Active ingredients: Paracetamol
PERFALGAN 10 mg / ml solution for infusion
Why is Perfalgan used? What is it for?
This medicine is an analgesic (relieves pain) and antipyretic (lowers fever).
The use of the 100 ml vial or the 100 ml bag is reserved for adults, adolescents and children weighing more than 33 kg.
The use of the 50 ml vial is suitable for infants born at term, infancy, children starting to walk and children weighing less than 33 kg.
It is indicated for the short-term treatment of moderate pain, especially following surgery, and for the short-term treatment of fever.
Contraindications When Perfalgan should not be used
Do not use PERFALGAN 10 mg / ml solution for infusion
- if you are allergic (hypersensitive) to paracetamol or any of the other ingredients of Perfalgan
- if you are allergic (hypersensitive) to propacetamol (another infusion pain reliever and precursor to paracetamol)
- if you have severe liver disease
Precautions for use What you need to know before taking Perfalgan
Take special care with PERFALGAN 10 mg / ml solution for infusion
- use adequate analgesic treatment for oral use as soon as this route of administration is possible
- if you have liver or kidney disease or alcohol abuse
- if you are taking other medicines containing paracetamol
- in case of nutrition problems (malnutrition) or dehydration
Tell your doctor before treatment if you have any of the above conditions.
Interactions Which drugs or foods can modify the effect of Perfalgan
This medicinal product contains paracetamol and this should be taken into consideration if other medicinal products containing paracetamol or propacetamol are taken, in order not to exceed the recommended daily dose (see section below). Tell your doctor if you are taking any other medicines containing paracetamol or propacetamol. In case of concomitant treatment with probenecid a dose reduction of paracetamol should be considered.
Tell your doctor or pharmacist if you are taking oral anticoagulants. More frequent checks of the effect of the anticoagulant may be necessary.
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Warnings It is important to know that:
Pregnancy
Tell your doctor if you are pregnant. PERFALGAN can be used in pregnancy. However, in this case the doctor will have to evaluate whether the treatment is advisable.
Ask your doctor or pharmacist for advice before using any medicine.
Feeding time
PERFALGAN can be used during breastfeeding.
Ask your doctor or pharmacist for advice before using any medicine. Important information about some of the ingredients of PERFALGAN 10 mg / ml solution for infusion
This medicine contains less than 1 millimole of sodium (23 mg) per 100 ml of PERFALGAN, ie it is essentially "sodium-free".
Dosage and method of use How to use Perfalgan: Dosage
Perfalgan will be given to you by a healthcare professional by infusion into one of your veins.
The dose will be adjusted individually by your doctor, based on your body weight and general condition.
If you have the impression that the effect of PERFALGAN 10 mg / ml solution for infusion is too strong or too weak, talk to your doctor.
Overdose What to do if you have taken too much Perfalgan
If you use more PERFALGAN 10 mg / ml solution for infusion than you should, contact your doctor or pharmacist immediately.
In the event of an overdose, symptoms usually appear within the first 24 hours and include: nausea, vomiting, anorexia, paleness and abdominal pain and risk of liver damage.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Perfalgan
Like all medicines, PERFALGAN 10 mg / ml solution for infusion can cause side effects, although not everybody gets them.
- In rare cases (more than 1 in 10,000 patients, less than 1 in 1,000 patients), the following may be observed: malaise, drop in blood pressure or abnormal laboratory values - abnormal increase in liver enzyme levels found in blood tests. If this happens, tell your doctor, as regular blood tests may be needed later.
- In very rare cases (less than 1 in 10,000 patients, including isolated cases), severe rash or allergic reactions have been reported. In these cases, stop treatment immediately and tell your doctor.
- In isolated cases, other changes in laboratory values have been observed which required regular blood tests: abnormal decrease in the levels of certain types of blood cells (platelets, white blood cells), possibly resulting in bleeding from the nose or gums. In these cases, tell your doctor.
- There have been reports of redness of the skin, redness, itching and abnormal acceleration of the heartbeat.
