Paracetamol

Anilides. Analgesics and antipyretics

ATC code: N02BE01 (Paracetamol)

Brand names

Acetaminophen, Tylenol, Panadol, Ofirmev

Mechanism of action

The analgesic mechanism is not fully established. Proposed pathways include central COX-2 inhibition and, per current data, interaction with the endocannabinoid system via the active metabolite AM404. Unlike NSAIDs, it does not appreciably inhibit peripheral COX and has no anti-inflammatory effect. The antipyretic effect is mediated through the hypothalamic thermoregulatory center.

Indications

Fever

First line

Paracetamol is first-line for symptomatic fever reduction in adults and children. Pediatric dose: 15 mg/kg every 4–6 hours, up to 60 mg/kg/day. Lowering fever does not speed recovery from infection and is only used when fever is poorly tolerated. In children with a history of febrile seizures, paracetamol does not prevent recurrences.

Sources

Migraine

First line

In mild to moderate migraine attacks, paracetamol 1000 mg is an acceptable first-line option in patients who cannot tolerate NSAIDs or triptans. Efficacy in severe attacks is lower than triptans and NSAIDs. Taking it early in the attack (within 30 minutes of pain onset) improves efficacy.

Sources

Mild to moderate pain in adults

First line

Mild to moderate pain is a core indication. Adults: 500–1000 mg every 4–6 hours, up to 4 g/day in healthy adults, up to 3 g/day in the elderly, chronic alcohol users, or malnourished patients. Paracetamol is less effective than NSAIDs for inflammatory pain (osteoarthritis, dysmenorrhea) but is preferred in patients with NSAID contraindications: peptic ulcer, anticoagulants, renal failure, heart failure, aspirin-exacerbated respiratory disease.

Sources

Osteoarthritis

Second line

In current OA 2022 and 2019 recommendations, paracetamol has moved to a second-line position in osteoarthritis in favor of topical NSAIDs and short-course systemic NSAIDs. It is recommended as an alternative in patients with NSAID contraindications. Long-term paracetamol for osteoarthritis has not shown substantial benefit over placebo in recent systematic reviews.

Sources

NICE: Depression in adults: treatment and management (NG222) (2022)

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Anti-aging and longevity

Not recommended

Paracetamol (acetaminophen) is a non-opioid analgesic and antipyretic. It is taken for acute pain (headache, dental, muscular), fever, and dysmenorrhea (AEMPS Ficha Técnica). Paracetamol is often taken for any discomfort or prophylactically before exercise as a universal analgesic. Prophylactic use is not justified: 2020 guidelines for osteoarthritis rank paracetamol lower than previously thought; the Cochrane review by Leopoldino 2019 showed a clinically insignificant effect in knee and hip osteoarthritis versus placebo. Regular paracetamol use raises the risk of hepatotoxicity (especially with alcohol), and at high doses (over 4 g/day or less with liver disease) can cause acute liver failure. If paracetamol is being taken daily as discomfort prophylaxis, consider seeking a second opinion.

Sources

Practical notes

Timing and administration

Take with or without food. For pain, take as needed with a minimum 4-hour interval between doses. Effervescent and soluble formulations provide a faster onset of action (20–30 minutes versus 45–60 minutes for standard tablets) and may be preferred for acute pain.

Special situations

Maximum daily dose is 4 g in healthy adults and 3 g in the elderly, chronic alcohol users, low-body-weight patients (under 50 kg), or malnourished patients. In patients under 50 kg, calculate the dose at 60 mg/kg/day. Do not combine with other paracetamol-containing products (many combination cold medications): risk of unintentional overdose.

Common myths

Myth: 'paracetamol is the safest analgesic, take as much as you want'. Fact: paracetamol is a leading cause of acute liver failure worldwide. Safety critically depends on adhering to the maximum daily dose.

Myth: 'paracetamol relieves inflammation'. Fact: paracetamol lacks anti-inflammatory activity. Inflammatory conditions are best treated with NSAIDs when not contraindicated.

Myth: 'children can have it as needed'. Fact: in children the dose is strictly 15 mg/kg per dose no more often than every 4–6 hours and no more than 4–5 times daily. Overdose in children is hepatotoxic.

Drug–drug interactions

10 pairs found. Sorted from critical to minor.

Moderate

Ciclosporin

Immunosuppressants. Calcineurin inhibitors

Mechanism

Paracetamol does not interact significantly with ciclosporin in short courses. On long-term high-dose use (over 3 g/day for more than 7 days), mild hepatocyte suppression may slightly amplify ciclosporin hepatotoxicity.

Symptoms

Fatigue, nausea, jaundice, elevated liver enzymes. Symptoms with long-term therapy are rare.

