I. Pharmacological Profiles
1. Acetylsalicylic Acid
Suppository: 50–150 mg
Tablet: 100–500 mg
Uses: mild-to-moderate pain including dysmenorrhoea, and headache; pain and inflammation in rheumatic disease and other musculoskeletal disorders, including juvenile arthritis; pyrexia; acute migraine attack; antiplatelet.
Contraindications: hypersensitivity (including asthma, angioedema, urticaria, or rhinitis) to acetylsalicylic acid or any other non-steroidal anti-inflammatory medicine (NSAIM); children and adolescents under 16 years (to reduce risk of Reye’s syndrome); previous or active peptic ulceration; haemophilia and other bleeding disorders; not for treatment of gout.
Precautions:
Dose:
Mild-to-moderate pain, pyrexia, by mouth with or after food, ADULT, 300–900 mg every 4–6 hours if necessary; maximum, 4 g daily; CHILD under 16 years, not recommended.
Mild-to-moderate pain, pyrexia, by rectum, ADULT, 600–900 mg inserted every 4 hours if necessary; maximum, 3.6 g daily; CHILD under 16 years, not recommended.
Inflammatory arthritis, by mouth with or after food, ADULT, 4–8 g daily in divided doses in acute conditions; up to 5.4 g daily may be sufficient in chronic conditions.
Adverse effects: generally mild and infrequent for lower doses, but common with anti-inflammatory doses; gastrointestinal discomfort or nausea, ulceration with occult bleeding (occasionally major haemorrhage); also other haemorrhage including subconjunctival; hearing disturbances such as tinnitus (rarely deafness), vertigo, confusion, hypersensitivity reactions including angioedema, bronchospasm, and rash; increased bleeding time; rarely oedema, myocarditis and blood disorders (particularly thrombocytopenia).
2. Codeine Phosphate
Tablet: 15 mg, 30 mg, 60 mg
Oral solution: 25 mg/5 mL
Injection: 60 mg/mL
Medication subject to international control under the Single Convention on Narcotic Drugs, 1961.
NOTE: Codeine is a prodrug of morphine, requiring metabolism by CYP2D6 to morphine to provide an analgesic effect. Most of its analgesic effect results from the ≤10% of codeine which is converted to morphine by O-demethylation via CYP2D6 (1,2,3). There is a high degree of variability in CYP2D6 metabolism of codeine to morphine because of genetic differences between individuals and ethnic groups, making the benefits and risks of use unpredictable. On average, 77–92% of people extensively metabolize codeine to morphine while 5–10% are poor metabolizers and experience no analgesic benefit. The 1–2% of people who are ultra-rapid metabolizers are at the highest risk for morphine exposure and toxicity, including respiratory depression. Prevalence of ultra-rapid metabolizers varies considerably depending on ethnicity: Caucasian 1–10%; Arabs, Ethiopians and North Africans 16–28% (4). In 2015 the Ethiopian government temporarily banned codeine (5). In addition, some authorities assert that there is no pharmacological need for weak opioids such as codeine in cancer pain because low doses of morphine (or an alternative strong opioid) generally provide quicker and better relief from cancer pain (6,7). These authorities discourage any use of codeine (3).
Uses: mild-to-moderate pain; diarrhoea.
Contraindications: respiratory depression, obstructive airways disease, acute asthma attack; where there is risk of paralytic ileus.
Precautions:
renal impairment
hepatic impairment
dependence
pregnancy
breastfeeding
overdosage.
Interactions:
alcohol: enhanced sedative and hypotensive effect
amitriptyline: possibly increased sedation
chlorpromazine: enhanced sedative and hypotensive effect
clomipramine: possibly increased sedation
diazepam: enhanced sedative effect
fluphenazine: enhanced sedative and hypotensive effect
haloperidol: enhanced sedative and hypotensive effect
metoclopramide: antagonism of effect of metoclopramide on gastrointestinal activity
ritonavir: possibly increases plasma concentration of codeine
Dose: mild-to-moderate pain, by mouth, ADULT, 30–60 mg every 4 hours when necessary; maximum, 240 mg daily.
