Infulgan

Infulgan belongs to the group of drugs antipyretics and analgesics.

Paracetamol contained in the drug demonstrates antipyretic and analgesic activity. Due to the fact that the drug does not affect the processes of PG binding in peripheral tissues, it does not lead to the development of a negative effect on the indicators of EBV (fluid and sodium retention), as well as the mucous membrane in the digestive system. [ 1 ]

Indications Infulgan

It is used for short-term therapy for moderate pain (especially after surgery), as well as for short-term therapy of hyperthermic symptoms (in situations where there is a clinical justification for intravenous administration of the drug or when it is impossible to use other methods of administration).

Release form

The release of the medicine is realized in the form of infusion liquid - inside bottles with a capacity of 20, 50 or 100 ml. Inside the box - 1 such bottle.

Pharmacodynamics

Paracetamol has a blocking effect on the activity of COX-1 and COX-2 exclusively within the central nervous system – it acts on pain and thermoregulatory centers.

Within inflamed tissues, cellular peroxidases neutralize the effect that paracetamol has on COX, which may explain the almost complete lack of anti-inflammatory activity. [ 2 ]

Pharmacokinetics

Pain relief is observed after 5-10 minutes from the moment of Infulgan application. The maximum analgesic effect develops after 60 minutes, and the duration of this effect is usually 4-6 hours.

The medication reduces temperature within half an hour after use, and its antipyretic effect lasts for at least 6 hours.

Absorption.

With a single administration of up to 2 g of the drug and with repeated use in the following 24 hours, the pharmacokinetic characteristics of paracetamol remain linear.

The bioavailability level when using an infusion of 0.5 and 1 g of the drug is similar to the indicators observed in the case of using 1 and 2 g of propacetamol (it contains 0.5 and 1 g of paracetamol, respectively). The plasma level of Cmax is noted by the end of the infusion, which for 0.5 or 1 g of the substance lasts 15 minutes and is equal to 15 or 30 mcg/ml, respectively.

Distribution processes.

The distribution volume of the drug is approximately 1 l/kg. Paracetamol has poor synthesis with protein. When using 1 g of Infulgan, most of it (approximately 1.5 mcg/ml) is determined in the cerebrospinal fluid after 20 minutes from the moment of infusion.

Exchange processes.

Most of the paracetamol is involved in intrahepatic metabolism, passing through 2 main phases: conjugation with glucuronic and sulfuric acid. The latter phase has rapid saturation in the case of using doses exceeding medicinal ones.

A small amount (less than 4%) of the drug is involved in metabolism with the help of hemoprotein P450, during which an intermediate metabolic element (N-acetylbenzoquinoneimine) is formed, which under stable conditions is quickly neutralized by the action of reduced glutathione. Then it is excreted in the urine, having synthesized with mercaptopurine acid and cysteine. But in the case of massive intoxication, the volumes of this toxic metabolic element increase.

Excretion.

Metabolic components of paracetamol are mainly excreted with urine. Over a period of 24 hours, 90% of the administered portion is excreted - most of it in the form of glucuronide (60-80%), as well as sulfate (20-30%). Less than 5% of the drug is excreted unchanged. The half-life is 2.7 hours, and the systemic clearance is 18 l/hour.

Dosing and administration

The medication must be administered intravenously.

Adults, teenagers, and children weighing over 33 kg use liquid from 0.1 l bottles.

Children whose weight is less than 33 kg are prescribed the medicine from 20 or 50 ml bottles.

The portion size is determined based on the patient's weight:

• weight ≤10 kg: the dose is 7.5 mg/kg (the volume for 1 injection is 0.75 ml/kg). No more than 7.5 ml of the drug can be used per injection. No more than 30 mg/kg is administered per day;
• weight in the range of >10/≤33 kg: dosage size 15 mg/kg (volume 1.5 ml/kg). 49.5 ml can be used in 1 administration. Per day – maximum 60 mg/kg (no more than 2 g);
• weight within the range of >33/≤50 kg: the dosage is 15 mg/kg (volume 1.5 ml/kg). A maximum of 75 ml is allowed for 1 injection. No more than 60 mg/kg (maximum 3 g) is used per day;
• weight >50 kg (with risk of hepatotoxicity): portion size – 1 g (volume 0.1 l). No more than 0.1 ml can be administered per infusion. A maximum of 3 g is used per day;
• weight >50 kg (without risk of hepatotoxicity): dosage size – 1 g (volume 0.1 l). Do not use more than 0.1 l per injection. Do not administer more than 4 g per day.

There must be at least a 4-hour interval between procedures. Often no more than 4 infusions are administered per day.

In individuals with severe renal impairment, a minimum 6-hour interval must be observed between infusions.

The maximum daily doses are prescribed to people who do not use other medications that contain paracetamol, so if they need to use such drugs, they need to change the dosage of Infulgan accordingly.

Persons with severe renal failure.

When using paracetamol in people with CC values ≤30 ml per minute, the minimum interval between procedures should be increased to 6 hours.

