Voltaren^® Emulgel (Gel) Instructions for Use

ATC Code

M02AA15 (Diclofenac)

Active Substance

Diclofenac (Rec.INN registered by WHO)

Clinical-Pharmacological Group

NSAIDs for external use

Pharmacotherapeutic Group

Drugs for external use for muscle and joint pain; non-steroidal anti-inflammatory drugs for external use

Pharmacological Action

The active component Diclofenac is an NSAID with pronounced analgesic, anti-inflammatory, and antipyretic effects. By non-selectively inhibiting COX-1 and COX-2, it disrupts the metabolism of arachidonic acid.

Voltaren^® Emulgel is used to eliminate pain and inflammation in joints, muscles, and ligaments of traumatic or rheumatic origin, helping to reduce pain and swelling associated with the inflammatory process and increasing joint mobility.

Due to its water-alcohol base, Voltaren^® Emulgel has a soothing and cooling effect.

Clinical efficacy and safety

A randomized, double-blind, multicenter study in two parallel therapy groups evaluated the efficacy and safety of the drug Voltaren^® Emulgel, gel for external use, 2%, applied 2 times/day compared to the drug Voltaren^® Emulgel, gel for external use, 1%, applied 4 times/day for one week (7 days) involving 302 patients with acute ankle sprain.

The primary objective of the study, which was to demonstrate the non-inferior efficacy of Voltaren^® Emulgel, gel for external use, 2%, applied 2 times/day, relative to Voltaren^® Emulgel, gel for external use, 1%, applied 4 times/day in relieving pain in acute ankle sprain, was achieved.

Two secondary endpoints of this study were pain intensity and complete pain relief, assessed every 2.5 hours from day 1 to day 5 of treatment.

The results of the assessment of pain intensity and complete pain relief from day 1 to day 5 of treatment demonstrated not only a significant reduction in pain and an enhancement of the pain relief effect but also complete pain relief that persisted over a 12-hour interval with the use of Voltaren^® Emulgel, gel for external use, 2% (significantly on day 5).

The pain on movement (POM) score showed a marked decrease on day 3 compared to the start of treatment, as well as a further decrease by days 5 and 8. Similar trends were recorded for the group with the drug Voltaren^® Emulgel, gel for external use, 1%.

Pharmacokinetics

Absorption

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

After application to a skin surface area of 400 cm² of Voltaren^® Emulgel, gel for external use 2% (2 applications per day), the concentration of the active substance in plasma corresponds to its concentration when using 1% diclofenac gel (4 applications per day). On day 7, the relative bioavailability of the drug (AUC ratio) is 4.5% (for an equivalent dose of diclofenac sodium). When wearing a moisture-permeable bandage, absorption did not change.

Voltaren^® Emulgel, gel for external use 2% contains a permeability enhancer (oleyl alcohol). In an in vitro skin barrier penetration study, this drug was compared with the drug Voltaren^® Emulgel, gel for external use, 1%. Both drugs were applied to a skin area in an amount of 20 mg/cm² in a single dose. The study results indicate approximately 3 times higher cumulative skin permeability of Voltaren^® Emulgel, gel for external use, 2% compared to Voltaren^® Emulgel, gel for external use, 1% (6.11 ± 1.27 µg/cm² and 2.07 ± 0.38 µg/cm², respectively) after 24 hours.

Distribution

When the drug was applied to the area of the affected joint, the concentration of diclofenac in plasma, synovial membrane, and synovial fluid was determined. C_max in plasma was approximately 100 times lower than after oral administration of the same amount of diclofenac.

The binding of diclofenac to plasma proteins is 99.7%, mainly to albumin (99.4%).

Diclofenac accumulates in the skin, which acts as a reservoir that releases the active substance into the tissues.

Diclofenac is predominantly distributed and retained deep in tissues subject to inflammation (such as joints) rather than in the bloodstream. The concentration of diclofenac in tissues is up to 20 times higher than in plasma.

