India Product

Aclotol p Tablets

Aclotol p Tablets

Why you have been prescribed this medicine?


You have been prescribed this medicine if you have any of the following:
  Acute pain (muscle pain, headache, toothache, pain localized in the spine), in nonarticular rheumatism, rheumatoid arthritis, ankylosing spondylitis, osteoarthrosis, spondylarthritis, acute attacks of gout, primary dysmenorrhea, adnexitis, pharyngotonsillitis, otitis.
  Post-traumatic, postsurgical pain syndrome.

When you should consult your doctor?

You should consult your doctor if you experience any of the following:
Blood and lymphatic system:
Thrombocytopenia, neutropenia, leukopenia, anemia, including aplastic anemia, hemolytic anemia (especially for patients with glucose-6-phosphate dehydrogenase deficiency), sulfhemoglobinemia and methemoglobinemia (cyanosis, shortness of breath, pain in the heart), agranulocytosis, pancytopenia.
Immune system:
Hypersensitivity reactions, anaphylactic/anaphylactoid reactions, including hypotension and anaphylactic shock, angioedema (including facial edema).

Mental disorders:
Disorientation, depression, sleep disturbance, insomnia, nightmares, irritability, restlessness, apprehension, psychotic disorders, confusion, psychomotor agitation.

Nervous system:
Headache, dizziness, somnolence, paresthesia, sleep disturbance, insomnia, memory impairment, convulsions, anxiety, tremor, aseptic meningitis, dysgeusia, cerebrovascular disease.

Visual organs:
Visual impairment, blurred vision, diplopia.
Organs of hearing: vertigo, tingling, tinnitus, dysacousia.
Cardiovascular system:
Palpitation, tachycardia, shortness of breath, pain in the heart, cardiac failure, myocardial infarction, arterial hypertension, vasculitis.

Respiratory system:
Bronchial asthma (including shortness of breath), bronchospasm (especially in patients sensitive to acetylsalicylic acid), pain in the chest, pneumonitis.

Digestive tract:
Nausea, vomiting, diarrhea, dyspepsia, abdominal pain, meteorism; gastritis, gastrointestinal bleeding, vomiting with blood, hemorrhagic diarrhea, melena, stomach or intestinal ulcer (with/without bleeding or perforation), colitis (including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis, glossitis, disorders of the esophagus, diaphragm-like intestinal strictures, pancreatitis.

Hepatobiliary system:
Elevated transaminases; hepatic failure, hepatitis, hepatic necrosis, jaundice, hepatic disorders, fulminant hepatitis.

Skin and subcutaneous structures:
Itching sensation, 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, hair loss, photosensitivity reaction, purpura, allergic purpura, pruritus.

Urinary system:
Acute renal failure, hematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis, fluid retention.

General disorders:
Edema, asthenia, hyperhidrosis, hypoglycemia, even coma.
Acelofenac, especially in high doses (150 mg/day) and in long-term use may increase the risk of arterial thrombembolia (such as myocardial infarction or stroke).

What to do if you miss a dose?

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.
Otherwise take it as soon as you remember and then go back to taking it as you would normally.

Things you MUST NOT DO while on this medicine?

General Concomitant use with other systemic NSAIDs, such as selective COX-2 inhibitors, should be avoided due to the lack of any evidence of synergic effect and because of the possible additive adverse effects. Caution should be exercised in elderly patients. In particular, it is recommended to use the lowest effective dose in weak elderly patients with low body weight.

Bronchial asthma in anamnesis
In patients with bronchial asthma, seasonal allergic rhinitis, chronic obstructive pulmonary diseases or chronic respiratory tract infections (especially those associated with allergic symptom like rhinitis), such reactions to NSAIDs as exacerbation of asthma (so called intolerance to analgesics/analgesic asthma), Quincke's edema or urticaria occur more often. Therefore, special measures are recommended for such patients (readiness for emergency action), as well as for the patients with allergic reactions, such as rash, itching, urticaria, to other substances.

