Nurofen Intensive for the treatment of the musculoskeletal system, anti-inflammatory agent, non-steroidal agent, propionic acid derivative.
Ibuprofen, combinations. ATC code M01A E51.
Dosage form: film-coated tablets.
Main physicochemical properties: white to almost white, pearly, oval-shaped tablet, coated with a shell, embossed in the form of characteristic curls.
Appointment
Symptomatic treatment of back and muscle pain, rheumatic pain, pain in mild forms of arthritis, headache, including migraine, toothache, dysmenorrhea, symptoms of colds, flu and fever.
This drug is particularly suitable for the treatment of pain requiring a stronger analgesic effect than that of ibuprofen or paracetamol used alone.
Pharmacological properties
The pharmacological action of ibuprofen and paracetamol differs in site and mode of action, but is synergistic, leading to increased analgesic and antipyretic properties compared to those when each substance is used separately.
Ibuprofen is an NSAID (nonsteroidal anti-inflammatory drug), a derivative of propionic acid, which has demonstrated its effectiveness in suppressing the synthesis of prostaglandins - mediators of pain and inflammation.
Ibuprofen has analgesic, antipyretic and anti-inflammatory effects. In addition, ibuprofen can inhibit platelet aggregation.
Experimental data suggest that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when these drugs are used concomitantly.
Some pharmacodynamic studies show that when single doses of ibuprofen 400 mg were administered within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg), there was a reduction in the effect of aspirin and acetylsalicylic acid on thromboxane formation or platelet aggregation.
Although there is uncertainty about the extrapolation of these data to the clinical situation, the possibility cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid.
With non-systematic use of ibuprofen, such a clinically significant effect is considered unlikely.
The mechanism of action of paracetamol is still not fully understood; however, there is convincing evidence of an analgesic effect on the central nervous system.
Biochemical studies indicate inhibition of COX-2 activity in the central nervous system.
Paracetamol can also stimulate descending pathways of 5-hydroxytryptamine (serotonin) activation, which inhibits the transmission of pain signals in the spinal cord.
The drug is particularly suitable for the treatment of pain requiring a stronger analgesic effect than ibuprofen 400 mg and paracetamol 1000 mg separately.
Studies using this combination in a model of acute pain (postoperative dental pain) and chronic knee pain showed high efficacy of this combination in reducing the severity of acute pain (93.2%) and long-term treatment of chronic pain (60.2%).
This drug has a rapid onset of action with proven significant pain relief, which is noted on average after 18.3 minutes.
Significant pain relief is noted on average after 44.6 minutes.
The analgesic effect of this drug is significantly longer (9.1 hours) than that of paracetamol 500 mg (4:00).
Pharmacokinetics
Ibuprofen is rapidly absorbed from the gastrointestinal tract and is largely bound to blood plasma proteins.
Ibuprofen is detected in plasma within 5 minutes, reaching peak concentrations 1-2 hours after administration on an empty stomach.
Ibuprofen is metabolized in the liver and excreted by the kidneys. The half-life is approximately 2 hours.
Paracetamol is rapidly absorbed from the gastrointestinal tract. At therapeutic concentrations, the level of binding to plasma proteins is low, although dose-dependent.
Paracetamol in blood plasma is determined after 5 minutes, reaching maximum concentration 0.5-0.67 hours after administration on an empty stomach.
Paracetamol is metabolized in the liver and excreted in the urine mainly as conjugates.
Less than 5% of paracetamol is excreted unchanged. The hydroxylated metabolite, which is formed in very small quantities in the liver under the influence of mixed oxidases and is detoxified by binding to hepatic glutathione, can accumulate in paracetamol overdose and cause liver tissue damage.
The half-life is approximately 3 hours.
No significant difference in the pharmacokinetic profile of paracetamol and ibuprofen was found in elderly patients.
The bioavailability and pharmacokinetic profile of ibuprofen and paracetamol in this preparation do not change when taking a single or repeated dose of this combination.
The composition of this drug is developed using technology that ensures the simultaneous release of ibuprofen and paracetamol in such a way as to enhance the effects of each of the active ingredients.
Composition
1 film-coated tablet contains:
ibuprofen - 200 mg paracetamol - 500 mg
Excipients: croscarmellose sodium, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate, white stearic acid and pearlescent coating.
