Instructions for use PARACETAMOL

Instructions for use PARACETAMOL

IV in the form of infusion.

Paracetamol for infusion is used to quickly relieve pain and/or hyperthermic syndrome, when only intravenous administration of the drug is required. The IV duration is 15 minutes.

* Premature newborns:

there are no data on safety and effectiveness in this category of patients.

**Maximum daily dose.

The maximum daily dose for patients not receiving other drugs containing paracetamol, or the dose should be adjusted accordingly to take into account the use of paracetamol-containing drugs.

***Patients with lower body weight require less paracetamol.

The minimum interval between each administration of the drug should be at least 4 hours.

The minimum interval between each administration of the drug in patients with severe renal failure should be at least 6 hours.

No more than 4 doses can be administered within 24 hours.

In patients with severe renal failure (creatinine clearance <30 ml/min)

It is recommended to increase the minimum interval between each administration to 6 hours.

In adults with hepatocellular insufficiency, chronic alcoholism, chronic malnutrition (low hepatic glutathione reserves),

dehydration, the maximum daily dose should not exceed 3 g.

Patients weighing ≤10 kg:

a ready-made solution for infusion of 10 mg/ml in polymer containers is not suitable for administration to this group of patients, because it does not provide a 15-minute administration.

The volume of solution of 10 mg/ml required for administration should be taken from a polymer container and diluted in 0.9% sodium chloride solution or 5% glucose solution to one tenth (1 volume of paracetamol solution 10 mg/ml per 9 volumes of diluent) and administered within 15 min. To measure the required volume of solution according to the child’s body weight, 5 or 10 ml syringes should be used. However, the volume should never exceed 7.5 ml per administration.

For correct dosage of the drug, you should use the instructions for use.

As with all infusion solutions that are supplied in polymer containers, it should be remembered that the infusion process must be carefully monitored, especially at the end. Such monitoring at the end of the infusion is required to avoid air embolism.

Features of application

Caution should be used when prescribing and administering paracetamol for infusion to avoid dosing errors due to confusion between milligrams (mg) and milliliters (ml), which may lead to accidental overdose and death. Take care to ensure proper dose. When filling out prescriptions, it is necessary to include both the total dose in mg and the total volume of the prescribed solution. It is necessary to monitor the accuracy of dosing.

Paracetamol solution for infusion 10 mg/ml 100 ml No. 1

Name

Paracetamol infusion.

Release forms

Solution.

INN

Paracetamol.

FTG

Analgesic non-narcotic drug.

Compound

active ingredient – ​​paracetamol; 100 ml of solution contains 1 g of paracetamol; excipients: anhydrous glucose, sodium citrate, sodium acetate trihydrate, diluted acetic acid.

Pharmacotherapeutic group

Other analgesics and antipyretics. Anilides. PBX code: N02BE01

Pharmacological properties

Pharmacodynamics Paracetamol has analgesic and antipyretic effects. The drug blocks cyclooxygenase I and II 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 anti-inflammatory effect. There is no effect on the synthesis of prostaglandins in peripheral tissues, therefore it does not have a negative effect on water-salt metabolism (sodium and water retention) and the mucous membrane of the gastrointestinal tract. Pharmacokinetics The time of maximum concentration in blood plasma is reached 15 minutes after intravenous infusion and is 30 mcg/ml. The volume of distribution is 1 l/kg. Paracetamol is weakly bound to plasma proteins. Penetrates the blood-brain barrier; 20 minutes after intravenous infusion of 1 g, a significant concentration of paracetamol is detected in the cerebrospinal fluid (about 1.5 µm/ml). Metabolized in the liver to form glucuronides and sulfates. A small part (4%) of the drug is metabolized by cytochrome P450 to form an intermediate metabolite (N-acetylbenzoquinoneimine), which under normal conditions is quickly neutralized by reduced glutathione and excreted in the urine after binding to cysteine ​​and mercaptopuric acid. However, with massive intoxication, the amount of this toxic metabolite increases. The half-life in adults is 2.7 hours, in children – 1.5-2 hours, in newborns – 3.5 hours, total clearance 18 l/hour. Paracetamol is excreted mainly in the urine, 90% of the dose taken is excreted by the kidneys within 24 hours, mainly in the form of glucuronide (60-80%) and sulfate (20-30%). Less than 5% is excreted unchanged. In severe renal failure (creatinine clearance below 10-30 ml/min), the elimination of paracetamol slows down somewhat, and the half-life is 2-5.3 hours. The rate of excretion of glucuronide and sulfate in patients with severe renal failure is 3 times less than in healthy people patients.