Effect on digestive tract
As well as when using other NSAIDs, including acelofenac, medical supervision and special caution are obligatory in patients with the symptoms indicating digestive tract (DT) disorders or with the history of gastric or intestinal ulcer, bleeding or perforation. Risk of bleeding in the digestive tract grows with the increasing dose in patients with the history of ulcer, especially with complications, such as bleeding or perforation, and in elderly patients. To decrease the risk of such toxic effect on digestive tract, the treatment should be started and maintained with the lowest effective doses. For such patients, as well as those requiring concomitant use of drugs containing low doses of acetylsalicylic acid (ASA) or other drugs which are supposed to increase the risk of adverse effect on DT, the use of combined therapy with protective agents (e.g. proton pump inhibitors or misoprostol) should be considered. Patients with the history of gastro-intestinal toxicity, especially elderly patients, should report any unusual abdominal symptoms (especially bleeding in the digestive tract). Caution should also be exercised in patients concomitantly receiving drugs which may increase the risk of ulcer or bleeding, such as systemic corticosteroids, anticoagulants, antithrombotic agents or selective serotonin reuptake inhibitors.

Effect on liver
Careful medical supervision is required when using acelofenac in patients with impaired liver function, as their condition may aggravate.
As well as when using other NSAIDs, including acelofenac, the level of one or several enzymes may increase. The increased enzyme levels as a rule are restored after withdrawal of the drug.
During a long-term drug therapy, regular monitoring of liver function and levels of liver enzymes is prescribed as a precaution. If liver dysfunction persists or aggravates, and clinical manifestations or symptoms may be associated with progressing liver diseases, and there are other manifestations (e.g. eosinophilia, rash) the drug should be withdrawn. The course of diseases, such as hepatitis, may take place without prodromal symptoms. Caution should be exercised in case if the drug is used in patients with hepatic porphyria, due to the likelihood of provoking an attack.

Effect on kidneys
Long-term treatment with high doses of NSAIDs, including acelofenac, often (1-10%) causes edema and arterial hypertension. Special attention should be paid to the patients with the history of impaired cardiac and renal function, arterial hypertension, elderly patients receiving concomitant treatment with diuretics, which have a significant effect on renal function, as well as to the patients with a significant decrease in extracellular fluid volume for any reason, for example, before or after major surgery. In such cases, monitoring of renal function is recommended as a caution. Discontinuation of the therapy results in a return to the condition which preceded the treatment.

Effect on hematological indices
In long-term use of this drug, like other NSAIDs, complete blood count monitoring is recommended. Like other NSAIDs, the drug may temporarily inhibit platelet aggregation. Patients with impaired hemostasis should be carefully monitored.

Do not exceed the indicated doses.
Take into account that in patients with alcoholic non cirrhotic liver damage the risk of hepatotoxic effect of paracetamol is increased; the drug may affect the results of laboratory tests of blood glucose and uric acid levels.
Do not use the drug concomitantly with other drugs containing paracetamol of acelofenac.

Drug interactions:
Acelofenac.
Other analgesic agents including selective cyclooxygenase-2 inhibitors. It is necessary to avoid concomitant use of two or more NSAIDs (including acetylsalicylic acid) since it can lead to increased adverse reactions risk. Antihypertensive agents. Antihypertensive effect decrease.
Diuretics.
Decrease of diuretic effect. Diuretics may increase nephrotoxicity risk at NSAIDs administration. Despite the absence of bendrofluazide effect on arterial blood pressure, interaction with other diuretics should not be excluded. At concomitant use with potassium-sparing diuretics, it is required to control serum potassium level. Cardiac glycosides. NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase serum glycosides levels.
Lithium drugs. May cause decreased lithium elimination.
Methotrexate. Decreased methotrexate elimination. Special precautions should be taken in case the interval between NSAIDs and methotrexate administration is less than 24 hours since NSAIDs may contribute to serum methotrexate levels increasing, thus causing higher toxicity.
Cyclosporine. Nephrotoxicity risk is increased.
Mifepristone. NSAIDs should not be administered within 8–12 days upon mifepristone intake since mifepristone effect can be decreased.

