Acetaminophen (IV) | Medication Reference

Bedside Snapshot

Core Use: IV formulation provides rapid systemic exposure for analgesia and antipyresis when oral/enteral routes are not feasible (NPO, vomiting, bowel rest, perioperative)
Onset/Duration: Onset of analgesia within 5–10 minutes, peak effect ~15–30 minutes after infusion
Typical Dosing: Adults ≥50 kg: 650 mg IV q4h or 1,000 mg IV q6h, maximum 4 g/day (including all APAP sources)
Key Danger: Must be infused over at least 15 minutes to reduce risk of hypotension; same hepatotoxicity risks as oral acetaminophen—IV route does not make it safer at high doses
Special Note: Only more reliable than oral when GI absorption is an issue; same daily maximums apply

Brand & Generic Names

Generic Name: Acetaminophen (paracetamol)
Brand Names: Ofirmev and generics (IV acetaminophen)

Medication Class

Non-opioid analgesic and antipyretic (intravenous formulation)

Pharmacology

Mechanism of Action:

Primarily central inhibition of prostaglandin synthesis via weak cyclooxygenase (COX) inhibition, possibly COX-2 and variant COX enzymes in the CNS
Modulation of serotonergic descending pain pathways and potential endocannabinoid system effects contribute to analgesia
Minimal peripheral anti-inflammatory activity; not an NSAID and lacks platelet inhibition or significant GI mucosal toxicity at therapeutic doses

Pharmacokinetics:

Absorption: 100% systemic bioavailability as IV infusion; bypasses GI tract and first-pass variability
Distribution: Similar to oral acetaminophen; rapid achievement of therapeutic plasma and CSF concentrations following a 15-minute infusion
Metabolism: Same hepatic pathways (glucuronidation, sulfation, CYP2E1 to NAPQI) as oral acetaminophen
Elimination: Half-life ~2–3 hours in normal hepatic function
Clinical Note: PK advantages are primarily in speed and reliability of onset when enteral route is compromised, not in total exposure or intrinsic safety

Indications

Moderate pain requiring parenteral therapy when oral/enteral route is not available (e.g., immediate post-op, active vomiting, bowel obstruction)
Part of opioid-sparing multimodal analgesia in perioperative and trauma patients
Antipyresis in critically ill patients when rapid temperature reduction is desired and oral/enteral therapy is not feasible
Preferred over IV NSAIDs in some patients with renal insufficiency, bleeding risk, or NSAID intolerance

Dosing & Administration

Available Forms:

Ready-to-use IV solution: 1,000 mg/100 mL (10 mg/mL) in a glass bottle or bag (adult formulation)
Pediatric dosing often uses the same 10 mg/mL solution, dosed by weight and delivered via controlled infusion pump
Do not add other medications to the acetaminophen IV container; administer as a separate infusion line or ensure Y-site compatibility per institutional guidance

Dosing – IV Acetaminophen:

Patient Group	Dose	Frequency	Maximum Daily Dose
Adults and adolescents ≥50 kg	650 mg IV or 1,000 mg IV	Q4h (650 mg) or q6h (1,000 mg)	≤4,000 mg/day total APAP
Adults/adolescents <50 kg	12.5–15 mg/kg IV	Q4–6h	≤75 mg/kg/day, max 3,750 mg/day
Children 2–12 years	12.5 mg/kg IV	Q4h (or 15 mg/kg q6h)	≤75 mg/kg/day; confirm with pediatric protocols
Hepatic impairment / chronic EtOH	Reduce per-dose target	Extend interval; lower per-dose	Often ≤2,000 mg/day total APAP
Infusion duration	Over ≥15 minutes for all doses (rapid bolus may cause hypotension)

Contraindications

Absolute Contraindications:

Severe hepatic impairment or active severe hepatic disease
Known serious hypersensitivity to acetaminophen or IV formulation excipients

Major Precautions:

Same hepatotoxicity concerns as oral acetaminophen; IV does not reduce toxicity if total daily dose is excessive
Use caution in chronic alcohol use, malnutrition, low body weight, or any condition impairing glutathione stores
Monitor for hypotension during/after infusion, especially in hemodynamically unstable patients or those receiving other vasodilating agents
IV formulation may contain additional excipients (e.g., mannitol in some products); consider total osmolar and solute load in patients requiring fluid restriction or with renal issues

Critical Warning: IV acetaminophen carries the same hepatotoxicity risk as oral formulations. Overdosing IV acetaminophen is just as hepatotoxic as oral and may be easier to do via infusion errors. Must infuse over at least 15 minutes to reduce hypotension risk.

