Apotel

/ Easy Care

The drug is administered by intravenous infusion. It is usually dissolved in 100 ml Sodium Chloride 0.9% Sterile Solution (or alternative solutions) or according to doctor’s decision.
Alternative Solutions: 0.9% sodium chloride, Lactated Ringer’s, 3.33% Dextrose/0.3% NaCl, 5.0% Dextrose. The solution stable  for 4 hours in intravenous admixtures with these alternative solutions.
Adolescents and adults who weigh more than 50 kg: 1 g of paracetamol per dose up to four times a day. The ampoule content is dissolved in Sodium Chloride 0.9% Sterile Solution (or alternative solutions), usually in a 100 ml vial, and is administered immediately.
The minimum interval between each administration must be at least 4 hours.
The maximum daily dose must not exceed 4 g.
Pediatric dosing: Children adolescents and adults weighing 33 to 50 kg: 15 mg/kg up to four times a day. The maximum daily dose is 60 mg/kg of body weight, maximum 3 g.
Children weighing 10 to 33 kg (approx 1-11 years old): 15 mg/kg up to four times a day. The maximum daily dose is 60 mg/kg of body weight, maximum 2g.
Newborns (full term) and infants up to 10kg: 7.5 mg/kg up to four times a day. The maximum daily dose is 30 mg/kg of body weight. There is no information available concerning safety and effectiveness for premature infants.
Serious renal insufficiency (creatinine clearance ≤30 ml/min): The minimum interval between each administration must be at least 6 hours and a reduced total daily dose of paracetamol may be warranted.
Hepatocellular insufficiency, chronic alcoholism, chronic malnutrition  and dehydration: The maximum daily dose must not exceed 3g.
Solution preparation for intravenous infusion – Way of administration: The ampoule content is dissolved into a 100 ml of Sodium Chloride 0.9% Sterile Solution (or alternative solutions) or according to doctor’s decision. The 100 ml produced solution is administered by intravenous infusion, in a time interval of 15 min.

Short-term treatment of moderate pain, especially following surgery and for the short-term treatment of fever, when administration by intravenous route is clinically justified by an urgent need to treat pain or hyperthermia and/or when other routes of administration are not possible.

Hypersensitivity to paracetamol or to propacetamol hydrochloride (prodrug of paracetamol) or to one of the product’s excipients.
During pregnancy, due to the Glycerol Formal excipient which is implicated in teratogenicity in animals.
Cases of severe hepatocellular insufficiency.

Warnings and Precautions during Administration: It is recommended to use a suitable analgesic oral treatment as soon as this administration route is possible.
In order to avoid the risk of overdose, one should check that other medicinal products administered along with this drug  do not contain paracetamol or propacetamol.
Doses higher than the recommended ones entails risk for hepatic injury, including the risk of severe hepatotoxicity and death. Do not exceed the maximum recommended daily dose of paracetamol. Clinical symptoms and signs of liver damage are usually first seen after two days of drug administration, with a peak seen usually after 4 to 6 days.
Treatment with antidote should be given as soon as possible.
Caution is required regarding administration during lactation since there are no studies on the effects of Glycerol Formal in lactated women.
Paracetamol has been associated with a risk of rare but serious skin reactions. These skin reactions, known as Stevens- Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), can be fatal.
Reddening of the skin, rash, blisters, and detachment of the upper surface of the skin can occur with the use of drug products that contain paracetamol. These reactions can occur with first-time use of paracetamol or at any time while it is being taken.
Anyone who develops a skin rash or reaction while using paracetamol should stop the drug and seek medical attention right away. Anyone who has experienced a serious skin reaction with paracetamol should not take the drug again and should contact their health care professional to discuss alternative pain relievers/fever reducers.
Health care professionals should be aware of this rare risk and consider paracetamol along with other drugs already known to have such an association, when assessing patients with potentially drug induced skin reactions.
Precautions for use: Paracetamol should be used with caution in the following cases: Hepatocellular insufficiency, or active hepatic disease, Severe renal insufficiency (creatinine clearance ≤ 30 ml/min). Chronic alcoholism. Chronic malnutrition (low levels of hepatic glutathione). Severe hypovolemia (e.g., due to dehydration or blood loss).