Metabolism

The metabolism of diclofenac occurs partially by glucuronidation of the unchanged molecule, but predominantly through single and multiple hydroxylation, leading to the formation of several phenolic metabolites, most of which are converted into glucuronide conjugates. Two phenolic metabolites are biologically active, but to a significantly lesser extent than Diclofenac.

Excretion

The total systemic plasma clearance of diclofenac is 263±56 ml/min.

The terminal T_1/2 is 1-2 hours. The T_1/2 of metabolites, including 2 pharmacologically active ones, is also short and amounts to 1-3 hours. One of the metabolites (3'-hydroxy-4'-methoxydiclofenac) has a longer T_1/2, but this metabolite is completely inactive. Most of the diclofenac and its metabolites are excreted in the urine.

Pharmacokinetics in special clinical cases

Renal impairment. Accumulation of diclofenac and its metabolites is not expected in patients suffering from renal impairment.

Hepatic impairment. In patients with chronic hepatitis or uncompensated liver cirrhosis, the kinetics and metabolism of diclofenac are the same as in patients without liver disease.

Indications

• Back pain in inflammatory and degenerative diseases of the spine (radiculitis, osteoarthritis, lumbago, sciatica);
• Joint pain (finger joints, knee) in osteoarthritis;
• Muscle pain (due to sprains, strains, bruises, injuries);
• Inflammation and swelling of soft tissues and joints due to injuries and in rheumatic diseases (tenosynovitis, bursitis, lesions of periarticular tissues, carpal tunnel syndrome).

ICD codes

Dosage Regimen

Gel

The drug is used externally. For application to the skin only.

For adults and children over 12 years, the drug is applied to the skin 2 times/day (every 12 hours, preferably in the morning and evening), rubbing lightly into the skin. The required amount of the drug depends on the size of the painful area. A single dose of the drug – 2-4 g (which in volume is comparable to the size of a cherry or a walnut, respectively) is sufficient to treat an area of 400-800 cm².

The duration of treatment depends on the indications and the observed effect. The drug should not be used for more than 14 days for post-traumatic inflammation and rheumatic diseases of soft tissues without a doctor’s recommendation. If after 7 days of use the therapeutic effect is not observed or the condition worsens, the patient should consult a doctor to rule out an alternative cause of pain.

The use of Voltaren^® Emulgel in children under 12 years is contraindicated (see section “Contraindications”).

Method of application

To remove the protective membrane, use the screw cap as a key (the recess with protrusions on the outside of the cap). Align the recess on the outside of the cap with the shaped protective membrane of the tube and turn. The membrane should separate from the tube.

Tubes may have either a regular cap (round shape) or an innovative cap (triangular shape), which is especially convenient for use with limited mobility of the hand joints due to osteoarthritis or other joint diseases or injuries, as well as a flip-top cap.

Method of application for tubes with a flip-top cap

1. Lift the flip-top of the cap.

Using a finger, thumb, side of the hand, or even the edge of a table, open the cap easily. The side break-open control tabs will break when the cap is opened for the first time. Before first use, check if the side tabs are broken.

2. Squeeze out the gel and rub it in.

Gently squeeze a small amount of gel from the tube and apply to the painful or swollen area, rubbing slowly into the skin. The required amount of the drug will vary depending on the size of the area of pain or swelling; an amount the size of a cherry or a walnut is usually sufficient. A slight cooling effect may be felt while rubbing in the gel.

3. Press the flip-top of the cap to close it.

After use, if necessary, remove any remaining gel from the cap with a cotton towel or absorbent paper until visually clean and dry. To close the cap, press the flip-top with your fingers, palm, or even using the edge of a table or countertop until it clicks. Keep the tube upright when opening or closing the cap to avoid possible gel leakage.

Do not shower or bathe until Voltaren^® Emulgel has completely dried (see section “Special Precautions”). If the hands are not the area of pain localization, wash hands after applying the drug.

Adverse Reactions

The frequency of adverse reactions was determined in accordance with the WHO classification: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000).

Infections and infestations very rare – pustular rash.

Immune system disorders very rare – hypersensitivity reactions (including urticaria), angioedema.

