Diclofenac-teva

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DICLOFENAC-TEVA (DICLOFENAC-TEVA)

Composition:

Active substance: sodium diclofenac;

1 ampoule (3 ml) contains 75 mg of sodium diclofenac;

Excipients: benzyl alcohol, edetate disodium, acetylcysteine, propylene glycol, mannitol (E 421), sodium hydroxide, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear, colorless to greenish-yellow solution.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and anti-rheumatic drugs. Acetic acid derivatives and related compounds. ATC code M01A B05.

Pharmacological Properties.

Pharmacodynamics.

Diclofenac-Teva is a non-steroidal agent with pronounced analgesic and anti-inflammatory properties. It is an inhibitor of prostaglandin synthetase (cyclooxygenase). Prostaglandins play a key role in the development of inflammation, pain, and fever. In vitro, at concentrations equivalent to those achieved in humans, sodium diclofenac does not suppress proteoglycan biosynthesis in cartilage tissue. When administered concomitantly with opioids for postoperative pain relief, it significantly reduces the need for opioids.

Pharmacokinetics.

Absorption. After intramuscular injection of 75 mg of diclofenac, the mean peak plasma concentration of 2.5 µg/mL is reached within approximately 20 minutes. Following intramuscular injection or administration of enteric-coated tablets or suppositories, plasma concentrations decline rapidly immediately after peak levels are achieved. After oral or rectal administration, approximately half of the absorbed diclofenac undergoes first-pass metabolism in the liver. The area under the concentration-time curve (AUC) after intramuscular or intravenous administration is approximately twice that after oral or rectal administration. Pharmacokinetic properties do not change after repeated dosing. With adherence to recommended dosing intervals, no drug accumulation occurs.

Distribution. 99.7% of diclofenac is bound to plasma proteins, primarily to albumin (99.4%). The apparent volume of distribution is calculated to be 0.12–0.17 L/kg. Diclofenac penetrates into synovial fluid, where Cmax is achieved 2–4 hours after peak plasma concentration. The expected half-life in synovial fluid is 3–6 hours. Two hours after achieving Cmax, the concentration of diclofenac in synovial fluid exceeds that in plasma and remains higher for up to 12 hours. Diclofenac has been detected at low concentrations (100 ng/mL) in breast milk in one breastfeeding woman. The estimated amount of drug transferred to the infant via breast milk is equivalent to 0.03 mg/kg/day.

Metabolism. Biotransformation of diclofenac occurs partially via glucuronidation of the intact molecule, but primarily through single and multiple hydroxylations and methoxylations, leading to the formation of several phenolic metabolites (3'-hydroxy-, 4'-hydroxy-, 5-hydroxy-, 4',5-dihydroxy-, and 3'-hydroxy-4'-methoxydiclofenac), most of which are further converted into glucuronide conjugates. Two of these phenolic metabolites are pharmacologically active, although their activity is considerably less than that of diclofenac.

Elimination. Total systemic clearance of diclofenac from plasma is 263±56 mL/min (mean ± SD). The terminal half-life in plasma is 1–2 hours. Four metabolites, including two active ones, also have short plasma half-lives of 1–3 hours. One metabolite, 3'-hydroxy-4'-methoxydiclofenac, has a much longer half-life but is essentially inactive. Approximately 60% of the administered dose is excreted in urine as metabolites. Less than 1% is excreted unchanged. The remainder is eliminated as metabolites via bile into feces.

Linearity/Non-linearity. Plasma concentration demonstrates a linear relationship with dose.

Special Patient Groups. Elderly Patients. No differences in absorption, metabolism, or excretion of the drug related to patient age have been observed, except that in elderly patients, a 15-minute intravenous infusion resulted in a 50% higher plasma concentration compared to young healthy volunteers.

