Paracetamol Solution for Infusion 10mg/1ml – (100ml) Taj Pharma

1. NAME OF THE MEDICINAL PRODUCT

Paracetamol Solution for Infusion 10mg/1ml – (100ml) Taj Pharma
Paracetamol Solution for Infusion 300mg/2ml Taj Pharma

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

   a) Each ml of Infusion contains:
   Paracetamol…………………………..10mgb) Each ml of Infusion contains:
   Paracetamol………………………….150mg

Excipients: Sodium 0.994mg/ml

For a full list of excipients, see section 6.1

3. PHARMACEUTICAL FORM

Solution for infusion.

The solution is clear.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Paracetamol 10mg/ml / 300mg/2ml Solution for Infusion 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.

4.2 Posology and method of administration

Intravenous use.

The 50 ml vial is restricted to term newborn infants, infants, toddlers and children weighing less than 33kg.

The 100 ml vial is restricted to adults, adolescents, and children weighing more than 33 kg.

Posology: Dosing based on patient weight (please see the dosing table here below

* Pre-term newborn infants: No safety and efficacy data are available for pre-term newborn infants (see section 5.2).

**Maximum daily dose: The maximum daily dose as presented in the table above is for patients that are not receiving other paracetamol containing products and should be adjusted accordingly taking such products into account.

***Patients weighing less will require smaller volumes.

The minimum interval between each administration must be at least 4 hours.

The minimum interval between each administration in patients with severe renal insufficiency must be at least 6 hours.

No more than 4 doses to be given in 24 hours.

Severe renal insufficiency: it is recommended, when giving paracetamol to patients with severe renal impairment (creatinine clearance ≤30 mL/min), to increase the minimum interval between each administration to 6 hours (See section 5.2 Pharmacokinetic properties).

Method of administration

The paracetamol solution is administered as a 15-minute intravenous infusion.

Patients weighing ≤ 10 kg:

• The glass vial/bag of paracetamol, solution for infusion, should not be hung as an infusion due to the small volume of the medicinal product to be administered in this population
• The volume to be administered should be withdrawn from the vial/bag and diluted in a 0.9% sodium chloride solution or 5% glucose solution up to one tenth (one volume paracetamol, solution for infusion, into nine volumes diluent) and administered over 15 minute
• A 5 or 10 ml syringe should be used to measure the dose as appropriate for the weight of the child and the desired volume. However, this should never exceed 7.5ml per dose
• The user should be referred to the product information for dosing guidelines.

Text for the 50ml and 100ml vials:

To remove solution, use a 0.8 mm needle (21 gauge needle) and vertically perforate the stopper at the spot specifically indicated.

Text for the 50ml vial:

Paracetamol of 50ml vial can also be diluted in a 0.9% sodium chloride solution or 5% glucose solution up to one tenth (one volume Paracetamol Actavis into nine volumes diluent) In this case, use the diluted solution within the hour following its preparation (infusion time included).

As for all solutions for infusion presented in glass vials, it should be remembered that close monitoring is needed notably at the end of the infusion, regardless of administration route. This monitoring at the end of the infusion applies particularly for central route infusions, in order to avoid air embolism

4.3 Contraindications

• in patients with hypersensitivity to paracetamol or to propacetamol hydrochloride (prodrug of paracetamol) or to any of the excipients.
• in cases of severe hepatocellular insufficiency.

4.4 Special warnings and precautions for use

Warnings

It is recommended that a suitable analgesic oral treatment be used as soon as this route of administration is possible.

In order to avoid the risk of overdose, check that no other medicines containing paracetamol are administered at the same time.

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. Treatment with antidote should be given as soon as possible (See section 4.9 Overdose).

This medicinal product contains 4.32mmol sodium per dose. To be taken into consideration by patients on a controlled sodium diet.

Precautions for use

Paracetamol should be used with caution in cases of :

• hepatocellular insufficiency,
• severe renal insufficiency (creatinine clearance ≤30 mL/min) (see sections 4.2 Posology and method of administration and 5.2 Pharmacokinetic properties),
• chronic alcoholism,
• chronic malnutrition (low reserves of hepatic glutathione),
• dehydration.

4.5 Interaction with other medicinal products and other forms of interaction

• 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.
• Salicylamide may prolong the elimination t½ of paracetamol.
• Caution should be taken with the concomitant intake of enzyme-inducing substances (see section 4.9 Overdose).
• Concomitant use of paracetamol (4 g per day for at least 4 days) with oral anticoagulants may lead to slight variations of INR 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.

4.6 Fertility, pregnancy and lactation

Pregnancy:

Clinical experience of the intravenous administration of paracetamol is limited. However, epidemiological data from the use of oral therapeutic doses of paracetamol indicate no undesirable effects in pregnancy or on the health of the foetus / newborn infant.

Prospective data on pregnancies exposed to overdoses did not show any increase in the risk of malformation.

No reproductive studies with the intravenous form of paracetamol have been performed in animals. However, studies with the oral route did not show any malformation or foetotoxic effects.

