for medical use
active substances: paracetamol, diclofenac sodium;
1 tablet contains paracetamol 500 mg, diclofenac sodium 50 mg;
excipients: corn starch, povidone К-30, сroscarmellose sodium, microcrystalline cellulose, magnesium stearate, Sunset Yellow FCF (Е 110).
Basic physico-chemical properties:orangecapsule-shaped tablets with white speckles.
Non-steroidal anti-inflammatory and antirheumatic drugs. ATC code М01А В55.
Fanigan is a combined drug with a pronounced anti-inflammatory, analgesic and antipyretic effect. Pharmacological activity of the drug is due to the properties of diclofenac and paracetamol, which are the components of the drug.
Diclofenac sodium has a pronounced anti-inflammatory and analgesic, and a moderate antipyretic effect. Paracetamol has a pronounced analgesic, slight antipyretic and anti-inflammatory effect. The mechanism of action is associated with inhibition of prostaglandin synthesis.
Diclofenac sodium is rapidly absorbed in blood; the maximum plasma concentration is achieved after 1-2 hours. Binding with the plasma proteins is over 99%. It easily penetrates into the tissues and synovial liquid, where its concentration grows slowly, after 4 hours it reaches higher levels than in the blood plasma. Food may slow down the absorption rate, without any effect on completeness of absorption. Bioavailability is about 5%.
The half-life in plasma is 1-2 hours; in synovial fluid it is 3-6 hours. About 35% are excreted in the form of metabolites with the feces; about 65% are metabolized in the liver and excreted by the kidneys in the form of inactive derivatives, about 1% in the unchanged form.
Paracetamol is rapidly and almost completely absorbed in the gastrointestinal tract. Its maximum plasma concentration is achieved after n30-60 minutes. The half-life is 1-4 hours. It is well distributed in all the body fluids. Binding with the blood proteins is variable. Paracetamol is metabolized in the liver and excreted mainly by the kidneys in the form of conjugated metabolites.
After a repeated dose of the drug, pharmacokinetic parameters of the active substances remain unchanged. On condition of compliance with the recommended intervals between taking the tablets, cumulation of the drug is not detected.
– Acute pain (muscular, headache, toothache localized in the spine), nonartricular rheumatism, rheumatoid arthritis, ankylosing spondylitis, osteoarthrosis, spondylarthritis, acute gout attacks, primary dysmenorrhea, adnexitis, pharyngotonsillitis, otitis.
– Post-traumatic and post-operative pain syndrome.
Hypersensitivity to diclofenac, paracetamol or to any other component of the drug.
Acute gastric or intestinal ulcer; gastrointestinal bleeding or perforation.
Bleeding or perforation of the gastrointestinal tract in anamnesis related to previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs).
Active form of peptic ulcer/bleeding or recurrent peptic ulcer/bleeding in anamnesis (two or more separate episodes of diagnosed ulcer or bleeding).
High risk of development of post-operative bleeding, blood incoagulability, hemostasis disorders, hematopoietic disorders or cerebrovascular bleeding.
Congestive heart failure (NYHA II–IV).
Ischemic heart disease in patients with angina, who have had myocardial infarction.
Patients having asthma attacks (“aspirin asthma”), angioedema, urticaria or acute rhinitis, nasal polyps and other allergic symptoms in response to the use of ibuprofen, diclofenac, paracetamol, acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs).
Diseases of the blood, hemodyscrasia of unknown genesis, leukopenia, pronounced anemia.
Deficiency of glucose-6-phosphate dehydrogenase.
Inflammatory diseases of the intestine (Crohn's disease or ulcerative colitis).
Treatment of post-operative pain in coronary artery bypass graft surgery (or using the artificial blood circulation apparatus).
Peripheral arterial disease.
Cerebrovascular diseases in patients who have had stroke or have episodes of transitory ischemic attacks.
Interaction with other medicinal products and other forms of interaction.
Lithium. If used simultaneously, diclofenac may increase the plasma concentration of lithium. It is recommended to monitor serum levels of lithium.
