Наклофен®

General characteristics. Structure:

Active ingredient: 75 mg of diclofenac of sodium.

Excipients: benzyl alcohol, propylene glycol, sodium disulphite, sodium hydroxide, water for injections.

Non-steroidal anti-inflammatory drug with the expressed antiinflammatory and analgetic effect.

Pharmacological properties:

Pharmacodynamics. Diclofenac is the non-steroidal anti-inflammatory drug (NPVP) possessing analgeziruyushchy, antiinflammatory and febrifugal action.

The main mechanism of its action consists in not selective oppression of activity of enzyme of cyclooxygenase 1 and 2 (TsOG1 and TsOG2) that leads to disturbance of metabolism of arachidonic acid, decrease in synthesis of prostaglandins, prostacyclin and thromboxane.

It is most effective at pains of inflammatory character. At rheumatic diseases antiinflammatory and analgeziruyushchy effect of diclofenac promotes considerable reduction of expressiveness of pain, morning constraint, a swelling of joints that improves a functional condition of a joint. At injuries, in the postoperative period diclofenac reduces pain and inflammatory hypostasis. As all NPVP, diclofenac has antiagregantny activity. In therapeutic doses diclofenac practically does not exert impact on a bleeding time. At prolonged treatment the analgeziruyushchy effect of diclofenac does not decrease.

Pharmacokinetics. Time of achievement of the maximum concentration at intramuscular introduction of 75 mg (in oil) of-15-30 min. Communication with proteins of plasma, it is preferential with albumine - 99%. Diclofenac actively gets into synovial fluid where reaches 60 - 70% of serumal concentration. In 3-6 hours after introduction of concentration in oil of active agent and metabolites in synovial fluid is higher, than in serum. Diclofenac from synovial fluid is removed quicker, than from serum. 50% of drug are exposed to metabolism during "the first passing" through a liver. It is almost completely metabolized in a liver, it is preferential by a hydroxylation with the subsequent conjugation with glucuronic acid and sulphations.

The elimination half-life (T1/2) makes 1 - 2 hour. At lungs of an abnormal liver function or kidneys of T1/2 remains not changed. At patients with the expressed renal failure (the clearance of creatinine (CC) less than 10 ml/min.) removal of metabolites with bile increases, at the same time increase in their concentration in blood is not observed.

At patients with chronic hepatitis or the compensated cirrhosis pharmacokinetic parameters do not change.

About 70% of diclofenac are removed by kidneys in the form of pharmacological inactive metabolites. Only 1% of drug is removed in not changed look, other part of metabolites – through intestines.

Patients of advanced age have pharmacokinetic parameters without significant changes.

Indications to use:

Diseases at which achievement of bystry antiinflammatory or analgeziruyushchy effect is required:

• Inflammatory and degenerative diseases of a musculoskeletal system:
 pseudorheumatism, the psoriasis, juvenile chronic arthritis ankylosing a spondylitis (Bekhterev's disease), gouty arthritis, arthritis at a disease of Reuters, rheumatic defeat of soft tissues, an osteoarthrosis of peripheral joints and a backbone including with a radicular syndrome, a tendovaginitis, a periarthritis, a bursitis, a miositis, a synovitis.

• Pain syndrome of weak or moderate expressiveness: neuralgia, mialgiya,
lumbar ishialgia, the posttraumatic pain syndrome which is followed by an inflammation, postoperative pain, a headache, migraine, альгодисменорея, an adnexitis, a proctitis, a dentagra, renal and bilious colic.

Diclofenac is intended for symptomatic therapy and does not influence progressing of a disease.

Route of administration and doses:

Intramusculary. A single dose for adults – 75 mg (1 ampoule). If necessary perhaps repeated introduction, but not earlier than in 12 hours (patients with renal colic can repeatedly administer the drug in 30 minutes). When using other dosage forms of diclofenac it is not necessary to exceed the maximum daily dose of-150 mg. Use duration no more than 2 days, if necessary further is passed to peroral, or rectal use of diclofenac.