Nevertheless, Paracetamol 10 mg/ml Solution for Infusion should only be used during pregnancy after a careful benefit-risk assessment. In this case, the recommended posology and duration must 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 10 mg/ml Solution for Infusion may be used in breast-feeding women.

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

The frequency of adverse events listed below is defined using the following convention:

very common (≥ 1/10); common (≥ 1/100 to 1/10); uncommon (≥ 1/1,000 to 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data).

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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

There is a risk of poisoning, 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.

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 coma and death. Simultaneously, increased levels of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin are observed together with decreased prothrombin levels that may appear 12 to 48 hours after administration. Clinical symptoms of liver damage are usually evident initially after two days, and reach a maximum after 4 to 6 days.

Emergency measures

Immediate hospitalisation.

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 i.v. or oral route, if possible before the 10th hour. NAC 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 24 hours. 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.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group : other analgesics and antipyretics

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

Paracetamol 10 mg/ml Solution for Infusion provides onset of pain relief within 5 to 10 minutes after the start of administration. The peak analgesic effect is obtained in 1 hour and the duration of this effect is usually 4 to 6 hours.

Paracetamol 10 mg/ml Solution for Infusion reduces fever within 30 minutes after the start of administration with a duration of the antipyretic effect of at least 6 hours.

5.2 Pharmacokinetic properties

Adults

Absorption:

Paracetamol pharmacokinetics is linear up to 2 g after single administration and after repeated administration during 24 hours.

The bioavailability of paracetamol following infusion of 500mg and 1 g of Paracetamol 10 mg/ml Solution for Infusion is similar to that observed following infusion of 1g and 2 g propacetamol (containing 500mg and 1 g paracetamol respectively). The maximal plasma concentration (Cmax) of paracetamol observed at the end of 15-minutes intravenous infusion of 500mg and 1 g of Paracetamol 10 mg/ml Solution for Infusion is about 15μg/ml and 30 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 paracetamol, significant concentrations 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 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 use, is rapidly detoxified by reduced glutathione and eliminated in the urine after conjugation 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 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 clearance is 18 L/h.

Neonates, infants and children:

The pharmacokinetic parameters 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 h) 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 conjugates than adults.

Table – Age related pharmacokinetic values (standardised clearance, *CLstd/Foral (L.h-1 70kg-1)

*CL_std is the population estimate for CL

Special populations:

Renal insufficiency:

In cases of severe renal impairment (creatinine clearance 10-30 mL/min), the elimination of paracetamol is slightly delayed, the elimination half-life ranging from 2 to 5.3 hours. For the glucuronide and sulphate conjugates, the elimination rate is 3 times slower in subjects with severe renal impairment than in healthy subjects. Therefore when giving paracetamol to patients with severe renal impairment (creatinine clearance ≤30 mL/min), the minimum interval between each administration should be increased to 6 hours (see section 4.2. Posology and method of administration).

Elderly subjects :

The pharmacokinetics and the metabolism of paracetamol are not modified in elderly subjects. No dose adjustment is required in this population.

5.3 Preclinical safety data

Preclinical data reveal no special hazard for humans beyond the information included in other sections of the SmPC.

Studies on local tolerance of Paracetamol 10 mg/ml Solution for Infusion in rats and rabbits showed good tolerability. Absence of delayed contact hypersensitivity has been tested in guinea pigs.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Cysteine hydrochloride monohydrate, Disodium phosphate dehydrate, Hydrochloric acid 1M (for pH-adjustment), Mannitol, Sodium hydroxide 1M (for pH-adjustment), Water for Injections

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except for dilution with 0.9% sodium chloride or 5% glucose solution

6.3 Shelf life

24 months.

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, in-use storage times and conditions are the responsibility of the user.

6.4 Special precautions for storage

Store below 30°C. Protect from light. Store in the original package. Do not refrigerate or freeze.

6.5 Nature and contents of container

50ml and 100 ml Type II colourless glass vial with bromobutyl stopper and an aluminium cap.

Pack size: pack of 1, 10 or 12 vials.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Before administration, the product should be visually inspected for any particulate matter and discolouration. For single use only. Any unused solution should be discarded.

7. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

PACKAGE LEAFLET: INFORMATION FOR THE USER

PARACETAMOL SOLUTION FOR INFUSION
10MG/ML / 300MG/2ML
TAJ PHARMA

Paracetamol

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

WHAT IS IN THIS LEAFLET:

1. What Paracetamol is and what it is used for
2. What you need to know before you use Paracetamol
3. How to use Paracetamol
4. Possible side effects
5. How to store Paracetamol
6. Contents of the pack and other information1. WHAT PARACETAMOL IS AND WHAT IT IS USED FOR

This medicine is an analgesic (it relieves pain) and an antipyretic (it lowers fever).

It is indicated for the short-term treatment of moderate pain, especially following surgery, and for the short-term treatment of fever.

The 100 ml container is restricted to adults, adolescents and children weighing more than 33 kg

2. WHAT YOU NEED TO KNOW BEFORE YOU USE PARACETAMOL

You should not be given Paracetamol:

• If you are allergic to paracetamol or any of the other ingredients of this medicine (listed in section 6) or to propacetamol hydrochloride (prodrug of paracetamol).
• If you are allergic to propacetamol (another analgesic and a precursor of paracetamol)
• If you suffer from a severe liver disease

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Paracetamol

• If you suffer from a liver or kidney disease, or from alcohol abuse,
• If you are taking other medicines containing paracetamol,
• In cases of nutrition problems (malnutrition) or dehydration.

