Olfen®-af

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Olfen®-AF (Olfen®-AF)

Composition:

Active substance: aceclofenac;

1 tablet contains 200 mg of aceclofenac;

Excipients: microcrystalline cellulose, povidone, sodium croscarmellose, sodium stearyl fumarate, poloxamer, hypromellose, carbomer, Opadry White (OY-C-7000A).

Pharmaceutical form. Modified-release tablets.

Main physicochemical properties: white, elongated, biconvex modified-release tablets coated with a film layer, embossed with "UT" on one side and "CL CR" on the other side.

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

Pharmacological properties.

Pharmacodynamics.

Aceclofenac is an effective non-steroidal agent of the phenylacetic acid group, possessing anti-inflammatory, analgesic, and antipyretic properties. Its mechanism of action is considered to be inhibition of the enzyme cyclooxygenase, which is involved in the synthesis of prostaglandins.

Pharmacokinetics.

Absorption. Aceclofenac is well absorbed from the gastrointestinal tract (GIT). Peak plasma concentrations are reached within 1–3 hours after oral administration, and its bioavailability is almost 100%. The time to reach maximum concentration (Tmax) is delayed when taken with food, but this does not affect the extent of absorption.

Distribution. Aceclofenac is highly bound to plasma proteins (> 99.7%). It penetrates into synovial fluid, where concentrations reach approximately 60% of plasma levels. 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, mainly as conjugated hydroxymetabolites. Only 1% of a single oral dose is excreted unchanged.

Aceclofenac is metabolized in hepatocytes and microsomes, forming [2-(2,6-dichloro-4-hydroxy-phenylamino) phenyl] acetoxyacetic acid as the main metabolite, which then undergoes further conjugation. Secondary metabolites include [2-(2,6-dichlorophenylamino)-5-hydroxyphenyl] acetoxyacetic acid and [2-(2,6-dichlorophenylamino) phenyl] acetic acid, as well as hydroxylated derivatives: [2-(2,6-dichloro-4-hydroxyphenylamino) phenyl] acetic acid and [2-(2,6-dichlorophenylamino)-5-hydroxyphenyl] acetic acid.

Clinical characteristics.

Indications.

Pain associated with rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, periarthritis of the shoulder and scapula, lumbar pain (lumbago), sciatica, and periarticular rheumatism.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients of the medicinal product;
• History of gastrointestinal bleeding or perforation related to previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs);
• As with other NSAIDs, aceclofenac is contraindicated in patients in whom administration of acetylsalicylic acid or other NSAIDs induces asthma attacks, bronchospasm, angioedema, urticaria, or acute rhinitis, as well as in patients with hypersensitivity to these drugs;
• Bronchial asthma;
• Active peptic ulceration/hemorrhage or recurrent peptic ulceration/hemorrhage in history (two or more distinct episodes of established ulceration or bleeding);
• Active bleeding or diseases associated with bleeding (hemophilia, coagulation disorders);
• Severe hepatic or renal insufficiency;
• Congestive heart failure [NYHA (New York Heart Association) functional class II–IV];
• Ischemic heart disease (angina pectoris or history of myocardial infarction);
• Peripheral arterial disease;
• Cerebrovascular diseases, including history of stroke or transient ischemic attack;
• Not to be used for the treatment of perioperative pain in coronary artery bypass graft (CABG) surgery (or when using cardiopulmonary bypass);
• Inflammatory bowel diseases (e.g., Crohn’s disease or ulcerative colitis);
• Third trimester of pregnancy or breastfeeding period;
• Pediatric age.

Interaction with other medicinal products and other forms of interaction.

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

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

Pharmacokinetic interaction studies of aceclofenac are limited; the information below is based on data from other NSAIDs.

Should 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 be avoided when high-dose methotrexate is administered.

Cardiac glycosides, digoxin. NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and inhibit renal clearance of glycosides, leading to increased plasma levels. Concomitant use should be avoided unless digoxin levels are monitored.

Anticoagulants. NSAIDs inhibit platelet aggregation and damage the gastrointestinal mucosa, which may enhance 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 performed. NSAIDs may potentiate the effects of anticoagulants such as warfarin. Close monitoring is required in patients receiving combined therapy with anticoagulants and aceclofenac.

