Active ingredients: Diclofenac
DICLOFENAC MYLAN GENERICS 100 mg prolonged-release tablets
Why is Diclofenac used - Generic Drug? What is it for?
DICLOFENAC MYLAN GENERICS contains the active substance diclofenac which belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs).
This medicine is indicated in the treatment of:
- inflammatory rheumatic diseases such as rheumatoid arthritis, ankylosing spondylitis, arthrosis, non-joint rheumatism;
- pain caused by inflammation of non-rheumatic origin or by trauma;
- menstrual cramps.
Contraindications When Diclofenac - Generic Drug should not be used
Do not take DICLOFENAC MYLAN GENERICS
- if you are allergic to diclofenac or any of the other ingredients of this medicine (listed in section 6);
- if you suffer from injury (ulcer), bleeding or perforation in the stomach or intestines;
- if in the past you have suffered from bleeding or perforation in the stomach or intestines caused by NSAID treatments or if you have suffered from recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding);
- if you are in the last trimester of pregnancy or if you are breast-feeding (see section "Pregnancy and breast-feeding");
- if you have severe liver, kidney or heart disease (liver, kidney or heart failure);
- if you have ever had a heart attack, stroke or 'blockage of blood vessels to the heart or brain;
- if you have or are prone to blood loss (haemorrhage or haemorrhagic diathesis);
- if you have or have suffered from blood circulation problems (peripheral arterial disease);
- if you have previously had an allergic reaction such as asthma, sneezing or skin irritation when taking pain relievers containing acetylsalicylic acid or other pain / inflammation / fever medicines that belong to the NSAID group;
- if you are taking high doses of medicines that help pass urine (diuretics);
- if you have an "alteration in the production of blood cells;
- if you are under the age of 14.
Precautions for use What you need to know before taking Diclofenac - Generic Drug
Talk to your doctor or pharmacist before taking DICLOFENAC MYLAN GENERICS.
Tell your doctor and take this medicine with caution in the following cases:
- if you are elderly or debilitated, in this case the use of the lowest effective dose is recommended to avoid an increase in the frequency of side effects, especially stomach bleeding and perforation, which can be fatal;
- if you have stomach or bowel problems such as lesions (ulcer), ulcerative colitis or Crohn's disease, in these cases an accurate diagnosis and close supervision of the doctor is necessary during treatment;
- if you have mild or moderate heart problems (congestive heart failure, high blood pressure - hypertension, ischemic heart disease, circulation problems) or have a high risk of developing them, in these cases it is recommended to use the lowest effective dose and for shortest time possible;
- if you have liver function problems, or if you have a disease affecting the liver called liver porphyria, in these cases an accurate diagnosis and close supervision by your doctor is required during treatment.
- If you develop signs and symptoms of a liver problem or other manifestations, for example eosinophilia (a blood problem) or skin irritation, your doctor may tell you to stop treatment.
- if you have problems with kidney function, as the medicine can cause fluid retention and swelling due to a build up of fluids (edema);
- if you suffer from asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (nasal polyps), obstructive lung disease or chronic respiratory tract infections or other allergic reactions such as skin reactions, itching or hives. In these cases you may have difficulty breathing (bronchospasm) or even severe allergic reactions such as anaphylactic shock.
- if you have blood disorders, in this case the platelet aggregation must be carefully monitored because there could be problems with coagulation especially for prolonged treatments.
Like other NSAIDs, diclofenac can mask the signs and symptoms of infection.
Tell your doctor if you experience the following symptoms during treatment:
- stomach or bowel bleeding or ulceration. In this case stop the treatment. Caution is advised in people taking other medicines that may increase the risk of ulceration or bleeding such as acetylsalicylic acid, systemic corticosteroids, anticoagulants, antiplatelet agents or selective inhibitors reuptake of serotonin (see section "Other medicines and DICLOFENAC MYLAN GENERICS"). In these cases, your doctor may also prescribe a medicine to protect your stomach;
- if you experience severe skin reactions (exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis). These can mainly occur within the first month of treatment. Stop treatment at the first appearance of a rash or mucosal lesion or any other reaction.
This medicine can lead to an increased risk of heart attack or stroke, especially if high dosages of the medicine are used or for prolonged treatments. Do not exceed the recommended dose or duration of treatment.
