Diclofenac, sustained release pills 100mg 20pcs

Composition

One long-acting film-coated tablet contains:

Active ingredient:  

Diclofenac sodium 100,0000 mg;

Auxiliary substances:  

Sucrose-94.7880 mg,

Cetyl alcohol-54.8200 mg,

Colloidal silicon dioxide-0.7900 mg,

Talcum powder — 3,9500 mg,

Povidone K-25 — 1.0530 mg,

Magnesium stearate — 7,8990 mg;

Shell:  

Hypromelose — 3,4355 mg,

Titanium dioxide E 171 CI 77891-0.8649 mg,

Talcum powder — 2,4178 mg,

Polysorbate 80 — 0.3826 mg,

Macrogol 6000-0.6894 mg,

Red dye [Ponceau 4R] [E124] — 0.0441 mg, brown dye [sunny sunset yellow dye [E110] + azorubin dye [E122] + diamond black dye [E151]] – 0.0147 mg, aluminum varnish based on sunny sunset yellow dye [E110] – 0.0500 mg.

Pharmacological action

A nonsteroidal anti-inflammatory drug (NSAID) derived from phenylacetic acid.

Diclofenac has anti-inflammatory, analgesic, antiplatelet and antipyretic effects.

Indiscriminately inhibiting cyclooxygenase 1 and 2 (COX 1 and COX 2), disrupts the metabolism of arachidonic acid, reduces the amount of prostaglandins in the focus of inflammation. It is most effective for inflammatory pain.

In rheumatic diseases, the anti-inflammatory and analgesic effect of diclofenac significantly reduces the severity of pain, morning stiffness, and joint swelling, which improves the functional state of the joint.

In case of injuries, in the postoperative period, diclofenac reduces pain and inflammatory edema.

Absorption-fast and complete, food slows down the rate of absorption by 1-4 hours and reduces the maximum concentration (Cmax) by 40%.

After oral use of 100 mg tablets, the cmax of 0.5 mcg / ml is reached in 4-5 hours. The plasma concentration is linearly dependent on the amount of the administered dose.

There were no changes in the pharmacokinetics of diclofenac during repeated use. It does not accumulate if the recommended interval between meals is observed.

Bioavailability — 50%. Binding to plasma proteins is more than 99% (most of them are bound to albumins). Penetrates the synovial fluid; Cmax in synovial fluid is observed 2-4 hours later than in plasma.

The half-life (half-life) from synovial fluid is 3-6 hours (the concentration of the Active ingredient in synovial fluid 4-6 hours after use of the drug is higher than in plasma, and remains higher for another 12 hours).

The relationship of the drug concentration in synovial fluid with the clinical efficacy of the drug has not been clarified.

Metabolism: 50% of the Active ingredient is metabolized during the” first pass ” through the liver.

Metabolism occurs as a result of repeated or single hydroxylation and conjugation with glucuronic acid.

The drug is metabolized by the isoenzyme CYP2C9. The pharmacological activity of the metabolites is lower than that of diclofenac.

The systemic clearance is about 260±50 ml / min, the volume of distribution is 550 ml / kg

. The plasma half-life is on average about 2.5 hours. 65% of the administered dose is excreted as metabolites by the kidneys; less than 1% is excreted unchanged, the rest of the dose is excreted as metabolites in the bile.

In patients with severe renal insufficiency (creatinine clearance less than 10 ml/min), the excretion of metabolites in the bile increases, while their concentration in the blood does not increase.

In patients with chronic hepatitis or compensated cirrhosis of the liver, the pharmacokinetic parameters of diclofenac do not change.

Diclofenac passes into breast milk.

Indications

Symptomatic treatment of diseases of the musculoskeletal system (rheumatoid arthritis, psoriatic arthritis, juvenile chronic arthritis, ankylosing spondylitis (Ankylosing spondylitis);

gouty arthritis, rheumatic soft tissue damage, osteoarthritis of the peripheral joints and spine, including those with radicular syndrome, tendovaginitis, bursitis).

The drug relieves or reduces pain and inflammation during treatment, but does not affect the progression of the disease.

Mild or moderate pain syndrome: neuralgia, myalgia, lumboishialgia, post-traumatic pain syndrome accompanied by inflammation, postoperative pain, headache, migraine, algodismenorrhea, adnexitis, proctitis, toothache.