Indications for use

Paracetamol infusion is indicated for the short-term treatment of moderate pain, especially after surgery and for the short-term treatment of fever when intravenous administration is clinically justified or there is an urgent need for analgesic treatment or control of hyperthermia and/or when administration by other routes of administration is not possible.

Directions for use and doses

Paracetamol for infusion is used to quickly relieve pain and/or hyperthermic syndrome, when exclusively intravenous administration of the drug is required. The duration of the intravenous infusion should be 15 minutes. The drug should not be mixed in the same infusion bottle with other medications. The infusion should be carried out immediately after opening the bottle; the unused remainder of the drug is destroyed. Before starting the infusion, the bottle with the drug should be carefully inspected for the absence of visible mechanical particles and changes in the color of the solution. A 100 ml polymer container contains a single dose of paracetamol recommended for use in adult patients, children and adolescents weighing > 50 kg. Table 1. Dosing based on patient weight Patient weight Dose per dose Volume to be administered Maximum volume of paracetamol infusion (10 mg/ml) per dose, which is based on the upper limits of patient group weight (ml)*** Maximum daily dose** 10 kg up to ≤ 33 kg 15 mg/kg 1.5 ml/kg 49.5 ml 60 mg/kg not more than 2 g > 33 kg up to ≤ 50 kg 15 mg/kg 1.5 ml/kg 75 ml 60 mg/ kg not more than 3 g > 50 kg with additional risk factors for hepatotoxicity 1 g 100 ml 100 ml 3 g > 50 kg and without additional risk factors for hepatotoxicity 1 g 100 ml 100 ml 4 g * Premature neonates: No data on safety and effectiveness in this category of patients. **Maximum daily dose. The maximum daily dose as indicated in the table above for patients not receiving other drugs containing paracetamol or the dose should be adjusted accordingly to take into account the use of drugs containing paracetamol. ***Patients with lower body weight will require smaller volumes. The minimum interval between each dose should be at least 4 hours. The minimum interval between each dose in patients with severe renal failure should be at least 6 hours. No more than 4 doses should be administered within 24 hours. It is recommended when prescribing paracetamol in patients with severe renal impairment (creatinine clearance

Features of application

Use caution when prescribing and administering paracetamol for infusion to avoid dosing errors due to confusion between milligrams (mg) and milliliters (ml), which may lead to accidental overdose and death. Take care to ensure proper dose. When filling out prescriptions, it is necessary to include both the total dose in mg and the total volume of the prescribed solution. It is necessary to monitor the accuracy of the dosage.

Side effect

As with all paracetamol drugs, adverse reactions are rare (>1/10000, 1/10000,

Contraindications

Paracetamol solution for infusion is contraindicated: • in patients with hypersensitivity to paracetamol or propacetamol hydrochloride (prodrug of paracetamol) or to one of the excipients; • in cases of severe hepatocellular failure.