Digoxin. If used simultaneously, diclofenac may increase the plasma concentration of digoxin. It is recommended to monitor serum levels of digoxin.
Diuretics and antihypertensive agents. As well as other NSAIDs, concomitant use of diclofenac with diuretics and antihypertensive agents, (such as β-blockers, angiotensin-converting enzyme (ACE) inhibitors) may reduce their antihypertensive effect by inhibition of synthesis of vasodilatory prostaglandins. Thus, such a combination is used with caution and patients, especially the elderly, should be under close supervision regarding their blood pressure. Patients should receive adequate hydration, it is also recommended to monitor the renal function after initiation of concomitant therapy and at regular intervals thereafter, especially for diuretics and ACE inhibitors due to the increased risk of nephrotoxicity.
Drugs that are known to cause hyperkalemia. Concomitant treatment with potassium-sparing diuretics, cyclosporine, tacrolimus or trimethoprim may be associated with increased levels of potassium in the blood serum, so monitoring of the patient should be performed more frequently.
Anticoagulants and antithrombotic agents. Concomitant use can increase the risk of bleeding, so it is recommended to take precautions. Although there are no conclusive data on the effect of diclofenac on the activity of anticoagulants, there are some evidence of increased bleeding risk in patients who used both diclofenac and anticoagulants. Therefore, to assure that no change in anticoagulant dosage is not required, careful monitoring of these patients is recommended. Like other nonsteroidal anti-inflammatory drugs, diclofenac at high doses may temporarily inhibit platelet aggregation.
Other NSAIDs, including selective cyclooxygenase-2 inhibitors and corticosteroids. Concomitant administration of diclofenac and other NSAIDs or corticosteroids may increase the risk of gastrointestinal bleeding or ulcers. Avoid simultaneous use of two or more NSAIDs.
Selective serotonin reuptake inhibitors (SSRIs).
Concomitant use of NSAIDs and SSRIs may increase the risk of gastrointestinal bleeding.
Antidiabetic drugs. It has been proved that diclofenac may be used with oral antidiabetics without changing their therapeutic effect. However, there are some reports about the development of both hypoglycemia and hyperglycemia in these cases, which required antidiabetic agents’ dosage adjustment during the use of diclofenac. For this reason, it is recommended to control blood glucose level during the combined therapy as a precautionary measure.
Methotrexate. Diclofenac may inhibit clearance of methotrexate in the renal tubules, leading to the increased levels of methotrexate. Caution should be exercised when prescribing NSAIDs, including diclofenac, less than 24 hours before the use of methotrexate, since in such cases the blood concentration of methotrexate may increase, and its toxic effect may intensify. There is evidence of serious cases of toxicity when the interval between the use of methotrexate and NSAIDs, including diclofenac, was within 24 hours. This interaction is mediated through accumulation of methotrexate resulting in violation of renal excretion in the presence of NSAIDs.
Cyclosporine. The effect of diclofenac, as well as other NSAIDs, on prostaglandin synthesis in the kidneys may increase cyclosporine nephrotoxicity; in this regard, diclofenac should be used in lower doses than in patients who do not use cyclosporine.
Tacrolimus. When using NSAIDs with tacrolimus, the risk of nephrotoxicity may increase, which may be mediated with renal antiprostaglandin effects of NSAIDs and calcineurin inhibitors.
Antibacterial quinolones. The development of seizures in patients who used both NSAIDs and quinolone derivatives is possible. This may be observed in patients both with and without epilepsy and seizures in the anamnesis. Therefore, caution should be exercised when deciding on the use of quinolone in patients who are already receiving NSAIDs.
Phenytoin. When using phenytoin concomitantly with diclofenac, it is recommended to monitor plasma phenytoin concentrations due to the expected increase in exposure of phenytoin.
Colestipol and cholestyramine. These drugs can delay or reduce the absorption of diclofenac. It is therefore recommended to prescribe diclofenac at least one hour before or 4-6 hours after application colestipol / cholestyramine.
Cardiac glycosides. Concomitant use of cardiac glycosides and NSAIDs may enhance heart failure, reduce GFR and increase the level of glycosides in blood plasma.
