Active ingredients: diclofenac
VOLTAREN 50 mg gastro-resistant tablets
Voltaren package inserts are available for pack sizes:- VOLTAREN 50 mg gastro-resistant tablets
- VOLTAREN 100 mg prolonged-release tablets VOLTAREN 75 mg prolonged-release tablets
- VOLTAREN 50 mg soluble tablets
- VOLTAREN 75 mg / 3 ml solution for injection for intramuscular use
- VOLTAREN 100 mg suppositories
Why is Voltaren used? What is it for?
Pharmacotherapeutic group
Non-steroidal anti-inflammatory and antirheumatic.
Therapeutic indications
Inflammatory and degenerative rheumatic diseases such as:
- rheumatoid arthritis, ankylosing spondylitis
- arthrosis
- non-articular rheumatism
Pain from inflammation of non-rheumatic origin or following a trauma.
Treatment of menstrual pains.
Contraindications When Voltaren should not be used
- Hypersensitivity to the active substance or to any of the excipients
- Hypersensitivity to other analgesics, antipyretics, non-steroidal anti-inflammatory drugs and in particular to 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 (see "Special warnings").
- Severe hepatic insufficiency.
- Severe renal insufficiency.
- Overt congestive heart failure (NYHA class II-IV), ischemic heart disease, peripheral arterial disease and / or cerebral vascular disease.
- 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").
- Voltaren 50 mg gastro-resistant tablets is also contraindicated in pediatric age (
Precautions for use What you need to know before taking Voltaren
General informations
Undesirable effects can be minimized by administering the lowest effective dose for the shortest duration necessary to control symptoms (see "Dose, method and time of administration" and the paragraphs below on gastrointestinal and cardiovascular risks).
The use of diclofenac concomitantly with other systemic NSAIDs, including selective cyclo-oxygenase-2 inhibitors, should be avoided due to the lack of any evidence showing synergistic benefits and based on potential additive side effects.
Elderly: 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, Voltaren can mask the signs and symptoms of infections due to its pharmacodynamic properties.
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 diclofenac to patients with symptoms indicative of gastrointestinal (GI) disorders or with a history indicative of gastric or intestinal ulceration, bleeding or perforation (see "Side effects"). 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 Voltaren 50 mg gastro-resistant tablets 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 insufficiency, 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 (eg before or after major surgery) (see "Contraindications").
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. Voltaren 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 hypertension and / or congestive heart failure (NYHA class I) as fluid retention and edema have been reported in association with NSAID treatment.
Clinical trials and epidemiological data consistently indicate an increased risk of arterial thrombotic events (eg, myocardial infarction or stroke) associated with the use of diclofenac, especially at high doses (150 mg / day) and with long-term treatment.
Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with diclofenac after careful consideration.
Since the cardiovascular risks of diclofenac may increase with dose and duration of exposure, the shortest possible duration and the lowest effective daily dose should be used. The response to therapy and the need for symptom improvement should be reassessed periodically.
Patients with congestive heart failure (NYHA class I), established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with diclofenac after careful consideration.
Patients should be alert for signs and symptoms of serious atherothrombotic events (e.g. chest pain, shortness of breath, weakness, slurred speech), which can occur without warning. Patients should be instructed to contact a physician immediately if any of these events occur.
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 allergic to other substances, eg. with skin reactions, itching or hives.
Interactions Which drugs or foods can modify the effect of Voltaren
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
The following interactions include those seen 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 Voltaren 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 concomitant 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): Co-administration of systemic NSAIDs, including diclofenac, and SSRIs may increase the risk of gastrointestinal bleeding (see "Precautions for use").
Antidiabetici: 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, monitoring of blood glucose levels is recommended as a precautionary measure in case of concomitant therapy.
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 methotrexate treatment 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 doses 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:
Fertility, pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Fertility
As with other NSAIDs, the use of Voltaren may impair female fertility and is not recommended in women wishing to conceive. Discontinuation of diclofenac in women who have difficulty conceiving or who are undergoing infertility testing should be considered.
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% 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.
Consequently, Voltaren 50 mg gastro-resistant tablets are 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 Voltaren during breastfeeding to avoid undesirable effects in the infant.