- There have been reports of pain and burning sensation at the administration site.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Expiry and Retention
Keep out of the reach and sight of children.
Do not use PERFALGAN 10 mg / ml solution for infusion after the expiry date which is stated on the package after "EXP".
The expiry date refers to the last day of the month.
Do not store above 30 ° C. Do not refrigerate or freeze. Store the 100 ml bag in the outer foil packaging.
50 ml vial, after dilution in 0.9% sodium chloride or 5% glucose: do not store for more than one hour (including the time required for the infusion).
Before administration, the medicinal product should be checked visually. PERFALGAN should not be used if particles or discolouration are observed.
100 ml bag: note that there may be some humidity between the bag and the external container, due to the sterilization process, which does not affect the quality of the product.
For single use only. The medicinal product should be used immediately after opening. Any unused solution should be discarded.
Composition and pharmaceutical form
What PERFALGAN 10 mg / ml solution for infusion contains
- The active ingredient is paracetamol. 1 ml contains 10 mg of paracetamol.
- The other ingredients are: cysteine hydrochloride monohydrate, disodium phosphate dihydrate, hydrochloric acid, mannitol, sodium hydroxide, water for injections.
What PERFALGAN 10 mg / ml solution for infusion looks like and contents of the pack
Vials of 50 ml and 100 ml
100 ml bags
PERFALGAN 10 mg / ml solution for infusion is a clear and slightly yellowish solution.
PERFALGAN 10 mg / ml solution for infusion is available in packs of 12 vials.
PERFALGAN 10 mg / ml solution for infusion is available in packs of 50 bags.
Not all pack sizes or presentations may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
PERFALGAN 10 mg / ml SOLUTION FOR INFUSION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml contains 10 mg of paracetamol.
One vial of 50 ml contains 500 mg of paracetamol.
One vial of 100 ml contains 1000 mg of paracetamol.
One 100 ml bag contains 1000 mg of paracetamol.
Excipients: 0.04 mg / ml of sodium.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Solution for infusion.
The solution is clear and slightly yellowish.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Perfalgan is indicated for the short-term treatment of pain of moderate intensity, especially following surgery, and for the short-term treatment of fever, when intravenous administration is clinically justified by the urgent need to treat. pain or hyperthermia and / or when other routes of administration are impossible to practice.
04.2 Posology and method of administration
For intravenous use.
The 100 ml vial or 100 ml bag are reserved for adults, adolescents and children weighing more than 33 kg.
The 50 ml vial is reserved for infants born at term, infancy, children who start to walk and children weighing less than 33 kg.
Dosage
Adolescents and adults weighing more than 50 kg
1 g of paracetamol for each administration, i.e. 1 vial of 100 ml or 1 bag of 100 ml, up to four times a day.
The minimum interval between single administrations should be 4 hours.
The maximum daily dose should not exceed 4 g.
Children weighing more than 33 kg (approximately 11 years), adolescents and adults weighing less than 50 kg
15 mg / kg of paracetamol for each administration, i.e. 1.5 ml of solution per kg, up to four times a day.
The minimum interval between single administrations should be 4 hours.
The maximum daily dose should not exceed 60 mg / kg (without exceeding 3 g).
Children weighing more than 10 kg (approximately 1 year) and less than 33 kg
15 mg / kg of paracetamol for each administration, i.e. 1.5 ml of solution per kg, up to four times a day.
The minimum interval between single administrations should be 4 hours.
The maximum daily dose should not exceed 60 mg / kg (without exceeding 2 g).
Term newborn infants, infants, children starting to walk and children weighing less than 10 kg (up to approximately 1 year)
7.5 mg / kg of paracetamol for each administration, i.e. 0.75 ml of solution per kg up to four times a day.
The minimum interval between single administrations should be 4 hours.
The maximum daily dose should not exceed 30 mg / kg.
No safety and efficacy data are available for preterm infants (see also section 5.2).
Severe renal insufficiency
In case of administration of paracetamol to patients with severe renal impairment (creatinine clearance ≤ 30 ml / min), it is recommended to increase the minimum interval between single administrations to 6 hours (see section 5.2).
