Diclomec (Diclofenac) 3 ML 75 Mg 10 pieces Vial (Bulb)

4. CLINICAL FEATURES

4.1. Therapeutic Indication

Treatment of symptoms and signs of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis are indicated for the treatment of acute gouty arthritis, acute musculoskeletal pain, postoperative pain and dysmenorrhea.

4.2. Posology and method of administration

The dose is generally 75 mg per day and is administered as a deep intragluteal injection into the upper outer quadrant. In severe cases (eg colic), the daily dose may be exceptionally removed by two injections of 75 mg (one for each hip) by several hours. Alternatively, 1 ampoule of 75 mg per day may be combined with other forms of DICLOMEC (tablet), provided that it does not exceed 150 mg per day.

Frequency and duration of application:

DİCLOMEC bulb should not be applied longer than 2 days. If necessary, treatment can be continued with DICLOMEC tablets.

Method of:

administration Intramuscular injection is performed in the form of deep intragluteal injection into the upper outer quadrant.

Additional information on special populations:

Pediatric population:

DICLOMEC bulb is not suitable for children and adolescents due to dose strength (see section 5.2).

DİCLOMEC should not be given to premature babies and newborns. Benzyl alcohol can cause toxic and anaphylactoid in infants and children up to 3 years of age.

Geriatric population: (age 65 and over)

Although the pharmacokinetics of Diclomec are not clinically significant in elderly patients, non-steroidal anti-inflammatory drugs should be used with caution in such patients who are generally more prone to adverse effects. It is recommended that the lowest effective dose should be used in elderly patients with particularly sensitive or low body weight, and the patient should be followed for the possibility of gastrointestinal bleeding during NSAID drug treatment (see section 4.4).

Known cardiovascular disease or significant cardiovascular risk factors

Treatment with Diclomec is not recommended in patients with known cardiovascular disease or uncontrolled hypertension. If necessary, known cardiovascular disease, with uncontrolled hypertension or cardiovascular patients with significant risk factors for disease Diclomec only after careful consideration and 4 by prolonged treatment week only <should be treated at a 100 mg daily dose (see., Section

4.4.)

Renal Failure

Diclomec In patients with renal impairment is contraindicated (see., section 4.3.).

Since specific studies are not conducted in patients with renal insufficiency, recommendations for specific dose adjustment cannot be made. Caution should be exercised when administering Diclomec to patients with mild to moderate renal impairment (see section 4.4.)

Liver failure

Diclomec is contraindicated in patients with hepatic impairment (see section 4.3.). Since specific studies are not carried out in patients with hepatic impairment, recommendations for specific dose adjustment cannot be made. Care should be taken when applying Diclomec to patients with mild to moderate hepatic impairment (see section 4.4.).

4.3. Contraindications

• In persons with known hypersensitivity to the active substance, sodium metabisulfite or any of the excipients,

• Active gastritis or intestinal ulcer, bleeding or perforation (see Sections 4.4 and 4.8),

• During the last trimester of pregnancy (see Section 4.6. )

• liver failure

• renal failure

• ischemic heart disease, peripheral artery disease, cerebrovascular disease and congestive heart failure (NYHA classification II-IV) conditions

• previously other nonsteroidal antiinflammatory (such as NSAIDs) drugs, Diclomec acetyl saline silicic acid or other NSAID inhibiting prostaglandin synthetase enzyme is contraindicated in patients with asthma, urticaria and acute rhinitis attacks (see Chapters 4.4 and 4.5).

Severe, rarely fatal, anaphylaxis-like reactions to NSAids have been reported in these patients.

• Contraindicated in the treatment of peri-operative pain in coronary artery bypass graft (CABG) surgery (see WARNINGS)

• A history of gastrointestinal bleeding or perforation associated with NSAID therapy history of

• Aactive, recurrent peptic ulcer / bleeding

4.4. Special warnings and precautions for use

Cardiovascular (CV) Risk:CVD

• NSAIDs may cause an increased risk of thrombotic events, myocardial infarction and stroke, which can be fatal. This risk may increase depending on the duration of use. The risk may be higher in patients with CV or disease risk factors.

