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

The main mechanism of its action and associated side effects are indiscriminate inhibition of the activity of the enzyme cyclooxygenase 1 and 2 (COX1 and COX2), which leads to a disruption of the metabolism of arachidonic acid, a decrease in the synthesis of prostaglandins, prostacyclin and thromboxane.The synthesis of prostaglandins in the kidneys, mucous membrane of the stomach and synovial fluid decreases. The most effective for inflammatory pain. In rheumatic diseases, the anti-inflammatory and anchoring effect of diclofenac significantly reduces the severity of pain, morning stiffness, swelling of the joints, which improves the functional state of the joints. With injuries, in the postoperative period diclofenac reduces pain and inflammatory swelling. Like all NSAIDs, diclofenac has antiaggregant activity. In therapeutic doses diclofenac practically does not affect the time of bleeding. With prolonged treatment, the analgesic effect of diclofenac does not decrease.

Pharmacokinetics:

Suction. Diclofenac is rapidly absorbed after rectal administration. The maximum serum concentrations (C max) are achieved (TCmax) after 1 hour. With rectal administration, eating does not affect the absorption of diclofenac.

Distribution. 99% of the absorbed diclofenac binds to plasma proteins, mainly albumins. Diclofenac actively penetrates into the synovial fluid, where it reaches 60 to 70% of serum concentrations. After 3-6 hours after the application of the concentration of the active substance and metabolites in the synovial fluid is higher than in the serum. Diclofenac of the synovial fluid is excreted more slowly than from the blood serum.

Metabolism and excretion. The half-life (T1 / 2) diclofenac is 1-2 hours. Diclofenac almost completely metabolized in the liver, mainly by hydroxylation and methoxylation. In the metabolism of the drug, the enzyme system P450 CYP2C9. The pharmacological activity of metabolites is lower than that of diclofenac. T1 / 2 from the plasma - 2 hours. About 70% of the administered dose is excreted as pharmacologically inactive 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 (clearance of creatinine (CK) less than 10 ml / min) increases the excretion of metabolites with bile, and there is no increase in their concentration in the blood.

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

Indications:

Diseases that require the achievement of a rapid anti-inflammatory or analgesic effect:

- Inflammatory diseases of the musculoskeletal system (rheumatoid arthritis, seronegative spondylitis, juvenile chronic arthritis, arthritis of another etiology);

- degenerative diseases of the musculoskeletal system (osteoarthritis);

- microcrystalline arthritis (gouty arthritis, pseudo-arthritis arthritis);

- rheumatic soft tissue damage;

- periarthritis, bursitis, myositis, tendinitis, synovitis;

- Other inflammatory diseases of the musculoskeletal system, accompanied by pain syndrome.

As an analgesic, Naklofen is used in soft tissue injuries, in dentistry, after surgical interventions, in severe migraine attacks, primary algodismorrhea, adnexitis, as well as in renal or biliary colic. Diclofenac is intended for symptomatic therapy and does not affect the progression of the disease.

Contraindications:

- Hypersensitivity to diclofenac; complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid and otherNSAIDs (including in the anamnesis).

- The period after aortocoronary bypass surgery.

- Erosive-ulcerous changes in the mucous membrane of the stomach or duodenum, active gastrointestinal bleeding.

- Inflammatory bowel disease (Nonspecific ulcerative colitis (NJC), Crohn's disease) in the phase of exacerbation.

- Rectal bleeding, hemorrhoids, trauma or inflammation of the rectum.

- Cerebrovascular bleeding.

- Hemophilia and other coagulation disorders.

- Severe hepatic impairment or active liver disease.

- Severe renal insufficiency (QC less than 30 ml / min), including confirmed hyperkalemia, progressive kidney disease.

- Decompensated heart failure.

- Inhibition of bone marrow hematopoiesis.

- III trimester of pregnancy, the period of breastfeeding.

- Children's age (up to 15 years).

Carefully:coronary heart disease (IHD), cerebrovascular disease, dyslipidemia / hyperlipidemia, diabetes mellitus, peripheral arterial disease, smoking, CC less than 60 ml / min; anamnestic data on the development of ulcerative lesions of the gastrointestinal tract,the presence of Helicobacter pylori infection, advanced age, prolonged use of NSAIDs, frequent alcohol use, severe physical illness, pregnancy I-II trimester, concomitant therapy with anticoagulants (eg, warfarin), antiplatelet agents (e.g., acetylsalicylic acid, clopidogrel), fibrinolytics, oral glucocorticosteroids (for example, prednisolone), selective serotonin reuptake inhibitors (for example, citalopram, fluoxetine, paroxetine, sertraline).

Pregnancy and lactation:

The use of diclofenac in pregnant women is possible only when the expected benefit for the mother exceeds the potential risk to the fetus. Diclofenac do not use during the last trimester of pregnancy. Although diclofenac is found in breast milk in small amounts, its use during breastfeeding is not recommended.

Dosing and Administration:Rectally. If patients with oral diclofenac forms are not well tolerated, Naklofen can be administered rectally in the form of suppositories at appropriate doses.When combining several dosage forms (in addition to oral administration of the drug), it should be borne in mind that the daily dose of diclofenac should not exceed 150 mg. Adults with an initial dose of 100 - 150 mg per day (1 suppository 2-3 times a day), depending on the severity of the disease. To adolescents aged 15 years and over, one suppository is recommended no more than 2 times a day. The maintenance dose is usually 100 mg per day (1 suppository 2 times a day). The minimum effective dose should be used as little as possible.

