Active ingredients: Diclofenac
Dicloreum 50mg gastro-resistant tablets
Dicloreum 100mg gastro-resistant tablets
Dicloreum package inserts are available for pack sizes: - Dicloreum 50mg gastro-resistant tablets, Dicloreum 100mg gastro-resistant tablets,
- Dicloreum 150mg prolonged-release hard capsules
- Dicloreum 50mg granules for oral suspension
- Dicloreum 50mg suppositories, Dicloreum 100mg suppositories,
- Dicloreum 75mg / 3ml solution for injection for intramuscular use
- Dicloreum 3% skin foam
Why is Dicloreum used? What is it for?
Non-steroidal anti-inflammatory and antirheumatic.
Therapeutic indications
Joint localization rheumatic diseases: rheumatoid arthritis, osteoarthritis.
Rheumatic diseases with extra-articular localization: periarthritis, bursitis, tendinitis, myositis, lumbosciatica.
Inflammation and edema of post-traumatic origin.
Contraindications When Dicloreum should not be used
- Known hypersensitivity to the active substance or to any of the excipients, generally towards other analgesics, antipyretics, non-steroidal anti-inflammatory drugs and in particular towards acetylsalicylic acid.
- Previous liver disease.
- Active gastrointestinal ulcer, bleeding or perforation.
- History of gastrointestinal bleeding or perforation related to previous NSAID treatment or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
- Last trimester of pregnancy and during lactation.
- Severe liver failure, severe renal failure or severe heart failure
- In subjects with ongoing bleeding and bleeding diathesis.
- Like other NSAIDs, diclofenac is also contraindicated in patients who have experienced asthma attacks, urticaria or acute rhinitis after taking acetylsalicylic acid or other NSAIDs.
- In case of alterations in the production of blood cells.
- In case of intensive diuretic therapy (see "Interactions").
DICLOREUM is also contraindicated in pediatric age (
Precautions for use What you need to know before taking Dicloreum
If in doubt, ask your doctor or pharmacist for clarification on the use of the medicine.
General informations
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible treatment duration needed to control symptoms.
The concomitant use of diclofenac with other systemic NSAIDs, including selective cyclo oxygenase-2 inhibitors, should be avoided due to the lack of any evidence demonstrating synergistic benefits and based on potential additive side effects.
In the treatment of underweight patients it is recommended to administer the lowest effective dose.
Senior citizens: on a basic medical level, caution is required in the elderly. Particularly in frail elderly patients or in those with a low body weight, the use of the lowest effective dose is recommended.
As with other NSAIDs, allergic reactions, including anaphylactic / anaphylactoid reactions, may also occur in rare cases without prior exposure to diclofenac.
Like other NSAIDs, DICLOREUM can mask the signs and symptoms of infections due to its pharmacodynamic properties.
Due to the importance of prostaglandins for the maintenance of renal blood flow, particular caution is required or the exclusion from the use of DICLOREUM in case of renal hypoperfusion, renal insufficiency, thromboembolic phenomena in the history, in patients treated with diuretics and in those after major surgery.
Gastrointestinal effects
During treatment with all NSAIDs including diclofenac, they have been reported and may appear at any time, with or without warning symptoms or a previous history of serious gastrointestinal events, gastrointestinal bleeding, ulceration and perforation, which can be fatal.
They generally have more serious consequences in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the medicinal product should be discontinued.
As with all NSAIDs, including diclofenac, close medical surveillance is mandatory and particular caution should be used when prescribing DICLOREUM to patients with symptoms suggestive of gastrointestinal (GI) disorders or with a history indicative of gastric or intestinal ulceration, bleeding or perforation.
The risk of GI bleeding is higher with increased doses of NSAIDs and in patients with a history of ulcer, especially if complicated with haemorrhage or perforation. The elderly have a higher frequency of adverse reactions, especially gastrointestinal bleeding and perforation which can be fatal (see "Undesirable effects"). To reduce the risk of GI toxicity in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly, treatment should be initiated and maintained at the lowest effective dose.
Concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking low doses of acetylsalicylic acid ASA / aspirin or other drugs that may increase the risk of gastrointestinal events (see below and "Interactions").
Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the early stages of treatment.
Caution is advised 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 "Interactions").
When gastrointestinal bleeding or ulceration occurs in patients taking Dicloreum the treatment should be discontinued.
Close medical surveillance and caution should also be exercised in patients with ulcerative colitis or Crohn's disease, as these conditions may be exacerbated (see "Undesirable Effects").
Hepatic effects
Close medical surveillance is required when prescribing diclofenac to patients with hepatic insufficiency, as the condition may be exacerbated.
As with other NSAIDs, including diclofenac, the values of one or more liver enzymes may increase. During prolonged treatment with diclofenac, regular checks of liver function are indicated as a precautionary measure.
If liver function parameters are persistently altered or worsened, if clinical signs or consistent symptoms of liver disease develop, or if other manifestations (e.g. eosinophilia, rash) occur, diclofenac treatment should be discontinued. A "hepatitis with the use of diclofenac" can occur without prodromal symptoms.
Particular caution should be exercised in the use of diclofenac in patients with hepatic porphyria, as it could trigger an attack.
Kidney effects
Since fluid retention and edema have been reported in association with NSAID therapy, including diclofenac, particular caution is required in case of cardiac or renal failure, history of hypertension, in the elderly, in patients receiving concomitant diuretics or medicinal products that may significantly affect renal function and in those patients with substantial extracellular volume depletion due to any cause (e.g. before or after major surgery).
In such cases, monitoring of renal function is recommended as a precaution when administering diclofenac. Discontinuation of therapy is usually followed by a return to pre-treatment conditions.
Skin effects
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 "Undesirable Effects"). Patients in the early stages of therapy they appear to be at higher risk for these reactions: the onset of the reaction occurs in most cases within the first month of treatment. DICLOREUM should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
Cardiovascular and cerebrovascular effects
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.
Clinical studies and epidemiological data suggest that the use of diclofenac, especially at high doses (150 mg / day) and in long-term treatments, may be associated with a modest increased risk of arterial thrombotic events (eg. myocardium or stroke).
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with diclofenac after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular events (eg, hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Hematological effects
During prolonged treatment with diclofenac, as with other NSAIDs, blood count checks are indicated.
Like other NSAIDs, diclofenac may temporarily inhibit platelet aggregation. Patients with haemostatic defects should be carefully monitored.
Pre-existing asthma
In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (e.g. nasal polyps), chronic obstructive pulmonary diseases or chronic respiratory tract infections (especially when linked to symptoms similar to allergic rhinitis), they are more frequent than in other patients reactions to NSAIDs such as exacerbation of asthma (so-called analgesic intolerance / analgesic asthma), Quincke's edema or urticaria. Special precaution is therefore recommended in such patients (preparing for emergency). This also applies to patients who are allergic to other substances, eg. with skin reactions, itching or hives
Interactions Which drugs or foods can modify the effect of Dicloreum
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
The following interactions include those observed with diclofenac gastro-resistant tablets and / or other pharmaceutical forms of diclofenac.
Lithium: when administered together with preparations containing lithium, diclofenac can raise its plasma concentration. Monitoring of serum lithium levels is recommended.
Digoxin: when administered together with other preparations containing digoxin, diclofenac can raise their plasma concentration. Monitoring of serum digoxin levels is recommended.
Diuretics and antihypertensive agents: Like other NSAIDs, concomitant use of diclofenac with diuretics or antihypertensive agents (eg beta blockers, angiotensin converting enzyme (ACE) inhibitors may cause a decrease in their antihypertensive effect. Therefore, the combination must be taken with caution and patients, especially the elderly, should receive periodic monitoring of their blood pressure.
In some patients with impaired renal function (e.g. dehydrated patients or elderly patients with impaired renal function) the co-administration of an ACE inhibitor or angiotensin II antagonist and agents that inhibit the cyclooxygenase system may lead to further deterioration of renal function, including possible acute renal failure, usually reversible These interactions should be considered in patients taking DICLOREUM concomitantly with ACE inhibitors or angiotensin II antagonists.