Overdose

There is a risk of liver damage (including fulminant hepatitis, liver failure, cholestatic hepatitis, cytolytic hepatitis), especially in elderly patients, in young children, in patients with liver disease, in chronic alcoholism, in patients with chronic malnutrition and in patients receiving enzyme inducers. Overdose can lead to death in these cases. Symptoms usually appear within the first 24 hours and include: nausea, vomiting, anorexia, pallor, abdominal pain. An overdose of 7.5 g or more of paracetamol with a single dose in adults and 140 mg/kg of body weight with a single dose in children can cause hepatic cytolysis, which can lead to complete and irreversible necrosis, as a result of hepatocellular failure to metabolic acidosis and encephalopathy, which can lead to coma and death. At the same time, increased levels of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin are observed along with a decrease in prothrombin levels, which can appear from 12 to 48 hours after administration. Clinical symptoms of liver damage usually initially appear after two days and peak after 4 to 6 days. Emergency measures • Immediate hospitalization. • Before starting treatment, a blood test should be taken to measure plasma paracetamol levels. • Treatment involves administering the antidote N-acetylcysteine ​​(NAC) intravenously or orally, if possible, within the first 10 hours. Administration of NAC after 10 hours may also provide some degree of protection, but will require long-term treatment. • Symptomatic treatment. • Liver tests should be performed at the start of treatment and repeated every 24 hours. In most cases, liver transaminases return to normal levels within one to two weeks, with complete restoration of liver function. In very severe cases, a liver transplant may be necessary.

Precautionary measures

Paracetamol should be used with caution in the following cases: • with hepatobiliary disorders; • with Gilbert's syndrome; • with simultaneous use of liver enzyme inducers or hepatotoxic drugs; • with hereditary deficiency of glucose-6-phosphate dehydrogenase; • in patients receiving parenteral nutrition, • with hepatocellular insufficiency; • in case of severe renal failure (creatinine clearance

special instructions

Risk of Medication Errors Be careful to avoid dosing errors due to confusion between milligrams (mg) and milliliters (ml), which can lead to accidental overdose and death. It is recommended to use suitable oral analgesics as soon as possible. To avoid the risk of overdose, make sure that other medicines you take do not contain paracetamol or propacetamol hydrochloride. Doses higher than recommended carry a risk of very serious liver damage. Clinical symptoms and signs of liver damage (including fulminant hepatitis, liver failure, cholestatic hepatitis, cytolytic hepatitis), as a rule, are first recorded after two days of taking the drug with a peak manifestation, usually on days 4–6. Antidote treatment should be started as soon as possible.

Interaction with other drugs

• Probenecid causes an almost 2-fold decrease in the clearance of paracetamol by inhibiting conjugation with glucuronic acid. A reduction in the dose of paracetamol should be considered when concomitantly treated with probenecid. • Salicylamide may prolong the elimination of T1/2 of paracetamol. • Attention should be paid to concomitant use of enzyme-inducing substances. The metabolism of paracetamol is impaired in patients taking enzyme-inducing drugs such as rifampicin, barbiturates, tricyclic antidepressants and some antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, primidone). In patients taking alcohol or enzyme-inducing drugs simultaneously with paracetamol, the risk of hepatotoxicity increases. • Concomitant administration of paracetamol and chloramphenicol may prolong the effect of chloramphenicol. • The simultaneous use of paracetamol and zidovudine increases the tendency to neutropenia. • Concomitant use with oral contraceptives may shorten the half-life of paracetamol. • Concomitant use of paracetamol (4 g daily for 4 days) with oral anticoagulants may result in slight variations in the INR. In this case, enhanced INR monitoring should be carried out during the simultaneous use of paracetamol and anticoagulants, as well as for 1 week after stopping treatment with paracetamol.

Pregnancy

Clinical experience with intravenous paracetamol is limited. However, epidemiological data from the use of oral therapeutic doses of paracetamol indicate no adverse effects on pregnancy or fetal/newborn health. Prospective data in pregnant women exposed to overdose did not show an increased risk of malformations. Reproduction studies with intravenous paracetamol have not been conducted in animals. However, studies with the oral route have not shown any malformations or fetotoxic effects. However, paracetamol infusion should only be used during pregnancy after a careful assessment of the benefits and risks. In this case, the recommended dosage and duration must be strictly followed.

Lactation

After oral administration, paracetamol is excreted into breast milk in small quantities. There are no reports of adverse effects in infants. Therefore, paracetamol infusion can be used by women who are breastfeeding.

Impact on the ability to drive a car and operate machinery

Does not affect.

Storage conditions

In a place protected from light at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Best before date

2 years. Do not use after the expiration date stated on the packaging.

Vacation conditions

By doctor's prescription.

Package

100 ml in polymer containers for infusion solutions in package No. 1. For hospitals: 100 ml in polymer containers for infusion solutions in package No. 80, 100.

