin synthesis inhibitors such as diclofenac may induce cardiopulmonary and renal toxicity in the fetus. At the end of pregnancy, prolonged bleeding time in the mother and child may occur, and labor may be delayed.

Consequently, any use of DICLOFENAC ZENTIVA 1 %, gel, is contraindicated from the beginning of the sixth month of pregnancy (24 weeks of amenorrhea) (see section Contraindications.).

Breast-feeding

As NSAIDs pass into breast milk, 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

As with all NSAIDs, the use of this medicine may temporarily impair female fertility by affecting ovulation; it is therefore not recommended for women wishing to conceive a child. In women having difficulty conceiving or undergoing fertility testing, discontinuation of treatment should be considered.

Adverse effects are classified by decreasing order of frequency, according to the following conventions: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10 000 to <1/1000); 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.

System organ class	Adverse reaction	Frequency
Infections and infestations	Pustular rash	Very rare
Immune system disorders	Angioedema (Quincke's edema hypersensitivity reactions (including urticaria)	Very rare
Respiratory, thoracic and mediastinal disorders	Asthma attack*	Very rare
Skin and subcutaneous tissue disorders	Dermatitis (including contact dermatitis), skin rashes, erythema, eczema, pruritus.	Common
	Bullous dermatitis	Rare
	Photosensitivity reactions, purpura and local ulceration	Very rare

* 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  

They depend on the transdermal passage of the active substance and therefore on the quantity of gel applied, the area treated, the degree of skin integrity, the duration of treatment and whether or not an occlusive dressing is used (digestive, 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%, estimated from its urinary excretion and that of its hydroxylated metabolites, after single administration. Occlusion for 10 hours leads to a threefold increase in the quantity 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 approximately 100 times lower than those measured after oral administration of the same quantity of diclofenac. 99,7% of diclofenac is bound to serum proteins, essentially albumin (99,4%).

Diclofenac accumulates in the skin, which acts as a reservoir from which the medicinal product 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 glucuro-conjugation 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 related to 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.

Marketing authorisation (AMM)

CIP 3400938980363 (T/50g). CIP 3400927593215 (T/100g).

Price:

1,74 euros (T/50g). 2,49 euros (T/100g).

Social Security reimbursement at 30% (T/50g, T/100g).
Collection.