Fanigan

General characteristics. Structure:

Active ingredients: paracetamol, sodium diclofenac; 1 tablet contains paracetamol 500 mg, diclofenac of sodium of 50 mg.

Excipients: starch corn, K-30 povidone, sodium of a kroskarmelloz, cellulose microcrystallic, magnesium stearate, yellow decline of FCF (Е 110).

Pharmacological properties:

Pharmacodynamics. Fanigan - the combined drug rendering the expressed antiinflammatory, analgeziruyushchy and febrifugal action. Pharmacological activity of drug is caused by properties of diclofenac and paracetamol, being a part of drug.
Diclofenac of sodium renders the expressed antiinflammatory and analgeziruyushchy, and also moderate febrifugal action. Paracetamol renders the expressed analgetic, insignificant antipyretic and antiinflammatory effect. The mechanism of action is connected with inhibition of synthesis of prostaglandins.

Pharmacokinetics. After intake drug is quickly and completely absorbed. Food does not influence drug absorption.
Concentration of active agents in a blood plasma have linear dependence on a dose, the maximum levels are reached in 60-90 minutes after reception.
Linkng of diclofenac with proteins of a blood plasma (it is preferential with albumine) reaches 99,7%. The expected volume of distribution makes 0,12-0,17 l/kg. Diclofenac gets into synovial fluid where its maximum concentration is reached at 2-4 o'clock later, than in a blood plasma. The elimination half-life makes 3-6 hours of synovial fluid.
Metabolism of diclofenac is carried out by a glyukuronization of not changed molecule and a metoksilirovaniye which leads to formation of several phenolic metabolites which biological activity considerably concedes to activity of initial substance.
The general system plasma clearance of diclofenac makes about 300 ml/min. A final elimination half-life - 1-2 hours. 60% of the entered dose are removed with urine in the form of glucuronic conjugates of not changed diclofenac, the rest - with bile and a stake.
Paracetamol is metabolized in a liver and removed, generally with urine.
After repeated use of drug pharmacokinetic indicators of active agents do not change. At observance of the recommended intervals between reception of tablets cumulation of drug is not noted.

Indications to use:

– An acute pain (muscular, head, tooth, with localization in a backbone), at not joint rheumatism, a pseudorheumatism, an ankylosing spondylitis, an osteoarthrosis, a spondylarthritis, bad attacks of gout, primary dysmenorrhea, an adnexitis, a pharyngotonsillitis, otitis.
– Posttraumatic and postoperative pain syndrome.

Route of administration and doses:

The dose is defined by the doctor for each patient individually, depending on age of the patient, character and the course of a disease, individual portability and medical efficiency of drug.
To adults and children 14 years - on 1 tablet 2-3 times a day after food are more senior.
Duration of treatment makes no more than 5-7 days and depends on the course of a disease.
The maximum daily dose for adults and children is more senior than 14 years makes no more than 3 tablets.

Features of use:

The general cautions concerning use of system NPVS
Gastrointestinal ulcers, bleedings and perforation can arise during any period during treatment of NPVS, irrespective of selectivity of TsOG-2, even in the absence of precautionary symptoms. To minimize this risk, treatment should be begun with the smallest effective dose during the shortest span.
There is an increased risk of trombotichesky cardiovascular and cerebrovascular complications with certain selection TsOG-2 inhibitors. It is unknown whether this risk directly depends on selectivity of TsOG-1/TsOG-2 of separate NPVS. There are no available data on prolonged treatment by the maximum dose of diclofenac now, the possibility of similarly increased risk cannot be excluded. Until such data become available, it is necessary to carry out careful assessment of a ratio of risk and advantage of diclofenac use to patients with clinically confirmed coronary heart disease, cerebrovascular disorders, occlusal diseases of peripheral arteries or considerable risk factors (for example arterial hypertension, a lipidemia, a diabetes mellitus, tobacco smoking). In this regard it is necessary to apply the lowest effective dose during the shortest period of treatment.
Renal effects of NPVS include a liquid delay with hypostasis and/or arterial hypertension. Therefore diclofenac should be applied with the reservation to patients with cardiac dysfunction and other states which lead to a liquid delay. The attention is also required by patients who apply accompanying diuretics or APF inhibitors or having the increased risk of emergence of a hypovolemia. Effects, as a rule, more serious at patients of advanced age. If gastrointestinal bleedings or ulcers arise at the patients undergoing treatment using drug it it is necessary to cancel.
Due to the reception of NPVS including diclofenac, it was very seldom reported about skin reactions, some of them lethal, including exfoliative dermatitis, Stephens-Johnson's syndrome and a toxic epidermal necrolysis. The highest risk of these reactions exists at the beginning of therapy, and development of these reactions is noted in most cases in the 1st month of treatment. Drug should be cancelled at the first displays of skin rash, ulcers of a mucous membrane or any other manifestations of hypersensitivity. In rare instances, as well as at use of other NPVS, allergic reactions, including anaphylactic/anaphylactoid reactions, even without preliminary influence of diclofenac can be observed. Thanks to the pharmakodinamichesky properties drug, as well as other NPVS, can mask signs and symptoms of an infection.