Patients should be adequately hydrated and renal function monitoring should be considered after initiation of concomitant therapy and periodically thereafter, particularly for diuretics and ACE inhibitors due to an increased risk of nephrotoxicity.
Concomitant treatment with potassium-sparing drugs may be associated with an increase in serum potassium levels, which should therefore be monitored frequently (see "Precautions for use").
Other NSAIDs and corticosteroids: the concomitant administration of diclofenac and other systemic non-steroidal anti-inflammatory drugs may increase the frequency of gastrointestinal side effects (see "Precautions for use").
Anticoagulants and antiplatelet agents: Caution is recommended as co-administration may increase the risk of bleeding (see "Precautions for use"). Although there is no indication from clinical trial data that "diclofenac influences the anticoagulant effect", there are There have been isolated reports of an increased risk of bleeding with concomitant use of diclofenac and anticoagulant therapy. Careful monitoring is recommended for these patients.
Selective Serotonin Reuptake Inhibitors (SSRIs): Concomitant administration of systemic NSAIDs, including diclofenac, and SSRIs may increase the risk of gastrointestinal bleeding.
Antidiabetics: Clinical studies have shown that diclofenac can be taken concomitantly with oral antidiabetics without changing their clinical effect. However, there have been isolated reports of both hypo- and hyperglycaemic effects, with the need to modify the dosage of the antidiabetic agents administered during treatment with diclofenac. For this reason, in case of concomitant therapy, monitoring of blood glucose levels is recommended as a precautionary measure.
Methotrexate: diclofenac may inhibit renal tubular release of methotrexate by increasing its levels. Caution is advised when administering NSAIDs, including diclofenac, 24 hours before or after treatment with methotrexate as blood concentrations of methotrexate and consequently the toxicity of this substance may increase.
Cyclosporine: due to its effect on renal prostaglandins, diclofenac, like other NSAIDs, may increase the nephrotoxicity of cyclosporine.
Therefore, diclofenac should be administered at lower dosages than would be used in patients not on cyclosporine therapy.
Quinolone antibacterials: There have been isolated reports of seizures, probably due to the concomitant use of quinolones and NSAIDs.
Phenytoin: When using phenytoin together with diclofenac, monitoring of phenytoin plasma concentrations is recommended due to an expected increase in phenytoin exposure.
Colestipol and cholestyramine: These agents may induce a delay or decrease in the absorption of diclofenac. Therefore, it is recommended that diclofenac be administered at least one hour before or 4-6 hours after colestipol / cholestyramine administration.
Potent CYP2C9 inhibitors: Caution is advised when prescribing diclofenac together with potent CYP2C9 inhibitors (such as sulfinpyrazone and voriconazole); this could lead to a significant increase in peak plasma concentrations and exposure to diclofenac, due to inhibition of its metabolism.
Warnings It is important to know that:
The drug can cause bronchospasm and possibly shock and other allergic phenomena in asthmatics and predisposed subjects.
Fertility, pregnancy and lactation
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy
Inhibition of prostaglandin synthesis can adversely affect pregnancy and / or embryo / fetal development.
Results of 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 cardiac malformations increased from less than 1% up to approximately 1.5%. The risk has been considered to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased loss of pre- and post-implantation and of embryo-fetal mortality.
In addition, an 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, diclofenac should not be administered except in strictly necessary cases.
If diclofenac is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose and duration of treatment should be kept as low 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 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 DICLOREUM is contraindicated during the third trimester of pregnancy.
Feeding time
Like other NSAIDs, diclofenac passes into breast milk in small quantities, it is therefore recommended not to administer DICLOREUM during breastfeeding to avoid undesirable effects in the infant.
Fertility
As with other NSAIDs, the use of DICLOREUM may impair female fertility and is not recommended in women wishing to conceive. Discontinuation of diclofenac should be considered in women who have difficulty conceiving or are undergoing investigation of infertility.
Effects on ability to drive and use machines
Patients who experience visual disturbances, dizziness, vertigo, somnolence or other central nervous system disorders with the use of diclofenac, should refrain from driving a vehicle or operating machinery.
Important information about some of the ingredients
Lactose
The gastro-resistant tablets contain lactose: if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Dosage and method of use How to use Dicloreum: Dosage
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms.