Before taking diclofenac make sure your doctor knows:
- if you have heart problems, a history of stroke or think you may be at risk for these conditions;
- if you smoke;
- if you have diabetes;
- if you suffer from chest pain caused by heart problems (angina), blood clots, high blood pressure, high cholesterol or triglycerides.
Do not exceed the recommended dose or duration of treatment. Undesirable effects can be minimized by using the lowest effective dose for the shortest duration necessary.
Children and adolescents
DICLOFENAC MYLAN GENERICS is not recommended for children below 14 years due to a lack of data on the safety and efficacy of this medicine.
Interactions Which drugs or foods can modify the effect of Diclofenac - Generic Drug
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
DICLOFENAC MYLAN GENERICS may affect or be affected by other medicines containing the following active substances:
- lithium, a medicine used for psychiatric disorders;
- digoxin, a medicine used to treat heart problems;
- medicines used to lower high blood pressure such as diuretics, beta blockers, angiotensin converting enzyme (ACE) inhibitors or angiotensin II antagonists;
- other anti-inflammatory medicines, both NSAIDs and corticosteroids;
- anticoagulant and antiplatelet medicines used to improve blood circulation such as warfarin;
- medicines used for depression such as selective serotonin reuptake inhibitors (SSRIs);
- medicines used for diabetes;
- methotrexate, a medicine used for psoriasis, rheumatism and some cancers;
- cyclosporine, a medicine used after transplants;
- quinolone antibiotics, used to treat infections;
- phenytoin, a medicine used for epilepsy;
- colestipol and cholestyramine, medicines used to reduce the intestinal absorption of fat;
- sulfinpyrazone, voriconazole or other medicinal products inhibiting the metabolism of diclofenac, as they may lead to an increase in the effects of the medicinal product.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Do not take this medicine during the third trimester of pregnancy as it may cause fetal toxicity and problems during delivery
Take this medicine only if strictly necessary and under the direct supervision of your doctor in the first and second trimester of pregnancy or if you are planning to become pregnant.
Feeding time
Do not take this medicine while breastfeeding because diclofenac passes into breast milk.
Fertility
The use of diclofenac may impair female fertility and is not recommended in women attempting to conceive. Stop using this medicine if you have difficulty conceiving or are undergoing an infertility test.
Driving and using machines
This medicine can cause visual disturbances, dizziness, vertigo, somnolence. Avoid driving vehicles or using machines if you experience these symptoms.
DICLOFENAC MYLAN GENERICS contains lactose
This medicine contains a sugar, lactose monohydrate. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Dose, Method and Time of Administration How to use Diclofenac - Generic Drug: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
Swallow the tablets whole with some liquid, preferably with a meal.
Undesirable effects can be minimized by administering the lowest effective dose for the shortest duration necessary to control symptoms.
The recommended starting dose is 100-150 mg per day.
In milder cases, as well as in long-term therapy, 75 - 100 mg per day is usually sufficient. The daily dosage should be divided into 2-3 administrations.
To eliminate night pain and morning stiffness, treatment with tablets during the day can be supplemented by the administration of a suppository at bedtime (up to a maximum daily dosage of 150 mg).
Treatment of menstrual pain:
the recommended starting dose is 50-100 mg per day and may be increased to a maximum of 150 mg per day as needed. Start the treatment when the first symptoms appear and, depending on the symptoms, continue for a few days.
The daily dosage will be divided into 2-3 administrations.
Use in the elderly
When treating older people, the doctor will adjust the dosage according to the patient's condition
Overdose What to do if you have taken an overdose of Diclofenac - Generic Drug
If you take more DICLOFENACMYLAN GENERICS than you should
Overdose can cause symptoms such as vomiting, stomach or bowel bleeding, diarrhea, dizziness, ringing in the ears or seizures and in severe cases severe kidney and liver problems can occur.
In case of accidental ingestion / intake of an excessive dose of DICLOFENAC MYLAN GENERICS, notify your doctor immediately or contact the nearest hospital emergency department.
If you forget to take DICLOFENAC MYLAN GENERICS
Do not take a double dose to make up for a forgotten dose.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Diclofenac - Generic Drug
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience severe complaints, especially stomach or bowel pain or bleeding and dark stools, stop treatment immediately and tell your doctor.