Adverse effects: constipation particularly troublesome in long-term use; dizziness, nausea, vomiting; difficulty with micturition; ureteric or biliary spasm; dry mouth, headaches, sweating, facial flushing; in therapeutic doses, codeine is much less liable than morphine to produce tolerance, dependence, euphoria, sedation or other adverse effects.
3. Fentanyl
Transmucosal lozenge: 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1200 mcg, 1600 mcg (as citrate).
Transdermal patch (extended-release): 12 mcg/hr, 25 mcg/hr, 50 mcg/hr, 75 mcg/hr, 100 mcg/hr, (as base).
Injection: 50 mcg/mL in various vial sizes (as citrate)
Indications: moderate-to-severe persisting pain.
Contraindications: hypersensitivity to opioid agonists or to any component of the formulation; acute respiratory depression; acute asthma; paralytic ileus; concomitant use with, or use within 14 days after ending, monoamine oxidase inhibitor therapy; raised intracranial pressure and/or head injury, if ventilation not controlled; coma.
Precautions: impaired respiratory function; avoid rapid injection which may precipitate chest wall rigidity and difficulty with ventilation; bradycardia; asthma; hypotension; shock; obstructive or inflammatory bowel disorders; biliary tract disease; convulsive disorders; hypothyroidism; adrenocortical insufficiency; avoid abrupt withdrawal after prolonged treatment; diabetes mellitus; impaired consciousness; acute pancreatitis; myasthenia gravis; hepatic impairment; renal impairment; toxic psychosis; (patches:) increased serum levels in patients with fever >40 °C (104 °F).
Skilled tasks: warn the patient or caregiver about the risk of undertaking tasks requiring attention or coordination, e.g. operating heavy machinery.
Dosage:
Starting dose for opioid-naive patients:
SC/IV injection:
start with a stat dose of 25–100 mcg and then 25–50 mcg p.r.n.
reduce the dose in the elderly and debilitated, e.g. 12.5–25 mcg p.r.n.
traditionally p.r.n. dosing intervals are q1h, but more frequent dosing with close monitoring may be required in severe acute pain
give IV by slow injection over 3–5 minutes; this reduces the risk of muscular rigidity.
Continuous SC/IV infusion:
initial dose 240–480 mcg/24h
for breakthrough pain, allow 10% of the 24h infusion dose p.r.n. q1h
titrate the infusion dose as needed
Dose for transmucosal lozenge (oral transmucosal fentanyl citrate): Start with lowest dose and use only for breakthrough pain in opioid-tolerant patients: patients on a regular strong opioid for chronic cancer pain for ≥1 week. The minimum dose of the regular strong opioid should be morphine 60 mg/24h PO, or fentanyl 25 mcg/h transdermal, or hydromorphone 8 mg/24h PO, or oxycodone 30 mg/24h PO, or an equivalent dose of another opioid. Prescribers of transmucosal fentanyl products should:
be experienced in the management of opioid therapy in cancer patients;
limit use to patients who can adhere to the instructions regarding indication, administration, storage and returns;
provide ongoing supervision;
keep in mind the potential for fentanyl to be misused; and
understand that the various transmucosal formulations are not bio-equivalent and not directly interchangeable, and thus:
Adverse effects:
common – nausea, vomiting, constipation, dry mouth, biliary spasm, respiratory depression, muscle rigidity, apnoea, myoclonic movements, bradycardia, hypotension, abdominal pain, anorexia, dyspepsia, mouth ulcer, taste disturbance, vasodilation, anxiety, drowsiness, diaphoresis;
uncommon – flatulence, diarrhoea, laryngospasm, dyspnoea, hypoventilation, depersonalization, dysarthria, amnesia, incoordination, paraesthesia, malaise, agitation, tremor, muscle weakness, hypertension, dizziness, itching, bronchospasm;
rare – circulatory depression, cardiac arrest, hiccups, arrhythmia, paralytic ileus, haemoptysis, psychosis, seizures, shock, asystole, pyrexia, ataxia, muscle fasciculation, local irritation (with patches).