Buy Paracetamol solution d/inf. 10 mg/ml in container polymer. 100 ml in pack No. 1 in the pharmacy

Price for Paracetamol solution d/inf. 10 mg/ml in polymer container 100 ml in pack No. 1

Instructions for use for Paracetamol solution d/inf. 10 mg/ml in polymer container 100 ml in pack No. 1

Newspaper "News of Medicine and Pharmacy" 3 (401) 2012

History of intravenous paracetamol

Paracetamol is a poorly soluble compound, which prevented the development of its injectable form for many years. Therefore, in clinical practice in children and adults, intravenous propacetamol, a prodrug of paracetamol, was used, the main disadvantage of which was that it caused pain at the injection site in 20–40% of patients. However, over time, scientists managed to create an intravenous form of paracetamol in the form of a very diluted solution (1000 mg/100 ml), which causes pain upon injection in 2% of patients. Intravenous paracetamol is approved and used for the treatment of acute pain in more than 80 countries. It was approved in the European Union in 2002 and is currently the most commonly prescribed injectable analgesic. Several years ago, in the UK, the instructions for intravenous use of paracetamol were expanded to a new age group - it was approved for use in newborns and infants aged < 1 year. In the United States, clinical trials of intravenous paracetamol have been completed in adults and children, and it is currently undergoing approval by the Food and Drug Administration (FDA) [2].

Brief characteristics of intravenous paracetamol

The maximum concentration of paracetamol after intravenous administration in the blood plasma is reached after 15 minutes, the half-life in adults is 2.7 hours, in children - 1.5–2 hours, in infants - 3.5 hours [3]. Despite the fact that paracetamol was synthesized more than 100 years ago, its mechanism of action continues to be refined. In particular, whether it acts peripherally and/or centrally and which pain pathway is most affected when administered is still under debate. Potential mechanisms of action may include inhibition of cyclooxygenase isoenzymes, interaction with endogenous opioid pathways, activation of the serotonergic bulbospinal tract, involvement of nitric oxide, or activation of the cannabinoid-vanilloid system [4]. Nevertheless, many authors are inclined to believe that the mechanism of action is central and is associated with inhibition of cyclooxygenase isoenzymes. Paracetamol differs from non-steroidal anti-inflammatory drugs and narcotic analgesics in that it rarely causes side effects from the gastrointestinal tract and cardiovascular system [5]. Intravenous paracetamol is well tolerated, causes virtually no side effects and does not interact with other drugs. It does not have a pronounced effect on platelet aggregation and therefore may be the preferred non-narcotic analgesic in operations with problematic surgical bleeding. Intravenous paracetamol is a safe and effective first-choice analgesic agent for the treatment of mild to moderate postoperative pain in cases where oral agents are impractical or where a rapid onset of therapeutic effect with a predictable amount of dose administered is required [6].

In adults and children weighing more than 50 kg, the maximum single dose is 1 g of paracetamol, the maximum daily dose is 4 g of paracetamol. The interval between administration of the drug should be at least 4 hours. Usually, 1 to 4 infusions are used on the first day from the onset of pain (postoperative period), if necessary, the duration of treatment can be increased, but it should not exceed 72 hours (3 days) and a total of 12 infusions [4].

In a study by Candiotti et al. [7] showed that paracetamol (1000 mg 4 times a day or 650 mg 6 times a day) has a favorable safety profile even with long-term use (5 days).

Broad evidence base for intravenous paracetamol (as monotherapy or as one component of multimodal analgesia)

