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Ibuprofen + Caffeine Ibuprofen + Caffeine
Ibuprofen + Caffeine Ibuprofen + Caffeine

Ibuprofen plus caffeine is a well-tolerated combination in which ibuprofen acts as an anti-inflammatory, antipyretic and analgesic drug. Caffeine is a central nervous system stimulant and smooth muscle relaxant which helps in increasing the blood flow.

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Ibuprofen plus caffeine is a well tolerated combination in which ibuprofen acts as an anti-inflammatory, antipyretic and analgesic drug. Caffeine is a central nervous system stimulant and smooth muscle relaxant which helps in increasing the blood flow. Its combination with ibuprofen has shown better results in acute pain.

Pharmacological Class: NSAID and central nervous system stimulant


  • Tension type headache and migraine
  • Post oral surgery dental pain
  • Rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, cervical spondylitis, intervertebral disc syndrome, and sciatica
  • Non-articular rheumatic conditions including fibrositis, myositis, bursitis and low back pain
  • Soft tissue injuries such as sprains, strains and sports injuries
  • Painful inflammatory conditions in gynecology
  • Post-operative and post-traumatic inflammation
  • Acute gout

Pharmachologic action

Ibuprofen is a non-selective inhibitor of cyclooxygenase which is responsible for the synthesis of prostaglandin via arachidonic acid pathway. Cyclooxygenase-2 decreases the synthesis of prostaglandins required in mediating inflammation, pain, fever, and swelling. The antipyretic effects may arise due to action on the hypothalamus which further leads to vasodilation, subsequent heat dissipation, and an increase in the peripheral blood flow.

Caffeine works by stimulating central nervous system promoting bradycardia, increased respiratory rate, and vasoconstriction. It happens due to increased intracellular cyclic AMP following inhibition phosphodiesterase that degrades cyclic AMP. Sometimes, it is combined with some analgesics or with alkaloids to treat migraine and other headache related issues.


The dose of ibuprofen range from 50-400 mg at every 6-8 hour and not more than three times a 24 hour period while the dose of caffeine is 400mg once daily.


Ibuprofen is well absorbed from the gastrointestinal tract and is extensively bound to plasma proteins. Ibuprofen diffuses into the synovial fluid. Peak plasma concentrations achieved within 1-2 hours after ingestion on an empty stomach. When taken with food, peak plasma levels are lower. It is broken down in the liver into two major metabolites with rapid and complete primary excretion via the kidneys. The elimination half life is approximately 2-4 hours.

Caffeine is well absorbed from the gastrointestinal tract and widely distributed throughout the body. The peak plasma level for caffeine range from 6-10mg/L and the mean time to reach peak concentration ranged from 30 minutes to 2 hours. It is metabolized in liver via oxidation, demethylation and acetylation. Excretion is done by the kidney and about 80% of a dose of caffeine is metabolized to paraxanthine (1,7-dimethylxanthine), 10% to theobromine (3,7-dimethylxanthine), and 4% to theophylline (1,3-dimethylxanthine). The elimination half life is approximately 3-7 hours.


The combination is contraindicated in the following conditions:

  • Tobacco Smoking
  • Increased Cardiovascular Event Risk
  • After Coronary Bypass Surgery
  • Acute Thromboembolic Stroke
  • High Blood Pressure
  • Heart Attack
  • Stomach or Intestinal Ulcer
  • Liver Problems
  • Bleeding of the Stomach or Intestine
  • Kidney Disease
  • Pregnancy
  • Blood Clotting Disorder

Drug interaction

It may cause interactions with the following drugs and not advised to be taken along them:

  • Aspirin
  • Aminoglycosides
  • ACE inhibitors
  • Azole antifungal agents
  • Beta-blockers
  • Bisphosphonates
  • Clopidogrel
  • Corticosteroids
  • Heparin
  • Loop diuretics
  • Methotrexate
  • Quinolones
  • Serotonin reuptake inhibitors
  • Warfarin

Side effects

Common (affecting between 1 in 10 to 1 in 100 people)

  • Nausea and Vomiting
  • Flatulence
  • Diarrhea

Uncommon (affecting between 1 in 100 to 1 in 1000 people)

  • Hypertension
  • Neutropenia
  • Anemia
  • Hemorrhage
  • Hypoproteinemia
  • Thrombocythemia


  • Caffeine should not to be used as a substitute for sleep
  • Caffeine may alter blood sugar levels. So, use in diabetic patients is advised with caution
  • As ibuprofen may cause serious allergic reactions, knowledge of patient’s medical history is a must

Clinical evidence

  • Ibuprofen and caffeine if administered together provide greater analgesic activity than ibuprofen alone, caffeine, and placebo. Caffeine acts as an adjuvant to ibuprofen in acute pain. A double-blind study with this method indicates that ibuprofen and caffeine if administered together provides greater analgesic effectiveness than either component alone or also act as a pain reliever in tension-type headache 1
  • The patients with upper respiratory tract illnesses (URTIs) have reduced alertness and have slower reaction times. The combination of ibuprofen and caffeine is the optimum treatment for malaise associated with URTIs as it provides significant effects on objective performance and subjective measures in comparison to the treatment with ibuprofen or caffeine alone 2


    1. Diamond S, Balm TK, Freitag FG. Clin Pharmacol Ther. 2000 Sep;68(3):312-9 ncbi.nlm.nih.gov/pubmed/11014413
    2. Smith AP, Nutt DJ. Psychopharmacology (Berl). 2014 May; 231(9):1963-74. ncbi.nlm.nih.gov/pubmed/24287602
    3. Andrzej Polski, Regina Kasperek, Karolina Sobotka-Polska, Ewa Poleszak. Curr. Issues Pharm. Med. Sci., Vol. 27, No. 1, Pages 10-13
    4. Diamond S, Balm TK, Freitag FG. Clin Pharmacol Ther 2000; 68:312-19. jfponline.com/home/article/is-the-combination-of-ibuprofen-and-caffeine-effective-for-the-treatment-of-a-tension-type-headache/bc0081b998e17a7059e56f9f3a7be9cf.html
    5. Mc Quay HJ, Angell K, Carroll D, Moore RA, Juniper RP. Pain. 1996 Aug; 66(2-3):247-51. ncbi.nlm.nih.gov/pubmed/8880847
    6. Springer : link.springer.com/article/10.1007%2Fs11916-001-0060-8
    7. Wiley online library:  onlinelibrary.wiley.com/
    8. DrugLib.com:  druglib.com/
    9. PharmgKB:  pharmgkb.org/pathway/PA165884757
    10. Drug Bank drugbank.ca/drugs/DB00201

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