Adverse Effects

Common:

Injection-site discomfort or irritation
Nausea, vomiting
Mild hypotension or flushing during infusion

Serious:

Hepatotoxicity and acute liver failure with supratherapeutic dosing or chronic overuse (same as oral)
Anaphylaxis or serious hypersensitivity reactions (rare)
Severe hypotension in susceptible patients with rapid administration

Special Populations

Hepatic Impairment:

Reduce total daily dose; often limited to ≤2,000 mg/day total acetaminophen
Extend dosing interval and reduce per-dose amount
Consider alternative analgesic/antipyretic in severe hepatic disease

Renal Impairment:

No major dose adjustment for isolated renal impairment
Consider extending interval to q8h in severe CKD or hemodialysis
Monitor for fluid overload from IV formulation volume

Geriatric Patients:

Use lower doses in frail or low-body-weight elderly patients
Maximum often limited to ≤2–3 g/day
Monitor carefully for hypotension during infusion

Pregnancy & Lactation:

Generally considered safe in pregnancy when used at therapeutic doses
Crosses placenta; appears in breast milk at low concentrations
Use lowest effective dose for shortest duration

Pediatric Considerations:

Weight-based dosing: 12.5 mg/kg IV q4h or 15 mg/kg IV q6h
Maximum: 75 mg/kg/day, not to exceed 3,750 mg/day
Use specialized pediatric references for infants and younger children

Monitoring

Clinical Monitoring:

Track total daily acetaminophen from all routes and formulations (IV, oral, rectal, combo products)
Observe blood pressure during infusion, particularly in unstable or vasodilated patients
Assess pain and fever control; adjust dosing as needed

Laboratory Monitoring:

Monitor liver function tests in patients receiving repeated IV doses, especially with liver disease or high-dose therapy
For suspected overdose or dosing errors, obtain serum acetaminophen levels and contact toxicology/poison center promptly

Clinical Pearls

Route Transition: IV acetaminophen is most useful in the first 24–48 hours post-op or in NPO patients; switch to oral/enteral as soon as feasible for cost and simplicity.

Hepatotoxicity Risk: Do not assume IV is more benign—overdosing IV acetaminophen is just as hepatotoxic as oral and may be easier to do via infusion errors. Always track total daily dose from all sources.

Multimodal Analgesia: In multimodal analgesia bundles, scheduled IV acetaminophen can reduce early opioid requirements, particularly in major surgery or trauma.

Medication Reconciliation: Be meticulous with medication reconciliation so that IV acetaminophen orders are adjusted or stopped once oral/enteral acetaminophen is started to avoid duplicate dosing.

Infusion Rate: Always infuse over at least 15 minutes. Rapid administration can cause significant hypotension, especially in hemodynamically unstable patients.

References

1. Lexicomp. (2024). Acetaminophen (intravenous): Drug information. Wolters Kluwer.
2. Ofirmev (acetaminophen) [Package insert]. (2020). Mallinckrodt Pharmaceuticals.
3. Dunn, J. S., & Durieux, M. E. (2017). Perioperative use of intravenous acetaminophen. Anesthesiology Clinics, 35(2), 341–349.
4. Jibril, F., Sharaby, S., Mohamed, A., & Wilby, K. J. (2015). Intravenous versus oral acetaminophen for pain: Systematic review of current evidence to support clinical decision-making. Canadian Journal of Hospital Pharmacy, 68(3), 238–247.
5. Oscier, C. D., & Milner, Q. J. (2009). Peri-operative use of paracetamol. Anaesthesia, 64(1), 65–72.