Ibuprofen + Acetaminophen vs Ibuprofen for Orofacial Pain

Overseen By Clifton M Carey, PhD

Age: Any Age

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Colorado, Denver

Must not be taking: Antibiotics, Analgesics, Blood thinners

Disqualifiers: Pregnancy, Kidney disease, Liver disease, Alcoholism, others

Compensation: Varies

Number of Visits: Unknown

Duration: 4 days

375 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial requires that you are not currently taking antibiotics or pain relievers (analgesics) before participating.

Will I have to stop taking my current medications?

The trial requires that you are not currently taking antibiotics or pain relievers (analgesics) to participate.

What data supports the idea that Ibuprofen + Acetaminophen vs Ibuprofen for Orofacial Pain is an effective drug?

The available research does not directly compare the combination of Ibuprofen and Acetaminophen to Ibuprofen alone for orofacial pain. However, it does show that Ibuprofen is effective for various types of pain, including toothache and other oral pain conditions. Additionally, Acetaminophen is often used for pain relief. While there is no specific data on the combination for orofacial pain, the individual effectiveness of these drugs suggests that their combination could be beneficial. Other studies mentioned show that Ibuprofen is effective for children's pain and has a good safety profile, while Acetaminophen is commonly used for pain relief. Therefore, combining these two could potentially enhance pain relief, although specific studies on orofacial pain are needed to confirm this. ^{1 2 3 4 5}

What evidence supports the effectiveness of using ibuprofen and acetaminophen together for orofacial pain?

Ibuprofen has been shown to be effective for various types of pain, including toothache and inflammatory conditions in the mouth and throat, making it a reasonable choice for orofacial pain. Additionally, acetaminophen has been effective in reducing pain, as demonstrated in studies comparing it to other pain relievers. ^{1 2 3 4 5}

What safety data exists for the combination of ibuprofen and acetaminophen for orofacial pain?

The combination of ibuprofen and acetaminophen has been shown to provide effective pain relief with a safety profile similar to ibuprofen alone. Studies indicate that both drugs are safe at recommended doses, but high doses or chronic use can pose risks. Acetaminophen is linked to liver injury, while ibuprofen can cause gastric bleeding and thromboembolic events. However, using them together offers superior analgesia without exceeding safe daily dose limits. In children, ibuprofen is effective for various pain conditions with mild side effects, though caution is advised in cases of dehydration. Overall, the combination is considered safe and effective for managing pain. ^{1 6 7 8 9}

Is the combination of ibuprofen and acetaminophen safe for treating pain?

The combination of ibuprofen and acetaminophen is generally considered safe at recommended doses, providing effective pain relief without exceeding daily dose limits. However, high doses or long-term use can increase risks, such as liver damage from acetaminophen and stomach bleeding from ibuprofen. In children, ibuprofen is effective for various pains with mild side effects, but it should be avoided if the child is dehydrated. ^{1 6 7 8 9}

Is the drug Acetaminophen, Ibuprofen, Placebo a promising treatment for orofacial pain?

Yes, Ibuprofen is a promising drug for orofacial pain. It is effective for various types of pain, including dental pain, and is well-tolerated compared to other pain relievers like aspirin. Acetaminophen is also commonly used for pain relief, but the studies highlight Ibuprofen's effectiveness in similar situations. ^{1 10 11 12 13}

How does the drug combination of ibuprofen and acetaminophen differ from other treatments for orofacial pain?

The combination of ibuprofen and acetaminophen for orofacial pain is unique because it combines two well-tolerated pain relievers, each with different mechanisms of action, potentially offering enhanced pain relief compared to using ibuprofen alone. Ibuprofen is an anti-inflammatory drug, while acetaminophen works primarily to relieve pain and reduce fever, making their combination potentially more effective for managing pain with an inflammatory component. ^{1 10 11 12 13}

What is the purpose of this trial?

The purpose of this study is to compare the effectiveness of a combined ibuprofen and acetaminophen regimen in controlling discomfort for 4 days after initial orthodontic appliance placement as compared to ibuprofen alone or a placebo. The hypothesis is that combined ibuprofen and acetaminophen therapy will effectively provide better pain control than ibuprofen alone or a placebo after orthodontic appliance placement.

Eligibility Criteria

This trial is for healthy individuals aged 12 and above who are about to start comprehensive orthodontic treatment, have not taken antibiotics or painkillers recently, and have no allergies to ibuprofen or acetaminophen. It excludes those under 12 or over 80, pregnant women, prisoners, people with decision-making impairments, kidney disease, liver issues, alcoholism, stomach ulcers or bleeding.

Inclusion Criteria

I am not currently taking any antibiotics or painkillers.

I had any necessary teeth extractions done at least 2 weeks before my braces were put on.

I am healthy with no major medical issues.

Exclusion Criteria

I have had bleeding in my stomach.

I have difficulty making decisions due to a cognitive or mental health condition.

