Paracetamol, tablets 500 mg 20 pcs

An analgesic-antipyretic. It has analgesic, antipyretic and weak anti-inflammatory action. The mechanism of action is associated with inhibition of prostaglandin synthesis, predominant effect on the thermoregulation center in the hypothalamus.

Pharmacokinetics

After oral administration, paracetamol is rapidly absorbed from the gastrointestinal tract, mainly in the small intestine, mainly by passive transport. After a single dose of 500 mg, the C_max in plasma is reached after 10-60 min and is about 6 µg/ml, then gradually decreases and is 11-12 µg/ml after 6 h.

Widely distributed in tissues and mainly in the fluid media of the body, with the exception of adipose tissue and cerebrospinal fluid.

Protein binding is less than 10% and increases slightly in overdose. Sulfate and glucuronide metabolites do not bind to plasma proteins even at relatively high concentrations.

Paracetamol is metabolized primarily in the liver through conjugation to glucuronide, conjugation to sulfate and oxidation with the participation of mixed liver oxidases and cytochrome P450.

The hydroxylated metabolite with negative effects, 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 accumulate in paracetamol overdose and cause tissue damage.

In adults, most paracetamol binds to glucuronic acid and to a lesser extent to 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 h. In patients with cirrhosis, the T_1/2 is slightly longer. Renal clearance of paracetamol is 5%.

Extracted in the urine mainly as glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol.

Indications

Active ingredient

Composition

In one tablet

the active ingredient: paracetamol – 500 mg;

excipients:

potato starch,

croscarmellose sodium (sodium croscarmellose),

povidone (polyvinylpyrrolidone low molecular weight medical),

stearic acid,

talk.

How to take, the dosage

Orally or rectally in adults and adolescents with body weight over 60 kg is used in a single dose of 500 mg, the frequency of administration – up to 4 times a day. Maximum duration of treatment is 5-7 days.

Maximum doses: single dose 1 g, daily – 4 g.

Dose for oral administration in 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 in rectal administration in children aged 6-12 years – 250-500 mg, 1-5 years – 125-250 mg.

The frequency of use is 4 times a day with an interval of at least 4 hours. Maximum duration of treatment is 3 days.

Maximum dose: 4 single doses per day.

Interaction

In concomitant use with inducers of microsomal liver enzymes, agents with hepatotoxic effects, there is a risk of increased hepatotoxic effects of paracetamol.

In concomitant use with anticoagulants a slight to moderately pronounced increase in prothrombin time may occur.

Concomitant use with anticholinergic agents may reduce absorption of paracetamol.

In concomitant use with oral contraceptives, excretion of paracetamol from the body is accelerated and its analgesic effects may be reduced.

Concomitant use with uricosuric agents decreases their effectiveness.

The concomitant use of activated charcoal decreases the bioavailability of paracetamol.

Concomitant use with diazepam may decrease the excretion of diazepam.

There have been reports about the possibility of enhancing the myelodepressive effect of zidovudine when used concomitantly with paracetamol. A case of severe toxic liver damage has been described.

In cases of toxic effects of paracetamol during concomitant use with isoniazid have been described.

Concomitant use with carbamazepine, phenytoin, phenobarbital, primidone decreases the effectiveness of paracetamol due to increased metabolism (glucuronidation and oxidation processes) and excretion. There have been described cases of hepatotoxicity with concomitant use of paracetamol and phenobarbital.

When using colestyramine for a period less than 1 hour after taking paracetamol, absorption of the latter may decrease.

Concomitant use with lamotrigine moderately increases excretion of lamotrigine.

Concomitant use with metoclopramide may increase absorption of paracetamol and increase its plasma concentrations.

Concomitant use with probenecid may decrease clearance of paracetamol; with rifampicin, sulfinpyrazone may increase clearance of paracetamol due to increased metabolism in the liver.

Concomitant use with ethinylestradiol increases absorption of paracetamol from the intestine.

Special Instructions

With caution is used in patients with hepatic and renal dysfunction, with benign hyperbilirubinemia, as well as in elderly patients.

In long-term use of paracetamol it is necessary to monitor the peripheral blood picture and the functional state of the liver.

Contraindications

Side effects

The digestive system: rare – dyspeptic phenomena, with prolonged use in high doses – hepatotoxic effect.

Hematopoietic system: rarely – thrombocytopenia, leukopenia, pancytopenia, neutropenia, agranulocytosis.

Allergic reactions: rare – skin rash, itching, urticaria.

Pregnancy use

Paracetamol penetrates the placental barrier. To date, no adverse effects of paracetamol on the fetus in humans have been noted.

Paracetamol is excreted in breast milk: the content in milk is 0.04-0.23% of the dose taken by the mother.

If it is necessary to use paracetamol during pregnancy and lactation (breastfeeding), the expected benefit to the mother and the potential risk to the fetus or baby should be carefully weighed.

In experimental studies no embryotoxic, teratogenic and mutagenic effects of paracetamol have been established.

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