In adults with hepatocellular insufficiency, chronic alcoholism, chronic malnutrition (low reserves of hepatic glutathione), dehydration
The maximum daily dose should not exceed 3 g (see section 4.4).
Method of administration
The paracetamol solution is administered as an intravenous infusion over 15 minutes.
Vials of 50 ml and 100 ml
Use a 0.8 mm needle and vertically pierce the stopper at the precise point indicated.
50 ml vial
The 50 ml vial of PERFALGAN can also be diluted with 0.9% sodium chloride or 5% glucose solution, up to one-tenth of the concentration. In this case, the diluted solution must be used within the hour following its preparation (including the time required for the infusion).
Vials of 50 ml and 100 ml
As with all solutions for infusion contained in glass vials, it should be remembered that close monitoring is required especially at the end of the infusion, regardless of the route of administration. Such monitoring at the end of perfusion should be adopted especially in the case of infusions through central ways, in order to avoid gas embolism.
04.3 Contraindications
Perfalgan is contraindicated:
• in patients with hypersensitivity to paracetamol or propacetamol hydrochloride (prodrug of paracetamol) or to any of the excipients.
• in case of severe hepatocellular insufficiency.
04.4 Special warnings and appropriate precautions for use
Warnings
Adequate oral analgesic treatment is recommended as soon as this route of administration is possible.
In order to avoid the risk of overdose, check that other drugs administered do not contain either paracetamol or propacetamol.
Dosages higher than those recommended carry the risk of very serious liver damage. Symptoms and clinical signs of hepatic injury (including fulminant hepatitis, hepatic failure, cholestatic hepatitis, cytolytic hepatitis) usually occur after two days of drug administration with a peak after 4-6 days. Treatment with the antidote should be given as soon as possible (see section 4.9).
This medicine contains less than 1 millimole of sodium (23 mg) per 100 ml of PERFALGAN, which means it is essentially sodium-free.
Vials of 50 ml and 100 ml: As with all solutions for infusion contained in glass vials, close monitoring is required especially at the end of the infusion (see section 4.2).
Precautions for use
Paracetamol should be used with caution in case of:
• hepatocellular insufficiency,
• severe renal insufficiency (creatinine clearance ≤ 30 ml / min) (see sections 4.2 and 5.2)
• chronic alcoholism,
• chronic malnutrition (low hepatic glutathione reserve),
• dehydration.
04.5 Interactions with other medicinal products and other forms of interaction
Probenecid causes an approximately two-fold reduction in paracetamol clearance by inhibiting its conjugation with glucuronic acid. In case of concomitant treatment with probenecid a dose reduction of paracetamol should be considered.
Salicylamide may prolong the elimination half-life of paracetamol.
Caution should be exercised in case of concomitant intake of enzyme inducers (see section 4.9).
Concomitant use of paracetamol (4 g per day for at least 4 days) with oral anticoagulants may induce slight changes in INR values. In this case, increased monitoring of INR values should be performed during the concomitant treatment period and for a longer period of time. week after stopping paracetamol treatment.
04.6 Pregnancy and lactation
Pregnancy
Clinical experience with intravenous administration of paracetamol is limited. However, epidemiological data on the use of oral therapeutic doses of paracetamol reveal no adverse effects on pregnancy or on the health of the fetus / newborn.
Prospective data on pregnancies exposed to overdose did not show an increased risk of malformations.
Reproductive studies with the intravenous form of paracetamol have not been performed in animals. However, studies with the oral form did not show any malformations or foetotoxic effects.
Despite this, Perfalgan should only be used during pregnancy after a careful assessment of the benefit / risk ratio. In this case, the recommended dosage and duration of treatment must be strictly observed.
Feeding time
After oral administration, paracetamol is excreted in breast milk in small quantities. No undesirable effects have been reported in nursing infants. Consequently, Perfalgan can be used in women who are breastfeeding.
04.7 Effects on ability to drive and use machines
Not relevant.
