Active ingredients: Aceclofenac
KAFENAC 100 mg coated tablets
KAFENAC 100 mg powder for oral suspension
Why is Kafenac used? What is it for?
KAFENAC contains the active substance aceclofenac which belongs to the category of non-steroidal anti-inflammatory drugs (NSAIDs) and antirheumatic drugs (drugs used for bone, cartilage and muscle diseases).
This medicine is indicated in adults for the treatment of:
- Inflammatory rheumatic diseases such as arthrosis (a disease affecting the joints), rheumatoid arthritis (a disease of progressive and chronic autoimmune origin affecting the joints), ankylosing spondylitis (severe disabling rheumatic disease that can cause the joints to fuse).
- Extra-articular rheumatism such as periarthritis (inflammatory disease involving the fibrous tissues surrounding a joint), bursitis (inflammation of the fluid-filled bags that form a cushion between the bones and tendons and / or muscles surrounding a "joint) , tendonitis (inflammation of the tendons), enthesitis (inflammation of the insertion of a muscle on a bone).
- Acute painful states of different causes such as sciatica (sensation of intense pain in the leg caused by "irritation of the sciatic nerve), low back pain (back pain), myalgia (pain in the muscles), primary dysmenorrhea (painful menstrual cycle), pain resulting from trauma of various kinds, odontalgia (pain in the teeth).
Contraindications When Kafenac should not be used
Do not take KAFENAC
- If you are allergic to the active substance, to other NSAIDs (including acetylsalicylic acid) or to any of the other ingredients of this medicine.
- If you have experienced in the past, after taking acetylsalicylic acid or other NSAIDs, asthma attacks or other allergic reactions such as hives (skin reaction), rhinitis (inflammation of the nasal mucosa), edema (fluid build-up), rash (sudden redness of the skin) or bronchospasm (narrowing of the lumen of the bronchi). This applies to all non-steroidal anti-inflammatory drugs.
- If you have heart and / or cerebrovascular disease (in the vessels of the brain), for example if you have had a heart attack, stroke (damage to the brain which occurs when the flow of blood to the brain suddenly stops), a mini-stroke (TIA), blockages in the blood vessels of the heart or brain, or if you have had surgery to clear these blockages or a coronary artery bypass graft (surgery that creates an artificial bridge that allows you to bypass an obstacle to blood circulation).
- If you have or have had blood circulation problems (peripheral arterial disease).
- If you have an ongoing gastroduodenal ulcer (erosion of the lining of the lining of the stomach or intestines) or bleeding (haemorrhages) in the gastrointestinal tract.
- If you have active bleeding and bleeding disorders (blood loss).
- If you have ever had gastrointestinal bleeding or perforation caused by previous treatment with non-steroidal anti-inflammatory drugs or if you have had in the past a "recurrent" bleeding / peptic ulcer (two or more distinct episodes of proven ulceration or bleeding).
- If you suffer from decreased liver function (severe hepatic impairment).
- If you suffer from decreased kidney function (renal impairment).
- If you are pregnant, especially in the third trimester and breastfeeding, unless there are valid reasons for taking it. In this case the lowest effective dosage should be used (see "Pregnancy, breastfeeding and fertility").
KAFENAC must not be given to children (see "Children and adolescents").
Precautions for use What you need to know before taking Kafenac
Talk to your doctor or pharmacist before taking KAFENAC.
Do not take KAFENAC in combination with other NSAIDs, including selective COX-2 inhibitors.
Take KAFENAC with caution:
- If you smoke
- If you have diabetes (increased blood sugar levels).
- If you suffer from angina (chest pain caused by insufficient oxygen supply to the heart).
- If you have blood clots.
- If you have hypertension (high blood pressure).
- If you have a high level of cholesterol or triglycerides (fats) in your blood.
- In case of liver dysfunction (liver malfunction).
- In case of heart or kidney failure.
- If you have undergone a major surgery.
- If you are elderly
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms.
If you are elderly, bear in mind that the frequency of side effects is higher, especially gastrointestinal bleeding and perforation, which can be fatal.
Gastro-intestinal system (stomach and intestines)
During treatment with all NSAIDs, at any time, with or without warning symptoms or a history of serious gastrointestinal events (disorders of the stomach or intestines), bleeding in the stomach and intestines, ulceration have been reported. or perforation, which can be fatal.
Stop treatment with KAFENAC immediately and consult your doctor if you experience gastrointestinal bleeding or ulceration while taking the medicine.
As with all NSAIDs, you need to take KAFENAC with particular caution and under close medical supervision if you have symptoms suggestive of upper or lower gastrointestinal disorders, have had stomach or intestinal ulceration in the past, bleeding, perforation, ulcerative colitis or Crohn's disease (inflammatory bowel disease), haematological changes (in the blood) as these conditions may be worsened.
If you are elderly or if you have had an ulcer in the past, especially if complicated with haemorrhage or perforation, the risk of gastrointestinal bleeding, ulceration or perforation is higher, especially with increased doses of NSAIDs. In these cases, start treatment with the lower effective dose in order to reduce the risk of gastrointestinal toxicity.
