For external use in the treatment of pain, inflammation and swelling associated with:

·         injuries to tendons, ligaments, muscles and joints, e.g. sprains, contusions, muscle strains and back pain following sporting activity or an accident.

·         localised rheumatism, (tennis elbow), shoulder-hand, syndrome, bursitis, periarthropathies;

·         and for the symptomatic treatment of osteoarthritis of the small and medium-sized superficial e.g., or joints, finger knee joints.

Dosage/Administration

The product is for external use only.

Adults and adolescents aged 12 years and above

Depending on the size of the painful area to be treated, gently rub 2-4 g of Avotrene Emulgel into the skin (an amount the size of a cherry to a walnut is enough to treat an area of approximately 400- 800 cm2) 3 to 4 times per day.

Treatment duration depends on the indication and the response elicited. It is recommended to review treatment after 2 weeks if the symptoms have not improved. Avotrene Emulgel should not be used for more than 14 days.

After use

·         Wipe hands with a dry paper towel, then wash them thoroughly (except when treating the of paper towel with the household waste.fingers). Dispose the household waste.

·           The patient must wait for the Emulgel to dry on the skin before taking a shower or a bath.

Children under 12 years of age

The use and safety of Avotrene Emulgel in children under 12 years of age have not yet been studied systematically and its use is therefore not recommended in this age group.

Patients over 65 years of age

The normal daily dose for adults can be used.

- Known hypersensitivity to diclofenac (active substance) or to any of the excipients. - Patients who react with an asthma attack, angioedema, urticaria or acute rhinitis to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs, such as ibuprofen - During the third trimester of pregnancy (see the note in the "Pregnancy/ Lactation " section).

Warnings and precautions

Only apply Avotrene Emulgel to undamaged, healthy skin with no lesions or open wounds. Avoid contact between the product and the eyes and mucous membranes. Do not swallow. Immediately stop treatment if a rash appears after use.

Avotrene Emulgel contains propylene glycol: this excipient may cause mild, localised skin irritation in some patients.

Avotrene Emulgel must not be used with airtight, occlusive dressings.

When Avotrene Emulgel is applied to a larger area and for a longer period of time than recommended (see "Dosage/Administration"), the occurrence of systemic adverse effects cannot be completely ruled out.

It is unlikely that interactions will occur considering the low systemic absorption when applied topically. See also the last paragraph of the "Warnings and precautions" and the "Undesirable effects” sections.

Pregnancy

No controlled studies are available on pregnant women. Therefore, Avotrene Emulgel should not be used on pregnant women.

Avotrene Emulgel is contraindicated during the third trimester of pregnancy owing to the potential risk of premature closure of the ductus arteriosus, possible inhibition of uterine contractions, as well as possible impairment of foetal renal function that may progress to renal failure with oligohydramnios.

In animal studies, no direct or indirect adverse effects on pregnancy, embryonic/foetal development, delivery or postnatal development have been identified (see "Preclinical data").

Breastfeeding

It is not known whether topically applied diclofenac is excreted in breast milk. Therefore, Avotrene Emulgel should not be used on breastfeeding women. Where indicated as a matter of necessity, do not apply Avotrene Emulgel to the breasts, to large areas of skin or over a prolonged period of time.

Not applicable.

Undesirable effects are listed by system organ class and by frequency. Within each frequency grouping, undesirable effects are classed in order of decreasing severity.

Frequencies

" Very common" (21/10), “common" (21/100, <1/10), "uncommon" (21/1,000, <1/100), "rare" (21/10,000, <1/1,000), “very rare" (<1/10,000).

Infections and infestations

Very rare: pustular skin eruption.

Immune system disorders

Very rare: angioedema, hypersensitivity reactions (including urticaria).

Respiratory, thoracic and mediastinal disorders Very rare: asthma.

Skin and subcutaneous tissue disorders

Common: dermatitis (including contact dermatitis), rash, redness, eczema, pruritus.

Rare: bullous dermatitis. Very rare: photosensitisation.

The probability of systemic undesirable effects occurring with the topical form of diclofenac is low in comparison with the frequency of undesirable effects observed during treatment with oral diclofenac. However, the occurrence of systemic adverse effects cannot be completely ruled out when Avotrene Emulgel is applied to a larger area and for a prolonged period of time.