Lithium. NSAIDs cause increased plasma lithium levels and reduced renal lithium clearance. Therefore, careful monitoring for signs of lithium toxicity is required when used concomitantly. Concomitant use should be avoided unless lithium concentrations are monitored.

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

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs). Increased risk of gastrointestinal bleeding.

Combinations requiring dose adjustment and caution in use.

Methotrexate. Potential interaction between NSAIDs and methotrexate should be considered, even at low methotrexate doses, particularly in patients with impaired renal function. Renal function parameters should be monitored during concomitant use. Caution is required if NSAIDs and methotrexate have been used within 24 hours, as methotrexate concentration may increase, enhancing its toxicity.

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

Mifepristone. NSAIDs should not be used within 8–12 days after mifepristone administration, as NSAIDs may reduce the effect of mifepristone. Due to the anti-prostaglandin effect of NSAIDs, mifepristone should be used cautiously in women, as it may theoretically reduce the efficacy of NSAIDs. The clinical significance of this interaction is unknown.

Zidovudine. Concurrent use with NSAIDs increases the risk of hematologic toxicity. Increased risk of hemarthrosis and hematomas has been confirmed in HIV-infected patients with hemophilia receiving zidovudine and ibuprofen.

Antihypertensive medicinal products. NSAIDs may 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, usually reversible, increases in certain patients with renal impairment, such as elderly or dehydrated patients. Therefore, caution is required when used concomitantly with NSAIDs, 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).

Corticosteroids. Increased risk of gastrointestinal ulcers and bleeding.

Diuretics. Aceclofenac, like other NSAIDs, may reduce the effect of diuretics, decrease the diuretic effect of furosemide and bumetanide, and reduce the antihypertensive effect of thiazides. Diuretics increase the risk of nephrotoxicity with NSAID use. Although concomitant use with bendroflumethiazide did not affect blood pressure control, interactions with other diuretics cannot be ruled out. Concomitant use with potassium-sparing diuretics may lead to increased potassium levels—serum potassium levels should be monitored.

Antidiabetic medicinal products. It has been shown that diclofenac, when used concomitantly with oral antidiabetic agents, does not affect their clinical efficacy. However, isolated reports of hypoglycemic and hyperglycemic effects have been reported. Therefore, dose adjustment of hypoglycemic agents may be necessary when prescribing aceclofenac.

Other analgesics, NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors. Concomitant use with acetylsalicylic acid or other NSAIDs should be avoided, as this may increase the frequency of adverse reactions, including increased risk of gastrointestinal bleeding.

Special precautions for use.

Undesirable effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see below for risks associated with gastrointestinal and cardiovascular systems).

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

Cardiovascular, renal, and hepatic disorders

NSAID use may cause dose-dependent reduction in prostaglandin production and renal failure. Patients at high risk of such reactions include those with impaired renal function, heart failure, hepatic dysfunction, patients taking diuretics, and elderly patients. These patients require monitoring of renal function.

Renal effects

The important role of prostaglandins in maintaining renal blood flow should be considered when administering the drug to patients with heart failure or impaired renal function, those taking diuretics or recovering from major surgery, and elderly patients. NSAID use may lead to dose-dependent reduction in prostaglandin synthesis and acute renal failure. Effects on renal function are usually reversible, and condition normalizes after discontinuation of aceclofenac.

Caution should be exercised when administering the drug to patients with mild to moderate hepatic or renal impairment, as well as to patients with other conditions associated with fluid retention. In these patients, NSAID use may lead to renal dysfunction 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 usually resolve after discontinuation of aceclofenac.

Hepatic effects

Careful medical monitoring is required in patients with mild to moderate hepatic impairment. If abnormalities in liver function tests persist or worsen, or if clinical symptoms/signs of liver disease or other manifestations (e.g., eosinophilia, rash) appear, aceclofenac should be discontinued. Hepatitis may develop without prodromal symptoms. Use of aceclofenac in patients with hepatic porphyria may provoke an acute attack.

