Diclofenac 1% - Anti-inflammatory gel - Biogaran - Pressurized bottle 100ml

1. MEDICINAL PRODUCT NAME

DICLOFENAC Biogaran 1%, gel

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Diethylamine diclofenac 1.16 g

Quantity corresponding to diclofenac sodium 1.00 g

Per 100 g gel.

Notable excipient: this product contains 125 mg propylene glycol for an application of 2.5 g gel.

For full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM Back to top Gel.

4. CLINICAL DATA

4.1 Therapeutic indications

Adults (15 years and over): - Short-term local treatment of minor trauma: sprains, contusions;

- Local adjunctive treatment of pain of muscular and tendino-ligamentary origin;

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

4.2. Dosage and administration 

Dosage For adults only (15 years and over).

Dosage depends on indication.

The occurrence of adverse effects can be minimized by using the lowest possible dose for the shortest duration of treatment necessary to relieve symptoms (see section 4.4).

Minor trauma: sprain, contusion 1 local application, 2 to 3 times a day, for up to 4 days.

If pain persists beyond this period, a doctor should be consulted. On medical advice, the maximum duration of treatment is 7 days.

The dose for each application should not exceed 2.5 g of gel (approx. 6 cm of gel). Pain of muscular and tendino-ligamentary origin As adjunctive treatment: 1 local application, 3 to 4 times a day, for a maximum of 7 days. If pain persists beyond this period, a doctor should be consulted. On medical advice, the maximum duration of treatment is 14 days. The dose administered per application should not exceed 2.5 g of gel (i.e. around 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 7 days. Treatment may be continued, if necessary, for up to 14 days. If pain persists beyond this period, medical advice should be sought. The dose administered per application should not exceed 4 g of gel (equivalent to approximately 10 cm of gel). Special populations Pediatric population Diclofenac is contraindicated in children under 15 years of age (see section 4.3).

Elderly This drug should be used with caution in the elderly, who are more prone to adverse reactions (see sections 4.4 and 4.8). Method of administration Local use. Gently massage the gel into the painful or inflammatory area. After application: - Hands should be wiped with absorbent paper (for example), then washed (except in the event of a flare-up of digital osteoarthritis, see section 4.4). Absorbent paper should be disposed of in the garbage can after use. - Patients should wait for DICLOFENAC VIATRIS 1% gel to dry before taking a shower or bath. 4.3. Contraindications Back to top This medicine is contraindicated in the following cases: - Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Pregnancy, from the beginning of the 6th month (beyond 24 weeks of amenorrhea) (see section 4.6). - Injured skin, whatever the lesion: oozing dermatitis, eczema, infected lesions, burns or wounds. - In children and adolescents under 15 years of age. 4.4. Special warnings and precautions for use Back to top Special warnings Do not apply to mucous membranes or eyes. If a rash appears after application, discontinue use immediately. This medicine contains 125 mg propylene glycol for an application of 2.5 g of gel. Special precautions for use Wearing gloves is recommended for intensive use by physiotherapists.

4.5. Interactions with other medicinal products and other forms of interaction Back to top Due to the low systemic passage during normal use of the gel, the drug interactions reported for diclofenac per os are unlikely.