Mifepristone. NSAIDs should not be used for 8-12 days after mifepristone use, as NSAIDs can reduce the effect of mifepristone.
Strong inhibitors of CYP2C9. Caution should be exercised when concomitant administration of diclofenac with potent inhibitors of CYP2C9 (e.g., voriconazole), which may lead to a significant increase in the maximum plasma concentration, and exposure of diclofenac due to inhibition of diclofenac metabolism.
Drugs that stimulate enzymes that metabolize drugs. Drugs that stimulate enzymes, such as rifampicin, carbamazepine, phenytoin, St. John's wort (Hypericum perforatum), etc., theoretically can reduce concentrations of diclofenac in plasma.
The rate of absorption of paracetamol may be increased when using metoclopramide and domperidone and decreased when using cholestyramine. The anticoagulation effect of warfarin and other coumarins may be enhanced when prolonged regular daily use of paracetamol with increased risk of bleeding. Periodic use has no significant effect.
Barbiturates reduce the antipyretic effect of paracetamol.
Anticonvulsant drugs (including phenytoin, barbiturates, carbamazepine) that stimulate the activity of microsomal liver enzymes may increase the toxic effects of paracetamol on the liver due to an increase in the conversion of the drug to the hepatotoxic metabolites. Concomitant administration of paracetamol with hepatotoxic agents increases toxic effects on the liver.
Concomitant use of high doses of paracetamol with isoniazid, rifampicin increases the risk of hepatotoxic syndrome. Paracetamol reduces the effectiveness of diuretics.
Do not use with alcohol.
To minimize the adverse effects, the treatment should be started with the lowest effective dose for the shortest period of time necessary to control the symptoms.
Avoid concomitant use of diclofenac with systemic NSAIDs, such as cyclooxygenase-2 inhibitors, because of the absence of any evidence of a synergistic effect and due to the potential additive side effects.
Caution should be exercised with elderly patients. In particular, it is recommended to use the lowest effective dose of debilitated elderly patients or with low body weight.
As with other NSAIDs, allergic reactions may be observed, including anaphylactic/anaphylactoid reactions, even without prior effect of diclofenac.
Due to its pharmacodynamic properties, diclofenac, like other NSAIDs, may mask the signs and symptoms of infection.
Effect on the gastrointestinal tract.
When using all NSAIDs, including diclofenac, there have been registered the cases of gastrointestinal bleedings (cases of hematemesis, melena), ulcer formation or perforation, which may be lethal and occur at any time during treatment with or without the warning symptoms or previous anamnesis of serious gastrointestinal events. These events usually have more serious consequences in the elderly patients. If the events of gastrointestinal bleeding or ulcer formation are observed in patients receiving diclofenac, the drug should be discontinued.
As with other NSAIDs, including diclofenac, for patients with symptoms that indicate digestive tract (DT) disorders, medical supervision and special caution are mandatory. The risk of bleeding, ulceration or perforation in DT increases with increasing doses of NSAIDs, including diclofenac.
Elderly patients have an increased frequency of adverse reactions to the use of NSAIDs, especially regarding the gastrointestinal bleeding and perforation which may be lethal.
To reduce the risk of toxic effects on DT, the treatment is started and continued with the lowest effective doses. For such patients, as well as those requiring concomitant use of medicinal products containing low doses of acetylsalicylic acid (ASA/aspirin) or other medicinal agents that may increase the risk of the adverse effect on DT, the use of combined therapy with protective agents (e.g., proton pump inhibitors or misoprostol) should be considered. Patients with gastrointestinal toxicity in the anamnesis, especially the elderly, should report any unusual abdominal symptoms (especially DT bleedings). Caution is also required for patients concomitantly receiving the drugs that may increase the risk of ulcer or bleeding, such as systemic corticosteroids, anticoagulants (e.g., warfarin), antithrombotic agents (e.g., ASA) or selective serotonin reuptake inhibitors.
Effect on the liver.