Interactions with other medicines*:
amiodarone – profound bradycardia, sinus arrest and hypotension have been reported;
beta-adrenergic blockers – severe hypotension reported;
calcium channel blockers – severe hypotension reported;
central nervous system depressants – additive or potentiating effects with fentanyl;
imidazole antifungals – possible enhanced or prolonged effects of fentanyl;
macrolide antibiotics – possible enhanced or prolonged effects of fentanyl;
monoamine oxidase inhibitors
* – severe and unpredictable potentiation of opioids;
naloxone
* – precipitates opioid withdrawal symptoms;
naltrexone
* – precipitates opioid withdrawal symptoms;
neuroleptics – possible reduced pulmonary arterial pressure, hypotension and hypovolaemia;
nitrous oxide – possible cardiovascular depression;
opioid antagonists/partial agonists – may precipitate opioid withdrawal symptoms;
phenytoin – may reduce plasma concentration of fentanyl; and
protease inhibitors – possible enhanced or prolonged effects of fentanyl.
- *
4. Hydromorphone
Injection: 1 mg/mL ampoule, 2 mg/mL ampoule, 4 mg/mL ampoule, 10 mg/mL ampoule (as hydrochloride)
Tablet: 2 mg, 4 mg, 8 mg (as hydrochloride)
Oral liquid: 1 mg (as hydrochloride)/mL
Sustained-release capsules: 2 mg, 4 mg, 8 mg, 16 mg, 24 mg
Indications: moderate-to-severe persisting pain.
Contraindications: hypersensitivity to opioid agonists or to any component of the formulation; acute respiratory depression; acute asthma; paralytic ileus; concomitant use with, or use within 14 days after ending, monoamine oxidase inhibitors; raised intracranial pressure and/or head injury, if ventilation not controlled; coma.
Precautions: impaired respiratory function; avoid rapid injection which may precipitate chest wall rigidity and difficulty with ventilation; bradycardia; asthma; hypotension; shock; obstructive or inflammatory bowel disorders; biliary tract disease; convulsive disorders; hypothyroidism; adrenocortical insufficiency; avoid abrupt withdrawal after prolonged treatment; diabetes mellitus; impaired consciousness; acute pancreatitis; myasthenia gravis; hepatic impairment; renal impairment; toxic psychosis.
Skilled tasks: warn the patient or caregiver about the risk of undertaking tasks requiring attention or coordination, e.g. operating heavy machinery.
Dosage:
Starting dose for opioid-naive patients:
Oral: 1–4 mg every 4 hours as needed
SC/IV injection: 0.3–0.7 mg every 3–4 hours as needed
SC/IV continuous infusion: 0.1–0.2 mg/h.
Renal impairment: moderate (GFR 10–20 mL/min or serum creatinine 300–700 micromol/L) and severe (GFR <10 mL/min or serum creatinine >700 micromol/L) – reduce dose, start with lowest dose and titrate according to response.
Hepatic impairment: use with caution and reduce initial dose in all degrees of impairment.
Adverse effects:
common – nausea, vomiting, constipation, dry mouth, sedation, biliary spasm, respiratory depression, muscle rigidity, apnoea, myoclonic movements, asthenia, dizziness, confusion, dysphoria, euphoria, light-headedness, pruritus, rash, somnolence, sweating;
uncommon – hypotension, hypertension, bradycardia, tachycardia, palpitation, oedema, postural hypotension, miosis, visual disturbances, abdominal cramps, anorexia, paraesthesia, malaise, agitation, tremor, muscle weakness, hallucinations, vertigo, mood changes, dependence, drowsiness, anxiety, sleep disturbances, headache, taste disturbance, agitation, urinary retention, laryngospasm, bronchospasm;
rare – circulatory depression, cardiac arrest, respiratory arrest, shock, paralytic ileus, seizures.
