Naklofen Duo (Diclofenac) 75mg 20 tablets

The composition and form of issue: 

Capsules with modified release 1 capsule.

enteric coated pellets:

diclofenac sodium 25 mg

excipients: sugar spheres (sucrose content of not more than 92%) of hyprolose (hydroxypropyl cellulose) hypromellose magnesium carbonate heavy methacrylic acid and ethylacrylate copolymer (1:1) dispersion 30% triethylcitrate talc, titanium dioxide, carboxymethylcellulose sodium, macrogol, sodium hydroxide

pellets with sustained release:

diclofenac sodium 50 mg

excipients: sugar spheres (sucrose content of not more than 92%) of hyprolose (hydroxypropyl) ammonium methacrylate copolymer (type b) ammonium methacrylate copolymer (type a) talc triethylcitrate

the composition of the capsule: enteric coated pellets pellets with sustained release of the talc (0, 2% of talc was mixed with the pellets prior to filling into capsules talc prevents electrostatic charging of the pellets in the capsule filling process)

the composition of the capsule shell:

the body of the capsule: gelatin EP titanium dioxide (E171)

the cap of the capsule: gelatin EP titanium dioxide (E171), Indigo Carmine dye FD& C Blue2 (E132)

in blister packs of 10 capsules with modified release 75 mg packs cardboard 2 blister.

Description pharmaceutical form:

Capsule No. 2, filled-pellets from white to yellowish. The capsule body is white, the cap capsule blue.

Pharmacokinetics:

Absorption is rapid and complete. Diclofenac contained in capsules Naklofen Duo in the form of enteric coated pellets and pellets with sustained release, so capsules Naklofen Duo have a rapid and prolonged effect.

Cmax in plasma observed after 30-60 min after administration. Therapeutic concentration be maintained twice as long than when using tablets, enteric coated with a film cover. Concentration in plasma is in linear dependence on the received dose. Changes in the pharmacokinetics of diclofenac amid repeated introduction is not marked. Not koumouliruet in compliance with the recommended interval between doses. Bioavailability of 50%. The plasma protein binding is more than 99% (the majority is bound to albumin). Penetrates into synovial fluid Cmax in synovial fluid is observed in 2-4 hours later than in plasma. Diclofenac excreted more slowly from the synovial fluid than from plasma.

Metabolism: 50% of the active substance is metabolized during the first pass through the liver. Metabolism occurs as a result of repeated or single hydroxylation and conjugation with glucuronic acid. In the metabolism of the drug involved enzyme system P450CYP2C9. The pharmacological activity of metabolites below, than diclofenac.

Systemic Cl is 260 ml/min, the volume of 550 ml/kg. T1/2 from plasma — about 2 h About 70% of the administered dose was excreted in the form of pharmacologically inactive metabolites by the kidneys less than 1% in an unmodified form, the rest of the dose as metabolites in the bile.

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

In patients with chronic hepatitis or compensated liver cirrhosis and elderly patients the pharmacokinetic parameters of diclofenac are not changed. Diclofenac passes into breast milk.

Description pharmacological action:

Diclofenac sodium is a NSAID that has analgesic, anti-inflammatory and antipyretic activity. The main mechanism of its action and the associated side effects are indiscriminate inhibition of the activity of enzymes COX-1 and COX-2 that leads to the violation of arachidonic acid metabolism, reduce the synthesis of PG, prostacyclin and thromboxane. Reduced levels of various GHGs in the urine, the gastric mucosa and synovial fluid.

Most effective for pain of an inflammatory nature. In rheumatic diseases anti-inflammatory and analgesic effect of diclofenac contributes to a significant decrease in severity of pain, morning stiffness, swelling of joints that improves a functional condition of the joint. In trauma, postoperative diclofenac reduces pain and inflammatory swelling. Like all NSAIDs, diclofenac has antiplatelet activity. At therapeutic doses of diclofenac sodium has almost no effect on bleeding time. Prolonged treatment analgesic effect of diclofenac sodium is not reduced.

Indications:

• inflammatory and degenerative diseases of the musculoskeletal system: rheumatoid arthritis, psoriatic, juvenile chronic arthritis, ankylosing spondylitis (Bechterew’s disease), gouty arthritis, arthritis with disease Reiter’s, rheumatic soft tissue osteoarthritis of peripheral joints and spine, including those with radicular syndrome, tenosynovitis, periarthritis, bursitis, myositis, synovitis)
• pain syndrome weak or moderate intensity: neuralgia, myalgia, sciatica, post traumatic pain syndrome accompanied by inflammation, postoperative pain, headache, migraine, algomenorrhea, adnexitis, proctitis, dental pain, renal and biliary colic
• in the complex therapy of infectious-inflammatory diseases of ear, throat, nose with marked pain syndrome (pharyngitis, tonsillitis, otitis media)
• febrile syndrome.

