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

The duration of analgesic action is 4-6 hours, antipyretic for at least 6 hours. The exact mechanism of analgesic and antipyretic effects of paracetamol is not established.Apparently, it includes the central and peripheral components.

It is known that paracetamol blocks cyclooxygenase I and II type mainly in the central nervous system, affecting the centers of pain and thermoregulation. In inflamed tissues, cellular peroxidases neutralize the effect of paracetamol on cyclooxygenase, which explains the almost complete absence of significant anti-inflammatory effect. The absence of influence on the synthesis of prostaglandins in peripheral tissues causes the absence of a negative influence on the water-salt metabolism (sodium and water retention) and the mucous membrane of the gastrointestinal tract.

Pharmacokinetics:

Suction. Absorption in rectal administration is slower than with oral paracetamol. The maximum concentration in the blood plasma is achieved in 2-3 hours.

Distribution. The distribution volume in adults is 1 l / kg. Paracetamol weakly binds to blood plasma proteins. Penetrates through the blood-brain barrier.

Metabolism. In adults paracetamol is metabolized mainly in the liver with the formation of glucuronides and sulfates.A small part (4%) of paracetamol is metabolized by cytochrome P450 to form an active intermediate metabolite (N-acetylbenzoquinopimine), which under normal conditions is rapidly rendered harmless by reduced glutathione and is excreted in the urine after binding to cysteine and mercapturic acid. However, with a massive overdose, the amount of this toxic metabolite increases. The half-life in adults is 2.7 hours, in children 1.5-2 hours, and the total clearance is 18 liters per hour.

Excretion. Paracetamol is excreted mainly in the urine; 90% of the dose is excreted by the kidneys within 24 hours, mainly in the form of glucuronide (60-80%) and sulfate (20-30%). Less than 5% is displayed unchanged. In severe renal failure (creatinine clearance <10-30 ml / min) excretion of paracetamol somewhat slows down, and the half-life is 2-5.3 hours.

The rate of elimination of glucuronide and sulfate in patients with severe renal failure is 3 times lower than in healthy volunteers.

The pharmacokinetics of paracetamol do not change in elderly patients; in children only the half-life of blood plasma is different, which is somewhat shorter in comparison with adults (1.5-2 h). In addition, children under 10 years paracetamol more deduced in the form of sulphate, and not glucuronide, which is typical for adult patients. The total excretion of paracetamol and its metabolites in patients of all age groups is the same.

Indications:

- as a febrifuge with fever;

- as an analgesic for pain of mild to moderate intensity.

Contraindications:

- hypersensitivity to paracetamol or other components of the drug;

- severe violations of liver function;

- children under 4 years;

- inflammation of the rectum, bleeding from the rectum.

Carefully:

Severe renal failure (creatinine clearance <30 mL / min), benign hyperbilirubinemia (including Gilbert's syndrome, viral hepatitis, alcoholic liver disease), chronic alcoholism, chronic malnutrition, anorexia, bulimia, cachexia, hypovolemia, dehydration, advanced age, deficits glucose-6-phosphate dehydrogenase.

Dosing and Administration:

Rectal (into the rectum). After spontaneous bowel cleansing enema or suppository free from blisters and injected into the rectum.

The duration of the course of treatment with paracetamol without consulting a doctor is no more than 3 days as an antipyretic agent, no more than 5 days as an analgesic.

Dosing regimen in adults and children 10 years and older

One suppository with a dosage of 500 mg 2-4 times a day; the maximum single dose is 1 g; the maximum daily dose is 4 g.

Dosage regimen in children under 10 years of age

The dose of paracetamol is calculated according to age and body weight, according to the table. The recommended single dose is 15 mg / kg body weight every 6 hours. The maximum daily dose of paracetamol should not exceed 60 mg / kg of body weight of the child.

Due to the risk of local toxicity (on the rectum), it is recommended not to inject suppositories more than 4 times a day. It is necessary to strive for a minimum duration of treatment.

Age	Body mass	Single dose
4-9 years	15-24 kg	1 suppository of 250 mg

Side effects:

If any of the undesirable effects specified in the instruction are aggravated, or if you notice any other undesirable phenomena not listed in the manual, inform the doctor about it.

The frequency of unwanted reactions is given in accordance with the following scale: very often (> 10%); often (> 1% and <10%); infrequently (> 0.1% and <1%); rarely (> 0.01% and <0.1%); very rarely (<0.01%).

