Elimination:
PROVAS® Infusion The metabolites of paracetamol are mainly excreted in the urine. 90% of the dose
(Paracetamol) 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
COMPOSITION: hours and total body clearance is 18 L/h
Each 100ml PROVAS® vial contains 1000mg Paracetamol
Neonates, Infants and Children:
DESCRIPTION: The pharmacokinetic parameters of paracetamol observed in infants and children are
PROVAS® (Paracetamol/Acetaminophen) is an established antipyretic and analgesic similar to those observed in adults, except for the plasma half-life that is slightly shorter
(1.5 to 2 h) than in adults. In neonates, the plasma half-life is longer than in infants i.e.
CHEMISTRY: around 3.5 hours. Neonates, infants and children up to 10 years excrete significantly less
PROVAS® (Paracetamol/Acetaminophen) is part of the class of drug known as "aniline glucuronide and more sulphate conjugates than adults
analgesic". It is the active metabolite of Phenacetin
PHARMACODYNAMICS:
MECHANISM OF ACTION: PROVAS® provides onset of pain relief within 5 to 10 minutes after the start of administration.
PROVAS® (Paracetamol/Acetaminophen) reduces the production of prostaglandins (Pro- The peak analgesic effect is obtained in 1 hour and the duration of this effect is usually
inflammatory chemicals). PROVAS® (Paracetamol/Acetaminophen) reduces the oxidized 4 to 6 hours
form of Cyclo-Oxygenase enzyme, preventing from forming pro-inflammatory chemicals. PROVAS® reduces fever within 30 minutes after the start of administration with duration
PROVAS® (Paracetamol/Acetaminophen) also modulates the endogenous cannabinoid of the antipyretic effect of at least 6 hours
system. Paracetamol is metabolized to AM404, a compound with several actions; most
important, it inhibits the uptake of endogenous cannabinoid/vanilloid anandamide by INDICATIONS:
neuron. Anandamide uptake would result in the activation of main pain receptor of the PROVAS® is indicated for the short-term treatment of moderate pain, especially following
body. Furthermore, AM404 inhibits sodium channels 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
PHARMACOKINETICS: other routes of administration are not possible
Adults:
Absorption: DOSAGE AND ADMINISTRATION:
Paracetamol pharmacokinetics is linear up to 2 g after single administration and after
repeated administration during 24 hours w Adolescents and adults weighing more than 50 kg:
The maximal plasma concentration (Cmax) of paracetamol observed at the end of 15- Paracetamol 1g per administration, i.e. one 100 ml vial, up to four times a day
minutes intravenous infusion of 1 g of PROVAS® (Paracetamol/Acetaminophen) is 30 The minimum interval between each administration must be 4 hours
µg/ml The maximum daily dose must not exceed 4g
w Children weighing more than 33 kg (approximately 11 years old), adolescents
Distribution: and adults weighing less than 50kg:
The volume of distribution of paracetamol is approximately 1 L/kg Paracetamol 15mg/kg per administration, i.e. 1.5ml solution per kg up to four times a day
Paracetamol is not extensively bound to plasma proteins The minimum interval between each administration must be 4 hours
Following infusion of 1 g paracetamol, significant concentrations of paracetamol (about The maximum daily dose must not exceed 60 mg/kg (without exceeding 3g)
1.5 µg/mL) were observed in the cerebrospinal fluid at and after the 20 minute following w Children weighing more than 10kg (approximately 1 year old) and weighing
infusion less than 33kg:
Paracetamol 15mg/kg per administration, i.e. 1.5ml solution per kg up to four times a day
Metabolism: The minimum interval between each administration must be 4 hours
Paracetamol is metabolised mainly in the liver following two major hepatic pathways: The maximum daily dose must not exceed 60mg/kg (without exceeding 2g)
w Term newborn infants, infants, toddlers and children weighing less than 10kg
glucuronic acid conjugation and sulphuric acid conjugation
(up to approximately 1 year old):
Paracetamol 7.5mg/kg per administration i.e. 0.75ml solution per kg up to four times a day
The minimum interval between each administration must be 4 hours OVERDOSAGE:
The maximum daily dose must not exceed 30mg/kg There is a risk of poisoning, particularly in elderly subjects, in young children, in patients
No safety and efficacy data are available for premature neonates with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition
w Severe renal insufficiency: it is recommended, when giving paracetamol to patients and in patients receiving enzyme inducers. Overdosing may be fatal in these cases
