Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
Analgetic-antipyretic. Has analgesic, antipyretic and weak anti-inflammatory effect. The mechanism of action is associated with the inhibition of the synthesis of prostaglandins, a predominant effect on the center of thermoregulation in the hypothalamus.
PHARMACOKINETICS
After oral administration, paracetamol is rapidly absorbed from the digestive tract, mainly in the small intestine, mainly through passive transport. After a single dose of 500 mg C max in blood plasma is reached after 10-60 minutes and is about 6 Ојg / ml, then gradually decreases and after 6 hours is 11-12 Ојg / ml.
It is widely distributed in tissues and mainly in liquid media of the body, with the exception of adipose tissue and cerebrospinal fluid.
Binding with proteins is less than 10% and slightly increases with an overdose. Sulfate and glucuronide metabolites do not bind to plasma proteins even at relatively high concentrations.
Paracetamol is metabolized predominantly in the liver by conjugation with glucuronide, conjugation with sulfate, and oxidation involving mixed liver oxidases and cytochrome P450.
Hydroxylated metabolite with negative action - N-acetyl-p-benzoquinonimine, which is formed in very small amounts in the liver and kidneys under the influence of mixed oxidases and is usually detoxified by binding to glutathione, can be heated by overdose of paracetamol and cause tissue damage.
In adults, most paracetamol binds to glucuronic acid and to a lesser extent sulfuric acid. These conjugated metabolites have no biological activity. In premature infants, newborns and in the first year of life, the sulfate metabolite predominates.
T 1/2 is 1-3 hours. In patients with liver cirrhosis, T 1/2 is slightly larger. The renal clearance of paracetamol is 5%.
It is excreted in the urine mainly in the form of glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol.
INDICATIONS
Pain syndrome of mild and moderate intensity of various genesis (including headache, migraine, toothache, neuralgia, myalgia, algodismenorea, pain with injuries, burns). Fever with infectious and inflammatory diseases.
DOSING MODE
Inside or rectally in adults and adolescents with a body weight of more than 60 kg used in a single dose of 500 mg, the frequency of admission - up to 4 times / day.The maximum duration of treatment is 5-7 days.
Maximal doses: single dose - 1 g, daily - 4 g.
Single doses for ingestion for children aged 6-12 years - 250-500 mg, 1-5 years - 120-250 mg, from 3 months to 1 year - 60-120 mg, up to 3 months - 10 mg / kg.Single doses for rectal application in children aged 6-12 years - 250-500 mg, 1-5 years - 125-250 mg.
Multiplicity of application - 4 times / day with an interval of at least 4 hours. The maximum duration of treatment is 3 days.
The maximum dose: 4 single doses per day.
SIDE EFFECT
On the part of the digestive system: rarely - dyspeptic phenomena, with prolonged use in high doses - hepatotoxic effect.
From the hemopoietic system: rarely - thrombocytopenia, leukopenia, pancytopenia, neutropenia, agranulocytosis.
Allergic reactions: rarely - skin rash, itching, urticaria.
CONTRAINDICATIONS
Chronic alcoholism, hypersensitivity to paracetamol.
PREGNANCY AND LACTATION
Paracetamol penetrates the placental barrier. To date, there has been no adverse effect of paracetamol on the fetus in humans.
Paracetamol is excreted in breast milk: the content in milk is 0.04-0.23% of the dose taken by the mother.
If paracetamol is needed during pregnancy and lactation (breastfeeding), the expected benefit of therapy for the mother and the potential risk to the fetus or child should be carefully weighed.
In experimental studies , embryotoxic, teratogenic and mutagenic effects of paracetamol have not been established.
APPLICATION FOR FUNCTIONS OF THE LIVER
Use with caution in patients with impaired renal function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Use with caution in patients with impaired hepatic function.
APPLICATION FOR CHILDREN
The application is possible according to the dosing regimen.
APPLICATION IN ELDERLY PATIENTS
Use with caution in elderly patients.
SPECIAL INSTRUCTIONS
Caution is used in patients with impaired liver and kidney function, with benign hyperbilirubinemia, as well as in elderly patients.
With prolonged use of paracetamol, monitoring of the peripheral blood pattern and the functional state of the liver is necessary.
It is used for the treatment of premenstrual tension syndrome in combination with pamabrom (diuretic, xanthine derivative) and mepirinamine (histamine H 1 -receptor blocker).
DRUG INTERACTION
At simultaneous application with inductors of microsomal liver enzymes, the means possessing hepatotoxic action, there is a risk of intensifying the hepatotoxic effect of paracetamol.
With simultaneous use with anticoagulants, a slight or moderate increase in prothrombin time is possible.
With simultaneous use with anticholinergics, a reduction in paracetamol absorption is possible.
When used simultaneously with oral contraceptives, the excretion of paracetamol from the body is accelerated and its analgesic effect may decrease.
When used simultaneously with uricosuric agents, their effectiveness is reduced.
With the simultaneous use of activated carbon, the bioavailability of paracetamol is reduced.
With simultaneous use with diazepam, a decrease in the excretion of diazepam is possible.
There are reports of the possibility of enhancing the myelodepressant effect of zidovudine when used concomitantly with paracetamol. A case of severe toxic liver damage is described.
Cases of toxic effects of paracetamol when used with isoniazid are described.
With simultaneous use with carbamazepine, phenytoin, phenobarbital, primidone, the effectiveness of paracetamol decreases, which is caused by increased metabolism (glucuronization and oxidation processes) and excretion from the body. The cases of hepatotoxicity with simultaneous application of paracetamol and phenobarbital are described.
When using colestyramine for a period of less than 1 hour after taking paracetamol, a decrease in absorption of paracetamol is possible.
With simultaneous use with lamotrigine, the removal of lamotrigine from the body is moderately increased.
With simultaneous use with metoclopramide, it is possible to increase the absorption of paracetamol and increase its concentration in the blood plasma.
With simultaneous application with probenecid, a decrease in paracetamol clearance is possible; with rifampicin, sulfinpyrazone - it is possible to increase the clearance of paracetamol due to an increase in its metabolism in the liver.
With simultaneous use with ethinyl estradiol, the absorption of paracetamol from the intestine is increased.