From the skin: very rarely - redness of the skin, itching, rashes on the skin and mucous membranes (usually erythematous or urticaria).

From the liver and bile ducts: rarely - increased activity of "liver" enzymes, usually without the development of jaundice.

From the cardiovascular system: rarely - lowering blood pressure; very rarely - tachycardia.

From the hematopoiesis: very rarely - thrombocytopenia.

General Characteristics: rarely - malaise.

The following undesirable reactions were also noted in the post-marketing use of the drug, however, their frequency was not established:

Allergic reactions: hypersensitivity reactions, anaphylactic shock, anaphylaxis, angioedema.

From the liver and bile ducts: fulminant hepatitis, liver necrosis, hepatic insufficiency.

From the gastrointestinal tract: nausea, vomiting.

Overdose:

When an overdose (exceeding the dose of 1 g per day for children 4-9 years, excess dose of 3 g per day in children 10-18 years, exceeding the dose of 4 g per day in adults) is necessary immediately seek medical attention.

When an overdose is possible 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 inducers of microsomal liver enzymes, which can develop fulminant hepatitis, hepatic insufficiency, cholestatic hepatitis, cytolytic hepatitis, in the cases indicated above - sometimes with lethal outcome.

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

Symptoms: gastrointestinal disorders (nausea, vomiting, decreased appetite, abdominal discomfort and / or abdominal pain), pale skin. With the simultaneous administration of 7.5 g or more to adults or children over 140 mg / kg, cytolysis of hepatocytes with complete irreversible necrosis of the liver, the development of hepatic insufficiency, metabolic acidosis and encephalopathy, which can lead to coma and death. 12-48 hours after the introduction of paracetamol, an increase in the activity of "hepatic" transaminases, lactate dehydrogenase, bilirubin concentration and a decrease in the prothrombin content was noted.

Clinical symptoms of liver damage are manifested after 2 days after drug overdose and reach a maximum of 4-6 days.

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 - within 10 hours after an overdose.

- 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 administration.

- Symptomatic treatment.

- Hepatic tests should be performed at the beginning of treatment and then every 24 hours.

In most cases, the activity of liver transaminases normalizes within 1-2 weeks. In very serious cases, liver transplantation may be required.

Interaction:

Phenytoin reduces the activity of paracetamol and increases the risk of hepatotoxicity. Patients receiving phenytoin, paracetamol should be avoided in high doses.

Probenecid almost 2 times reduces the clearance of paracetamol, inhibiting the process of its conjugation with glucuronic acid. With a simultaneous appointment, consideration should be given to reducing the dose of paracetamol.

Inducers of microsomal liver enzymes (eg, ethanol, barbiturates, isoniazid, rifamgschin, anticoagulants, zidovudine, amoxicillin + clavulanic acid) increase the production of hydroxylated active metabolites, which makes it possible to develop severe intoxication with small overdoses. Ethanol promotes the development of acute pancreatitis.

Inhibitors of microsomal liver enzymes (including cimetidine) reduce the risk of hepatotoxic effects.

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

Long-term simultaneous use of paracetamol and other non-steroidal anti-inflammatory drugs (salicylamide) increases the risk of developing analgesic nephropathy and renal papillary necrosis, the onset of the terminal stage of renal failure.

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

Special instructions:

The risk of developing liver damage increases when the recommended doses are exceeded (including with the simultaneous use of the drug Paracetamol and other drugs containing paracetamol), as well as in patients with chronic alcoholism.

Do not use the drug in patients with diarrhea.

Effect on the ability to drive transp. cf. and fur:Information on the impact on the ability to drive vehicles and work with mechanisms are absent.

Form release / dosage:

Suppositories rectal by 250 mg and 500 mg.

Packaging:

For 5 or 6 suppositories (for a dosage of 250 mg), or for 5 suppositories (for a dosage of 500 mg) in a contour cell pack.

Two contour packs with 5 suppositories or one contour pack of six suppositories together with instructions for medical use of the drug are placed in a pack of cardboard.

Storage conditions:

Store in a dry place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:Without recipe

Registration number:LP-002211

Date of registration:30.08.2013

The owner of the registration certificate:FARMPROJECT, CJSC FARMPROJECT, CJSC Russia

Manufacturer: & nbsp

FARMPROJECT, CJSC Russia

Information update date: & nbsp02.10.2015

Illustrated instructions

Instructions

Paracetamol (Paracetamol)