The tablets should be swallowed whole with some liquid, and should not be split or chewed.
Adults
Gastro-resistant tablets 50 mg:
Attack therapy: 1 tablet, 3 times a day.
Extended therapy: 1 tablet, 2 times a day (morning and evening); in some cases a further reduction of the dosage is possible. Administration during or after meals (breakfast and dinner) is preferable.
Prolonged-release tablets 100 mg:
1 tablet a day, after breakfast.
Rectal formulations of DICLOREUM are available; rectal therapy can be associated with oral therapy: 1 suppository, preferably in the evening and 1 50 mg tablet of DICLOREUM at breakfast in the morning.
Senior citizens
In the treatment of elderly patients, the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above.
Children and adolescents
DICLOREUM should not be used in children and adolescents under the age of 14.
Overdose What to do if you have taken too much Dicloreum
Symptoms
There is no typical clinical picture resulting from diclofenac overdose. Overdose can cause symptoms such as vomiting, gastrointestinal bleeding, diarrhea, dizziness, tinnitus or convulsions. In the case of significant poisoning, acute renal failure and liver damage are possible.
Therapeutic measures
The treatment of acute poisoning by non-steroidal anti-inflammatory drugs, including diclofenac, essentially consists of supportive measures and symptomatic treatment.
In case of complications such as hypotension, renal insufficiency, convulsions, gastrointestinal disturbances and respiratory depression, supportive measures and symptomatic treatment should be adopted.
Specific therapies, such as forced diuresis, dialysis or haemoperfusion, are unlikely to help eliminate non-steroidal anti-inflammatory drugs, including diclofenac, due to their high plasma protein binding and extensive metabolism.
After ingestion of a potentially toxic overdose, the use of activated charcoal may be considered, while gastric emptying (eg vomiting, gastric lavage) may be considered after ingestion of a potentially life-threatening overdose.
In case of accidental ingestion / intake of an excessive dose of DICLOREUM, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of DICLOREUM, ask your doctor or pharmacist.
Side Effects What are the side effects of Dicloreum
Like all medicines, DICLOREUM can cause side effects, although not everybody gets them.
Adverse reactions are listed by frequency, most frequent first, using the following convention: common (≥ 1/100 to <1/10); uncommon (≥ 1 / 1,000 to <1/100); rare (≥ 1 / 10,000, <1 / 1,000); very rare (<1 / 10,000), not known (cannot be estimated from the available data).
The following side effects include those reported with short or long term use.
Disorders of the blood and lymphatic system
Very rare: thrombocytopenia, leukopenia, anemia (including haemolytic and aplastic anemia), agranulocytosis.
Disorders of the immune system
Rare: hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension and shock).
Very rare: angioneurotic edema (including face edema).
Psychiatric disorders
Very rare: disorientation, depression, insomnia, nightmares, irritability, psychotic reactions.
Nervous system disorders
Common: headache, dizziness.
Rare: somnolence.
Very rare: paraesthesia, memory impairment, convulsions, anxiety, tremors, aseptic meningitis, taste disturbances, cerebrovascular accidents, excitement.
Eye disorders
Very rare: visual disturbances, blurred vision, diplopia.
Ear and labyrinth disorders
Common: dizziness.
Very rare: tinnitus, hearing impairment.
Cardiac pathologies
Very rare: palpitations, chest pain, heart failure, myocardial infarction.
Vascular pathologies
Very rare: hypertension, vasculitis.
Respiratory, thoracic and mediastinal disorders
Rare: asthma (including dyspnoea).
Very rare: pneumonia.
Gastrointestinal disorders
Common: nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, anorexia.
Rare: gastritis, gastrointestinal haemorrhage, haematemesis, haemorrhagic diarrhea, melaena, gastrointestinal ulcer (with or without haemorrhage and perforation).
Very rare: colitis (including haemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, oesophageal disorders, diaphragm-like intestinal stenosis, pancreatitis.
Hepatobiliary disorders
Common: increased transaminases.
Rare: hepatitis, jaundice, liver disorders.
Very rare: fulminant hepatitis, hepatic necrosis, hepatic failure.