As part of the complex therapy of infectious and inflammatory diseases of the ear, throat, nose with severe pain syndrome (pharyngitis, tonsillitis, otitis media).

Use during pregnancy and lactation

There are insufficient data on the safety of diclofenac in pregnant women.

Therefore, prescribe diclofenac in the first and second trimesters of pregnancy only in cases where the expected benefit to the mother exceeds the potential risk to the fetus.

Diclofenac, like other prostaglandin synthesis inhibitors, is contraindicated in the last 3 months of pregnancy (possible suppression of uterine contractility and premature closure of the arterial duct in the fetus).

Diclofenac is absorbed in small amounts in breast milk. To prevent undesirable effects on the child, the drug should not be prescribed to nursing women.

If it is necessary to use the drug, breastfeeding should be discontinued.

Recommendations for use

In all patients receiving diclofenac, it should be used at the lowest effective dose for the shortest possible time required to reduce the severity of symptoms. Inside, without chewing, during or after a meal, with a sufficient amount of water. Take 1 tablet 1 time a day. If you need an additional dose of the drug, use tablets of 50 mg. The maximum daily dose is 150 mg.

Contraindications

• Hypersensitivity to the Active ingredient (including other NSAIDs) or auxiliary components;
• Complete or incomplete combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis, and intolerance to acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (including in the anamnesis);
• Erosive and ulcerative changes in 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;
• the third trimester of pregnancy, the period of breastfeeding;
• Confirmed chronic heart failure (NYHA functional class II-IV);
• Coronary heart disease;
• Damage to peripheral arteries or cerebrovascular disorders;
• Hematopoietic disorders, hemostasis disorders (including hemophilia);
• Severe liver failure or active liver disease;
• Severe renal insufficiency (creatinine clearance less than 30 ml / min); progressive kidney disease;
• Confirmed hyperkalemia;
• sucrose/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption (the drug contains sucrose).
• Children under 18 years of age.
• With caution
• Anemia, bronchial asthma, confirmed NYHA Functional Class I chronic heart failure, arterial hypertension, edematous syndrome, hepatic or renal insufficiency (creatinine clearance 30-60 ml/min), dyslipidemia, hyperlipoproteinemia, diabetes mellitus, smoking, inflammatory bowel diseases, condition after extensive surgery, induced porphyria, diverticulitis, systemic connective tissue diseases, pregnancy I-II trimester.
• Anamnestic data on the development of peptic ulcer of the gastrointestinal tract, the presence of Helicobacter pylori infection, old age, long-term use of NSAIDs, frequent alcohol consumption, severe somatic diseases.
• Concomitant therapy with anticoagulants (e. g., warfarin), antiplatelet agents (e. g., acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (e. g., prednisone), selective serotonin reuptake inhibitors (e. g., citalopram, fluoxetine, paroxetine, sertraline).
• In patients with seasonal allergic rhinitis, swelling of the nasal mucosa (including nasal polyps), chronic obstructive pulmonary disease, chronic respiratory tract infections (especially associated with allergic rhinitis-like symptoms), with allergies to other medications, in patients with a significant decrease in the volume of circulating blood, diclofenac should be used with caution.

Side effects

Criteria for evaluating the frequency of adverse reactions: very common (>1/10), common (≥1/100, ><1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000) and very rare (

Disorders of the gastrointestinal tract: 

often, epigastric pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, anorexia;

rare — gastritis, proctitis, bleeding from the gastrointestinal tract (GI) tract (vomiting blood, melena, diarrhea mixed with blood), ulcers of the gastrointestinal tract (with or without bleeding or perforation);

very rarely — stomatitis, glossitis, esophagitis, nonspecific haemorrhagic colitis, exacerbation of ulcerative colitis or Crohn’s disease, the occurrence of diaphragmatic strictures in the intestines, constipation, pancreatitis.

Liver and biliary tract disorders: 

often-increased activity of aminotransferases;

rarely-hepatitis, jaundice, impaired liver function;

very rarely-lightning-fast hepatitis, liver necrosis, liver failure.