It is recommended that a suitable analgesic oral treatment be used as soon as this route of administration is possible.

Other medicines and Paracetamol

Tell your doctor or pharmacist if you are taking or have recently taken any other medicine.

Do not give anything else containing paracetamol while giving this medicine. This medicine contains paracetamol and this must be taken into account if other medicines containing paracetamol or propacetamol are taken, in order not to exceed the recommended daily dose (see following section). Inform your doctor if you are taking other medicines containing paracetamol. or propacetamol .

A dose reduction should be considered for concomitant treatment with probenecid.

Please inform your doctor or pharmacist if you are taking oral anticoagulants. More check-ups to look at the effect of the anticoagulant might be needed.

Pregnancy and Breastfeeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Inform your doctor if you are pregnant. Paracetamol may be used during pregnancy. However, in this case the doctor must evaluate if the treatment is advisable.

Paracetamol may be used during breast-feeding.

Driving and using machines

The product does not affect the ability to drive or use machines

This medicine contains less than 1 mmol sodium (23 mg) per unit volume, that is to say essentially “sodium-free”.

3. HOW TO USE PARACETAMOL

Paracetamol will be administered to you by a healthcare professional.

The recommended dose is

Dosing based on patient weight (please see the dosing table here below)

*Maximum daily dose: The maximum daily dose as presented in the table above is for patients that are not receiving other paracetamol containing products and should be adjusted accordingly taking such products into account.

**Patients weighing less will require smaller volumes.

The minimum interval between each administration must be at least 4 hours.

The minimum interval between each administration in patients with severe renal insufficiency must be at least 6 hours.

No more than 4 doses to be given in 24 hours.

Method of administration

Intravenous use.

RISK OF MEDICATION ERRORS

Take care to avoid dosing errors due to confusion between milligram (mg) and millilitre  (ml),

Paracetamol will be given by infusion into one of your veins. The infusion will last approximately 15 minutes.

If you have the impression that the effect of your medicine is too strong or too weak, talk to your doctor.

For the 100 ml vials, a 0.8 mm needle (21 gauge needle) has to be used and the stopper vertically perforated at the spot indicated.

If you take more Paracetamol Acccord than you should

If you or your child use more Paracetamol 10 mg/ml solution for infusion than if you or your child should use, talk to a doctor at once if you or your child take too much of this medicine even if you or your child seem feel well. This is because too much paracetamol can cause delayed, serious liver damage.

In overdose cases, symptoms generally appear within the first 24 hours and comprise: nausea, vomiting, anorexia, pallor, abdominal pain and risk of liver injury. Immediate medical advice should be sought in the event of overdosage, because of the risk of irreversible liver damage. Please inform your doctor if you notice any of these symptoms.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them.

• In very rare cases (may affect up to 1 in 10,000 people, including isolated reports), a serious skin rash or allergic reaction may occur. Stop the treatment immediately and inform your doctor.

In rare cases (may affect up to 1 in 1,000 people), the following may occur: a malaise, a drop in blood pressure or changes in laboratory test results: abnormally high levels of hepatic enzymes found during blood checks. Should this occur, inform your doctor as regular blood checks may be required later.

• In isolated cases, other changes in laboratory test results have been observed which have necessitated regular blood checks: abnormally low levels of some types of blood cells (platelets, white cells), possibly leading to bleeding from the nose or gums. Should this occur, inform your doctor.
• Cases of redness of the skin, flushing, itching and abnormally rapid beating of the heart have been reported.
• Cases of pain and burning sensation at injection site have been reported.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

5. HOW TO STORE PARACETAMOL

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the packaging after EXP. The expiry date refers to the last day of that month.

Glass vials: Do not refrigerate or freeze. Store in the original package in order to protect from light. Plastic bags: Do not store above 25ºC. Do not refrigerate or freeze. Store in the original package in order to protect from light

For single use only. The product should be used immediately after opening. Any unused solution should be discarded.

Before administration the product should be visually inspected. Do not use this medicine if you notice any particulate matter and discolouration.

Do not throw away any medicine via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. CONTENTS OF THE PACK AND OTHER INFORMATION

What Paracetamol contains

• The active substance is paracetamol. One ml contains 10 mg paracetamol, this container contains 1000 mg paracetamol in 100 ml.
• The other ingredients are mannitol, sodium dihydrogen phosphate dihydrate, sodium hydroxide (for pH adjustment), povidone K-12 and water for injections.

What Paracetamol looks like and contents of the pack

Paracetamol is a clear, free from visible particles and colourless to slightly brownish solution for infusion.

Paracetamol is supplied in packs of 1, 10, 12 and 20 glass vials of 100 ml or 10, 12 and 50 polyolefin plastic bags of 100 ml with a plastic overpouch.

Not all pack sizes may be marketed.

7. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com