Among the integrative studies that assessed the use of intravenous paracetamol for several indications at once, noteworthy is the study by Göröcs et al. [8], which was performed as an open-label, uncontrolled observational study at 6 clinical centers. It included 601 patients aged 46.7 ± 15.4 years who underwent outpatient surgical interventions: minor interventions on the knee joint (71.4%), minor gynecological interventions (19.0%) and operations for varicose veins (9.6%). The average duration of operations was 37 ± ± 21 minutes. Paracetamol was administered intravenously at a dose of 1 g approximately 30 min before the planned end of surgery, and patients were monitored until discharge (mean 123 ± 58 min). As a result, it turned out that 57% of patients needed additional pain medication. The average pain intensity on the visual analogue scale (VAS) 15 minutes after the end of the operations was 33.2 mm, and by the time of discharge it was 19.2 mm (–13.9 points). The relative reduction in pain was similar for all three types of surgery. The majority of patients achieved VAS values ​​<30 mm and were classified as responders (sensitive to treatment). Paracetamol was well tolerated, no serious side effects were recorded (only 1 side effect was recorded, which may have been related to the treatment). The majority of doctors (80.5%) and patients (81.6%) rated the effectiveness of treatment and satisfaction with it as “very good” or “good.” In summary, intravenous paracetamol, used alone or in combination with other analgesics, is effective for postoperative pain and is well tolerated by ambulatory surgery patients.

Evidence-based medicine (important studies)

To answer the question of what benefits intravenous paracetamol can provide to adults with postoperative pain, one of the authors' teams performed a systematic review of 16 relevant prospective randomized controlled trials (RCTs) from 9 countries published between January 2005 and January 2010. [1]. All RCTs were qualified as studies performed at a high methodological level (5 points on the Jadad scale for assessing the quality of clinical studies). The result was that in 7 of 8 studies in which intravenous paracetamol was compared with another drug (intravenous parecoxib - 3 studies, intravenous analgin - 4 studies, oral ibuprofen - 1 study), the analgesic effect of paracetamol was comparable to that of the listed funds. Twelve of 14 studies that compared intravenous paracetamol with intravenous placebo found paracetamol to be more effective than placebo. Ten of these 14 studies reported that the use of paracetamol resulted in a reduction in the dose of opioid administered, a reduction in the number of patients requiring backup pain medication (these were prescribed when primary therapy was ineffective), and an increase in the time to the first use of backup medications. Based on the study results, the authors concluded that intravenous paracetamol is an effective pain reliever for a wide range of surgical procedures. Another study reviewed the literature on the same topic in children [2]. Available evidence suggests that intravenous paracetamol is an effective and safe drug for the control of postoperative pain in children if dosing guidelines are followed in this age group. Intravenous paracetamol can be used either as monotherapy for mild to moderate postoperative pain or in combination with regional analgesia methods. The drug in question has the potential to reduce the administered dose of opioids. The authors report that far fewer studies have studied intravenous paracetamol in children than in adults. Therefore, the findings should be refined as new research is completed.

general surgery

In the work of D. Cornesse et al. [9] compared the effectiveness and safety of intravenous paracetamol in doses of 1 and 2 g in adult patients (n = 60) with minor hand surgery. The drug was administered before surgery and then every 6 hours. The result was that after 24 hours, pain intensity on a verbal numerical scale was lower in the group taking 2 g of paracetamol compared to 1 g of the drug. There were no differences between groups in the need for backup pain medications, sleep quality, or patient satisfaction. Thus, paracetamol in a dose of 2 g was more effective than a dose of 1 g of the same drug without the development of visible side effects.

Wide evidence base:

Ø In general surgery Ø Pediatric surgery Ø ENT surgery Ø Oncosurgery Ø Cardiac surgery Ø Obstetrics and gynecology Ø Urology Ø Dental surgery

Pediatric surgery

In a prospective, randomized, double-blind study, Hong et al. [10] studied 55 children aged 1 to 5 years who underwent outpatient hernioplasty of inguinal hernia. After induction of general anesthesia, 28 children received 1 mg/kg ketorolac and 20 mg/kg paracetamol intravenously, 27 children received a similar volume of saline. All children received 1 mcg/kg fentanyl intravenously before incision. The results showed that in the ketorolac/paracetamol group, fewer patients received fentanyl postoperatively (28.6 vs. 81.5%) and the total dose of fentanyl administered was lower (0.54 vs. 1.37 μg/kg). . Immediately after surgery, pain intensity was significantly higher in the control group, but eventually decreased. The authors concluded that preoperative intravenous ketorolac and paracetamol are a simple, safe, and effective way to reduce postoperative pain while reducing the amount of fentanyl administered in children undergoing outpatient inguinal hernia repair.