• DİCLOMEC Ampoule is contraindicated in the treatment of peri-operative pain in coronary artery bypass graft (CABG) surgery

Gastrointestinal (GI) Risk:

• NSAID drugs lead to an increased risk of serious GI adverse effects such as bleeding, ulceration, stomach or intestinal perforation. These undesirable effects may occur at any time, with or without a prior warning. Older patients have a higher risk of severe GI effects.

General:

Undesirable effects can be minimized using the lowest effective dose required to control symptoms (see section 4.2).

There is no evidence of synergistic benefit and additional potential for adverse impacts; Diclomec should not be used concomitantly with systemic NSAIDs such as cyclooxygenase-2 selective inhibitors (see section 4.5). It should be used with caution in the elderly because of basic medical reasons. In particular, it is recommended to use the lowest effective dose in the elderly with low or low body weight (see section 4.2).

8.4. Undesirable effects As with

other NSAIDs, diclofenac may hide signs and symptoms of infection due to its pharmacodynamic properties.

Gastrointestinal Effects:

Fatal, gastrointestinal bleeding, ulceration or puncture has been reported with all NSAIDs, including diclofenac, and may be seen at any time during the course of treatment, whether or not there is a stimulus symptom or a history of a serious gastrointestinal event. These often lead to more serious consequences in older patients. If patients receiving DICLOMEC develop gastrointestinal bleeding or ulceration, the medicinal product should be discontinued.

Other factors increasing the risk of GI bleeding in patients undergoing NSAID therapy include the use of oral corticosteroids or anticoagulants, prolongation of NSAIDs, smoking, alcohol use, advanced age and poor general health. Since most of the spontaneous reports of lethal GI events are related to elderly and weak-bodied patients, special attention should be paid to the treatment of such patients.

Close medical monitoring is mandatory in patients with a history of gastrointestinal (GI) disease symptoms such as diclofenac, or gastrointestinal (GI) disease symptoms, or in patients with a history suggesting gastric or intestinal ulceration, bleeding, or perforation, and special care should be taken when prescribing DICLOMEC (see section 4.8). The risk of GI bleeding increases as the NSAID dose increases in patients with a history of ulcers complicated by bleeding or perforation.

To reduce the risk of GI bleeding in patients with a history of ulcers complicated by bleeding or perforation, the lowest effective dose should be initiated and continued.

In these patients, combined therapy with protective agents (eg proton pump inhibitors or misoprostol) should be considered in patients who require low doses of acetylsalicylic acid (ASA) or other medicinal products that may increase the risk of gastrointestinal risk.

Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding).

Careful caution is recommended in patients receiving medications that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants, antiplatelet agents, or selective serotonin reuptake inhibitors (see section 4.5).

Close medical follow-up should be performed in patients with ulcerative colitis or Crohn's disease, as the clinical picture may be aggravated and caution is required (see section 4.8).

Hepatic effects:

Close medical follow-up should be performed when DICLOMEC is prescribed in patients with impaired liver function as the clinical picture may be aggravated.

As with other NSAIDs, one or more of the liver enzymes may increase with diclofenac sodium. Laboratory anomalies may progress, remain unchanged, or be transient by continued therapy. In clinical studies with NSAIDs, significant increases in ALT and AST levels (three times the upper limit of normal level) were reported in approximately 1% of patients. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and liver failure, have also been reported. During long-term treatment with DICLOMEC (eg with a tablet), hepatic function should be monitored regularly as a preventive measure. DİCLOMEC therapy should be discontinued if the clinical signs and symptoms of liver function tests deteriorate or deteriorate, or if other signs (eg eosinophilia, skin rash, etc.) occur. With the use of diclofenac sodium, hepatitis may occur without prodromal symptoms. Care should be taken when using DICLOMEC in patients with hepatic porphyria, because the attack may be triggered.

