Diclotol

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT DICTOL® (DICLOTOL®)

Composition:

Active substance: aceclofenac;

1 sachet (1 g of granules) contains aceclofenac 100 mg;

Excipients: sucrose, sodium saccharin, colloidal anhydrous silicon dioxide, orange flavor, hydroxypropylmethylcellulose, pregelatinized corn starch, citric acid.

Pharmaceutical form. Granules.

Main physicochemical properties: white or almost white granules.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and antirheumatic agents. Acetic acid derivatives and related substances. ATC code M01AB16.

Pharmacological properties.

Pharmacodynamics.

Aceclofenac is a non-steroidal agent with anti-inflammatory and analgesic effects. The mechanism of action of this drug is believed to be based on inhibition of prostaglandin synthesis.

Pharmacokinetics.

Absorption

After oral administration, aceclofenac is rapidly absorbed, with its bioavailability being almost 100%. Maximum plasma concentration is reached approximately within 1.25–3 hours after administration. Food intake slows absorption but does not affect its extent.

Distribution

Aceclofenac is highly bound to plasma proteins (>99.7%). It penetrates into synovial fluid, where its concentration reaches approximately 60% of the plasma concentration. The volume of distribution is approximately 30 L.

Elimination

The mean elimination half-life is 4–4.3 hours. Clearance is 5 liters per hour. Approximately two-thirds of the administered dose is excreted in the urine, primarily as conjugated hydroxylated metabolites. Only 1% of a single oral dose is excreted unchanged.

Aceclofenac is likely metabolized via CYP2C9 to its major metabolite, 4-OH-aceclofenac, which has negligible clinical activity. Diclofenac and 4-OH-diclofenac have been identified among several metabolites.

Special patient groups

No changes in aceclofenac pharmacokinetics have been observed in elderly patients.

In patients with impaired liver function, slower elimination of aceclofenac was observed after a single dose. However, in multiple-dose studies with 100 mg daily, no differences in pharmacokinetic parameters were observed between patients with mild to moderate hepatic cirrhosis and healthy volunteers.

In patients with mild or moderate renal impairment, no clinically significant differences in pharmacokinetics were observed after a single dose.

Clinical characteristics.

Indications.

• Osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and other musculoskeletal disorders associated with pain (e.g., periarthritis of the shoulder and scapula, and other extra-articular manifestations of rheumatism).
• Conditions associated with pain (including back pain, dental pain, and primary dysmenorrhea).

Contraindications.

Aceclofenac is contraindicated:

• in patients with hypersensitivity to aceclofenac or to any excipient of the medicinal product (see section "Composition");
• in patients in whom acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs) induce asthma attacks, bronchospasm, acute rhinitis, angioedema, or urticaria, as well as in patients with hypersensitivity to these agents;
• in patients with a history of gastrointestinal bleeding or ulcer perforation associated with previous NSAID therapy;
• in patients with active peptic ulcer or gastrointestinal bleeding, including those with a history of two or more documented episodes of ulcer development or bleeding;
• in patients with active bleeding or bleeding disorders (hemophilia or coagulation disorders);
• in patients with congestive heart failure (NYHA functional class II–IV), ischemic heart disease, peripheral arterial disease, or cerebrovascular disorders;
• in patients with cerebrovascular disease who have experienced stroke or transient ischemic attacks;
• in patients with ischemic heart disease who have angina or a history of myocardial infarction;
• for the treatment of perioperative pain in coronary artery bypass grafting (or when using cardiopulmonary bypass);
• in patients with severe hepatic or renal impairment;
• during breastfeeding;
• in the third trimester of pregnancy;
• in patients under 18 years of age.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have not been conducted, except for interactions with warfarin.

Aceclofenac is metabolized via cytochrome P450 2C9, and in vitro data indicate that aceclofenac may act as an inhibitor of this enzyme. Therefore, a risk of pharmacokinetic interaction exists when co-administered with phenytoin, cimetidine, tolbutamide, phenylbutazone, amiodarone, miconazole, and sulfaphenazole. As with other NSAIDs, there is an increased risk of pharmacokinetic interaction with other drugs eliminated via active renal secretion, such as methotrexate and lithium salts. Aceclofenac is almost completely bound to plasma albumin; therefore, displacement-type interactions with other protein-bound drugs are possible.

