Paracetamol + codeine

Oral
Mild to moderate pain
Adult: Each tab contains paracetamol 500 mg and codeine phosphate 8 mg: 1-2 tab 4-6 hrly. Max: 8 tab/24 hr. Each 5 mL oral soln contains paracetamol 120 mg and codeine phosphate 12 mg: 15 mL 4 hrly as needed.
Child: Tab: 12-18 yr 1-2 tab 6 hrly. Max: 8 tab/24 hr. Oral soln: 3-6 yr 5 mL 3 or 4 times daily; 7-12 yr 10 mL 3 or 4 times daily.

Post-op pain management in childn who underwent tonsillectomy and/or adenoidectomy.

Patient w/ paralytic ileus, GI obstruction, adrenal insufficiency, CNS depression, history of drug abuse or acute alcoholism, head trauma, prostatic hyperplasia and/or urinary stricture, pre-existing resp disease, thyroid dysfunction, known G6PD deficiency, history of seizure disorder. Hepatic or renal impairment. Pregnancy and lactation. Patient Counselling May impair ability to drive and operate machinery. Monitoring Parameters Monitor relief of pain, resp and mental status, BP, bowel function and signs or symptoms of hypogonadism or hypoadrenalism.

Nausea, vomiting, constipation, abdominal pain, pruritus, dizziness, drowsiness, lightheadedness, shortness of breath, sedation, euphoria, dysphoria, voice disorder, dyspnoea, allergic reactions, rash, thrombocytopenia, agranulocytosis.
Potentially Fatal: Hepatotoxicity. Rarely, Stevens-Johnson syndrome, acute generalised exanthematous pustulosis, toxic epidermal necrolysis.

Symptoms: Paracetamol: Pallor, nausea, vomiting, anorexia, abdominal pain, metabolic acidosis, glucose metabolism disturbances, liver damage. In severe cases, encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, acute renal failure and death. Codeine: Nausea, vomiting, CNS and resp depression, pinpoint pupils, convulsion, coma. Management: Paracetamol: If presented w/in 1 hr of poisoning, admin activated charcoal. If needed, admin IV N-acetylcysteine or oral methionine. Codeine: Symptomatic and supportive treatment. Consider activated charcoal if an adult presents w/in 1 hr of ingestion. Admin naloxone if in state of coma or resp depression. Repeated doses may be needed in a seriously poisoned patient.

Increased paracetamol absorption w/ metoclopramide and domperidone. May increase risk of bleeding w/ warfarin and other coumarins. Codeine may antagonise GI effects of metoclopramide and domperidone. Increased CNS depression w/ CNS depressants (e.g. anaesth, anxiolytics, hypnotics, TCAs, and antipsychotics).

Sedative effects may be potentiated when used w/ alcohol.

Paracetamol may cause false-positive result for urinary 5-hydroxyindoleacetic acid.

Paracetamol, a para-aminophenol derivative, exhibits analgesic action by peripheral blockage of pain impulse generation; produces antipyresis by inhibiting the hypothalamic heat-regulating centre; and its weak anti-inflammatory activity is related to inhibition of prostaglandin synthesis in the CNS. Codeine, a phenanthrene derivative, binds to opiate receptor in the CNS, causing inhibition of ascending pain pathways.
Absorption: Readily absorbed from GI tract. Bioavailability: 53% (codeine). Time to peak plasma concentration: Approx 10-60 min (paracetamol); approx 1 hr (codeine).
Distribution: Distributed into most body tissues; crosses the placenta and present in breast milk. Volume of distribution: Approx 1 L/kg (paracetamol); approx 3-6 L/kg (codeine). Plasma protein binding: 10-25% (paracetamol); approx 7-25% (codeine).
Metabolism: Paracetamol: Undergoes hepatic metabolism. N-acetyl-p-benzoquinoneimine (minor metabolite) is produced in minute amounts mainly by CYP2E1 and CYP3A4 isoenzymes in the liver and kidney. Codeine: Metabolised by O- and N-demethylation in the liver to morphine, norcodeine, normorphine, hydrocodone and other metabolites.
Excretion: Paracetamol: Via urine mainly as glucuronide and sulfate conjugates w/ <5% excreted as unchanged drug. Codeine: Via urine mainly as conjugates w/ glucuronic acid. Half-life: Approx 1-3 hr (paracetamol); 3-4 hr (codeine).

Oral: Store between 20-25°C. Protect from light.

Analgesics (Non-Opioid) & Antipyretics / Analgesics (Opioid)

N02BE01 - paracetamol ; Belongs to the class of anilide preparations. Used to relieve pain and fever.
R05DA04 - codeine ; Belongs to the class of opium alkaloids and derivatives. Used as cough suppressant.