This drug is contraindicated:
patients with individual hypersensitivity to ibuprofen, paracetamol or other components of the drug patients with a history of hypersensitivity reactions (e.g. bronchospasm, angioedema, bronchial asthma, rhinitis or urticaria) after taking ibuprofen, aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) with gastric and duodenal ulcer/bleeding in active form or recurrences in history (two or more severe episodes of ulcer or bleeding) patients with a history of gastrointestinal bleeding or perforation associated with the use of NSAIDs patients with blood clotting disorders patients with severe hepatic, severe renal or severe heart failure (class IV according to the NYHA classification) when used simultaneously with other drugs containing paracetamol, due to an increased risk of serious adverse reactions during the last trimester of pregnancy
Interaction with other drugs
Ibuprofen (like other NSAIDs) should not be used in combination with:
aspirin (acetylsalicylic acid), as this may increase the risk of adverse reactions, except in cases where aspirin (dose not exceeding 75 mg per day) has been prescribed by a doctor. Experimental data suggest that ibuprofen may inhibit the effect of low-dose acetylsalicylic acid (aspirin) on platelet aggregation when used concomitantly. However, the limitations of extrapolation of these data to the clinical situation do not allow definitive conclusions to be drawn that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. With non-systematic use of ibuprofen, such clinically significant effects are considered unlikely; other non-steroidal anti-inflammatory drugs (including selective COX-2 inhibitors), as this may lead to an increased incidence of side effects.
Ibuprofen should be used with caution in combination with the following medicines.
GCS may increase the risk of adverse reactions in the digestive tract.
Antihypertensives and diuretics. Nonsteroidal anti-inflammatory drugs may reduce the therapeutic effect of these drugs and increase the risk of nephrotoxicity.
Anticoagulants. NSAIDs may increase the therapeutic effect of anticoagulants such as warfarin. The anticoagulant effect of warfarin and other coumarins may be potentiated by prolonged regular daily use of paracetamol, with an increased risk of bleeding.
Antiplatelet and selective serotonin reuptake inhibitors: The risk of gastrointestinal bleeding may be increased.
Cardiac glycosides. NSAIDs increase the level of glycosides in plasma, can increase cardiac dysfunction, and reduce kidney filtration function.
Lithium and methotrexate: There is evidence of a potential increase in plasma levels of lithium and methotrexate.
Cyclosporine: Increased nephrotoxicity.
Mifepristone. NSAIDs should not be used earlier than 8-12 days after mifepristone administration, as they reduce its effectiveness.
Tacrolimus: There may be an increased risk of nephrotoxicity with concomitant use of NSAIDs and tacrolimus.
Zidovudine: Increased risk of hematological toxicity with concomitant use of zidovudine and NSAIDs. There is evidence of an increased risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia receiving concomitant treatment with zidovudine and ibuprofen.
Quinolone antibiotics: Concomitant use of NSAIDs and quinolone antibiotics may increase the risk of seizures.
Means for. The rate of absorption of paracetamol may be increased by metoclopramide or domperidone.
Cholestyramine: Absorption of paracetamol may be reduced by cholestyramine.
Application features
Paracetamol should be administered with caution to patients with severe renal and hepatic impairment.
The risk of paracetamol overdose is higher in patients with non-cirrhotic alcoholic liver disease.
In case of overdose, seek medical attention immediately, even if the patient feels well, due to the risk of delayed serious liver damage.
Side effects can be minimized by using the lowest effective dose necessary to relieve symptoms, for the shortest period of time necessary to relieve symptoms, and with meals.
Respiratory effects: Bronchospasm may occur in patients who suffer from bronchial asthma or allergic diseases after using nonsteroidal anti-inflammatory drugs or have a history of these diseases.
Effects on the kidneys. Risk of kidney failure due to deterioration of kidney function.
Effect on the liver. Liver dysfunction.
Clinical trial data suggest that ibuprofen use, particularly at high doses (2400 mg/day), may be associated with an increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). Overall, epidemiological data do not suggest that low-dose ibuprofen use (e.g. ≤ 1200 mg/day) is associated with an increased risk of arterial thrombotic events.
Patients with uncontrolled hypertension, congestive heart failure (NYHA class II-III), established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be treated with ibuprofen only after careful clinical assessment. High doses (2400 mg/day) should be avoided.
The clinical picture should also be carefully assessed before starting long-term treatment in patients with risk factors for cardiovascular complications (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking), especially if high doses of ibuprofen (2400 mg per day) are required.
Gastrointestinal effects: Gastrointestinal bleeding, perforation, and ulceration, which can be fatal, have been reported at any stage of NSAID treatment, regardless of the presence of convincing symptoms or a history of severe gastrointestinal disorders.
The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing NSAID dose, with a history of ulcer, especially ulcers with complications such as bleeding or perforation, and in elderly patients.
For these patients, treatment should be initiated with the lowest effective dose.
Patients with a history of gastrointestinal disorders, especially elderly patients, should be informed of any adverse gastrointestinal symptoms (especially bleeding), especially at the beginning of treatment.