Cardiovascular and cerebrovascular effects

Appropriate monitoring and recommendations are necessary for patients with a history of mild to moderate arterial hypertension and/or congestive heart failure, as NSAID therapy may be associated with fluid retention and edema. Clinical studies and epidemiological data suggest that some NSAIDs (particularly at high doses and with prolonged use) slightly increase the risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

Treatment with aceclofenac in patients with congestive heart failure (NYHA I) and significant cardiovascular risk factors (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) should only be initiated after careful assessment of potential risks and with particular caution.

Cardiovascular risk may increase with higher doses and longer duration of NSAID use; therefore, the lowest effective daily dose for the shortest possible duration should be used. The need for symptomatic treatment and response to therapy should be reviewed periodically.

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 gastrointestinal disease, including upper and lower gastrointestinal tract involvement;

− history of peptic ulcer, gastrointestinal bleeding, or perforation;

− ulcerative colitis;

− Crohn’s disease;

− bleeding tendency, systemic lupus erythematosus, porphyria, hematopoietic disorders, and hemostasis disorders.

Gastrointestinal effects

Peptic ulcers, gastrointestinal perforation, and gastrointestinal bleeding, sometimes fatal, have been reported with all NSAIDs at any time during treatment, with or without warning symptoms, regardless of prior history of serious gastrointestinal pathology.

Careful medical monitoring is essential in patients with suspected history of peptic ulcers, those with gastrointestinal symptoms, ulcerative colitis, Crohn’s disease, hemorrhagic diathesis, or hematological disorders.

The risk of gastrointestinal ulceration, perforation, and bleeding increases with high NSAID doses, particularly in patients with a history of peptic ulcer disease, especially if complicated by bleeding or perforation, and in elderly patients. These patients should start treatment with the lowest doses. Concomitant therapy with protective agents (such as misoprostol or proton pump inhibitors) should be considered for these patients, as well as for those requiring concomitant low-dose acetylsalicylic acid or other drugs that may increase gastrointestinal complications.

Patients with a history of gastrointestinal toxicity, especially elderly patients, should report any unusual abdominal symptoms (particularly gastrointestinal bleeding), including at the beginning of treatment. Particular caution is required in patients receiving concomitant medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (warfarin), SSRIs, or antiplatelet agents (acetylsalicylic acid).

If peptic ulcer or gastrointestinal bleeding occurs in a patient taking aceclofenac, treatment should be discontinued. NSAIDs should be used cautiously in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn’s disease), as these conditions may worsen.

Systemic lupus erythematosus (SLE) and mixed connective tissue disease

Patients with SLE and mixed connective tissue disease have an increased risk of developing aseptic meningitis.

Hypersensitivity and skin reactions

As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur in patients who have not previously taken this drug.

Severe skin reactions, sometimes fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been very rarely reported with NSAID use. The highest risk of such reactions occurs early in therapy (within the first month).

Aceclofenac should be discontinued at the first signs of skin reactions (rash, mucosal lesions, hypersensitivity reactions).

In special cases, such as varicella, complications may occur, including serious skin and soft tissue infections. The role of NSAIDs in worsening these infections cannot currently be excluded; therefore, aceclofenac should be avoided in varicella.

Impairment of fertility in women

Aceclofenac use may impair fertility in women. This drug is not recommended for women wishing to become pregnant. Women experiencing difficulty conceiving or undergoing infertility evaluation should discontinue aceclofenac.

Hematological disorders

Aceclofenac may reversibly inhibit platelet aggregation (see "Anticoagulants" in 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, particularly if present in history, as NSAID use may provoke sudden bronchospasm in such patients.

Elderly patients

In elderly patients (aged 65 years and older), NSAID use is associated with an increased frequency of adverse reactions, particularly gastrointestinal perforation and bleeding, which may be fatal. In addition, elderly patients more commonly suffer from renal, hepatic, or cardiovascular diseases.

Long-term treatment

All patients taking NSAIDs should be under medical supervision for timely detection of renal failure, hepatic dysfunction (elevated liver enzyme activity), and blood count changes.

Use during pregnancy or breastfeeding.

Pregnancy

There is no information on the use of aceclofenac during pregnancy. Inhibition of prostaglandin synthesis may have a negative effect on pregnancy progression 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 cause pre- and post-implantation embryo-fetal loss and increased embryonic and fetal mortality. In addition, an increased incidence of various malformations, including cardiac defects, has been observed in animals treated with prostaglandin synthesis inhibitors during organogenesis.