Patients with Renal Impairment. In patients with impaired renal function, accumulation of unchanged active substance is not expected with standard dosing regimens, based on the pharmacokinetics after single-dose administration. With creatinine clearance less than 10 mL/min, theoretical steady-state plasma levels of metabolites are approximately four times higher than in healthy volunteers. However, metabolites are ultimately eliminated via bile.

Patients with Hepatic Disease. In patients with chronic hepatitis or compensated cirrhosis of the liver, the pharmacokinetics and metabolism of diclofenac are similar to those in patients without liver disease.

Clinical Characteristics.

Indications.

The drug is indicated for intramuscular administration in the treatment of:

• Inflammatory and degenerative forms of rheumatism, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis, vertebral pain syndrome, non-articular rheumatism;
• Acute gout attacks;
• Renal and biliary colic;
• Pain and swelling following trauma and surgery;
• Severe migraine attacks.

Contraindications.

• Known hypersensitivity to the active substance or to any of the other components of the drug.
• History of gastrointestinal bleeding or perforation related to previous treatment with non-steroidal anti-inflammatory drugs (NSAIDs).
• Active peptic ulcer/hemorrhage or recurrent peptic ulcer/hemorrhage in history (two or more separate episodes of established ulcer or bleeding).
• Active gastric and/or duodenal ulcer, gastrointestinal bleeding or perforation.
• Third trimester of pregnancy.
• As with other NSAIDs, diclofenac is contraindicated in patients in whom administration of ibuprofen, acetylsalicylic acid, or other NSAIDs induces attacks of bronchial asthma, bronchospasm, angioedema, urticaria, or rhinitis/nasal polyps, or allergy-like symptoms.
• Inflammatory bowel diseases (e.g., Crohn's disease or ulcerative colitis).
• Hepatic failure.
• Renal failure (glomerular filtration rate (GFR) < 15 mL/min/1.73 m²).
• Heart failure (NYHA II–IV).
• High risk of postoperative bleeding, coagulation disorders, hemostatic disturbances, hematopoietic disorders, or cerebrovascular hemorrhage.
• Treatment of postoperative pain following coronary artery bypass grafting (or use of cardiopulmonary bypass).
• Ischemic heart disease in patients with angina pectoris or history of myocardial infarction.
• Cerebrovascular diseases in patients with history of stroke or transient ischemic attacks.
• Peripheral arterial disease.

This medicinal product is contraindicated in children in this pharmaceutical form.

Interaction with other medicinal products and other forms of interaction.

The following interactions may occur between Diclofenac-Teva and/or other diclofenac-containing preparations and other drugs.

Lithium. When used concomitantly, diclofenac may increase lithium plasma concentrations. Monitoring of serum lithium levels is recommended.

Digoxin. When used concomitantly, diclofenac may increase digoxin plasma concentrations. Monitoring of serum digoxin levels is recommended.

Diuretics and antihypertensive agents. As with other NSAIDs, concomitant use of diclofenac with diuretics and antihypertensive agents (e.g., beta-blockers, angiotensin-converting enzyme (ACE) inhibitors) may reduce their antihypertensive effect. Therefore, such combinations should be used with caution, and patients, especially elderly patients, should be closely monitored for blood pressure. Adequate hydration is recommended, and renal function should also be monitored after initiation of concomitant therapy and regularly thereafter, particularly when using diuretics and ACE inhibitors, due to increased risk of nephrotoxicity.

Medicinal products causing hyperkalemia. Concomitant use with potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may be associated with increased serum potassium levels; therefore, more frequent monitoring of patients is required.

Anticoagulants and antithrombotic agents. Precaution is advised, as concomitant administration may increase the risk of bleeding. Although clinical studies have not shown an effect of diclofenac on anticoagulant activity, there are individual reports of increased bleeding risk in patients receiving diclofenac and anticoagulants simultaneously. Therefore, careful monitoring of such patients is recommended.

Other NSAIDs and corticosteroids. Concomitant administration of diclofenac with other systemic NSAIDs or corticosteroids may increase the frequency of gastrointestinal adverse effects.

