Diclofenac + Paracetamol (Diclophenacum + Paracetamolum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

NSAIDs - Derivatives of acetic acid and related compounds

Non-narcotic analgesics, including non-steroidal and other anti-inflammatory drugs

Included in the formulation
  • Dolaren®
    pills inwards 
    Outline Pharma Pvt. Ltd.     India
    • АТХ:

    M.01.A.B.55   Diclofenac in combination with other drugs

    Pharmacodynamics:
    The effect of the drug is due to the properties of its constituent components. Diclofenac has anti-inflammatory, analgesic, antiplatelet and antipyretic effect. Indiscriminately inhibiting cyclooxygenase 1 and 2, disrupts the metabolism of arachidonic acid, reduces the amount of prostaglandins in the inflammatory focus. In rheumatic diseases, the anti-inflammatory and analgesic effect of diclofenac significantly reduces the severity of pain, morning stiffness, swelling of the joints, which improves the functional state of the joint. With injuries, in the postoperative period diclofenac reduces pain and inflammatory swelling.
    Paracetamol is a non-narcotic analgesic, blocks cyclooxygenase 1 and 2 predominantly in the CNS, affecting pain centers and thermoregulation. In inflamed tissues, cellular peroxidases neutralize the effect of paracetamol on cyclooxygenase, which explains the almost complete absence of anti-inflammatory effect.
    Pharmacokinetics:
    Suction and distribution
    Absorption of active components (diclofenac and paracetamol) - fast and complete, food slows the absorption rate of diclofenac for 1-4 hours and reduces the maximum concentration by 40%. The concentration of active components in the plasma is linearly dependent on the amount of the administered dose, not cumulated.
    Link with plasma proteins diclofenac - more than 99% (most of it binds to albumins), paracetamol binds to blood proteins by 15%. Both components in a small amount penetrate into the mother's milk. Diclofenac penetrates into the synovial fluid; the maximum concentration in the synovial fluid is observed 2-4 hours later than in the plasma. The half-life of the synovial fluid is 3-6 hours (the concentration of the active substance in the synovial fluid 4-6 hours after the administration of the drug is higher than in the plasma, and remains higher for another 12 hours). The relationship between the concentration of the drug in the synovial fluid and the clinical efficacy of the drug has not been elucidated.
    Metabolism
    Diclofenac - 50% of the active substance is metabolized during the "first pass" through the liver. Metabolism occurs as a result of multiple or one-time hydroxylation and conjugation with glucuronic acid. The enzyme system of cytochrome P450 CYP2C9 takes part in the metabolism of the drug.The pharmacological activity of metabolites is lower than that of diclofenac.
    The system clearance is 350 ml / min, the volume of distribution is 550 ml / kg. Half-life from the plasma - 2 hours 65% of the administered dose is excreted as metabolites by the kidneys; less than 1% is unchanged, the rest of the dose is excreted as metabolites with bile.
    In patients with severe renal failure (creatinine clearance less than 10 ml / min), the excretion of metabolites with bile is increased, while there is no increase in their concentration in the blood.
    In patients with chronic hepatitis or compensated cirrhosis, the pharmacokinetic parameters of diclofenac do not change.
    Paracetamol is metabolized in the liver (90-95%): 80% enters the conjugation reaction with glucuronic acid and sulfates with the formation of inactive metabolites; 17% undergoes hydroxylation with the formation of 8 active metabolites, which are conjugated with glutathione with the formation of already inactive metabolites. With a lack of glutathione, these metabolites can block the enzyme systems of hepatocytes and cause their necrosis. The isozyme CYP2E1 also participates in the metabolism of the drug.The half-life is 1-4 hours. It is excreted by the kidneys in the form of metabolites, mainly conjugates, only 3% in unchanged form. In elderly patients, the clearance of the drug decreases and the half-life increases.
    Indications:
    - short-term therapy of pain syndrome in rheumatic diseases (rheumatoid arthritis, osteoarthrosis);
    - Neuralgia, myalgia, lumboschialgia, posttraumatic pain syndrome, accompanied by inflammation, postoperative pain, headache, migraine, algodismenorea, adnexitis, proctitis, toothache;
    - in the complex therapy of infectious and inflammatory diseases of the ear, throat, nose with severe pain and febrile syndrome (pharyngitis, tonsillitis, otitis).
    ICD-10