Due to the lack of pharmacokinetic interaction studies with aceclofenac, the information below is based on data from other NSAIDs.

Combinations to be avoided:

Methotrexate. NSAIDs inhibit tubular secretion of methotrexate; in addition, a minor metabolic interaction may occur, leading to reduced methotrexate clearance. Therefore, NSAIDs should always be avoided when high-dose methotrexate is administered.

Cardiac glycosides, digoxin. NSAIDs may exacerbate heart failure, reduce glomerular filtration rate (GFR), and inhibit renal clearance of glycosides, resulting in increased plasma levels of glycosides. Concomitant use should be avoided unless frequent monitoring of digoxin concentration is performed.

Lithium preparations and digoxin. Some NSAIDs inhibit renal clearance of lithium and digoxin, leading to increased serum concentrations of both substances. Concomitant use should be avoided unless frequent monitoring of lithium and digoxin concentrations is performed.

Anticoagulants. NSAIDs inhibit platelet aggregation and damage the gastrointestinal mucosa, which may potentiate the effect of anticoagulants and increase the risk of gastrointestinal bleeding in patients taking anticoagulants. Concomitant use of aceclofenac with oral anticoagulants of the coumarin group, ticlopidine, thrombolytics, and heparin should be avoided unless careful patient monitoring is conducted.

Quinolone antibiotics. Animal studies show that NSAIDs increase the risk of seizures associated with quinolone antibiotics. Patients receiving NSAIDs and quinolone antibiotics have an increased risk of developing seizures.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs). When used concomitantly with NSAIDs, they increase the risk of gastrointestinal bleeding (see section "Special precautions for use").

Combinations requiring dose adjustment and caution in use:

Methotrexate. Potential interaction between NSAIDs and methotrexate should be considered even at low methotrexate doses, especially in patients with impaired renal function. Renal function parameters should be monitored during concomitant use. Caution is required if NSAIDs and methotrexate are administered within 24 hours of each other, as methotrexate concentration may increase, thereby increasing the drug's toxicity.

Cyclosporine, tacrolimus. When NSAIDs are used concomitantly with cyclosporine or tacrolimus, the risk of increased nephrotoxicity due to reduced renal prostacyclin production should be considered. Therefore, renal function parameters should be closely monitored during concomitant use.

Other analgesics, NSAIDs, including selective cyclooxygenase-2 inhibitors. Concomitant use of two or more NSAIDs (including acetylsalicylic acid) should be avoided, as this increases the frequency of adverse effects.

Mifepristone. NSAIDs should not be taken within 8–12 days after mifepristone administration, as they may reduce the efficacy of mifepristone.

Corticosteroids. Increased risk of gastrointestinal ulceration or bleeding (see section "Special precautions for use").

Diuretics. Aceclofenac, like other NSAIDs, may suppress diuretic activity, reduce the diuretic effect of furosemide and bumetanide, and diminish the antihypertensive effect of thiazides. Concomitant use with potassium-sparing diuretics may lead to increased potassium levels; therefore, serum potassium levels should be monitored regularly.

Antihypertensive agents. NSAIDs may also reduce the effectiveness of antihypertensive drugs. Concomitant use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists with NSAIDs may lead to impaired renal function. The risk of acute renal failure, which is usually reversible, increases in certain patients with impaired renal function, such as elderly or dehydrated patients. Therefore, caution is required when using NSAIDs concomitantly, especially in elderly patients. Patients should consume adequate fluids and be under appropriate surveillance (monitoring of renal function at the start of concomitant therapy and periodically during treatment).

Aceclofenac did not affect blood pressure control when used concomitantly with bendroflumethiazide, although interactions with other diuretics cannot be excluded.

