Empaped 125mg. 250mg Suppositories

Empaped u00ae is indicated for the relief of mild to moderate pain and fever when oral therapy is not feasible.

Posology
DO NOT EXCEED THE RECOMMENDED DOSE. The dose of Empaped u00ae depends on the patientu2019s age and body weight. In general, the single dose is usually between 10 to 15 mg/kg body weight, and the maximum daily dose is 60 mg/kg body weight. The dosage interval depends on the symptoms and the maximum daily dose, and should be at least 6 hours. A medical practitioner should be consulted if symptoms persist for more than three days.

Paediatric population
Infants (6 months to u2264 2 years) One 125 mg suppository up to 4 times daily.
Children (2 to 8 years) One 250 mg suppository up to 4 times daily. The suppository should be inserted per rectum.

Special populations
Hepatic insufficiency and mild renal insufficiency: In patients with disorders of liver and kidney function or Gilbertu2019s syndrome, the dose should be reduced and the dosage interval should be increased. Without medical advice, a daily dose of 2 g should not be exceeded.
Patients with severe renal insufficiency: In the presence of severe kidney failure (GFR u2264 30 ml/min) the dosage interval should be at least eight hours.
Elderly patients: Dose adjustment is not required in the elderly. However, in debilitated, immobilized elderly patients with impaired liver / kidney function, a dose reduction or prolongation of the dosing interval may be required. Without medical advice, the maximum daily dose of 60 mg/kg body weight (up to a maximum of 2 g/day) should not be exceeded in the following cases:

• Body weight less than 50 kg
• Chronic alcoholism
• Dehydration
• Chronic malnutrition

Method of administration
Empaped u00ae suppositories should be inserted deeply into the rectum after a bowel movement. They may be warmed up in the hands or dipped for a short time into warm water to improve their sliding properties.

Empaped u00ae should not be used in the presence of:

• Hypersensitivity to paracetamol or any of the ingredients listed in section 6.1.

This medicine 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. Dosages of Empaped u00ae in excess of those recommended may cause severe liver damage. Patients suffering from hepatitis, or recovering from any form of liver disease, should not use excessive quantities of Empaped u00ae.

To avoid the risk of overdose, it must be ensured that any concurrently used medication does not contain paracetamol. In the presence of the following disorders, Empaped u00ae should be used with great caution (longer interval between doses or in reduced doses) and under careful medical supervision:

• hepatocellular insufficiency (Child-Pugh < 9),
• chronic alcohol abuse,
• severe renal insufficiency (GFR < 30 ml/min (see section 4.2),
• Gilbertu2019s syndrome (Meulengrachtu2019s disease),
• concomitant use of medicines impairing the liver function,
• disorders associated with reduced glutathione levels (dose adjustment, e.g. in patients with diabetes mellitus, HIV, Downu2019s syndrome, tumours, if applicable),
• Glucose-6-phosphate dehydrogenase deficiency (favism)
• Haemolytic anaemia
• Glutathione deficiency
• Dehydration
• Chronic malnutrition
• Body weight less than 50 kg
• Elderly patients

As a rule, medicines containing paracetamol should be used for a few days only, and should not be given in large doses without a medical practitioneru2019s or a dentistu2019s advice. If large amounts of analgesics are taken for extended periods of time, or if these medicines are not used properly, they may cause headache, which may not be treated with increased doses of EMPAPED. In general, the habitual use of analgesics, especially of those containing more than one active ingredient, may lead to permanent kidney damage, including the risk of kidney failure (analgesic nephropathy). Headache, fatigue, muscular pain, nervousness and vegetative symptoms may occur after abrupt discontinuation of prolonged, improper use of large amounts of analgesics. These symptoms will subside after a couple of days. No analgesics should be taken within this period. The use of analgesics should not be resumed without a medical practitioneru2019s advice. Use with caution in renal disease. The risk of neutropenia is increased with the concomitant use of Empaped u00ae with zidovudine (see section 4.5).

The administration of probenecid inhibits the binding of paracetamol to glucuronic acid, reducing paracetamol clearance by a factor of about 2. The dose of Empaped u00ae should therefore be reduced if the patient concomitantly receives probenecid.

