Diclofenac Retard-Akrikhin (Tablets) Instructions for Use

Marketing Authorization Holder

Akrikhin Chemical and Pharmaceutical Plant, JSC (Russia)

Contact Information

AKRIKHIN JSC (Russia)

ATC Code

M01AB05 (Diclofenac)

Active Substance

Diclofenac (Rec.INN registered by WHO)

Dosage Form

Diclofenac Retard-Akrikhin

Prolonged-release film-coated tablets, 100 mg: 10, 20, 30, or 40 pcs.

Dosage Form, Packaging, and Composition

Prolonged-release film-coated tablets light brown or pinkish-brown in color, round, biconvex; roughness is allowed; on the break – white with a creamy or yellowish tint.

Excipients: Ludipress LCE (lactose monohydrate – 94.7-98.3%, povidone – 3-4%), hypromellose (hydroxypropyl methylcellulose), microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide (Aerosil 200), stearic acid.

Shell composition hypromellose (hydroxypropyl methylcellulose), macrogol (polyethylene glycol 6000), glycerol (glycerin), talc, titanium dioxide, iron oxide red dye.

10 pcs. – contour cell packs (1) – cardboard packs.
10 pcs. – contour cell packs (2) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

NSAID

Pharmacological Action

Nonsteroidal anti-inflammatory drug (NSAID), a derivative of phenylacetic acid. It has anti-inflammatory, analgesic, antipyretic, and antiplatelet effects. By non-selectively inhibiting COX-1 and COX-2, it disrupts the metabolism of arachidonic acid, reduces the amount of prostaglandins at the site of inflammation, and suppresses the exudative and proliferative phases of inflammation.

In rheumatic diseases, the anti-inflammatory and analgesic effect of diclofenac contributes to a significant reduction in the severity of pain, morning stiffness, and joint swelling, which improves the condition of the joint.

In injuries, in the postoperative period, Diclofenac reduces pain and inflammatory edema.

Pharmacokinetics

Absorption

Absorption is rapid and complete; food slows down the rate of absorption. Plasma concentration is linearly dependent on the administered dose. Due to the slow release of the active substance, C_max in plasma is lower than that formed when administering the short-acting drug; however, it remains high for a long time after administration. C_max is 0.5-1 µg/ml, the time to reach C_max is 5 hours after taking the prolonged-release tablet at a dose of 100 mg. Bioavailability is 50%.

Distribution

Binding to plasma proteins is more than 99% (most is bound to albumin). Penetrates into the synovial fluid; C_max in the synovial fluid is observed 2-4 hours later than in plasma.

No changes in the pharmacokinetics of diclofenac during repeated administration have been noted. Does not accumulate when the recommended interval between doses is observed.

Metabolism

50% of the active substance undergoes the first-pass effect through the liver. Metabolism occurs as a result of multiple or single hydroxylation and conjugation with glucuronic acid. The isoenzyme CYP2C9 is also involved in the metabolism of diclofenac. The pharmacological activity of the metabolites is lower than that of diclofenac.

Excretion

Systemic clearance is 260 ml/min. T_1/2 from plasma is 1-2 hours, from synovial fluid is 3-6 hours (the concentration of the active substance in the synovial fluid 4-6 hours after drug administration is higher than in plasma and remains higher for another 12 hours). 60% of the administered dose is excreted by the kidneys as metabolites; less than 1% is excreted unchanged, the remainder of the dose is excreted as metabolites with bile.

Pharmacokinetics in special clinical cases

In patients with severe renal impairment, the excretion of metabolites with bile increases, while no increase in their concentration in the blood is observed.

In patients with chronic hepatitis or compensated liver cirrhosis, the pharmacokinetic parameters are the same as in patients with normal liver function.

Indications

Inflammatory and degenerative diseases of the musculoskeletal system

• Rheumatoid arthritis;
• Psoriatic arthritis;
• Juvenile chronic arthritis;
• Ankylosing spondylitis (Bekhterev’s disease);
• Gouty arthritis (for acute gout attacks, fast-acting dosage forms are preferred);
• Rheumatic soft tissue lesions;
• Osteoarthritis of peripheral joints and spine, incl. with radicular syndrome;
• Tenosynovitis, bursitis.

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, and does not affect the progression of the disease.