Hypoglycemic agents. Clinical studies show that diclofenac can be used together with oral hypoglycemic agents without affecting their clinical efficacy. However, isolated reports of hypoglycemic and hyperglycemic effects have been reported. Therefore, when taking aceclofenac, dosage adjustments of agents that may cause hypoglycemia should be considered.

Zidovudine. Concomitant use of NSAIDs and zidovudine increases the risk of hematological toxicity. Data exist on increased risk of hemarthrosis and hematomas in HIV(+) patients with hemophilia who are receiving zidovudine and ibuprofen.

Special precautions for use.

Concomitant use of aceclofenac and other NSAIDs, including selective COX-2 inhibitors, should be avoided.

Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Dosage and administration" and the risks related to gastrointestinal (GI) and cardiovascular systems described below).

Gastrointestinal (GI) effects

GI bleeding, ulceration, or perforation, sometimes fatal, have been reported with all NSAIDs at any time during therapy, both with and without warning symptoms, and independently of prior serious GI events in medical history.

The risk of GI bleeding, ulceration, and perforation increases with higher NSAID doses, in patients with a history of peptic ulcer, particularly if complicated by bleeding or perforation (see section "Contraindications"), and in elderly patients. These patients should receive the lowest effective dose. Concomitant use of gastroprotective agents (e.g., misoprostol or proton pump inhibitors) is recommended for these patients, as well as for those receiving low-dose acetylsalicylic acid or other drugs that negatively affect the GI tract (see section "Interaction with other medicinal products and other forms of interaction").

Patients with GI disorders, including elderly patients, should report any unusual GI symptoms (especially GI bleeding), particularly in the initial stages of treatment. Particular caution is required in patients receiving concomitant medications that increase the risk of bleeding or ulceration, such as systemic corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents (such as acetylsalicylic acid) (see section "Interaction with other medicinal products and other forms of interaction").

If GI bleeding or ulceration occurs in patients taking aceclofenac, treatment must be discontinued.

Cardiovascular and cerebrovascular effects

Patients with mild to moderate arterial hypertension and/or congestive heart failure require appropriate monitoring and special caution, as fluid retention and edema have been reported with NSAID use.

There are insufficient data to exclude this risk with aceclofenac.

Clinical trials and epidemiological data suggest that some NSAIDs (particularly at high doses and with prolonged use) may slightly increase the risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

Patients with congestive heart failure (NYHA functional class I) and those with cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) should exercise particular caution when using aceclofenac. Since the adverse cardiovascular effects increase with higher doses and longer treatment duration, the lowest effective daily dose for the shortest possible duration should be used. The need for continued symptomatic treatment and the effectiveness of therapy should be reviewed regularly.

Aceclofenac should be used with caution and under close medical supervision in patients with a history of cerebrovascular hemorrhage.

Aceclofenac should be used with caution and under close medical supervision in patients with the following conditions (due to the risk of exacerbation) (see section "Adverse reactions"):

− symptoms indicating GI disease, including upper and lower GI tract;

− history of GI ulcer, bleeding, or perforation;

− ulcerative colitis;

− Crohn’s disease;

− bleeding tendencies, systemic lupus erythematosus (SLE), porphyria, and disorders of hematopoiesis and hemostasis.

Effects on liver and kidneys

NSAID use may cause dose-dependent reduction in prostaglandin synthesis and lead to acute renal failure. The importance of prostaglandins in maintaining renal blood flow should be considered when administering the drug to patients with impaired cardiac, renal, or hepatic function, patients receiving diuretics, postoperative patients, and elderly patients.

Caution should be exercised when using the drug in patients with mild to moderate hepatic or renal impairment, as well as in patients with other conditions associated with fluid retention. In these patients, NSAID use may lead to deterioration of renal function and fluid retention. Caution is also advised when using aceclofenac in patients taking diuretics or those at increased risk of hypovolemia. The lowest effective dose should be used, and renal function should be monitored regularly. Renal adverse effects are usually reversible upon discontinuation of aceclofenac.

Aceclofenac therapy should be discontinued if liver function test abnormalities persist or worsen, or if clinical symptoms of liver disease or other manifestations (e.g., eosinophilia, rash) occur. Hepatitis may develop without prodromal symptoms. NSAID use in patients with hepatic porphyria may provoke an attack.