Corticosteroids.
Ulcer and gastrointestinal bleedings risk is increased.
Anticoagulating agents. NSAIDs may increase anticoagulant effect of warfarin. Patients with combined therapy of anticoagulants and Aclotol should have meticulous control of their state.
Quinolone antibacterial drugs. Animal experiments tests show that NSAIDs may increase risk of convulsions caused by quinolone antibacterial drugs use. Patients administering NSAIDs and quinolones may have increased risk of convulsions development.
Antiplatelet drugs and selective serotonin reuptake inhibitors (SSRI). Increased risk of gastrointestinal bleedings.

Tacrolimus.
Concomitant use of NSAIDs and tacrolimus may result in nephrotoxicity risk increase.

Zidovudine.
When used concomitantly with NSAIDs may cause higher risk of hematological toxicity. There are proven facts of hemarthrosis and hematomas risks growth in AIDS patients with hemophilia at concomitant use of zidovudine and ibuprofen.

Antidiabetic drugs. It is discovered that acelofenac used concomitantly with oral antidiabetic drugs may influence their clinical efficacy. Yet, there are some reports of hypoglycemic and hyperglycemic effects. Thus, indication of Aclotol requires adjustment of hypoglycemic agents dose. Other NSAIDs. Concomitant use with acetylsalicylic acid or other NSAIDs may result in higher frequency of undesirable adverse reactions, including gastrointestinal bleedings risk increase.

Paracetamol.
Absorption rate of paracetamol may increase when using metoclopramide and domperidone, and may decrease when using cholestyramine. Anticoagulant effect of warfarin and other coumarins may increase in concomitant regular daily use of paracetamol, with an increased risk of bleeding. When administered periodically, it has no significant effect.
Barbiturates reduce the antipyretic effect of paracetamol.
Anticonvulsants (including phenytoin, barbiturates, carbamazepine) which stimulate the activity of microsomal liver enzymes may increase the toxic effects of paracetamol on the liver due to increased metabolism of the drug into hepatotoxic metabolites. In concomitant use of paracetamol with hepatotoxic agents, their toxic effect on the liver increases.
Concomitant use of high doses of paracetamol and isoniazid, rifampicin increases the risk of hepatotoxic syndrome. Paracetamol reduces the efficacy of diuretics. Do not use with alcohol.

What to do if you accidentally take too much (overdose) of the medicine?
Acelofenac.
There is no typical clinical presentation characteristic of acelofenac overdose. Overdose may cause vomiting, gastrointestinal bleeding, diarrhea, vertigo, tinnitus and convulsions. Acute renal failure and hepatic damage are possible in case of severe intoxication.

Paracetamol.
Hepatic damage may occur in adults who have taken 10 g paracetamol and more, and in children who have taken more than 150 mg/kg of body weight. In patients with risk factors (long-term use of carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, Hypericum perforatum or other drugs that induce hepatic enzymes, alcohol abuse, insufficiency of glutathione system, e.g. malnutrition, AIDS, starvation, cystic fibrosis, cachexia) intake of paracetamol 5 g or more may bring on hepatic damage.

Symptoms of overdose during the first 24 hours:
Pallor, nausea, vomiting, anorexia and abdominal pain. Hepatic damage may become apparent within 12-48 hours after the overdose. Impaired glucose metabolism and metabolic acidosis may occur. In severe intoxication, hepatic failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma and result in death. Acute renal failure with acute tubular necrosis may be manifested by back pain, hematuria, and occur even without severe hepatic damage. Cardiac arrhythmia and pancreatitis have also been marked.

In case of prolonged use of large doses, hematopoietic system disorders may occur:
Aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia. Large doses may bring on nervous system disorders, such as dizziness, psychomotor agitation, and disorientation, urinary system

Disorders: nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis), digestive system disorders: hepatonecrosis.

