Paracetamol

Paracetamol has an analgesic and antipyretic effect.

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Indications Paracetamol

It is used for therapy in the following cases:

• various pain syndromes (dental or headaches, myalgia, algomenorrhea, and in addition arthralgia, neuralgia and migraine);
• a state of fever that occurs as a result of the development of infectious diseases.

If there is a need for rapid relief of inflammation and pain (for example, after a surgical procedure), and also in cases where oral administration of the drug (suspension or tablets) is not possible, intravenous administration of the substance may be prescribed.

The medication is prescribed for symptomatic treatment, as well as to reduce the intensity of pain and inflammation at the time of its use. It does not affect the progression of the pathology.

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Release form

The drug is released:

• in tablets (in the amount of 6 or 10 pieces inside blister or cell-free plates);
• in the form of a 2.4% syrup (in 50 ml bottles), as well as a 2.4% suspension (in 0.1 l bottles);
• in rectal suppositories of 0.08, 0.17, and 0.33 g (5 pieces in a blister pack; 2 blisters in a box).

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Pharmacodynamics

Paracetamol is a non-narcotic analgesic. Its medicinal effect and properties are based on its ability to block (mainly within the CNS) elements of COX-1 and COX-2. At the same time, the substance affects pain and thermoregulatory centers.

The drug has no anti-inflammatory properties (this effect is extremely insignificant, which allows one to ignore it), because its effect on COX is neutralized by the enzyme peroxidase inside the inflamed tissues.

Since the drug does not block the binding of Pg within peripheral tissues, it does not have a negative effect on the processes of water-electrolyte metabolism within the body and on the mucous membrane of the digestive tract.

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Pharmacokinetics

The absorption of the drug is quite high, its Cmax values are within 5-20 mcg/ml. Paracetamol reaches these values after 0.5-2 hours. The active element is able to penetrate the BBB.

During breastfeeding, the drug is excreted in breast milk (its concentration does not exceed 1%).

The drug undergoes liver biotransformation processes. Metabolism, which occurs with the participation of microsomal liver enzymes, leads to the formation of toxic intermediate metabolic products (including N-acetyl-b-benzoquinone imine). These components can lead to damage and necrosis of liver cells if the body has reduced glutathione levels. Depletion of this element is observed with the use of 10+ g of paracetamol.

Two other metabolic pathways of paracetamol are the process of conjugation with sulfates (often observed in newborns, especially premature ones), and with glucuronides (mostly observed in adults).

Conjugated metabolic products have weak medicinal activity (this includes the toxic effect).

Half-life is within 1-4 hours (in elderly people this value may be higher). Excretion occurs mainly through the kidneys, in the form of conjugates. Only 3% of the used paracetamol is excreted unchanged.

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Dosing and administration

Serving sizes for adolescents (12 years and over if they weigh over 40 kg) and adults are a maximum of 4 g per day (20 tablets of 0.2 g or 8 tablets of 0.5 g).

For 1 use, you should take 0.5 g of the substance (if necessary, it can be 1 g). Tablets of the drug are allowed to be used up to 4 times a day. Duration of therapy is 5-7 days.

Children's Paracetamol tablets can be used starting from 2 years of age. Children of the younger age category are required to take 0.5 tablets of 0.2 g at 4-6 hour intervals. A child over 6 years of age is allowed to take a whole tablet, with the frequency indicated above.

Tablets of 325 mg can be taken from the age of 10. For children aged 10-12 years, they are prescribed for oral administration 2-3 times a day (the maximum dose should not be exceeded - for this category of patients it is 1500 mg per day).

Teenagers aged 12 and over and adults should take 1-3 tablets at 4-6 hour intervals. You should not take more than 4 g of the drug per day, and the intervals between doses should be at least 4 hours.

Use of suppositories.

Suppositories are inserted rectally – into the rectum. Before the procedure, it is necessary to cleanse the intestines.

The dosage of the drug in suppositories for a child should be calculated taking into account the age and weight of the patient. Suppositories with a volume of 80 mg are used for infants from 3 months of age; suppositories with a volume of 170 mg - for children aged 1-6 years; suppositories with a volume of 330 mg - for children aged 7-12 years.