If you are taking low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events (such as other NSAIDs or corticosteroids - see "Other medicines and KAFENAC") you may consider concomitant use of stomach protective agents (eg misoprostol) or proton pump inhibitors).
If you have suffered from gastrointestinal toxicity (ie stomach and bowel problems), particularly if you are elderly, you should report any abdominal symptoms (especially gastrointestinal bleeding) to your doctor, particularly in the initial stages of treatment.
Take care to take KAFENAC if you are being treated concomitantly with medicines that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants, antiplatelet agents or selective serotonin reuptake inhibitors (see "Other medicines and KAFENAC").
Cardiovascular (at the level of the vessels of the heart) and cerebrovascular (at the level of the vessels of the brain) system
- Undergo appropriate monitoring and take KAFENAC with caution:
- If you have had mild to moderate hypertension and / or congestive heart failure (inability of the heart to supply blood in adequate quantities to the body's needs) in the past as fluid retention and edema have been reported in association with treatment with NSAIDs.
- If you have significant risk factors for cardiovascular events (high blood pressure, high blood fat, diabetes) or if you smoke.
- If you have ever had cerebrovascular bleeding.
The use of KAFENAC may be associated with an increased risk of myocardial infarction (heart attack).
As the cardiovascular risks of KAFENAC may increase with dose and duration of treatment, use the lowest effective daily dose for the shortest period necessary. The response to therapy and the need for symptom improvement should be reassessed periodically.
Hypersensitivity (allergy) reactions and skin (skin) reactions Avoid the use of KAFENAC in case of chickenpox; in some cases chickenpox can cause severe infectious complications of the skin and soft tissues and the role of NSAIDs in the "aggravation of these infections.
As with other NSAIDs, allergic reactions, including anaphylactic / anaphylactoid reactions (rapid onset allergic reactions), may also occur in rare cases, even without prior exposure to aceclofenac.
Serious skin (skin) reactions, some of them fatal, including exfoliative dermatitis (skin irritation with peeling), Stevens-Johnson syndrome (skin and mucosal lesions) and toxic epidermal necrolysis (severe skin disease in which the epidermis breaks off into laminae), have been reported very rarely in association with the use of NSAIDs. The risk appears to be higher in the early stages of therapy as the onset of the reaction occurs in most cases within the first month of treatment.
Stop taking KAFENAC at the first appearance of a skin rash, mucosal lesions or any other signs of hypersensitivity (allergy).
Renal function
Take KAFENAC with caution:
- In case of mild to moderate renal impairment as the use of NSAIDs may lead to deterioration of renal function. In these cases, take the lowest effective dose and undergo regular checks of renal function.
- If you are being treated concomitantly with diuretics (medicines that increase urine production).
Effects on renal function are generally reversible with discontinuation of aceclofenac.
Hepatic (liver) function
Stop treatment with KAFENAC if liver function parameters are persistently altered or worsened, if you develop clinical signs or consistent symptoms of liver disease (liver disease) or if other manifestations such as eosinophilia (high concentration of white blood cells) occur or rash (sudden redness of the skin). With the use of KAFENAC, hepatitis (inflammation of the liver) can occur without promoting symptoms.
Take KAFENAC with caution if you have liver porphyria (a rare disease in which liver enzymes are deficient), as this could trigger an attack.
Get regular medical checks in case of mild to moderate liver function impairment.
Haematological (blood) problems
Aceclofenac can temporarily block platelet aggregation.
Respiratory disorders
Take special care when taking KAFENAC if you have or have had in the past from bronchial asthma (a disease caused by obstruction of the bronchi) as NSAIDs can aggravate bronchospasm.
Long-term treatments
As a preventive measure, if you are on long-term treatment with NSAIDs you should be checked for your blood cell counts and parameters of kidney and liver function.
Children and adolescents
Clinical data on the use of the drug in children are not currently available, therefore its administration is not recommended.
Interactions Which drugs or foods can change the effect of Kafenac
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Take caution when taking KAFENAC with:
- Diuretics (drugs used to increase urine production); aceclofenac, like other NSAIDs, may inhibit the activity of diuretics. When co-administered with potassium-sparing diuretics, blood potassium should be monitored.
- Antihypertensives (drugs used to reduce blood pressure); NSAIDs may reduce the effect of antihypertensive drugs. If your kidney function is impaired (for example if you have lost a lot of fluids or if you are elderly) co-administration of antihypertensive drugs such as ACE inhibitors or angiotensin II antagonists and NSAIDs may increase the risk of acute renal failure, which is usually reversible. In these cases you should be adequately hydrated and monitoring of renal function should be considered after initiation of concomitant therapy and periodically thereafter.
- Corticosteroids (anti-inflammatory drugs); you may have an increased risk of stomach and intestinal ulceration or bleeding (gastrointestinal bleeding).
- Anticoagulants; like other NSAIDs, aceclofenac may increase the activity of anticoagulant drugs such as warfarin and therefore should be closely monitored in case of combined therapy.
- Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs); concomitant use with NSAIDs may increase the risk of gastrointestinal bleeding
- Antidiabetics. There have been isolated reports of hypoglycaemic (decreased blood sugar level) and hyperglycemic (increased blood sugar level) effects; it is therefore advisable to consider the possibility of adjusting the dosage of hypoglycaemics (drugs that reduce the level of blood sugar) concomitantly with aceclofenac.
- Methotrexate (antineoplastic and antirheumatic drug, used for the treatment of some diseases such as leukemia, lymphomas, rheumatoid arthritis, lupus and psoriasis); the possible interaction between NSAIDs and methotrexate should be kept in mind even when low doses of methotrexate are administered, especially if you have reduced kidney function. When combination therapy is to be administered, renal function should be monitored. Use particular caution in case of concomitant intake of NSAIDs and methotrexate within 24 hours, as it may cause an increase in the concentrations of the anticancer agent in the blood with a consequent increase in the toxicity of the latter.
- Lithium (a mood stabilizer drug, used in the treatment of depression and bipolar disorder) and digoxin (a drug that stimulates heart function); several NSAIDs inhibit the elimination of lithium and digoxin, resulting in an increase in their concentration in the blood. The combination should therefore be avoided unless frequent monitoring of lithium and digoxin levels is possible.
- Other NSAIDs; concomitant use of acetylsalicylic acid and other NSAIDs may increase the frequency of undesirable effects.
- Ciclosporin and tacrolimus (immunosuppressive drugs); it is believed that co-administration of NSAIDs with cyclosporine or tacrolimus may increase the risk of nephrotoxicity (kidney toxicity). It is therefore important to closely monitor renal function during combination therapy.
- Zidovudine (antiviral drug); when NSAIDs are given with zidovudine, the risk of haematic (blood) toxicity increases; there are indications of an increased risk of haemarthrosis (shedding of blood in a "joint) and hematoma in HIV-positive haemophiliacs receiving concomitant treatment with zidovudine and ibuprofen (a drug belonging to the NSAID category).
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy Do not take KAFENAC:
- During the first and second trimester of pregnancy, unless strictly necessary. In these cases the dose and duration of treatment should be kept as low as possible and the duration of treatment should be as short as possible.
- During the third trimester of pregnancy. During this period, all prostaglandin synthesis inhibitors (NSAIDs) can expose the fetus to toxicity to the heart and lungs (with premature closure of the arterial duct and high pressure in the lungs) and kidney failure, which can progress to renal failure with oligo -hydroamnios (reduction of amniotic fluid) while they can expose the mother and the newborn, at the end of pregnancy, to possible prolongation of the bleeding time, and antiplatelet effect that can occur even at very low doses and inhibition of uterine contractions resulting in delay or prolongation of labor.
Inhibition of prostaglandin synthesis by NSAIDs can adversely affect pregnancy and / or the development of the embryo and fetus. Results of epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis (defect in the abdominal wall in which the intestine and sometimes other organs develop outside the abdomen of the fetus) after use of an inhibitor. of prostaglandin synthesis in the early stages of pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. The risk was considered to increase with dose and duration of therapy.
Feeding time
Do not take KAFENAC if you are breastfeeding, to avoid side effects in the infant unless the potential benefit to the mother outweighs the possible risk to the fetus.
Fertility
NSAIDs may impair fertility and use is not recommended in women intending to become pregnant. Aceclofenac should be discontinued in women who have fertility problems or are undergoing fertility investigations.
If you take KAFENAC in such cases, the dose should be kept as low as possible and the duration of treatment should be as short as possible.
Driving and using machines
Administration of aceclofenac, as occurs with other NSAIDs and in particularly predisposed patients, could give rise to dizziness, vertigo or other central nervous system disorders. You should be made aware of these possible effects before driving a vehicle or operating machinery that requires integrity of alertness.
KAFENAC 100 mg powder for oral suspension contains sorbitol. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
KAFENAC 100 mg powder for oral suspension contains a source of phenylalanine (aspartame). It can be harmful to you if you have phenylketonuria (a disease of amino acid metabolism).
Dosage and method of use How to use Kafenac: Dosage
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
KAFENAC 100 mg coated tablets
Adults
The recommended dose is 2 tablets per day (200 mg per day), 1 tablet every 12 hours.
Swallow the tablets with a sufficient amount of water.
Take this medicine preferably with meals.
KAFENAC 100 mg powder for oral suspension
The recommended dose is 2 sachets per day (200 mg per day), 1 sachet every 12 hours.
Dissolve the contents of one sachet in a glass of water (40-60 ml) and swallow immediately.
Take this medicine preferably with meals.
Senior citizens
It is not considered necessary to change the posology.
Patients suffering from hepatic insufficiency
In patients with liver problems (hepatic insufficiency) it is advisable to reduce the starting dose to 100 mg per day
However, as with other NSAIDs, take KAFENAC with caution if you are elderly and have impaired kidney or liver function, cardiovascular dysfunction or if you are receiving other drug treatments at the same time.