When using intravenous paracetamol for postoperative analgesia in children, the maximum effect is achieved 1–2 hours after administration of the drug. A number of studies (Anderson B., Arana A. et al.; Autret EDJ et al.) showed that the lowest pain scale was determined when the plasma concentration of paracetamol was 11 mg/ml and above, and when the plasma paracetamol concentration was 25 mg/ml provided adequate pain control in 60% of children after tonsillectomy.

ENT surgery

In a randomized controlled trial, F. Capici et al. [11] included 50 children aged 2 to 5 years who were to undergo adenotonsillectomy. After induction of anesthesia, which also included the administration of 2 μg/kg fentanyl, children were administered 15 mg/kg paracetamol intravenously or 40 mg/kg paracetamol rectally. As a result, it turned out that paracetamol, with both methods of administration, provided good analgesia during the first 6 hours of the study. However, the duration of analgesia with the rectal form was longer (median 10 hours, interquartile range 9–11 hours) than with the intravenous form (7 hours, 6–10 hours). The study results confirm that when using intravenous paracetamol to combat mild to moderate pain, the drug should be administered every 6 hours (4 times a day). To reduce the frequency of administration, the rectal form of the drug can be used.

In a prospective, double-blind, placebo-controlled study, T. Kemppainen et al. [12] included 74 patients who were administered intravenous paracetamol at a dose of 1 g (n = 36) or saline (n = 38) endoscopic sinus surgery The result was a reduction in pain in the paracetamol group compared to the placebo group. Fewer patients in the paracetamol group (9 of 36 - 25%) required backup pain medication (oxycodone) compared to the placebo group (27 of 38 - 71%). There were no significant differences between the groups in terms of side effects that occurred. The authors concluded that paracetamol provided adequate pain relief in patients undergoing endoscopic sinus surgery.

Oncosurgery

In a randomized, double-blind, placebo-controlled study, H. Ohnesorge et al. [13] included 87 patients aged at least 18 years who underwent breast cancer surgery, including segmental resections or mastectomies with or without axillary lymphadenectomy. Three separate groups of patients received intravenous paracetamol 1 g, intravenous analgin 1 g or placebo 20 minutes after surgery and 4, 10 and 16 hours after surgery. As a result, it was found that there were no significant differences between the groups in the total amount of morphine consumed. However, the proportion of patients who did not receive morphine at all postoperatively was higher in the paracetamol group (42%) compared to the placebo group (4%). The ability to move occurred earlier in the group with paracetamol (4.0 ± 0.2 hours) compared to the group with analgin (4.6 ± ± 0.2 hours) and the placebo group (5.5 ± 1.0 hours) . The authors' main conclusion was that the administration of paracetamol led to a significant reduction in the number of patients requiring opioid analgesics during surgery for breast cancer.

Cardiac surgery

One prospective randomized trial [14] showed that the administration of intravenous paracetamol during coronary artery bypass graft leads to a slight reduction in the amount of opioids administered compared with the tablet form of paracetamol (17.4 ± 7.9 mg compared with 22.1 ± 8.6 mg; p = 0.016). However, the question of whether this decrease is clinically significant remains open.

obstetrics and gynecology

In a randomized, double-blind, placebo-controlled study, YE Moon et al. [15] included 76 women who were administered intravenous paracetamol at a dose of 2 g or placebo abdominal hysterectomy In the postoperative period, patients were administered hydromorphine (0.2 mg per bolus injection) using a special device that was controlled by the patients themselves. As a result, it was found that in the paracetamol group, hydromorphine consumption was significantly lower at all control time points (1, 2, 5, 12 and 24 hours after surgery; p = 0.013), and the total amount of hydromorphine administered over 24 hours was was 30% less. In the same group, the incidence of postoperative nausea and vomiting was significantly lower (p < 0.05). The authors concluded that intravenous paracetamol reduced the amount of hydromorphine administered and the incidence of opioid-related side effects in patients with abdominal hysterectomy.

