Paracetamol - instructions for use, dose, side effects, contraindications

Paracetamol has an analgesic, antipyretic and extremely weak anti-inflammatory effect, which is associated with its influence on the center of thermoregulation in the hypothalamus and a weak ability to inhibit the synthesis of prostaglandins

in peripheral tissues. The absence of a blocking effect on the synthesis of prostaglandins in peripheral tissues determines the absence of a negative effect on water-salt metabolism (retention of sodium and water ions) and the mucous membrane of the gastrointestinal tract.

Pharmacokinetics:

Absorption is high, the drug is quickly and almost completely absorbed from the gastrointestinal tract. The connection with plasma proteins is about 15%. The peak concentration in plasma is achieved in 30-60 minutes. Penetrates through the blood-brain barrier. Less than 1% of the dose of paracetamol taken by the lactating mother penetrates into breast milk. The therapeutic effective concentration of paracetamol in plasma is achieved when it is administered at a dose of 10-15 mg / kg.

Metabolised in the liver (90-95%): 80% enters the conjugation reaction with the formation of inactive glucuronides and sulfates; 17% undergoes hydroxylation with the formation of 8 active metabolites, which are conjugated with glutathione with the formation of already inactive metabolites.With a lack of glutathione, these metabolites can block the enzyme systems of hepatocytes and cause their necrosis. In the metabolism of the drug also involved isoenzymes CYP2E1, CYP1A2 and to a lesser extent isoenzyme CYP3A4. The half-life is 1-4 hours. It is excreted by the kidneys in the form of metabolites, mainly conjugates, less than 5% unchanged. In elderly patients, the clearance of the drug decreases and the half-life increases. Additional metabolic pathways include hydroxylation to 3-hydroxyparacetamol and methoxylation to 3-methoxyparacetamol, which are subsequently conjugated to glucuronides or sulfates.

In adults, glucuronation predominates, in newborns (including premature infants) and small children, sulfation. Conjugated metabolites of paracetamol (glucuronides, sulfates and conjugates with glutathione) have low pharmacological (including toxic) activity.

Indications:

Antipyretics for acute respiratory infections and other infectious and inflammatory diseases, accompanied by an increase in body temperature.

Anesthetic for pain syndrome of mild and moderate severity:arthralgia, myalgia, neuralgia, migraine, dental and headache pain, Algodismenorea, pain with injuries and burns.

Contraindications:

- Hypersensitivity to paracetamol or any other ingredient in the drug;

- deficiency of lactase, lactose intolerance, glucose-galactose malabsorption;

- Children under 3 years old (for this dosage form).

Carefully:

Renal and hepatic insufficiency, benign hyperbilirubinemia (including Gilbert's syndrome), dehydration, hypovolemia, anorexia, bulimia and cachexia (insufficient glutathione in the liver), viral hepatitis, alcoholic liver damage, alcoholism, pregnancy, lactation, advanced age .

In these cases, before taking the drug should consult with a doctor.

Pregnancy and lactation:

Paracetamol penetrates the placental barrier. In studies on animals and humans, there was no risk of any use of the drug during pregnancy or the adverse effects of paracetamol on the development of the embryo and fetus. Paracetamol can be used during pregnancy, but it is advisable to use the minimum effective dose and the shortest course.

In small amounts penetrates into breast milk.In studies, there was no adverse effect of paracetamol on the baby's body during breastfeeding.

Dosing and Administration:

Inside, with a lot of liquid, 1-2 hours after eating (taking immediately after a meal leads to a delay in the onset of action).

Adults and children over 12 years of age (body weight over 40 kg) single dose - 500 mg; the maximum single dose is 1 g. The multiplicity of the destination is up to 4 times a day. The maximum daily dose is 4 g. For children over 12 years of age, it is recommended that the interval between taking the drug be at least 6 hours.

Children the average single dose depends on the weight of the child and is 15 mg / yag 4 times a day every 6 hours. The maximum daily dose should not exceed 60 mg / kg per day.

The maximum daily dose for children older than 3-6 bed is 1000 mg, 6-9 years - 1500 mg, 9-12 years - 2000 mg. Multiplicity of destination - 3-4 times a day.

The maximum duration of treatment without consulting a doctor is 3 days (when taken as an antipyretic drug) and 5 days (as analgesic).