04.8 Undesirable effects
Like all acetaminophen drugs, adverse reactions are rare (> 1 / 10,000,
During clinical trials, frequent administration site adverse reactions (pain and burning sensation) were reported.
Very rare cases of hypersensitivity reactions, from simple skin rash or urticaria to anaphylactic shock, requiring discontinuation of treatment have been reported.
Cases of erythema, redness, itching and tachycardia have been reported.
04.9 Overdose
There is a risk of liver damage (including fulminant hepatitis, liver failure, cholestatic hepatitis, cytolytic hepatitis), especially in the elderly, in children, in patients with liver disease, in the case of chronic alcoholism, in patients with chronic malnutrition, and in patients receiving enzyme inducers. In these cases, overdose can be fatal.
Symptoms usually appear within the first 24 hours and include: nausea, vomiting, anorexia, paleness, and abdominal pain.
Overdose, 7.5 g or more of paracetamol in single administration in adults and 140 mg / kg body weight in single administration in children, causes hepatic cytolysis, possibly leading to complete and irreversible necrosis, resulting in hepatocellular failure, metabolic acidosis and encephalopathy which can lead to coma and death. At the same time, increased levels of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin are observed, together with a decrease in the prothrombin value which may occur 12 to 48 hours after administration. Clinical symptoms of liver damage usually occur as early as two days, and peak 4 to 6 days later.
Emergency measures
Immediate hospitalization.
Before starting treatment and as soon as possible after the overdose, take a blood sample to determine the plasma levels of paracetamol.
Treatment includes the administration of the antidote, N-acetylcysteine (NAC), intravenously or orally, preferably first of the 10th hour. The NAC can, however, give a certain degree of protection even after 10 hours, but in these cases it is necessary to prolong the treatment.
Symptomatic treatment
Liver tests should be performed at the start of treatment, which will be repeated every 24 hours. In most cases, liver transaminases return to normal within a week or two with full recovery of liver function. In very severe cases, however. , liver transplantation may be required.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: OTHER ANALGESICS AND ANTIPYRETICS, ATC code: N02BE01.
The exact mechanism by which the analgesic and antipyretic properties of paracetamol are expressed is still to be established; it can involve central and peripheral actions.
The analgesic action of Perfalgan begins 5-10 minutes after the start of administration. The peak of the analgesic effect is obtained in 1 hour and the duration of this effect is usually from 4 to 6 hours.
Perfalgan reduces fever in 30 minutes from the start of administration with a duration of the antipyretic effect of at least 6 hours.
05.2 Pharmacokinetic properties
Adults
Absorption
The pharmacokinetics of paracetamol are linear up to 2 g after single administration and after repeated administration over 24 hours.
The bioavailability of paracetamol after infusion of 500 mg and 1 g of Perfalgan is similar to that observed after infusion of 1 and 2 g of propacetamol (corresponding, respectively, to 500 mg and 1 g of paracetamol).
The maximum plasma concentration (Cmax) of paracetamol observed at the end of an intravenous infusion of 500 mg and 1 g of Perfalgan over 15 minutes is approximately 15 mg / ml and 30 mg / ml, respectively.
Distribution
The volume of distribution of paracetamol is approximately 1 l / kg.
Paracetamol does not bind extensively to plasma proteins.
Following the infusion of 1 g of paracetamol, significant concentrations (approximately 1.5 mg / ml) were observed in the cerebrospinal fluid 20 minutes after the infusion.
Metabolism
Paracetamol is metabolised mainly in the liver following two major hepatic pathways: conjugation with glucuronic acid and conjugation with sulfuric acid. This last route is rapidly saturated at dosages exceeding the therapeutic doses. A small fraction (less than 4%) is metabolized by cytochrome P450 into a reactive intermediate (N-acetyl benzoquinone imine) which, under normal conditions of use, is rapidly detoxified from reduced glutathione and eliminated in the urine after conjugation with cysteine and mercaptouric acid. However, in massive overdoses, the amount of this toxic metabolite is increased.
