Paracetamol Medisorb
Orally, with plenty of liquid, 1-2 hours after eating (taking immediately after eating leads to a delay in the onset of action). Paracetamol should be taken orally at a dose of 200 or 500 mg up to 4 times a day. Adults and children over 12 years of age (body weight over 40 kg) 1-2 tablets (0.5-1 g) up to 4 times a day, if necessary. The maximum single dose is 2 tablets (1 g).
The maximum daily dose is 8 tablets (4 g). The interval between doses is at least 4 hours. In children over 12 years of age, it is recommended to maintain an interval between doses of the drug of at least 6 hours. The drug is not recommended for use for more than 5 days as an analgesic and for more than 3 days as an antipyretic without a doctor’s prescription and supervision.
For children, the dose is calculated based on the child’s body weight: the maximum single dose is 15 mg/kg body weight 4 times a day every 6 hours, the maximum daily dose is 60 mg/kg body weight.
For children (3−6 years old). For a body weight of 15−21 kg, the maximum single dose is 15 mg/kg body weight, the maximum daily dose is 60 mg/kg body weight. Children aged 3−6 years should use pediatric dosage forms to ensure more accurate dosing of the drug.
For children (6−9 years old) . 250 mg (½ 500 mg tablet) up to 4 times daily if needed. The maximum single dose is 250 mg (½ tablet 500 mg). The maximum daily dose is 1 g (2 tablets). The interval between doses is at least 4 hours.
For children (9−12 years old) . 500 mg (1 tablet) up to 4 times a day, if necessary. The maximum single dose is 500 mg (1 tablet). The maximum daily dose is 2 g (4 tablets). The interval between doses is at least 4 hours.
In children, the drug is not recommended for use for more than 3 days without a doctor’s prescription and supervision. Do not exceed the indicated dose. If you exceed the recommended dose, consult your doctor immediately, even if you feel well, because there is a risk of delayed serious liver damage. Increasing the daily dose of the drug or the duration of treatment is possible only under the supervision of a physician. In patients with chronic or decompensated liver diseases, patients with liver failure, chronic alcoholism, in malnourished patients and in cases of dehydration, the daily dose should not exceed 3 g.
Shelf life: 3 years. Do not use the drug after the expiration date indicated on the package.
Storage conditions: In a dry place, protected from light, at a temperature not exceeding 25 °C. Keep out of the reach of children.
Conditions of release: Dispensed without a prescription.
Attention! Until May 2022, drugs may be found in the old packaging design!
Atorvastatin medisorb film-coated tablets 20 mg No. 30
Interaction
During treatment with HMG-CoA recutase inhibitors, with simultaneous use of cyclosporine, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day) or inhibitors of the CYP3A4 isoenzyme (for example, erythromycin, clarithromycin, antifungal agents - azole derivatives), the risk of developing myopathy increases ( see section Special instructions).
CYP3A4 isoenzyme inhibitors
Since atorvastatin is metabolized by the CYP3A4 isoenzyme, co-administration of atorvastatin with inhibitors of the CYP3A4 isoenzyme may lead to increased plasma concentrations of atorvastatin. The degree of interaction and potentiation effect is determined by the variability of the effect on the CYP3A4 isoenzyme.
It was found that potent inhibitors of the CYP3A4 isoenzyme lead to a significant increase in the concentration of atorvastatin in the blood plasma. The simultaneous use of strong inhibitors of the CYP3A4 isoenzyme (for example, cyclosporine, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole and HIV protease inhibitors, including ritonavir, lopinavir, atazanavir, indinavir, darunavir, etc.) should be avoided whenever possible. If concomitant use of these drugs is necessary, initiating therapy at the lowest dose should be considered and the possibility of reducing the maximum dose of atorvastatin should be evaluated.
Moderate inhibitors of the CYP3A4 isoenzyme (for example, erythromycin, diltiazem, verapamil and fluconazole) may lead to increased plasma concentrations of atorvastatin.
With the simultaneous use of HMG-CoA recutase (statins) and erythromycin, an increased risk of developing myopathy was noted.
Interaction studies between amiodarone or verapamil and atorvastatin have not been conducted. Both amiodarone and verapamil are known to inhibit the activity of the CYP3A4 isoenzyme, and concomitant use of these drugs with atorvastatin may lead to increased atorvastatin exposure. In this regard, it is recommended to reduce the maximum dose of atorvastatin and carry out appropriate monitoring of the patient's condition when used simultaneously with moderate inhibitors of the CYP3A4 isoenzyme. Monitoring should be carried out after the start of therapy and against the background of changing the dose of the inhibitor.