Management

Paracetamol remains the analgesic and antipyretic of choice in transplant patients. For chronic need, cap at 2 g/day. Check ALT, AST, GGT monthly. If enzymes rise 2–3-fold above the upper limit, stop paracetamol temporarily.

Sources

FDA: Sandimmune (cyclosporine) prescribing information (2015)

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Moderate

Warfarin

Vitamin K antagonist anticoagulants

Mechanism

Paracetamol at doses above 3 g/day for more than 7 days raises INR by 1–1.5 via hepatocyte suppression and weak effect on warfarin metabolism. A single 0.5–1 g dose is safe.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, black or tarry stools, haematuria. Higher risk in older patients, prior peptic ulcer disease, and chronic kidney disease.

Management

Paracetamol remains the analgesic and antipyretic of choice on warfarin, but for chronic use cap at 2 g/day. For full-dose courses longer than 4 days: check INR after a week; if above target, reduce warfarin by 10%.

Sources

Pair details →

Minor

Bisoprolol

Selective beta-adrenergic blockers

Mechanism

Paracetamol and bisoprolol are metabolised by different pathways. No direct pharmacokinetic interaction.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. Paracetamol remains the analgesic of choice in patients on bisoprolol.

Sources

FDA: Acetaminophen prescribing information (OTC monograph) (2020)

Pair details →

Minor

Cetirizine

Second-generation antihistamines

Mechanism

Paracetamol and cetirizine are metabolised by different pathways. No direct pharmacokinetic interaction.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. The combination is standard in symptomatic formulations for acute respiratory infections and allergy.

Sources

FDA: Acetaminophen prescribing information (OTC monograph) (2020)

Pair details →

Minor

Curcumin (Curcuma longa extract)

Herbal anti-inflammatory agents

Mechanism

Curcumin (Curcuma longa extract) theoretically weakly inhibits CYP2E1, which produces paracetamol's hepatotoxic metabolite NAPQI. For short paracetamol courses, hepatotoxicity risk may be slightly reduced. Clinical data are limited.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. Dietary curcumin (curry, golden milk) does not clinically affect paracetamol metabolism. At supplement doses of curcumin (500–1000 mg/day), no clinically significant interaction has been documented. Paracetamol limit: up to 3 g/day.

Sources

FDA: Acetaminophen prescribing information (OTC monograph) (2020)

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Minor

Echinacea purpurea (juice/extract)

Herbal immunomodulators (local classification)

Mechanism

Echinacea purpurea modulates CYP1A2 and CYP3A4 in vitro, but the in vivo effect is minimal. No direct pharmacokinetic interaction with paracetamol has been described.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. The combination is standard in over-the-counter use for acute respiratory infections. Echinacea's efficacy as an immunostimulant is not confirmed by large randomised trials (Cochrane Review 2014).

Sources

Indiana University: Flockhart Table of Drug Interactions (CYP isoforms) (2023)

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Minor

Hypericum perforatum

Antidepressants. Other antidepressants of herbal origin

Mechanism

St John's wort is a CYP3A4 inducer and a weak CYP2E1 inducer. It may theoretically increase formation of paracetamol's hepatotoxic metabolite NAPQI on long-term combination, but clinical cases are rare.

Symptoms

Fatigue, nausea, jaundice, elevated liver enzymes. Symptoms possible on long-term combination (over 1 month) and high paracetamol dose (over 3 g/day).

Management

For short paracetamol courses (3–7 days), no specific adjustment needed. On long-term combination (St John's wort as phytotherapy for depression), cap paracetamol at 2 g/day. St John's wort has many interactions via CYP3A4 induction (contraceptives, warfarin, SSRIs) — reconsider its use.

Sources

Indiana University: Flockhart Table of Drug Interactions (CYP isoforms) (2023)

Pair details →

Minor

Loratadine

Second-generation antihistamines

Mechanism

Paracetamol and loratadine are metabolised by different pathways. No direct pharmacokinetic interaction.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. The combination is standard in symptomatic formulations for acute respiratory infections and allergy.

Sources

FDA: Acetaminophen prescribing information (OTC monograph) (2020)

Pair details →

Minor

Metoprolol

Selective β1-adrenoceptor blockers

Mechanism

Paracetamol is metabolised by CYP2E1 (5%) and predominantly by glucuronidation; metoprolol by CYP2D6. No direct pharmacokinetic interaction.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. Paracetamol remains the analgesic of choice in patients on metoprolol.

Sources

FDA: Acetaminophen prescribing information (OTC monograph) (2020)

Pair details →

Minor

Metronidazole

Imidazole derivatives (antiprotozoal / antibacterial)

Mechanism

No direct pharmacokinetic interaction. Co-administration at standard doses is safe.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. Paracetamol remains the analgesic and antipyretic of choice on metronidazole.