Nervous system disorders: 

often-headache, dizziness; rarely-drowsiness; very rarely-sensitivity disorders, including paresthesia, memory disorders, tremor, convulsions, anxiety, cerebrovascular disorders, aseptic meningitis.

Mental disorders: very rarely — disorientation, depression, insomnia, night “nightmares”, irritability, mental disorders.

Sensory disorders: 

often — vertigo; 

very rarely-visual impairment (blurred vision, diplopia), hearing impairment, tinnitus, impaired taste sensations.

Kidney and urinary tract disorders: 

very rarely — acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary necrosis.

Disorders of the blood and lymphatic system: 

very rarely — thrombocytopenia, leukopenia, hemolytic and aplastic anemia, agranulocytosis, eosinophilia.

Immune system disorders: 

anaphylactic / anaphylactoid reactions, including marked lowering of blood pressure (BP) and shock;

very rarely — angioedema (including facial edema).

Disorders of the cardiovascular system: 

very rarely — palpitations, chest pain, high blood pressure, vasculitis, heart failure, myocardial infarction.

Respiratory system disorders: 

chest and mediastinal organs: rarely-exacerbation of bronchial asthma, cough, laryngeal edema; very rarely — pneumonitis.

Skin and subcutaneous tissue disorders: 

often — skin rash; rarely-urticaria; 

very rarely — bullous rashes, eczema, including multiforme and Stevens-Johnson syndrome, Lyell’s syndrome, exfoliative dermatitis, itching, hair loss, photosensitization, purpura, including allergic.

General disorders and disorders at the injection site: 

rarely-edema.

Interaction

Lithium preparations, digoxin: diclofenac may increase plasma concentrations of lithium and digoxin. Monitoring of lithium and digoxin concentrations in plasma is recommended when used concomitantly with diclofenac. Methotrexate: caution should be exercised when prescribing diclofenac less than 24 hours before or 24 hours after taking methotrexate, as in such cases, the concentration of methotrexate in the blood may increase and its toxic effect may increase. Cyclosporine: the effect of diclofenac on prostaglandin synthesis in the kidneys may increase the nephrotoxicity of cyclosporine. Therefore, the dose of diclofenac used should be lower than in patients who do not use cyclosporine. Diuretic and antihypertensive drugs: diclofenac may reduce the antihypertensive effect of diuretic and antihypertensive drugs (for example, beta-blockers, angiotensin — converting enzyme-ACE inhibitors). These combinations should be used with caution in patients, especially the elderly, and blood pressure should be monitored regularly. Patients should be adequately hydrated. Renal function should be monitored after initiation and periodically during treatment, especially with concomitant use of diuretics and ACE inhibitors, due to the increased risk of nephrotoxicity. Drugs that may cause hyperkalemia: concomitant use of diclofenac with potassium-sparing diuretics, cyclosporine, tacrolimus or trimethoprim may lead to an increase in the concentration of potassium in the blood serum (in the case of such a combination of drugs, this indicator should be regularly monitored). Antimicrobial agents-quinolone derivatives: there have been isolated reports of seizures in patients treated simultaneously with quinolone derivatives and diclofenac. Anticoagulants and antiplatelet agents: it is necessary to combine diclofenac with drugs of these groups with caution due to the risk of bleeding. Although clinical studies have not established the effect of diclofenac on the action of anticoagulants, there are isolated reports of an increased risk of bleeding in patients taking this combination of drugs. Therefore, in the case of such a combination of drugs, regular and careful monitoring of patients is recommended. Acetylsalicylic acid reduces the concentration of diclofenac in the blood. NSAIDs and corticosteroids: concomitant systemic use of diclofenac and other systemic NSAIDs or corticosteroids may increase the frequency of side effects (in particular, from the gastrointestinal tract). Selective serotonin reuptake inhibitors (SSRIs): concomitant use of diclofenac and SSRIs increases the risk of gastrointestinal bleeding. Hypoglycemic drugs: in clinical studies, it was found that when used together, diclofenac does not affect the effectiveness of hypoglycemic drugs. However, there are isolated reports of both hypoglycemia and hyperglycemia in such cases, which required a change in the dose of hypoglycemic drugs during diclofenac therapy. Therefore, during the combined use of diclofenac and hypoglycemic drugs, it is recommended to monitor the concentration of blood glucose. Phenytoin: with simultaneous use of phenytoin and diclofenac, it is necessary to monitor the concentration of phenytoin in blood plasma due to the possible increase in its systemic effects. Tacrolimus: nephrotoxicity may be increased when used concomitantly with diclofenac. Cefamandol, cefoperazone, cefotetan, valproic acid, and plicamycin increase the incidence of hypoprothrombinemia. The effect of diclofenac on prostaglandin synthesis in the kidneys may increase the toxic effect of gold preparations. Concomitant use with ethanol, colchicine, corticotropin and St. John’s wort preparations increases the risk of bleeding in the gastrointestinal tract. Potent inhibitors of the CYP2C9 isoenzyme: caution should be exercised when co-prescribing diclofenac and potent inhibitors of the CYP2C9 isoenzyme (such as voriconazole) due to the possible increase in the concentration of diclofenac in the blood serum and increased systemic action.