Selective serotonin reuptake inhibitors (SSRIs). Concomitant administration of systemic NSAIDs and SSRIs may increase the risk of gastrointestinal bleeding.

Antidiabetic agents. Clinical studies have shown that diclofenac can be used together with oral antidiabetic agents without affecting their clinical efficacy. However, isolated cases of both hypoglycemic and hyperglycemic effects have been reported after diclofenac administration, requiring dosage adjustments of antidiabetic agents during diclofenac treatment. In such cases, blood glucose monitoring is necessary as a precautionary measure during concomitant therapy.

There are also isolated reports of metabolic acidosis when used concomitantly with diclofenac, particularly in patients with pre-existing renal function impairment.

Methotrexate. Caution is recommended when NSAIDs, including diclofenac, are administered less than 24 hours before methotrexate treatment, as this may increase methotrexate blood concentration and enhance its toxicity.

Cyclosporine and tacrolimus. Diclofenac, as with other NSAIDs, may increase the nephrotoxicity of cyclosporine and tacrolimus due to effects on renal prostaglandins. Therefore, it should be administered at lower doses than in patients not receiving cyclosporine or tacrolimus.

Quinolone antibacterials. There are isolated reports of seizures that may result from concomitant use of quinolones and NSAIDs.

Phenytoin. When phenytoin is used concomitantly with diclofenac, monitoring of plasma phenytoin concentrations is recommended due to expected increased phenytoin exposure.

Cholestyramine and colestipol. These agents may cause delayed or reduced absorption of diclofenac. Therefore, diclofenac should be administered at least 1 hour before or 4–6 hours after cholestyramine/colestipol administration.

Cardiac glycosides. Concomitant use of cardiac glycosides and NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase glycoside plasma levels.

Mifepristone. NSAIDs should not be used within 8–12 days after mifepristone administration, as NSAIDs may reduce its effect.

CYP2C9 inhibitors. Caution is required when diclofenac is used concomitantly with CYP2C9 inhibitors (e.g., voriconazole, sulfaphenazole). This may lead to a significant increase in plasma Cmax and exposure to diclofenac.

CYP2C9 inducers. Caution is required when diclofenac is co-administered with CYP2C9 inducers (e.g., rifampicin). This may lead to a significant increase in plasma concentration and exposure to diclofenac.

Special precautions for use.

General. Gastrointestinal ulcers, bleeding, or perforation may occur at any time during nonsteroidal anti-inflammatory drug (NSAID) therapy, regardless of COX-2 selectivity, even in the absence of warning symptoms or a favorable medical history. Concomitant use of Diclofenac-Teva with systemic NSAIDs, including selective COX-2 inhibitors, should be avoided due to the potential for additional adverse effects.

Adverse effects can be minimized by using the lowest effective dose for the shortest possible duration required to control symptoms.

Placebo-controlled studies have shown an increased risk of thrombotic cardiovascular and cerebrovascular complications with certain selective COX-2 inhibitors. A direct correlation between this risk and the COX-1/COX-2 selectivity of individual NSAIDs has not yet been established. Due to the lack of comparative clinical trial data on long-term treatment with maximum doses of diclofenac, the possibility of a similar increased risk cannot be excluded. In the absence of such data, a careful risk-benefit assessment should be performed before initiating diclofenac in patients with clinically confirmed ischemic heart disease, cerebrovascular disorders, peripheral arterial disease, or significant risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking). Given this risk, the lowest effective dose should be used for the shortest possible duration.

Effects of NSAIDs on the kidneys include fluid retention with edema and/or arterial hypertension. Therefore, diclofenac should be used with caution in patients with impaired cardiac function and other conditions predisposing to fluid retention. Caution is also advised in patients receiving concomitant diuretics or angiotensin-converting enzyme (ACE) inhibitors, or those prone to hypovolemia.

Hypersensitivity reactions may progress to Kounis syndrome, a severe allergic reaction that may lead to myocardial infarction. Symptoms may include chest pain occurring in conjunction with an allergic reaction to diclofenac.