4.6. Fertility, pregnancy and lactation Back to top Pregnancy Inhibition of prostaglandin synthesis by NSAIDs may affect the course of pregnancy and/or the development of the embryo or fetus. Risks associated with use in the 1st trimester Epidemiological data suggest an increased risk of miscarriage, cardiac malformations and gastroschisis, following 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 people 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 embryo-fetal lethality. In addition, a higher incidence of certain malformations, including cardiovascular, has been reported in animals given a prostaglandin synthesis inhibitor during the organogenesis phase of gestation. Risks associated with use from 12 weeks of amenorrhea to birth From 12 weeks of amenorrhea to birth, all NSAIDs, by inhibiting prostaglandin synthesis, may expose the fetus to renal impairment: - in utero, which may be observed from 12 weeks of amenorrhea (initiation of fetal diuresis) : oligohydramnios (usually reversible on discontinuation of treatment), or even anamnios, particularly in the case of prolonged exposure; - at birth, renal failure (reversible or not) may persist, particularly in the case of late and prolonged exposure (with a risk of delayed severe hyperkalemia). Risks associated with use beyond the 24th week of amenorrhea and up to birth Beyond the 24th week of amenorrhea, NSAIDs may expose the fetus to cardiopulmonary toxicity (premature closure of the ductus arteriosus and pulmonary hypertension). Constriction of the ductus arteriosus can occur from the beginning of the 6th month (beyond the 24th week of amenorrhea) and can lead to fetal or neonatal right heart failure, or even fetal death in utero. This risk is all the greater the closer to term the dose is taken (less reversibility). This effect exists even when a single dose is taken. At the end of pregnancy, both mother and newborn may experience: - prolonged bleeding time, due to an anti-aggregation action which may occur even after very low doses of the drug have been administered; - inhibition of uterine contractions, leading to delayed term or prolonged delivery. Consequently, unless absolutely necessary, this drug should not be prescribed to women contemplating pregnancy or during the first 5 months of pregnancy (first 24 weeks of amenorrhea). If this drug is administered to a woman wishing to become pregnant or who is less than 6 months pregnant, 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 month (beyond 24 weeks of amenorrhea): any intake of this drug, even punctual, is contraindicated. Inadvertent use after this date warrants cardiac, renal, fetal and/or neonatal monitoring, depending on the term of exposure. The duration of monitoring should be adapted to the compound's elimination half-life. Breast-feeding As A.I.N.S. is excreted in breast milk, this drug is not recommended for nursing mothers. In the event of breast-feeding, this drug should never be applied to the breasts. Fertility As with all NSAIDs, use of this drug may temporarily impair female fertility by affecting ovulation; it is therefore not recommended for women wishing to conceive a child. In women experiencing difficulties conceiving, or undergoing fertility tests, discontinuation of treatment should be considered.

4.7. Effects on ability to drive and use machines Back to top Not applicable.

4.8. Adverse reactions Back to top Adverse reactions are classified in order of frequency, decreasing, 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); - undetermined frequency (cannot be estimated from available data). Within each frequency group, adverse reactions are presented in descending order of severity. Immune system disorders Very rare: hypersensitivity reactions (including urticaria), angioneurotic edema (angioedema). Respiratory, thoracic and mediastinal disorders Very rare: the occurrence of asthma attacks may be linked in some subjects to an allergy to aspirin or NSAIDs. In such cases, this drug is contraindicated. Skin and subcutaneous tissue disorders Common: dermatitis (including contact dermatitis), rash, erythema, eczema, pruritus. Rare: bullous dermatosis. Very rare: pustular rash, photosensitivity reactions, purpura and local ulcerations. Indeterminate: burning sensation at application site, cutaneous dryness.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, renal effects). Reporting suspected adverse reactions It is important to report suspected adverse reactions after the drug has been authorized. It enables ongoing monitoring of the drug's risk/benefit ratio. Healthcare professionals report any suspected adverse reaction via the national reporting system: Agence nationale de sécurité du médicament et des produits de santé (ANSM) and the network of Regional Pharmacovigilance Centers - Website: www.signalement-sante.gouv.fr. 4.9. Overdose Back to top In case of overdose, wipe off excess gel with absorbent paper and rinse with plenty of water. In the event of accidental ingestion, effects similar to those observed in the case of oral diclofenac overdosage, resulting in adverse reactions, may occur. Therapeutic measures are those generally adopted in cases of NSAID intoxication. Gastric lavage and the administration of activated charcoal should be considered, especially when ingestion is recent.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic properties Back to top Pharmacotherapeutic class: non-steroidal anti-inflammatory drugs for topical use, ATC code: M02AA15. Diclofenac is a non-steroidal anti-inflammatory agent derived from phenylacetic acid of the arylcarboxylic acid group. In gel form, it has local anti-inflammatory and analgesic activity.