Effects on ability to drive or 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 excipients
Voltaren 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 medicinal product.
Hydrogenated polyhydric castor oil
Voltaren gastro-resistant tablets contain hydrogenated polyhydric castor oil. It can cause stomach upset and diarrhea.
Dosage and method of use How to use Voltaren: Dosage
Undesirable effects can be minimized by administering the lowest effective dose for the shortest duration necessary to control symptoms (see "Precautions for use").
General population
As a rule, the starting daily dosage of diclofenac is 100-150 mg. In milder cases, as well as in long-term therapies, 75-100 mg per day is usually sufficient. The daily dosage should generally be prescribed in 2-3 divided doses.
In primary dysmenorrhea, the daily dosage, which must be individually adjusted, is 50-150 mg; A dose of 50-100 mg should be given initially and, if necessary, increased during subsequent menstrual cycles, up to a maximum of 150 mg per day. Treatment should begin when the first symptoms appear and, depending on the symptoms, continue for a few days.
To eliminate nighttime pain and morning stiffness, tablet treatment during the day can be supplemented by the administration of a suppository at bedtime (up to a maximum total daily dosage of 150 mg).
The tablets should be swallowed whole with some liquid, and should not be crushed or chewed. Therefore, in all cases where 75 mg unit doses are required, another pharmaceutical form of Voltaren should be used.
Special populations
Pediatric patients
Voltaren gastro-resistant tablets should not be used in children and adolescents under 14 years of age.
Senior citizens
In the treatment of elderly patients, the dosage should be carefully established by the physician who will have to evaluate a "possible reduction of the dosages indicated above (see" Precautions for use ").
Patients with congestive heart failure (NYHA 1) or significant cardiovascular risk factors Patients with significant risk factors for cardiovascular disease should only be treated with diclofenac after careful consideration (see "Precautions for use").
Renal impairment
Voltaren is contraindicated in patients with severe renal insufficiency (see "Contraindications").
Caution is recommended when administering Voltaren to patients with mild to moderate renal impairment (see "Precautions for use"). Hepatic impairment Voltaren is contraindicated in patients with severe hepatic impairment (see "Contraindications").
Caution is recommended when administering Voltaren to patients with mild to moderate hepatic impairment (see "Precautions for use").
Overdose What to do if you have taken too much Voltaren
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
Treatment of acute non-steroidal anti-inflammatory poisoning, including diclofenac, essentially consists of supportive measures and symptomatic treatment. In case of complications such as hypotension, renal failure, seizures, gastrointestinal disturbances and respiratory depression, supportive and treatment measures should be adopted. symptomatic.
Therapeutic measures to be taken in the event of an 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 used in case of complications (hypotension, renal failure, 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 their high binding to plasma proteins and their considerable metabolism.
In case of accidental ingestion / intake of an excessive dose of Voltaren, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of Voltaren, ask your doctor or pharmacist.
Side Effects What are the side effects of Voltaren
Like all medicines, Voltaren 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,
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.
Eye disorders
Very rare: visual disturbances, blurred vision, diplopia.
Ear and labyrinth disorders
Common: dizziness.
Very rare: tinnitus, hearing impairment.
Cardiac pathologies
Uncommon *: myocardial infarction, heart failure, palpitations, chest pain.
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, decreased appetite.
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 dermatitis, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, hair loss, photosensitivity reactions, purpura, anaphylactoid 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.
* Frequency reflects high dose long-term treatment data (150 mg / day).
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. Undesirable effects can also be reported directly via the national reporting system at "https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse". By reporting undesirable effects you can help provide more information on the safety of this medicine
Expiry and Retention
Expiry: 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.
Conservation conditions
Store below 30 ° C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the sight and reach of children.
Composition
One tablet contains
Active ingredient: diclofenac sodium 50 mg.
Excipients: corn starch; magnesium stearate; anhydrous colloidal silica; lactose monohydrate; microcrystalline cellulose; povidone; sodium starch carboxymethyl A; talc; hypromellose; hydrogenated polyhydric castor oil; red iron oxide; yellow iron oxide; titanium dioxide; polyacrylate dispersion 30 percent copolymer; macrogoli; silicone anti-foam emulsion.