Skin and subcutaneous tissue disorders
Common: rash.
Rare: urticaria.
Very rare: Bullous eruptions, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, hair loss, photosensitivity reactions, purpura, allergic purpura, pruritus.
Renal and urinary disorders
Very rare: acute renal failure, haematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis.
General disorders and administration site conditions
Rare: edema.
Very rare: asthenia
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
Expiry and Retention
Expiration: see the expiry date printed on the package.
The expiry date refers to the product in intact packaging, correctly stored. Warning: do not use the medicine after the expiry date shown on the package.
Storage conditions:
This medicinal product does not require any storage conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Keep this medicine out of the sight and reach of children.
Composition
Gastro-resistant tablets 50 mg
One tablet contains:
Active ingredient: Diclofenac sodium 50 mg.
Excipients: Microcrystalline cellulose, lactose monohydrate, maize starch, magnesium stearate, cellulose acetate phthalate, diethyl phthalate, titanium dioxide, povidone
Prolonged-release tablets 100 mg
One tablet contains:
Active ingredient: Diclofenac sodium 100 mg.
Excipients: Talc, ethylcellulose, magnesium stearate, povidone, hydroxypropylcellulose, diethyl phthalate, titanium dioxide
Pharmaceutical form and content
Gastro-resistant tablets 50 mg for oral use. Box of 30 tablets
Prolonged-release tablets 100 mg for oral use. Box of 20 tablets
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
DICLOREUM tablets
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Gastro-resistant tablets 50 mg: Diclofenac sodium 50 mg
Prolonged-release tablets 100 mg: Diclofenac sodium 100 mg
For excipients, see 6.1
03.0 PHARMACEUTICAL FORM
Gastro-resistant tablets.
Prolonged-release tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Joint localization rheumatic diseases: rheumatoid arthritis, osteoarthritis.
Rheumatic diseases with extra-articular localization: periarthritis, bursitis, tendinitis, myositis, lumbosciatica.
Inflammation and edema of post-traumatic origin.
04.2 Posology and method of administration
Gastro-resistant tablets 50 mg: Attack therapy: 1 tablet, 3 times a day.
Extended therapy: 1 tablet, 2 times a day (morning and evening); in some cases a further reduction of the dosage is possible.
Administration during or after meals (breakfast and dinner) is preferable.
Prolonged-release tablets 100 mg: 1 tablet a day, after breakfast.
Rectal formulations of DICLOREUM are available; rectal therapy can be associated with oral therapy: 1 suppository, preferably in the evening and 1 50 mg tablet of DICLOREUM at breakfast in the morning.
In the treatment of elderly patients, the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above.
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.4).
The product should not be given to children under 14 years of age.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
History of gastrointestinal bleeding or perforation related to previous active treatments or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
The product must not be used in cases of gastric or duodenal ulcer, severe gastrointestinal disorders, severe renal and / or hepatic insufficiency, during intensive diuretic therapy, in subjects with ongoing bleeding and haemorrhagic diathesis, in case of alteration of the "hematopoiesis, during concomitant treatment with anticoagulants as it enhances their action (see section 4.5).
Severe heart failure.
Like other non-steroidal anti-inflammatory drugs, diclofenac is contraindicated in those subjects in whom they have occurred after taking acetylsalicylic acid or other prostaglandinsynthetase inhibitors, asthmatic attacks, urticaria, acute rhinitis.
DICLOREUM is also contraindicated in pregnancy and during lactation (see section 4.6).
04.4 Special warnings and appropriate precautions for use
Undesirable effects can be minimized with the use of 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).
The use of DICLOREUM should be avoided concomitantly with NSAIDs, including selective COX-2 inhibitors.
Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.8).
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 increased 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 taking low doses of 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 oral 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 Dicloreum the treatment should be discontinued.
NSAIDs should be administered with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section 4.8).
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.
Clinical studies and epidemiological data suggest that the use of diclofenac, especially at high doses (150 mg / day) and for long-term treatment, may be associated with a modest increased risk of arterial thrombotic events (eg. myocardium or stroke).