Renal Effects:

Long-term use of NSAIDs leads to renal papillary necrosis and other renal damage. In addition, renal toxicity has been observed in patients in whom renal prostaglandins play a compensatory role in the maintenance of renal perfusion. Administration of nonsteroidal antiinflammatory drugs in such patients may lead to a dose-dependent reduction in prostaglandin formation and secondary renal blood flow, which can accelerate obvious renal decompensation. Patients with the highest risk of such a reaction are impaired in kidney function, heart failure, liver dysfunction, diuretic and ACE inhibitor users and the elderly. After stopping NSAID treatment, it is usually returned to pretreatment status.

NSAID drug treatment including diclofenac, fluid retention and edema, as well as in patients with cardiac or renal dysfunction, patients with a history of hypertension, elderly patients, diuretics or medicinal products that significantly affect kidney function, and for any reason Special attention is required in patients with a significant lack of extracellular volume that may develop and after (see section 4.3). In such cases, it is recommended to monitor renal function as a preventive measure when using DICLOMEC. After discontinuation of the drug, it is usually returned to the pre-treatment state.

Advanced Kidney Diseases:

There is no data available in controlled studies on the use of DICLOMEC in patients with advanced renal disease. Therefore, DICLOMEC treatment is not recommended in patients with advanced renal disease. If DICLOMEC treatment is initiated, it is recommended to monitor the renal function of the patient closely.

Skin Reactions:

Serious skin reactions have been reported, including fatal exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, some of which are fatal, associated with the use of NSAIDs, including DICLOMEC (see section 4.8). Patients appear to be at risk for these reactions at the earliest stage of treatment and most of the cases occur in the first month of treatment. DİCLOMEC should be discontinued when skin rash and mucosal lesions appear first or any other signs of hypersensitivity occur.

SLE and Connective Tissue Disease: In patients with

systemic lupus erythematosus (SLE) and mixed connective tissue diseases, the risk of aseptic meningitis may increase.

Cardiovascular and Cerebrovascular Effects:

Diclofenac therapy should be initiated in patients with significant risk factors for cardiovascular events (eg, hypertension, hyperlipidemia, diabetes mellitus, smoking) but only after careful evaluation. This increased risk was observed especially in high doses (150 mg daily) and long-term treatment. Therefore, the shortest duration of treatment and the lowest effective dose should be preferred in diclofenac treatment. The healthcare professional should regularly reevaluate the need to continue to treat patients with diclofenac.

An increase in the risk of severe cardiovascular (CV) thrombotic event, myocardial infarction and stroke has been shown, which may be fatal in clinical trials up to 3 years with a large number of selective and non-selective COX-2 inhibitors. C0X-2 selective and non-selective NSAIDs may be of similar risk. Patients with known cardiovascular disease or those at risk for cardiovascular disease may be at higher risk. Even if there is no cardiovascular symptom seen before, the physician and the patient should be alert to such events. The patient should be informed about the symptoms and / or symptoms of serious cardiovascular events and what to do if they are seen.

Concurrently, there is no consistent evidence that the use of aspirin reduces the increased risk of severe cardiovascular thrombotic events associated with NSAID use. The simultaneous use of NSAIDs with aspirin increases the risk of severe GI events.

Two large, controlled clinical trials performed on a COX-2 selective NSAID for the treatment of pain in the first 10-14 day period following CABG surgery showed an increased incidence of myocardial infarction and stroke (see section Contraindications).

NSAIDs, including diclofenac, may be associated with a small increase in severe cardiovascular thrombotic events (including myocardial infarction and stroke), especially with high doses and long-term treatment.

Patients should be alert to signs and symptoms of severe atherothrombotic events (eg, chest pain, shortness of breath, weakness, cuddling) that can be seen without warning. Patients should be told to consult a physician immediately in the event of such an event.

Hematologic effects:

Patients with NSAIDs, including DICLOMEC, may occasionally experience anemia. This may be due to fluid retention, latent or gross GI blood loss, or post-erythropoiesis effects.

As with other NSAIDs, blood count monitoring is recommended during long-term treatment with DICLOMEC.

Like other NSAIDs, DICLOMEC can temporarily inhibit platelet aggregation. Patients with haemostasis defects should be monitored carefully.