It is impossible to mix solution Naklofen with other drugs in one syringe!

Features of use:

Naklofen solution should be applied to intramuscular introduction with care: coronary heart disease, cerebrovascular diseases, дислипидемия / lipidemia, diabetes mellitus, diseases of peripheral arteries, smoking, clearance of creatinine of 30-60 ml/min.; anamnestic data on development of a canker of digestive tract, existence of an infection of Helicobacter pylori, long use of NPVP, frequent alcohol intake, heavy somatopathies, the induced porphyria, epilepsy, a diverticulitis, general diseases of connecting fabric, considerable decrease in the volume of the circulating blood (VCB) (including after extensive surgical intervention), patients of advanced age (including the receiving diuretics weakened patients and with low body weight), pregnancy (the I-II trimester), the accompanying therapy by the following drugs: anticoagulants (for example, warfarin), antiagregant (for example, acetylsalicylic acid, klopidogret), peroral glucocorticosteroids (for example, Prednisolonum), selective serotonin reuptake inhibitors (for example, to tsitalopra, fluoxetine, пароксетин, sertraline).

For decrease in risk of development of the undesirable phenomena from digestive tract it is necessary to use a minimal effective dose minimum possible course.

 Use of diclofenac in the I-II trimesters of pregnancy is possible only when the expected advantage exceeds potential risk for a fruit. In the III trimester and during feeding by a breast drug use Naklofen is contraindicated.

During treatment reduction of speed of mental and motor reactions therefore it is necessary to abstain from occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions is possible.

Side effects:

Often - 1-10%; sometimes - 0.1-1%; seldom - 0.01-0.1%; very seldom - less than 0.01%, including separate cases.

From the alimentary system: often - epigastric pain, nausea, vomiting, diarrhea, dyspepsia, a meteorism, anorexia, increase in activity of aminotransferases; seldom - gastritis, a proctitis, bleeding from the digestive tract (DT) (vomiting with blood, a melena, diarrhea with blood impurity), GIT ulcers (with or without bleeding or perforation), hepatitis, jaundice, an abnormal liver function; very seldom - stomatitis, a glossitis, dryness of mucous membranes (including oral cavities), gullet erosive cankers, diafragmopodobny strictures of intestines, nonspecific hemorrhagic colitis, an exacerbation of ulcer colitis or a disease Krone, a lock, pancreatitis, fulminant hepatitis.

From a nervous system: often - a headache, dizziness; seldom - drowsiness; very seldom - sensitivity disturbance, including paresthesias, dysmnesias, a tremor, spasms, alarm, cerebrovascular disturbances, aseptic meningitis, a disorientation, a depression, sleeplessness, night "nightmares", irritability, mental disturbances.

From sense bodys: often - вертиго; very seldom - a vision disorder (sight misting, a diplopia), a hearing disorder, a sonitus, disturbance of flavoring feelings.

From an urinary system: very seldom - an acute renal failure, a hamaturia, a proteinuria, intersticial nephrite, a nephrotic syndrome, a papillary necrosis.

From bodies of a hemopoiesis: very seldom - thrombocytopenia, a leukopenia, an eosinophilia, hemolitic and aplastic anemia, an agranulocytosis.

Allergic reactions: anaphylactic/anaphylactoid reactions, including the expressed lowering of arterial pressure (ABP) and shock; very seldom - a Quincke's disease (including persons).

From cardiovascular system: very seldom - heartbeat, premature ventricular contraction, a stethalgia, increase in the ABP, a vasculitis, heart failure, a myocardial infarction.

From respiratory system: seldom – cough, bronchial asthma (including an asthma); very seldom – a pneumonitis, throat hypostasis.

