Drug reference

Ibuprofen + Paracetamol

NSAID · Analgesic, Antipyretic, Anti-inflammatory

Also known as Combiflam, Ibugesic Plus, Flexon, Febrex Plus, Sumo, Pacimol-IB

NSAIDAnalgesic, Antipyretic, Anti-inflammatoryATC M01AE51

CDSCO approvedATC M01AE51

Pharmacokineticsplasma · t hours

ONSET: 45min · Ibuprofen: ~30-60 minutes. Paracetamol: ~15-30 minutes.
PEAK: 1.5h · Ibuprofen: ~1-2 hours. Paracetamol: ~0.5-2 hours.
t½: 2.7h · Ibuprofen: ~1.8-3.5 hours. Paracetamol: ~1.5-3 hours.
DURATION: 5h · Ibuprofen: ~4-6 hours. Paracetamol: ~4-6 hours.

EXCRETION

—

not curated

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

Ibuprofen is Pregnancy Category C (first and second trimester) and D (third trimester). Paracetamol is Pregnancy Category B. The combination is generally considered Category C, becoming D in the third trimester due to the NSAID component. NSAIDs should be avoided in late pregnancy due to risk of premature closure of the ductus arteriosus and renal dysfunction in the foetus. Use only if potential benefit justifies the potential risk to the fetus.

FDA category + note

Top interactionssee all 12 →

SulfasalazineContraindicatedTextbookG&G 14e · p1112
AminoglycosideSevereTextbookKDT 7e · p746
AminoglycosidesSevereTextbookKDT 7e
AnticoagulantsSevereTextbookKDT 7e

Mechanism

Ibuprofen inhibits prostaglandin synthesis by non-selectively blocking cyclooxygenase (COX-1 and COX-2) enzymes, providing anti-inflammatory, analgesic, and antipyretic effects primarily at peripheral sites. Paracetamol (acetaminophen) primarily acts centrally, inhibiting prostaglandin synthesis in the brain and spinal cord, and may involve other mechanisms like activation of descending serotonergic pathways and modulation of the endocannabinoid system, contributing to its analgesic and antipyretic actions. The combination offers complementary mechanisms, targeting both peripheral inflammation and central pain pathways. Combination rationale: The combination of ibuprofen and paracetamol provides synergistic analgesic and antipyretic effects with distinct mechanisms of action, allowing for potentially lower individual doses and a broader spectrum of pain and fever relief. Ibuprofen addresses inflammation peripherally through COX inhibition, while paracetamol acts centrally, leading to enhanced efficacy, particularly for inflammatory pain and conditions requiring both anti-inflammatory and potent analgesic action.

Indications

Mild to moderate pain (e.g., headache, dental pain, muscular pain, menstrual pain)FeverSymptomatic relief of inflammatory conditions (e.g., osteoarthritis, rheumatoid arthritis, sprains, strains)Post-operative pain

Dosing

Adult: Oral: One tablet containing Ibuprofen 400mg + Paracetamol 325mg (or similar strengths like 300mg/500mg) 2-3 times daily, or as directed by physician. Should be taken with food to minimize GI upset.
Pediatric: Generally not recommended for children under 12 years due to fixed dose combination. For older children (12-18 years), dosing should be carefully considered, typically 1 tablet (Ibuprofen 400mg + Paracetamol 325mg) 1-2 times daily, with strict adherence to weight-based limits for paracetamol. Consult a pediatrician for precise dosing and consider individual components if combination is unsuitable.
Renal adjustment: Exercise caution in mild-moderate renal impairment. Contraindicated in severe renal impairment (Creatinine Clearance < 30 mL/min) due to ibuprofen, which can exacerbate renal dysfunction. Paracetamol requires dose reduction in severe impairment and monitoring.
Hepatic adjustment: Contraindicated in severe hepatic impairment due to both components. Use with extreme caution and reduced doses in mild-moderate impairment. Paracetamol carries a risk of hepatotoxicity, especially with pre-existing liver disease.
Geriatric: Initiate at lower end of dosing range. Increased risk of gastrointestinal adverse effects (bleeding, ulceration), renal dysfunction, and cardiovascular events. Monitor closely for adverse reactions.
Max dose: The maximum daily dose for Ibuprofen is typically 1200mg-2400mg (for anti-inflammatory effect); for Paracetamol, it is 3000mg-4000mg. The combination dose should not exceed 3 tablets of 400mg Ibuprofen + 325mg Paracetamol strength per day (i.e., Max Ibuprofen 1200mg, Max Paracetamol 975mg), ensuring neither component exceeds its individual maximum.

Pharmacokinetics

Onset

Ibuprofen: ~30-60 minutes. Paracetamol: ~15-30 minutes.

Peak effect

Ibuprofen: ~1-2 hours. Paracetamol: ~0.5-2 hours.

Duration

Ibuprofen: ~4-6 hours. Paracetamol: ~4-6 hours.

Half-life

Ibuprofen: ~1.8-3.5 hours. Paracetamol: ~1.5-3 hours.

Bioavailability

Ibuprofen: ~80-100% (oral). Paracetamol: ~60-90% (oral).

Protein binding

Ibuprofen: >99%. Paracetamol: ~10-25% at therapeutic concentrations.

Metabolism

Ibuprofen: Extensively metabolized in the liver by oxidation via CYP2C9 to inactive metabolites. Paracetamol: Primarily metabolized in the liver by glucuronidation and sulfation. A small portion is metabolized by CYP2E1/1A2 to a toxic intermediate (NAPQI), which is rapidly detoxified by glutathione.

Excretion

Both primarily excreted renally as inactive metabolites and conjugates.

Contraindications

Hypersensitivity to ibuprofen, paracetamol, or other NSAIDs
Active or history of recurrent peptic ulcer/haemorrhage
Severe heart failure
Severe renal or hepatic impairment
Patients with asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs
Third trimester of pregnancy
Recent coronary artery bypass graft (CABG) surgery
History of gastrointestinal bleeding or perforation related to previous NSAID therapy

Side effects

Common

Gastrointestinal disturbances (nausea, dyspepsia, abdominal pain, diarrhea, constipation)HeadacheDizzinessSkin rashFluid retention (due to ibuprofen)Elevated liver enzymes

Serious

Gastrointestinal bleeding and ulceration
Renal impairment (acute kidney injury, renal papillary necrosis)
Hepatic toxicity (especially with paracetamol overdose)
Cardiovascular thrombotic events (e.g., myocardial infarction, stroke) with ibuprofen
Severe cutaneous adverse reactions (e.g., Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis)
Hypersensitivity reactions (bronchospasm, angioedema, anaphylaxis)
Blood dyscrasias (e.g., anaemia, thrombocytopenia)

Pregnancy & lactation

Pregnancy

Lactation

Ibuprofen is generally considered compatible with breastfeeding at usual analgesic doses (Lactation Risk Category L2). Paracetamol is also considered safe for breastfeeding mothers (Lactation Risk Category L1). However, caution is advised, and use of the combination should be under medical supervision, especially for prolonged use or high doses.