Treatment:
Urgent measures of supportive and symptomatic therapy.
If the excessive dose has been taken within 1 hour, advisability of use of the activated carbon should be considered. Plasma concentration of paracetamol should be measured 4 hours after the intake or later (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be applied within 24 hours since the drug intake, but maximum protective effect is achieved when using it within 8 hours since the intake. The efficacy of antidote is sharply reduced after this time. If necessary, the patient is given N-acetylcysteine according to the established list of doses. If vomiting is absent, methionine may be used orally as an appropriate alternative in remote areas outside hospital.
Supportive and symptomatic treatment is indicated in case of such complications as arterial hypotension, renal failure, convulsions, gastrointestinal tract disorders and respiratory depression. It is unlikely that forced diuresis, hemodialysis, or hemoperfusion are effective for elimination of nonsteroidal anti-inflammatory drugs (NSAIDs), as the active ingredients of the drug are largely bound to plasma proteins and subjected to intensive metabolism.

What to do if you accidentally take too much (overdose) of the medicine?

Acelofenac.
There is no typical clinical presentation characteristic of acelofenac overdose. Overdose may cause vomiting, gastrointestinal bleeding, diarrhea, vertigo, tinnitus and convulsions. Acute renal failure and hepatic damage are possible in case of severe intoxication.

Paracetamol.
Hepatic damage may occur in adults who have taken 10 g paracetamol and more, and in children who have taken more than 150 mg/kg of body weight. In patients with risk factors (long-term use of carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, Hypericum perforatum or other drugs that induce hepatic enzymes, alcohol abuse, insufficiency of glutathione system, e.g. malnutrition, AIDS, starvation, cystic fibrosis, cachexia) intake of paracetamol 5 g or more may bring on hepatic damage.

Symptoms of overdose during the first 24 hours:
Pallor, nausea, vomiting, anorexia and abdominal pain. Hepatic damage may become apparent within 12-48 hours after the overdose. Impaired glucose metabolism and metabolic acidosis may occur. In severe intoxication, hepatic failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma and result in death. Acute renal failure with acute tubular necrosis may be manifested by back pain, hematuria, and occur even without severe hepatic damage. Cardiac arrhythmia and pancreatitis have also been marked.

In case of prolonged use of large doses, hematopoietic system disorders may occur:
Aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia. Large doses may bring on nervous system disorders, such as dizziness, psychomotor agitation, and disorientation, urinary system

Disorders:
Nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis), digestive system disorders: hepatonecrosis.

Treatment:
Urgent measures of supportive and symptomatic therapy.
If the excessive dose has been taken within 1 hour, advisability of use of the activated carbon should be considered. Plasma concentration of paracetamol should be measured 4 hours after the intake or later (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be applied within 24 hours since the drug intake, but maximum protective effect is achieved when using it within 8 hours since the intake. The efficacy of antidote is sharply reduced after this time. If necessary, the patient is given N-acetylcysteine according to the established list of doses. If vomiting is absent, methionine may be used orally as an appropriate alternative in remote areas outside hospital.
Supportive and symptomatic treatment is indicated in case of such complications as arterial hypotension, renal failure, convulsions, gastrointestinal tract disorders and respiratory depression. It is unlikely that forced diuresis, hemodialysis, or hemoperfusion are effective for elimination of nonsteroidal anti-inflammatory drugs (NSAIDs), as the active ingredients of the drug are largely bound to plasma proteins and subjected to intensive metabolism.

Is it safe in pregnancy and breast-feeding?

Tell your doctor immediately if you become pregnant while taking this medication.
For safety of any drug during pregnancy or breastfeeding – please consult your doctor.

Storage Conditions:

Store at a temperature not more than 25 °c in the original package. Keep out of reach of children.

Drug Description

Active substances:
Paracetamol, acelofenac; 1 tablet contains paracetamol 325 mg, acelofenac 100 mg;

Excipients:
MCC PH 102, Cross Carmellose Sodium, Colloidal Anhydrous Silicon, Stearic Acid.

Indications and dosage.