Respiratory, thoracic and mediastinal disorders very rare – asthma.

Skin and subcutaneous tissue disorders common – dermatitis (including contact dermatitis), rash, erythema, eczema, pruritus; rare – bullous dermatitis; very rare – photosensitivity reactions.

If any of the above adverse reactions worsen, or the patient notices any other adverse reactions, they should inform their doctor.

Contraindications

• Hypersensitivity to diclofenac or any of the excipients included in the drug;
• Tendency to develop attacks of bronchial asthma, angioedema, urticaria, or acute rhinitis when using acetylsalicylic acid or other NSAIDs;
• Pregnancy after 20 weeks;
• Period of breastfeeding;
• Children under 12 years of age;
• Violation of the integrity of the skin at the intended site of application.

With caution: in patients with hepatic porphyria (in the acute phase), erosive and ulcerative lesions of the gastrointestinal tract, severe impairment of liver and kidney function, blood clotting disorders (including hemophilia, prolonged bleeding time, tendency to bleed), chronic heart failure, bronchial asthma, in the elderly, during pregnancy up to 20 weeks.

Use in Pregnancy and Lactation

Pregnancy

Due to the lack of data on the use of Voltaren^® Emulgel in pregnant women, the drug should not be used during pregnancy.

NSAIDs should not be used by women from the 20th week of pregnancy due to the possible development of oligohydramnios and/or kidney pathology in newborns (neonatal renal dysfunction).

Animal studies have not shown direct or indirect adverse effects on pregnancy, embryonic and fetal development, childbirth, or postnatal development.

Breastfeeding period

It is unknown whether Diclofenac passes into breast milk after external application, therefore Voltaren^® Emulgel is not recommended for use during breastfeeding.

If the use of the drug is necessary, it should not be applied to the breast area, to large areas of the body surface, or used for a long time.

Use in Hepatic Impairment

Use with caution in severe liver dysfunction.

Use in Renal Impairment

Use with caution in severe kidney dysfunction.

Pediatric Use

Contraindicated: children under 12 years of age.

Geriatric Use

The drug should be prescribed with caution to elderly patients.

Special Precautions

Voltaren^® Emulgel should be applied only to intact skin, avoiding contact with open wounds. Avoid getting the drug in the mouth, eyes, and mucous membranes; do not swallow.

After applying the drug, a bandage dressing is allowed, but an airtight occlusive dressing should not be applied.

If a skin rash develops after applying the drug, its use must be discontinued.

The possibility of adverse reactions in various organs and systems (similar to the use of systemic forms of diclofenac) should be considered if Diclofenac for external use is used in a higher dose or for a longer time than recommended.

Caution should be exercised when smoking or near an open flame due to the risk of severe burns. Voltaren^® Emulgel contains liquid paraffin, which can potentially ignite when it accumulates on fabric (clothing, bedding, dressings, etc.). Washing clothes and bedding may reduce the accumulation of the substance but will not remove it completely.

Excipients

The drug contains propylene glycol, which may cause mild local irritation in some people. It also contains butylated hydroxytoluene, which can cause local skin reactions (e.g., contact dermatitis) or irritation of the eyes and mucous membranes.

Effect on ability to drive vehicles and operate machinery

Voltaren^® Emulgel does not affect the ability to drive vehicles and operate machinery.

Overdose

Due to the extremely low systemic absorption when applying the gel, overdose is unlikely.

Symptoms: with accidental ingestion of 50 g of gel, equivalent to 1 g of diclofenac sodium, systemic adverse reactions may develop.

Treatment for accidental ingestion , leading to significant systemic adverse reactions: gastric lavage, induction of vomiting, activated charcoal, symptomatic therapy. Hemodialysis and forced diuresis are not effective due to the high degree of binding of diclofenac to plasma proteins (about 99%).

Drug Interactions

Voltaren^® Emulgel may enhance the effect of drugs that cause photosensitization.

Clinically significant interaction with other drugs has not been described.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 3 years.

Dispensing Status

The drug is available without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.