The following side effects may occur:
Common (may affect up to 1 in 10 people)
- headache, dizziness;
- dizziness;
- nausea, vomiting, diarrhea, digestive disorders, abdominal pain, flatulence, decreased appetite.
- liver function problems (aume
Rare (may affect up to 1 in 1000 people)
- even severe allergic reactions such as anaphylactic and anaphylactoid reactions (including decrease in blood pressure and shock);
- drowsiness;
- asthma, breathlessness;
- stomach disorders such as gastritis, bleeding in the stomach and intestines, blood in the vomit, blood in the stool, stomach or bowel ulcer (with or without bleeding or perforation);
- liver problems such as hepatitis and jaundice;
- skin irritation (hives);
- swelling caused by a buildup of fluid (edema).
Very rare (may affect up to 1 in 10,000 people)
- decrease in blood platelets (thrombocytopenia);
- decrease in white blood cells (leukopenia, agranulocytosis);
- decrease in red blood cells (anemia, including haemolytic and aplastic anemia);
- swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing (angioneurotic edema);
- disorientation, depression, insomnia, nightmares, irritability, psychotic reactions;
- change in sensitivity in the limbs (paraesthesia), tremors,
- memory impairment, seizures, anxiety, inflammation of the brain (aseptic meningitis), taste disturbance, stroke;
- vision disturbances, blurred vision, double vision;
- perception of ringing in the ear (tinnitus) and worsening of hearing;
- increased perception of heartbeat, chest pain, impaired heart function (heart failure), heart attack;
- increased blood pressure, inflammation of the blood vessels;
- inflammation of the lung (pneumonia);
- inflammation of the intestines (colitis), Crohn's disease, constipation, intestinal blockage, inflammation of the mouth, tongue, esophagus or pancreas;
- severe liver problems (fulminant hepatitis, liver necrosis, liver failure);
- rash, blistering of the skin, redness of the skin, severe skin condition which can affect the areas around the mouth and other parts of the body (erythema multiforme), rare skin condition with blistering and bleeding of the lips, eyes, mouth, nose and genitals (Stevens-Johnson syndrome), severe skin disease (toxic epidermal necrolysis), peeling of the skin (exfoliative dermatitis);
- hair loss;
- increased sensitivity of the skin to sunlight, unusual bleeding and bruising under the skin (purpura), itching;
- kidney problems such as acute renal failure, nephrotic syndrome, interstitial nephritis, renal papillary necrosis;
- presence of blood or protein in the urine (haematuria, proteinuria).
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at: https: //www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after "EXP". The expiry date refers to the last day of that month
Store in the original package to protect the medicine from moisture.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What DICLOFENAC MYLAN GENERICS contains
DICLOFENAC MYLAN GENERICS 100 mg prolonged-release tablets:
- The active ingredient is diclofenac sodium. Each tablet contains 100 mg of diclofenac sodium.
- The other ingredients are: hydroxypropylcellulose, microcrystalline cellulose, maize starch, lactose monohydrate, povidone, cellulose acetate phthalate, magnesium stearate, triethyl citrate, titanium dioxide (E171)
Description of the appearance of DICLOFENAC MYLAN GENERICS and contents of the package
Prolonged-release tablets of 100 mg: box of 21 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
DICLOFENAC MYLAN GENERICS 100 MG PROLONGED RELEASE TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 100 mg prolonged-release tablet contains:
Active ingredient: diclofenac sodium 100 mg.
Excipient (s) with known effect: lactose monohydrate.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Prolonged-release tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Inflammatory and degenerative rheumatic diseases such as:
- rheumatoid arthritis and spondylitis
- ankylosing 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 administering the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
Dosage
As a rule, the starting daily dosage of diclofenac is 100 - 150 mg. In milder cases, as well as in long-term therapy, 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 night pain and morning stiffness, treatment with tablets 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, preferably with meals and should not be crushed or chewed.
Therefore, in all cases where 75 mg unit doses are required, another pharmaceutical form of diclofenac should be used.
Senior citizens
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).
Pediatric population
Diclofenac Mylan Generics should not be used in children and adolescents under 14 years of age.
04.3 Contraindications
- Hypersensitivity to the active substance, to other analgesics, antipyretics, non-steroidal anti-inflammatory drugs and in particular to acetylsalicylic acid or to any of the excipients listed in section 6.1
- 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 section 4.6).