Pharmaceutical form and content
Gastro-resistant tablets: box of 30 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
VOLTAREN 50 MG FOOD-RESISTANT TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One gastro-resistant tablet contains:
Active ingredient: diclofenac sodium 50 mg.
Excipients: lactose monohydrate, hydrogenated polyhydric castor oil.
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Gastro-resistant tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Inflammatory and degenerative rheumatic diseases:
• rheumatoid arthritis, ankylosing spondylitis;
• arthrosis;
• extra-articular rheumatism.
Painful states of inflammation of extra-rheumatic or post-traumatic origin.
Symptomatic treatment of primary dysmenorrhea.
04.2 Posology and method of administration
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 tablets should be swallowed whole with some liquid, and should not be split or chewed.
Adults
As a rule, the starting daily dosage is 100-150 mg. In milder cases, as well as in long-term therapies, 75-100 mg per day is usually sufficient.
The daily dosage should generally be prescribed in 2-3 divided doses. To eliminate nighttime pain and morning stiffness, tablet treatment during the day can be supplemented by the administration of a suppository at bedtime (up to a maximum total daily dosage of 150 mg).
In primary dysmenorrhea, the daily dosage, which must be individually adjusted, is 50-150 mg; A dose of 50-100 mg should be given initially and, if necessary, increased during subsequent menstrual cycles, up to a maximum of 150 mg per day. Treatment should begin when the first symptoms appear and, depending on the symptoms, continue for a few days.
In the treatment of elderly patients, the posology must be carefully established by the physician who will have to evaluate a possible reduction of the dosages indicated above (see also section 4.4).
Children and adolescents
Voltaren 50 mg gastro-resistant tablets should not be used in children and adolescents under 14 years of age.
04.3 Contraindications
• 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 active treatments or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
• Last trimester of pregnancy and during lactation (see section 4.6).
• Severe cardiac, hepatic or renal failure (see section 4.4).
• In subjects with ongoing bleeding and bleeding diathesis.
• Like other non-steroidal anti-inflammatory drugs (NSAIDs), Voltaren is also contraindicated in those subjects who have experienced asthma attacks, urticaria, acute rhinitis after taking acetylsalicylic acid or other anti-inflammatory drugs.
• The product should not be used during intensive diuretic therapy
• In case of alterations in hematopoiesis
• Voltaren 50 mg gastro-resistant tablets is also contraindicated in pediatric age (
04.4 Special warnings and appropriate precautions for use
General informations
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 diclofenac concomitantly with other systemic NSAIDs, including selective cyclo-oxygenase-2 inhibitors, should be avoided due to the lack of any evidence showing synergistic benefits and based on potential additive side effects.
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, Voltaren can mask the signs and symptoms of infections due to its pharmacodynamic properties.
Important information about some of the excipients
Voltaren gastro-resistant tablets contain lactose and therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Voltaren gastro-resistant tablets contain hydrogenated polyhydric castor oil which can cause stomach upset and diarrhea.
Gastrointestinal effects
During treatment with all NSAIDs, including diclofenac, they have been reported and may occur, 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 diclofenac to patients with symptoms suggestive of gastrointestinal disorders or with a history indicative of gastric or intestinal ulceration, bleeding or perforation (see section 4.8. ).
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 section 4.8).
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 (see also section 4.2).
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 paragraph 4.5).
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 section 4.5).
Close surveillance and caution should also be exercised in patients with ulcerative colitis or Crohn's disease, as these conditions may be exacerbated (see section 4.8).
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, special caution is required in case of heart 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) (see section 4.3).
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 section 4.8). In the early stages of therapy, patients appear to be at highest risk for these reactions: the onset of the reaction occurs in most cases within the first month of treatment. Voltaren 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 (eg, nasal polyps), chronic obstructive pulmonary disease or chronic respiratory tract infections (especially when linked to symptoms similar to allergic rhinitis), are more common than in others patients reactions to NSAIDs such as asthma exacerbations (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 allergic to other substances, eg. with skin reactions, itching or hives.
Other effects
The use of diclofenac, as well as any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women intending to become pregnant.
Voltaren 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
The following interactions include those seen with diclofenac gastro-resistant tablets and / or other pharmaceutical forms of diclofenac.