Undesirable effects can be minimized by administering the lowest effective dose for the shortest duration necessary to control symptoms.
If you forget to take KAFENAC
Do not take a double dose to make up for a forgotten dose.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Kafenac
In case of accidental ingestion / intake of an overdose of KAFENAC, notify your doctor immediately or go to the nearest hospital.
There is currently insufficient information on the clinical picture resulting from overdose with KAFENAC.
Therapeutic measures to be taken in case of acute poisoning with oral aceclofenac are those commonly employed in case of acute NSAID poisoning:
- Absorption should be prevented as soon as possible by gastric lavage (stomach emptying and washing) and treatment with activated charcoal.
- Supportive and symptomatic treatments should be used for complications such as hypotension (low blood pressure), renal failure, seizures, gastrointestinal irritation, and respiratory depression.
- Specific therapies, such as forced diuresis (method used to increase the elimination of substances already absorbed), dialysis (therapy that replaces kidney physical function) or haemoperfusion (passage of blood through an absorbent resin column to remove a substance) do not allow to eliminate non-steroidal anti-inflammatory drugs, due to the high percentage of binding to blood proteins and their considerable metabolism.
Side Effects What are the side effects of Kafenac
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking KAFENAC and see your doctor immediately if any of the following side effects occur:
- Bleeding in the stomach and intestines (gastrointestinal)
- Stomach injury (peptic ulcers).
- Persistently altered or worsened liver function parameters, consistent clinical signs or symptoms of liver disease, other manifestations such as eosinophilia.
- Skin rash (sudden redness of the skin), mucosal lesions or any other signs of allergy.
Possible side effects that may occur after taking KAFENAC are:
Common side effects (may affect up to 1 in 10 people)
- Dizziness (dizziness).
- Increase in some liver enzymes.
- Nausea, diarrhea, abdominal pain, dyspepsia (digestive pain).
Uncommon side effects (may affect up to 1 in 100 people)
- Gastritis (inflammation of the stomach), mouth ulcers (canker sores), flatulence (gas in the intestine), constipation (constipation), vomiting.
- Urticaria (skin disorder), rash (sudden redness of the skin), itching, dermatitis (inflammation of the skin).
- Increased levels of urea and creatinine in the blood.
- Constipation (constipation).
Rare side effects (may affect up to 1 in 1,000 people)
- Anemia (decrease in the concentration of hemoglobin in the blood).
- Angioedema (sudden swelling of the skin or mucous membranes).
- Vision disturbances.
- Hypertension (high blood pressure).
- Anaphylactic reaction (rapid onset allergic reaction) including shock, allergy.
- Heart failure (inability of the heart to supply an adequate amount of blood for the needs of the whole body).
- Dyspnea (difficulty breathing).
- Melena (bleeding in stools), gastrointestinal ulcer and bleeding (peptic ulcers, gastrointestinal perforation or bleeding may occur, sometimes fatal, particularly in the elderly).
Very rare side effects (may affect up to 1 in 10,000 patients)
- Thrombocytopenia (decrease in the number of blood platelets), haemolytic anemia (decrease in the concentration of hemoglobin in the blood caused by the destruction of red blood cells), granulocytopenia (severe decrease in the number of granulocytes in the blood), bone marrow depression (decrease in the function of the blood bone marrow that produces blood cells).
- Depression, insomnia, abnormal dreams.
- Paresthesia (altered sensitivity), dysgeusia (altered taste), headache, drowsiness.
- Tinnitus (ringing in the ears), dizziness.
- Palpitations.
- Redness.
- Vasculitis (inflammation of the veins), flushing.
- Bronchospasm (decrease in the lumen of the bronchi).
- Aggravation of ulcerative colitis or Crohn's disease (inflammatory bowel disease), stomatitis (inflammation of the lining of the mouth), pancreatitis (inflammation of the pancreas), intestinal perforation, haematemesis (vomiting of blood).
- Stevens-Johnson syndrome (acute allergy reaction involving the skin and mucous membranes), toxic epidermal necrolysis (or "Lyell's syndrome", severe skin disease induced by an "allergy to certain drugs, characterized by the destruction of the skin epithelium" and mucous membranes), purpura (hematoma-like lesion resulting from the rupture of capillaries under the skin's surface), rash (rash).
- Renal failure, nephrotic syndrome (a combination of symptoms and clinical signs caused by an alteration of the renal glomeruli resulting in the loss of protein in the urine).
- Hepatic (liver) injury including hepatitis (inflammation of the liver), increased blood alkaline phosphatase.
- Edema (fluid accumulation), fatigue.
- Weight gain.
Clinical trials and epidemiological data indicate that there may be an increased risk of arterial thrombotic events (eg myocardial infarction or stroke) associated with the use of aceclofenac, especially at high doses and in long-term treatments (see "Warnings and precautions"). .
Exceptionally, severe infectious skin and soft tissue complications have been reported in conjunction with NSAID treatment during chickenpox. To date, it is not possible to exclude the role of NSAIDs in the "aggravation of these infections (see" Warnings and precautions ").