Consequences are generally more severe in elderly patients. Caution is required when prescribing the drug to elderly individuals. In particular, the lowest effective doses are recommended for elderly patients with poor general health or low body weight. If gastrointestinal bleeding or ulceration occurs in patients receiving Diclofenac-Teva, treatment should be discontinued.

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

Gastrointestinal effects. Gastrointestinal bleeding (hematemesis, melena), ulceration, or perforation have been reported with diclofenac, as with other NSAIDs. These events may be fatal and may occur at any time during treatment, with or without warning symptoms, and may be associated with a history of serious gastrointestinal events. These events generally have more serious consequences in elderly patients. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, treatment must be discontinued. Careful medical monitoring is required when using diclofenac, as with all NSAIDs. Particular caution is advised when prescribing diclofenac to patients with symptoms suggesting gastrointestinal disturbances or with a history of gastric or intestinal ulcers, bleeding, or perforation. The risk of gastrointestinal bleeding increases with higher NSAID doses, in patients with a history of ulcers (especially complicated by bleeding or perforation), and in elderly patients. Elderly patients have an increased frequency of adverse reactions with NSAID use, particularly gastrointestinal bleeding and perforation, which may be fatal.

To reduce the risk of gastrointestinal toxicity in patients with a history of ulcers (especially complicated by bleeding or perforation) and in elderly patients, treatment should be initiated and maintained at the lowest effective doses. For these patients, as well as those requiring concomitant use of low-dose acetylsalicylic acid (ASA) or other drugs likely to increase gastrointestinal adverse effects, consideration should be given to combination therapy with protective agents (e.g., proton pump inhibitors or misoprostol). Patients with a history of gastrointestinal toxicity, particularly elderly patients, should report any unusual abdominal symptoms (especially gastrointestinal bleeding). Caution is also required in patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants (e.g., warfarin), antiplatelet agents (e.g., ASA), or SSRIs.

Patients with ulcerative colitis or Crohn’s disease require careful medical supervision and caution, as their condition may worsen. NSAIDs, including diclofenac, may be associated with an increased risk of gastrointestinal anastomotic insufficiency. Careful medical monitoring and caution are recommended when using diclofenac after gastrointestinal surgery.

Hepatic effects. Close medical monitoring is required when administering the drug to patients with impaired liver function, as their condition may worsen. As with other NSAIDs, treatment with diclofenac may increase levels of one or more liver enzymes. This has been very frequently observed in clinical trials with diclofenac (approximately 15% of patients), but rarely associated with clinical symptoms. Most cases involve borderline elevations. Moderate increases (≥3 to <8 times the upper limit of normal) have been frequently observed (in 2.5% of cases), while marked increases (≥8 times the upper limit of normal) occurred in approximately 1% of cases. Clinically evident liver injury occurred in 0.5% of cases in the aforementioned clinical trials. Elevated enzyme levels were generally reversible upon discontinuation of the drug. In patients receiving diclofenac, diseases such as hepatitis may progress without prodromal symptoms.

Caution is required when Diclofenac-Teva is administered to patients with hepatic porphyria, as there is a risk of provoking an attack.

Renal effects. Due to the importance of prostaglandins in maintaining renal blood flow, prolonged treatment with high doses of NSAIDs, including diclofenac, frequently (1–10%) leads to edema and arterial hypertension. Since fluid retention and edema have been reported with NSAID treatment, including diclofenac, particular attention should be paid to patients with cardiac or renal dysfunction, a history of arterial hypertension, elderly patients, those receiving concomitant diuretic therapy or drugs significantly affecting renal function, and patients with significant extracellular fluid volume depletion due to any cause, such as before or after major surgery. In such cases, monitoring of renal function is recommended as a precautionary measure when using diclofenac. Discontinuation of therapy usually leads to reversal to the pre-treatment state.

