Description
Latin name
Perfalgan
Release form
Perfalgan. Injection.
A clear, colorless or slightly yellowish solution without visible mechanical impurities.
Packing
In 1 bottle of 100 ml of solution. In a cardboard bundle of 12 bottles.
Pharmacological action
Analgesic-antipyretic. It has an analgesic, antipyretic and weak anti-inflammatory effect. The mechanism of action is associated with inhibition of prostaglandin synthesis, the 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 Cmax in plasma is reached after 10-60 minutes and is about 6 μg / ml, then gradually decreases and after 6 hours it is 11-12 μg / ml.
It is widely distributed in tissues and mainly in body fluids, with the exception of adipose tissue and cerebrospinal fluid.
Protein binding is less than 10% and increases slightly with an overdose. Sulfate and glucuronide metabolites do not bind to plasma proteins even in relatively high concentrations.
Paracetamol is metabolized primarily in the liver by conjugation with glucuronide, conjugation with sulfate and oxidation involving mixed liver oxidases and cytochrome P450.
A negatively hydroxylated metabolite, N-acetyl-p-benzoquinoneimine, which is produced in very small amounts in the liver and kidneys by the influence of mixed oxidases and is usually detoxified by binding to glutathione, can become heated during an overdose of paracetamol and cause tissue damage.
In adults, most paracetamol binds to glucuronic acid and, to a lesser extent, to sulfuric acid. These conjugated metabolites do not have biological activity. In preterm infants, newborns and in the first year of life, the sulfate metabolite predominates.
T1 / 2 is 1-3 hours. In patients with cirrhosis of the liver, T1 / 2 is slightly larger. The renal clearance of paracetamol is 5%.
Excreted in urine mainly in the form of glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol.
Indications
Pain of moderate intensity, especially after surgery.
Feverish syndrome against a background of infectious and inflammatory diseases.
The drug is indicated for the rapid relief of pain and fever syndrome, including when the oral route of administration is difficult.
Contraindications
Hypersensitivity to paracetamol or propacetamol hydrochloride (paracetamol prodrug) or any other component of the drug.
Severe impaired liver function.
Children under 12 years old.
Precautions – severe renal failure (creatinine clearance <30 ml / min), benign hyperbilirubinemia (including Gilbert syndrome, viral hepatitis, alcoholic liver damage), alcoholism, old age, glucose-6-phosphate dehydrogenase deficiency. Use during pregnancy and lactation Paracetamol crosses 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 you need to use paracetamol during pregnancy and lactation (breastfeeding), you should carefully weigh the expected benefits of therapy for the mother and the potential risk to the fetus or child. In experimental studies, the embryotoxic, teratogenic and mutagenic effects of paracetamol have not been established. Composition One ml of solution contains: Active substances: Paracetamol – 10 mg Excipients: mannitol, cysteine hydrochloride monohydrate, disodium phosphate dihydrate, sodium hydroxide, concentrated hydrochloric acid, water for injection, nitrogen. Dosage and Administration Intravenous single infusion over 15 minutes. An open and unused drug must be destroyed. An additional dilution of 0.9% sodium chloride solution is allowed, a maximum of ten times. Such a diluted solution should be used within an hour after its preparation (including the time of infusion). Adolescents (over 12 years old) and adults with a body weight of 35 to 50 kg: 15 mg / kg of paracetamol per administration, i.e. 1.5 ml / kg. The maximum daily dose should not exceed 60 mg / kg body weight. The minimum interval between administrations should be 4 hours. Adolescents (over 12 years old) and adults weighing more than 50 kg: the maximum single dose is I g of paracetamol, i.e. I bottle (100 ml). The maximum daily dose is 4 g. The interval between injections of the drug should be at least 4 hours. Side effects From the skin: itching, rash on the skin and mucous membranes (usually erythematic or urtikarnaya), Quincke’s edema. From the digestive tract: increased activity of liver enzymes (usually without the development of jaundice). From the cardiovascular system: arterial hypotension. From the hemopoietic organs: thrombocytopenia. Drug Interaction Inductors of microsomal oxidation in the liver (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) increase the production of hydroxylated active metabolites, which causes even more parasitic reactions. Prolonged use of barbiturates reduces the effectiveness of paracetamol. Microsomal oxidation inhibitors (incl. cimetidine) reduce the risk of hepatotoxic action. Prolonged use with other NSAIDs increases the risk of nephropathy, renal papillary necrosis, and end-stage renal failure. Prolonged use of high doses of paracetamol with salicylate increases the risk of kidney or bladder cancer. Diflunisal increases the concentration of paracetamol in blood plasma by 50% (risk of hepatotoxicity). Overdose Symptoms of acute overdose (develop within 24 h after administration of paracetamol): gastrointestinal disorders (diarrhea, decreased appetite, nausea and vomiting, abdominal discomfort and / or abdominal pain), b. 12 13 h after administration of paracetamol, there was an increase in the activity of hepatic transaminases, lactate dehydrogenase, and bilirubin levels, as well as a decrease in prothrombin levels. At a single injection in adults of 7.5 g or more or in children greater than 140 mg / kg cytolysis of hepatocytes occurs with complete and irreversible liver necrosis, development of hepatic failure, metabolic acidosis and encephalopathy, which can lead to coma and death. Symptoms of chronic overdose (manifested 2-4 days after drug overdose): hepatotoxic effect characterized by general (pain, weakness, adynamia, sweating) and specific (from the liver) symptoms. The hepatotoxic effect can lead to the development of hepatonecrosis and be complicated by the development of hepatic encephalopathy (impaired thinking, suppression of higher nervous activity, agitation and stupor), convulsions, respiratory depression, coma, brain edema, disorders of blood coagulation, development of DIC, hypoglycemia, metabolic acidosis, arrhythmia, collapse. Rarely, liver dysfunction develops rapidly and is complicated by renal failure (tubular necrosis). Treatment of acute overdose: administration of SH-group donors and precursors of glutathione-methionine synthesis (8 9 h after overdose) and N-acetylcysteine (12 h). The need for further administration of methionine and N-acetylcysteine is determined by the concentration of paracetamol in the blood, as well as by the time elapsed after its administration. Storage conditions The drug should be stored at a temperature of 15 ° to 30 ° C. Expiration 2 Year Deystvuyuschee substances Paracetamol Pharmacy terms Prescription Bristol-Myers Squibb, United States