The drug should be prescribed with caution to patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors, or antiplatelet agents such as aspirin.
The occurrence of gastrointestinal bleeding or ulceration in patients receiving ibuprofen-containing drugs requires immediate discontinuation of treatment with this drug.
Nonsteroidal anti-inflammatory drugs are prescribed with caution to patients with a history of gastrointestinal disorders (ulcerative colitis and Crohn's disease), as these conditions may be exacerbated.
Systemic lupus erythematosus and mixed connective tissue disease: Patients with systemic lupus erythematosus and mixed connective tissue disease may be at increased risk of developing aseptic meningitis.
Skin: Very rarely, skin reactions, sometimes fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have occurred with prolonged use of NSAIDs. The risk of developing such reactions is highest at the beginning of treatment: in most cases, such reactions occur within the first month of taking the drug. This drug should be discontinued at the first sign of skin rash, mucosal lesions or other manifestations of hypersensitivity.
Effects on female fertility: There is limited evidence that drugs that inhibit cyclooxygenase/prostaglandin synthesis may affect ovulation. This is reversible upon discontinuation of treatment.
Elderly patients: Elderly patients are more likely to experience adverse reactions to NSAIDs, especially gastrointestinal bleeding or perforation, which can be fatal. If NSAIDs are necessary, they should be used at the lowest effective dose for the shortest duration possible.
The patient should be regularly monitored for the possibility of gastrointestinal bleeding during NSAID therapy.
Use during pregnancy or breastfeeding
The use of the drug should be avoided during the first and second trimesters of pregnancy.
The drug is contraindicated during the third trimester of pregnancy.
According to limited data, ibuprofen passes into breast milk in very low concentrations, so the likelihood of its harmful effects on infants is very low.
Paracetamol passes into breast milk, but in clinically insignificant quantities. Therefore, there is no need to discontinue breastfeeding during short-term therapy with this drug at recommended doses.
Ability to influence reaction speed when driving vehicles or other mechanisms
A single dose or short-term use of the drug usually does not require the use of special precautions.
Method of application
For short-term use only.
The minimum effective dose should be used for the minimum period necessary to eliminate symptoms.
Adults should take 1 tablet up to 3 times a day with an interval between doses of at least 6 hours. Take the tablets with water.
If 1 tablet does not eliminate the symptoms of the disease, 2 tablets should be used per dose, but not more than 3 times a day.
You should not take more than 6 tablets (3000 mg of paracetamol, 1200 mg of ibuprofen) per day.
If the symptoms of the disease persist for more than 3 days, it is necessary to consult a doctor to clarify the diagnosis and correct the treatment regimen. The duration of treatment is determined by the doctor individually depending on the course of the disease and the patient's condition.
There is no need to adjust the dose for elderly patients.
Children. Not for use in children under 18 years of age.
Overdose
Paracetamol
Liver damage is possible in adults who have taken 10 g (equivalent to 20 tablets) or more of paracetamol. Taking 5 g (equivalent to 10 tablets) or more of paracetamol can lead to liver damage if:
the patient is receiving long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, or drugs that induce liver enzymes the patient regularly drinks alcohol the patient is likely to have a glutathione deficiency, for example, has fibrocystic degeneration, HIV infection, cachexia, or is fasting
Symptoms
Symptoms of paracetamol overdose in the first 24 hours are pallor, nausea, vomiting, food aversion and abdominal pain. Liver damage may be manifested by
12-48 hours after overdose, manifested by abnormal liver function tests. Glucose metabolism disorders and metabolic acidosis may occur. In severe poisoning, liver failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma, and death. Acute renal failure with acute tubular necrosis may present with severe back pain, hematuria, and proteinuria and may occur even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have also been reported.
Treatment
In case of paracetamol overdose, emergency medical attention is required.
The patient should be taken to hospital immediately for medical examination, even if there are no early symptoms of overdose.
Symptoms may be limited to nausea and vomiting and may not reflect the severity of the overdose or the risk of organ damage. Treatment should be carried out in accordance with established treatment guidelines.
Treatment with activated charcoal should be considered within 1 hour of taking an overdose of paracetamol.
The concentration of paracetamol in blood plasma should be measured 4 hours or later after ingestion (earlier concentrations are unreliable).
N-acetylcysteine treatment can be given up to 24 hours after taking paracetamol, but the maximum protective effect is obtained when it is administered within 8 hours of taking the overdose. The effectiveness of the antidote decreases sharply after this time.
If necessary, the patient is given intravenous N-acetylcysteine according to the established dose list. In the absence of vomiting, oral methionine can be used as a suitable alternative in remote areas outside the hospital.
