Instructions Zotek-400 film-coated tablets 400 mg blister No. 10
Composition
active ingredient: dexibuprofen;
1 film-coated tablet contains 200 mg or 300 mg or 400 mg of dexibuprofen;
excipients: microcrystalline cellulose, colloidal anhydrous silica, talc, carmellose calcium, coating composition: hypromellose, titanium dioxide (E 171), talc, dichloromethane, isopropyl alcohol.
Dosage form
Film-coated tablets.
Main physicochemical properties:
Zotec®-200: round biconvex tablets, film-coated white.
Zotec®-300 and Zotec®-400: oblong biconvex tablets, film-coated white with a score line on one side.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Propionic acid derivatives. Dexibuprofen. ATC code M01A E14.
Pharmacological properties
Pharmacodynamics.
Dexibuprofen is a pharmacologically active isomer of racemic ibuprofen, which belongs to the non-selective non-steroidal anti-inflammatory drugs (NSAIDs). Its mechanism of action is associated with the inhibition of prostaglandin synthesis. The drug has antipyretic, analgesic and anti-inflammatory properties.
The results of comparative clinical studies in the treatment of osteoarthritis, dysmenorrhea, and pain (including dental) indicate that dexibuprofen at a dose 2 times lower than ibuprofen has similar efficacy.
Pharmacokinetics.
After oral administration, dexibuprofen is rapidly and completely absorbed from the small intestine. Maximum blood concentrations are reached approximately 2 hours after oral administration of 200 mg of the drug. Plasma protein binding is approximately 99%.
Dexibuprofen is metabolized in the liver (hydroxylation, carboxylation), after which it is excreted as inactive metabolites, mainly (90%) by the kidneys, the rest with bile. The half-life is 1.8-3.5 hours.
Indication
Symptomatic therapy of mild to moderate pain of various origins: toothache, back pain, joint pain, muscle pain, rheumatic pain, dysmenorrhea.
Contraindication
Hypersensitivity to dexibuprofen, other NSAIDs or to other components of the drug; use in patients in whom substances with a similar mechanism of action, such as acetylsalicylic acid and other NSAIDs, cause attacks of bronchial asthma, bronchospasm, acute rhinitis or lead to the development of nasal polyps, urticaria or angioedema; history of bleeding or perforation in the digestive tract associated with the use of NSAIDs; active phase of peptic ulcer disease/bleeding in the digestive tract, history of peptic ulcer disease/bleeding in the digestive tract (at least two confirmed facts of ulcer or bleeding); Crohn's disease or nonspecific ulcerative colitis in the active phase; cerebrovascular bleeding or other bleeding in the active phase; disorders of blood formation or blood clotting; severe hepatic insufficiency, severe renal insufficiency, severe heart failure.
Interaction with other medicinal products and other types of interactions
The concomitant use of dexibuprofen with the following medicines is not recommended:
Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin. In case of concomitant use, it is recommended to monitor coagulation processes and, if necessary, adjust the dose of anticoagulants.
Other NSAIDs, including acetylsalicylic acid (at a dose of more than 100 mg/day): concomitant use of other NSAIDs, including selective COX-2 inhibitors, may increase the risk of ulcers and bleeding in the gastrointestinal tract.
Lithium: NSAIDs may increase plasma lithium levels by reducing its renal clearance. In case of concomitant use, frequent monitoring of lithium plasma levels should be performed and, if necessary, a reduction in its dose should be considered.
Methotrexate at doses of 15 mg/week or more: when NSAIDs are used within 24 hours before or after taking methotrexate, the level of the latter in the blood plasma may increase due to a decrease in renal clearance and increase the toxic effect.
The simultaneous use of dexibuprofen with the following drugs should be carried out with caution:
Aminoglycosides, tacrolimus, sirolimus, cyclosporine: with simultaneous use with NSAIDs, the risk of nephrotoxicity may increase due to reduced prostaglandin synthesis. In case of simultaneous use, renal function should be constantly monitored, especially in elderly patients.
Antihypertensives: NSAIDs may reduce the effectiveness of beta-blockers, possibly by inhibiting the synthesis of vasodilator prostaglandins.
Antiplatelet agents, selective serotonin reuptake inhibitors: when used concomitantly with NSAIDs may increase the risk of gastrointestinal bleeding.
Acetylsalicylic acid (at a dose below 100 mg/day): simultaneous use with NSAIDs may impair the ability of low-dose acetylsalicylic acid to inhibit platelet aggregation;
Digoxin: NSAIDs may increase plasma levels of digoxin and increase its toxicity.