Thorough medical supervision is required when prescribing diclofenac in patients with impaired hepatic function, as their condition may worsen.
As with other NSAIDs, including diclofenac, the level of one or several liver enzymes may increase.
During prolonged treatment with the drug Fanigan, regular monitoring of liver function and liver enzyme levels s prescribed as a precautionary measure. If liver function abnormalities persist or worsen and if clinical signs or symptoms may be associated with progressive liver disease, or if other manifestations occur (e.g., eosinophilia, rash), the use of the drug Fanigan should be stopped. The course of diseases such as hepatitis can occur without prodromal symptoms. Caution is required if Fanigan is used in patients with hepatic porphyria, because of the likelihood of provoking an attack.
Effect on the kidneys.
Since during treatment with NSAIDs, including diclofenac, cases of fluid retention and edema have been reported, particular attention should be given to patients with impaired function of the heart or kidney disease, arterial hypertension in the anamnesis, elderly patients, patients receiving concomitant treatment with diuretics or drugs that have significant effect on the renal function, as well as patients with a significant decrease in extracellular fluid volume from any cause, e.g., before or after a major surgery. In such cases, monitoring of the renal function is recommended as a precautionary measure. Discontinuation of the therapy usually leads to a return to the condition which preceded treatment.
Effect on the skin.
Resulting from the use of NSAIDs, including diclofenac, in very rare cases serious skin reactions have been registered (some of them were lethal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis). In patients the highest risk of these reactions is observed at the beginning of the therapy course: the emergence of the reaction in most cases is marked during the first month of treatment. The drug Fanigan should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
SLE and mixed connective tissue diseases.
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue diseases, increased risk of aseptic meningitis may be observed.
Cardiovascular and cerebrovascular effects.
For patients with a history of hypertension and/or congestive heart failure of mild to moderate severity, it is necessary to conduct the appropriate monitoring and give advice, since cases of fluid retention and edema due to the use of NSAIDs, including diclofenac, have been reported.
The data of clinical studies and epidemiological data suggest that the use of diclofenac, especially at high doses (150 mg/day) and long-term treatment may be associated with an insignificant increase in the risk of development of the arterial thrombotic events (e.g., myocardial infarction or stroke).
It is not recommended to administer diclofenac in patients with uncontrolled hypertension, congestive heart failure, stable coronary heart disease, peripheral arterial disease and/or cerebrovascular disease, if necessary, the use is possible only after a careful risk-benefit assessment only at the dosage of not more than 100 mg per day. Such assessment should be carried out before starting the long-term treatment in patients with risk factors of cardiovascular events (e.g. with arterial hypertension, hyperlipidemia, diabetes mellitus, and patients who smoke).
Patients should be informed about the possibility of serious antithrombotic cases (chest pain, shortness of breath, weakness, speech disorder), which may occur at any time. In this case it is necessary to consult the doctor.
Effect on hematological parameters.
During prolonged use of this drug, as well as other NSAIDs, it is recommended to monitor the complete blood count.
Diclofenac may temporarily inhibit platelet aggregation. Patients with impaired hemostasis, hemorrhagic diathesis or hematological disorders should be under careful observation.
Asthma in the anamnesis.
In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (i.e. nasal polyps), chronic obstructive pulmonary diseases or chronic infections of the respiratory tract (especially those associated with allergic similar to rhinitis, symptoms) often have reactions to NSAIDs such as aggravation of asthma (so-called intolerance to analgesics/analgesic asthma), angioedema or urticaria. In this regard, special precautions are recommended for such patients (readiness for emergency aid). This also applies to the case of patients with allergic reactions to other substances, such as rash, itching or urticaria.
As with other drugs that inhibit prostaglandin synthetase activity, diclofenac sodium and other NSAIDs can trigger the development of bronchospasm when applied in patients with a history of asthma.
Fertility in women.
The use of diclofenac may affect fertility in women and is not recommended for women attempting to conceive. Discontinuation of the drug Fanigan is should be considered in women who may have difficulties conceiving or who are undergoing investigation for infertility.