Skin effects. Serious skin reactions (some of which were fatal), including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been very rarely reported with sodium diclofenac, as with other NSAIDs. The highest risk of these reactions occurs early in the course of therapy, mostly within the first month of treatment. Treatment with Diclofenac-Teva must be discontinued at the first appearance of skin rash, mucosal lesions, or any other signs of hypersensitivity. As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may rarely occur even without prior exposure to diclofenac.

Systemic lupus erythematosus (SLE) and mixed connective tissue diseases. Patients with SLE and mixed connective tissue diseases may have an increased risk of developing aseptic meningitis.

Cardiovascular and cerebrovascular effects. Diclofenac may be prescribed to patients with significant cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) only after careful clinical evaluation. Treatment with NSAIDs, including diclofenac, especially at high doses and for prolonged periods, may be associated with a slightly increased risk of serious cardiovascular thrombotic events (including myocardial infarction and stroke). Treatment with Diclofenac-Teva is generally not recommended in patients with diagnosed cardiovascular diseases (heart failure, ischemic heart disease, peripheral arterial disease) or uncontrolled arterial hypertension. If such treatment is necessary in patients with diagnosed cardiovascular diseases, uncontrolled hypertension, or significant cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking), Diclofenac-Teva should be prescribed only after careful evaluation and at doses not exceeding 100 mg/day when treatment exceeds 4 weeks.

Since cardiovascular risks of diclofenac may increase with dose and duration of treatment, it should be used for the shortest possible duration and at the lowest effective dose. The patient's need for diclofenac and response to therapy should be periodically reviewed, especially when treatment exceeds 4 weeks. Use with caution in patients aged 65 years and older.

Patients with a history of arterial hypertension and/or mild to moderate congestive heart failure require appropriate monitoring and counseling, as fluid retention and edema have been reported with NSAID use, including diclofenac.

Clinical and epidemiological data indicate that diclofenac use, particularly at high doses (150 mg/day) and for prolonged periods, may be associated with a slight increase in the risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

Diclofenac is not recommended for patients with uncontrolled arterial hypertension, congestive heart failure, stable ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease; if use is necessary, it may be considered only after careful risk-benefit assessment and at a dosage not exceeding 100 mg/day. A similar assessment should be performed before initiating long-term treatment in patients with risk factors for cardiovascular events (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

Patients should be informed about signs and symptoms of serious arterial thromboembolic events (e.g., chest pain, dyspnea, weakness, speech disturbances), which may occur without warning symptoms. In such cases, immediate medical attention is required.

Hematological effects. With prolonged use of the drug, as with other NSAIDs, monitoring of blood counts is recommended. Like other NSAIDs, diclofenac may temporarily inhibit platelet aggregation. Careful monitoring is required in patients with coagulation disorders, hemorrhagic diathesis, or hematological disorders.

Respiratory effects (asthma in history). Patients with bronchial asthma, seasonal allergic rhinitis, nasal mucosal edema (nasal polyps), chronic obstructive pulmonary diseases, or chronic respiratory infections (especially those associated with allergic, rhinitis-like symptoms) are more likely than others to experience NSAID-related reactions resembling asthma exacerbation (so-called analgesic intolerance/analgesic-induced asthma), Quincke's edema, or urticaria. Therefore, special precautionary measures (readiness for emergency intervention) are recommended for these patients. This also applies to patients with allergies to other substances manifesting as skin reactions, pruritus, or urticaria.

Particular caution is recommended when parenterally administering diclofenac to patients with bronchial asthma, as symptoms may worsen. Like other drugs that inhibit prostaglandin synthetase activity, sodium diclofenac and other NSAIDs may provoke bronchospasm in patients with bronchial asthma or a history of bronchial asthma.

Female fertility. Use of Diclofenac-Teva may impair fertility in women and is not recommended for women attempting to conceive. Consideration should be given to discontinuing the drug in women who may have difficulty conceiving or who are undergoing infertility evaluation.

