DRUGAMOL® INTRAVENOUS INJECTION
(Paracetamol 1g/100ml)
Composition
One 100ml vial contains:
Paracetamol ……………….. 1000mg
Sodium Chloride …………… 900mg
Water for Injection ………… q.s
CLINICAL PHARMACOLOGY
Paracetamol’s exact mechanism of action is unknown unlike other NSAIDS, Paracetamol acts primarily in the Central Nervous System and increases the pain threshold by inhibiting cyclooxygenase, an enzyme involved in prostaglamdin (PG) synthesis. Paracetamol may also inhibit the synthesis or actions of chemical mediators that sensitize the pain receptors to mechanical or chemical stimulation. The antipyrectic activity of paracetamol is exerted.
INDICATIONS
- Pyrexia of unknown origin
- Symptomatic relief of fever and pain associated with common childhood disorders, tonsillitis, Urinary Tract infections and post immunization reactions
- Other conditions where the patient is unable to take oral medications but where paracetamol can be administered with advantage.
- For prevention of febrile convulsion
- Myalgia, post partum pain, headache and other circumstances in which aspirin is an effective analgesic.
- Indicated for short-term treatment of mild to moderate pain especially following surgery.
CONTRAINDICATIONS
Drugamol® Infusion is contraindicated in
- Patients with hypersensitivity to paracetamol
- Cases of severe hepatocellular insufficiency.
- Hypersensitivity to Sodium chloride, hypertonic uterus, hypernatremia and fluid retention.
INTERACTIONS
- Probenecid causes an almost two-fold reduction in clearance of paracetamol by inhibiting its conjugation with glucuronic acid.
A reduction in the paracetamol dose should be considered if it is to be used concomitantly with probenecid.
- The risk of developing hepatotoxicity from paracetamol appears to be increased in patients who regularly consume ethanol. In these patients, hepatotoxicity is possible even at normal therapeutic dosages of paracetamol. Chronic ethanol use increases paracetamol – induced hepatotoxicity by inducing cytochrome P450 (CYP)ZE leading to increased formation of the hepatotoxic metabolite and by depleting liver glutathione stores. Administration of paracetamol should be limited or avoided altogether in alcoholics or patients who consume ethanol regularly.
WARNINGS/PRECAUTION:
1) Paracetamol should be used with caution in cases of:
-Hepatocellular insufficiency,
-Severe renal insufficiency (Creatinine clearance ≤30ml)
-Chronic alcoholism
-Chronic malnutrition (low reserves of hepatic glutathione).
-Dehydration.
2) Doses higher than those recommended entail the risk of very serious liver damage.
3) It is recommended that a suitable analgesic oral treatment be used as soon as this route of administration is possible.
KEEP OUT OF THE REACH OF CHILDREN!
ADVERSE REACTIONS
As with all paracetamol products, adverse drug reactions are rare.
Very rare cases of hypersensitivity reactions ranging from simple skin rash or urticaria to anaphylactic shock have been reported and required discontinuation of treatment.
SYMPTOMS OF OVERDOSE AND ANTIDOTE
There is a risk of liver injury (including fulminant hepatitis, hepatic failure, cholestatic hepatitis, cytolytic hepatitis), particularly in elderly subjects, in young children, in patients with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition and in patients receiving enzyme inducers. Overdosing may be fatal in these cases.
Symptoms generally appear within the first 24 hours and comprise: nausea, vomiting, anorexia, pallor and abdominal pain.
Before beginning treatment, take a blood sample for plasma paracetamol assay, as soon as possible after the overdose.
The treatment includes administration of the antidote, N-acetylcysteine (NAC) by the intravenous or oral route, if possible before the 10th hour, N-acetylcysteine can, however, give some degree of 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 24hours. In most cases hepatic transaminases return to normal in one to two weeks with full return of normal liver function. In very severe cases, however, liver transplantation may be necessary.
DOSAGE AND ADMINISTRATION
The 100ml vial is restricted to adults, adolescents and children weighing more than 33kg (approximately 11 years old).
The 50ml vial is restricted in term new born, infants, toddlers and children weighing less than 33kg.
Adolescents and adults weighing more than 50kg
Paracetamol 1g per administration i.e one 100ml, up to four times a day. The minimum interval between each administration must be 4 hours.
The maximum daily dose must not exceed 4kg.
Children weighing more than 33kg (approximately 2 years old). Adolescents and adults weighing less than 50kg
Paracetamol15mg/kg per administration i.e. 1.5ml solution per kg up to four times a day the minimum interval between each administration must be 4 hours.
The maximum daily dose must not exceed 60mg/kg (without exceeding 3g).
Children weighing more than 10kg (approximately 1 year old) and weighing less than 33kg.
Paracetamol 15mg/kg per administration i.e. 5ml solution per kg up to 4 times a day. The minimum between each administration must be 4 hours. The maximum daily dose must not exceed 60mg/kg (without exceeding 2g)
Term newborn infants, infants, toddlers and children weighing less than 10kg up to approximately 1 year old.
Paracetamol 7.5mg/kg per administration 1.e. 0.75ml solution per kg up to four times a day. The minimum interval between each administration must be 4 hours. The maximum daily dose must no exceed 30mg/kg.
NOTE
Sever renal insufficiency
It is recommended, when giving paracetamol to patients with severe renal impairment (Creatinine clearance ≤ 30ml/min) to increase the minimum interval between each administration to 6 hours.
In Adults with hepatocellular insufficiency.
Chronic alcoholism, chronic malnutrition (low reserve of hepatic glutathione). Dehydration: The maximum daily dose must not exceed 3g.
Method of administration
The paracetamol is administered as a 15-minute intravenous infusion.
Following intravenous administration of paracetamol 10mg/kg/body weight, the distribution half life ranges between 3 -19 minutes, which is indicative of rapid tissue distribution. Between 90-95% of the normal therapeutic dose is metabolized in the liver via glucoronidation and sulphate conjugation and is excreted in the urine as glutathione and sulphate conjugate.
In neonates and children (3-9 years)
Paracetamol is excreted primarily as the sulphate conjugates.
The elimination half-life of paracetamol is 2-4 hours in patient with normal liver function. Half-life can be prolonged in patients with hepatic disease.
Administration of intramuscular or intravenous Drugamol results in absolute bioavailability (100%) of the administered dose. Peak plasma concentrations of 30µ/ml are observed immediately after infusion. Drugamol rapidly crosses the blood brain barrier, and achieves appreciable concentration, but possibly the reported peak concentrated in the serebrospinal fluid.
PRESENTATION
Drugamol® infusion is presented in a bottle with total content of 100ml.
STORAGE CONDITION
Store at room temperature