OATP1B1 transport protein inhibitors
Atorvastatin and its metabolites are substrates of the transport protein OATP1B1. OATP1B1 inhibitors (eg, cyclosporine) may increase the bioavailability of atorvastatin. Thus, the combined use of atorvastatin at a dose of 10 mg and cyclosporine at a dose of 5.2 mg/kg/day leads to an increase in the concentration of atorvastatin in the blood plasma by 7.7 times. The effect of inhibition of hepatic uptake transporter function on the concentration of atorvastatin in hepatocytes is unknown. If it is impossible to avoid the simultaneous use of such drugs, it is recommended to reduce the dose and monitor the effectiveness of therapy.
Gemfibrozil/fibrates
During the use of fibrates in monotherapy, adverse reactions (including rhabdomyolysis) affecting the musculoskeletal system were periodically noted. The risk of developing such reactions increases with simultaneous use of fibrates and atorvastatin. If the simultaneous use of these drugs cannot be avoided, the minimum effective dose of atorvastatin should be used, and patients should be regularly monitored.
Ezetimibe
The use of ezetimibe is associated with the development of adverse reactions, including rhabdomyolysis, from the musculoskeletal system. The risk of developing such reactions increases with simultaneous use of ezetimibe and atorvastatin. For such patients, careful monitoring is recommended.
Erythromycin/clarithromycin
With the simultaneous use of atorvastatin and erythromycin (500 mg 4 times a day) or clarithromycin (500 mg 2 times a day), inhibitors of the CYP3A4 isoenzyme, an increase in the concentration of atorvastatin in the blood plasma was observed (see section Special instructions).
Protease inhibitors
The simultaneous use of atorvastatin with protease inhibitors, known as inhibitors of the CYP3A4 isoenzyme, is accompanied by an increase in the concentration of atorvastatin in the blood plasma.
Diltiazem
The combined use of atorvastatin at a dose of 40 mg with diltiazem at a dose of 240 mg leads to an increase in the concentration of atorvastatin in the blood plasma.
Cimetidine
No clinically significant interaction of atorvastatin with cimetidine was found.
Itraconazole
Concomitant use of atorvastatin at doses of 20 to 40 mg and itraconazole at a dose of 200 mg led to an increase in the AUC of atorvastatin.
Grapefruit juice
Since grapefruit juice contains one or more components that inhibit the CYP3A4 isoenzyme, excessive consumption (more than 1.2 L per day) may cause an increase in plasma concentrations of atorvastatin.
Inducers of the CYP3A4 isoenzyme
The combined use of atorvastatin with inducers of the CYP3A4 isoenzyme (for example, efavirenz, rifampicin or St. John's wort preparations) may lead to a decrease in the concentration of atorvastatin in the blood plasma. Due to the dual mechanism of interaction with rifampicin (an inducer of the CYP3A4 isoenzyme and an inhibitor of the hepatocyte transport protein OATP1B1), simultaneous use of atorvastatin and rifampicin is recommended, since delayed administration of atorvastatin after taking rifampicin leads to a significant decrease in the concentration of atorvastatin in the blood plasma. However, the effect of rifampicin on the concentration of atorvastatin in hepatocytes is unknown and if concomitant use cannot be avoided, the effectiveness of such therapy should be carefully monitored.
Antacids
Simultaneous oral administration of a suspension containing magnesium hydroxide and aluminum hydroxide reduced the concentration of atorvastatin in the blood plasma by approximately 35%, but the degree of reduction in the concentration of LDL-C did not change.
Phenazone
Atorvastatin does not affect the pharmacokinetics of phenazone, so interaction with other drugs metabolized by the same cytochrome isoenzymes is not expected.
Colestipol
When used simultaneously with colestipol, the plasma concentration of atorvastatin decreased by approximately 25%. However, the lipid-lowering effect of the combination of atorvastatin and colestipol was superior to that of each drug alone.
Digoxin
With repeated administration of digoxin and atorvastatin at a dose of 10 mg, the equilibrium concentrations of digoxin in the blood plasma did not change. However, when digoxin was used in combination with atorvastatin at a dose of 80 mg/day, digoxin concentrations increased by approximately 20%. Patients receiving digoxin in combination with atorvastatin require appropriate monitoring.
Azithromycin
With simultaneous use of atorvastatin at a dose of 10 mg 1 time per day and azithromycin at a dose of 500 mg 1 time per day, the concentration of atorvastatin in the blood plasma did not change.
Oral contraceptives
When atorvastatin was co-administered with oral contraceptives containing norethisterone and ethinyl estradiol, significant increases in the AUC of norethisterone and ethinyl estradiol by approximately 30% and 20%, respectively, were observed. This effect should be taken into account when choosing an oral contraceptive for a woman taking atorvastatin.
Terfenadine
With simultaneous use of atorvastatin and terfenadine, no clinically significant changes in the pharmacokinetics of terfenadine were detected.