Precautions for use. When administering injections, strict adherence to sterilization, aseptic, and antiseptic procedures is required. Injection techniques for intramuscular administration must be strictly followed to avoid adverse local reactions, which may lead to muscle weakness, paralysis, paresthesia, cutaneous drug embolism (Nicolau syndrome), and injection site necrosis. Injection site reactions, including necrosis and cutaneous drug embolism (Nicolau syndrome), have been reported after intramuscular administration of diclofenac (particularly after inadvertent subcutaneous injection). Appropriate needle selection and injection technique should be followed when administering diclofenac intramuscularly.

Diclofenac-Teva, solution for injection, contains:

• Sodium: this medicinal product contains less than 1 mmol (23 mg) of sodium per ampoule, i.e., essentially "sodium-free";
• Benzyl alcohol: this medicinal product contains 120 mg of benzyl alcohol per 3 mL ampoule. Benzyl alcohol may cause allergic reactions; large volumes should be used with caution and only if necessary, especially in patients with hepatic or renal insufficiency due to the risk of accumulation and toxicity (metabolic acidosis);
• Propylene glycol: this medicinal product contains 600 mg of propylene glycol per 3 mL ampoule.

Use during pregnancy or breastfeeding.

Pregnancy. During the first and second trimesters of pregnancy, Diclofenac-Teva may be prescribed only if the expected benefit to the mother outweighs the potential risk to the fetus, and only at the lowest effective dose. The duration of treatment should be as short as possible. Like other NSAIDs, the drug is contraindicated during the third trimester of pregnancy (possible inhibition of uterine contractility and premature closure of the fetal ductus arteriosus).

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data suggest an increased risk of miscarriage and/or congenital heart defects and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%. The risk increases with higher doses and longer duration of treatment. Animal studies have shown that prostaglandin synthesis inhibitors increase pre- and post-implantation loss and embryonic/fetal mortality. In addition, increased incidence of various developmental abnormalities, including cardiovascular defects, has been observed in animals treated with prostaglandin synthesis inhibitors during organogenesis. From the 20th week of pregnancy, diclofenac use may cause oligohydramnios due to impaired fetal renal function. This may occur soon after initiation of treatment and is usually reversible upon discontinuation. There have also been reports of ductus arteriosus constriction after treatment in the second trimester, most of which resolved after stopping treatment. If Diclofenac-Teva is used in women attempting to conceive or during the first or second trimester of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible. After several days of diclofenac use starting from the 20th week of pregnancy, consideration should be given to antenatal monitoring for oligohydramnios and ductus arteriosus constriction. Diclofenac should be discontinued if oligohydramnios or ductus arteriosus constriction is detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus as follows:

• Cardio-pulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
• Impaired renal function (see above).

Effects of diclofenac on the mother and newborn, particularly at the end of pregnancy:

• Possible: prolonged bleeding time; anti-aggregatory effect, which may occur even at very low doses;
• Inhibition of uterine contractions, leading to delayed or prolonged labor.

Therefore, the drug is contraindicated during the third trimester of pregnancy.

Breastfeeding. Like other NSAIDs, sodium diclofenac passes into breast milk in small amounts. Therefore, the drug should not be used during breastfeeding to avoid adverse effects on the infant. If treatment is considered necessary, the infant should be switched to artificial feeding.

Fertility. Sodium diclofenac may affect female fertility. The drug is not recommended for women planning to become pregnant. Women experiencing conception difficulties or undergoing infertility evaluation should discontinue the drug.

Based on relevant animal studies, impairment of male reproductive function cannot be excluded. The relevance of these findings to humans has not been established.

Ability to affect reaction speed when driving or operating machinery.

Patients who experience visual disturbances, dizziness, vertigo, somnolence, or other central nervous system disturbances during treatment with Diclofenac-Teva should refrain from driving or operating machinery.

Method of Administration and Dosage.

The general recommendation is to determine the dose individually. Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.