In patients with chronic or decompensated liver disease, with hepatic insufficiency, chronic alcoholism, in depleted patients and during dehydration, the daily dose should not exceed 3 g.

In patients with severe renal insufficiency (creatinine clearance <10 ml / min), it is recommended to apply the drug with an interval of not less than 8 hours.

Side effects:

The frequency of adverse drug reactions is classified according to the recommendations of the World Health Organization.

System-Organ Classes for MedDRA

Frequently: ≥1 / 100 to <1/10

Uncommon: ≥1 / 1000 to <1/100

Rarely: ≥1 / 10,000 to <1/1000

Very rarely: <1/10000.

The frequency is unknown: it is impossible to estimate from the available data.

On the part of the digestive system: rarely - pain in the abdomen, nausea, vomiting.

From the liver and bile ducts: rarely - increased activity of hepatic enzymes; frequency unknown - hepatic insufficiency, hepatitis, necrosis of the liver.

From the hematopoiesis: Very rarely - anemia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis; frequency unknown - sulfogemaglobinemia, methemoglobinemia.

From the cardiovascular system: rarely - a decrease or increase in the progrombin index, a decrease in blood pressure.

From the immune system: rarely - allergic reactions (including skin rash, itching, hives, angioedema); very rarely - acute generalized exanthematous pustules, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), bronchospasm (analgesic bronchial asthma) in predisposed individuals.

From the central and peripheral nervous system: frequency unknown - dizziness, psychomotor agitation, disorientation (when taking high doses).

From the skin: frequency is unknown - exanthema.

Other: the frequency is unknown - an increase in creatinine (mainly secondary, with respect to hepatorenal syndrome).

If any side effects occur, discontinue use and consult a doctor.

Overdose:

Liver damage in adults is possible with 10 g or more of paracetamol, ingestion of 5 g or more of paracetamol can lead to liver damage in the presence of risk factors (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidon, rifampicin, St. John's wort or other drugs that are inducers of microsomal liver enzymes, abuse of ethanol, glutathione deficiency, indigestion, cystic fibrosis, HIV infection, starvation, cachexia).

Symptoms:

The clinical picture of acute overdose develops within 24 hours after taking paracetamol.

There are gastrointestinal disorders (nausea, vomiting, decreased appetite, a feeling of discomfort in the abdominal cavity and (or) abdominal pain), pallor of the skin. With the simultaneous administration of 7.5 g or more to adults or children over 140 mg / kg, cytolysis of hepatocytes occurs with complete and irreversible necrosis of the liver, the development of hepatic insufficiency, metabolic acidosis and encephalopathy, which can lead to coma and fatal outcome. After 12-48 hours after the injection of paracetamol, the activity of microsomal liver enzymes, lactate dehydrogenase, bilirubin concentration and a decrease in prothrombin content are noted. Clinical symptoms of liver damage are manifested after 2 days after drug overdose and reach a maximum of 4-6 days.

Overdose may lead to intoxication, especially in elderly patients, children, patients with liver diseases (caused by chronic alcoholism), in patients with eating disorders, as well as in patients taking inductors of microsomal liver enzymes, with the development of fulminant hepatitis, hepatic insufficiency, cholestatic hepatitis, cytolytic hepatitis, sometimes fatal.

Treatment: Immediate hospitalization.

Determination of the quantitative content of paracetamol in blood plasma before the start of treatment at the earliest possible time after an overdose. Introduction donators SH- groups and precursors of the synthesis of glutathione - methionine and acetylcysteine - is most effective in the first 8 hours. The need for additional therapeutic measures (further introduction of methionine, intravenous injection of acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as on the time elapsed after its application. Symptomatic treatment. Laboratory studies of the activity of microsomal liver enzymes should be performed at the beginning of treatment and then every 24 hours. In most cases, the activity of microsomal liver enzymes normalizes within 1-2 weeks. In very serious cases, liver transplantation may be required.

Interaction:

Inducers of microsomal liver enzymes

Inducers of microsomal liver enzymes or potentially hepatotoxic substances (eg, alcohol, rifampicin, isoniazid, sleeping pills and antiepileptic agents, including phenobarbital, phenytoin, carbamazepine and others) increase the toxicity of paracetamol, can lead to liver damage even with non-toxic doses of paracetamol, therefore, liver function should be monitored.

