Diclofenac - instructions for use, dose, side effects, contraindications

auxiliary substances: benzyl alcohol 40 mg, sodium disulfite 3 mg, propylene glycol 250 mg, sodium hydroxide for pH adjustment, water for injection up to 1 ml.

Description:Transparent colorless or slightly yellowish solution with a faint smell of benzyl alcohol

Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug (NSAID).

ATX: & nbsp

S.01.B.C.03 Diclofenac

M.01.A.B.05 Diclofenac

Pharmacodynamics:NSAID, a phenylacetic acid derivative; has anti-inflammatory, analgesic, 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. The most effective for inflammatory pain. Like all NSAIDs, the drug has antiplatelet activity.

Pharmacokinetics:The time to reach the maximum concentration with intramuscular injection at a dose of 75 mg is 15-30 minutes, the maximum concentration is 1.9-4.8 μg / ml (mean 2.7 μg / ml). After 3 hours after administration, the plasma concentration averages 10% of the maximum. Changes in the pharmacokinetics of diclofenac against the background of repeated administration are not noted. Do not cumulate while observing the recommended interval between administrations.

Bioavailability - 50%. The connection with plasma proteins is more than 99% (most of it is associated with albumins). Penetrates into breast milk, synovial fluid; the maximum concentration (C max) in the synovial fluid is observed 2-4 hours later than in the plasma (the concentration of the drug in the synovial fluid 4-6 hours after its administration is higher than in the plasma, and remains higher for another 12 hours).

50% of the drug 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 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. The half-life of plasma is 2 hours, of synovial fluid is 3-6 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 insufficiency (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.

Indications:

For short-term treatment of pain of different genesis of moderate intensity.

- Diseases of the musculoskeletal system (rheumatoid arthritis, psoriatic, juvenile chronic arthritis, ankylosing spondylitis, gouty arthritis,rheumatic damage of soft tissues, osteoarthritis of peripheral joints and spine (including radicular syndrome);

- lumbago, sciatica, neuralgia;

- algodismenorea, inflammatory processes of the pelvic organs, incl. adnexitis;

- post-traumatic pain syndrome, accompanied by inflammation;

- postoperative pain.

Contraindications:

- Hypersensitivity to the active substance or ancillary components (including other NSAIDs);

- complete or incomplete combination of bronchial asthma, recurrent nasal polyposis or paranasal sinuses, and intolerance to acetylsalicylic acid (ASA) and other NSAIDs (including in the anamnesis);

- erosive and ulcerative lesions of the gastrointestinal tract (in the phase of exacerbation), bleeding from the gastrointestinal tract (GI tract), cerebrovascular or other bleeding;

- inflammatory bowel disease (Crohn's disease, ulcerative colitis) during the exacerbation phase;

- hemopoiesis, hemophilia and other disorders of blood coagulability;

- Decompensated heart failure;

- hepatic insufficiency, liver disease in acute period;

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

- period after aortocoronary shunting;

- pregnancy, lactation;

- children's age (under 18 years).

Carefully:

Coronary heart disease, cerebrovascular disease, congestive heart failure, peripheral arterial disease, diabetes mellitus, dyslipidemia / hyperlipidemia, smoking, kidney failure (creatinine clearance less than 60 ml / min), anemia, bronchial asthma (risk of exacerbation), arterial hypertension, edematous syndrome , a significant decrease in the volume of circulating blood (including after massive surgery), induced porphyria, systemic connective tissue diseases.

Anamnestic data on the development of erosive and ulcerative gastrointestinal damage and liver disease, the presence of Helicobacter pylori infection, prolonged use of NSAIDs, alcoholism, elderly patients (including those receiving diuretics, weakened patients and low-weight patients), severe somatic diseases, concomitant therapy with the following drugs:

- anticoagulants (for example, warfarin),

- antiaggregants (for example, acetylsalicylic acid, clopidogrel),

- oral glucocorticosteroids (eg, prednisolone),

- selective serotonin reuptake inhibitors (eg, citalopram, fluoxetine, paroxetine, sertraline).