Mild to moderate pain syndrome

• Lumbago, sciatica;
• Neuralgia;
• Myalgia;
• Post-traumatic pain syndrome accompanied by inflammation;
• Postoperative pain;
• Headache;
• Migraine;
• Toothache;
• Algodysmenorrhea;
• Adnexitis;
• Proctitis;

As part of the complex therapy of infectious and inflammatory diseases of the ENT organs with severe pain syndrome

• Pharyngitis;
• Tonsillitis;
• Otitis.

ICD codes

Dosage Regimen

The drug is taken orally, during or after meals. The tablets should be swallowed whole without chewing and with a small amount of water.

Adults are prescribed 100 mg once a day.

For algodysmenorrhea and migraine attacks – up to 200 mg/day for no more than 1-2 days.

When taking prolonged-release tablets of 100 mg, if it is necessary to increase the daily dose to 150 mg/day, one regular tablet (50 mg) can be additionally taken. The maximum daily dose is 150 mg.

Adverse Reactions

Definition of the frequency of adverse reactions: very common – ≥10%; common – ≥1% to <10%; uncommon - ≥0.1% to <1%; rare - ≥0.01% to <0.1%; very rare - <0.01%, including isolated cases.

From the digestive system common – epigastric pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, anorexia, increased activity of aminotransferases; uncommon – gastritis, proctitis, gastrointestinal bleeding (hematemesis, melena, diarrhea with blood), gastrointestinal ulcers (with or without bleeding or perforation), hepatitis, jaundice, impaired liver function; very rare – stomatitis, glossitis, esophagitis, nonspecific hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn’s disease, constipation, pancreatitis, fulminant hepatitis.

From the nervous system common – headache, dizziness; uncommon – drowsiness; very rare – sensory disturbances (incl. paresthesia), memory disorders, tremor, convulsions, anxiety, cerebrovascular disorders, aseptic meningitis, disorientation, depression, insomnia, nightmares, irritability, mental disorders.

From the senses common – vertigo; very rare – visual impairment (blurred vision, diplopia), hearing impairment, tinnitus, taste disturbance.

From the urinary system very rare – acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary necrosis.

From the hematopoietic system very rare – thrombocytopenia, leukopenia, hemolytic and aplastic anemia, agranulocytosis.

From the cardiovascular system very rare – palpitations, chest pain, increased blood pressure, vasculitis, heart failure, myocardial infarction.

From the respiratory system uncommon – exacerbation of bronchial asthma (including shortness of breath); very rare – pneumonitis.

From the skin common – skin rash; very rare – erythema, bullous eruptions, exfoliative dermatitis, itching, hair loss, photosensitivity, purpura, incl. allergic.

Allergic reactions anaphylactic/anaphylactoid reactions, including severe hypotension and shock; uncommon – urticaria; very rare – erythema multiforme and Stevens-Johnson syndrome, Lyell’s syndrome, angioedema (incl. facial).

Contraindications

• Complete or incomplete combination of bronchial asthma, recurrent polyposis of the nasal mucosa and paranasal sinuses and intolerance to acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (incl. in history);
• Erosive and ulcerative lesions of the gastric or duodenal mucosa, active gastrointestinal bleeding;
• Inflammatory bowel diseases (ulcerative colitis, Crohn’s disease) in the acute phase;
• The period after coronary artery bypass grafting;
• Decompensated heart failure;
• Hematopoiesis disorders, hemostasis disorders (incl. hemophilia);
• Severe hepatic failure or active liver disease;
• Severe renal failure (creatinine clearance less than 30 ml/min);
• Progressive kidney diseases;
• Confirmed hyperkalemia;
• III trimester of pregnancy;
• Lactation period;
• Childhood and adolescence under 18 years;
• Hereditary lactose intolerance, glucose-galactose malabsorption, lactase deficiency;
• Hypersensitivity to the active substance (incl. to other NSAIDs) or excipients.

With caution

Anemia, bronchial asthma, cerebrovascular diseases, coronary artery disease, chronic heart failure, arterial hypertension, peripheral artery diseases, edematous syndrome, hepatic and renal failure (creatinine clearance 30-60 ml/min), dyslipidemia/hyperlipidemia, diabetes mellitus, inflammatory bowel diseases, conditions after extensive surgical interventions, induced porphyria, diverticulitis, systemic connective tissue diseases, history of peptic ulcer disease, presence of Helicobacter pylori infection, long-term use of NSAIDs, alcoholism, severe somatic diseases, simultaneous use of glucocorticosteroids (e.g., prednisolone), anticoagulants (e.g., warfarin), antiplatelet agents (e.g., acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, paroxetine, sertraline), smoking, I and II trimesters of pregnancy, elderly age.