Interactions with other medicines:
- *
5. Ibuprofen
Tablet: 200 mg; 400 mg
Uses: pain and inflammation in rheumatic disease and other musculoskeletal disorders; mild-to-moderate pain including dysmenorrhoea and headache; acute migraine attack.
Contraindications: hypersensitivity (including asthma, angioedema, urticaria, or rhinitis) to acetylsalicylic acid or any other NSAIM; active peptic ulceration.
Precautions: renal impairment; hepatic impairment; preferably avoid if history of peptic ulceration; cardiac disease; older persons; pregnancy and breastfeeding; coagulation defects; allergic disorders; interactions.
Dose:
Mild-to-moderate pain, pyrexia, inflammatory musculoskeletal disorders, by mouth with or after food, ADULT, 1.2–1.8 g daily in 3–4 divided doses, increased if necessary to maximum 2.4 g daily (3.2 g daily in inflammatory disease); maintenance dose of 0.6–1.2 g daily may be sufficient.
Adverse effects: gastrointestinal disturbances, including nausea, diarrhoea, dyspepsia, ulceration, and haemorrhage; hypersensitivity reactions including rash, angioedema and bronchospasm; headache, dizziness, nervousness, depression, drowsiness, insomnia, vertigo, tinnitus, photosensitivity, haematuria; fluid retention (rarely precipitating congestive heart failure in older persons), raised blood pressure, renal failure; rarely hepatic damage, alveolitis, pulmonary eosinophilia, pancreatitis, visual disturbances, erythema multiforme (Stevens-Johnson syndrome), toxic dermal necrolysis (Lyell syndrome), colitis and aseptic meningitis.
6. Methadone
Injection: 10 mg/mL in various vial sizes (as hydrochloride)
Tablet: 5 mg, 10 mg, 40 mg (as hydrochloride)
Oral liquid: 1 mg/mL, 2 mg/mL, 5 mg/mL (as hydrochloride)
Oral concentrate: 10 mg/mL (as hydrochloride)
CAUTION: Due to the complex nature and wide inter-individual variation in the pharmacokinetics of methadone, methadone should be commenced only by practitioners experienced with its use.
Titration should be carried out with close clinical observation of the patient over several days.
Indications: moderate-to-severe persisting pain.
Contraindications: hypersensitivity to opioid agonists or to any component of the formulation; acute respiratory depression; acute asthma; paralytic ileus; concomitant use with, or use within 14 days after ending, monoamine oxidase inhibitors; raised intracranial pressure and/or head injury, if ventilation not controlled; coma.
Precautions: impaired respiratory function; avoid rapid injection which may precipitate chest wall rigidity and difficulty with ventilation; history of cardiac conduction abnormalities; family history of sudden death (electrocardiograph [ECG] monitoring recommended); QT interval prolongation; asthma; hypotension; shock; obstructive or inflammatory bowel disorders; biliary tract disease; convulsive disorders; hypothyroidism; adrenocortical insufficiency; avoid abrupt withdrawal after prolonged treatment; diabetes mellitus; impaired consciousness; acute pancreatitis; myasthenia gravis; hepatic impairment; renal impairment; toxic psychosis.
Skilled tasks: warn the patient about the risk of undertaking tasks requiring attention or coordination, e.g. operating heavy machinery.
Dosage: In general, methadone should be reserved for patients who fail to respond well to morphine or another strong opioid. See Table 1 and referenced documents for details on switching from other opioids to methadone (3). However, the following doses can be used for initiating methadone therapy in an opioid-naïve patient when necessary:
2.5 mg (1–2 mg in older persons) PO q8h regularly and q6h p.r.n.
if necessary, titrate the regular dose upwards once a week, guided by p.r.n. use.