Diclofenac is intended for symptomatic treatment and on disease progression is not affected.

Contraindications:

• hypersensitivity to diclofenac full or partial combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance of acetylsalicylic acid and other NSAIDs (including history)
• since the coronary artery bypass surgery
• erosive-ulcerative changes of the gastric mucosa or duodenal ulcers, active gastrointestinal bleeding
• inflammatory bowel diseases in acute phase (ulcerative colitis — ulcerative colitis, Crohn’s disease)
• cerebrovascular bleeding or other bleeding disorders
• severe hepatic impairment or active liver disease
• expressed kidney failure (Cl creatinine less than 30 ml/min), including confirmed hyperkalemia, progressive disease of the kidney
• decompensated heart failure
• oppression kostnomozgovy blood
• III trimester of pregnancy, breastfeeding
• children’s age (under 18).

Caution: IHD, cerebrovascular diseases, dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral artery disease, Smoking, and Cl creatinine less than 60 ml/min anamnestic data about the development of ulcerative shock syndrome, infection of Helicobacter pylori, older age, prolonged use of NSAIDs, frequent use of alcohol, serious somatic diseases induced porphyria, epilepsy, diverticulitis, systemic diseases of connective tissue, a significant decrease in BCC (including after the massive surgery), elderly patients (prescribed in lower doses) (including receiving diuretics, the weakened patients and patients with low body mass), I–II trimesters of pregnancy, concomitant therapy with the following drugs: anticoagulants (e.g. warfarin), antiplatelet agents (e.g. acetylsalicylic acid, clopidogrel), oral corticosteroids (e.g. prednisolone), selective inhibitors of reverse takeover serotonin (e.g. citalopram, fluoxetine, paroxetine, sertraline).

Application of pregnancy and breast-feeding:

The use of diclofenac in pregnant women is possible only when the expected benefit outweighs the potential risk to the fetus. Diclofenac is not recommended during the last trimester of pregnancy.

Despite the fact that diclofenac is found in breast milk in small amounts, its use in breastfeeding is not recommended.

Side effects:

Often 1-10% sometimes — 0, 1-1% rare — 0, 01-0, 1% very rarely — less than 0, 01%, including isolated cases.

From the digestive system: often — epigastric pain, abdominal cramps, nausea, vomiting, diarrhea, dyspepsia, flatulence, anorexia, elevation of transaminases rarely — gastritis, bleeding from the gastrointestinal tract (vomiting blood, melena, diarrhea mixed with blood), gastrointestinal ulcer (with or without bleeding or perforation), hepatitis, jaundice, abnormal liver function very rarely — stomatitis, glossitis, dryness of mucous membranes (including of the mouth), damage to the esophagus, diaphragmatically strictures of the intestine (non-specific haemorrhagic colitis, exacerbation of ulcerative colitis or Crohn’s disease), constipation, pancreatitis, fulminant hepatitis.

From the nervous system: often — headache, dizziness, rarely — drowsiness very rare — disturbance of sensitivity, including paresthesias, memory disorders, tremors, convulsions, anxiety, cerebrovascular disorders, aseptic meningitis, confusion, depression, insomnia, nightmares, irritability, excitement, mental disorders.

From the sensory organs: often — vertigo very rarely — impaired vision (blurred vision, diplopia), impaired hearing, tinnitus, breach of taste sensations.

From the urinary system: very rarely — acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary necrosis, swelling.

Organs of hematopoiesis: rarely — thrombocytopenia, leukopenia, eosinophilia, hemolytic and aplastic anemia, agranulocytosis.

Allergic reactions: anaphylactic/anaphylactoid reactions, including marked reduction in blood pressure and shock very rarely — angioneurotic edema (including face). The drug contains methyl parahydroxybenzoate and parahydroxybenzoate which may cause allergic reactions.

From the side of cardiovascular system: very rarely — palpitations, tachycardia, arrythmia, chest pain, increased blood pressure, vasculitis, heart failure, myocardial infarction.

The respiratory system: rarely — cough, bronchial asthma (including dyspnoea) very rare pneumonitis, edema of the larynx.