- Severe hepatic insufficiency, severe renal insufficiency (see section 4.4).
- Overt congestive heart failure (NYHA class II-IV), ischemic heart disease, peripheral arterial disease and / or cerebrovascular vasculopathy.
- In subjects with ongoing bleeding and bleeding diathesis.
- Like other non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac is also contraindicated in patients who have experienced asthma attacks, urticaria or acute rhinitis after taking acetylsalicylic acid or other NSAIDs.
- During intensive diuretic therapy.
- In case of alterations in hematopoiesis.
Diclofenac should not be given to children under 14 years of age.
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 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 basic medical grounds, caution is required in the elderly. In particular, in frail elderly patients or in those with a low body weight, the use of the lowest effective dose is recommended.
Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.8).
As with other NSAIDs, allergic reactions, including anaphylactic / anaphylactoid reactions, may also occur in rare cases without prior exposure to diclofenac.
Like other NSAIDs, diclofenac 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 or 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 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 section 4.2).
Concomitant use of protective agents (proton pump inhibitors or misoprostol) should be considered for these patients and also for patients requiring concomitant use of medicinal products containing low dose acetylsalicylic acid (ASA) / aspirin or other medicinal products that may increase gastrointestinal risk (see below and section 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, antiplatelet agents such as aspirin or selective serotonin reuptake inhibitors (see section 4.5).
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 section 4.8).
Hepatic effects
Close medical surveillance is required when prescribing Diclofenac to patients with hepatic insufficiency as their 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, treatment with diclofenac 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 cases of heart and 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. Diclofenac Mylan Generics should be discontinued at the first appearance of 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 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 myocardial infarction). or stroke).
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. Response to therapy and the need for symptom improvement should be evaluated 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.
Hematological effects
During prolonged treatment with diclofenac, as with other NSAIDs, blood count checks are recommended.
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), they 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 who are allergic to other substances, eg. with skin reactions, itching or hives.
Other effects
The use of diclofenac, like any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women who intend to become pregnant.
Diclofenac Mylan Generics should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
Important information about some of the ingredients
Diclofenac Mylan Generics prolonged-release tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
The following interactions include those seen with diclofenac prolonged-release tablets and / or other pharmaceutical forms of diclofenac.
Lithium : when administered concomitantly, diclofenac can elevate plasma lithium concentrations. Monitoring of serum lithium levels is recommended.
Digoxin: When administered concomitantly, diclofenac can elevate plasma digoxin 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 should 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) coadministration 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 Diclofenac Mylan Generics 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 it may be associated with increased 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 or corticosteroids may increase the incidence of gastrointestinal side 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 effect of anticoagulants", there have been isolated reports of an increased risk of haemorrhage in patients receiving diclofenac concomitantly with anticoagulants. Careful monitoring is therefore 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 section 4.4).
Antidiabetics: Clinical studies have shown that diclofenac can be administered together with oral antidiabetic agents without affecting their clinical effect. However, isolated cases of both hypo- and hyperglycemic effects have been reported, with the need to modify the dosage of the agents. antidiabetics 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 treatment with methotrexate as blood concentrations of methotrexate and consequently the toxicity of this substance may increase.
Ciclosporin: Diclofenac, like other NSAIDs, may increase the nephrotoxicity of cyclosporine due to its effect on renal prostaglandins. Therefore, diclofenac should be administered at lower dosages than would be used in patients not on cyclosporine therapy.
Quinolone antibacterials: isolated cases of convulsions have been reported, 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 lactation
Inhibition of prostaglandin synthesis may adversely affect pregnancy and / or embryo / fetal development. Results of epidemiological studies suggest an increased risk of abortion and cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor in early stages of pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. The risk was considered to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased pre- and post-implantation loss 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 Mylan Generics is contraindicated during the third trimester of pregnancy.
Feeding time
Like other NSAIDs, diclofenac passes into breast milk in small amounts. Therefore, diclofenac should not be administered during breastfeeding to avoid undesirable effects in the infant.
Fertility
As with other NSAIDs, the use of Diclofenac Mylan Generics may impair female fertility and is not recommended in women attempting to conceive.
Discontinuation of diclofenac should be considered in women who have difficulties conceiving or who are undergoing investigation of infertility (see also section 4.4).