INDICATIONS:
> Acute pain (muscle pain, headache, toothache, pain localized in the spine), in nonarticular rheumatism, rheumatoid arthritis, ankylosing spondylitis, osteoarthrosis, spondylarthritis, acute attacks of gout, primary dysmenorrhea, adnexitis, pharyngotonsillitis, otitis.
> Post-traumatic, postsurgical pain syndrome.
DOSAGE:
The dose is determined by physician individually for each patient, depending on the patient's age, nature and course of the disease, individual tolerance and therapeutic efficacy of the drug. Adults and children older than 14: 1 tablet 2-3 times per day after meal.
The duration of treatment is not more than 5-7 days, and does not depend on the course of disease. The maximum daily dose for adults and children older than 14 in not more than 3 tablets.

Side effects and drug interactions.

ADVERSE REACTIONS: Blood and lymphatic system: thrombocytopenia, neutropenia, leukopenia, anemia, including aplastic anemia, hemolytic anemia (especially for patients with glucose-6-phosphate dehydrogenase deficiency), sulfhemoglobinemia and methemoglobinemia (cyanosis, shortness of breath, pain in the heart), agranulocytosis, pancytopenia.

Immune system:
hypersensitivity reactions, anaphylactic/anaphylactoid reactions, including hypotension and anaphylactic shock, angioedema (including facial edema).

Mental disorders:
Disorientation, depression, sleep disturbance, insomnia, nightmares, irritability, restlessness, apprehension, psychotic disorders, confusion, psychomotor agitation.

Nervous system:
Headache, dizziness, somnolence, paresthesia, sleep disturbance, insomnia, memory impairment, convulsions, anxiety, tremor, aseptic meningitis, dysgeusia, cerebrovascular disease.

Visual organs:
Visual impairment, blurred vision, diplopia.
Organs of hearing: vertigo, tingling, tinnitus, dysacousia.
Cardiovascular system: palpitation, tachycardia, shortness of breath, pain in the heart, cardiac failure, myocardial infarction, arterial hypertension, vasculitis.
Respiratory system: bronchial asthma (including shortness of breath), bronchospasm (especially in patients sensitive to acetylsalicylic acid), pain in the chest, pneumonitis.

Digestive tract:
Nausea, vomiting, diarrhea, dyspepsia, abdominal pain, meteorism; gastritis, gastrointestinal bleeding, vomiting with blood, hemorrhagic diarrhea, melena, stomach or intestinal ulcer (with/without bleeding or perforation), colitis (including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis, glossitis, disorders of the esophagus, diaphragm-like intestinal strictures, pancreatitis.

Hepatobiliary system: elevated transaminases; hepatic failure, hepatitis, hepatic necrosis, jaundice, hepatic disorders, fulminant hepatitis.

Skin and subcutaneous structures:
Itching sensation, 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, hair loss, photosensitivity reaction, purpura, allergic purpura, pruritus.
Urinary system: acute renal failure, hematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis, fluid retention.
General disorders: edema, asthenia, hyperhidrosis, hypoglycemia, even coma.
Acelofenac, especially in high doses (150 mg/day) and in long-term use may increase the risk of arterial thrombembolia (such as myocardial infarction or stroke).
Drug interactions:
Acelofenac.
Other analgesic agents including selective cyclooxygenase-2 inhibitors. It is necessary to avoid concomitant use of two or more NSAIDs (including acetylsalicylic acid) since it can lead to increased adverse reactions risk. Antihypertensive agents. Antihypertensive effect decrease.

Diuretics.
Decrease of diuretic effect. Diuretics may increase nephrotoxicity risk at NSAIDs administration. Despite the absence of bendrofluazide effect on arterial blood pressure, interaction with other diuretics should not be excluded. At concomitant use with potassium-sparing diuretics, it is required to control serum potassium level. Cardiac glycosides. NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase serum glycosides levels.

Lithium drugs.
May cause decreased lithium elimination.
Methotrexate.
Decreased methotrexate elimination. Special precautions should be taken in case the interval between NSAIDs and methotrexate administration is less than 24 hours since NSAIDs may contribute to serum methotrexate levels increasing, thus causing higher toxicity.