Pre-existing asthma:

Reactions such as seasonal allergic rhinitis, swelling of the nasal mucosa (eg, nasal polyps), chronic obstructive pulmonary diseases, or chronic infections of the respiratory system (especially in association with symptoms such as allergic rhinitis) in patients with asthma, NSAIDs, asthma exacerbations Quincke edema or urticaria is more common than other patients (also called analgesic intolerance / analgesic asthma). Therefore, it is recommended to pay special attention to these patients (prepared for an emergency). This recommendation also applies to patients who are allergic to other substances, such as skin reactions, itching or urticaria.

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can result in death. As aspirin and other nonsteroidal antiinflammatory drugs in patients with aspirin sensitivity, including bronchospasm, cross-reaction has been reported, patients with this form of aspirin susceptibility should not be given DICLOMEC and should be used with caution in patients with asthma.

Special attention is required when using DICLOMEC for parenteral use, as it may exacerbate symptoms in patients with bronchial asthma.

Anaphylactoid Reactions: As with

other nonsteroidal anti inflammatory (NSAID) drugs, in rare cases with diclofenac, allergic reactions, including anaphylactic / anaphylactoid reactions, may occur without prior exposure to the drug. DİCLOMEC should not be given to patients with aspirin triad. This symptom complex typically occurs in asthmatic patients with nasal polyps or without polyps or with bronchospasm, which may be severe and fatal following their use of aspirin or NSAIDs (see Contraindications and Precautions - Asthma). In case of anaphylactoid reaction, emergency department should be consulted.

Masking signs of infection:

Like other NSAIDs, DICLOMEC may also mask signs and symptoms of infection due to its pharmacodynamic properties.

DİCLOMEC contains propylene glycol. May cause alcohol-like symptoms.

The presence of sodium metabisulphite can cause isolated hypersensitivity reactions and bronchospasm.

Fertility in women: The

use of Diclomec adversely affects female fertility and is not recommended for women trying to become pregnant. Stopping the use of Diclomec should be considered in women who are forced to become pregnant or undergoing infertility examination.

Geriatric patients: In

elderly patients, basic medical principles should be observed. In particular, it is recommended that the lowest effective dose should be given to elderly patients with frail or weak body weight.

DICLOMEC should not be expected to replace corticosteroids or to treat corticosteroid deficiency. A sudden cessation of corticosteroids may cause an exacerbation of the disease. Patients on long-term treatment with corticosteroids should reduce their treatment gradually and gradually if the decision to stop corticosteroid therapy is discontinued.

The pharmacological activity of DICLOMEC in reducing inflammation can reduce the utility of these symptoms, which are important in the recognition of complications of painful conditions considered to be infectious.

4.5. Interactions with other medicinal products and other forms of interaction

DICLOMEC should be avoided in combination with other systemic NSAIDs, including selective cyclooxygenase-2 inhibitors. The following interactions include those observed with DICLOMEC ampoule and / or other pharmaceutical forms of diclofenac.

:

Strong CYP2C9 inhibitors:

Because of the inhibition of diclofenac metabolism, peak plasma concentration and diclofenac exposure may result in a significant increase in diclofenac is strongly

Observed observations 7/17

recommended when prescribed with CYP2C9 inhibitors (such as voriconazole).

Lithium:

NSAIDs result in increased plasma lithium levels and reduced renal lithium clearance. The mean minimum lithium concentration increased by 15% and renal clearance decreased by about 20%. These effects are attributed to inhibition of renal prostaglandin synthesis by NSAIDs. Therefore, when NSAIDs and lithium are administered simultaneously, the patient should be carefully monitored for lithium toxicity. When used together, diclofenac may increase plasma concentrations of lithium. Serum lithium level monitoring is recommended.

Digoxin:

When used together, diclofenac may increase the plasma concentrations of digoxin. Follow-up of serum digoxin level is recommended.

