Reset ER (Paracetamol/Acetaminophen Extended Release): A Non-Opioid Analgesic

Reset ER contains Paracetamol (Acetaminophen) in an extended-release formulation. It is indicated for the relief of fever and various types of pain, from common aches to post-operative discomfort and joint stiffness. It belongs to the therapeutic class of Non-Opioid Analgesics.

How Reset ER Works (Pharmacology)

Paracetamol's exact mechanism isn't fully understood, but it mainly acts in the Central Nervous System (CNS):

• Analgesic Action: It increases the pain threshold by inhibiting cyclooxygenase (COX) enzymes (COX-1, COX-2, and potentially COX-3) involved in prostaglandin (PG) synthesis, primarily in the CNS. Unlike NSAIDs, its effect on peripheral COX is minimal, contributing to its weak anti-inflammatory activity.
• Antipyretic Action: It reduces fever by acting on the hypothalamic heat-regulating center, leading to peripheral vasodilation and sweating, which promotes heat loss.
• Indirect COX Inhibition: Research suggests Paracetamol indirectly blocks COX, and this blockade is less effective in the presence of peroxides. This might explain why it's effective in the CNS and endothelial cells but less so in platelets and immune cells with high peroxide levels.

Key Indications & Benefits

Reset ER is indicated for:

• Fever, common cold, and influenza.
• Various types of pain: Headache, toothache, earache, bodyache, myalgia (muscle pain), neuralgia, dysmenorrhea (menstrual pain), sprains, colic pain, back pain, post-operative pain, postpartum pain, and inflammatory pain.
• Post-vaccination pain in children.
• Rheumatic & osteoarthritic pain and stiffness of joints.

Dosage & Administration

Reset ER comes in an extended-release tablet form. It's crucial to swallow these tablets whole and not crush them. Always consult a registered physician for specific dosage instructions.

• Extended Release Tablet:
  • Adults & Children over 12 years: Two tablets, swallowed whole, every 6 to 8 hours (maximum of 6 tablets in any 24 hours). The tablet must not be crushed.

The provided text also includes dosages for other Paracetamol formulations (standard tablets, syrup/suspension, suppository, paediatric drop, and IV infusion) under the general "Reset" brand. Please ensure you refer to the specific dosage instructions for the "ER" (Extended Release) formulation you are using.

Important Considerations & Warnings

It's crucial to discuss your full medical history with your doctor before taking Reset ER.

Contraindications:

• Known hypersensitivity to Paracetamol.

Side Effects:

• Side effects are usually mild.
• Rarely reported: Haematological reactions (e.g., thrombocytopenia, leucopenia, pancytopenia, neutropenia, agranulocytosis), pancreatitis, skin rashes, and other allergic reactions.

Pregnancy & Lactation:

• Pregnancy: Epidemiological studies in humans show no ill effects with recommended dosages of Paracetamol, but always follow your doctor's advice regarding its use during pregnancy.
• Lactation: Paracetamol is excreted in breast milk, but not in a clinically significant amount. Available published data do not contraindicate breastfeeding.

Precautions & Warnings:

• Hepatic Injury/Overdose: Taking doses higher than recommended can lead to hepatic injury, severe hepatotoxicity, and even death.Never exceed the maximum recommended daily dose.
• High-Risk Patients for Hepatotoxicity: Use caution when administering Reset ER to patients with hepatic impairment or active hepatic disease, alcoholism, chronic malnutrition, severe hypovolemia (e.g., due to dehydration or blood loss). The risk of overdose is higher in those with non-cirrhotic alcoholic liver disease.
• Renal Impairment: Care is advised in patients with severe renal impairment (creatinine clearance < 30 ml/min).
• Other Paracetamol-containing products: Patients should be advised not to take other Paracetamol-containing products concurrently to avoid overdose. Reset ER should only be used by the patient for whom it is prescribed.
• Hypersensitivity/Allergy: There have been infrequent reports of life-threatening anaphylaxis requiring emergency medical attention. Discontinue Reset ER immediately if symptoms of allergy or hypersensitivity occur. Do not use if there's a known allergy to Paracetamol.

Drug Interactions:

• Enzyme Inducers: Patients who have taken barbiturates, tricyclic antidepressants, and alcohol may show a diminished ability to metabolize large doses of Reset ER, potentially increasing the risk of toxicity.
• Alcohol: Can increase the hepatotoxicity of Reset ER overdosage.
• Anticonvulsants or Oral Steroid Contraceptives: Chronic ingestion of these drugs can induce liver enzymes, potentially leading to lower therapeutic levels of Reset ER by increasing its metabolism or clearance.

Use in Special Populations

• Pediatric Use: The safety and effectiveness of Paracetamol IV (mentioned in the original text as "Reset ER IV") for acute pain and fever in pediatric patients ages 2 years and older is supported by evidence from adult studies. (Note: The specific Reset ER tablet is typically for ages 12 and over).
• Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and younger subjects.
• Patients with Hepatic Impairment: Reset ER is contraindicated in patients with severe hepatic impairment or severe active liver disease. Use with caution in other cases of hepatic impairment or active liver disease, as a reduced total daily dose may be warranted.
• Patients with Renal Impairment (creatinine clearance < 30 ml/min): Longer dosing intervals and a reduced total daily dose of Reset ER may be warranted.

Overdose Effects

• Liver damage: Possible in adults who have taken 10 g or more of Reset ER. Ingestion of 5 g or more may lead to liver damage if the patient has risk factors such as long-term treatment with liver enzyme-inducing drugs (e.g., Carbamazepine, Phenobarbitone, Phenytoin, Primidone, Rifampicin, St John’s Wort), regular excessive alcohol consumption, or glutathione depletion (e.g., due to eating disorders, cystic fibrosis, HIV infection, starvation, cachexia).
• Symptoms (first 24 hours): Pallor, nausea, vomiting, anorexia, and abdominal pain.
• Delayed Symptoms (12-48 hours): Liver damage may become apparent. Abnormalities of glucose metabolism and metabolic acidosis can occur.
• Severe poisoning: Hepatic failure may progress to encephalopathy, hemorrhage, hypoglycemia, cerebral edema, and death. Acute renal failure (acute tubular necrosis) may develop even without severe liver damage. Cardiac arrhythmias and pancreatitis have also been reported.
• Immediate Treatment is Essential:
  • Consider activated charcoal if the overdose was taken within 1 hour.
  • Measure plasma Paracetamol concentration at 4 hours or later after ingestion (earlier concentrations are unreliable).
  • N-acetylcysteine is the antidote and can be used up to 24 hours after ingestion, with the maximum protective effect obtained up to 8 hours post-ingestion (effectiveness declines sharply thereafter).
  • Intravenous N-acetylcysteine should be given if required, following the established dosage schedule. Oral Methionine may be an alternative in remote areas if vomiting is not a problem.
  • Management of patients with serious hepatic dysfunction beyond 24 hours from ingestion should involve specialists (e.g., NPIS or a liver unit).

Storage Conditions

Keep in a dry place away from light and heat. Keep out of the reach of children.