The suppositories should be inserted one at a time, keeping at least a 4-hour interval between procedures; 3-4 suppositories are inserted per day (the number of suppositories depends on the patient's condition).

Children are often prescribed Paracetamol in suppositories or syrup. When comparing their therapeutic effectiveness, it is noted that syrup has a faster effect, and suppositories have a longer effect.

Because suppositories are safer and more convenient to use (compared to tablets), it is recommended to prescribe them to small children (for example, for newborns they are considered the optimal dosage form of this medication).

For a child, the toxic dose of the drug is 150+ mg/kg. Thus, a child weighing 20 kg can die from taking 3 g of the substance per day.

The selection of a single dose is made according to the formula 10-15 mg/kg with 2-3 times a day (with 4-6 hour intervals). The maximum dosage of the drug for a child is 60 mg/kg per day.

Directions for use of suspension and syrup for children.

The syrup can be prescribed to infants from 3 months of age, and the suspension can be used from the 1st month of life (because it does not contain sugar).

Sizes of 1-dose syrup servings for different age groups:

• infants 3-12 months – 0.5-1 teaspoon;
• children 1-6 years old – 1-2 teaspoons;
• children 6-14 years old – 2-4 teaspoons.

The frequency of administration ranges from 1 to 4 times a day (the child should take the drug at minimum 4-hour intervals).

The dosages of the children's suspension are similar to those used for the syrup. The scheme for using the medicine for infants under 3 months of age is selected exclusively by the attending physician.

The dose sizes of the medicine should be selected taking into account the child's weight. It is possible to prescribe a maximum of 10-15 mg/kg per dose and no more than 60 mg/kg per day. Thus, a 3-year-old child with an average weight of 15 kg should take 150-225 mg of the medicine per dose.

If there is no result when using the suspension or syrup in the specified portions, it is necessary to replace Paracetamol with some analogue that has a different active component.

To eliminate fever, a combination of paracetamol and analgin is sometimes used (if the temperature is 38.5°C and difficult to bring down). The portion sizes are as follows: paracetamol in the dosages indicated above (taking into account age and weight); analgin - 0.3-0.5 mg/kg.

This combination cannot be used frequently, because the use of analgin leads to irreversible changes in the blood composition.

A "troychatka" can also be used, which in addition to paracetamol includes aspirin and analgin. Paracetamol can also be supplemented with suprastin and no-shpa, analgin and no-shpa, or suprastin and analgin.

No-shpa (papaverine can also be used instead) helps to open spasmodic capillaries, and antihistamines (such as tavegil or suprastin) potentiate the effect of antipyretics.

If the drug is required to provide an antipyretic effect, it can be used for a maximum of 3 days in a row.

If the medicine is used to relieve pain, the treatment cycle should last a maximum of 5 days. The possibility of its subsequent use is determined by the attending physician.

It is important to remember that the drug helps to eliminate the symptoms of the disease (such as toothaches or headaches), but does not treat the cause of their occurrence.

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Use Paracetamol during pregnancy

The drug can cross the placenta, but no negative effects on fetal development have been identified so far.

During the tests it was determined that the use of Paracetamol during pregnancy (especially in the second half) increases the likelihood of the child developing asthma, respiratory disorders, wheezing and signs of allergies.

It is necessary to take into account that in the 3rd trimester the toxic effect of infectious diseases can be as dangerous as the effect of individual drugs. In case of hyperthermia in the mother there is a possibility of hypoxia in the fetus.

When using the drug in the 2nd trimester (more specifically, starting from the 3rd month and approximately until the 18th week), the child may develop abnormalities in the development of internal organs, often manifesting themselves after birth. Because of this, the drug is used only occasionally and exclusively as a last resort during this period.

But at the same time, this particular medication is considered the safest pain reliever for pregnant women.

Taking large doses of the drug during pregnancy may have a negative effect on the kidneys and liver. If a pregnant woman has a fever due to ARVI or flu, she should take Paracetamol 0.5 tablets per dose. This therapy should last a maximum of 7 days.

Only a minimal amount of the drug gets into the mother's milk during lactation. This allows not to interrupt breastfeeding in cases where the drug is used for a maximum of 3 days in a row.

During lactation, it is allowed to take a maximum of 3-4 tablets of 0.5 g per day (the tablets are taken after the feeding procedure). It is recommended to feed the next time at least 3 hours after taking the drug.