Agents that increase plasma potassium levels (e.g. potassium-sparing diuretics, ACE inhibitors, angiotensin-II antagonists, ciclosporin, tacrolimus, trimethoprim, heparin): NSAIDs may increase plasma potassium levels. Monitoring of plasma potassium levels is recommended in case of concomitant use.
Zidovudine: Concomitant use of NSAIDs and zidovudine increases the risk of hemarthrosis and hematoma in patients with hemophilia.
Potassium-sparing, loop and thiazide diuretics: when used simultaneously with NSAIDs, there may be an increased risk of renal failure due to reduced renal blood flow.
Corticosteroids: Concomitant use with NSAIDs may increase the risk of gastrointestinal bleeding and ulcers.
Methotrexate at doses less than 15 mg/week: Dexibuprofen may increase plasma levels of methotrexate. In the case of concomitant use of dexibuprofen and low doses of methotrexate (less than 15 mg/week), the patient's blood parameters should be monitored, especially at the beginning of treatment. The combination should be used with particular caution in patients with impaired renal function (even moderate), in particular in elderly patients, and renal function should be monitored regularly.
Pemetrexed: High doses of NSAIDs may increase pemetrexed plasma levels. Patients with renal impairment should avoid NSAIDs for 2 days before and 2 days after pemetrexed administration.
Oral antidiabetic agents: Concomitant use of NSAIDs with sulfonylureas may lead to fluctuations in plasma glucose levels. Monitoring of plasma glucose levels may be necessary.
Thrombolytics, antiplatelet agents: dexibuprofen enhances the antithrombotic effect of the latter by inhibiting platelet aggregation.
Phenytoin: Some NSAIDs may increase phenytoin plasma levels and increase its toxicity. In case of concomitant use, phenytoin plasma levels should be monitored and the dose adjusted if necessary.
Phenytoin, phenobarbital, rifampicin: with simultaneous use, the effectiveness of dexibuprofen may be reduced.
Alcohol: Excessive alcohol consumption while taking NSAIDs may increase the risk of digestive side effects.
Application features
Adverse reactions that occur with the use of dexibuprofen can be reduced by using the minimum effective dose necessary to treat symptoms for the shortest period of time.
With prolonged use of dexibuprofen, patients should have regular monitoring of renal, hepatic and hematological functions.
Continuous use of analgesics, especially combinations of different painkillers, can lead to severe kidney damage with the development of renal failure (analgesic nephropathy).
The concomitant use of dexibuprofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
Effect on the digestive tract.
Gastrointestinal bleeding, perforation, and ulceration, sometimes fatal, have been reported at any time during treatment with NSAIDs, regardless of the presence of warning symptoms or a previous history of severe gastrointestinal disorders.
Elderly patients have an increased incidence of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal.
The risk of gastrointestinal bleeding, perforation, and ulceration increases with increasing doses of NSAIDs, in patients with a history of ulcer, especially if complicated by bleeding or perforation, in alcoholics, and in the elderly. These patients should start treatment with the lowest possible dose.
NSAIDs should be used with caution in patients with chronic inflammatory bowel diseases (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated.
NSAIDs should be used with caution in patients receiving concomitant medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g. warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents (e.g. acetylsalicylic acid). In these patients, as well as in patients with a history of ulcer, especially if complicated by bleeding or perforation, in alcohol-dependent patients, and in elderly patients, the physician should consider the advisability of combination therapy with misoprostol or proton pump inhibitors.
Patients with a history of gastrointestinal disorders, especially elderly patients, should be informed of any unusual gastrointestinal symptoms (predominantly bleeding), especially gastrointestinal bleeding at the beginning of treatment.
Effect on the cardiovascular system.
Patients with a history of hypertension and/or heart failure (mild to moderate) should start treatment with caution (doctor's consultation is required), as cases of fluid retention and edema have been reported with NSAID therapy.
Clinical trial and epidemiological data suggest that the use of ibuprofen (especially at high doses of 2400 mg/day) and long-term treatment may be associated with a slightly increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). Overall, epidemiological data do not suggest that low doses of ibuprofen (e.g. ≤ 1200 mg/day) may lead to an increased risk of myocardial infarction. There are insufficient data to exclude this risk with dexibuprofen.
For patients with uncontrolled hypertension, congestive heart failure, diagnosed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease, long-term treatment may be prescribed by a physician only after careful analysis.
Patients with significant risk factors for cardiovascular complications (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking) should be prescribed long-term NSAID treatment only after careful consideration.