Cautions
The general
It is necessary to avoid simultaneous use with system NPVS, such as the selection TsOG-2 inhibitors, due to the lack of any proofs of synergy effect, and in connection with potential additive side effects.
Care concerning patients of advanced age is necessary. In particular weak patients of advanced age are recommended to apply the lowest effective dose with low body weight.

Bronchial asthma in the anamnesis
Patients with bronchial asthma, with seasonal allergic rhinitis, chronic obstructive diseases of lungs or persistent infections of the airways (which are especially tied with allergic, similar to rhinitises, symptoms) have reactions to NPVS, such as an exacerbation of bronchial asthma more often (so-called intolerance of analgetics / analgetic asthma), a Quincke's edema or a small tortoiseshell. In this regard special measures (readiness for rendering acute management) are recommended to such patients. It also concerns patients with allergic reactions, for example rash, an itch, urticaria on other substances.

Influence on a digestive tract
As well as at use of other NPVP, including diclofenac, to patients with the symptoms testimonial of disturbances from the digestive tract (DT) or with the anamnesis which means existence of stomach ulcer or intestines, bleeding and perforation medical observation and extra care is obligatory. The risk of developing of bleeding in a digestive tract increases with increase in a dose and at patients with an ulcer in the anamnesis, especially with complications in the form of bleeding or perforation and at patients of advanced age. To reduce risk of such toxic impact on a digestive tract, treatment is begun and supported by the lowest effective doses. For such patients, and also those which demand simultaneous use of the medicines containing low doses of acetylsalicylic acid (ASK) or other medicines which presumably increase risk of undesirable influence on FRIDAY it is necessary to consider a question of use of a combination therapy using protective equipment (for example, inhibitors of a proton pomp or mizoprostol). Patients with gastrointestinal toxicity in the anamnesis, especially advanced age, have to report about any unusual abdominal symptoms (especially bleedings in a digestive tract). It is also necessary to be careful the patient, receiving at the same time medicines which can increase risk of an ulcer or bleeding, such as system corticosteroids, anticoagulants, antitrombotichesky means or selective serotonin reuptake inhibitors.

Influence on a liver
Careful medical observation is required in case diclofenac is appointed to patients with an abnormal liver function as their state can worsen.
As well as at use of other NPVS, including diclofenac, the level of one or several enzymes of a liver can increase. The increased enzyme levels, as a rule, are recovered after drug phase-out.
During prolonged treatment drug appoint regular observation of functions of a liver and levels of liver enzymes as precautionary measures. If abnormal liver functions remain or worsen and if clinical signs or symptoms can be connected with the progressing diseases of a liver or if other manifestations are observed (for example an eosinophilia, rash), use of drug should be stopped. The course of diseases, such as hepatitises, can pass without prodromal symptoms. It is necessary to be careful a case when drug is used to patients with a hepatic porphyria, because of probability of provoking of an attack.

Influence on kidneys
Prolonged treatment by high doses of NPVS, including diclofenac, often (1-10%) leads to hypostasis and arterial hypertension. Special attention should be paid to patients with dysfunctions of heart or kidneys, arterial hypertension in the anamnesis, to the patients of advanced age, patients receiving the accompanying therapy by diuretics or drugs which significantly influence function of kidneys, and also to patients with essential decrease in extracellular volume of liquid for any reason, for example, to or after serious surgical intervention. In such cases as precautionary measures monitoring of function of kidneys is recommended. The therapy termination usually causes return to the state preceding treatment.