Treatment of patients who develop severe liver dysfunction within 24 hours of taking paracetamol should be carried out in accordance with established recommendations.
ibuprofen
The use of ibuprofen in doses exceeding 400 mg/kg in children may cause symptoms of overdose. In adults, the dose-dependent effect is less pronounced. The half-life in overdose is 1.5-5 hours.
Symptoms
Most patients who have taken clinically significant amounts of NSAIDs may experience only nausea, vomiting, epigastric pain, or very rarely diarrhea.
Tinnitus, headache, and gastrointestinal bleeding may occur.
In more severe poisoning, toxic lesions of the central nervous system may occur in the form of drowsiness, sometimes nervous excitement and disorientation or coma.
Sometimes patients experience seizures.
In severe poisoning, metabolic acidosis may occur, and the prothrombin index/international normalized ratio (INR) may be elevated, probably due to effects on blood clotting factors.
Acute renal failure and liver damage may occur in the presence of dehydration.
Patients with bronchial asthma may experience an exacerbation of the disease.
Treatment
Treatment should be symptomatic and supportive, and include maintaining a patent airway and monitoring cardiac symptoms and vital signs until the condition returns to normal.
Oral administration of activated charcoal is recommended within 1 hour after ingestion of a potentially toxic amount of the drug.
For frequent or prolonged seizures, diazepam or lorazepam should be administered intravenously.
Bronchodilators should be used to treat bronchial asthma.
Adverse reactions
The results of clinical studies conducted with this drug do not indicate the presence of any other adverse reactions than those observed with the use of ibuprofen or paracetamol separately.
The following are adverse reactions that have been observed in patients receiving ibuprofen or paracetamol alone during short-term and long-term use.
The first signs are: fever, sore throat, mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding, bruising, and nosebleeds.
Immune system disorders: Uncommon (≥ 1/1000 and <1/100) - hypersensitivity reactions including urticaria and pruritus; very rare (<1/10,000) - severe hypersensitivity reactions.
Symptoms may include swelling of the face, tongue and larynx, shortness of breath, tachycardia and hypotension (anaphylaxis, angioedema or severe shock).
Hypersensitivity reactions may include:
(A) non-specific allergic reactions and anaphylaxis (B) airway reactivity including asthma, asthma exacerbation, bronchospasm and dyspnoea or (C) various forms of skin reactions including pruritus, urticaria, purpura, angioedema and less commonly exfoliative and bullous dermatoses including toxic epidermal necrolysis, Stevens-Johnson syndrome and erythema multiforme
Nervous system disorders: Uncommon (≥ 1/1000 and <1/100) - headache; very rare (<1/10,000) - aseptic meningitis, some symptoms of which (rigidity of the occipital muscles, headache, nausea, vomiting, fever and loss of appetite) may occur in patients with existing autoimmune diseases, such as systemic lupus erythematosus, mixed connective tissue disease.
Cardiovascular system: Frequency unknown - heart failure, edema.
Clinical trial data and epidemiological data suggest that the use of ibuprofen, especially in high doses (2400 mg per day) and long-term treatment, may be associated with an increased incidence of arterial thrombotic complications (e.g. myocardial infarction or stroke).
Vascular system: Frequency unknown - arterial hypertension.
Respiratory system: Frequency unknown - airway reactivity includes: bronchial asthma, bronchospasm and dyspnea.
Gastrointestinal tract. Adverse reactions from the gastrointestinal tract were observed more often. Infrequently (≥ 1/1000 and <1/100) - stomach pain, nausea, dyspepsia rarely (≥ 1/1000 and <1/1000) - diarrhea, flatulence, constipation, vomiting very rarely (<1/10,000) - gastric and duodenal ulcers, gastrointestinal perforation or gastrointestinal bleeding, melena, bloody vomiting (sometimes fatal), ulcerative stomatitis, gastritis, frequency unknown - exacerbation of colitis and Crohn's disease.
Liver and biliary tract disorders: Very rare (<1/10,000) - liver dysfunction.
Skin and subcutaneous tissue disorders: Common (≥ 1/100 and <1/10) - hyperhidrosis; uncommon (≥ 1/1000 and <1/100) - skin rash; very rare (<1/10,000) (<1/10,000) - bullous reactions, including Stevens-Johnson syndrome, erythema multiforme and toxic epidermal necrolysis.
From the kidneys and urinary system. Very rare (<1/10,000) - acute renal failure, especially with prolonged use of NSAIDs, in combination with an increase in serum urea and the appearance of edema. Also papillonecrosis.
Laboratory tests: Common (≥ l/100 and Storage conditions
Shelf life: 3 years.
Store at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging: 6 or 12 tablets in a blister, 1 blister in a cardboard box.
Release category: Over-the-counter.