Prisoners

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either a combined ibuprofen and acetaminophen regimen, ibuprofen alone, or placebo for pain management after orthodontic appliance placement

4 days

Daily self-administration

Follow-up

Participants are monitored for pain levels and compliance using a visual analogue score (VAS) over the treatment period

4 days

Treatment Details

Interventions

• Acetaminophen
• Ibuprofen
• Placebo oral tablet

Trial Overview The study aims to determine if a combination of ibuprofen (200 mg) and acetaminophen (650 mg) is more effective in managing pain after orthodontic appliance placement than just ibuprofen alone or a placebo. Participants will be randomly assigned to one of these three treatments for four days.

Participant Groups

Group I: Ibuprofen and acetaminophen Experimental Treatment 1 Intervention

one 200 mg table of ibuprofen and two 325 mg tablets of acetaminophen

Group II: Ibuprofen Active Control 1 Intervention

one 200 mg tablet of ibuprofen and 2 placebo tablets

Group III: Placebo Placebo Group 1 Intervention

3 tablets of tableting compounds with no active ingredients

Acetaminophen is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Tylenol for:

• Pain relief
• Fever reduction

Approved in European Union as Paracetamol for:

• Pain relief
• Fever reduction

Approved in Canada as Tylenol for:

• Pain relief
• Fever reduction

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Findings from Research

Ibuprofen is an effective analgesic for various pain conditions in children, including musculoskeletal pain, ear pain, and postoperative pain, making it a suitable choice for treating mild to moderate pain.

The safety profile of ibuprofen is favorable, with mild side effects and the lowest gastrointestinal toxicity among NSAIDs, although it should be avoided in dehydrated patients due to potential renal risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibuprofen in the treatment of children's inflammatory pain: a clinical and pharmacological overview. Barbagallo, M., Sacerdote, P.[2019]

In a study of 60 patients, strepfen (flurbiprofen) provided similar pain relief for throat pain compared to paracetamol, but acted much faster, with effects starting within 5-15 minutes versus 30-45 minutes for paracetamol.

Strepfen was well tolerated with no serious side effects reported, making it a safe option for treating throat pain in both acute and chronic pharyngeal conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of an open prospective controlled randomized comparative trial of flurbiprofen and paracetamol efficacy and tolerance in patients with throat pain]. Sedinkin, AA., Balandin, AV., Dimova, AD.[2013]

In a study involving 159 oral surgery outpatients, diflunisal at doses of 500 mg and 1,000 mg was found to be significantly more effective than acetaminophen alone for pain relief, with effects lasting throughout a 12-hour observation period.

Diflunisal's analgesic efficacy was comparable to that of a combination of acetaminophen and codeine, and importantly, none of the active treatments caused more side effects than the placebo, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diflunisal. A new oral analgesic with an unusually long duration of action. Forbes, JA., Beaver, WT., White, EH., et al.[2020]

In a study of 22 children with fever, both ibuprofen and paracetamol effectively reduced body temperature, but ibuprofen showed a greater effect at 6 and 8 hours post-administration.

Ibuprofen not only had a longer duration of action compared to paracetamol but also offered additional anti-inflammatory benefits, making it potentially more advantageous for treating certain upper respiratory infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measurement of antipyretic activity of ibuprofen and paracetamol in children. Sheth, UK., Gupta, K., Paul, T., et al.[2019]

In a double-blind study comparing flurbiprofen and acetaminophen with codeine in 96 postoperative hours after foot surgery, both treatments showed similar efficacy in pain relief, with no significant differences in pain intensity or patient evaluations.

However, the acetaminophen with codeine group had a higher incidence of study termination due to side effects, suggesting that flurbiprofen may be a safer option for postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of flurbiprofen and acetaminophen with codeine in postoperative foot pain. Ottinger, ML., Kinney, KW., Black, JR., et al.[2020]

The fixed-dose combination (FDC) of ibuprofen (250 mg) and acetaminophen (500 mg) demonstrated superior pain relief compared to individual doses of ibuprofen (250 mg) and acetaminophen (650 mg) in two phase 3 studies involving a total of 691 patients, with significant efficacy observed within the first hour and lasting over 8 hours.

The FDC was well tolerated, showing the lowest rates of adverse events compared to the individual components, making it a promising non-opioid option for managing acute dental pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Single and Multiple Doses of a Fixed-dose Combination of Ibuprofen and Acetaminophen in the Treatment of Postsurgical Dental Pain: Results From 2 Phase 3, Randomized, Parallel-group, Double-blind, Placebo-controlled Studies. Searle, S., Muse, D., Paluch, E., et al.[2021]

The European Medicines Agency's Pharmacovigilance Risk Assessment Committee has issued a warning about the serious risks associated with the combination of codeine and ibuprofen, particularly concerning renal and gastrointestinal harms.

