Novamol PARACETAMOL 1000 mg/ 109 m, SOLUTION FOR INFUSION

PATIENT INFORMATION LEAFLET

PARACETAMOL 1000 mg/ 109 m, SOLUTION FOR INFUSION

Composition

Each 100 mL contains:1000 mg

Paracetamol BP q.s

Water for Injection

DOSAGE FORM

Solution for Infusion

PHARMACOLOGY

The precise mecihanism of the analgesic properties of paracetamol has yet to be established: it may involve central and peripheral actions.

Paracetamol provides onset of pain relief within 5 to 10 minutes of administration. The peak analgesic effect is obtained in 1 hour and the duration of this effect is usually 4 to 6 hours.

Paracetamol reduces fever within 30 minutes after the start of administration with duration of the antipyretic effect of at least 6 hours.

Pharmacokinetics

Absorption:

Paracetamol pharmacokinetics is linear up to 2 g after single administration and repeated administration for 24 hours. The maximum plasma concentration ( Cmax ) of paracetamol.

Observed at the end of 15 minutes intravenous infusion of 1g of paracetamol observed at the end of 15 minutes intravenous infusion of 1 g of paracetamol is 30 ug/ml.

Distribution:

Following an infusion of 1g of Paracetamol, significant concentration of paracetamol (about 1.5ug/ml) were observed in the cerebrospinal fluid at and after the 20th minute following infusion.

Metabolism

Paracetamol is metabolized manly in the liver following two major hepatic pathways, glucuronic Acid conjunction and Sulphur acid conjugation, The later rout is rapidly saturable at doses that exceed the therapeutic doses. A small proportion (less than 4%) is transformed by cytochrome P 450 into a reactive intermediate (N-acety! benzoquinone imine) which, under normal conditions of use, is rapidly detoxified by reduced glutathione and eliminated in the urine. after conjugation with cysteine and mercapturic acid. On the other hand, during massive overdosing, the amount 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 as glucuronide (60-80%) and sulphate (20-30%) conjugates, Less than 5% is eliminated unchanged. Plasma half-life is 2.7 hours and total body clearance18 Lh.

Special population

Renal insufficiency

In severe renal impairment (creatinine clearance 10-30 ml / min), the elimination of paracetamol is slightly delayed the elimination half-life varying from 2 to 5.3 h. The rate of elimination of glucuronide and sulphate conjugates is 3 times slower in severe renal impairment than in healthy subjects. Consequently, it is recommended to observe at interval of at least 6 hours between two administrations in patients with severe renal impairment (creatinine clearance 30 ml/min).

Elderly subjects

The pharmacokinetics and metabolism of paracetamol are not modified in the elderly NO dose

adjustment is required in this population.

INDICATIONS

Paracetamol is indicated for the short-term treatment of pain of moderate intensity, particularly

in the postoperative period, and for the short-term treatment of fever when the intravenous route

is clinically justified Dy the urgency to treat pain or hyperthermia and / or when other routes of

administration is not possible.

DOSAGE AND METHOD OF ADMINISTRATION

For Intravenous use

Note: The 100 mL bottle a restricted to adults, adolescents and children weighing more than 3kg (approximately 11 years old).

Posology.

Adolescents and adults weighing more than 50 ka: Paracetamol 1 g per administration one100 ml bottle, up 4 tines a day. The minimum interval between each administration must be 4 hours. The maximum daily dose must not exceed 4g.

Children weighing more than 33 kg (approximately 11 years old). adolescents and adult 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 interval between each administration must be 4 hours. The maximum daily dose must not exceed 60 mg/kg (without exceeding 3 g). Sever renal impairment (creatinine clearance 3Omi/min): Increase the minimum interval between each administration to6 hours. in adults with hepatic cellular insufficiency, chronic, alcoholism, chronic malnutrition (Low reserves of hepatic glutathione), dehydration, a maximum dose most not exceed 3g. The paracetamol solution is administrated as 15 minutes intravenous solution.

Paracetamol solution is supplied in single use, ready to use infusion bottles. Paracetamol drug products should be inspected visually for particulate matter prior administration, check or damages by firmly squeezing the bags. If leaks are detected, discard the solution, as sterility may be impaired.

Do not use the bags in series of connections.

Additives should not be introduced into this solution. If paracetamol solution is to be given. Concomitantly with other drugs, each drug should be given separately in accordance with the recommended dosage and route of administration for each product. If the same iv lines is used. For sequential infusion of several drugs, the lines should be flushed before and after infusion

CONTRAINDICATIONS

PARACETAMOL is contraindicated:

In patient with hypersensitivity to paracetamol or to propacetamol hydrochloride (prodrug of paracetamol) or any of the excipients.