If one or more of the side effects described above occur, it is recommended to stop treatment with aceclofenac and contact your doctor.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.it/it/responsabili.
By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the package. The expiry date refers to the last day of that month and to the product in intact packaging, correctly stored.
KAFENAC 100 mg coated tablets
Store at a temperature not exceeding 30 ° C.
KAFENAC 100 mg powder for oral suspension
No special storage precautions are required.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other Information
What KAFENAC contains
KAFENAC 100 mg coated tablets
One coated tablet contains
Active ingredient: aceclofenac 100 mg.
Other components: microcrystalline cellulose, croscarmellose sodium, glyceryl palmitostearate, povidone, hypromellose, polyoxyethylenestearate, titanium dioxide. KAFENAC 100 mg powder for oral suspension One sachet contains:
Active ingredient: aceclofenac 100 mg.
Other components: sorbitol, sodium saccharin, caramel flavor, cream flavor, milk flavor, anhydrous colloidal silica, aspartame, hypromellose, titanium dioxide.
Description of what KAFENAC looks like and contents of the pack
KAFENAC 100 mg coated tablets
White circular coated tablets.
Blister packs of 10 coated tablets in a cardboard box.
Blister packs of 40 coated tablets in a cardboard box.
KAFENAC 100 mg powder for oral suspension
White or creamy white powder for oral suspension.
Pack of 30 sachets.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
KAFENAC
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
KAFENAC 100 mg coated tablets
Each coated tablet contains:
Active principle:
Aceclofenac 100 mg
KAFENAC 100 mg powder for oral suspension
Each sachet contains:
Active principle:
Aceclofenac 100 mg
Excipients with known effects:
sorbitol (E420), aspartame (E951).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Coated tablets
Powder for oral suspension
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Aceclofenac is a non-steroidal anti-inflammatory drug belonging to the class of phenylacetic acid analogues.
Treatment of chronic osteo-articular diseases such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and extra-articular rheumatism such as periarthritis, tendinitis, bursitis, enthesitis.
Treatment of acute painful states of different etiology such as sciatica, lumbago, myalgia, primary dysmenorrhea, pain resulting from various types of trauma, odontalgia.
04.2 Posology and method of administration
KAFENAC 100 mg coated tablets
Adults
The recommended daily dose is 2 coated tablets per day (200 mg / day), one coated tablet every 12 hours.
The coated tablets should be swallowed with a sufficient amount of water.
KAFENAC 100 mg powder for oral suspension
The daily dose is 2 sachets per day (200 mg / day) 1 sachet every 12 hours. The sachets must be dissolved in 40-60 ml of water and swallowed immediately.
Both coated tablets and sachets should be taken preferably with meals.
Undesirable effects can be minimized by administering the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4 Special warnings and precautions for use).
Children
Clinical data on the use of the drug in pediatrics are not currently available, therefore its administration is not recommended.
Senior citizens
In elderly patients, the pharmacokinetic profile of aceclofenac is not modified, therefore it is not considered necessary to modify the posology. However, as with other NSAIDs, care should be taken when treating elderly patients with impaired renal or hepatic function, with cardiovascular alterations or undergoing concomitant drug treatments.
Patients with mild renal insufficiency
As with other NSAIDs, the drug should be administered with caution even if there is no clinical evidence to induce a dose reduction.
Patients suffering from hepatic insufficiency
In patients with hepatic insufficiency it is advisable to reduce the starting dose to 100 mg / day.
04.3 Contraindications
Hypersensitivity to the active substance or to non-steroidal anti-inflammatory drugs, including acetylsalicylic acid, or to any of the excipients listed in section 6.1.
Like other non-steroidal anti-inflammatory drugs, aceclofenac is contraindicated in patients who have experienced asthma attacks or other allergic reactions (urticaria, acute rhinitis, edema, rash, bronchospasm) after taking acetylsalicylic acid or other NSAIDs.
The product should not be used in cases of gastro-duodenal ulcer or bleeding in the gastrointestinal tract and in subjects with active bleeding or bleeding disorders.
KAFENAC is contraindicated in patients with a history of gastrointestinal bleeding or perforation related to previous NSAID treatment or with a history / active phase of recurrent peptic haemorrhage / ulcer (two or more distinct episodes of proven ulceration or bleeding).
Furthermore, the drug is contraindicated in patients with severe hepatic or renal impairment and in patients with overt congestive heart failure (NYHA class II-IV), ischemic heart disease, peripheral arterial disease and / or cerebral vasculopathy.
KAFENAC is also contraindicated in pregnancy, especially in the last 3 months, and during lactation unless there are valid reasons for taking it. In this case the lowest effective dosage should be used (see section 4.6).
04.4 Special warnings and appropriate precautions for use
Warnings
The use of KAFENAC should be avoided in conjunction with selective COX-2 inhibitor NSAIDs.
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.2 and the paragraphs below on gastrointestinal and cardiovascular risks).
Senior citizens. Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2).