Hypersensitivity and skin reactions

Like other NSAIDs, aceclofenac may cause allergic reactions, including anaphylactic/anaphylactoid reactions, even upon first administration. Severe skin reactions (some potentially fatal), including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely after NSAID use (see section "Adverse reactions"). The highest risk of these reactions occurs early in treatment, and most of these adverse reactions develop during the first month of therapy. If skin rashes, mucosal lesions in the oral cavity, or other signs of hypersensitivity occur, aceclofenac should be discontinued.

In special cases, complications such as severe skin and soft tissue infections may occur with chickenpox. At present, a role of NSAIDs in worsening these infections cannot be excluded. Therefore, aceclofenac should be avoided in patients with chickenpox.

Systemic lupus erythematosus (SLE) and mixed connective tissue disease

Patients with SLE and mixed connective tissue diseases have an increased risk of developing aseptic meningitis (see section "Adverse reactions").

Hematological disorders

Aceclofenac may cause reversible inhibition of platelet aggregation (see section "Interaction with other medicinal products and other forms of interaction").

Respiratory system disorders

Caution should be exercised when administering the drug to patients with bronchial asthma, including those with a history of asthma, as NSAID use may provoke sudden bronchospasm in such patients.

Elderly patients

Caution should be exercised when using the drug in elderly patients (aged 65 years and older), as they are more likely to experience adverse effects (particularly GI bleeding and perforation) with NSAID use. Complications may be fatal. Elderly patients also more frequently suffer from renal, hepatic, or cardiovascular diseases.

Long-term use

All patients receiving long-term NSAID therapy should be under close medical supervision (including complete blood count, liver and kidney function tests).

Excipients

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., essentially "sodium-free".

If intolerance to certain sugars is known, consult a physician before taking this medicinal product, as it contains sucrose.

Use during pregnancy or breastfeeding

Pregnancy

There are no data on the use of aceclofenac during pregnancy.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development.

Epidemiological data indicate an increased risk of miscarriage, congenital heart defects, and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of congenital heart defects increases from less than 1% to approximately 1.5%. The risk increases with higher doses and longer duration of treatment.

In animal studies, prostaglandin synthesis inhibitors have led to pre- and post-implantation embryo loss and fetal mortality. Increased incidence of various malformations, including cardiovascular defects, has also been observed in animals receiving prostaglandin synthesis inhibitors during organogenesis.

From the 20th week of pregnancy, aceclofenac use may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after initiation of treatment and is usually reversible upon discontinuation. Additionally, there have been reports of arterial duct constriction after second-trimester treatment, most of which resolved after stopping therapy. Therefore, Diklotol® should not be prescribed during the first and second trimesters of pregnancy except in cases of extreme necessity. If aceclofenac is used by a woman trying 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.

Fetal monitoring for oligohydramnios and arterial duct constriction should be considered after aceclofenac exposure of several days or more starting from the 20th week of pregnancy. Diklotol® use should be discontinued if oligohydramnios or arterial duct constriction is detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors:

• may affect the fetus by causing cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
• may affect the fetus by causing renal dysfunction, which may progress to renal failure with oliguria (see above).

In women (late in pregnancy) and newborns, the drug may:

• affect bleeding time due to antiplatelet effects, which may occur even after very low doses;
• inhibit uterine contractions, leading to delayed or prolonged labor.

Therefore, aceclofenac is contraindicated during the third trimester of pregnancy (see sections "Contraindications" and "Special precautions for use").

Breastfeeding period

There is no information on the passage of aceclofenac into human breast milk. However, minimal penetration of radiolabeled (C14) aceclofenac into rat milk has been observed.

Like other NSAIDs, aceclofenac is excreted in small amounts into breast milk; therefore, the drug is contraindicated in breastfeeding women to avoid undesirable effects on the infant.