Starting from the 20th week of pregnancy, aceclofenac use may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after starting treatment and is usually reversible after discontinuation. Additionally, there have been reports of arterial duct constriction after treatment in the second trimester, most of which resolved after treatment cessation. Therefore, aceclofenac-containing drugs should not be prescribed during the first and second trimesters unless clearly necessary. If aceclofenac is used by a woman planning pregnancy or during the first or second trimester, the dose should be as low as possible and treatment duration as short as possible.

After several days of aceclofenac use starting from the 20th week of pregnancy, consideration should be given to antenatal monitoring for oligohydramnios and arterial duct constriction. Aceclofenac should be discontinued if oligohydramnios or arterial duct constriction is detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may pose the following risks:

• risks to the fetus:

• cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);

• renal dysfunction (see above);

• risks to the mother at the end of pregnancy and to the newborn:

• possible prolongation of bleeding time, anti-aggregatory effect, which may develop even after very low doses;

• inhibition of uterine contractions, leading to delayed or prolonged labor.

Therefore, aceclofenac use is contraindicated during the third trimester of pregnancy.

Breastfeeding

There is no information on the passage of aceclofenac into breast milk. However, radiolabeled (C14) aceclofenac showed minimal transfer into rat milk. Limited available data suggest that NSAIDs are excreted in breast milk in very low concentrations. The drug is contraindicated in breastfeeding women to avoid undesirable effects on the infant. If treatment is necessary, breastfeeding should be discontinued.

Fertility

NSAIDs may impair fertility; therefore, their use is not recommended in women planning pregnancy. Women experiencing difficulty conceiving or undergoing infertility evaluation should discontinue aceclofenac.

Ability to affect reaction speed when driving vehicles or operating machinery.

After taking NSAIDs, adverse effects such as dizziness, vertigo, somnolence, fatigue, and visual disturbances, or other CNS symptoms, may occur. If such reactions occur, patients should not drive vehicles or operate machinery.

Method of Administration and Dosage

Olphen®-AF, modified-release tablets, should be swallowed whole, without chewing or crushing. Take with at least ½ glass of water.

Adverse events can be minimized by using the medicinal product for the shortest duration necessary to control symptoms.

Adults

The recommended dose is 200 mg once daily (every 24 hours).

Elderly Patients

Dose reduction is generally not required. However, 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 serious adverse reactions. When NSAIDs are necessary, they should be prescribed at the lowest effective dose and for the shortest possible duration. Careful monitoring is required to detect gastrointestinal bleeding during NSAID therapy.

Hepatic Impairment

For patients with mild to moderate hepatic impairment, the dose of aceclofenac should be reduced. The recommended initial dose is 100 mg daily (administer aceclofenac in another pharmaceutical form).

Renal Impairment

There is insufficient information to recommend dose adjustment of aceclofenac in patients with mild renal impairment; however, caution should be exercised when administering the medicinal product to these patients.

Children

There are no clinical data on the use of aceclofenac in children; therefore, this medicinal product is contraindicated in this age group.

Overdose

There are no reported cases of aceclofenac overdose in humans.

Symptoms

Symptoms may include headache, nausea, vomiting, epigastric pain, gastrointestinal irritation and gastrointestinal bleeding, rarely diarrhea, disorientation, excitement, coma, drowsiness, dizziness, tinnitus, arterial hypotension, respiratory depression, loss of consciousness, and occasionally seizures. In cases of severe poisoning, acute renal failure and hepatic injury may develop.

Treatment

Management of acute NSAID poisoning includes the use, if necessary, of antacids and other supportive and symptomatic treatments for complications such as arterial hypotension, renal failure, seizures, gastrointestinal mucosal irritation, and respiratory depression. Within one hour after ingestion of a potentially toxic amount of the drug, activated charcoal should be administered or gastric lavage performed.

Specific therapeutic measures such as dialysis or hemoperfusion are likely to be ineffective in removing NSAIDs due to their high degree of protein binding and extensive metabolism.

Forced diuresis, along with monitoring of renal and hepatic function, should be instituted.

Patients should be observed for at least 4 hours after ingestion of a potentially toxic amount of the drug. In cases of frequent or prolonged seizures, intravenous diazepam should be administered.