This warning highlights the need for careful consideration of the safety profile of this medication combination, emphasizing potential adverse effects that could impact patient health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety warning: combination products containing codeine and ibuprofen. [2023]

A fixed-dose combination of acetaminophen (APAP) and ibuprofen (IBP) was found to be well tolerated in a study involving 922 patients, with adverse events similar to or lower than those seen with either drug alone or placebo.

The combination therapy provided superior pain relief compared to monotherapy, while maintaining a strong safety profile without increasing the risk of common adverse events like gastrointestinal issues or postoperative bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An integrated safety analysis of combined acetaminophen and ibuprofen (Maxigesic &#174; /Combogesic&#174;) in adults. Aitken, P., Stanescu, I., Playne, R., et al.[2023]

In a study of 8677 patients, the use of analgesics like paracetamol, aspirin, and ibuprofen showed that the main risk factors for serious adverse events (SAE) included the type of pain being treated and the number of other medications taken, with higher risks associated with more medications.

Patients taking aspirin had a higher risk of SAE compared to those taking paracetamol, while ibuprofen was associated with fewer gastrointestinal adverse events, highlighting the importance of medication choice and patient history in managing pain safely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for adverse events in analgesic drug users: results from the PAIN study. Moore, N., Charlesworth, A., Van Ganse, E., et al.[2013]

In a study of 43 children undergoing bilateral myringotomy and tube placement, preoperative administration of either acetaminophen or ibuprofen did not significantly reduce postoperative pain compared to a placebo.

The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores showed no differences among the groups at various time points, indicating that neither analgesic provided effective pain relief in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative analgesia with preoperative oral ibuprofen or acetaminophen in children undergoing myringotomy. Bennie, RE., Boehringer, LA., McMahon, S., et al.[2019]

In a study of 2,815 patients with mild to moderate pain from cold/flu symptoms or sore throat, ibuprofen was found to be significantly better tolerated than aspirin, with a lower rate of significant adverse events (12.0% for ibuprofen vs. 15.7% for aspirin).

Ibuprofen's tolerability was comparable to that of paracetamol (12.3%), indicating that it is a safe over-the-counter option for pain relief in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of ibuprofen, aspirin and paracetamol for the treatment of cold and flu symptoms and sore throat pain. Moore, N., Le Parc, JM., van Ganse, E., et al.[2013]

In five studies using the Dental Pain Model, ibuprofen 400 mg was consistently more effective than aspirin 650 mg and acetaminophen 600 mg for managing acute postsurgical pain.

Ibuprofen 400 mg was found to be at least as effective as zomepirac sodium 100 mg, and no serious or prolonged side effects were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five studies on ibuprofen for postsurgical dental pain. Cooper, SA.[2020]

In a survey of 5000 patients, nearly 50% were found to have contraindications for ibuprofen, suggesting that many individuals may not safely use this common over-the-counter pain reliever, while only 6.8% had contraindications for paracetamol.

The findings indicate that the results of the PAIN study, which suggested similar tolerability for ibuprofen and paracetamol, may not apply to the general population, as the study excluded many patients who could be at risk when using ibuprofen without medical supervision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective survey to compare the suitability profiles of over-the-counter ibuprofen and paracetamol use in a French general practitioner-controlled population. Pigeon, P., Robillard, E., Clarke, GD., et al.[2018]

References

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Ibuprofen in the treatment of children's inflammatory pain: a clinical and pharmacological overview. [2019]

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[Results of an open prospective controlled randomized comparative trial of flurbiprofen and paracetamol efficacy and tolerance in patients with throat pain]. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Diflunisal. A new oral analgesic with an unusually long duration of action. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Measurement of antipyretic activity of ibuprofen and paracetamol in children. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Comparison of flurbiprofen and acetaminophen with codeine in postoperative foot pain. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Single and Multiple Doses of a Fixed-dose Combination of Ibuprofen and Acetaminophen in the Treatment of Postsurgical Dental Pain: Results From 2 Phase 3, Randomized, Parallel-group, Double-blind, Placebo-controlled Studies. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Safety warning: combination products containing codeine and ibuprofen. [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

An integrated safety analysis of combined acetaminophen and ibuprofen (Maxigesic &#174; /Combogesic&#174;) in adults. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Risk factors for adverse events in analgesic drug users: results from the PAIN study. [2013]

10. France pubmed.ncbi.nlm.nih.gov

Postoperative analgesia with preoperative oral ibuprofen or acetaminophen in children undergoing myringotomy. [2019]

11. India pubmed.ncbi.nlm.nih.gov

Tolerability of ibuprofen, aspirin and paracetamol for the treatment of cold and flu symptoms and sore throat pain. [2013]

12. United States pubmed.ncbi.nlm.nih.gov

Five studies on ibuprofen for postsurgical dental pain. [2020]

13. New Zealand pubmed.ncbi.nlm.nih.gov

A prospective survey to compare the suitability profiles of over-the-counter ibuprofen and paracetamol use in a French general practitioner-controlled population. [2018]