Paracetamol Paediatric 100 Mg Solution

PARACETAMOL PAEDIATRIC 100 mg B. BRAUN is indicated for term newborn infants, infants and toddlers weighing up to 10 kg for:

• the short-term treatment of mild to moderate pain e.g. following minor surgery
• the short-term treatment of fever, when the oral route is unsuitable.

Posology
BRAUN DO NOT EXCEED THE RECOMMENDED DOSE PARACETAMOL PAEDIATRIC 100 mg B. BRAUN 10 ml ampoule is restricted to term newborn infants, infants and toddlers weighing up to 10 kg. Unintentional overdose can lead to serious liver damage and death (see section 4.9). Healthcare providers are reminded that it is essential to follow both the weight-related dose recommendations and to consider individual patient minimum risk factors for hepatotoxicity, including hepatocellular insufficiency, chronic alcoholism, chronic malnutrition (low reserves of hepatic glutathione), and dehydration (see section 4.2, Recommended dosage in patients with hepatic impairment).

DOSING IS BASED ON PATIENT WEIGHT
Maximum of 7,5 mg/kg of paracetamol per administration (i.e. 0,75 mL solution per kg) of PARACETAMOL PAEDIATRIC 100 mg B. BRAUN up to four times a day. The minimum interval between each administration must be at least 4 hours. The maximum daily dose must not exceed 30 mg/kg.

DOSING RECOMMENDATIONS ARE PRESENTED IN THE TABLE BELOW.

Patient weight (non - oedematous weight) Paracetamol dose (10 mg/ml) per administration Minimum interval between each administration Maximum daily dose*

10 ml ampoule

• u2264 10 kg** 7,5 mg/kg*** (i.e. 0,75 ml solution per kg) up to 4 times a day 4 hours u2264 30 mg/kg

* The maximum daily dose takes into account all the medicines containing paracetamol. **Preterm newborn infants: No safety and efficacy data are available for premature newborn infants (see also section 5.2) ***Patients weighing less will require smaller volumes. 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. The dosage should be calculated on non-oedematous weight.

Recommended dosage in patients with renal impairment
It is recommended to leave a minimum interval of 6 hours between each administration in patients with severe renal impairment (creatinine clearance u2264 30 ml/min) (see section 5.2).

Recommended dosage in patients with hepatic impairment
In patients with impaired hepatic function, the dose must be reduced or the dosing interval prolonged. The maximum daily dose should not exceed 30 mg/kg/day in the following situations:

• chronic or compensated active hepatic disease, especially those with mild to moderate hepatocellular insufficiency
• Gilbertu2019s syndrome (familial hyperbilirubinaemia)
• chronic malnutrition (low reserves of hepatic glutathione)
• dehydration

PARACETAMOL PAEDIATRIC 100 mg B. BRAUN is contraindicated in patients with severe hepatic impairment.

Method of administration
Take care when prescribing and administering PARACETAMOL PAEDIATRIC 100 mg B. BRAUN to avoid dosing errors due to confusion between milligram (mg) and milliliter (ml), which could result in accidental overdose and death. Take care to ensure the proper dose is communicated and dispensed. When writing prescriptions, include both the total dose in mg and the total dose in volume. Take care to ensure the dose is measured and administered accurately.

Intravenous use.
General
PARACETAMOL PAEDIATRIC 100 mg B. BRAUN is to be administered as a 15-minute intravenous infusion. Before administration, the product should be visually inspected for any particulate matter and discolouration. It is intended for single-use only. Once opened, the vial should be used immediately.

• Any unused solution should be discarded.
• PARACETAMOL PAEDIATRIC 100 mg B. BRAUN should not be mixed with other medicinal products.

Patients weighing 10 kg or less
The volume to be administered should be withdrawn from the container and diluted in a sodium chloride 9 mg/ml (0,9 %) solution or glucose 50 mg/ml (5 %) solution or a combination of both solutions up to one tenth (one volume PARACETAMOL PAEDIATRIC 100 mg B. BRAUN into nine volumes diluent) and administered over 15 minutes (see section 6.6). Care must be taken to administer excessive fluid volumes of the diluent.

• The dose to be administered and the container size to be used depend exclusively on the patient`s weight. The volume to be administered must not exceed the determined dose. If applicable the desired volume must be diluted in a suitable solution for infusion prior to administration (see section 6.6) or a syringe driver must be used.
• 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 7,5 ml per dose.
• The user should be referred to the product information for dosing guidelines.