Effect on the blood system.
Like other NSAIDs, dexibuprofen may reversibly inhibit platelet aggregation and prolong bleeding time. Use with caution in patients with bleeding diathesis, other coagulation disorders and when dexibuprofen is used concomitantly with oral anticoagulants.
Experimental data suggest that ibuprofen may inhibit the effects of low-dose acetylsalicylic acid on platelet aggregation when used concomitantly. However, the limited data and uncertainty regarding the extrapolation of ex vivo data to the clinical situation prevent definitive conclusions from being drawn regarding regular ibuprofen use; effects are considered unlikely with occasional ibuprofen use.
Effect on the urinary system.
Like other prostaglandin synthesis inhibitors, dexibuprofen may adversely affect renal function, which may lead to glomerular or interstitial nephritis, renal papillary necrosis, nephrotic syndrome and acute renal failure.
Like other NSAIDs, dexibuprofen may increase plasma concentrations of urea nitrogen and creatinine.
In patients with impaired renal function, dexibuprofen should be used with caution at the lowest effective dose, taking into account the risk of fluid retention, edema and deterioration of renal function, and regular monitoring of renal function should be performed.
Effect on the hepatobiliary system.
As with other NSAIDs, slight increases in some liver function tests and significant increases in AST and ALT may occur. In the event of significant increases in ALT and AST, dexibuprofen should be discontinued.
In patients with impaired liver function, dexibuprofen should be used with caution at the lowest effective dose and liver function should be monitored regularly.
Effects on the skin and subcutaneous tissue.
Very rarely, severe skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, may occur with NSAIDs. The highest risk of such reactions is observed in the early stages of therapy, in most cases the onset of such reactions occurs within the first month of treatment. Dexibuprofen should be discontinued at the first sign of skin rash, pathological changes in the mucous membranes or any other sign of hypersensitivity.
Impact on fertility in women.
There is limited evidence that medicinal products that inhibit cyclooxygenase/prostaglandin synthesis may affect fertility and are not recommended in women attempting to conceive. Dexibuprofen should be discontinued in women who have difficulty conceiving or are undergoing investigation for infertility.
Impact on the immune system.
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur. In patients with a history of bronchial asthma, NSAIDs may cause bronchospasm.
Dexibuprofen should be used with caution in patients with systemic lupus erythematosus and mixed connective tissue diseases due to an increased risk of developing adverse reactions from the nervous system and kidneys, including aseptic meningitis.
Like other NSAIDs, dexibuprofen may mask the symptoms of infectious diseases.
Varicella can rarely cause serious skin and soft tissue infections. At present, a role for NSAIDs in worsening the severity of these infections cannot be excluded. Consequently, it is recommended that dexibuprofen be avoided in patients with varicella.
Use during pregnancy or breastfeeding
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo-foetal 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 cardiovascular malformations has increased from less than 1% to approximately 1.5%. The risk is thought to increase with dose and duration of therapy. In animal studies, prostaglandin synthesis inhibitors have been shown to increase pre- and post-implantation and embryo-foetal mortality. There has also been an increase in the incidence of various malformations, including cardiovascular. During the third trimester of pregnancy, the use of any prostaglandin synthesis inhibitors may have effects on the fetus such as cardiopulmonary toxicity (premature closure of the fetal ductus arteriosus with pulmonary hypertension) and renal dysfunction, which may progress to renal failure with oligohydramnios; on the mother: suppression of uterine contractile function, which may lead to an increase in the duration of labor with a possible increase in bleeding time in the mother and child, even when using very low doses.
The use of dexibuprofen should be avoided during the first and second trimesters of pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus. If used during the first or second trimester of pregnancy, the lowest effective dose should be used for the shortest possible period of time. From the beginning of the 6th month of pregnancy, the use of dexibuprofen is contraindicated.
Breastfeeding period.
Dexibuprofen passes into breast milk in very low concentrations. Use during breastfeeding is only possible in low doses for a short period of time.
Fertility.
The use of NSAIDs may affect fertility and is not recommended in women attempting to conceive (see section "Special warnings and precautions for use").
Ability to influence reaction speed when driving vehicles or other mechanisms
Provided that the recommendations regarding dosage and duration of treatment are followed, the drug does not affect the reaction speed when driving or using other mechanisms. However, in case of dizziness, increased fatigue, drowsiness, disorientation or visual disturbances, driving or using other mechanisms should be avoided.
