Paracetamol Use in Dengue Fever
Yes, paracetamol can be given in dengue, but standard doses (4 g/day) significantly increase liver injury and should be avoided—limit to ≤3 g/day (1000 mg every 8 hours) to minimize hepatotoxicity while managing fever. 1, 2
Evidence Against Standard-Dose Paracetamol in Dengue
The most recent and highest-quality evidence comes from a 2019 randomized controlled trial that was terminated early due to safety concerns:
Standard-dose paracetamol (median 1.5 g/day) increased transaminase elevation >3× upper limit of normal from 10% (placebo) to 22% (paracetamol group), with an incidence rate ratio of 3.77 (95% CI 1.36-10.46, p=0.011). 1
Paracetamol caused significantly higher daily increases in both AST (mean difference 12.43 U/L per day, p<0.0001) and ALT (7.40 U/L per day, p=0.0001) compared to placebo, without providing any counterbalancing benefit in fever or pain reduction. 1
A 2015 prospective observational study confirmed that acetaminophen doses >8 g total (not per day, but cumulative during illness) were independently associated with transaminitis (OR 4.62,95% CI 1.37-13.18), along with male gender. 2
Why Paracetamol Does NOT Mask the Critical Phase
The concern about "masking" the critical phase is a common misconception. Here's why paracetamol is still recommended despite hepatotoxicity concerns:
Dengue itself causes transaminitis in 97% of patients (AST elevation) and 75% (ALT elevation) independent of paracetamol use. 2 The liver injury is intrinsic to dengue pathophysiology, not solely drug-induced.
The critical phase of dengue (plasma leakage, thrombocytopenia, hemorrhage) is monitored through hematocrit changes, platelet counts, and clinical signs of plasma leakage—not fever patterns. Fever typically defervesces at the onset of the critical phase regardless of antipyretic use, so paracetamol does not obscure this transition. 1, 2
In a retrospective analysis of 113 dengue patients with severe hepatitis receiving paracetamol, 88.5% showed improvement in ALT levels, and only 11.5% had worsening liver function. Of those with worsening, 61.5% were discharged without clinical deterioration, and the 5 deaths observed were unrelated to liver dysfunction. 3
Recommended Dosing Algorithm for Dengue Patients
Use the lowest effective dose and shortest duration:
Maximum 1000 mg every 8 hours (total 3 g/day maximum) rather than the standard 4 g/day dosing. 2, 4
Avoid cumulative doses >8 g total during the illness course. 2
Monitor liver function tests (AST/ALT) at baseline and during treatment, especially in male patients who have higher risk of transaminitis. 2
For patients with baseline AST or ALT >3× upper limit of normal, consider avoiding paracetamol entirely or using even lower doses (≤2 g/day). 5, 1
Critical Pitfalls to Avoid
Do not use standard 4 g/day dosing in dengue patients—the 2019 RCT provides Level I evidence that this increases hepatotoxicity without clinical benefit. 1
Dengue patients already have compromised liver function (97% have elevated AST), making them analogous to the high-risk populations described in acetaminophen toxicity guidelines where maximum doses should be 2-3 g/day. 5, 2
NSAIDs remain contraindicated due to bleeding risk from thrombocytopenia, though recent data suggest low-dose ibuprofen (≤0.6 g cumulative) may have comparable safety to acetaminophen with potentially better efficacy and less hepatotoxicity. 4, 6 However, this remains investigational and current guidelines still favor paracetamol over NSAIDs.
Combination products containing paracetamol (e.g., cold/flu remedies) must be accounted for to prevent inadvertent overdose. 5
Monitoring Strategy
Monitor hematocrit and platelet counts daily to detect the critical phase—these parameters, not fever patterns, define disease progression. 1
Repeat liver function tests if paracetamol is continued beyond 2-3 days or if clinical deterioration occurs. 1, 3
Discontinue paracetamol immediately if ALT rises >3× baseline or if new hepatic symptoms develop (right upper quadrant pain, jaundice, coagulopathy). 5, 1