For instructions on dilution of the medicinal product before administration, see section 6.6.

PARACETAMOL PAEDIATRIC 100 mg B. BRAUN is contraindicated in:

• Known hypersensitivity to paracetamol or to paracetamol hydrochloride (pro-drug of paracetamol) or to any of the excipients listed in section 6.1.
• Cases of severe hepatocellular insufficiency or decompensated active liver disease.

Prolonged or frequent use is discouraged. It is recommended that a suitable analgesic oral treatment will be used as soon as this route of administration is possible. In order to avoid the risk of overdose, check that other medicines administered do not contain either paracetamol or proparacetamol. The dose may require adjustment (see section 4.2). Doses of PARACETAMOL PAEDIATRIC 100 mg B. BRAUN in excess of those recommended entail the risk of very serious liver damage. Clinical signs and symptoms of liver damage (including fulminant hepatitis, hepatic failure, cholestatic hepatitis, cytolytic hepatitis) are usually first seen after two days of drug administration with a peak seen, usually after 4 to 6 days. Treatment with antidote should be given as soon as possible (see section 4.9). PARACETAMOL PAEDIATRIC 100 mg B. BRAUN Solution for Infusion contains paracetamol which may be fatal in overdose. In the event of overdosage or suspected overdose and notwithstanding the fact that the person may be asymptomatic, the nearest doctor, hospital or Poison Centre must be contacted immediately.

Risk of medication errors
Take care to avoid dosing errors due to confusion between milligram (mg) and milliliter (ml), which could result in accidental overdose and death (see section 4.2).

PARACETAMOL PAEDIATRIC 100 mg B. BRAUN can cause serious skin reactions such as acute generalised exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions and use of the medicine should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

PARACETAMOL PAEDIATRIC 100 mg B. BRAUN should be used with caution in cases of:

• Hepatocellular insufficiency, including Gilbertu2019s syndrome (familial hyperbilirubinaemia), (see section 4.2 and 5.2).
• Severe renal insufficiency (creatinine clearance u2264 30 ml/ min) (see sections 4.2 and 5.2).
• Glucose 6 Phosphate Dehydrogenate (G6PD) deficiency (may lead to haemolytic anaemia).
• Anorexia, bulimia or cachexia, chronic malnutrition (low reserves of hepatic glutathione).
• Dehydration, hypovolaemia.

Patients suffering from hepatitis or alcoholism, or recovering from any form of liver disease should not use excessive quantities of PARACETAMOL PAEDIATRIC 100 mg B. BRAUN.

Use with caution in renal disease.

PARACETAMOL PAEDIATRIC 100 mg B. BRAUN contains mannitol
Mannitol may have a mild laxative effect.

PARACETAMOL PAEDIATRIC 100 mg B. BRAUN contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per container, this is to say essentially u2018sodium-freeu2019.

Effect of other medicines on PARACETAMOL PAEDIATRIC 100 mg B. BRAUN

• Probenecid - causes an almost two-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 half-life of paracetamol, as contained in PARACETAMOL PAEDIATRIC 100 mg B. BRAUN.
• Caution should be paid to the concomitant use of PARACETAMOL PAEDIATRIC 100 mg B. BRAUN and enzyme-inducing substances as these substances increase the risk of paracetamol induced liver injury. These substances include but are not limited to: barbiturates, isoniazid, anticoagulants, zidovudine, amoxicillin + clavulanic acid, and ethanol (see section 4.9).
• Phenytoin administered concomitantly with PARACETAMOL PAEDIATRIC 100 mg B. BRAUN may result in decreased paracetamol effectiveness and an increased risk of hepatotoxicity. Patients receiving phenytoin therapy should avoid large and/or chronic doses of paracetamol. Patients should be monitored for evidence of hepatotoxicity.
• Flucloxacillin - caution is advised when paracetamol is administered concomitantly with flucloxacillin due to the increased risk of high anion gap metabolic acidosis (HAGMA), particularly in patients with a risk factor for glutathione deficiency such as severe renal impairment, sepsis, malnutrition, and chronic alcoholism. Close monitoring is recommended in order to detect the appearance of acid base disorders, namely HAGMA, including the urinary 5-oxoproline.

Effect of PARACETAMOL PAEDIATRIC 100 mg B. BRAUN on other medicines

• PARACETAMOL PAEDIATRIC 100 mg B. BRAUN may increase the chance of unwanted effects when administered with other medicines.
• Oral anticoagulants - concomitant use of paracetamol, as in PARACETAMOL PAEDIATRIC 100 mg B. BRAUN, (4 000 mg 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.