Adults

Sodium diclofenac, solution for injection, should not be used for more than 2 days. If continued treatment is necessary, therapy may be continued with sodium diclofenac in the form of gastro-resistant tablets or suppositories.

Intramuscular injection

To prevent nerve or other tissue damage at the site of intramuscular injection, the following instructions must be observed. Such damage may lead to muscle weakness, paralysis, and hypoesthesia.

The usual dose is 75 mg (one ampoule) daily administered by deep injection into the upper outer quadrant of the gluteus maximus muscle using an aseptic technique. In severe cases (e.g., colic), the daily dose may be increased to two injections of 75 mg each, administered several hours apart (one injection into each buttock). As an alternative, the 75 mg injection solution may be combined with other dosage forms of the drug (e.g., tablets or suppositories) up to a maximum total daily dose of 150 mg of sodium diclofenac.

In the treatment of migraine attacks, clinical experience is limited to cases where an initial dose of one 75 mg ampoule is administered, preferably immediately after using a 75 mg suppository on the same day (if necessary). The total daily dose should not exceed 175 mg on the first day.

There are no available data on the use of sodium diclofenac for the treatment of migraine attacks beyond one day. If further therapy is required on subsequent days, the maximum daily dose should be up to 150 mg (as divided doses administered in the form of suppositories).

Special Patient Groups

Elderly patients (aged 65 years and older). Dose adjustment is generally not required for elderly patients. However, caution is recommended based on the patient's condition, particularly in frail elderly patients or those with low body weight.

Paediatric population (under 18 years). Diclofenac in the form of solution for injection is contraindicated for use in children and adolescents.

Established cardiovascular disease or serious cardiovascular risk factors. Treatment with Diclofenac-Teva is generally not recommended in patients with cardiovascular disease or uncontrolled arterial hypertension. If treatment is necessary, patients with cardiovascular disease, uncontrolled arterial hypertension, or significant cardiovascular risk factors should only be treated with Diclofenac-Teva after careful assessment and only at doses up to 100 mg daily for treatment courses exceeding 4 weeks.

Renal impairment. Diclofenac-Teva is contraindicated in patients with renal impairment (GFR <15 ml/min/1.73 m²). Specific studies in patients with renal function impairment have not been conducted; therefore, no dosage recommendations can be made. Diclofenac-Teva should be used with caution in patients with impaired renal function.

Hepatic impairment. Diclofenac-Teva is contraindicated in patients with hepatic impairment. Specific studies in patients with hepatic function impairment have not been conducted; therefore, no dosage recommendations can be made. Diclofenac-Teva should be used with caution in patients with mild to moderate hepatic impairment.

Children.

Diclofenac-Teva in the form of solution for injection is contraindicated for use in children and adolescents.

Overdose.

Symptoms. There is no typical clinical picture of diclofenac overdose. Overdose may cause symptoms such as vomiting, gastrointestinal bleeding, diarrhea, dizziness, tinnitus, or convulsions. In cases of severe poisoning, acute renal failure and liver damage are possible.

Treatment. Management of acute poisoning with NSAIDs, including diclofenac, consists primarily of supportive measures and symptomatic therapy necessary to address complications such as hypotension, renal failure, convulsions, gastrointestinal disturbances, and respiratory depression. Specific interventions such as forced diuresis, dialysis, or hemoperfusion cannot guarantee the elimination of NSAIDs, including diclofenac, due to their high plasma protein binding and extensive metabolism.

Adverse Reactions

Adverse reactions to the medicinal product are listed by frequency: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); frequency not known (cannot be estimated from available data). The adverse effects listed below include those associated with sodium diclofenac administration under both short-term and long-term use.

Infections and infestations: very rare – abscess at injection site.

Blood and lymphatic system disorders: very rare – thrombocytopenia, leukopenia, anemia (including hemolytic and aplastic anemia), agranulocytosis.

Immune system disorders: rare – hypersensitivity, anaphylactic and anaphylactoid reactions (including arterial hypotension and shock); very rare – angioedema (including facial swelling).