with severe renal impairment (creatinine clearance 30 mL/min), to increase the minimum
interval between each administration to 6 hours SHELF LIFE:
w Method of administration: The paracetamol solution is administered as a 15-minute From a microbiological point of view, unless the method of opening precludes the risk
of microbial contamination, the product should be used immediately. If not used immediately,
intravenous infusion in-use storage times and conditions are the responsibility of the user
If diluted in 0.9% sodium chloride or 5% glucose, the solution should also be used
CONTRAINDICATIONS: immediately. However, if the solution is not used immediately, do not store for more than
- Patients with hypersensitivity to paracetamol or to propacetamol hydrochloride (prodrug 1 hour (infusion time included)
of paracetamol) or to any of the excipients
- In cases of severe hepatocellular insufficiency STABILITY: See expiry on the pack
PRECAUTIONS: PRESENTATION:
Paracetamol should be used with caution in cases of: PROVAS® 100ml IV solution for infusion
hepatocellular insufficiency, severe renal insufficiency (creatinine clearance 30 mL/min),
chronic alcoholism, chronic malnutrition (low reserves of hepatic glutathione) and INSTRUCTIONS:
dehydration Dosage as directed by the physician
Keep out of reach of children
WARNINGS: Avoid exposure to heat and light
It is recommended that a suitable analgesic oral treatment be used as soon as this route Store at 25ºC or below
of administration is possible Improper storage may deteriorate the medicine
In order to avoid the risk of overdose, check that no other medicines administered do not Avoid freezing and injection should not be used if container is leaking,
contain paracetamol solution is cloudy or it contains undissolved particles
Doses higher than those recommended entail the risk of very serious liver damage
Clinical signs and symptoms of liver damage are not usually seen until two days, and
up to a maximum of 4-6 days, after administration Manufactured by:
SAMI PHARMACEUTICALS (PVT) LTD.
DRUG INTERACTIONS: F-95, S.I.T.E., Karachi-Pakistan
w 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
considered if it is to be used concomitantly with probenecid
w Salicylamide may prolong the elimination t1/2 of paracetamol
w Caution should be taken with the concomitant intake of enzyme-inducing substances
w Concomitant use of paracetamol (4 g per day for at least 4 days) with oral anticoagulants
may lead to slight variations of INR (International Normalized Ratio) values. In this
case, increased monitoring of INR values should be conducted during the period of
concomitant use as well as for 1 week after paracetamol treatment has been
discontinued
UNDESIRABLE EFFECTS:
Very rare cases of hypersensitivity reactions ranging from simple skin rash or urticaria
to anaphylactic shock have been reported and require discontinuation of treatment
PROVAS® Injection
(Paracetamol)
COMPOSITION:
Each 2ml contains:
Paracetamol BP .300mg
For intramuscular use only
MODE OF ACTION:
Paracetamol inhibits the synthesis of prostaglandin in the central nervous
system and peripherally blocks pain impulse generation; produces
antipyresis from inhibition of hypothalamic heat-regulating center
INDICATIONS:
For symptomatic relief of fever and pain associated with common
infections like tonsillitis, upper respiratory tract infections, post-
immunization reactions, after operations, pyrexia of unknown origin
and other febrile and painful conditions where patient is unable to take
oral medication
PRECAUTIONS:
Hypersensitivity to Paracetamol. Impaired liver or kidney function
CONTRAINDICATIONS:
Renal and Hepatic insufficiency
ADVERSE REACTIONS:
Hematological, skin and other allergic reactions
SIDE EFFECTS:
Nausea, vomiting and urticaria can be reported
DOSAGE AND ADMINISTRATION:
Adults: 2ml, intramuscularly six hourly
Children: ½ - 1ml, intramuscularly six hourly or 6mg/kg of the body
weight. Not recommended for children under the age of two years. The
dosage can be increased depending upon severity of the condition or
as directed by the physician
STABILITY:
See expiry on the pack
PRESENTATION:
Provas® Injection in pack of 5s
INSTRUCTIONS:
Keep out of reach of children
Avoid exposure to heat and light
Store at 25°C or below
Improper storage may deteriorate the medicine
Avoid freezing and Injection should not be used if container is leaking,
solution is cloudy or it contains un-dissolved particles
Manufactured by:
SAMI PHARMACEUTICALS (PVT) LTD.
F-95, S.I.T.E., Karachi-Pakistan
6th June 2009