How to take, course of use and dosage

In all patients receiving diclofenac, it should be used at the lowest effective dose for the shortest possible time required to reduce the severity of symptoms.

Inside, without chewing, during or after a meal, with a sufficient amount of water.

Take 1 tablet 1 time a day. If you need an additional dose of the drug, use tablets of 50 mg. The maximum daily dose is 150 mg.

Overdose

Symptoms: 

vomiting, gastrointestinal bleeding, epigastric pain, diarrhea, dizziness, tinnitus, lethargy, convulsions, rarely – increased blood pressure, acute renal failure, hepatotoxic effect, respiratory depression, coma.

Treatment: 

gastric lavage, activated charcoal, symptomatic therapy aimed at eliminating increased blood pressure, impaired renal function, convulsions, gastrointestinal irritation, respiratory depression. Forced diuresis and hemodialysis are ineffective (due to significant protein binding and intensive metabolism).

Purpose

Nonsteroidal Anti-inflammatory drug (NSAID)

Description

Round biconvex tablets covered with a film-coated pink color; on a cross-section, the core is white to almost white in color.

Functional features

Absorption-fast and complete, food slows down the rate of absorption by 1-4 hours and reduces the maximum concentration (Cmax) by 40%. After oral use of 100 mg tablets, Cmax-0.5 mcg / ml is reached in 4-5 hours. The plasma concentration is linearly dependent on the amount of the administered dose. There were no changes in the pharmacokinetics of diclofenac during repeated use. It does not accumulate if the recommended interval between meals is observed.Bioavailability — 50%. Binding to plasma proteins is more than 99% (most of them are bound to albumins). Penetrates the synovial fluid; Cmax in synovial fluid is observed 2-4 hours later than in plasma. The half-life (half-life) from synovial fluid is 3-6 hours (the concentration of the Active ingredient in synovial fluid 4-6 hours after use of the drug is higher than in plasma, and remains higher for another 12 hours). The relationship of the drug concentration in synovial fluid with the clinical efficacy of the drug has not been clarified. Metabolism: 50% of the Active ingredient is metabolized during the” first pass ” through the liver. Metabolism occurs as a result of repeated or single hydroxylation and conjugation with glucuronic acid. The drug is metabolized by the isoenzyme CYP2C9. The pharmacological activity of the metabolites is lower than that of diclofenac. The systemic clearance is about 260±50 ml / min, the volume of distribution is 550 ml / kg. The plasma half-life is on average about 2.5 hours. 65% of the administered dose is excreted as metabolites by the kidneys; less than 1% is excreted unchanged, the rest of the dose is excreted as metabolites in the bile. In patients with severe renal insufficiency (creatinine clearance less than 10 ml/min), the excretion of metabolites in the bile increases, while their concentration in the blood does not increase. In patients with chronic hepatitis or compensated cirrhosis of the liver, the pharmacokinetic parameters of diclofenac do not change. Diclofenac passes into breast milk.

Complete set

Long-acting film-coated tablets,100 mg. 10 tablets in a contour cell package (blister) made of polyvinyl chloride/polyvinylidene chloride film and aluminum foil printed varnished. 2 contour cell packages together with instructions for use in a cardboard pack.

Special instructions

In order to reduce the risk of adverse events, the drug should be used at the lowest effective dose for the shortest period necessary to relieve symptoms.