Gastro-intestinal system. Gastrointestinal bleeding, ulceration and perforation: Gastrointestinal bleeding, ulceration and perforation, which can be fatal, have been reported during treatment with all NSAIDs, at any time, with or without warning symptoms or a previous history of serious gastrointestinal events.
In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), the risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing doses of NSAIDs. These patients should start treatment with the lowest available dose. Concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients requiring concomitant low dose aspirin or other drugs that may increase the risk of gastrointestinal events (see below and section 4.5 ).
Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.
Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as aspirin (see section 4.5).
When gastrointestinal bleeding or ulceration occurs in patients taking KAFENAC the treatment should be discontinued.
NSAIDs should be administered with caution in patients with symptoms indicative of upper or lower intestinal tract related gastrointestinal disease, history of gastrointestinal ulcer, bleeding or perforation, ulcerative colitis, Crohn's disease and haematological abnormalities as these conditions may be exacerbated ( see section 4.8).
Cardiovascular and cerebrovascular system. Adequate monitoring and instruction are required in patients with a history of mild to moderate hypertension and / or congestive heart failure as fluid retention and edema have been reported in association with NSAID treatment.
Patients with congestive heart failure (NYHA class I) and patients with significant risk factors for cardiovascular events (eg hypertension, hyperlipidemia, diabetes mellitus, smoking) should only be treated with aceclofenac after careful consideration. cardiovascular diseases of aceclofenac may increase with dose and duration of exposure, the shortest possible duration and the lowest effective daily dose should be used. The patient's response to therapy and the need for improvement in symptoms should be reassessed periodically.
Aceclofenac should be administered with caution and under close medical supervision in patients with a history of cerebrovascular bleeding.
Liver function. Close medical supervision is required for patients with severe hepatic impairment. Aceclofenac should be discontinued in the event of persistent abnormalities or worsening of liver function tests or if typical signs or symptoms of liver disease occur or in the presence of other manifestations (eosinophilia, rash). Hepatitis can occur without prodromal signs. The use of aceclofenac in people with hepatic porphyria can lead to an attack.
Hypersensitivity reactions and skin reactions. As with other NSAIDs, allergic reactions, including anaphylactic and anaphylactoid reactions, are possible, even in the absence of previous exposure to the medicinal product.
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). In the early stages of therapy, patients appear to be at higher risk: the onset of the reaction occurs in most cases within the first month of treatment. KAFENAC should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
Exceptionally, chickenpox can cause severe infectious skin and soft tissue complications. To date, it is not possible to exclude the role of NSAIDs in the aggravation of these infections. It is therefore advisable to avoid the use of aceclofenac in case of chickenpox.
Precautions :
Renal function. Individuals with mild to moderate renal impairment should be monitored as the use of NSAIDs may lead to deterioration of renal function. The lowest effective dose should be used in such individuals and renal function should be regularly monitored.
Administration of an NSAID can cause a dose-dependent reduction in prostaglandin formation and aggravate renal insufficiency. The importance of prostaglandins in regulating renal blood flow should always be taken into account in subjects with impaired cardiac or renal function, hepatic dysfunction. , in those treated with diuretics and in those who have undergone major surgery and in the elderly. Effects on renal function are generally reversible with discontinuation of aceclofenac.
Hematological. Aceclofenac can reversibly inhibit platelet aggregation (see anticoagulants in section 4.5).
Respiratory pathologies. Caution is required when administering to patients with or who have suffered from bronchial asthma since NSAIDs can aggravate bronchospasm.
Long-term treatments. As a preventive measure, subjects undergoing long-term NSAID treatment should be monitored for blood cell counts and renal and hepatic function parameters.
Important information about some of the excipients
The sachets contain Sorbitol (E420), therefore patients with rare hereditary problems of fructose intolerance should not take this medicine.
The sachets contain aspartame (E951) as a source of phenylalanine and can therefore be dangerous for patients with phenylketonuria.
04.5 Interactions with other medicinal products and other forms of interaction
Diuretics. Aceclofenac, like other NSAIDs, may inhibit the activity of diuretics. Although no influence on blood pressure control was observed when administered concomitantly with bendrofluazide, interactions with other diuretics cannot be excluded. In case of concomitant administration with diuretics. potassium sparing, serum potassium should be checked.
Antihypertensives. NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (eg dehydrated patients or elderly patients) co-administration of an ACE inhibitor or angiotensin II antagonist and NSAIDs may increase the risk of acute renal failure, which is usually reversible. These interactions should be considered in patients taking KAFENAC concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with caution, especially in elderly patients.
Patients should be adequately hydrated and monitoring of renal function should be considered after initiation of concomitant therapy and periodically thereafter.
Corticosteroids. Increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Anticoagulants. Like other NSAIDs, aceclofenac may increase the activity of anticoagulant drugs such as warfarin (see section 4.4) and therefore patients undergoing combination therapy should be closely monitored.
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs). Concomitant use with NSAIDs may increase the risk of gastrointestinal bleeding (see section 4.4).