People with chronic alcoholism, hepatocellular insufficiency, as well as people with dehydration or chronic malnutrition (low levels of intrahepatic glutathione reserves).

A maximum of 3 g of the medication can be used per day. Paracetamol is administered via infusion, the duration of which is 15 minutes.

Children weighing ≤10 kg.

Due to the small volume of the substance used, the bottle with the medicine is not suspended for infusion. The required amount of the drug is drawn from the bottle through a syringe and then administered undissolved (or dissolved in 5% glucose or 0.9% NaCl (in a 1:9 ratio)) over a 15-minute period.

The diluted medicinal liquid must be used within 60 minutes from the moment of its preparation (this period includes the time of the infusion).

A 5 or 10 ml syringe is used to select the required dosage (taking into account the child's weight). The portion size should not exceed 7.5 ml.

• Application for children

It can be used from the moment of birth of the child. It cannot be prescribed only to premature newborns.

Use Infulgan during pregnancy

There is limited information regarding the clinical use of the drug. Epidemiological information regarding the administration of therapeutic doses of paracetamol shows no adverse effects on the course of pregnancy or fetal development.

Prospective data on drug poisoning during pregnancy have not shown an increased risk of developmental anomalies.

During pregnancy, Infulgan is used only after careful assessment of all possible risks and benefits, and when selecting the dosage and duration of therapy, you must strictly follow the instructions.

Orally administered paracetamol is excreted in small amounts in breast milk. No adverse symptoms have been observed in breastfed infants when paracetamol is used during breastfeeding.

Contraindications

Contraindicated for people with severe intolerance to paracetamol, propacetamol hydrochloride (a precursor of paracetamol) or other components of the drug. In addition, do not use in severe hepatocellular insufficiency.

Side effects Infulgan

Main side effects:

• systemic disorders: malaise occasionally appears. Signs of intolerance are noted sporadically;
• cardiac disorders: occasionally a decrease in blood pressure values is observed;
• problems with digestive function: occasionally there is an increase in liver transaminase levels;
• lesions of the blood and lymph system: leuko-, thrombocyto- or neutropenia are observed occasionally.

Clinical tests resulted in frequent occurrence of negative symptoms at the injection site (burning and pain).

Signs of severe intolerance appeared sporadically: from rashes or urticaria to the development of anaphylaxis, which required discontinuation of therapy.

In addition, there are reports of the appearance of redness, erythema, itching or tachycardia.

Overdose

The risk of liver damage (including cholestatic, fulminant or cytolytic hepatitis, as well as liver failure) increases in young children, the elderly, people with chronic alcoholism, liver pathologies, alimentary dystrophy and with reduced enzyme activity. In such cases, poisoning with Infulgan can be fatal.

Symptoms develop over the first 24 hours and include anorexia, abdominal pain, vomiting, pallor and nausea.

Intoxication develops with a single use of a portion of 7.5+ g (for an adult) and 0.14 g/kg (for a child). In such cases, liver failure, hepatic cytolysis, and also metabolic acidosis and encephalopathy appear, which can provoke a comatose state and death. Over a period of 12-48 hours, the indicators of intrahepatic transaminases (AST and ALT) and bilirubin with LDH increase, and prothrombin values decrease.

Clinical signs of liver damage are observed after 2 days, reaching their maximum after 4-6 days.

Among the urgent measures required are:

• emergency hospitalization;
• detection of plasma paracetamol levels (must be carried out before the start of therapy, as quickly as possible after poisoning);
• oral administration or intravenous injection of an antidote - NAC. It is recommended to carry out this procedure within 10 hours after intoxication. NAC can be used later, but the therapy will last longer;
• symptomatic actions.

Liver function tests should be performed before therapy is started (they should be repeated at 24-hour intervals). Intrahepatic transaminase values often return to normal after 1-2 weeks; liver function is completely restored. However, sometimes patients may require a liver transplant.

Interactions with other drugs

When combined with probenecid, the clearance rate of paracetamol is halved due to blocking the synthesis of the latter with glucuronic acid. In this regard, when these drugs are administered simultaneously, a reduction in the dose of paracetamol is required.

Salicylates can prolong the half-life of paracetamol.

Substances that induce intrahepatic oxidation of microsomes (these include barbiturates, phenylbutazone with phenytoin, tricyclics, ethyl alcohol and rifampicin) can lead to the development of severe poisoning even in the case of a slight excess of dosage.

Combination of paracetamol (4 g per day for at least 4 days) and oral anticoagulants may cause minor changes in INR values. With such combinations, it is necessary to monitor the INR level during therapy and for 7 days after stopping the use of Infulgan.

Storage conditions

Infulgan must be stored in a place inaccessible to children. Do not freeze the medicine. Temperature values - maximum 25°C.

Shelf life

Infulgan can be used within 24 months from the date of production of the therapeutic agent.

Analogues

The analogs of the drug are Elgan, Panadol with Grippocitron, Anapiron, Piaron and Efferalgan with Paracetamol, Cefekon D and Ifimol with Rodapap DC 90 HSP.