As all paracetamol products, adverse reactions are rare (>1/10000 to <1/1000) or very rare: Malaise, Hypotension, Increased levels of hepatic transaminas, Hypersensetivity.
See prescribing information for full details.

Drug Interactions and other forms of interaction:
– Probenecid causes an almost 2-fold reduction in clearance of paracetamol by
inhibiting its conjugation with glucuronic acid. A reduction of the paracetamol dose should be considered for concomitant treatment with probenecid.
– Salicylamide may prolong the elimination t1/2 of paracetamol.
– Caution should be paid to the concomitant intake of enzyme-inducing substances.
Effects of other Substances on Paracetamol:
Substances that induce or regulate hepatic cytochrome enzyme CYP2E1 may alter the metabolism of paracetamol and increase its hepatotoxic potential. The clinical consequences of these effects have not been established. Effects of ethanol are complex, because excessive alcohol usage can induce hepatic cytochromes, but ethanol also acts as a competitive inhibitor of the metabolism of paracetamol.
Chronic oral paracetamol use at a dose of 4000 mg/day has been shown to cause an increase in international normalized ratio (INR) values in some patients who have been stabilized on sodium warfarin as an anticoagulant. As no studies have been performed evaluating the short-term use of APOTEL in patients on oral anticoagulants, increased monitoring of INR values should be conducted in such circumstances.

Pregnancy: Clinical experience of intravenous administration of paracetamol is limited. However, epidemiological data from the use of oral therapeutic doses of paracetamol indicate no undesirable effects on the pregnancy or on the health of the foetus / newborn infant.
However, studies with the oral route did not show any malformation of foetotoxic effects. The product is contraindicated during pregnancy, due to the Glycerol Formal excipient which is implicated in teratogenicity in animals.
Lactation: After oral administration, paracetamol is excreted in small quantities into breast milk. No undesirable effects on nursing infants have been reported. Consequently, this drug may be used in breast-feeding women.
Caution is required regarding administration during lactation since there are no studies on the effects of Glycerol Formal in lactated women.          

In acute paracetamol overdose, dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and thrombocytopenia may also occur. Plasma paracetamol levels > 300 mcg/ml at 4 hours  after oral ingestion were associated with hepatic damage in 90% of patients; minimal hepatic damage is anticipated if plasma levels at 4 hours are < 150 mcg/ml or < 37.5 mcg/ml at 12 hours after ingestion. There is a risk of liver injury (including fulminant hepatitis, hepatic failure, cholestatic hepatitis, cytolytic hepatitis), particularly in elderly patients and young children, patients with liver disease, in cases of chronic alcoholism, patients with chronic malnutrition and patients receiving enzyme inducers. Overdosing can be fatal in these cases. Symptoms generally appear within the first 24 hours and comprise: nausea, vomiting, anorexia, pallor, abdominal pain, diaphoresis, and general malaise. Overdose of 7.5 g or more of paracetamol in a single administration in adults or 140 mg/Kg of body weight in a single administration in children, causes hepatic cytolysis likely to induce complete and irreversible necrosis, resulting in hepatocellular insufficiency, metabolic acidosis and encephalopathy, which may lead to coma and death. Simultaneously, increased levels of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin are observed together with decreased prothrombin levels that may appear 12 to 48 hours after administration.
Clinical symptoms of liver damage are usually evident initially after two days, and reach a maximum after 4 to 6 days.
Emergency measures: Immediate  hospitalization. Before beginning treatment, take a tube of blood for plasma paracetamol assay, as soon as possible after the overdose. The treatment includes administration of the antidote, N-acetylcysteine (NAC), by the IV or oral route, if possible before the 10th hour. NAC can, however, give some degree protection even after 10 hours, but in these cases, prolonged treatment is given.
Symptomatic treatment. Hepatic tests must be carried out at the beginning of treatment and repeated every 24 hours. In most cases, hepatic transaminases peak after 4 to 6 days and return to normal in one to two weeks, with full restitution of liver function. In very rare cases, however, liver transplantation may be necessary. 

Storage: Do not store above 25°C.
Shelf life: After reconstitution: 4 hours.
Compatibility: This drug should not be mixed with other medicinal products.