Pregnancy
Not relevant

Breastfeeding
Not relevant

Not relevant.

Tabulated adverse reactions

System Organ Class Less frequent Frequency not known (cannot be estimated from the available data)

• Blood and lymphatic system disorders
  Thrombocytopenia, Agranulocytosis, Leucopenia, Pancytopenia, Neutropenia, Anaemia
• Immune system disorders
  Hypersensitivity reaction Anaphylactic shock, Anaphylaxis, Angio-oedema
• Cardiac disorders
  u2014 Tachycardia
• Vascular disorders
  Hypotension Flushing
• Hepatobiliary disorders
  Increased levels of hepatic transaminases, Hepatitis, Pancreatitis u2014
• Renal and urinary disorders
  Renal colic, Renal failure, Sterile Pyuria
• Gastrointestinal disorders
  Nausea, Vomiting
• Skin and subcutaneous tissue disorders
  Serious skin reactions Pruritus, Erythema, Acute generalised exanthematous pustulosis, Toxic epidermal necrolysis, Stevens-Johnson syndrome
• General disorders and administration site conditions
  Malaise Administration site reactions

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://primaryreporting.who-umc.org/ZA.

Prompt treatment is essential. In the event of an overdosage consult a doctor immediately, or take the person to a hospital directly. A delay in starting treatment may mean that antidote is given too late to be effective. Evidence of liver damage is often delayed until after the time for effective treatment has lapsed. Susceptibility to PARACETAMOL PAEDIATRIC 100 mg B. BRAUN toxicity is increased in patients who have taken repeated high doses (greater than 5 - 10 g/day) of paracetamol for several days. 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, AIDS and with the use of drugs that induce liver microsomal oxidation such as barbiturates, isoniazid, rifampicin, phenytoin and carbamazepine. Overdosing may be fatal in these cases.

Symptoms
Symptoms generally appear within the first 24 hours and comprise: nausea, vomiting, anorexia, pallor and abdominal pain. Immediate emergency measures are necessary in case of paracetamol overdose, even when no symptoms are present. Liver damage may become apparent 12 to 48 hours or later after administration, initially by elevation of the serum transaminase and lactic dehydrogenase activity, increased serum bilirubin concentration and prolongation of the prothrombin time/INR. Liver damage may lead to encephalopathy, coma and death. Overdose with a single administration of 7,5 g or more of paracetamol in adults or 140 mg/kg of body weight in children, causes cytolytic hepatitis likely to induce complete and irreversible hepatic necrosis, resulting in acute or fulminant hepatic failure, 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. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Abnormalities of glucose metabolism and metabolic acidosis may occur. Cardiac dysrhythmias have been reported.

Treatment
Immediate hospitalisation. Before beginning treatment, take a blood sample for plasma paracetamol assay, as soon as possible after the overdose. N-acetylcysteine (NAC) should be administered to all cases of suspected overdose as soon as possible preferably within eight hours of overdosage; although treatment up to 36 hours after ingestion may still be of benefit especially if more than 150 mg/kg of paracetamol was taken. An initial dose of 150 mg/kg N-acetylcysteine in 200 ml dextrose injection given intravenously over 15 minutes, followed by an infusion of 50 mg/kg in 500 ml dextrose injection over the next four hours and then 100 mg/kg in 1 000 ml dextrose injection over the next sixteen hours. The volume of intravenous fluid should be modified for children. Although the oral formulation is not the treatment of choice, 140 mg/kg dissolved in water may be administered initially, followed by 70 mg/kg every four hours for seventeen doses.

Those whose plasma paracetamol levels are above the u201cnormal treatment lineu201d, should continue N-acetylcysteine treatment with 100 mg/kg IV over sixteen hours repeatedly until recovery. Patients with increased susceptibility to liver damage as identified above, should continue treatment if concentrations are above the u201chigh risk treatment lineu201d. (Refer to paracetamol nomogram above). Prothrombin index correlates best with survival. Monitor all patients with significant ingestion for at least 96 hours. Symptomatic treatment. Hepatic tests must be carried out at the beginning of treatment and repeated every 24 hours. In most cases hepatic transaminases restitution to normal in one to two weeks with full return of normal liver function. In very severe cases, however, liver transplantation may be necessary.