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with diclofenac after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular events (eg, hypertension, hyperlipidaemia, diabetes mellitus, smoking).
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. DICLOREUM should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
Due to the importance of prostaglandins for the maintenance of renal blood flow, particular caution is required or the exclusion from the use of DICLOREUM in case of renal hypoperfusion, renal insufficiency, thromboembolic phenomena in the history, in patients treated with diuretics and in those after major surgery.
During prolonged treatment with Dicloreum, as with other non-steroidal anti-inflammatory drugs, checks of blood count and liver and kidney function are indicated as a precautionary measure.
Accurate diagnosis and close medical surveillance are mandatory in patients with severe hepatic insufficiency.
If liver function parameters are persistently altered or worsened, treatment with DICLOREUM should be discontinued. Particular caution should be exercised in patients with hepatic porphyria as DICLOREUM could trigger an attack.
Due to the interaction with the metabolism of arachidonic acid, the drug can cause bronchospasm and possibly shock and other allergic phenomena in asthmatics and predisposed subjects.
In the treatment of underweight patients it is recommended to administer the lowest effective dose.
The use of DICLOREUM, like any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women who intend to become pregnant.
DICLOREUM should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
04.5 Interactions with other medicinal products and other forms of interaction
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4).
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).
When administered together with other preparations containing digoxin, diclofenac may raise its plasma concentration, but clinical signs of overdose have not yet been observed in such cases. The simultaneous administration of lithium salts is not recommended as it can lead to an increase in lithemia.
Diuretics, ACE inhibitors and angiotensin II antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g. dehydrated patients or elderly patients with impaired renal function) the co-administration of an ACE inhibitor or angiotensin II antagonist and agents that inhibit the cyclo-oxygenase system may lead to further deterioration of renal function, including possible acute renal failure, usually reversible. These interactions should be considered in patients taking Dicloreum 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.
Several non-steroidal anti-inflammatory drugs may potentiate the effect of potassium-sparing diuretics, requiring control of serum potassium levels.
The concomitant administration of systemic non-steroidal anti-inflammatory drugs may increase the manifestation of undesirable effects.
Like other NSAIDs, high-dose diclofenac can temporarily inhibit platelet aggregation.
Administration of non-steroidal anti-inflammatory drugs less than 24 hours before or after treatment with methotrexate should be done with caution, as these drugs can elevate blood concentrations and increase toxicity.
Although largely bound to proteins, it does not interfere for example with the protein binding of salicylates and prednisolone.
It does not negatively affect glucose metabolism in diabetics and in healthy subjects.
Some clinical studies have shown that diclofenac can be administered in combination with oral antidiabetic agents, without affecting their clinical effect. However, there are isolated reports of hypoglycemic and hyperglycemic effects due to diclofenac; hypoglycemic therapy then requires a dosage adjustment.
DICLOREUM may increase the nephrotoxicity of cyclosporine through its inhibitory effect on kidney prostaglandins.
04.6 Pregnancy and lactation
The product should not be used during pregnancy and breastfeeding.
Pregnancy:
Inhibition of prostaglandin synthesis can adversely affect pregnancy and / or embryo / fetal development.
Results of 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 cardiac malformations increased from less than 1% up to approximately 1.5%. The risk has been considered to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased loss of pre- and post-implantation and of embryo-fetal mortality.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose
the fetus to:
cardiopulmonary toxicity (with premature closure of the arterial duct 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.
Feeding time:
Although diclofenac passes into breast milk in negligible quantities at a dose of 150 mg per day, it is recommended not to administer the product during lactation.
04.7 Effects on ability to drive and use machines
Patients who experience dizziness or other central nervous disorders after the use of diclofenac should refrain from driving a vehicle or operating machinery that requires integrity of alertness.
04.8 Undesirable effects
Gastrointestinal: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or haemorrhage, sometimes fatal, may occur, particularly in the elderly (see section 4.4).
Should epigastric pain occur, the doctor should be consulted.
Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena (dark stools), haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of DICLOREUM (see section 4.4).
Gastritis and colon disorders have been observed less frequently.
Edema, hypertension and heart failure have been reported in association with NSAID treatment.