From integuments: often - skin rash; seldom - a small tortoiseshell; very seldom - violent rashes, an erythema, including multiformny and Stephens-Johnson's syndrome, a Lyell's disease, exfoliative dermatitis, an itch, a hair loss, a photosensitization, a purpura, including allergic.

Others: in the place in oil of introduction the irritation, pain, hypostasis and reddening of integuments are possible.

Interaction with other medicines:

Increases concentration in plasma of digoxin, a methotrexate, drugs of lithium and cyclosporine.

Reduces effect of diuretics, against the background of kaliysberegayushchy diuretics the risk of development of a hyperpotassemia amplifies; against the background of anticoagulants, antiagregantny and thrombolytic medicines (an alteplaza, Streptokinasa, an urokinase) the risk of development of bleedings increases (more often than a GIT).

Reduces effect of hypotensive and somnolent medicines.

Increases probability of emergence of side effects of other NPVP and glucocorticosteroids (bleeding from a GIT), toxicity of a methotrexate and nephrotoxicity of cyclosporine.

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

Reduces effect of hypoglycemic medicines.

Tsefamandol, цефоперазон, цефотетан, valproic acid and пликамицин increase the frequency of development of a prothrombinopenia.

Cyclosporine and drugs of gold increase influence of diclofenac on synthesis of prostaglandins in kidneys that is shown by increase in nephrotoxicity.

Selective serotonin reuptake inhibitors increase risk of development of bleedings from a GIT.

Co-administration with ethanol, colchicine, corticotropin and drugs of the St. John's Wort which is made a hole increases risk of development of bleedings in a GIT.

The medicines causing a photosensitization increase the sensibilizing effect of diclofenac to ultra-violet radiation.

The medicines blocking canalicular secretion increase concentration in diclofenac plasma, thereby, increasing its toxicity.

Antibacterial medicines from group of a hinolon - risk of development of spasms.

It is impossible to mix solution Naklofen with other drugs in one syringe!

Patients should inform doctors on development of side effects.

Contraindications:

• Hypersensitivity (including to other NPVP), a full or incomplete combination of bronchial asthma, the nose recuring a polypose of a mucous membrane and okolonosovy bosoms and intolerance of acetylsalicylic acid or others
NPVP (including in the anamnesis).

• The period after performing aortocoronary shunting.
• Erosive and ulcer changes of a mucous membrane of a stomach or 12-perstny gut, active gastrointestinal bleeding.
• Inflammatory diseases of intestines (including the nonspecific ulcer colitis (NUC), a disease Krone) in an aggravation phase.
• Cerebrovascular bleeding or other bleedings and disturbances of a hemostasis.
• The expressed liver failure or an active disease of a liver.
• The expressed renal failure (KK less than 30 ml/min.),
• including the confirmed hyperpotassemia, the progressing disease of kidneys.
• Dekompensirovanny heart failure.
• Oppression of a marrowy hemopoiesis.
• III trimester of pregnancy, breastfeeding period.
• Children's age (up to 18 years).

Overdose:

Symptoms: at parenteral administration the overdose is improbable. Clinical symptoms of overdose at parenteral administration are similar to that which can be observed when using other dosage forms: vomiting, bleeding from a GIT, diarrhea, dizziness, a sonitus, spasms, increase in the ABP, respiratory depression; at considerable overdose - an acute renal failure, a hepatotoxic action.

Treatment: the symptomatic therapy directed to elimination of increase in the ABP, a renal failure, spasms, irritations of a GIT, respiratory depression. The artificial diuresis, a hemodialysis are ineffective (considerable communication with proteins and intensive metabolism).

Storage conditions:

List B. To store at a temperature not higher than 25 degrees of S. Hranit in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Solution for intramuscular introduction of 75 mg/3 ml. On 3 ml in an ampoule from neutral glass. On an ampoule the color point specifying the line of a fiasco of an ampoule, and color a quoted ring is put. 5 ampoules in the blister or 5 ampoules in the plastic pallet. 1 blister/pallet in a pack cardboard together with the application instruction.