To Report any side effects:

The National Pharmacovigilance Centre (NPC) o  SFDA call center: 19999 o  E-mail: npc.drug@sfda.gov.sa o Website: https://ade.sfda.gov.sa

Other GCC States:

- Please contact the relevant competent authority

An overdose is unlikely, considering the low systemic absorption of diclofenac when applied topically.

The expected adverse effects following accidental ingestion of Avotrene Emulgel (one 100g tube corresponds to 1g sodium diclofenac) are similar to those observed following overdose with diclofenac tablets. If significant systemic undesirable effects occur following misuse or accidental consumption (e.g. in children), the general therapeutic measures recommended for intoxication with non-steroidal anti-inflammatory drugs should be adopted.

ATC code M02AA15

Mechanism of action and pharmacodynamics

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) with significant analgesic, anti- inflammatory and antipyretic properties. Avotrene Emulgel is an anti-inflammatory and analgesic product for external use. The Emulgel is a non-greasy, white cream and is easily absorbed into the skin. As a result of its water-alcohol base, it has a soothing and cooling effect.

The proven inhibition by diclofenac of prostaglandin biosynthesis is considered to be a significant component of its mechanism of action.

Avotrene Emulgel relieves the pain and reduces the oedema associated with inflammation of traumatic origin.

Absorption

The quantity of diclofenac absorbed by the skin is proportional to the time Avotrene Emulgel is in contact with the skin, and to the surface area treated; it also depends on the total dose applied and skin hydration. Approximately 6% of the diclofenac dose is absorbed after topical application of 2.5 g of Avotrene Emulgel over a skin surface area of 500 cm?, calculated in relation to total renal elimination compared with that obtained with diclofenac tablets.

Diclofenac absorption is tripled if the treated area is covered by an occlusive dressing for 10 hours.

Distribution

After topical application of Avotrene Emulgel to hand and knee joints, diclofenac levels can be measured in plasma, synovial tissue and synovial fluid. Maximum plasma concentrations of diclofenac obtained after topical application of Avotrene Emulgel are approximately 100 times lower than those obtained with diclofenac tablets. 99.7% of diclofenac is bound to serum proteins, primarily to albumin (99.4%).

Metabolism

Diclofenac biotransformation is partly by glucuronidation of the whole molecule, but especially by simple or multiple hydroxylation, leading to the formation of phenolic metabolites, which are then eliminated mostly in glucuronidated form. Two of these phenolic metabolites are biologically active, but to a much lower degree than diclofenac.

Elimination

The total plasma clearance of diclofenac is 263 + 56 mL/min (mean + standard deviation).

Terminal plasma half-life is 1-2 hours. Four of the metabolites, including the active two, also have a short plasma half-life of 1-3 hours. Another metabolite, 3'-hydroxy-4' methoxydiclofenac, has a significantly longer half-life, but is practically inactive. Diclofenac and its metabolites are excreted mainly in the urine.

Kinetics in specific patient groups

Diclofenac and its metabolites are unlikely to accumulate in patients with renal failure.

The kinetics and metabolism of diclofenac are the same in patients with chronic hepatitis or compensated cirrhosis as in patients without liver disease.

Preclinical data from studies with diclofenac on acute toxicity, repeated dose toxicity, genotoxicity, mutagenicity and carcinogenicity did not identify any specific risk to humans at the recommended therapeutic doses.

No teratogenic effect was observed in mice, rats and rabbits.

Diclofenac had no effect on the fertility of the parents (rats) or the pre-, peri- or post-natal development of the offspring.

Different studies did not provide any indications that Avotrene Emulgel induces phototoxicity or skin sensitisation.

Propylene glycol, Isopropyl alcohol, Carbomer 980, Diethylamine, Cetomacrogol 1000, Coco Caprylate/Caprate, Paraffin oil and Purified Water.

None known.

Shelf life of unopened tube is 24 months. Shelf life after first opening is 11 months. .

Store below 30°C.

Aluminium Laminate Tube and White PP Screw Cap.

Available in 50 g and 100 g.

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