Pregnancy and lactation:

The safety of diclofenac in pregnant women has not been studied. Assign diclofenac in I and II trimester of pregnancy should be only in cases where the expected benefit for the mother exceeds the potential risk to the fetus. Diclofenac, like other inhibitors of prostaglandin synthesis, is contraindicated in the last 3 months of pregnancy (possibly suppressing the uterine contractility and premature closure of the arterial duct in the fetus). In studies on animals, no negative effect of diclofenac on the course of pregnancy, embryonic and postnatal development has been established.

Although diclofenac, like other NSAIDs, penetrates into breast milk in small quantities, the drug should not be given to nursing women to avoid undesirable effects on the child.If it is necessary to prescribe diclofenac in a nursing woman, breastfeeding is discontinued. Because the diclofenac, like other NSAIDs, can have a negative effect on fertility, women planning a pregnancy are not recommended to take the drug. In patients undergoing examination and treatment for infertility, the drug should be canceled.

Dosing and Administration:

It is administered intramuscularly. Single dose for adults - 75 mg (1 ampoule). If necessary, repeated administration is possible, but not earlier than 12 hours later.

Duration of use no more than 2 days, if necessary, further pass to oral, or rectal administration of diclofenac.

Use the minimum effective dose of the drug with the minimum possible short course.

Side effects:

Often -1-10%; sometimes - 0,1 - 1%; rarely - 0,01 - 0,1%; very rarely - less than 0.01%,

including individual cases.

Co side of the digestive system:

often - epigastric pain, flatulence, diarrhea, nausea, vomiting, flatulence, dyspepsia, anorexia, increased activity of aminotransferases; rarely - gastritis, proctitis, gastrointestinal ulcers (with or without bleeding or perforation), bleeding from the gastrointestinal tract (vomiting with blood, melena, diarrhea with an admixture of blood), hepatitis, jaundice, dysfunction of the liver;

very rarely - stomatitis, glossitis, dry mouth, esophagitis, diaphragm-like intestinal strictures (nonspecific hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn's disease), constipation, pancreatitis, fulminant hepatitis.

Co side of the nervous system: often - headache, dizziness; rarely - sleep disturbance, drowsiness;

very rarely - a violation of sensitivity, incl. paresthesia, memory disorders, tremor, convulsions, anxiety, cerebrovascular disorders, depression, irritability, aseptic meningitis (more common in patients with systemic lupus erythematosus and other systemic connective tissue diseases), general weakness, disorientation, nightmares, insomnia, fear, mental disorders .

From the sense organs: often - vertigo;

very rarely - visual impairment (blurred vision, diplopia, scotoma), a taste disorder, hearing impairment, tinnitus, small-spot hemorrhage.

Co skin: often - skin rash; rarely - hives;

very rarely - hair loss, bullous eruptions, eczema, incl. multiform and Stevens-Johnson syndrome, Lyell's syndrome, exfoliative dermatitis, itching,photosensitization, purpura, incl. allergic.

Co the urinary tract side: often - peripheral edema;

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

Co side of the organs of hematopoiesis and the immune system:

Very rarely - anemia (including hemolytic and aplastic anemia),

leukopenia, thrombocytopenia, agranulocytosis.

Co the respiratory system:

rarely - bronchial asthma (including dyspnea);

very rarely - pneumonitis.

Co cardiovascular system:

very rarely - palpitations, increased blood pressure; congestive heart failure, extrasystole, chest pain, myocardial infarction, vasculitis.

Allergic reactions:

anaphylactic / anaphylactoid reactions, including a marked decrease

blood pressure and shock, allergic vasculitis;

very rarely - angioedema (including face).

Local reactions with intramuscular injection:

Burning, infiltration, aseptic necrosis, necrosis of adipose tissue.