Special caution is necessary for patients receiving Empaped u00ae in combination with active substances causing induction of liver transaminases (phenytoin, phenobarbital, carbamazepine, rifampicin) or with potentially hepatotoxic compounds (see section 4.9). Patients receiving Empaped u00ae in combination with AZT (zidovudine), are more likely to develop a neutropenia. These substances should be used in combination with paracetamol only on medical advice (see section 4.4). Cholestyramine reduces the uptake of paracetamol. The concomitant use of anticoagulants, especially warfarin, may increase INR levels and may increase the risk of bleeding. Therefore, long-term administration of paracetamol (longer than 10 days) to patients treated with anticoagulants should only be done under medical supervision. Monitoring the INR values is recommended. The occasional use of paracetamol has no significant influence on the bleeding tendency. Prolonged concurrent use of Empaped u00ae with salicylates increases the risk of adverse renal effects. Effect on laboratory tests: Paracetamol may influence tests for uric acid with phosphotungstic acid as well as blood glucose determination with glucose oxidase peroxidase.

Pregnancy
A large amount of data on pregnant women indicate neither malformative, nor foeto/neonatal toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy however it should be used at the lowest effective dose for the shortest possible time, at the lowest possible frequency and not in combination with other medicines.

Breastfeeding
Small amounts of paracetamol are excreted in human milk. No deleterious effects or adverse reactions during lactation have been observed. Thus, paracetamol may be given to nursing women in therapeutic doses.

Fertility
No information available

Empaped u00ae has no or negligible influence on the ability to drive and use machines.

Very common (u2265 1/10); common (u2265 1/100, < 1/10); uncommon (u22651/1 000, <1/100); rare (u2265 1/10 000, < 1/1 000); very rare (u2264 1/ 10 000), including isolated reports, not known (cannot be estimated from available data).

System Organ Class Frequency category Adverse reaction
Blood and lymphatic system disorders Very rare Changes to the blood count such as thrombocytopenia, agranulocytosis.
Immune system disorders Very rare In predisposed persons bronchospasm (analgesic asthma), hypersensitivity reactions ranging from erythema to urticaria and anaphylactic shock.
Hepato-biliary disorders Rare Increase in liver transaminases
Skin and subcutaneous tissue disorders Very rare Cases of serious skin reactions have been reported.

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://www.sahpra.org.za/Publications/Index/8

Prompt treatment is essential. In the event of overdosage, consult a doctor or take the person to the nearest hospital immediately. 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 toxicity is increased in patients who have taken repeated high doses (greater than 5 - 10 g/day) of paracetamol for several days, in chronic alcoholism, chronic liver disease, AIDS, malnutrition, and with the use of medicines that induce liver microsomal oxidation such as barbiturates, isoniazid, rifampicin, phenytoin and carbamazepine. Symptoms of paracetamol overdosage in the first 24 hours include pallor, nausea, vomiting, anorexia, and possibly abdominal pain. Mild symptoms during the first two days of acute poisoning, do not reflect the potential seriousness of the overdosage. Liver damage may become apparent 12 to 48 hours, or later after ingestion, initially by elevation of serum transaminase and lactic dehydrogenase activity, increased serum bilirubin concentration and prolongation of prothrombin time. Liver damage may lead to encephalopathy, coma and death.

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 for paracetamol overdosage: Although evidence is limited it is recommended that any adult person who has ingested 5 - 10 grams or more of paracetamol (or a child who has had more than 140 mg/kg) within the preceding four hours, should have the stomach emptied by lavage (emesis may be adequate for children) and a single dose of 50 g activated charcoal given via the lavage tube. Ingestion of amounts of paracetamol smaller than this may require treatment in patients susceptible to paracetamol poisoning (see above). In patients who are stuperose or comatose endotracheal intubation should precede gastric lavage in order to avoid aspiration. N-acetylcysteine should be administered to all cases of suspected overdose as soon as possible, preferably within eight hours of an 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.

IV Administration: 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 of dextrose injection over the next 4 hours, and then 100 mg/kg in 1000 ml dextrose injection over the next 16 hours. The volume of intravenous fluid should be modified for children.

Oral administration: Although the oral formulation is not the treatment of choice, 140 mg/kg N-acetylcysteine dissolved in water may be administered initially, followed by 70 mg/kg every four hours for seventeen doses. A plasma paracetamol level should be determined four hours after ingestion in all cases of suspected overdosage. Levels done before four hours may be misleading. Patients at risk of liver damage, and hence requiring continued treatment with N-acetylcysteine, can be identified according to their 4-hour plasma paracetamol level. The plasma paracetamol level can be plotted against time since ingestion in the nomogram below. The nomogram should be used only in relation to a single acute ingestion. 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. Prothrombin index correlates best with survival. All patients with significant ingestion should be monitored for at least 96 hours.