Fertility

Aceclofenac, like other cyclooxygenase/prostaglandin synthesis inhibitors, may reduce fertility and is therefore not recommended for women attempting to conceive. Women experiencing difficulties in conceiving or undergoing fertility investigations should discontinue aceclofenac.

Ability to influence reaction speed when driving or operating machinery

Patients who experience symptoms such as weakness, dizziness, vertigo, or other central nervous system effects while taking NSAIDs should refrain from driving or operating machinery.

Dosage and Administration

Administration

Diclotol®, granules, is intended for oral administration. Dissolve the contents of one sachet in 40–60 mL (mL) of water and take immediately.

Concomitant food intake slows the rate of absorption of the active substance but does not reduce the extent of absorption from the gastrointestinal tract.

Dosage

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Special Warnings and Precautions for Use").

Adults. The recommended dose is one sachet twice daily (one sachet in the morning and one in the evening).

Elderly patients. Dose reduction is usually not required; however, precautionary measures outlined in the section "Special Warnings and Precautions for Use" should be considered.

Careful monitoring of these patients is essential, as they more frequently have impaired renal or hepatic function, cardiovascular disorders, and are often receiving concomitant therapy for other conditions, which increases the risk of developing serious adverse reactions. If NSAIDs are necessary, they should be administered at the lowest possible dose and for the shortest possible duration. Dose reduction is generally not required. Patients should be closely monitored for gastrointestinal bleeding during NSAID therapy, and recommendations described in the section "Special Warnings and Precautions for Use" should be followed.

Hepatic impairment. In patients with mild to moderate hepatic impairment, the dose of aceclofenac should be reduced. The recommended initial dose is 100 mg daily (see section "Special Warnings and Precautions for Use").

Renal impairment. There is no information indicating that dose adjustment of aceclofenac is required in patients with mild renal impairment; however, caution should be exercised when administering the drug to these patients (see section "Special Warnings and Precautions for Use").

Children.

The safety and efficacy of aceclofenac in children and adolescents have not been established; therefore, this medicinal product is not recommended for use in this age group (see section "Contraindications").

Overdose.

There are no data on aceclofenac overdose in humans.

Possible symptoms

Headache, nausea, vomiting, stomach pain, dizziness, drowsiness, gastrointestinal irritation, gastrointestinal bleeding, diarrhea, disorientation, excitement, coma, tinnitus, arterial hypotension, respiratory depression, loss of consciousness, seizures. In severe poisoning, acute renal failure and hepatic dysfunction may occur.

Treatment

Management of acute NSAID poisoning includes administration of antacids (if necessary) and other supportive symptomatic therapy for complications such as arterial hypotension, renal failure, seizures, gastrointestinal mucosal irritation, and respiratory depression.

Management of acute poisoning following oral intake of aceclofenac includes prevention of drug absorption by gastric lavage and administration of activated charcoal (repeated doses) as soon as possible after overdose. Forced diuresis, dialysis, or hemoperfusion may be insufficiently effective in eliminating NSAIDs due to their high degree of protein binding and extensive metabolism.

However, adequate urine output should be maintained.

Renal and hepatic function must be carefully monitored.

The patient should be observed for at least four hours after ingestion of a potentially toxic amount of the drug.

In cases of frequent or prolonged seizures, intravenous diazepam should be administered. Other interventions may be indicated depending on the patient's clinical condition.

Adverse Reactions

Gastrointestinal tract: The most frequently reported adverse reactions were gastrointestinal (GI) in nature. Gastrointestinal ulcers, perforation, or gastrointestinal bleeding, sometimes fatal, may occur during NSAID therapy, particularly in elderly patients (see section "Special Warnings and Precautions for Use"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbations of colitis and Crohn's disease have been reported during NSAID use (see section "Special Warnings and Precautions for Use"). Gastritis is less frequently observed.

Cardiovascular and cerebrovascular events: Edema, hypertension, and heart failure have been reported in association with NSAID therapy.

Aceclofenac is structurally and metabolically related to diclofenac, which, according to extensive clinical and epidemiological data, is associated with a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke), particularly with high-dose or long-term use. Epidemiological data also suggest an increased risk of acute coronary syndrome and myocardial infarction associated with aceclofenac use (see sections "Contraindications" and "Special Warnings and Precautions for Use").