With the skin: often — skin rash rare — urticaria very rare — bullous rash, eczema, including multiforme and Stevens-Johnson syndrome, Lyell’s syndrome, exfoliative dermatitis, itching, hair loss, photosensitivity, purpura, including allergic.

Drug interactions:

Increases concentration in plasma digoxin, methotrexate, lithium preparations and cyclosporine. Reduces effect of diuretics against kalisberegath dioretikov increases risk giperkaliemii against the background of anticoagulants, antiplatelet and thrombolytic drugs (alteplase, streptokinase, urokinase) increases the risk of haemorrhage (often gastrointestinal).

Reduces effect of hypotensive and hypnotic drugs. Increases the likelihood of side effects of other NSAIDs and corticosteroids (bleeding from the gastrointestinal tract), toxicity of methotrexate and nephrotoxicity of cyclosporine.

Acetylsalicylic acid reduces the concentration of diclofenac in the blood. Simultaneous use with paracetamol increases the risk of nephrotoxic effects of diclofenac.

Hypoglycemic drugs — you may experience Hypo – or hyperglycemia. When this combination of funds is necessary to control the level of sugar in the blood.

Cefamandole, cefoperazone, cefotetan, valproic acid and plicamycin increase the frequency of gipoprotrombinemii.

Cyclosporine and gold drugs increase the effect of diclofenac on the synthesis of PG in the kidney, which is manifested by increased nephrotoxicity.

Selective inhibitors of serotonin reuptake increase the risk of bleeding from the gastrointestinal tract.

Coadministration with ethanol, colchicine, corticotropin, and drugs St. John’s wort increases the risk of bleeding in the digestive tract.

Drugs that cause photosensitivity, increase the sensitizing action of diclofenac to UV irradiation.

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

Antibacterial drugs from the group chinolone — the risk of seizures.

Method of application and dose:

Inside, the capsule should be swallowed whole with water at the end or after a meal, usually in the morning. Are assigned individually, taking into account the severity of the disease. Adults usually appoint 1 KAPS. 75 mg 1-2 times a day. The maximum daily dose — 150 mg.

Overdose:

Symptoms: vomiting, nausea, abdominal pain, bleeding from the gastrointestinal tract, diarrhea, headache, dizziness, tinnitus, irritability, symptoms of hyperventilation with increased convulsive readiness, convulsions, in large overdose, acute renal failure, hepatotoxic effects.

Treatment: gastric lavage, activated charcoal, symptomatic therapy, aimed at addressing the increase in BP, renal dysfunction, seizures, irritation of the gastrointestinal tract, respiratory depression. Forced diuresis, hemodialysis is ineffective (significant relationship with the squirrels and intensive metabolism).

Special instructions:

In order to quickly achieve the desired therapeutic effect take the drug 30 minutes before a meal. In other cases, taking before, during or after a meal whole, squeezed enough water.

To reduce the risk of adverse effects from the blood should use the minimum effective dose minimum possible short course.

With caution should use the drug in ulcerative colitis and Crohn’s disease because of possible exacerbation of the disease.

Long-term use of diclofenac is possible, although in rare cases, the development of serious hepatotoxic reactions, therefore it is recommended to investigate the function of the liver.

Due to the important role of PG in maintaining renal blood flow should be particularly careful when prescribing the drug to patients with cardiac or renal insufficiency and in the treatment of elderly people taking diuretics, and patients who, for any reason, a decrease in BCC (for example after major surgery). If in such cases, prescribe diclofenac, recommended as a precaution to monitor kidney function.

With caution should designate diclofenac in patients with coagulation disorders of blood, porphyria, epilepsy, as well as patients receiving anticoagulants or fibrinolytic.

When conducting long-term therapy should be monitored picture peripheral blood, analysis of stool for occult blood.

In connection with negative effect on fertility, women wishing to become pregnant, the drug is not recommended. In patients with infertility (including passing the examination) are advised to stop the drug.

Patients taking the drug, you must abstain from alcohol.

Infectious diseases anti-inflammatory and antipyretic effects of diclofenac sodium may mask the symptoms of these diseases.

The amount of sucrose contained in the product, does not affect patients with the following conditions: the enzyme lactase deficiency, galactosemia and malabsorption syndrome glucose/galactose.

Impact on the ability to drive a car or other mechanical means. During the period of treatment may decrease the speed of mental and motor reactions, so you should refrain from activities potentially hazardous activities, require high concentration and psychomotor speed reactions.