-In cases of severe hepatocellular insufficiency

WARNING AND PRECAUTIONS

It is recommended to have recourse toa suitable analgesic treatment orally as soon as this route of administration is possible. To avoid a risk of overdose, check the absence of paracetamol in the composition of other associated drugs. Doses higher than recommended carry a risk of very severe liver damage. Symptoms and clinical signs of liver damage (including fulminant hepatitis, hepatitis failure, cholestatic hepatitis, cytolytic hepatitis) are usually seen after 2 days and usually peak after 4-6 days. Treatment with antidote should be given as soon as possible.

Precautions for use

Paracetamol should be used with caution in case of hepatocellular insufficiency
Severe renal insufficiency (creatinine clearance 30 ml/min)
Chronic alcoholism
Chronic malnutrition
Dehydration

Drug Interactions

Probenecid causes an almost two-fold reduction in clearance of paracetamol by inhibiting its Conjugation with gltucuronic acid. A reduction in paracetamol dose should be considered if it is to be used concomitantly with probenecid.

Pregnancy and Lactation

Pregnancy

Clinical experience win intravenous administration of paracetamol is limited. However, epidenioiagical data on the use of oral therapeutic doses of paracetamol do not show any adverse effects on pregnancy or on the health of the fetus or newborn. Epiderniolocical studies devoted to the neurodevelopment of children exposed to paracetamol in utero produce inconclusive results. In animals, reproduction studies have not been performed with the intravenous form. However, Paracetamol should only be used during pregnancy after carful assessment of the benefit/ risk ratio. In this case the recommended dosage and duration treatment should be strictly observed

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

UNDESIRABLE EFFECTS

Adverse reactions were classified according to their incidence using the following classification:

Very common (211 10), common (21100, <1/10}, uncommon (1 1,0O0, <1100), rare 10,000, <1/1000), very rare (<1110,000) not known (frequency cannot be estimated from available data)

Very rare cases of hypersensitivity reactions ranging from simple skin rash or urticaria to anaphylactic shock has been reported and require discontinuation of treatment. Very rare cases of serious skin reactions have been reported. Erythema, flushing, pruritus and tachycardia has been reported.

OVERDOSE

The risk of hepatic damage (including futrninant hepatitis, hepatitis, insufficiency, cholestatic hepatitis, cytolytic hepatitis) is particularly to he feared in the elderly and young children, in patients with hepatic impairment in the event of chronic alcoholic, in chronically malnourished patients, and in patients receiving enzyme inducers. In these cases, poisoning can be fatal. Symptoms usually appear within the first 24 hors and include nausea, vomiting, anorexia, Pallor, an abdominal pain. An overdose from 7 5 a of paracetamol in a single dose in adults and 140 mg/kg of body weight in a single dose in children, causes hepatic cytolysis which may lead to complete necrosis and irreversible resulting in hepatocellular insufficiency, metabolic acidosis, encephalopathy which can lead to comma and death. At the same time, there is an increase in hepatic transaminases (AST ALT) lactate-dehydrogenase, bilirubin, as well as decrease in the level of prothrombin which may appear 12 to 48 hours after administration. Clinical symptoms of liver damage are usually seen after wo days, and peak after 4- days.

Emergency measures Immediate Hospitalized

Immediate hospitalization.
Before starting treatment, take a tube of blood for the plasma dosage of paracetamol, as soon as possible after the overdose.
Treatment of overdose includes administration of the antidote N-acetylcysteine (NAC) intravenously or orally, if possible before the tenth hour. NAC may however provide some protection even after 10 hours, but in this case prolonged treatment is given.

Symptomatic treatment.

Hepatic tests should be done at the start and repeated every 24 hours
Usually, hepatic transaminases normalize after one or two weeks with complete recovery of liver function. However, in very severe cases, liver transplantation may be necessary

STORAGE:

Store at a temperature not exceeding 3O protected from light. Do not freeze.

Manufactured For/ Fabriqué Pour:

Pharmnanova Limited

Okodan Stteet, Osu-Manhean

Accra - Ghana

www.pharmanovagh.com

Manufactured in Ghana by /Fabriqué au Ghana par

Atlantic Lifesciences Limited

Plot no:16/01, Larpleku,

Tema-Alao Road,

Greater Accra,Ghana.