Cyclosporine.
Nephrotoxicity risk is increased.

Mifepristone.
NSAIDs should not be administered within 8–12 days upon mifepristone intake since mifepristone effect can be decreased.
Corticosteroids.
Ulcer and gastrointestinal bleedings risk is increased.
Anticoagulating agents.
NSAIDs may increase anticoagulant effect of warfarin. Patients with combined therapy of anticoagulants and Aclotol should have meticulous control of their state.
Quinolone antibacterial drugs.
Animal experiments tests show that NSAIDs may increase risk of convulsions caused by quinolone antibacterial drugs use. Patients administering NSAIDs and quinolones may have increased risk of convulsions development. Antiplatelet drugs and selective serotonin reuptake inhibitors (SSRI). Increased risk of gastrointestinal bleedings.

Tacrolimus.
Concomitant use of NSAIDs and tacrolimus may result in nephrotoxicity risk increase.

Zidovudine.
When used concomitantly with NSAIDs may cause higher risk of hematological toxicity. There are proven facts of hemarthrosis and hematomas risks growth in AIDS patients with hemophilia at concomitant use of zidovudine and ibuprofen.

Antidiabetic drugs.
It is discovered that acelofenac used concomitantly with oral antidiabetic drugs may influence their clinical efficacy. Yet, there are some reports of hypoglycemic and hyperglycemic effects. Thus, indication of Aclotol requires adjustment of hypoglycemic agents dose.

Other NSAIDs.
Concomitant use with acetylsalicylic acid or other NSAIDs may result in higher frequency of undesirable adverse reactions, including gastrointestinal bleedings risk increase.

Paracetamol. Absorption rate of paracetamol may increase when using metoclopramide and domperidone, and may decrease when using cholestyramine. Anticoagulant effect of warfarin and other coumarins may increase in concomitant regular daily use of paracetamol, with an increased risk of bleeding. When administered periodically, it has no significant effect.
Barbiturates reduce the antipyretic effect of paracetamol. Anticonvulsants (including phenytoin, barbiturates, carbamazepine) which stimulate the activity of microsomal liver enzymes may increase the toxic effects of paracetamol on the liver due to increased metabolism of the drug into hepatotoxic metabolites. In concomitant use of paracetamol with hepatotoxic agents, their toxic effect on the liver increases.
Concomitant use of high doses of paracetamol and isoniazid, rifampicin increases the risk of hepatotoxic syndrome. Paracetamol reduces the efficacy of diuretics. Do not use with alcohol.

Warnings and precautions

General Concomitant use with other systemic NSAIDs, such as selective COX-2 inhibitors, should be avoided due to the lack of any evidence of synergic effect and because of the possible additive adverse effects. Caution should be exercised in elderly patients. In particular, it is recommended to use the lowest effective dose in weak elderly patients with low body weight.

Bronchial asthma in anamnesis
In patients with bronchial asthma, seasonal allergic rhinitis, chronic obstructive pulmonary diseases or chronic respiratory tract infections (especially those associated with allergic symptom like rhinitis), such reactions to NSAIDs as exacerbation of asthma (so called intolerance to analgesics/analgesic asthma), Quincke's edema or urticaria occur more often. Therefore, special measures are recommended for such patients (readiness for emergency action), as well as for the patients with allergic reactions, such as rash, itching, urticaria, to other substances.

Effect on digestive tract
As well as when using other NSAIDs, including acelofenac, medical supervision and special caution are obligatory in patients with the symptoms indicating digestive tract (DT) disorders or with the history of gastric or intestinal ulcer, bleeding or perforation. Risk of bleeding in the digestive tract grows with the increasing dose in patients with the history of ulcer, especially with complications, such as bleeding or perforation, and in elderly patients. To decrease the risk of such toxic effect on digestive tract, the treatment should be started and maintained with the lowest effective doses. For such patients, as well as those requiring concomitant use of drugs containing low doses of acetylsalicylic acid (ASA) or other drugs which are supposed to increase the risk of adverse effect on DT, the use of combined therapy with protective agents (e.g. proton pump inhibitors or misoprostol) should be considered. Patients with the history of gastro-intestinal toxicity, especially elderly patients, should report any unusual abdominal symptoms (especially bleeding in the digestive tract). Caution should also be exercised in patients concomitantly receiving drugs which may increase the risk of ulcer or bleeding, such as systemic corticosteroids, anticoagulants, antithrombotic agents or selective serotonin reuptake inhibitors.