Hypersensitivity and skin reactions: Non-specific allergic reactions may occur during NSAID therapy, including anaphylactic reactions, respiratory tract reactivity (including asthma, worsening of asthma, bronchospasm, or dyspnea), and various skin reactions such as rashes of different types, pruritus, urticaria, purpura, and angioedema. Less frequently, exfoliative and bullous dermatitis (including Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme) have been reported.

Neurological disorders and sensory organ disorders: Optic neuritis, cases of aseptic meningitis (particularly in patients with autoimmune disorders such as systemic lupus erythematosus or mixed connective tissue disease) have been reported. Symptoms may include neck stiffness (rigidity), fever, disorientation, confusion, hallucinations, and malaise.

Hematological disorders: Agranulocytosis, aplastic anemia.

Clinical studies and epidemiological data indicate that some NSAIDs (particularly when used at high doses or for prolonged periods) may slightly increase the risk of arterial thrombotic events (e.g., myocardial infarction or stroke) (see section "Special Warnings and Precautions for Use").

The table below lists adverse reactions reported during aceclofenac use, grouped by system organ class and frequency of occurrence: 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).

System organ class by MedDRA	Common ≥1/100, <1/10	Uncommon ≥1/1000, <1/100	Rare ≥1/10000, <1/1000	Very rare <1/10000
Blood and lymphatic system disorders			anaemia	bone marrow suppression, granulocytopenia, thrombocytopenia, neutropenia, haemolytic anaemia
Immune system disorders			anaphylactic reactions (including shock), hypersensitivity
Metabolism and nutrition disorders				hyperkalaemia
Psychiatric disorders				depression, abnormal dreams, insomnia
Nervous system disorders	confusion			paraesthesia, tremor, somnolence, headache, dysgeusia (taste disturbances)
Eye disorders			visual disturbances
Ear and labyrinth disorders				vertigo, tinnitus
Cardiac disorders			heart failure	palpitations
Vascular disorders			arterial hypertension, worsening of arterial hypertension	flushing, hot flushes, vasculitis
Respiratory, thoracic and mediastinal disorders			dyspnoea	bronchospasm, stridor
Gastrointestinal disorders	dyspepsia, abdominal pain, nausea, diarrhoea	flatulence, gastritis, constipation, vomiting, ulcerative stomatitis	melena, gastrointestinal ulcers, haemorrhagic diarrhoea, gastrointestinal haemorrhage	stomatitis, haematemesis, intestinal perforation, gastrointestinal haemorrhage, exacerbation of Crohn’s disease and ulcerative colitis, pancreatitis
Hepatobiliary disorders	increased liver enzyme activity			liver injury (including hepatitis), increased blood alkaline phosphatase activity, jaundice
Skin and subcutaneous tissue disorders		pruritus, rash, dermatitis, urticaria	angioneurotic oedema	purpura, eczema, severe skin and mucosal reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis)
Renal and urinary disorders		increased blood urea concentration, increased blood creatinine concentration		nephrotic syndrome, renal failure
General disorders and administration site conditions				oedema, increased fatigue, muscle cramps (in legs)
Investigations				weight increased

Other adverse reactions observed with NSAIDs

Rare:

Renal and urinary disorders: interstitial nephritis.

Skin and subcutaneous tissue disorders: bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), photosensitization.

In exceptional cases, serious skin infections and soft tissue infections have been observed during the use of NSAIDs in patients with varicella (see also sections "Special precautions for use" and "Interaction with other medicinal products and other forms of interaction").

Reporting suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 25 °C.

Keep out of reach of children.

Packaging.

1 g of granules in a sachet. 20 sachets in a cardboard package.

Prescription status.

Prescription only.

Manufacturer.

KUSUM HEALTHCARE PVT LTD.

Manufacturer's address and location of operations.

Plot No. M-3, Indore Special Economic Zone, Phase-II, Pithampur, Distt. Dhar, Madhya Pradesh, Pin 454774, India.