Antidiabetic. Clinical studies show that diclofenac can be administered with oral antidiabetic agents without influencing their clinical effects. Isolated cases of hypoglycemic and hyperglycemic effects have been reported: it is therefore recommended to consider the possibility of dose adjustment of hypoglycemic agents concomitantly with aceclofenac.
Methotrexate. The possible interaction between NSAIDs and methotrexate should also be kept in mind when low doses of methotrexate are administered, especially in patients with impaired renal function. When combination therapy is to be administered, renal function should be monitored. Particular caution should be exercised when administering NSAIDs and methotrexate concomitantly over a 24-hour period as an increase in plasma concentrations of the antitumor agent can be determined with a consequent increase in the toxicity of the latter.
Lithium and digoxin. Some NSAIDs inhibit the renal clearance of lithium and digoxin resulting in an increase in plasma concentration. The combination should therefore be avoided unless frequent monitoring of lithium and digoxin levels is possible.
Other NSAIDs. Concomitant use of acetylsalicylic acid and other NSAIDs may increase the frequency of side effects.
Ciclosporin, tacrolimus. It is believed that concomitant administration of NSAIDs with cyclosporine or tacrolimus may increase the risk of nephrotoxicity due to decreased synthesis of prostacyclin in the kidney. It is therefore important to closely monitor renal function during combination therapy.
Zidovudine. When NSAIDs are given with zidovudine, the risk of blood toxicity increases; there are indications of an increased risk of haemarthrosis and hematoma in HIV (+) haemophiliacs receiving concomitant treatment with zidovudine and ibuprofen.
04.6 Pregnancy and breastfeeding
PREGNANCY
There is no information on the use of aceclofenac in pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and / or embryo / fetal development.
Data from epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%. The risk has been believed to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased pre- and post-implantation loss and embryo-fetal mortality.
Furthermore, the increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
During the first and second trimester of pregnancy, aceclofenac should not be administered unless absolutely necessary. If aceclofenac is given to women who are trying to conceive or who are in the first and second trimester of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to:
- cardiopulmonary toxicity (with premature closure of the arterial duct in the uterus and pulmonary hypertension);
- renal dysfunction, which can progress to renal failure with oligo-hydroamnios;
the mother and the newborn, at the end of pregnancy, to:
- possible prolongation of bleeding time and antiplatelet effect which may occur even at very low doses;
- inhibition of uterine contractions resulting in delayed or prolonged labor
Consequently, aceclofenac is contraindicated in the third trimester of pregnancy (see section 4.3).
FEEDING TIME
It is not known whether aceclofenac is excreted in human milk and passage of (14C) labeled aceclofenac into the milk of lactating rats has not been detected. However, the use of aceclofenac should be avoided during pregnancy and lactation unless the potential benefit to the mother outweighs the possible risk to the fetus.
FERTILITY
NSAIDs may impair fertility and use is not recommended in women planning to become pregnant. Suspension of aceclofenac should be considered in women who have fertility problems or are undergoing fertility investigations.
04.7 Effects on ability to drive and use machines
As with other NSAIDs and in particularly predisposed patients, the administration of aceclofenac could give rise to dizziness or other central nervous disorders: those who are engaged in driving a vehicle or using machinery that require attention and vigilance should be informed of this.
04.8 Undesirable effects
The most commonly reported side effects are gastrointestinal upset.
Peptic ulcers, gastrointestinal perforation or haemorrhage, sometimes fatal, may occur, particularly in the elderly (see section 4.4).
Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of aceclofenac (see section 4.4).
Gastritis has been observed less frequently.
Dermatological disorders, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rarely) have been reported.
Exceptionally, severe infectious skin and soft tissue complications have been reported in conjunction with NSAID treatment during chickenpox. To date, it is not possible to exclude the role of NSAIDs in the aggravation of these infections
Edema, hypertension and heart failure have been reported in association with NSAID treatment.
Aceclofenac is structurally related and has a similar metabolism to diclofenac for which more clinical and epidemiological data are available showing an increased risk of general arterial thrombotic events (myocardial infarction or stroke, particularly at high doses and in long-term treatment) . Epidemiological data have also shown an increased risk of acute coronary syndrome and myocardial infarction following the use of aceclofenac (see sections 4.3 and 4.4 Contraindications and Special Warnings and Precautions for Use).
In the following table, adverse reactions reported during clinical trials and from post-registration experience with KAFENAC are presented and grouped by systemic and organ class (SOC) and by frequency. Very common (≥1 / 10); common (≥1 / 100,
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
There is currently insufficient information on the clinical picture resulting from overdose with KAFENAC.
Therefore the therapeutic measures to be adopted in case of acute poisoning with oral aceclofenac are those commonly used in case of acute NSAID poisoning:
- absorption should be prevented as soon as possible by gastric lavage and treatment with activated charcoal;
- supportive and symptomatic treatments should be adopted in case of complications (hypotension, renal insufficiency, convulsions, gastrointestinal irritation and respiratory depression);
- specific therapies, such as forced diuresis, dialysis or haemoperfusion, do not allow the elimination of non-steroidal anti-inflammatory drugs, due to the high percentage of binding to plasma proteins and their considerable metabolism.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: non-steroidal anti-inflammatory and antirheumatic drug.