Clinical studies and epidemiological data suggest that the use of diclofenac, especially at high doses (150 mg / day) and for long-term treatment, may be associated with a modest increased risk of arterial thrombotic events (eg. myocardium or stroke) (see section 4.4).
Rarely, allergic manifestations such as skin rash, itching, asthmatic attacks and / or anaphylactic or anaphylactoid reactions, accompanied or not by hypotension, may appear.
Bullous reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), photosensitivity reactions and severe skin reactions such as exudative erythema multiforme (very rarely).
CNS disturbances such as headache, excitation, irritability, insomnia, asthenia, dizziness, convulsions, sensory or visual disturbances, tinnitus have been reported sporadically.
Particularly in prolonged treatments, peripheral edema, increased transaminases, jaundice, alterations in hematopoiesis (leukopenia, thrombocytopenia, agranulocytosis, aplastic or haemolytic anemia), renal failure, nephrotic syndrome, hair loss may occur. In isolated cases: urinary abnormalities, interstitial nephritis, liver function disorders, including hepatitis with or without jaundice, in some rare cases fulminant.
04.9 Overdose
Treatment of acute poisoning with non-steroidal anti-inflammatory drugs essentially consists of supportive and symptomatic measures.
Nothing is yet known about the typical clinical picture resulting from an overdose.
Therapeutic measures to be taken in case of overdose are as follows:
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 failure, 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 their high binding to plasma proteins and their considerable metabolism.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anti-inflammatory and antirheumatic, non-steroidal (Diclofenac). ATC code: M01AB05.
Mechanism of action / pharmacodynamic effects:
Diclofenac sodium - active ingredient of DICLOREUM - is a non-steroidal anti-inflammatory substance belonging to the class of arylacetics.
Pharmacodynamic tests have shown:
anti-inflammatory activity;
analgesic activity;
antipyretic activity.
The inhibition of prostaglandin biosynthesis is considered to be a major part of its mechanism of action.
05.2 Pharmacokinetic properties
Absorption of the product after oral and rectal administration is complete and plasma concentration is dose-dependent.
Peak serum levels appear within 90 minutes with oral forms, within 30 minutes with suppositories, and at the 6th hour after administration of the delayed form.
The product has a serum protein binding of 99.7%, is metabolised in the liver and excreted in part (2/3) by the kidney and the remainder with the bile and faeces.
05.3 Preclinical safety data
In animal toxicity tests, the product shows, in relation to pharmacologically active doses, a wide tolerance margin for both acute and protracted treatment (chronic toxicity).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Gastro-resistant tablets 50 mg :
Microcrystalline cellulose, lactose, maize starch, magnesium stearate, cellulose acetophthalate, diethyl phthalate, titanium dioxide, polyvinylpyrrolidone.
Prolonged-release tablets 100 mg :
Talc, ethylcellulose, magnesium stearate, polyvinylpyrrolidone, hydroxypropylcellulose, diethylphthalate, titanium dioxide.
06.2 Incompatibility
None.
06.3 Period of validity
In intact packaging: 5 years.
06.4 Special precautions for storage
No special storage precautions.
06.5 Nature of the immediate packaging and contents of the package
Gastro-resistant tablets 50 mg: Cardboard box of 30 tablets containing 2 blisters of 15 tablets. each.
Prolonged-release tablets 100 mg: Cardboard box of 20 tablets containing 2 blisters of 10 tablets. each.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
ALFA WASSERMANN S.p.A.
Registered office: Contrada S. Emidio, s.n.civ.
65020 - ALANNO (Pescara)
Administrative office: Via Ragazzi del "99, 5
40133 - BOLOGNA
08.0 MARKETING AUTHORIZATION NUMBER
30 gastro-resistant tablets 50 mg: A.I.C. n ° 024515049
20 prolonged-release tablets 100 mg: A.I.C. n ° 024515088
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
30 gastro-resistant tablets 50 mg: 16.12.81 (OJ 23.01.82) / 01.06.05
20 prolonged-release tablets 100 mg: 20.12.84 (OJ 23.02.85) / 01.06.05
10.0 DATE OF REVISION OF THE TEXT
01/05/2007