Influence on hematologic indicators
At prolonged use of this drug, as well as other NPVS, monitoring of an integrated analysis of blood is recommended.
As well as other NPVS, drug can temporarily oppress aggregation of thrombocytes. It is necessary to watch carefully patients with disturbance of a hemostasis.
Not to exceed the specified doses.
To consider that at patients with alcoholic netsirotichesky damages of a liver the risk of a hepatotoxic action of paracetamol increases; drug can influence results of laboratory researches on content in blood of glucose and uric acid.
Not to accept drug along with other means containing paracetamol or diclofenac.

Ability to influence speed of response at control of motor transport or work with other mechanisms.
Patients at whom during treatment vision disorders, dizziness вертиго, drowsiness or other disturbances are observed from the central nervous system have to abstain from control of motor transport or work with mechanisms.

Use during pregnancy or feeding by a breast.
Drug протимвопоказан during pregnancy or feeding by a breast.

Children. Drug is contraindicated to children in a vozdasta up to 14 years.

Side effects:

- From system of blood and lymphatic system: thrombocytopenia, a neutropenia, a leukopenia, anemia, including an aplastic anem_yu, hemolitic anemia (especially for patients with deficit glyukozo-6-fosfatdegidrogenazy), a sulfhemoglobinemia and a methemoglobinemia (cyanosis, short wind, a heartache), an agranulocytosis, a pancytopenia.
- From immune system: hypersensitivity reactions, anaphylactic/anaphylactoid reactions, including hypotension and an acute anaphylaxis a Quincke's disease (including a face edema).
Mental disturbances: disorientation, depression, sleep disorder, sleeplessness, nightmares, irritability, concern, sensation of fear, psychotic frustration, confusion of consciousness, psychomotor excitement.
- From a nervous system: headache, dizziness, drowsiness, paresthesias, sleep disorders, sleeplessness, disturbance of memory, spasm, uneasiness, tremor, aseptic meningitis, disturbance of taste, disturbance of cerebral circulation.
- From organs of sight: visual disturbances, sight illegibility, diplopia.
- From acoustic organs: вертиго, a ring in ears, a sonitus, disorders of hearing.
- From cardiovascular system: a heart consciousness, tachycardia, short wind, pain in heart, heart failure, a myocardial infarction, arterial hypertension, a vasculitis.
- From respiratory system: bronchial asthma (including an asthma), a bronchospasm (especially at the patients sensitive to acetylsalicylic acid), a stethalgia, pneumonites.
- From a digestive tract: nausea, vomiting, diarrhea, dyspepsia, abdominal pain, meteorism; gastritises, gastrointestinal bleeding, vomiting with blood impurity, hemorrhagic diarrhea, a melena, stomach ulcer or intestines (with/without bleeding or perforation), colitis (including hemorrhagic colitis and an exacerbation of ulcer colitis or a disease Krone), a lock, stomatitis, a glossitis, frustration from a gullet, diafragmopodobny strictures of intestines, pancreatitis.
- From gepatobiliarny system: the increased level of transaminases; liver failure, hepatitis, liver necrosis, jaundice, disorders of a liver, fulminant hepatitis.
- From skin and hypodermic cellulose: feeling of an itch, skin rashes, an erythema, rashes on mucous membranes, urticaria, violent rashes, eczema, an exudative multiformny erythema, Stephens-Johnson's syndrome, a toxic epidermal necrolysis (Lyell's disease), exfoliative dermatitis, allergic dermatitis, loss of hair, reactions of photosensitivity, purple, an allergic purpura, an itch.
- From an urinary system: acute renal failure, hamaturia, proteinuria, nephrotic syndrome, intersticial nephrite, renal papillary necrosis, liquid delay.
- General frustration: hypostasis, the general weakness, the strengthened sweating, a hypoglycemia, up to a coma.
Diclofenac, especially in high doses (150 mg/days) and at prolonged use, can increase risk of developing of an arterial thrombembolia (for example a myocardial infarction or a stroke).