Effect on liver
Careful medical supervision is required when using acelofenac in patients with impaired liver function, as their condition may aggravate.
As well as when using other NSAIDs, including acelofenac, the level of one or several enzymes may increase. The increased enzyme levels as a rule are restored after withdrawal of the drug.
During a long-term drug therapy, regular monitoring of liver function and levels of liver enzymes is prescribed as a precaution. If liver dysfunction persists or aggravates, and clinical manifestations or symptoms may be associated with progressing liver diseases, and there are other manifestations (e.g. eosinophilia, rash) the drug should be withdrawn. The course of diseases, such as hepatitis, may take place without prodromal symptoms. Caution should be exercised in case if the drug is used in patients with hepatic porphyria, due to the likelihood of provoking an attack.

Effect on kidneys
Long-term treatment with high doses of NSAIDs, including acelofenac, often (1-10%) causes edema and arterial hypertension. Special attention should be paid to the patients with the history of impaired cardiac and renal function, arterial hypertension, elderly patients receiving concomitant treatment with diuretics, which have a significant effect on renal function, as well as to the patients with a significant decrease in extracellular fluid volume for any reason, for example, before or after major surgery. In such cases, monitoring of renal function is recommended as a caution. Discontinuation of the therapy results in a return to the condition which preceded the treatment.

Effect on hematological indices
In long-term use of this drug, like other NSAIDs, complete blood count monitoring is recommended. Like other NSAIDs, the drug may temporarily inhibit platelet aggregation. Patients with impaired hemostasis should be carefully monitored.

Do not exceed the indicated doses.
Take into account that in patients with alcoholic non cirrhotic liver damage the risk of hepatotoxic effect of paracetamol is increased; the drug may affect the results of laboratory tests of blood glucose and uric acid levels.
Do not use the drug concomitantly with other drugs containing paracetamol of acelofenac.

Overdosage and Contraindications

Overdose:
Acelofenac.
There is no typical clinical presentation characteristic of acelofenac overdose. Overdose may cause vomiting, gastrointestinal bleeding, diarrhea, vertigo, tinnitus and convulsions. Acute renal failure and hepatic damage are possible in case of severe intoxication.

Paracetamol.
Hepatic damage may occur in adults who have taken 10 g paracetamol and more, and in children who have taken more than 150 mg/kg of body weight. In patients with risk factors (long-term use of carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, Hypericum perforatum or other drugs that induce hepatic enzymes, alcohol abuse, insufficiency of glutathione system, e.g. malnutrition, AIDS, starvation, cystic fibrosis, cachexia) intake of paracetamol 5 g or more may bring on hepatic damage.
Symptoms of overdose during the first 24 hours: pallor, nausea, vomiting, anorexia and abdominal pain. Hepatic damage may become apparent within 12-48 hours after the overdose. Impaired glucose metabolism and metabolic acidosis may occur. In severe intoxication, hepatic failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma and result in death. Acute renal failure with acute tubular necrosis may be manifested by back pain, hematuria, and occur even without severe hepatic damage. Cardiac arrhythmia and pancreatitis have also been marked.
In case of prolonged use of large doses, hematopoietic system disorders may occur: aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia. Large doses may bring on nervous system disorders, such as dizziness, psychomotor agitation, and disorientation, urinary system disorders: nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis), digestive system disorders: hepatonecrosis.