Side effects:

Classification of the incidence of adverse events (WHO):

very often> 1/10

often from> 1/100 to <1/10

infrequently from> 1/1000 to <1/100

rarely from> 1/10000 to <1/1000

very rarely from <1/10000, including individual messages.

From the digestive system: often - epigastric pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, anorexia, increased activity of aminotransferases; rarely gastritis, proctitis, exacerbation of hemorrhoids, bleeding from the gastrointestinal tract (vomiting with blood, melena, diarrhea with a trace of blood), gastrointestinal ulcers (with or without bleeding or perforation), hepatitis, jaundice, dysfunction of the liver; very rarely - stomatitis, glossitis,dryness of the mucous membranes (including the mouth), damage to the esophagus, diaphragm-like bowel strains (nonspecific hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn's disease), constipation, pancreatitis, fulminant hepatitis. When using suppositories, local irritation and inflammation are possible.

From the nervous system: often - headache, dizziness; rarely - drowsiness; very rarely - a violation of sensitivity, incl. paresthesia, memory disorders, tremors, convulsions, anxiety, cerebrovascular disorders, aseptic meningitis, disorientation, depression, insomnia, nightmares, irritability, mental disorders.

From the sense organs: often - vertigo; very rarely - visual impairment (blurred vision, diplopia), hearing impairment, tinnitus, a violation of taste sensations.

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

From the hematopoiesis: very rarely - thrombocytopenia, leukopenia, eosinophilia, hemolytic and aplastic anemia, agranulocytosis.

Allergic reactions: anaphylactic / anaphylactoid reactions, including a marked decrease in blood pressure (BP) and shock; very rarely - angioedema (including face).

From the cardiovascular system: very rarely - palpitation, extrasystole, chest pain, increased blood pressure, vasculitis, heart failure, myocardial infarction. From the respiratory system: rarely - cough, bronchial asthma (including dyspnea); very rarely - pneumonitis, laryngeal edema.

From the skin: often - skin rash; rarely - hives; very rarely - bullous eruptions, eczema, incl. multiform and Stevens-Johnson syndrome, Lyell's syndrome, exfoliative dermatitis, itching, hair loss, photosensitivity, purpura, incl. allergic.

Overdose:

When using suppositories, an overdose is unlikely.

Symptoms: vomiting, nausea, abdominal pain, bleeding from the gastrointestinal tract, diarrhea, headache, dizziness, tinnitus, increased excitability, hyperventilation with increased convulsive readiness, convulsions, with a significant overdose-acute renal failure, hepatotoxic action.

Treatment: symptomatic therapy aimed at the elimination of high blood pressure (BP), violations of kidney function, seizures, irritation of the gastrointestinal tract, respiratory depression. Forced diuresis and hemodialysis are ineffective (significant association 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; on the background of anticoagulants, antiplatelet agents and thrombolytic drugs (alteplase, streptokinase, urokinase) increases the risk of bleeding (more often - the gastrointestinal tract).

Reduces the effect of hypotensive and hypnotic drugs. Increases the likelihood of side effects of other NSAIDs and glucocorticosteroids (GCS) (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 developing nephrotoxic effects of diclofenac.

With simultaneous administration with hypoglycemic agents, hypo- or hyperglycemia can be observed. With this combination of funds, it is necessary to monitor the concentration of glucose in the blood.

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 is manifested by increased nephrotoxicity. Selective serotonin reuptake inhibitors increase the risk of bleeding from the digestive tract.

Simultaneous administration with ethanol, colchicine, corticotropin and preparations of St. John's wort increases the risk of bleeding in the digestive tract. Medicines that cause photosensitivity, increase the sensitizing effect of diclofenac to ultraviolet radiation. 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:

Patients should inform the physician of any chronic illness, metabolic disorder, or sensitivity of the reaction in the history.When treating the drug Naklofen should carefully monitor patients who have a history of which there are diseases of the upper gastrointestinal tract.

With caution should use the drug with NNK and Crohn's disease because of the possible exacerbation of the disease.

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. With long-term use (more than 2 weeks) of diclofenac, it is necessary to monitor the indicators of liver function (the level of "liver" transaminases). Caution should be given diclofenac patients with severe renal or hepatic insufficiency, heart failure, with blood clotting disorders, porphyria, epilepsy, as well as patients receiving anticoagulants or fibrinolytics.

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 pregnancy.

In infectious diseases, the anti-inflammatory and antipyretic effects of diclofenac sodium can mask the symptoms of these diseases. In elderly patients, as with other drugs, Naklofen should be used in a minimally effective dose

Effect on the ability to drive transp. cf. and fur:

During the treatment period, it is possible to reduce the speed of mental and motor reactions, so it is necessary to refrain from engaging in potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Suppositories rectal by 50 mg.

Packaging:5 suppositories per strip. 2 strips are placed in a pack of cardboard along with instructions for use.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N013166 / 02

Date of registration:14.08.2008

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp27.02.2016

Illustrated instructions

Instructions

Naklofen (Naklofen)