Interaction with other medicines:

Diclofenac.
- Lithium, digoxin. Drug can increase concentration of lithium and digoxin in a blood plasma. Monitoring of lithium and digoxin in a blood plasma is recommended.
- Diuretic and anti-hypertensive means. Drug, as well as other NPVS, at simultaneous use with diuretics or anti-hypertensive drugs, for example, beta-blockers of calcium channels, inhibitors of an angiotensin-converting enzyme (APF) can reduce their hypotensive effect. Therefore it is necessary to appoint a combination of such drugs with care, and patients (especially advanced age) should control arterial pressure periodically. Patients should use enough water, and after the beginning and after the end of the accompanying therapy it is necessary to control periodically function of kidneys, in particular at use of diuretics and APF inhibitors owing to the increased risk of emergence of nephrotoxicity.
Simultaneous use of kaliysberegayushchy diuretics can lead to increase in level of potassium in blood serum therefore patients who at the same time use such drugs should control potassium level in blood serum.
- Other NPVS and corticosteroids. The accompanying use of drug with other NPVS or corticosteroids can increase the frequency of the undesirable phenomena from digestive tract. It is necessary to avoid simultaneous use of drug with other NPVS, including the selection inhibitors of cyclooxygenase-2, due to the lack of any proofs of possible advantage of synergy action.
Anticoagulants and antiplatelet drugs. Regular simultaneous use of drug with anticoagulants, especially warfarin and other coumarins and antithrombocytic medicines can lead to increase in risk of bleedings. Therefore in case of such combination of medicines careful and regular observation of patients is recommended.
- Selective Serotonin Reuptake Inhibitors (SSRI). Simultaneous use of system NPVS and SIOZS can increase risk of gastrointestinal bleeding.
- Antidiabetic drugs. At simultaneous use of drug and antidiabetic means efficiency of the last does not change. However separate messages on development in such cases both a hypoglycemia, and a hyperglycemia are known that caused need of change of a dose of antihyperglycemic means during drug use. Therefore during therapy by Fanigan it is necessary to control glucose level in blood.
- Methotrexate. It is necessary to be careful at use of NPVS less than in 24 hours prior to or after reception of a methotrexate as in such cases concentration of a methotrexate in blood can increase and amplify its toxic action.
- The drugs stimulating enzymes which metabolize medicines. The drugs stimulating enzymes, for example rifampicin, carbamazepine, Phenytoinum, a St. John's Wort (Hypericum perforatum), etc. are theoretically capable to reduce concentration of diclofenac in a blood plasma.
- Kolestipol and холестирамин. Simultaneous use of Fanigan with kolestipoly or Colestyraminum reduces diclofenac absorption approximately by 30% and 60% respectively.
- Cyclosporine. Influence of NPVS on synthesis of prostaglandins in kidneys can increase nephrotoxicity of cyclosporine therefore it is necessary to appoint drug in smaller doses, than in a case appointment to patients of cyclosporine.
- Antibacterial agents – derivatives of a hinolon. There are separate messages on development of spasms in the patients receiving at the same time derivative hinolon and NPVS.

Paracetamol.
Speed of absorption of paracetamol can increase at use of Metoclopramidum and domperidon and to decrease at use of a holestiramin. The anticoagulating effect of warfarin and other coumarins can amplify at simultaneous prolonged regular daily use of paracetamol, with increase in risk of bleeding. Periodic reception has no considerable effect.
Barbiturates reduce febrifugal effect of paracetamol.
Anticonvulsant drugs (including Phenytoinum, barbiturates, carbamazepine) which stimulate activity of microsomal enzymes of a liver, can strengthen toxic impact of paracetamol on a liver owing to increase in extent of transformation of drug into hepatotoxic metabolites. At simultaneous use of paracetamol with hepatotoxic means toxic influence of drugs on a liver increases.
Simultaneous use of high doses of paracetamol with an isoniazid, rifampicin increases risk of development of a hepatotoxic syndrome. Paracetamol reduces efficiency of diuretics.
Not to apply along with alcohol.