    VI.G40-G47.G43   Migraine

    VI.G40-G47.G44   Other headache syndromes

    XI.K55-K63.K62   Other diseases of anus and rectum

    XIII.M05-M14.M05.9   Seropositive rheumatoid arthritis, unspecified

    XIII.M05-M14.M05   Seropositive rheumatoid arthritis

    XIII.M15-M19.M15   Polyarthrosis

    XIII.M15-M19.M19   Other arthrosis

    XIII.M15-M19   Osteoarthritis

    XIII.M20-M25.M25.5   Pain in the joint

    XIII.M50-M54.M54.1   Radiculopathy

    XIII.M50-M54.M54.3   Sciatica

    XIII.M50-M54.M54   Dorsalgia

    XIII.M70-M79.M79.1   Myalgia

    Contraindications:

    - hypersensitivity (including other non-steroidal anti-inflammatory drugs);

    - erosive-ulcerative lesions of the gastrointestinal tract (in the phase of exacerbation);

    bleeding from the gastrointestinal tract;

    - anamnestic data on the attack of bronchial obstruction, rhinitis, urticaria after taking acetylsalicylic acid or other non-steroidal anti-inflammatory drug (complete or incomplete acetylsalicylic acid intolerance syndrome - rhinosinusitis, urticaria, polyps of the nasal mucosa, bronchial asthma);

    - period after aortocoronary shunting;

    - inflammatory bowel disease in the phase of exacerbation;

    - severe hepatic impairment or active liver disease;

    - severe renal failure (creatinine clearance less than 30 ml / min), progressive kidney disease;

    - disorders of hematopoiesis, hemostasis disorders (including hemophilia);

    - Pregnancy;

    - childhood;

    lactation period.