Renal impairment: severe (GFR <10 mL/min or serum creatinine >700 micromol/L) – reduce dose by 50% and titrate according to response; significant accumulation is not likely in renal failure, as elimination is primarily via the liver.
Hepatic impairment: avoid or reduce dose; may precipitate coma.
Adverse effects:
common – nausea, vomiting, constipation, dry mouth, biliary spasm, respiratory depression, drowsiness, muscle rigidity, hypotension, bradycardia, tachycardia, palpitation, oedema, postural hypotension, hallucinations, vertigo, euphoria, dysphoria, dependence, confusion, urinary retention, ureteric spasm;
uncommon – restlessness, dyspnoea, hypoventilation, depersonalization, dysarthria, amnesia, incoordination, paraesthesia, malaise, agitation, tremor, muscle weakness, hypertension, dizziness, itching, bronchospasm, dysmenorrhoea, dry eyes, hyperprolactinaemia; and
rare – QT interval prolongation, torsades de pointes, hypothermia, circulatory depression, cardiac arrest, hiccups, arrhythmia, paralytic ileus, haemoptysis, psychosis, seizures, shock, asystole, pyrexia, ataxia, muscle fasciculation, raised intracranial pressure.
Interactions with other medicines:
abacavir – plasma concentration of methadone possibly reduced;
amiodarone – may result in an increased risk of QT interval prolongation;
atomoxetine – increased risk of ventricular arrhythmias;
carbamazepine – plasma concentration of methadone reduced;
central nervous system depressants – additive or potentiating effects with methadone;
efavirenz – plasma concentration of methadone reduced;
fluvoxamine – plasma concentration of methadone possibly increased;
fosamprenavir – plasma concentration of methadone reduced;
medicines that prolong the QT interval – may result in an increased risk of QT interval prolongation;
monoamine oxidase inhibitors
* – severe and unpredictable potentiation of opioids;
naloxone
* – precipitates opioid withdrawal symptoms;
naltrexone
* – precipitates opioid withdrawal symptoms;
nelfinavir – plasma concentration of methadone reduced;
nevirapine – plasma concentration of methadone possibly reduced;
opioid antagonists/partial agonists – may precipitate opioid withdrawal symptoms;
phenobarbital – plasma concentration of methadone reduced;
phenytoin – metabolism of methadone accelerated by phenytoin resulting in reduced effect and risk of withdrawal symptoms;
quinine – may result in an increased risk of QT interval prolongation;
rifampicin – metabolism of methadone accelerated;
ritonavir – plasma concentration of methadone reduced;
voriconazole – plasma concentration of methadone increased; and
zidovudine – methadone possibly increases zidovudine concentration.
- *
7. Morphine
Injection: 10 mg (morphine hydrochloride or morphine sulfate) in 1 mL ampoule
Oral liquid: 10 mg (morphine hydrochloride or morphine sulfate)/5 mL
Tablet: 10 mg (morphine sulfate)
Tablet (prolonged-release): 10 mg; 30 mg; 60 mg (morphine sulfate)
Medication subject to international control under the Single Convention on Narcotic Drugs, 1961.
Uses: moderate and severe pain (acute and chronic); myocardial infarction, acute pulmonary oedema; adjunct during major surgery and postoperative analgesia.
Contraindications: avoid in acute respiratory depression, acute alcoholism and where risk of paralytic ileus; also avoid in raised intracranial pressure or head injury (affects pupillary responses vital for neurological assessment); avoid injection in phaeochromocytoma.
Precautions: renal impairment and hepatic impairment; reduce dose or avoid in older and debilitated patients; hypothyroidism; convulsive disorders; decreased respiratory reserve and acute asthma; hypotension; prostatic hypertrophy, pregnancy and breastfeeding. Severe withdrawal symptoms can develop if withdrawn abruptly.
Dose:
Acute pain, by subcutaneous injection (not suitable for oedematous patients), by intramuscular injection, or by intravenous injection: ADULT, 2–10 mg every 4 hours if necessary.