Contraindications:

•   Hypersensitivity to diclofenac, paracetamol or to any other component of drug.
•   Acute stomach ulcer or intestines; gastrointenstinalny bleeding or perforation.
•   A heavy liver failure (a class C on Chayld-Pyyu, cirrhosis or ascites).
•   Heavy renal failure (clearance of creatinine <30 ml/min.).
•   Heavy heart failure (CH III-IV).
•   Patients who in response to use of diclofenac, paracetamol, acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NPVS) have attacks of bronchial asthma ("aspirinovy asthma"), urticaria or acute rhinitis, polyps of a nose and other allergic symptoms.
•   Disturbance of a hemopoiesis of unspecified genesis.
•   Leukopenia.
•   Anemia of average and heavy degrees.
•   Inborn hyperbilirubinemia.
•   Deficit glyukozo-6-fosfatdegidrogenazy.
•   Patients at whom gastrointestinal bleeding or the perforation connected using non-steroidal anti-inflammatory drugs were noted in the anamnesis.
•   Inflammatory diseases of intestines (disease Krone or ulcer colitis).
•   Alcoholism.
•   Treatment of postoperative pain after operation of coronary shunting (or uses of the cardiopulmonary bypass).

Overdose:

Diclofenac.
The typical clinical picture characteristic of diclofenac overdose, does not exist. The overdose can cause vomiting, gastrointestinal bleeding, diarrhea, dizziness, a sonitus and spasms. The acute renal failure and damage of a liver are possible in case of heavy intoxication.

Paracetamol.
Damage of a liver can arise at adults who accepted 10 g and more paracetamol and at children who accepted more than 150 mg/kg of body weight. At patients with risk factors (long reception of carbamazepine, phenobarbital, Phenytoinum, Primidonum, rifampicin, a St. John's Wort or other drugs which induce liver enzymes, an alcohol abuse; insufficiency of glutationovy system, for example improper feeding, AIDS, starvation, a mucoviscidosis, a cachexia) can lead reception of 5 g or more paracetamol to damage of a liver.
Overdose symptoms in the first 24 hours: pallor, nausea, vomiting, anorexia and abdominal pain. Damage of a liver can become explicit in 12-48 hours after overdose. There can be disturbances of metabolism of glucose and a metabolic acidosis. At a serious poisoning the liver failure can progress in encephalopathy, hemorrhage, a hypoglycemia, a coma and to lead to a lethal outcome. The acute renal failure with an acute necrosis of tubules can be shown by severe pain in a waist, a hamaturia, a proteinuria and to develop even in the absence of severe damage of a liver. Also cardiac arrhythmia and pancreatitis was noted.
At prolonged use in high doses from bodies of a hemopoiesis aplastic anemia, a pancytopenia, an agranulocytosis, a neutropenia, a leukopenia, thrombocytopenia can develop. At reception of high doses from a nervous system - dizziness, psychomotor initiation and disturbance of orientation, from an urinary system - nephrotoxicity (renal colic, intersticial nephrite, a papillary necrosis), from system of digestion - гепатонекроз.

Treatment: urgent measures of the supporting and symptomatic therapy.
If the excess dose was accepted within 1 hour, it is necessary to consider expediency of use of absorbent carbon. Concentration of paracetamol should be measured in a blood plasma in 4 hours or later after reception (earlier concentration are doubtful). Treatment by N-Acetylcysteinum can be applied within 24 hours after administration of drug, but the maximum protective effect is gained at its use within 8 hours after reception. Efficiency of an antidote sharply decreases after this time. If necessary to the patient enter N-Acetylcysteinum according to the established list of doses. In the absence of vomiting methionine as the corresponding alternative in the remote areas out of hospital can be applied orally.
The supporting and symptomatic treatment is shown at such complications as arterial hypotension, a renal failure, spasms, disturbances from digestive tract and respiratory depression. It is improbable that an artificial diuresis, the hemodialysis or hemoperfusion are effective for a conclusion of non-steroidal anti-inflammatory drugs (NPVS) as active agents of drug substantially contact proteins of a blood plasma and are exposed to intensive metabolism.

Storage conditions:

To store at a temperature not above 25 °C in original packaging.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 4 tablets in the blister, on 25 blisters in cardboard packaging.
On 10 tablets in the blister, on 10 blisters in cardboard packaging.