Lithium: when administered together with lithium-containing preparations, 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 concentrations. 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 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 Voltaren concomitantly with ACE inhibitors or angiotensin II antagonists. Patients should be adequately hydrated and monitoring of renal function 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 section 4.4).
Other NSAIDs and corticosteroids: concomitant use of diclofenac and other systemic non-steroidal anti-inflammatory drugs may increase the frequency of gastrointestinal undesirable effects (see section 4.4).
Anticoagulants and antiplatelet agents: Caution is recommended as co-administration may increase the risk of bleeding (see section 4.4). Although there is no indication from clinical trial data of an "influence of diclofenac on the anticoagulant effect", there have been isolated reports of an increased risk of haemorrhage with concomitant use of diclofenac and anticoagulant therapy. For these patients it is recommended. careful monitoring.
Selective Serotonin Reuptake Inhibitors (SSRIs): co-administration of systemic NSAIDs, including diclofenac, and SSRIs may increase the risk of gastrointestinal bleeding (see section 4.4).
Antidiabetic: Clinical studies have shown that diclofenac can be taken concomitantly with oral antidiabetics without modifying 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, monitoring of blood glucose levels is recommended as a precautionary measure in case of concomitant therapy.
Methotrexate: diclofenac can inhibit renal tubular release of methotrexate by increasing its levels. Caution is advised when administering NSAIDs, including diclofenac, 24 hours before or after methotrexate treatment as blood concentrations of methotrexate and consequently the toxicity of this substance may increase.
Ciclosporin: due to its effect on renal prostaglandins, diclofenac, like other NSAIDs, may increase the nephrotoxicity of cyclosporine. Therefore, diclofenac should be administered at lower doses 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.
04.6 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 abortion 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% 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 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, diclofenac 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 Voltaren during breastfeeding to avoid undesirable effects in the infant.
Fertility
As with other NSAIDs, the use of Voltaren may impair female fertility and is not recommended in women wishing to conceive. Discontinuation of diclofenac in women who have difficulty conceiving or who are undergoing infertility testing should be considered (see also section 4.4).
04.7 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.
04.8 Undesirable effects
Adverse reactions (Table 1) are listed by frequency, most frequent first, using the following convention: common (≥ 1/100,
The following effects include those reported with short-term or long-term use.
Table 1
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).
04.9 Overdose
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
Treatment of acute non-steroidal anti-inflammatory poisoning, including diclofenac, essentially consists of supportive measures and symptomatic treatment. In case of complications such as hypotension, renal failure, seizures, gastrointestinal disturbances and respiratory depression, supportive and treatment measures should be adopted. symptomatic.
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.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: non-steroidal anti-inflammatory and antirheumatic, acetic acid derivatives and related substances
ATC code: M01A B05
Mechanism of action
Voltaren contains sodium diclofenac, a non-steroidal molecule with strong antirheumatic, anti-inflammatory, analgesic and antipyretic properties. The experimentally demonstrated inhibition of prostaglandin biosynthesis is considered fundamental for its mechanism of action. Prostaglandins play an important role in triggering inflammation, pain and fever.
Pharmacodynamic effects
In rheumatic diseases, Voltaren's anti-inflammatory and analgesic properties cause the clinical response to be characterized by a pronounced improvement in signs and symptoms, such as pain at rest, pain on movement, morning stiffness, joint swelling as well as by an improvement in function.
In post-traumatic and post-operative inflammatory conditions, Voltaren rapidly resolves both spontaneous pain and pain on movement, reduces inflammatory swelling and wound edema.
Voltaren has also shown a marked analgesic effect in moderate or severe pain of non-rheumatic origin in clinical trials. Clinical studies have also shown that Voltaren is able to relieve pain in primary dysmenorrhea.
05.2 Pharmacokinetic properties
Absorption
After passing through the stomach, diclofenac is completely absorbed by the gastro-resistant tablets. Although absorption is rapid, its onset may be delayed due to the gastro-resistant coating of the tablet.
The mean peak plasma concentration is 1.5 mcg / ml (5 mcmol / l) and is obtained approximately two hours after ingestion of a 50 mg tablet. The amount absorbed is proportional to the administered dose.
