Newpamol

Each mL contains: Paracetamol BP 10 mg, Water for Injection BP q.s to 1 mL.

Pharmacology: Pharmacokinetics: Paracetamol pharmacokinetics is linear up to 2 g after single administration and after repeated administration during 24 hours. The maximal plasma concentration (C_max) of paracetamol is observed at the end of 15-minutes. Intravenous Infusion of 500 mg and 1 g about 15 μg/mL respectively.
Distribution: The volume of distribution of paracetamol is approximately 1 L/kg.
Paracetamol is not extensively bound to plasma proteins.
Following infusion of 1 g to plasma proteins of paracetamol (about 1.5 μg/mL) were observed in the cerebrospinal fluid at and after the 20th minute following infusion.
Metabolism: Paracetamol is metabolised mainly in the liver following the two major hepatic pathways: glucuronic acid conjugation and sulphuric acid conjugation. The latter route is rapidly saturable at doses that exceed the therapeutic doses. A small fraction (less than 4%) is metabolised by cytochrome P450 to a reactive intermediate (N-acetyl benzoquinone imine), which under normal conditions of uses, is rapidly detoxified by reduced glutathione and eliminated in the urine after conjugated with cysteine and mercapturic acid. However, during massive overdosing, the quantity of this toxic metabolite is increased.
Elimination: The metabolites of paracetamol are mainly excreted in the urine. 90% of the dose administered is excreted within 24 hours, mainly in glucuronide (60-80%) and sulphate (20-30%) conjugates. Less than 5% is eliminated unchanged. Plasma half-life is 2.7 hours and total body clearance is 18 L/h.
Neonates, Infants and Children: The pharmacokinetics parameter of paracetamol observed in infants and children are similar to those observed in adults, except for the plasma half-life that is slightly shorter (1.5 to 2 hr) than in adults. In neonates the plasma half-life is longer than in infants i.e. around 3.5 hours. Neonates, infants and children up to 10 years excrete significantly less glucuronide and more sulphate than adults.
Special Populations: Renal insufficiency: In case of severe renal impairment (creatinine clearance 10-30 mL/min), the elimination of paracetamol is slightly delayed, the elimination half-life ranging from 2.5-3 hours for the glucuronide and sulphate conjugates, the elimination rate is 3 times slower in subjects with severe renal impairment than in heathy subjects. Therefore when giving paracetamol to patients with severe renal impairment (creatinine clearance 30 mL/min) the minimum intervals between each administration should be increased to 6 hours.
Elderly Subjects: The pharmacokinetics and the metabolism of paracetamol is not modified in elderly subjects.
No dose adjustment is required in this population.

Paracetamol is indicated for the 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.

Intravenous use: The 100 mL vial is restricted to adults, adolescent and children weighing more than 33 kg (approximately 1 year old).
Dosage: Adolescent and adults weighing more than 50 kg: Paracetamol 1 g per administration, i.e., 1.5 mL 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 4 g.
Children weighing more than 33 kg (approximately 11 years old), adolescent and adults weighing less than 50 kg: Paracetamol 15 mg/kg per administration, i.e., 1.5 mL solution per kg up to four times a day. The minimum intervals between each administration must be 4 hours. The maximum daily dose must not exceed 60 mg/kg (without exceeding 3 g).
Children weighing more than 10 kg (approximately 1 year old), and weighing less than 33 kg: Paracetamol 15 mg/kg per administration, i.e., 1.5 mL solution per kg up to four times a day. The minimum intervals between each administration must be 4 hours. The maximum daily dose must not exceed 60 mg/kg (without exceeding 2 g).
Term newborn daily infants, toddlers and children weighing less than 10 kg (up to approximately 1 year old): Paracetamol 7.5 mg/kg per administration, i.e., 0.75 mL solution per kg up to four times a day. The minimum intervals between administration must be 4 hours. The maximum daily dose must not exceed 30 mg/kg. No safety and efficacy data for premature neonates.
The paracetamol solution is administered as a 15-minute intravenous infusion. Paracetamol 50 mL vial can also be diluted in a 0.9% sodium chloride solution up to one tenth. In this case, use the diluted solution within the hours following its preparation (infusion time included). As for all solutions for infusion presented in glass vials, it should be remembered that close monitoring at the end of the infusion applies particularly for central route infusion, in order to avoid air embolism.
Severe Insufficiency: It is recommended, when giving paracetamol to patients with severe renal impairment (creatinine clearance 30 mL/min), to increase the minimum intervals between each administration to 6 hours.

There is a risk of poisoning, particularly in elderly subjects, in patients with liver disease, in cases of chronic alcoholism, in patient 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. Overdose, 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 comma and death. Simultaneously, increased levels of hepatic transaminases (AST, ALT) lactate dehydrogenase and bilirubin damage are usually evident initially after two days.
Emergency Measures: Immediate hospitalisation.
Before beginning treatment, take a blood sample for plasma paracetamol assay, as soon possible after the overdose. The treatment inducers includes administration of the antidote, N-acetylcysteine (NAC) by the i.v. or oral route if possible before than 10th hour. NAC can, however; give some degree of protection even after 10 hours but in these case prolonged treatment is given.
Symptomatic treatment.
Hepatic test must be carried out at the beginning of treatment and repeated 24 every hours. In most cases, hepatic transaminases return in to normal in one to two weeks with full return of normal liver function. In very rare cases, however, liver transplantation may be necessary.

In patient with hypersensitivity to paracetamol or to proparacetamol hydrochloride (prodrug of paracetamol).
In case of severe hepatocellular insufficiency.

It is recommended that a suitable analgesic oral treatment be used as soon as this route of administration is possible. Doses higher than those recommended entail the risk of very serious liver damage are not usually in two days, and up to maximum of 4-6 days, after administration. Treatment with antidote should be given as soon as possible.
Contains sodium metabisulfite a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life threatening or less severe asthmatic episodes in certain susceptible persons.

Paracetamol should be used with caution in cases of: Hepatocellular insufficiency.
Severe renal insufficiency (creatinine clearance 30 mL/min).
Chronic alcoholism.
Chronic malnutrition (low reserves of hepatic glutathione).
Dehydration.

Lactation: After oral administration, paracetamol is excreted into breast milk in small quantities. No undesirable effects on nursing infants have been reported. Consequently, paracetamol may be used in breast feeding women.

As with paracetamol products, adverse drug reactions are rare (>1/10000, <1/100) or very rare (1/1000). They are described as follows: See table.

Click on icon to see table/diagram/image

Very rare cases of hypersensitivity reaction from simple skin rash or urticaria to anaphylactic shock have been reported require discontinuation of treatment.

Probenecid causes an almost 2-fold reduction in clearance of paracetamol by inhibiting its conjugation with glucuronic acid. A reduction in the paracetamol dose should be used concomitantly with probenecid.
Salicylamide may prolong the elimination ½ life of paracetamol.
Caution should be taken with the concomitant intake of enzyme-inducing substances.
Concomitant use of paracetamol (4 g per day for at least 4 days) with oral anticoagulants may lead to slight variation of INR values.
In this case, increased monitoring of INR values should be conducted during the period of concomitant use as for 1 week after paracetamol treatment has been discontinued.

Store at temperatures not exceeding 30°C.
Do not freeze.

Analgesics (Non-Opioid) & Antipyretics

N02BE01 - paracetamol ; Belongs to the class of anilide preparations. Used to relieve pain and fever.

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