In a study by JA Alhashemi et al. [16] 45 patients with planned cesarean section (full-term pregnancy) were administered intravenous paracetamol 1 g + oral placebo or oral ibuprofen 400 mg + intravenous placebo 30 minutes before surgery. Then the administration of the drugs was repeated every 6 hours. As a result of the study, it turned out that the drugs had the same analgesic activity, determined the same amount of morphine administered and high, but equal patient satisfaction with the analgesia provided. The authors concluded that intravenous paracetamol is a rational alternative to oral ibuprofen for pain management after cesarean section.

Urology

In a prospective, randomized, double-blind study of children 6 to 24 months of age undergoing ureteroneocystostomy, it was reported that intravenous paracetamol resulted in a reduction in the amount of fentanyl administered and a reduction in the incidence of fentanyl-related side effects.

Surgical dentistry

In a study of pediatric dental surgery, intravenous paracetamol, although slightly inferior in pain-relieving effectiveness to intramuscular meperidine, led to earlier discharge of patients, which resulted in a significant economic effect. Therefore, the authors believe that further research should be conducted to explore the possibilities of using paracetamol in this type of surgery.

conclusions

When performing a large number of surgical interventions, the administration of paracetamol intravenously in standard dosages as monotherapy or as part of multimodal analgesia leads to the development of a pronounced analgesic effect, reducing the amount of opioids administered and the frequency of side effects caused by them.

On the Ukrainian pharmaceutical market, paracetamol for intravenous administration is registered under the trade name “Infulgan” (“Yuriya-Pharm”). "Infulgan" is available in bottles of 20, 50 and 100 ml containing 10 mg of paracetamol per 1 ml of solution.

Paracetamol Routek

The incidence of side effects is given according to the following scale: very common >10%; often >1% and 0.1% and 0.01% and

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

From the liver and biliary tract: rarely - increased activity of liver enzymes, usually without the development of jaundice.

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

From the hematopoietic organs: very rarely - thrombocytopenia.

General: rarely - malaise.

The following side effects have also been observed during post-registration use of the drug, but their frequency has not been established:

Allergic reactions: hypersensitivity reactions, anaphylactic shock, anaphylaxis, Quincke's edema.

From the liver and biliary tract: fulminant hepatitis, liver necrosis, liver failure, increased activity of liver enzymes.

From the gastrointestinal tract: nausea, vomiting.

Local reactions: pain and burning sensation at the injection site.

In case of an overdose of the drug, intoxication may develop, especially in elderly patients, children, patients with liver diseases (caused by chronic alcoholism), in patients with nutritional disorders, as well as in patients taking inducers of microsomal liver enzymes, in which fulminant hepatitis and liver failure may develop , cholestatic hepatitis, cytolytic hepatitis, in the above cases - sometimes with a fatal outcome.

The clinical picture of an acute overdose develops within 24 hours after taking paracetamol: gastrointestinal disorders (nausea, vomiting, decreased appetite, abdominal discomfort and/or abdominal pain), pale skin. When administered simultaneously to adults of 7.5 g or more or to children of more than 140 mg/kg, cytolysis of hepatocytes occurs with complete and irreversible liver necrosis, the development of liver failure, metabolic acidosis and encephalopathy, which can lead to coma and death. 12-48 hours after the administration of paracetamol, there is an increase in the activity of “liver” transaminases, lactate dehydrogenase, bilirubin concentration and a decrease in prothrombin content.

Clinical symptoms of liver damage appear 2 days after an overdose of the drug and reach a maximum on days 4-6.

In case of overdose the following are indicated:

- Immediate hospitalization.

— Determination of the quantitative content of paracetamol in blood plasma before starting treatment as early as possible after an overdose;

- Administration of sulfhydryl group donors and precursors for glutathione synthesis - methionine and N-acetylcysteine ​​- within 10 hours after an overdose.

— The need for additional therapeutic measures (further administration of methionine, intravenous administration of N-acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as on the time that has passed since its administration.

- Symptomatic treatment.

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

In most cases, liver transaminase activity returns to normal within 1-2 weeks. In very severe cases, a liver transplant may be required.