Treatment:
Urgent measures of supportive and symptomatic therapy.
If the excessive dose has been taken within 1 hour, advisability of use of the activated carbon should be considered. Plasma concentration of paracetamol should be measured 4 hours after the intake or later (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be applied within 24 hours since the drug intake, but maximum protective effect is achieved when using it within 8 hours since the intake. The efficacy of antidote is sharply reduced after this time. If necessary, the patient is given N-acetylcysteine according to the established list of doses. If vomiting is absent, methionine may be used orally as an appropriate alternative in remote areas outside hospital.
Supportive and symptomatic treatment is indicated in case of such complications as arterial hypotension, renal failure, convulsions, gastrointestinal tract disorders and respiratory depression. It is unlikely that forced diuresis, hemodialysis, or hemoperfusion are effective for elimination of nonsteroidal anti-inflammatory drugs (NSAIDs), as the active ingredients of the drug are largely bound to plasma proteins and subjected to intensive metabolism.

CONTRAINDICATIONS:
Hypersensitivity to acelofenac, paracetamol or to any other component of the drug.
» Acute gastric or intestinal ulcer; gastrointestinal bleeding or perforation.
» Severe hepatic failure (Child-Pugh grade C, cirrhosis or ascites).
»Severe kidney failure (creatinine clearance < 30 mL/min).
» Severe cardiac failure (СН III-IV).
» Patients who respond to acelofenac, paracetamol, aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) with bronchial asthma ("aspirin asthma"), urticaria or acute rhinitis, nasal polyps, and other allergic symptoms. » Violation of hematopoiesis of unknown origin.
» Leukopenia.
» Moderate and severe anemia.
» Congenital hyperbilirubinemia.
» Glucose-6-phosphate dehydrogenase deficiency.
» Patients who have history of gastrointestinal bleeding or perforation, related to the use of nonsteroidal anti-inflammatory drugs.
»Inflammatory bowel disease (Crohn's disease or ulcerative colitis).
» Alcoholism.
» Treatment of postsurgical pain after coronary artery bypass surgery (or using cardiopulmonary bypass).

Clinical pharmacology.


PHARMACOLOGICAL PROPERTIES:
Pharmacodynamics.
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 acelofenac and paracetamol, which are the components of the drug.
Acelofenac 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.

Pharmacokinetics.
After the intake, the drug is rapidly and completely absorbed. Food has no effect on absorption of the drug.
Plasma concentrations of active substances are linearly dependent on the dose; the maximum levels are reached in 60-90 minutes after ingestion.
Binding of acelofenac to plasma proteins (mainly albumin) reaches 99.7%. The expected volume of distribution is 0.12-0.17 L/kg. Acelofenac penetrates into synovial liquid, where its maximum concentration is reached 2-4 hours later than in blood plasma. The half-life for elimination from the synovial fluid is 3-6 hours.
Acelofenac is metabolized by glucuronidation of unchanged molecule and methoxylation, which forms several phenolic metabolites, the biological activity of which is considerably inferior to the activity of the parent substance.
General plasmatic clearance of acelofenac is approximately 300 mL/min. Terminal half-life is 1-2 hours. 60% of the administered dose is excreted in the urine as glucuronic conjugates of unchanged acelofenac; the rest is excreted in the bile and feces.
Paracetamol is metabolized in the liver and is mainly excreted in the urine.
After repeated administration of the drug, pharmacokinetic parameters of active substances remain unchanged. No accumulation occurs provided the recommended dosage intervals are observed.
PHARMACEUTICAL CHARACTERISTICS:
General physic-chemical properties:
Orange capsule-like tablets with white speckles.
Shelf-life:
3 years.
Storage:
Store at a temperature not more than 25°С in the original package. Keep out of reach of children.
Package:
10 tablets are in a blister, 1 blisters are in a carton.
Conditions of supply.
By prescription.

CERTIFICATES

KEEP IN TOUCH

Kusum Healthcare Pvt Ltd

Regd. Office: D-158A, Okhla Industrial Area

Phase-1, New Delhi-110020, India

Tel: 011-41005147, 40514919

Fax: +91-11-40527575

Email: kusumhealth@kusumhealthcare.com

CIN: U65929DL1997PTC085780

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