Наклофен® Duo

General characteristics. Structure:

Active ingredient: 75 mg of diclofenac of sodium (25 mg in the form of kishechnorastvorimy pellets, 50 mg in the form of pellets with the prolonged release).

Excipients:
- Kishechnorastvorimy pellets:
sugar spheres (content of sucrose no more than 92%), hypro rod (hydroxypropyl cellulose), gipromelloza, magnesium carbonate, heavy, methacrylic acid and ethyl acrylate copolymer (1: 1) dispersion of 30%, triethyl citrate, talc, titanium dioxide, sodium carboxymethylcellulose, macrogoal, sodium hydroxide.
- Pellets with the prolonged release: 
sugar spheres (content of sucrose no more than 92%), hypro rod (hydroxypropyl cellulose), ammonium methacrylate copolymer, Type B, ammonium methacrylate copolymer, Type A, triethyl citrate, talc. 
- Structure of contents of the capsule:
kishechnorastvorimy pellets, pellets with the prolonged release, talc (0,2% of talc mix with pellets before filling in capsules; talc prevents emergence of an electrostatic charge of pellets in the course of filling of capsules).
- Structure of a cover of the capsule:
Capsule body: gelatin of ER, titanium dioxide (E171);
Capsule lid: gelatin of ER, titanium dioxide (E171), dye FD&C Blue2 indigo carmine (E132).

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

Pharmacological properties:

Pharmacodynamics. Diclofenac of sodium is non-steroidal anti-inflammatory drug, possessing anesthetic, antiinflammatory and febrifugal action.

The main mechanism of its action and side effects connected with it consist 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. Level of various prostaglandins in urine, mucous a stomach and synovial fluid decreases.

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 non-steroidal anti-inflammatory drugs (NPVP), diclofenac has antiagregantny activity. In therapeutic doses sodium diclofenac practically does not exert impact on a bleeding time. At prolonged treatment the analgesic effect of diclofenac of sodium does not decrease.

Pharmacokinetics. Absorption – bystry and full. Diclofenac contains in capsules Naklofen Duo in the form of kishechnorastvorimy pellets and pellets with the prolonged release therefore Naklofen Duo's capsules have the immediate and prolonged effect. The maximum concentration in plasma is noted in 30-60 minutes after reception. Therapeutic concentration to be maintained twice longer, than when using the tablets covered with a kishechnorastvorimy film cover.

Concentration in plasma is in linear dependence on size of the accepted dose. Change of pharmacokinetics of diclofenac against the background of repeated introduction is not noted. Does not kumulirut at observance of the recommended interval between meals. Bioavailability – 50%. Communication with proteins of plasma – more than 99% (the most part contacts albumine). Gets into synovial fluid; the maximum concentration in synovial fluid is observed at 2-4 o'clock later, than in plasma. Diclofenac is more slowly excreted from synovial fluid, than from plasma.

Metabolism: 50% of active agent are exposed to metabolism during "the first passing" through a liver. Metabolism results from a repeated or single hydroxylation and a konjyugirovaniye with glucuronic acid. The fermental P450 CYP2C9 system takes part in metabolism of drug. Pharmacological activity of metabolites is lower, than diclofenac.

The system clearance makes 260 ml/min., distribution volume – 550 ml/kg. Plasma elimination half-life – 2 hours. About 70% of the entered dose are removed in the form of pharmacological inactive metabolites by kidneys; less than 1% are removed in not changed look, other part of a dose is removed in the form of metabolites with bile.

At patients with the expressed renal failure (clearance of creatinine 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, and also elderly patients pharmacokinetic parameters of diclofenac do not change. Diclofenac gets into breast milk.

Indications to use:

• Inflammatory and degenerative diseases of a musculoskeletal system: the pseudorheumatism, the psoriasis, juvenile chronic arthritis ankylosing a spondylarthritis (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, sinoviit).
• Pain syndrome of weak or moderate expressiveness: neuralgia, a mialgiya, a 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.
• As a part of complex therapy of infectious and inflammatory diseases of an ear, a throat, a nose with the expressed pain syndrome (pharyngitis, tonsillitis, otitis).
• Feverish syndrome.
• Diclofenac is intended for symptomatic therapy and on progressing
the disease does not influence.

Route of administration and doses:

Inside, the capsule should be swallowed entirely, washing down with water in the end or after meal, usually in the mornings. It is appointed individually taking into account disease severity.

The adult usually appoint on 1 capsule 75 mg 1-2 times a day. The maximum daily dose – 150 mg.

Features of use:

Naklofen Duo it is necessary to apply with care: coronary heart disease, cerebrovascular diseases, дислипидемия / lipidemia, diabetes mellitus, diseases of peripheral arteries, smoking, clearance of creatinine less than 60 ml/min.; anamnestic data on development of a canker of digestive tract, existence of an infection of Helicobacter pylori, advanced age, long use of non-steroidal anti-inflammatory drugs (NPVP), frequent alcohol intake, heavy somatopathies, the induced porphyria, epilepsy, advanced age, a diverticulitis, general diseases of connecting fabric, considerable decrease in the volume of the circulating blood (VCB) (including after massive surgical intervention), elderly patients (it is appointed in lower doses) (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 glucocorticoids (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 for pregnant women is possible only when the expected advantage exceeds potential risk for a fruit. Diclofenac is not recommended to be used during the last trimester of pregnancy. In spite of the fact that diclofenac is found in breast milk in small amounts, its use during breastfeeding is not recommended.

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, abdominal spasms, nausea, vomiting, diarrhea, dyspepsia, a meteorism, anorexia, increase in activity of aminotransferases; seldom - gastritis, 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 a mouth), injuries of a gullet, 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, excitement, 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, hypostases.

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). Drug contains marked parahydroxybenzoate and spent on drink parahydroxybenzoate which can cause allergic reactions.

From cardiovascular system: very seldom - heartbeat, tachycardia, 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, eczema, including multiformny and Stephens-Johnson's syndrome, a Lyell's disease, exfoliative dermatitis, a skin itch, a hair loss, a photosensitization, a purpura, including allergic.

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.

Hypoglycemic means – it can be observed hypo - or a hyperglycemia. At this combination of means control of level of sugar in blood is necessary;

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 a St. John's Wort 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.

Contraindications:

• Hypersensitivity to diclofenac; a full or incomplete combination of bronchial asthma, the nose recuring a polypose and okolonosovy bosoms and intolerance of acetylsalicylic acid and other NPVP (including in the anamnesis).
• The period after performing aortocoronary shunting.
• Erosive and ulcer changes mucous stomach or 12-perstny gut, active gastrointestinal bleeding.
• Inflammatory diseases of intestines, in an aggravation phase (The Nonspecific Ulcer Colitis (NUC), the Disease Krone).
• 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 (clearance of creatinine 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: vomiting, nausea, abdominal pains, bleeding from a GIT, diarrhea, a headache, dizziness, a sonitus, a hyperexcitability, the hyperventilation phenomena with the increased convulsive readiness, spasms, at considerable overdose – an acute renal failure, a hepatotoxic action.

Treatment: a gastric lavage, absorbent carbon, 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:

To store at a temperature not over 30 ºС. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Capsules with the modified release on 75 mg. On 10 capsules in the blister from a five-layer film. On 2 blisters place in a pack cardboard together with the application instruction.