Phenytoin reduces the effectiveness of paracetamol, therefore, patients receiving phenytoin, frequent use of paracetamol should be avoided, especially in high doses.

Urikozuric medicines

Paracetamol reduces the effectiveness of uricosuric medicines.

Chloramphenicol

Paracetamol may increase the risk of increased concentrations of chloramphenicol.

3-dovudine

Paracetamol may increase the risk of developing neutropenia, and therefore, hematological indicators should be monitored. Simultaneous application is possible only after consulting a doctor.

Probenecid

Probenecid reduces almost twice the clearance of paracetamol, which requires a narrowing of the dose of paracetamol.

Indirect anticoagulants

Multiple admission of paracetamol for more than 4 days increases the anticoagulant effect.Monitor the international normalized ratio (INR) during and after the concurrent use of paracetamol (especially at high doses and / or for extended periods) and coumarin derivatives. Irregular intake of paracetamol has no significant effect.

Propanthenin and other drugs that slow the evacuation from the stomach

Propanthenin and other drugs that slow the evacuation from the stomach, reduce the rate of absorption of paracetamol, which can delay or reduce the onset of the effect.

Metoclopramide and domperidone

Metoclopramide and domperidone increases the rate of absorption of paracetamol and, accordingly, the beginning of an analgesic and antipyretic action.

Barbiturates

Long-term use of barbiturates reduces the effectiveness of paracetamol.

Ethanol

Ethanol promotes the development of acute pancreatitis.

Non-steroidal anti-inflammatory drugs (NSAIDs)

Prolonged sharing of paracetamol and other NSAIDs increases the risk of developing "analgesic" nephropathy and renal papillary necrosis, the onset of the terminal stage of renal failure.

Salicylates

Simultaneous long-term administration of paracetamol in high doses and salicylates increases the risk of developing kidney or bladder cancer.

Diflunisal

Diflunisal increases the plasma concentration of paracetamol by 50% - the risk of developing hepatotoxicity.

Myelotoxic drugs

Myelotoxic drugs increase the manifestation of hematotoxicity of the drug.

Special instructions:

With the ongoing febrile syndrome in the background of the use of paracetamol more than 3 days and pain syndrome for more than 5 days, consultations of the doctor are required.

Patients with glutathione deficiency are overdose, precautions should be taken. There have been reports of liver failure and liver function disorders in patients with low glutathione levels, particularly in severely depleted patients with anorexia, chronic alcoholism, or in patients with low body mass index.

The risk of liver damage increases in patients with liver damage with alcoholism.

The use of paracetamol affects the indices of laboratory tests in the quantitative determination of glucose and uric acid in plasma.

During long-term treatment, monitoring of the peripheral blood pattern and the functional state of the liver is necessary.

Paracetamol can cause severe skin reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, which can be fatal. At the first manifestation of a rash or other hypersensitivity reactions, the drug should be discontinued and the doctor should be consulted immediately. If a patient has acute viral hepatitis, it is necessary to cancel taking the drug.

Simultaneous reception with ethanol is not recommended.

Do not take concomitantly with other medicines containing paracetamol.

Effect on the ability to drive transp. cf. and fur:

When Paracetamol is used in the recommended dose range, the influence on the ability to drive vehicles and the employment of other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions is not established.

Form release / dosage:

Tablets 200 mg and 500 mg.

Packaging:

For 10, 20 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 10, 20, 30, 40, 50 or 100 tablets in cans of polyethylene terephthalate for medicines, sealed with caps screwed on with the control of the first opening or a "push-turn" system of polypropylene or polyethylene, or polypropylene cans for drugs sealed with lids pulled with the control of the first opening from polyethylene, or cans of polypropylene for drugs sealed with lids pulled with the control of the first opening of high pressure polyethylene.

One jar or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 of the contour mesh packages together with the instruction for use are placed in cardboard packaging (bundle).

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date.

Terms of leave from pharmacies:Without recipe

Registration number:LP-004242

Date of registration:12.04.2017

Expiration Date:12.04.2022

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp08.06.2017

Illustrated instructions

Instructions

Paracetamol (Paracetamol)