Before using the drug, it is recommended to consult a doctor if the patient is using warfarin or similar drugs having anticoagulant effect.
Patients with mild arthritis who take analgesics every day should consult their doctor.
It is necessary to consult a doctor regarding the possibility of using the drug in patients with impaired renal and hepatic function.
Taking into account that in patients with alcohol-induced liver injury the risk of hepatotoxic effect of paracetamol is increased, the drug may have effect on the results of laboratory tests on blood content of glucose and uric acid.
Do not exceed the prescribed dosage.
Do not take the drug with other drugs containing paracetamol.
If symptoms persist, consult a doctor.
Use during pregnancy or breast-feeding.
The drug is contraindicated during pregnancy or breast-feeding.
Effects on ability to drive and use machines.
Patients who have visual impairment, dizziness (vertigo), somnolence or other disorders of the central nervous system during the drug treatment, should refrain from driving or other mechanisms.
Dosage and administration.
The dose is determined by the doctor for each patient individually, depending on the patient's age, the nature and course of the disease, individual tolerance and therapeutic efficacy. The drug should be used at the lowest effective dose for the shortest period of time, given the goal of treatment for each individual patient.
Adults and children aged over 14 – 1 tablet 2-3 times per day after meal.
The interval between the doses is not less than 4 hours.
The duration of treatment is not more than 5-7 days and depends on the course of the disease.
The maximum daily dose of the drug for adults and children aged over 14is not more than 3 tablets.
The maximum period of use without consulting a doctor is 3 days.
The drug is contraindicated in children aged less than 14.
There is no typical clinical picture characteristic of diclofenac overdose. The overdose may cause such as headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhea, dizziness, disorientation, agitation, coma, drowsiness, tinnitus or convulsions. Acute renal failure and liver damage are possible in case of severe intoxication.
Treatment of acute poisoning with NSAIDs, including diclofenac, consists in conducting supportive and symptomatic therapy. This relates to the treatment of such manifestations as hypotension, renal failure, convulsions, gastrointestinal disorder, respiratory depression. It is unlikely that such specific therapeutic measures as forced diuresis, dialysis or hemoperfusion would be effective for the withdrawal of NSAIDs, including diclofenac as active ingredients of these drugs are largely bound to blood proteins and subjected to intensive metabolism. After receiving potentially toxic doses, activated carbon may be used, and after receiving potentially life-threatening doses, disinfection of stomach may be used (e.g., inducing vomiting, gastric lavage).
Liber lesion may occur in adults who took 10 g and more paracetamol, and in children who took more than 150 mg/kg of body weight. In patients with risk factors (prolonged administration of carbamazepine, phenobarbitone, phenytoin, primidone, rifampin, St. John's Wort or other drugs that induce liver enzymes, alcohol abuse, failure of glutathione system, e.g., unhealthy diet, AIDS, fasting, cystic fibrosis, cachexia) using 5 g or more of paracetamol may cause liver lesion.
Symptoms of overdose during the first 24 hours: pallor, nausea, vomiting, anorexia and abdominal pain. Liver lesion may become apparent 12-48 hours after the overdose. Impairment of glucose metabolism and metabolic acidosis may occur. In case of severe poisoning, hepatic failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma and led to the lethal outcome. Acute renal failure with acute tubular necrosis may be manifested by severe pain in the lower back area, hematuria, proteinuria and develop even in the absence of severe liver lesion. Cardiac arrhythmia and pancreatitis have also been marked.
Such disorders of hematopoietic system as aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia may develop in case of prolonged use of high doses of the drug. When taking high doses of the drug, such disorders of nervous system as dizziness, psychomotor agitation and disorientation are possible; urinary system – nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis); digestive system – hepatonecrosis.
Treatment: urgent measures of supportive and symptomatic therapy.
In case of overdose, emergency medical assistance is necessary. The patient should be brought to the hospital immediately, even if there are no early symptoms of overdose. The symptoms may be limited to nausea and vomiting, or may not reflect the severity of overdose or the risk of organ damage.