ATC code M01AB16.
Aceclofenac is a non-steroidal anti-inflammatory drug belonging to the phenylacetic acid analogue class.
In studies conducted on different animal species, aceclofenac has shown in experimental models of acute and chronic inflammation an "analgesic and anti-inflammatory activity, in terms of both therapeutic and prophylaxis, similar to that of indomethacin and diclofenac.
The analgesic power evaluated on painful states experimentally induced by stimuli of different types was found to be comparable to that of indomethacin and diclofenac.
Aceclofenac, in the experimental models used, was also endowed with antipyretic activity.
No functional alterations were found in the cardiovascular, respiratory and central nervous systems. The effects on the kidney are comparable to those induced by other NSAIDs.
Mechanism of action
Aceclofenac was found to be a potent inhibitor of cyclooxygenase, an enzyme that catalyzes the conversion of arachidonic acid into the precursors of prostaglandins and thromboxane.
05.2 Pharmacokinetic properties
Absorption
Pharmacokinetic studies conducted in various animal species (rat, dog and monkey) show that aceclofenac administered orally and intramuscularly is rapidly absorbed in the form of unchanged drug.
Distribution
Peak plasma (Cmax) is reached approximately 2 hours (tmax) after oral administration of the drug. Bioavailability is close to 100%. The plasma half-life is 4 hours. No accumulation in the plasma compartment was observed after repeated administration. Aceclofenac electively penetrates the synovial fluid, where concentrations reach approximately 57% of plasma levels.
Metabolism
Aceclofenac and its metabolites have a "high affinity for plasma proteins (> 99%).
Aceclofenac is mainly present in the circulation as an unchanged drug.
Elimination
About two-thirds of the administered dose is excreted via the urine, mainly in the form of hydroxymetabolites.
The pharmacokinetic profile of aceclofenac is comparable in adults and the elderly.
05.3 Preclinical safety data
The results of preclinical studies conducted with aceclofenac are consistent with those of NSAIDs. The primary target organ is the gastrointestinal tract.
The toxicity of aceclofenac was evaluated in different animal species (mouse, rat, monkey) using different routes of administration and adopting single and repeated treatment regimens.
Acute toxicity (LD50): mouse i.v. 149-169 mg / kg, p.o. 211 mg / kg; rat i.v. 94-137 mg / kg (male-female).
Toxicity after repeated administration (p.o.): rat 4 weeks: no toxicity up to 3 mg / kg / day; rat 26 weeks: no toxicity up to 1.5 mg / kg / day; monkey 13 weeks: no toxicity up to 5 mg / kg / day; monkey 52 weeks: no toxicity up to 3 mg / kg / day.
Toxicity after repeated administration (IM): monkey 4 weeks: no toxicity up to 3 mg / kg / day.
After repeated treatment there was evidence of gastrointestinal toxicity only at the highest doses, which resulted in the rat 3-6 times, in the monkey 5-10 times higher than the therapeutic dose in humans. These toxic effects were reversible in both species. .
Aceclofenac did not show mutagenic or carcinogenic activity.
Animal studies show no evidence of teratogenesis in rats, although systemic exposure was low, and in rabbits; treatment with aceclofenac (10 mg / kg / day) resulted in a number of morphological changes in some fetuses.
There is no further information on preclinical data of prostaglandin synthesis inhibitors other than those already reported elsewhere in this SmPC (see 4.6).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Coated tablets:
Microcrystalline cellulose, croscarmellose sodium, glyceryl palmitostearate, povidone, hypromellose, polyoxyethylene stearate, titanium dioxide.
Powder for oral suspension:
sorbitol (E420), sodium saccharin, caramel flavor, cream flavor, milk flavor, anhydrous colloidal silica, aspartame (E951), hypromellose, titanium dioxide (E171).
06.2 Incompatibility
None.
06.3 Period of validity
Coated tablets: 3 years.
Powder for oral suspension: 4 years.
06.4 Special precautions for storage
Coated tablets
Store at a temperature not exceeding 30 ° C.
Powder for oral suspension
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
KAFENAC 100 mg coated tablets - 40 tablets: Al / Al blister
KAFENAC 100 mg coated tablets - 10 tablets: Al / Al blister
KAFENAC 100 mg powder for oral suspension - 30 sachets: aluminum / polyethylene paper sachets.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
ALMIRALL S.A.
Ronda General Miter 151
08022 Barcelona, Spain
Dealer for sale:
Crinos S.p.A.
Via Pavia 6
20136 Milan
08.0 MARKETING AUTHORIZATION NUMBER
40 coated tablets 100 mg AIC n ° 031842014
10 coated tablets 100 mg AIC n ° 031842065
30 sachets powder for oral suspension 100 mg AIC n ° 031842026
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
July 26, 2000 / Last renewal 2015
10.0 DATE OF REVISION OF THE TEXT
November 2015