Sources

Pair details →

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Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMA

Spanish Medicines Information Centre (CIMA)

Label dated: 04/03/2025

FDA / DailyMed

FDA — DailyMed Drug Labels

Label dated: 01/02/2026

GRLS

Russian State Register of Medicines

Label dated: 04/09/2026

Safety

Boxed warning

Hepatotoxicity in overdose. Daily doses above 4 g in adults (above 3 g in at-risk patients) can cause severe acute liver injury up to hepatic failure. The antidote is N-acetylcysteine.

Contraindications

Severe hepatic impairment
Acute hepatitis
Hypersensitivity

Serious adverse effects

Hepatotoxicity in overdose — acute liver failure (a leading cause of ALF worldwide)
Anaphylaxis (very rare)
Stevens-Johnson syndrome, toxic epidermal necrolysis (very rare)

Common adverse effects

At recommended doses, adverse effects are rare and minimal

Uncommon adverse effects

Allergic skin reactions
Transaminase elevation

PregnancyFDA B

Paracetamol is first-line for pain and fever in any trimester (historically FDA category B; the FDA pregnancy categories were retired in 2015). Earlier observational studies linked long-term third-trimester use to ADHD and autism, but the largest study to date — a Swedish sibling-controlled cohort (Ahlqvist VH et al. JAMA. 2024;331(14):1205–1214, n = 2.48 million children) — found no association after controlling for familial factors. Current view: standard doses for indicated use remain a safe option; unnecessary long-term high-dose use is still avoided.

Breastfeeding

Hale L1 · Compatible

Compatible with breastfeeding. Minimal concentrations in milk; one of the preferred analgesics in lactation.

Milk-to-plasma ratio: 0.91

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Frequently asked

What is Paracetamol used for?

Paracetamol is evaluated for the following indications with varying evidence strength: Fever (evidence tier A), Migraine (evidence tier A), Mild to moderate pain in adults (evidence tier A). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Paracetamol?

Common side effects of Paracetamol (≥ 1 in 100): At recommended doses, adverse effects are rare and minimal. See the Safety section for uncommon and serious reactions.

Is Paracetamol safe during pregnancy?

FDA category B. Paracetamol is first-line for pain and fever in any trimester (historically FDA category B; the FDA pregnancy categories were retired in 2015). Earlier observational studies linked long-term third-trimester use to ADHD and autism, but the largest study to date — a Swedish sibling-controlled cohort (Ahlqvist VH et al. JAMA. 2024;331(14):1205–1214, n = 2.48 million children) — found no association after controlling for familial factors. Current view: standard doses for indicated use remain a safe option; unnecessary long-term high-dose use is still avoided.

Is Paracetamol compatible with breastfeeding?

Compatible with breastfeeding. Minimal concentrations in milk; one of the preferred analgesics in lactation.

Who should not take Paracetamol?

Paracetamol is contraindicated in: Severe hepatic impairment; Acute hepatitis; Hypersensitivity. Full list in the Safety section.

Does Paracetamol carry an FDA boxed warning?

Hepatotoxicity in overdose. Daily doses above 4 g in adults (above 3 g in at-risk patients) can cause severe acute liver injury up to hepatic failure. The antidote is N-acetylcysteine.

paracetamol is the safest analgesic, take as much as you want

paracetamol is a leading cause of acute liver failure worldwide. Safety critically depends on adhering to the maximum daily dose.

paracetamol relieves inflammation

paracetamol lacks anti-inflammatory activity. Inflammatory conditions are best treated with NSAIDs when not contraindicated.

children can have it as needed

in children the dose is strictly 15 mg/kg per dose no more often than every 4–6 hours and no more than 4–5 times daily. Overdose in children is hepatotoxic.

Mechanism of action

Practical notes

Timing and administration

Special situations

Common myths

Drug–drug interactions

10 pairs found. Sorted from critical to minor.

Moderate

Ciclosporin

Immunosuppressants. Calcineurin inhibitors

Mechanism

Symptoms

Fatigue, nausea, jaundice, elevated liver enzymes. Symptoms with long-term therapy are rare.

Management

Sources

FDA: Sandimmune (cyclosporine) prescribing information (2015)

Pair details →

Moderate

Warfarin

Vitamin K antagonist anticoagulants

Mechanism

Paracetamol at doses above 3 g/day for more than 7 days raises INR by 1–1.5 via hepatocyte suppression and weak effect on warfarin metabolism. A single 0.5–1 g dose is safe.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, black or tarry stools, haematuria. Higher risk in older patients, prior peptic ulcer disease, and chronic kidney disease.

Management

Sources

Pair details →

Minor

Bisoprolol

Selective beta-adrenergic blockers

Mechanism

Paracetamol and bisoprolol are metabolised by different pathways. No direct pharmacokinetic interaction.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. Paracetamol remains the analgesic of choice in patients on bisoprolol.