Chronic pain, by mouth (immediate-release tablets) or by subcutaneous injection (not suitable for oedematous patients) or by intravenous injection, ADULT, 2–20 mg regularly every 4 hours; dose may be increased according to need; oral dose should be approximately double the corresponding injected dose; by mouth (sustained-release tablets), titrate dose first using immediate-release preparation, then every 12 hours according to daily morphine requirement.
Myocardial infarction, by slow intravenous injection (2 mg/minute), ADULT, 5–10 mg followed by a further 5–10 mg if necessary; older or debilitated patients, reduce dose by half.
Acute pulmonary oedema, by slow intravenous injection (2 mg/minute), ADULT, 5–10 mg.
NOTE: The doses stated above refer equally to morphine sulfate and morphine hydro-chloride. Sustained-release capsules designed for once-daily administration are also available [not included on the 15th World Health Organization (WHO) Model list of essential medicines; consult manufacturer’s literature. Dosage requirements should be reviewed if the brand of controlled-release preparation is altered.
PATIENT ADVICE. Sustained-release tablets should be taken at regular intervals and not on an as-needed basis for episodic or breakthrough pain. Sustained-release tablets should not be crushed.
Adverse effects: nausea, vomiting (particularly in initial stages), constipation; drowsiness; also dry mouth, anorexia, spasm of urinary and biliary tract; bradycardia, tachycardia, palpitation, euphoria, decreased libido, rash, urticaria, pruritus, sweating, headache, facial flushing, vertigo, postural hypotension, hypothermia, hallucinations, confusion, dependence, miosis; larger doses produce respiratory depression, hypotension, and muscle rigidity.
8. Naloxone
Injection: 0.4 mg/mL (hydrochloride) in 1 mL ampoule
Indications: opioid overdose.
Contraindications: no contraindications to the use of naloxone for treatment of severe or life-threatening opioid toxicity such as respiratory depression.
Precautions: Cautious dosing is needed to avoid severe withdrawal syndrome after prolonged administration of opioids and in opioid-tolerant patients; cardiovascular disease; post-operative patients (may reverse analgesia and increase blood pressure).
Dosage:
0.08–0.12 mg IV every 2–3 minutes until the patient is breathing adequately
After initial response, the intravenous dose may need to be repeated every 20–60 minutes because of the short duration of action
For continuous intravenous infusion, dilute to a concentration of 4 mcg/mL with glucose 5% or sodium chloride 0.9%
Renal impairment: excretion of some opioids and/or their active metabolites (codeine, dextropropoxyphene, dihydrocodeine, morphine, pethidine, oxycodone) is delayed in impairment so these opioids will accumulate; extended treatment with naloxone infusion may be required to reverse opioid effect.
Hepatic impairment: no dose adjustment necessary.
Adverse effects:
common – nausea, vomiting, sweating
uncommon – tachycardia, ventricular arrhythmias
rare – cardiac arrest.
Interactions with other medicines: there are no known interactions where it is advised to avoid concomitant use.
9. Oxycodone
Tablet: 5 mg, 10 mg, 15 mg, 20 mg, 30 mg (as hydrochloride)
Tablet (modified-release): 5 mg, 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, 160 mg (as hydrochloride)
Capsule: 5 mg, 10 mg, 20 mg (as hydrochloride)
Oral liquid: 1 mg/mL (as hydrochloride)
Concentrated oral liquid: 10 mg/mL, 20 mg/mL (as hydrochloride)
Indications: moderate-to-severe persisting pain.
Contraindications: hypersensitivity to opioid agonists or to any component of the formulation; acute respiratory depression; acute asthma; paralytic ileus; concomitant use with, or use within 14 days after ending, monoamine oxidase inhibitors; raised intracranial pressure and/or head injury, if ventilation not controlled; coma.