NSAID therapy, including diclofenac, especially long-term and high-dose therapy, may be associated with a small increase in the risk of serious cardiovascular thrombotic complications (including myocardial infarction and stroke).

In patients with significant risk factors for cardiovascular events (such as hypertension, hyperlipoproteinemia, diabetes mellitus, and smoking), treatment with diclofenac-containing drugs should only be initiated after a thorough examination and analysis.

Due to the important role of prostaglandins in maintaining renal blood flow should be particularly careful when prescribing the drug to patients with cardiac or renal insufficiency, hypertension,

elderly patients, patients taking diuretics or other drugs that affect kidney function, patients who for any reason there is a decrease in circulating blood volume (e. g. after extensive surgery).

If diclofenac is prescribed in such cases, it is recommended to monitor kidney function as a precautionary measure.

After discontinuation of therapy with the drug, normalization of renal function indicators to baseline values is usually noted.

When using diclofenac, such phenomena as bleeding or ulceration/perforation of the gastrointestinal tract were observed, in some cases with a fatal outcome.

These events may occur at any time when the drug is used in patients with or without previous symptoms and a history of serious gastrointestinal diseases.

In elderly patients, such complications can have serious consequences.

If patients receiving diclofenac develop bleeding or ulceration of the gastrointestinal tract, the drug should be discontinued.

To reduce the risk of toxic effects on the gastrointestinal tract, the drug should be used at the minimum effective dose for the shortest possible time, especially

in patients with ulcerative lesions of the gastrointestinal tract, especially complicated by bleeding or perforation in the anamnesis, as well as elderly patients.

Patients with an increased risk of developing gastrointestinal complications, as well as those receiving therapy with low doses of acetylsalicylic acid or other medications that may increase the risk of gastrointestinal damage, should take gastroprotectors.

Patients with a history of gastrointestinal disorders, especially the elderly, should inform the doctor about all symptoms of the digestive system.

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

With prolonged use of diclofenac, an increase in the activity of one or more “liver” enzymes may occur.

If liver function disorders persist and progress, or if signs of liver disease or other symptoms occur (for example, eosinophilia, rash, etc. ), the drug should be discontinued.

It should be borne in mind that hepatitis against the background of the use of diclofenac can develop without prodromal phenomena.

Caution should be exercised when using diclofenac in patients with hepatic porphyria, as the drug can provoke attacks of porphyria.

Diclofenac can reversibly inhibit platelet aggregation, so in patients with hemostatic disorders with prolonged use, careful monitoring of appropriate laboratory parameters should be carried out.

In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (i. e. nasal polyps), chronic obstructive pulmonary disease, chronic infections of the respiratory tract

(especially associated with allergic symptoms initoptions), and in patients who are allergic to other drugs (rash, itching, urticaria) in the appointment of diclofenac should be particularly careful (willingness to resuscitation).

Severe and sometimes fatal skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely with diclofenac.

The greatest risk and frequency of severe dermatological reactions were observed in the first month of diclofenac treatment.

If patients receiving the drug develop the first signs of skin rash, mucosal lesions, or other symptoms of hypersensitivity, diclofenac should be discontinued.

The anti-inflammatory effect of NSAIDs, including diclofenac, can make it difficult to diagnose infectious processes.

Due to the negative effect on fertility, women planning pregnancy are not recommended to use the drug. In patients with infertility (including those undergoing examination), it is recommended to cancel the drug.

When taking 100 mg tablets in patients with diabetes mellitus, the content of sucrose in the preparation should be taken into account (in 1 tablet — 94.7880 mg of sucrose).

Influence on the ability to drive vehicles and work with mechanisms

Patients who experience visual disturbances, dizziness, drowsiness, or other central nervous system disorders during the use of diclofenac should not drive vehicles or work with mechanisms.

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 25 C. Keep out of reach of children.

Shelf

life is 4 years. Do not use after the expiration date indicated on the package.

Active ingredient

Diclofenac

Conditions of release from pharmacies

By prescription

Dosage form

long-acting tablets

Purpose

For adults

Indications

Lumbago, Swelling after injuries and operations, Adnexitis, Osteoarthritis, Tendon Inflammation, Rheumatoid Arthritis, Bursitis, Arthritis, Sciatica, Periarthritis, Osteoarthritis