Psychiatric disorders: very rare – disorientation, depression, insomnia, nightmares, irritability, and other psychiatric disorders.

Nervous system disorders: common – headache, dizziness; rare – somnolence, fatigue; very rare – paresthesia, memory impairment, convulsions, anxiety, tremor, aseptic meningitis, taste disturbance, stroke; frequency not known – confusion, hallucinations, sensory disturbances, malaise.

Eye disorders: very rare – visual disturbances, blurred vision, diplopia; frequency not known – optic neuritis.

Ear and labyrinth disorders: common – vertigo; very rare – tinnitus, hearing impairment.

Cardiac disorders: uncommon* – palpitations, chest pain, heart failure, myocardial infarction; frequency not known – Kounis syndrome. *Frequency reflects data from long-term treatment with high doses (150 mg/day).

Vascular disorders: common – arterial hypertension; very rare – arterial hypotension, vasculitis.

Respiratory, thoracic and mediastinal disorders: rare – asthma (including dyspnea); very rare – pneumonitis.

Gastrointestinal disorders: common – nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, decreased appetite; rare – gastritis, gastrointestinal bleeding, hematemesis, hemorrhagic diarrhea, melena, gastric or intestinal ulcer (with or without bleeding, gastrointestinal stenosis or perforation (sometimes fatal, especially in elderly patients), which may lead to peritonitis); very rare – colitis (including hemorrhagic colitis, ischemic colitis, and exacerbation of ulcerative colitis or Crohn’s disease), constipation, stomatitis, glossitis, esophageal disorders, membranous intestinal strictures, pancreatitis.

Hepatobiliary disorders: common – increased transaminase levels; rare – hepatitis, jaundice, liver function abnormalities; very rare – fulminant hepatitis, hepatonecrosis, liver failure.

Skin and subcutaneous tissue disorders: common – skin rashes; rare – urticaria; very rare – bullous eruptions, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), exfoliative dermatitis, alopecia, photosensitivity reaction, purpura, allergic purpura of Henoch-Schönlein, pruritus.

Renal and urinary disorders: common – fluid retention, edema; very rare – acute kidney injury (acute renal failure), hematuria, proteinuria, nephrotic syndrome, tubulointerstitial nephritis, renal papillary necrosis.

General disorders and administration site conditions: common – injection site reaction, injection site pain, induration; rare – swelling, necrosis at injection site; very rare – abscess at injection site; frequency not known – cutaneous medication embolism (Nicolau syndrome).

Reproductive system and breast disorders: very rare – impotence.

Meta-analysis of clinical trial data and pharmacoepidemiological evidence indicate an increased risk of arterial thrombotic complications (e.g., myocardial infarction or stroke) associated with diclofenac use, particularly at high therapeutic doses (150 mg/day) and with prolonged treatment.

Visual disturbances. Visual disturbances such as blurred vision, visual impairment, and diplopia are class effects of NSAIDs and are generally reversible upon discontinuation of the drug. The most likely mechanism of visual disturbances is inhibition of prostaglandin synthesis and other related compounds, which may disrupt retinal blood flow regulation and contribute to visual disturbances. If such symptoms occur during diclofenac treatment, an ophthalmological examination should be performed to rule out other possible causes.

Reporting of suspected adverse reactions. All suspected adverse reactions and lack of drug efficacy should be reported via the following link: https://aisf.dec.gov.ua/.

Shelf life. 2 years

Storage conditions. Store at temperatures not exceeding 30 °C. Keep out of reach of children. Store ampoules in the original carton.

Incompatibilities. Due to lack of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Packaging. 3 mL of solution in an ampoule, 5 ampoules in a blister; 1 or 2 blisters per carton.

Prescription status. Prescription only.

Manufacturer. Merckle GmbH

Manufacturer's address and place of business.
Ludwig-Merckle-Straße 3, 89143 Blaubeuren, Germany