Overdose:

Symptoms: vomiting, dizziness, headache, dyspnea, confusion, in children - myoclonic cramps, nausea, vomiting, abdominal pain, bleeding, impaired liver and kidney function.

Treatment: symptomatic therapy aimed at eliminating the increase in blood pressure, impaired renal function, seizures, gastrointestinal irritation, respiratory depression, forced diuresis.

Hemodialysis is ineffective (due to a significant connection with proteins and intensive metabolism).

Interaction:

Increases the concentration in the plasma digoxin, methotrexate, lithium and cyclosporine.

Reduces the effect of diuretics, against the background of potassium-sparing diuretics increases the risk of hyperkalemia; against the background of anticoagulants, thrombolytic agents (alteplase, streptokinase, urokinase) - the risk of bleeding (more often from the gastrointestinal tract).

Reduces the effects of hypotensive and hypnotics.

Increases the likelihood of side effects of other NSAIDs and glucocorticosteroids (bleeding in the gastrointestinal tract), toxicity of methotrexate and nephrotoxicity of cyclosporine. ASA reduces the concentration of diclofenac in the blood.

Simultaneous use with paracetamol increases the risk of developing nephrotoxic effects of diclofenac. Reduces the effect of hypoglycemic agents.

Cefamandol, cefoperazone, cefotetan, valproic acid and plikamycin increase the incidence of hypoprothrombinemia.

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

Simultaneous administration with ethanol, colchicine, corticotropin, selective serotonin reuptake inhibitors and St. John's wort increases the risk of bleeding in the gastrointestinal tract.

Diclofenac enhances the effect of drugs that cause photosensitivity. Drugs that block tubular secretion, increase the concentration in the plasma of diclofenac, thereby increasing its toxicity.

Antibacterial drugs from the quinolone group increase the risk of seizures.

Special instructions:

If there are signs of liver damage (skin itching, yellowing of the skin, nausea, vomiting, abdominal pain, darkening of urine, increased level of "liver" transaminases), stop taking the drug and consult a doctor.

Do not use the drug simultaneously with other NSAIDs. The drug can change the properties of platelets, but does not replace the preventive effect of acetylsalicylic acid in cardiovascular diseases.

The use of the drug may adversely affect female fertility and is not recommended for women planning a pregnancy.

After 2 weeks of use, it is necessary to monitor the function of the liver ("transaminase"), the picture of peripheral blood, the analysis of feces for latent blood. During the treatment period, it is possible to reduce the speed of mental and motor reactions, so it is necessary to refrain from driving motor vehicles and practicing other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions, alcohol consumption.

Effect on the ability to drive transp. cf. and fur:In the period of treatment, patients who have visual disturbances, dizziness, snotty, vertigo, or other disturbances from the central nervous system against the background of the use of diclofenac should not control the vehicles and mechanisms. Patients should also be cautious when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Solution for intramuscular injection 25 mg / ml.

Packaging:

3 ml in a dark glass ampoule, with a notch in the narrowing of the neck of the ampoule and a marking color point indicating

direction of the fault.

By 5 ampoules in a plastic pallet or in a blister AL / PVC.

For 1, 2, 3, 4 pallets or blisters, together with the instruction, they are placed in a pack of cardboard or 5, 10, 15, 20 ampoules, together with instructions for use, in a cardboard box with a cardboard separator.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 30 ° C.

Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N014940 / 02

Date of registration:24.11.2008

The owner of the registration certificate:M. J. Biofarm Pvt. Ltd.M. J. Biofarm Pvt. Ltd. India

Manufacturer: & nbsp

M.J. BIOPHARM, Pvt. Ltd. India

Representation: & nbspM.J. BIOFARM Pvt. Ltd. division of the corporation MJ Group M.J. BIOFARM Pvt. Ltd. division of the corporation MJ Group India

Information update date: & nbsp26.02.2016

Illustrated instructions

Instructions

Diclofenac (Diclofenac)