If an excessive dose of the drug was taken within 1 hour, the appropriateness of using activated carbon should be considered. Plasma concentration of paracetamol should be measured 4 hours or later after the ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be used within 24 hours after using the drug, but the maximum protective effect is obtained when using it within 8 hours after the ingestion. The efficacy of antidote declines sharply after this time. If necessary, the patient gets an intravenous N-acetylcysteine according to the established list of doses. In the absence of vomiting, oral methionine may be used as an appropriate alternative in remote areas outside the hospital.
Supportive and symptomatic treatment is indicated in such complications as arterial hypotension, renal failure, seizures, disorders of the gastrointestinal and respiratory depression. It is unlikely that forced diuresis, hemodialysis or hemoperfusion are effective for removing nonsteroidal anti-inflammatory drugs (NSAIDs), since the active drug substance is largely bound to plasma proteins and subjected to intensive metabolism.
Blood system and lymphatic system: thrombocytopenia, neutropenia, leukopenia, anemia, including aplastic anemia and hemolytic anemia (especially for patients with deficiency of glucose-6-phosphate dehydrogenase), sulfhemoglobinemia and methemoglobinemia (cyanosis, shortness of breath, pain in the heart), agranulocytosis, pancytopenia.
Immune system: hypersensitivity reactions, anaphylactic / anaphylactoid reactions, including hypertension and anaphylactic shock; angioneurotic edema (including face edema).
Skin and subcutaneous tissue: itching, skin rash, erythema, rash on the mucous membranes, urticaria, bullous rash, eczema, exudative erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, allergic dermatitis, alopecia, photosensitivity reactions, purpura, including allergic purpura.
Psychiatric disorders: disorientation, depression, sleep disorders, insomnia, nightmares, irritability, agitation, fear, psychotic disorders, psychomotor agitation, hallucinations.
Nervous system: headache, dizziness, drowsiness, fatigue, paresthesia, sleep disturbances, insomnia, memory impairment, convulsions, anxiety, tremor, aseptic meningitis, taste disturbances, cerebrovascular accident, stroke, confusion, impaired sensitivity, malaise.
Visual organs: visual impairment, blurred vision, diplopia, optic neuritis.
Organs of hearing: vertigo, ringing in the ears, tinnitus, hearing disorders.
Cardiovascular system: palpitation, tachycardia, shortness of breath, pain in the heart, heart failure, myocardial infarction, hypertension, arterial hypotension, vasculitis.
Respiratory system, thorax and mediastinum: bronchial asthma (including dyspnea), bronchospasm (particularly in patients sensitive to aspirin and other NSAIDs to), chest pain, pneumonitis.
Gastrointestinal tract: nausea, vomiting, diarrhea, dyspepsia, abdominal pain, epigastric pain, flatulence, anorexia, gastritis, gastrointestinal bleeding (hematemesis, melena, blood-containing diarrhea), ulcers of the stomach and intestines accompanied or not accompanied by bleeding or perforation (sometimes lethal, especially in elderly patients), colitis (including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, esophagus dysfunction, diaphragm disease, pancreatitis.
Hepatobiliary system: increase in transaminases levels, hepatitis, jaundice, liver disorders, fulminant hepatitis, liver necrosis, liver failure.
Kidneys and urinary system: acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary necrosis of the kidney.
Endocrine system: hypoglycemia, until hypoglycemic coma.
General disorders: fluid retention, swelling, weakness, sweating.
Reproductive system and mammary glands: impotence.
Data of the clinical studies and epidemiological data indicate that there is an increased risk of thrombotic complications (e.g., myocardial infarction or stroke), associated with the use of diclofenac, particularly at high therapeutic doses (150 mg per day) and prolonged use.
Shelf life. 3 years.
Store at the temperature not more than 25°С in the original package.
Keep out of reach of children.
4 tablets are in a blister, 25 blisters are in a carton package.
10 tablets are in a blister, 10 blisters are in a carton package.
Conditions of supply. By prescription.
“KUSUM PHRAM” LLC
Ukraine, 40030, Sumy, Skryabina Str., 54
Date of last revision.