Sources

FDA: Acetaminophen prescribing information (OTC monograph) (2020)

Pair details →

Minor

Cetirizine

Second-generation antihistamines

Mechanism

Paracetamol and cetirizine are metabolised by different pathways. No direct pharmacokinetic interaction.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. The combination is standard in symptomatic formulations for acute respiratory infections and allergy.

Sources

FDA: Acetaminophen prescribing information (OTC monograph) (2020)

Pair details →

Minor

Curcumin (Curcuma longa extract)

Herbal anti-inflammatory agents

Mechanism

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

Sources

FDA: Acetaminophen prescribing information (OTC monograph) (2020)

Pair details →

Minor

Echinacea purpurea (juice/extract)

Herbal immunomodulators (local classification)

Mechanism

Echinacea purpurea modulates CYP1A2 and CYP3A4 in vitro, but the in vivo effect is minimal. No direct pharmacokinetic interaction with paracetamol has been described.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

Sources

Indiana University: Flockhart Table of Drug Interactions (CYP isoforms) (2023)

Pair details →

Minor

Hypericum perforatum

Antidepressants. Other antidepressants of herbal origin

Mechanism

Symptoms

Fatigue, nausea, jaundice, elevated liver enzymes. Symptoms possible on long-term combination (over 1 month) and high paracetamol dose (over 3 g/day).

Management

Sources

Indiana University: Flockhart Table of Drug Interactions (CYP isoforms) (2023)

Pair details →

Minor

Loratadine

Second-generation antihistamines

Mechanism

Paracetamol and loratadine are metabolised by different pathways. No direct pharmacokinetic interaction.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. The combination is standard in symptomatic formulations for acute respiratory infections and allergy.

Sources

FDA: Acetaminophen prescribing information (OTC monograph) (2020)

Pair details →

Minor

Metoprolol

Selective β1-adrenoceptor blockers

Mechanism

Paracetamol is metabolised by CYP2E1 (5%) and predominantly by glucuronidation; metoprolol by CYP2D6. No direct pharmacokinetic interaction.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. Paracetamol remains the analgesic of choice in patients on metoprolol.

Sources

FDA: Acetaminophen prescribing information (OTC monograph) (2020)

Pair details →

Minor

Metronidazole

Imidazole derivatives (antiprotozoal / antibacterial)

Mechanism

No direct pharmacokinetic interaction. Co-administration at standard doses is safe.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. Paracetamol remains the analgesic and antipyretic of choice on metronidazole.

Sources

Pair details →

Safety

Boxed warning

Hepatotoxicity in overdose. Daily doses above 4 g in adults (above 3 g in at-risk patients) can cause severe acute liver injury up to hepatic failure. The antidote is N-acetylcysteine.

Contraindications

Severe hepatic impairment
Acute hepatitis
Hypersensitivity

Serious adverse effects

Hepatotoxicity in overdose — acute liver failure (a leading cause of ALF worldwide)
Anaphylaxis (very rare)
Stevens-Johnson syndrome, toxic epidermal necrolysis (very rare)

Common adverse effects

At recommended doses, adverse effects are rare and minimal

Uncommon adverse effects

Allergic skin reactions
Transaminase elevation

PregnancyFDA B

Breastfeeding

Hale L1 · Compatible

Compatible with breastfeeding. Minimal concentrations in milk; one of the preferred analgesics in lactation.

Milk-to-plasma ratio: 0.91

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Frequently asked

What is Paracetamol used for?

What are the side effects of Paracetamol?

Common side effects of Paracetamol (≥ 1 in 100): At recommended doses, adverse effects are rare and minimal. See the Safety section for uncommon and serious reactions.

Is Paracetamol safe during pregnancy?

Is Paracetamol compatible with breastfeeding?

Compatible with breastfeeding. Minimal concentrations in milk; one of the preferred analgesics in lactation.

Who should not take Paracetamol?

Paracetamol is contraindicated in: Severe hepatic impairment; Acute hepatitis; Hypersensitivity. Full list in the Safety section.

Does Paracetamol carry an FDA boxed warning?

Hepatotoxicity in overdose. Daily doses above 4 g in adults (above 3 g in at-risk patients) can cause severe acute liver injury up to hepatic failure. The antidote is N-acetylcysteine.

paracetamol is the safest analgesic, take as much as you want

paracetamol is a leading cause of acute liver failure worldwide. Safety critically depends on adhering to the maximum daily dose.

paracetamol relieves inflammation

paracetamol lacks anti-inflammatory activity. Inflammatory conditions are best treated with NSAIDs when not contraindicated.

children can have it as needed

in children the dose is strictly 15 mg/kg per dose no more often than every 4–6 hours and no more than 4–5 times daily. Overdose in children is hepatotoxic.