    Carefully:Coronary heart disease, cerebrovascular disease, anemia, bronchial asthma, congestive heart failure, dyslipidemia / hyperlipidemia, arterial hypertension, edematous syndrome, hepatic or renal failure, benign hyperbilirubinemia (including Gilbert's syndrome), alcoholism,erosive and ulcerative diseases of the gastrointestinal tract without exacerbation, diabetes mellitus, peripheral arterial disease, the condition after extensive surgical interventions, porphyria induced, elderly age, systemic connective tissue diseases.
    Pregnancy and lactation:The drug is contraindicated in pregnancy and lactation.
    Dosing and Administration:
    Inside, without chewing, during or after a meal, with a small amount of water.
    Adults - 1 tablet 2-3 times a day. Duration of therapy up to 7 days.
    Side effects:
    From the digestive system: often - non-steroid gastropathy (erosive and ulcerative lesions), gastralgia, nausea, vomiting, diarrhea, flatulence, anorexia, increased activity of hepatic transaminases, gastrointestinal bleeding (hematemesis, melena), hepatitis (including fulminant), pancreatitis, colitis including those complicated by bleeding), exacerbation of ulcerative colitis, exacerbation of Crohn's disease, aphthous stomatitis, glossitis, dryness of the oral mucosa, erosive esophagitis, constipation.
    From the nervous system: headache, dizziness, increased fatigue,paresis, memory loss, disorientation, visual acuity reduction, diplopia, hearing loss, tinnitus, insomnia, irritability, convulsions, depression, anxiety, nightmarish dreams, tremor, psychosis, taste disorders, impaired perception, scotoma, aseptic meningitis .
    From the skin: alopecia, photosensitivity, erythematous skin rash, angioedema, eczema, itching, rash on the mucous membranes (erythematous, urticaria).
    From the urinary system: acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary necrosis, oliguria, cystitis, renal colic, nonspecific bacteriuria.
    From the hematopoiesis: thrombocytopenia, leukopenia, agranulocytosis, hemolytic anemia, aplastic anemia, methemoglobinemia, sulfgemoglobinemia, pancytopenia, neutropenia.
    Allergic reactions: bronchospasm, urticaria, Stevens-Johnson syndrome, Lyell's syndrome, allergic purpura, systemic anaphylactic reactions (including anaphylactic shock), skin rash, bullous dermatitis, erythroderma.
    From the cardiovascular system: arrhythmia, increased blood pressure, palpitation, pain in the chest.
    Other: hypoglycemia (including hypoglycemic coma), impotence.
    Overdose:
    Symptoms: dizziness, tinnitus, pale skin, anorexia, nausea, vomiting, abdominal pain, diarrhea, convulsions, gastrointestinal bleeding; impaired glucose metabolism, metabolic acidosis; with a significant overdose - hepatotoxic effect, acute renal failure with tubular necrosis, arrhythmia, pancreatitis, progressive encephalopathy, coma, death.
    Treatment: gastric lavage, Activated carbon, symptomatic therapy, the introduction of donors of SH-groups and precursors of the synthesis of glutathione-methionine (8-9 hours after an overdose), N-acetylcysteine ​​(after 12 hours). Hemodialysis, forced diuresis are ineffective.
    Interaction:
    Increases the concentration of digoxin, cyclosporine, lithium preparations.
    With simultaneous administration with potassium-sparing diuretics increases the risk of hyperkalemia, with anticoagulants - a risk of bleeding.
    Reduces the effectiveness of the action of diuretic, hypotensive and hypnotic drugs.
    Increases the risk of side effects of non-steroidal anti-inflammatory drugs, glucocorticosteroids (gastrointestinal bleeding), toxicity of methotrexate, nephrotoxicity of cyclosporine.
    When taken with thrombolytic drugs (alteplase, streptokinase, urokinase) increases the risk of bleeding (often GIT).
    Acetylsalicylic acid reduces the concentration of diclofenac in the blood.
    When used simultaneously with oral hypoglycemic drugs, hypo- or hyperglycemia is possible.
    When used simultaneously with cefamandol, cefoperazone, cefotetan, valproic acid, plikamycin, the frequency of hypoprothrombinemia increases.
    Cyclosporine and gold preparations enhance the effect of diclofenac on synthesis prostaglandins in the kidneys, which is manifested by increased nephrotoxicity. Simultaneous use with paracetamol increases the risk of developing nephrotoxic effects of diclofenac.
    Simultaneous use with colchicine, corticotropin, preparations of St. John's wort,ethanol increases the risk of developing gastrointestinal complications, accompanied by bleeding.
    Reduces hypotensive activity blockers of slow calcium channels, ACE inhibitors.
    Inductors of microsomal oxidation in the liver (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) increase the risk of hepatotoxic effects of paracetamol.
    Simultaneous long-term use with salicylates increases the risk of developing malignant diseases of the kidneys, bladder.
    Diflunisal increases the plasma concentration of paracetamol by 50%, increasing the risk of developing its hepatotoxic effect.
    Long-term use of barbiturates reduces the effectiveness of paracetamol.
    Special instructions:
    The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of application, the progression of the disease is not affected.
    When the drug is used by patients with concomitant chronic heart failure, chronic renal insufficiency, taking diuretics, with a reduced volume of circulating blood (including after surgery), it is necessary to monitor kidney function.
    With prolonged therapy, it is necessary to monitor liver function, the picture of peripheral blood, the analysis of feces for latent blood.
    Admission of the drug may distort the quantitative content of glucose and uric acid in the blood plasma (according to laboratory research).
    During the treatment period, it is necessary to refrain from driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.
    Instructions
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