04.7 Effects on ability to drive and use machines
Patients who have experienced disturbed vision, dizziness, vertigo, somnolence or other central nervous system disorders with the use of diclofenac, should refrain from driving or using machines.
04.8 Undesirable effects
Especially at the beginning of the treatment, gastrointestinal disorders such as nausea, heartburn, vomiting, diarrhea, flatulence may occur.
If more serious disorders occur, in particular epigastric pain or overt or occult gastrointestinal bleeding (dark stools), the treatment should be discontinued and the doctor consulted.
Cardiovascular safety of NSAIDs
Edema, hypertension and heart failure have been reported in association with NSAID treatment.
Adverse reactions (Table 1) 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.
Table 1
Clinical trials and epidemiological data consistently indicate an increased risk of arterial thrombotic events (for example, myocardial infarction or stroke) associated with the use of diclofenac, especially at high doses (150 mg / day) and with long-term treatment ( see sections 4.3 and 4.4).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address: www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
In case the patient has taken an excessive dose of the drug, the doctor should be consulted immediately.
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 NSAID 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 measures and symptomatic treatment should be adopted. .
Specific therapies, such as forced diuresis, dialysis or haemoperfusion, are not likely to help "eliminate NSAIDs., including diclofenac, due to their high plasma protein binding and significant 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 product, acetic acid derivatives and related substances.
ATC code: M01AB05.
Mechanism of action
Diclofenac Mylan Generics 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, the anti-inflammatory and analgesic properties of diclofenac cause the clinical response to be characterized by a pronounced improvement in signs and symptoms, such as pain at rest, pain with movement, morning stiffness, joint swelling as well as by an improvement in function.
In post-traumatic and postoperative inflammatory conditions, diclofenac rapidly resolves both spontaneous pain and pain on movement, reduces inflammatory swelling and wound edema. 75 and 100 mg prolonged-release diclofenac tablets are particularly useful for patients in whom a daily dosage of 75 or 100 mg is appropriate according to the clinical picture. The possibility of prescribing the drug in a single daily dose greatly simplifies long-term treatment and helps to avoid the possibility of dosing errors. 75 mg prolonged-release tablets also allow the maximum daily dose of 150 mg to be divided into two doses.
05.2 "Pharmacokinetic properties
Absorption
The amount of unchanged diclofenac and hydroxylated metabolites present in the urine show that the amount of diclofenac released and absorbed with a prolonged-release diclofenac tablet is the same as that of a gastro-resistant tablet. However, the systemic bioavailability of diclofenac released from a prolonged-release diclofenac tablet is on average approximately 82% of that achieved with the same dose of diclofenac given with a gastro-resistant tablet (possibly due to first pass metabolism that depends on the rate of release.) As a consequence of the slower release of active ingredient from the prolonged-release diclofenac tablets, the peak concentrations achieved are lower than those observed after administration of gastro-resistant tablets.
Mean peak concentrations of 0.5 or 0.4 mcg / ml (1.6 or 1.25 mcmol / l) are achieved on average 4 hours after taking a 100 or 75 mg prolonged-release tablet.
Food has no clinically relevant influence on the absorption and systemic availability of prolonged-release diclofenac tablets.
On the other hand, mean plasma concentrations of 13 ng / ml (40 nmol / l) can be observed 24 hours after administration of a 100 mg prolonged release diclofenac tablet respectively. The amount absorbed is proportional to the administered dose.
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.
During treatment with the 100 mg prolonged-release tablets administered once daily or with the 75 mg prolonged-release tablets administered twice daily, trough concentrations are approximately 22 ng / ml or 25 ng / ml ( 70 nmol / l or 80 nmol / l).
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 maximum 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 eliminated 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, 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
Hydroxypropylcellulose, microcrystalline cellulose, corn starch, lactose monohydrate, povidone, magnesium stearate, cellulose acetate phthalate, triethyl citrate, titanium dioxide.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
4 years.
06.4 Special precautions for storage
Keep the blister in the outer carton to protect the medicine from moisture.
06.5 Nature of the immediate packaging and contents of the package
Lithographed cardboard box containing PVC / Al blisters containing 21 tablets.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Mylan S.p.A, Via Vittor Pisani 20, 20124 Milan - Italy
08.0 MARKETING AUTHORIZATION NUMBER
AIC n. 033062050: 21 prolonged-release tablets 100 mg