5.2. Pharmacokinetic properties Back to top When applied topically as a gel, diclofenac is absorbed through the skin. Absorption The amount of diclofenac absorbed through the skin is proportional to the surface area treated, and depends on both the total dose applied and the degree of skin hydration. The systemic uptake of gel compared with oral forms of diclofenac in healthy volunteers is of the order of 6%, estimated on the basis of urinary excretion and that of its hydroxylated metabolites, after single administration. A 10-hour occlusion results in a threefold increase in the amount of diclofenac absorbed. The systemic uptake of diclofenac gel, compared with oral diclofenac in healthy volunteers, is 13.9% after repeated administration. Concentrations measured in synovial fluid and tissue are 40 times higher than plasma concentrations. Distribution Diclofenac concentrations were measured in plasma, synovial tissue and synovial fluid after local administration of the gel to the hand and knee joints. 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 sustainably into underlying tissues. From there, diclofenac is distributed and persists preferentially in deeply inflamed tissues, such as the joint, where it is found in concentrations up to 20 times that measured in plasma. Biotransformation The biotransformation of diclofenac involves in part glucuron-conjugation of the intact molecule, but essentially single and multiple hydroxylation of several phenolic metabolites, the majority of which are converted to glucuronide conjugates. Two of the phenolic metabolites are biologically active, but to a lesser extent than diclofenac. Elimination The total systemic clearance of diclofenac from plasma is 263 ± 56 mL/min. Terminal plasma half-lives are 1 to 2 hours. Four of the metabolites, including the two active metabolites, also have short plasma half-lives of between 1 and 3 hours. One metabolite, 3'-hydroxy-4'-methoxy-diclofenac, has a longer half-life, but is practically inactive. Diclofenac and its metabolites are excreted mainly in the urine. Patient characteristics No accumulation of diclofenac and its metabolites is expected in patients with impaired renal function. In patients with chronic hepatitis or non-decompensated cirrhosis, the kinetics and metabolism of diclofenac are the same as in patients without hepatic impairment.

5.3. Preclinical safety data Back to top Acute toxicity, repeated dose toxicity, genotoxicity and carcinogenicity studies did not reveal any risk associated with the use of diclofenac at therapeutic doses in humans. Diclofenac has no teratogenic potential in mice, rats or rabbits. Diclofenac had no effect on fertility in rats; prenatal, perinatal and postnatal development of offspring was unaffected. Studies have shown that diethylamine diclofenac 1.16 g/100 g gel is well tolerated. Diethylamine diclofenac 1.16 g/100 g gel has no phototoxic potential in mice and guinea pigs, and does not cause skin sensitization in guinea pig tests.

6. PHARMACEUTICAL DATA 

6.1. List of excipients Back to top Diethylamine, carbomer 974 P, caprylic and capric acid ester, isopropyl alcohol, liquid kerosene, propylene glycol, polyethylene glycol 1000, purified water.

6.2 Incompatibilities Back to top Not applicable.

6.3. Shelf life Back to top 3 years.

6.4. Special precautions for storage Back to top No special precautions for storage.

6.5. Nature and contents of packaging Back to top 50 g in tube (aluminum); box of 1.

6.6. Special precautions for disposal and handling Back to top No special requirements.

7. MARKETING AUTHORIZATION NUMBER(S) Back to top - 34009 383 374 6 4 : 50 g in tube (aluminum); box of 1.

8. DATE OF FIRST AUTHORIZATION/ OF RENEWAL OF AUTHORIZATION Back to top [To be completed later by the holder].

9. DATE OF TEXT UPDATE Back to top of page [To be completed later by holder].

10. DOSIMETRY Back to top Not applicable.

11. INSTRUCTIONS FOR THE PREPARATION OF RADIOPHARMACEUTICALS Back to top Not applicable.