Contraindications

Main contraindications:

• the presence of intolerance to the medication;
• congenital hyperbilirubinemia;
• G6PD enzyme deficiency;
• liver or kidney diseases of a severe form;
• blood diseases;
• alcohol addiction;
• severe anemia or leukopenia.

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Side effects Paracetamol

Adverse reactions after taking medications usually take the form of signs of severe sensitivity (allergy) – skin itching, angioedema, urticaria and rashes.

Sometimes the use of the drug leads to the development of hematopoiesis disorders (thrombocytopenia, neutro-, leukopenia or pancytopenia, as well as agranulocytosis) and dyspeptic symptoms.

Long-term use in large portions may cause hepatotoxic effects.

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Overdose

Manifestations of intoxication that occur on the first day: pale skin, pain in the abdominal area, nausea, metabolic acidosis, vomiting, anorexia and glucose metabolism disorder.

Symptoms of liver dysfunction may develop after 12-48 hours.

In case of severe overdose, pancreatitis, liver failure (with progressive encephalopathy), acute renal failure (accompanied by tubular necrosis), arrhythmia and coma are observed.

In some cases, Paracetamol poisoning can result in death (in cases of very severe intoxication).

To treat the disorder, the victim requires the administration of methionine with acetylcysteine (in the period of 8-9 hours), which are precursors of the glutathione binding processes, and along with this, donors of SH categories.

Subsequent therapy depends on how long the drug has been taken and its level in the blood.

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Interactions with other drugs

The drug reduces the effectiveness of uricosuric drugs. Use together with large doses of the drug enhances the effect of anticoagulants (by reducing the production of procoagulants in the liver).

Medicines that promote the induction of microsome oxidation processes inside the liver, as well as hepatotoxic drugs and ethyl alcohol, increase the production of hydroxylated metabolic products that have medicinal activity, which is why even with a minimal overdose, severe poisoning can develop.

Medicinal effectiveness is weakened by prolonged use of barbiturates. Ethyl alcohol causes acute pancreatitis. Medicines that inhibit the oxidation processes of microsomes inside the liver reduce the likelihood of hepatotoxic effects.

Long-term combination with other NSAIDs can provoke necrotic papillitis, analgesic nephropathy, and the development of the terminal (dystrophic) stage of renal failure.

The combination of Paracetamol (in large doses) with salicylates over a long period of time increases the risk of developing kidney or bladder carcinoma. Diflunisal increases plasma paracetamol levels by 50%, which increases the likelihood of hepatotoxicity.

Myelotoxic substances potentiate the hematotoxic properties of the drug; antispasmodics delay its absorption; cholesterol with enterosorbents reduce its bioavailability.

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Storage conditions

Paracetamol should be stored in a dark, dry place, out of reach of children. Temperature indicators for syrup are a maximum of 18°C (it cannot be frozen); for suppositories - a maximum of 20°C.

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Shelf life

Paracetamol in suppositories and syrup can be used within 24 months from the date of manufacture of the medicine. The shelf life of tablets is 36 months.

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Analogues

The drug's analogues are paracetamol-containing substances such as Strimol, Paracetamol 325, Perfalgan with Paracetamol MS, Cefekon D, Ifimol, Flutabs and Paracetamol Extratab with Panado Daleron, as well as Paracetamol UBF and Efferalgan.

Drugs that have a similar mechanism of action but a different active ingredient: Antiflu, Coldrex, Antigrippin, Novalgin and Solpadeine with Caffetin and Fervex, and in addition Maxikold, Teraflu, Panadol Extra and Femizol.

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Reviews

Paracetamol is most often mentioned in the context of treating children, as they are more likely to become infected with acute respiratory viral infections, and the drug is most effective for such diseases.

Parents generally leave positive reviews about the drug - it quickly lowers the temperature and reduces the severity of negative symptoms of fever. At the same time, it is well tolerated by people of different ages - it extremely rarely provokes the development of negative symptoms typical for NSAIDs.

Doctors urge us not to forget that the medicine only relieves the symptoms of the disease, without eliminating it itself, and also remind us that in order to obtain a positive effect, it is very important to choose the right form of the drug and calculate the necessary dosage.