Diuretics and antihypertensive agents: As with

other NSAIDs, the use of diclofenac with diuretics or antihypertensive agents (eg, beta-blockers, angiotensin converting enzyme (ACE) inhibitors) may cause a reduction in antihypertensive effects. Therefore, the combination should be administered with caution and the blood pressure of patients, especially in the elderly, should be monitored periodically. Patients should be appropriately hydrated and due to high nephrotoxicity, attention should be given to monitoring of renal function periodically, especially after use of the drug simultaneously with diuretics and ACE inhibitors (see section 4.4).

Cyclosporine and tacrolimus:

Diclofenac may increase the nephrotoxicity of cyclosporine due to its effect on renal prostaglandins such as other NSAIDs. Therefore, it should be given at lower doses than the dose used in patients not receiving cyclosporin. The use of NSAIDs in combination with tacrolimus may cause an increased risk of nephrotoxicity. This may be by means of the renal antiprostaglandin effects of both calcineurin and NSAID drugs.

Drugs known to cause hyperkalemia:

Concurrent treatment with potassium-sparing diuretics, cyclosporine, tacrolimus and trimethoprim may be associated with increased serum potassium levels. Therefore, serum potassium levels should be checked frequently (see section 4.4).

Quinolone-derived antibacterial drugs:

There are isolated convulsion reports from the co-use of NSAID drugs and quinolones.

Foreseen interactions to be considered:

Furosemide:

Clinical studies and post-marketing observations show that the use of DICLOMEC can reduce the natriuretic effect of furosemide and thiazides in some patients. This response is linked to inhibition of renal prostaglandin synthesis. When treated concurrently with NSAIDs, the patient should be closely monitored to ensure signs of renal insufficiency (see Precautions, Renal Effects) and diuretic activity.

Cardiac glycosides:

Co-administration of NSAIDs and cardiac glycosides can exacerbate heart failure, decrease GFR and increase plasma glycoside levels.

Other NSAIDs and corticosteroids:

Co-administration of diclofenac and other systemic NSAIDs or corticosteroids may increase the frequency of gastrointestinal adverse effects (see section 4.4).

Anticoagulants and antiplatelet agents:

Caution is recommended because their co-administration may increase the risk of bleeding (see section 4.4). Although there is no indication that DICLOMEC has an effect on the effect of anticoagulants in clinical trials, it has been rarely reported that the risk of bleeding is increased in patients taking DICOMOMEC and anticoagulants together. Careful monitoring of such patients is therefore recommended.

Warfarin: The

effect of warfarin and NSAIDs on GI bleedings is cynical; In other words, the risk of severe GI bleeding in patients using these two drugs is higher than those using these two drugs alone.

Aspirin: When

DICLOMEC is administered with aspirin, the protein binding rate decreases, although free DICLOMEC clearance does not change. Although the clinical significance of this interaction is not known, the simultaneous administration of diclofenac and aspirin, as in other NSAIDs, is generally not recommended, as it increases the likelihood of adverse effects.

Selective serotonin reuptake inhibitors ():

SSRI Administration of systemic NSAIDs, including diclofenac sodium, with SSRIs may increase the risk of gastrointestinal bleeding (see section 4.4).

Antidiabetics:

Clinical studies have shown that DICLOMEC can be administered with oral antidiabetic drugs without affecting their clinical effects. However, very rarely, hypoglycemic and hyperglycemic effects have been reported that may require adjustment of the dose of antidiabetic drugs during treatment with DICLOMEC. Therefore, follow-up of blood glucose level as a precaution is recommended.

Methotrexate:

NSAIDs have been reported to inhibit the accumulation of methotrexate competitively on rabbit kidney sections. This indicates that they can increase methotrexate toxicity. Caution should be exercised if NSAs are administered simultaneously with methotrexate. Care should be taken when using all NSAIDs, including diclofenac, before or after methotrexate treatment. Because the concentrations of methotrexate in the blood may increase and its toxicity may increase.

Colestipol and cholestyramine:

These agents may delay or decrease the absorption of diclofenac. Therefore, it is recommended that diclofenac administration be performed at least one hour before or 4 to 6 hours after administration of colestipol / cholestyramine.

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