Warfarin
In clinical studies in patients regularly receiving warfarin therapy, concomitant use of atorvastatin at a dose of 80 mg per day resulted in a slight increase in prothrombin time of approximately 1.7 seconds. during the first 4 days of therapy. The indicator returned to normal within 15 days of atorvastatin therapy. Although significant interactions affecting anticoagulant function have been observed only in rare cases, the prothrombin time should be determined before initiating atorvastatin therapy in patients receiving coumarin anticoagulant therapy and frequently enough during therapy to prevent a significant change in the prothrombin time. Once stable prothrombin time values are observed, its monitoring can be carried out in the same way as recommended for patients receiving coumarin anticoagulants. When changing the dose of atorvastatin or discontinuing therapy, prothrombin time should be monitored according to the same principles as described above.
Atorvastatin therapy was not associated with bleeding or changes in prothrombin time in patients who did not receive anticoagulant treatment.
Colchicine
Although studies have not been conducted on the simultaneous use of colchicine and atorvastatin, there are reports of the development of myopathy when using this combination. Caution should be exercised when atorvastatin and colchicine are used concomitantly.
Amlodipine
With simultaneous use of atorvastatin at a dose of 80 mg and amlodipine at a dose of 10 mg, the pharmacokinetics of atorvastatin at steady state did not change.
Fusidic acid
During post-marketing surveillance, cases of rhabdomyolysis have been reported in patients taking concomitant statins, including atorvastatin, and fusidic acid. The mechanism of this interaction is unknown. In patients for whom fusidic acid use is considered necessary, statin treatment should be discontinued for the duration of fusidic acid use. Statin therapy can be resumed 7 days after the last dose of fusidic acid.
In exceptional cases where long-term systemic therapy with fusidic acid is necessary, for example for the treatment of severe infections, the need for concomitant use of atorvastatin and fusidic acid should be considered on a case-by-case basis and under close medical supervision. The patient should seek immediate medical attention if symptoms of muscle weakness, tenderness, or pain occur.
Other concomitant therapy
In clinical studies, atorvastatin was used in combination with antihypertensive drugs and estrogens as part of hormone replacement therapy. There were no signs of clinically significant adverse interactions. Interaction studies with specific drugs have not been conducted.
In addition, an increase in the concentration of atorvastatin was observed when used simultaneously with HIV protease inhibitors (combinations of lopinavir and ritonavir, saquinavir and ritonavir, darunavir and ritonavir, fosamprenavir with ritonavir and nelfinavir), hepatitis C protease inhibitors (boceprevir), clarithromycin and itraconazole. Caution should be exercised when using these drugs together and the lowest effective dose of atorvastatin should be used.
METRONIDAZOLE MEDISORB TAB. 250MG No. 20
Blood and lymphatic system disorders: agranulocytosis, leukopenia, neutropenia, thrombocytopenia.
Immune system disorders: angioedema, anaphylactic shock.
Nervous system disorders: peripheral sensory neuropathy, headache, convulsions, dizziness, encephalopathy and acute cerebellar syndrome (impaired coordination and synergism of movements, ataxia, dysarthria, gait disturbances, nystagmus, tremor) have been reported, which are reversible after withdrawal metronidazole, aseptic meningitis.
Mental disorders: psychotic disorders, including confusion, hallucinations, depression, insomnia, irritability, increased excitability.
Visual disturbances: transient visual disturbances such as diplopia, myopia, blurred contours of objects, decreased visual acuity, impaired color perception, neuropathy/optic neuritis.
Gastrointestinal disorders: epigastric pain, nausea, vomiting, diarrhea, glossitis, stomatitis, metallic taste in the mouth, decreased appetite, anorexia, dry oral mucosa, constipation, pancreatitis (reversible cases), discoloration tongue / “coated tongue” (due to the growth of fungal microflora).
Disorders of the liver and biliary tract: increased activity of liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase), the development of cholestatic or mixed hepatitis and hepatocellular liver damage, sometimes accompanied by jaundice in patients treated with metronidazole in combination with other antibacterial agents, cases of liver failure requiring liver transplantation have been observed.
Skin and subcutaneous tissue disorders: rash, itching, skin flushing, urticaria, pustular skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Renal and urinary tract disorders: brownish-reddish coloration of urine due to the presence of a water-soluble metabolite of metronidazole in the urine, dysuria, polyuria, cystitis, urinary incontinence, candidiasis. General disorders and disorders at the injection site: fever, nasal congestion, arthralgia, weakness (for dosage forms for oral and parenteral use), thrombophlebitis (pain, hyperemia or swelling at the injection site) (for dosage forms for parenteral use). Laboratory and instrumental data: flattening of the T wave on the electrocardiogram. If any of the side effects indicated in the instructions worsen, or any other side effects not listed in the instructions are noted, you should immediately inform your doctor.