Elimination
The metabolites of paracetamol are mainly excreted in the urine. 90% of the administered dose is excreted in 24 hours, mostly in glucuronidated (60-80%) and sulphonated (20-30%) form. Less than 5% is eliminated unchanged. The plasma half-life is 2.7 hours and the total body clearance is 18 l / h.
Babies, early childhood and children
The pharmacokinetic parameters of paracetamol observed in infancy and children are similar to those seen in adults, with the exception of the plasma half-life which is slightly shorter (1.5-2 hours) than in adults. In neonates, the plasma half-life is longer than in childhood, about 3.5 hours. Significantly less excretion of glucuroconjugates and greater excretion of sulfur conjugates is observed in infants, infants and children up to 10 years of age compared to adults.
Table: Age-related pharmacokinetic values (standardized clearance, * CLstd / Fos (l.h-1 70 kg -1), are shown below
1 PCA: age after conception (Post-conceptional age)
2 NAP: age after birth (Post-natal age)
* CLstd is the estimated population for CL
Special populations
Kidney failure
In cases of severe renal impairment (creatinine clearance between 10 and 30 ml / min) the elimination of paracetamol is slightly delayed, with an elimination half-life of between 2 and 5.3 hours. For glucuroconjugates and sulfur conjugates, the elimination rate is 3 times slower in subjects with severe renal impairment than in healthy subjects. Therefore it is recommended to increase the minimum interval between two administrations to 6 hours when paracetamol is administered to patients with severe renal impairment (creatinine clearance ≤30 ml / min) (see section 4.2 Posology and method of administration).
Senior citizens
The pharmacokinetics and metabolism of paracetamol are not modified in elderly subjects. No dosage adjustment is required in this population.
05.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans beyond the information included in other sections of this Summary of Product Characteristics.
Local tolerance studies with Perfalgan in rats and rabbits showed good tolerability. The absence of delayed contact hypersensitivity was tested in guinea pigs.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Cysteine hydrochloride monohydrate
Disodium phosphate dihydrate
Hydrochloric acid
Mannitol
Sodium hydroxide
Water for injections
06.2 Incompatibility
Perfalgan must not be mixed with other medicinal products.
06.3 Period of validity
2 years.
From a microbiological point of view, unless the method of opening guarantees against the risk of microbial contamination, the drug should be used immediately. In case of non-immediate use, storage times and conditions are the responsibility of the user.
50 ml vial
Diluted 0.9% sodium chloride or 5% glucose solution should also be used immediately. However, if not used immediately, the solution should not be stored for more than one hour (including the time required for infusion).
06.4 Special precautions for storage
Do not store above 30 ° C. Do not refrigerate or freeze.
100 ml bag
Store the 100 ml bag in the outer foil packaging.
After opening the outer aluminum container, the product should be used immediately.
06.5 Nature of the immediate packaging and contents of the package
Vials of 50 ml and 100 ml
50 ml and 100 ml in clear type II glass vial with bromobutyl stopper and aluminum / plastic quick-open cap.
Pack of 12 vials.
100 ml bag
The 100ml bag is a multilayer plastic bag (polypropylene and polyolefin) packed in a sealed aluminum container.
Pack of 50 bags.
06.6 Instructions for use and handling
Vials of 50 ml and 100 ml
Use a 0.8 mm needle and vertically pierce the stopper at the precise point indicated.
Before use, the product should be checked visually for any particles and discolouration. Do not reuse. Unused solution should be discarded.
The diluted solution should be visually inspected and should not be used in the presence of opalescence, visible particles or precipitates.
100 ml bag
There may be moisture between the pouch and the outer container due to the sterilization process. This does not affect the quality of the solution.
07.0 MARKETING AUTHORIZATION HOLDER
BRISTOL-MYERS SQUIBB S.r.l., Via del Murillo, km 2,800 - Sermoneta (LT)
08.0 MARKETING AUTHORIZATION NUMBER
AIC n. 035475019 / M
AIC n. 035475021 / M
AIC n. 035475033 / M
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
2 August 2006
10.0 DATE OF REVISION OF THE TEXT
September 2010