The passage of a tablet through the stomach is slower when given with or after meals than when given before meals, but the amount of diclofenac absorbed remains the same.
Since approximately half of diclofenac is metabolised in the liver due to the first pass effect, the area under the curve (AUC) following oral or rectal administration is approximately half that obtained after administration of an equivalent dose. injecting.
The pharmacokinetic profile remains unchanged even after repeated administration. There is no accumulation phenomena if the recommended intervals between one dose and the next are observed.
Administration in children of equivalent doses (expressed in mg / kg body weight) results in plasma concentrations similar to those observed in adults.
Distribution
Protein binding: 99.7% of diclofenac is bound to plasma proteins, mainly albumin (99.4%). The calculated apparent volume of distribution is 0.12-0.17 l / kg.
Diclofenac penetrates the synovial fluid, where plasma concentrations are measured 2-4 hours after reaching the plasma peak. The apparent half-life for elimination from the synovial fluid is 3-6 hours.
2 hours after reaching peak plasma values, the concentrations of the active substance are already higher in the synovial fluid than in the plasma and remain so for up to 12 hours.
Biotransformation
The biotransformation of diclofenac occurs in part by glucuronidation of the molecule as such, but mainly by single or multiple hydroxylation and methoxylation, giving rise to different phenolic metabolites (diclofenac-3 "-hydroxy-, 4" -hydroxy-, 5-hydroxy-, 4 "-5-dihydroxy-, and 3" -hydroxy-4 "-methoxy-diclofenac). The latter are largely converted to glucuronic conjugates. Two of these phenolic metabolites are biologically active, but to a much lesser extent than diclofenac .
Elimination
Total systemic clearance of diclofenac from plasma is 263 ± 56 ml / min (mean value ± standard deviation). The terminal plasma half-life is 1-2 hours. Four of the metabolites, including the two active ones, have a short plasma half-life of 1-3 hours. One metabolite, 3 "-hydroxy-4" -methoxy-diclofenac, has a much longer "plasma half-life; however, this metabolite is virtually inactive.
About 60% of the administered dose is excreted in the urine in the form of glucuronic conjugate of the intact molecule and as metabolites, most of which are also converted to glucuronic conjugates; less than 1% is excreted as unchanged substance. The remainder of the administered dose is excreted as metabolites with the bile in the faeces.
Characteristics in patients
No relevant differences in drug absorption, metabolism, excretion related to age were observed.
In patients with renal insufficiency, if the normal dosage regimen is observed, there is no accumulation of the unchanged active substance after administration of a single dose. With creatinine clearance values, theoretical steady-state plasma levels of the hydroxylated metabolites are approximately 4 times higher than in normal subjects. However, the metabolites are eventually excreted via the bile.
In patients with chronic hepatitis or non-decompensated cirrhosis, the kinetics and metabolism of diclofenac are the same as in patients without liver disease.
05.3 Preclinical safety data
Diclofenac
Preclinical data from acute and repeated dose toxicity studies as well as those from genotoxicity, mutagenicity and carcinogenicity studies with diclofenac did not show any specific risk for humans at usual therapeutic doses.
Inhibitors of prostaglandin synthesis
There is no further information on preclinical data other than that already reported elsewhere in this Summary of Product Characteristics (see section 4.6).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Cornstarch; magnesium stearate; anhydrous colloidal silica; lactose monohydrate; microcrystalline cellulose; povidone; sodium starch carboxymethyl A; talc; hypromellose; hydrogenated polyhydric castor oil; red iron oxide; yellow iron oxide; titanium dioxide; polyacrylate dispersion 30 percent copolymer; macrogoli ,; silicone anti-foam emulsion.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Store below 30 ° C.
Voltaren gastro-resistant tablets should be kept out of the sight and reach of children.
06.5 Nature of the immediate packaging and contents of the package
PVC / PE / PVDC blisters; pack of 30 gastro-resistant tablets of 50 mg.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Novartis Farma S.p.A.
Largo Umberto Boccioni, 1 - 21040 Origgio (VA)
08.0 MARKETING AUTHORIZATION NUMBER
AIC n. 023181011
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 21 May 1979; renewal date: 1 June 2010
10.0 DATE OF REVISION OF THE TEXT
AIFA Determination of 9 January 2012