Precautions: impaired respiratory function; avoid rapid injection which may precipitate chest wall rigidity and difficulty with ventilation; bradycardia; asthma; hypotension; shock; obstructive or inflammatory bowel disorders; biliary tract disease; convulsive disorders; hypothyroidism; adrenocortical insufficiency; avoid abrupt withdrawal after prolonged treatment; diabetes mellitus; impaired consciousness; acute pancreatitis; myasthenia gravis; hepatic impairment; renal impairment; toxic psychosis.
Skilled tasks: warn the patient or caregiver about the risk of undertaking tasks requiring attention or coordination, e.g. operating heavy machinery.
Dosage for opioid-naïve patients:
Immediate-release formulation: 2.5–5 mg PO q4h as needed; and
For constant or frequently recurring pain, can use modified-release (sustained-release): 10 mg PO q12h, and add immediate release 2.5–5 mg PO q4h as needed for breakthrough pain.
Renal impairment: mild (GRF 20–50 mL/min or approximate serum creatinine 150–300 micromol/L) to severe (GFR <10mL/min or serum creatinine >700 micromol/L) – dose reduction may be required; start with lowest dose and titrate according to response.
Hepatic impairment: moderate and severe; reduce dose by 50% or avoid use.
Adverse effects:
common – nausea, vomiting, constipation, diarrhoea, dry mouth, sedation, biliary spasm, abdominal pain, anorexia, dyspepsia, pruritus, somnolence, dizziness;
less common – muscle rigidity, hypotension, respiratory depression, bronchospasm, dyspnoea, impaired cough reflex, asthenia, anxiety, chills, muscle fasciculation, postural hypotension, hallucinations, vertigo, euphoria, dysphoria, dizziness, confusion;
uncommon – bradycardia, tachycardia, palpitation, oedema, mood changes, dependence, drowsiness, sleep disturbances, headache, miosis, visual disturbances, sweating, flushing, rash, urticaria, restlessness, difficulty with micturition, urinary retention, ureteric spasm, gastritis, flatulence, dysphagia, taste disturbance, belching, hiccups, vasodilation, supraventricular tachycardia, syncope, amnesia, hypoesthesia, pyrexia, amenorrhoea, hypotonia, paraesthesia, disorientation, malaise, agitation, speech disorder, tremor, dry skin;
rare – raised intracranial pressure, circulatory depression, cardiac arrest, respiratory arrest, shock, paralytic ileus, seizures.
Interactions with other medicines:
- *
10. Paracetamol
Oral liquid: 120 mg/5 mL
Suppository: 100 mg
Tablet: 100–500 mg
Injection (for IV infusion): 10 mg/mL
Uses: mild-to-moderate pain, including dysmenorrhoea and headache; pain relief in osteoarthritis and soft tissue lesions; pyrexia including postimmunization pyrexia; acute migraine attack.
Precautions: hepatic impairment; renal impairment; alcohol dependence; breastfeeding. Unintentional overdose of paracetamol resulting in hepatotoxicity and death can occur. To reduce this risk, the dose of paracetamol should not exceed the maximum recommended dose, should be appropriate for the weight of the patient, and should be reduced when risk factors for hepatotoxicity exist.
Dose:
Mild-to-moderate pain, pyrexia, by mouth or by rectum, ADULT, 0.5–1 g every 4–6 hours, maximum 4 g daily.
IV paracetamol can be used when administration Per Oral or Per Rectal is not possible. The dose depends on body weight and the presence/absence of risk factors for paracetamol hepatotoxicity:
>50 kg, 1 g up to q4h, maximum recommended dose 4 g/24h
>50 kg plus any risk factors, restrict maximum dose to 3 g/24h
10–50 kg, 15 mg/kg up to q4h, maximum recommended dose 60 mg/kg/24h.
For patients with severe renal impairment, (creatinine clearance <30 mL/min) the minimum interval must be ≥q6h.
Adverse effects: rare but rash and blood disorders reported; important: liver damage (and less frequently renal damage) following overdosage.