Use in Pregnancy and Lactation

The use of the drug is contraindicated in the III trimester of pregnancy and during lactation.

The drug should be prescribed with caution in the I and II trimesters of pregnancy.

Use in Hepatic Impairment

The use of the drug is contraindicated in severe hepatic failure or active liver disease.

The drug should be prescribed with caution in hepatic failure.

Use in Renal Impairment

The use of the drug is contraindicated in severe renal failure (creatinine clearance less than 30 ml/min), progressive kidney diseases.

The drug should be prescribed with caution in renal failure (creatinine clearance 30-60 ml/min).

Pediatric Use

The use of the drug is contraindicated in children and adolescents under 18 years of age.

Geriatric Use

The drug should be prescribed with caution to elderly patients.

Special Precautions

To quickly achieve the desired therapeutic effect, the drug is recommended to be taken 30 minutes before meals. In other cases, take before, during, or after meals, without chewing, with a sufficient amount of water.

Due to the important role of prostaglandins in maintaining renal blood flow, special caution should be exercised when prescribing to patients with cardiac or renal failure, as well as when treating elderly patients taking diuretics, and patients who, for any reason, have a reduced circulating blood volume (e.g., after extensive surgery). If Diclofenac is prescribed in such cases, it is recommended to monitor renal function as a precaution.

In patients with hepatic failure (chronic hepatitis, compensated liver cirrhosis), the kinetics and metabolism do not differ from those in patients with normal liver function.

During long-term therapy, it is necessary to monitor liver function, peripheral blood picture, and stool for occult blood.

Due to the negative effect on fertility, the drug is not recommended for women wishing to become pregnant. In patients with infertility (incl. undergoing examination), it is recommended to discontinue the drug.

To reduce the risk of adverse events from the gastrointestinal tract, the drug should be used at the minimum effective dose for the shortest possible course.

Patients taking the drug must refrain from drinking alcohol.

Effect on the ability to drive vehicles and mechanisms

It is necessary to refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms vomiting, gastrointestinal bleeding, epigastric pain, diarrhea, dizziness, tinnitus, convulsions, increased blood pressure, respiratory depression, with significant overdose – acute renal failure, hepatotoxic effect.

Treatment gastric lavage, administration of activated charcoal; symptomatic therapy aimed at eliminating arterial hypertension, renal dysfunction, convulsions, gastrointestinal irritation, respiratory depression. Forced diuresis and hemodialysis are not very effective (due to the significant degree of protein binding and intensive metabolism).

Drug Interactions

Diclofenac increases the plasma concentration of digoxin, methotrexate, lithium preparations, and cyclosporine.

Diclofenac reduces the effect of diuretics.

When used concomitantly with potassium-sparing diuretics, the risk of hyperkalemia increases.

With simultaneous use of anticoagulants, thrombolytic agents (alteplase, streptokinase, urokinase), the risk of bleeding (more often from the gastrointestinal tract) increases.

Diclofenac reduces the effects of antihypertensive and hypnotic drugs.

Diclofenac increases the likelihood of side effects of other NSAIDs and glucocorticosteroids (gastrointestinal bleeding), the toxicity of methotrexate, and the nephrotoxicity of cyclosporine.

Acetylsalicylic acid reduces the concentration of diclofenac in the blood.

Paracetamol increases the risk of nephrotoxic effects of diclofenac.

Diclofenac reduces the effect of hypoglycemic medicinal products.

Cefamandole, cefoperazone, cefotetan, valproic acid, and plicamycin increase the incidence of hypoprothrombinemia.

Cyclosporine and gold preparations enhance the effect of diclofenac on the synthesis of prostaglandins in the kidneys, which increases nephrotoxicity.

Concomitant use with ethanol, colchicine, corticotropin, selective serotonin reuptake inhibitors, and St. John’s wort preparations increases the risk of gastrointestinal bleeding.

Diclofenac enhances the effect of drugs that cause photosensitization.

Drugs that block tubular secretion increase the plasma concentration of diclofenac, thereby increasing its toxicity.

When used concomitantly with diclofenac, antibacterial drugs from the quinolone group increase the risk of seizures.

Storage Conditions

The drug should be stored out of the reach of children, in a dry place, protected from light, at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years.

Dispensing Status

The drug is dispensed by 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.