Treatment is symptomatic and supportive.

Adverse Reactions

The most common adverse reactions of aceclofenac include gastrointestinal disorders, dizziness, and elevated liver enzyme levels.

Gastrointestinal tract: Adverse reactions most frequently involve the gastrointestinal tract (GI). Use of NSAIDs may lead to gastrointestinal ulcers, perforations, or gastrointestinal hemorrhage, sometimes fatal, particularly in elderly patients (see section "Special precautions"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, stomach pain, melena, hematemesis, ulcerative stomatitis, and exacerbations of colitis or Crohn’s disease have been reported during NSAID therapy (see section "Special precautions"). Gastritis has been observed less frequently.

Cardiovascular system: The structure and metabolism of aceclofenac are similar to those of diclofenac, which, according to extensive clinical and epidemiological data, is associated with a slightly increased risk of arterial thrombotic events (myocardial infarction, stroke), especially with high-dose or long-term use. Epidemiological data also indicate an increased risk of acute coronary syndrome and myocardial infarction associated with aceclofenac use. Edema, hypertension, and heart failure have been reported during NSAID therapy.

Hypersensitivity and skin reactions: Allergic reactions may occur during NSAID use, manifesting as anaphylactic reactions, respiratory tract reactivity (including asthma, worsening of asthma, bronchospasm, dyspnea), and various skin reactions, including rashes of different types, pruritus, urticaria, purpura, angioneurotic edema, and less commonly, exfoliative or bullous dermatitis (including epidermal necrolysis and erythema multiforme).

In rare cases, complications such as severe skin and soft tissue infections may occur during varicella (chickenpox).

Neurological disorders and sensory organ disorders: Optic neuritis, cases of aseptic meningitis (particularly in patients with autoimmune disorders such as SLE or mixed connective tissue disease), with symptoms including neck rigidity, fever, disorientation, confusion, hallucinations, and malaise.

Hematological disorders: Agranulocytosis, aplastic anemia.

Adverse reactions reported in clinical studies and post-marketing experience

Gastrointestinal tract: Peptic ulcers, perforations, or gastrointestinal hemorrhages, sometimes fatal (particularly in elderly patients), nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, exacerbations of non-specific ulcerative colitis or Crohn’s disease, gastritis, pancreatitis, stomatitis, hemorrhagic diarrhea.

Hepatobiliary disorders: Hepatitis, jaundice, increased liver enzyme activity.

Immune system: Anaphylactic reactions (including shock), hypersensitivity.

Cardiovascular system: Arterial hypertension, heart failure, tachycardia, hyperemia, flushing, vasculitis.

Renal and urinary system: Nephrotic syndrome, renal failure, nocturnal enuresis, interstitial nephritis.

Nervous system: Visual disturbances, headache, somnolence, tremor, dysgeusia, paresthesia, nuchal rigidity, fever, dysesthesia, agitation, hallucinations, tinnitus, exhaustion, drowsiness, dizziness, aseptic meningitis (particularly in SLE or mixed connective tissue disease).

Blood and lymphatic system: Bone marrow suppression, anemia, granulocytopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia.

Metabolism disorders: Hyperkalemia.

Psychiatric disorders: Dizziness, depression, abnormal dreams, insomnia.

Respiratory system: Dyspnea, bronchospasm, stridor.

Skin and subcutaneous tissue: Pruritus, rash, dermatitis, urticaria, facial swelling, purpura, eczema, bullous dermatitis, Stevens-Johnson syndrome or Lyell’s syndrome, photosensitivity, alopecia, angioneurotic edema, acute reactions of skin and mucous membranes.

General disorders and administration site conditions: Edema, fatigue, calf muscle cramps.

Laboratory test results: Increased blood urea concentration, increased serum creatinine concentration, elevated alkaline phosphatase activity in blood, weight gain.

Reporting 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 in the original packaging at a temperature not exceeding 30 °C. Keep out of reach of children.

Packaging. 10 tablets per blister. 1, 3, or 10 blisters per cardboard box.

Prescription status. Prescription only.

Manufacturer. Korea United Pharm., Inc.

Manufacturer's address and location of business activity.
25-23, Nochan-gongdan-gil, Jeongeun-myeon, Sejong City, Republic of Korea.