BACAGIN Tablet Ref.[115684] Active ingredients: Ibuprofen Paracetamol

Pharmacotherapeutic group: Musculoskeletal system, anti-inflammatory and antirheumatic products, non-steroids, propionic acid derivatives. Ibuprofen combinations.

The pharmacological actions of ibuprofen and paracetamol differ in their site and mode of action. These complementary modes of action are synergistic which results in greater antinociception and antipyresis than the single actives alone.

Ibuprofen is an NSAID that has demonstrated its efficacy in the common animal experimental inflammation models by inhibition of prostaglandin synthesis. Prostaglandins sensitise nociceptive afferent nerve terminals to mediators such as bradykinin. Ibuprofen therefore elicits an analgesic effect through peripheral inhibition of the cycloxygenase- 2 (COX-2) isoenzyme with a subsequent reduction in sensitisation of nociceptive nerve terminals. Ibuprofen has also been shown to inhibit induced-leucocyte migration into inflamed areas. Ibuprofen has a pronounced action within the spinal cord due, in part, to the inhibition of COX. Ibuprofen's antipyretic effects are produced by the central inhibition of prostaglandins in the hypothalamus. Ibuprofen reversibly inhibits platelet aggregation. In humans, ibuprofen reduces inflammatory pain, swellings and fever.

Experimental data suggest that ibuprofen may inhibit the effect of low dose acetylsalicylic acid on platelets aggregation when they are dosed concomitantly. In one study, when a single dose of ibuprofen 400mg was taken within 8 h before or within 30 min after immediate release acetylsalicylic acid (81mg), a decreased effect of acetylsalicylic acid on the formation of thromboxane or platelet aggregation occurred. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 4.5).

Paracetamol's exact mechanism of action is still not completely defined; however there is considerable evidence to support the hypothesis of a central antinociceptive effect. Various biochemical studies point to inhibition of central COX 2 activity. Paracetamol may also stimulate the activity of descending 5-hydroxytryptamine (serotonin) pathways that inhibit nociceptive signal transmission in the spinal cord. Evidence has shown that paracetamol is a very weak inhibitor of peripheral COX-1 and 2 isoenzymes.

The clinical efficacy of ibuprofen and paracetamol has been demonstrated in pain associated with headache, toothache and dysmenorrhoea, and fever, furthermore efficacy has been shown in patients with pain and fever associated with cold and influenza and in pain models such as sore throat, muscular pain or soft tissue injury and backache. This product is especially suitable for pain which has not been relieved by ibuprofen 400 mg or paracetamol 1000 mg alone, and faster pain relief than ibuprofen.

Randomised, double-blind placebo-controlled studies were conducted with the combination using the acute pain model of post-operative dental pain. The studies show that:

• This product provides more effective pain relief than paracetamol 1000 mg (p<0.0001) and ibuprofen 400mg (p<0.5) which are clinically and statistically significant
• Duration of analgesia was significantly longer for this product (8.4 hours) compared to paracetamol 500 mg (4 hours, p<0.0001) or 1000 mg (5.2 hours, p<0.0001).
• The global evaluation of the study medication by the subjects showed high levels of satisfaction with 88.0% rating the product as 'good', 'very good' or 'excellent' in achieving pain relief. The fixed combination product performed significantly better than ibuprofen 200mg, paracetamol 500mg and 1000 mg (p<0.001 in all cases).

A one tablet dose of this product provides more effective pain relief than a combination of paracetamol 1000 mg/codeine phosphate 30 mg (p=0.0001) and was shown to be non-inferior to a combination of ibuprofen 400 mg/codeine phosphate 25.6 mg.

This product has a fast onset of action with 'confirmed perceptible pain relief' achieved in a median of 15.6 minutes (1tablet dose) or 18.3 minutes (2 tablets dose), which is faster than for ibuprofen 200 mg (30.1 minutes, p<0.001), ibuprofen 400 mg (23.8 minutes, p=0.0001) and paracetamol 500 mg (23.7 minutes, p=0.0001). 'Meaningful pain relief' for this product was achieved in a median of 39.3 minutes (1 tablet dose) or 44.6 minutes (2 tablets dose), which was significantly faster than for ibuprofen 200 mg (80.0 minutes, p<0.0001), ibuprofen 400 mg (70.5 minutes, p=0.0001), paracetamol 500 mg (50.4 minutes, p=0.001) and paracetamol 1000 mg (45.6 minutes, p<0.05). Other randomised, double-blind placebo-controlled studies were conducted with the combination using the acute pain model of post-operative dental pain. The studies show that:

• This product provides more effective pain relief than paracetamol 1000 mg (p<0.0001) and ibuprofen 400 mg (p<0.05).
• Duration of analgesia was significantly longer for this product (9.1 hours) compared to paracetamol 500 mg (4 hours) or 1000 mg (5.2 hours).
• The global evaluation of the study medication by the subjects showed high levels of satisfaction with 93.2% rating the product as 'good', 'very good' or 'excellent' in achieving pain relief. The fixed combination product performed significantly better than paracetamol 1000 mg (p<0.0001).

Another randomised, double-blind controlled clinical study was conducted with the product in the treatment of chronic knee pain. The study showed that:

• The product provides more effective pain relief than paracetamol 1000 mg in short term treatment (p<0.01) and long term treatment (p<0.01).
• The global evaluation of the product by the subjects showed high levels of satisfaction with 60.2% Page 17 of 19 rating the product as 'good' or 'excellent' as a long term treatment for a painful knee. The product performed significantly better than paracetamol 1000 mg (p<0.001).

This product provides more effective pain relief than a combination of paracetamol 1000 mg/codeine phosphate 30 mg (p<0.0001), and a combination of ibuprofen 400 mg/codeine phosphate 25.6 mg (p=0.0001).