Method of administration and doses
The dosage regimen is set by the doctor individually, taking into account the intensity of the pain syndrome. Adults should usually be prescribed 1-2 tablets (200-400 mg of dexibuprofen) 3 times a day after meals. The recommended initial dose is 200 mg of dexibuprofen. The recommended daily dose is 600-900 mg of dexibuprofen, divided into 3 doses. The highest daily dose is 1200 mg, the highest single dose is 400 mg.
For dysmenorrhea, the highest single dose is 300 mg, the highest daily dose is 900 mg. It is advisable to take it with meals.
The drug is intended for symptomatic relief of pain, but if the symptoms of the disease persist for longer than 3 days, are accompanied by high fever, headache, or other phenomena, clarification of the diagnosis and additional correction of the treatment regimen are necessary.
Patients with impaired liver and kidney function.
Patients with moderate hepatic or renal impairment should start with reduced doses. Dexibuprofen is contraindicated in patients with severe hepatic or renal impairment.
Elderly patients.
Elderly patients are recommended to start therapy with lower doses. The dose can be increased to the recommended daily dose only after good tolerability of the drug has been established.
Children.
The drug should not be used in pediatric practice.
Overdose
Dexibuprofen is characterized by low acute toxicity. In most cases, overdose is asymptomatic. The risk of developing symptoms appears when using more than 80-100 mg/kg ibuprofen (equivalent to 40-50 mg/kg dexibuprofen).
Symptoms: abdominal pain, nausea, vomiting, lethargy, drowsiness, headache, nystagmus, tinnitus, ataxia, in rare cases – gastrointestinal bleeding, arterial hypotension, hypothermia, metabolic acidosis, convulsions, renal dysfunction, coma, adult respiratory distress syndrome, transient apnea attacks.
Treatment: symptomatic therapy, there is no specific antidote. In case of overdose, activated charcoal should be taken and gastric lavage should be performed (only within the first hour after poisoning). Forced diuresis, hemodialysis, hemoperfusion are ineffective due to the high degree of binding of dexibuprofen to blood proteins.
Adverse reactions
Infections and infestations: exacerbation of inflammatory infectious processes (necrotizing fasciitis).
From the side of the blood and lymphatic system: prolongation of blood clotting time, thrombocytopenia, leukopenia, granulocytopenia, pancytopenia, agranulocytosis, aplastic anemia, hemolytic anemia.
On the part of the psyche: anxiety, psychotic reactions, depression, irritability, hallucinations.
Nervous system: drowsiness, headache, vertigo, dizziness, insomnia, anxiety, disorientation, confusion, agitation, aseptic meningitis.
On the part of the organs of vision: visual impairment (including diplopia), reversible toxic amblyopia.
From the auditory system: tinnitus, hearing impairment.
From the digestive tract: dyspepsia, abdominal pain, diarrhea, nausea, vomiting, gastrointestinal ulcers and bleeding, gastritis, ulcerative stomatitis, melena, gastrointestinal perforations, flatulence, constipation, esophagitis, esophageal strictures, exacerbation of diverticulitis, nonspecific hemorrhagic colitis, ulcerative colitis, Crohn's disease.
In the event of gastrointestinal bleeding, anemia and hematomesis may develop.
From the urinary system: interstitial nephritis, nephrotic syndrome, renal failure cannot be excluded, taking into account the experience of using NSAIDs.
From the hepatobiliary system: liver dysfunction, hepatitis, jaundice.
Skin and subcutaneous tissue disorders: rash, urticaria, pruritus, purpura (including allergic purpura), erythema multiforme, epidermal necrolysis, systemic lupus erythematosus and other collagen diseases, alopecia, photosensitivity reactions, Stevens-Johnson syndrome, Lyell's syndrome, allergic vasculitis.
General disorders: increased fatigue, increased sweating.
When using NSAIDs, edema, development of heart failure, increased blood pressure, and fluid retention have also been reported, especially in patients with arterial hypertension or renal failure.
Clinical trial data and epidemiological data suggest that the use of ibuprofen (especially at high doses of 2400 mg per day) and long-term treatment may be associated with a slightly increased risk of arterial thrombotic complications (e.g. myocardial infarction or stroke) (see section "Special warnings and precautions for use").
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
10 tablets in a blister, 1 or 10 blisters in a cardboard pack.
Vacation category
According to the recipe.
Producer
Optimus Generics Limited.
Location of the manufacturer and its business address
Plot No S-8, S-9, S-13 & S-14, APIIC, Pharma Sez, Green Industrial Park, Polepally (V), Jadcherla (M), Mahabubnagar, In-509 301, India.
