You can trust Advil Cough, Cold and Flu and Sinus products to relieve your patient’s sore throat, headache, sinus pain, body pain and fever and other symptoms due to cold or flu¹

Advil Cold, Sinus and Flu Extra Strength works hard to relieve cold and flu symptoms

Proven safe and effective when used as directed, Advil Cold, Sinus and Flu Extra Strength contains 400 mg of ibuprofen available in caplet format to relieve sore throat, sinus pain, headache, fever and minor body aches and pains due to the common cold and flu. It also contains 60 mg of pseudoephedrine hydrochloride and 4 mg of chlorpheniramine maleate (see Advil Cold, Cough & Flu and Cold & Sinus Product Details section for more information)

When used as directed for acute pain, OTC ibuprofen is well tolerated^2*

In the PAIN study, which included over 8,500 patients, total GI events (including dyspepsia) and abdominal pain were less frequent with ibuprofen (200 mg) compared to ASA (500 mg) or acetaminophen (500 mg) ) (all p<0.035)^2,3

This large-scale randomized trial comparing nonprescription doses of ASA, acetaminophen, and ibuprofen in 8,677 adults measured rates of significant adverse events related to tolerability. The primary outcome measure was the number of patients with at least one significant adverse event, defined as an event that was serious, severe or moderate, resulted in a second physician consultation, led to cessation of treatment, or was of missing intensity. Statistical analysis tested for equivalence between ibuprofen and acetaminophen, and for difference with ASA.^2,3*

GI: gastrointestinal; ASA: acetylsalicylic acid; OTC = over the counter.

* This was a blinded, multicentre study in general practice of up to 7 days of ASA, acetaminophen (both up to 3 g daily) or ibuprofen (up to 1.2 g daily), administered for common painful conditions, using patient generated data with physician assistance. 1,108 general practitioners included 8,677 adults (2,900 ASA; 2,886 ibuprofen; 2,888 acetaminophen; 3 patients had no code label number). The main indications were musculoskeletal or back pain (48%), sore throat, the common cold and flu (31%).

Hepatic and renal safety profile

Clinical studies suggest that ibuprofen was associated with less acute liver injury compared to other NSAIDs:

Archives of Internal Medicine, 1994 (Garcia Rodriguez LA et al.)

• The lowest incidence of liver injury among 8 NSAIDs occurred in ibuprofen users and was 1.6/100000 (1.6/100k). The other incidence in increasing order is as follows: oral diclofenac (3.6/100K), naproxen (3.8/100K), mefenamic acid (2.5/100K), ketoprofen (8.8/100K), piroxicam (6.0/100K), fenbufen (11.9/100K), sulindac (148.1/100K)^12†

Postgraduate Medicine, 2018 (Moore N et al.)

• Compared to ibuprofen, risks of hepatoxicity are somewhat higher and better documented with acetaminophen, and reported to be higher amongst specific NSAIDs, such as oral diclofenac and sulindac^13†

Epidemiologic studies do not suggest that low dose ibuprofen (e.g., ≤1200 mg daily) is associated with an increased risk of renal adverse events (e.g., renal failure, renal injury)^‡

American Journal of Epidemiology, 2000 (Griffin MR et al.)

• Use of ibuprofen at ≤1200mg/day led to an odds ratio of 0.94 (95% CI: 0.58, 1.51) for renal AEs (i.e., renal failure)^9†

Pharmacotherapy, 1999 (Perez-Gutthann S et al.)

• No major adverse events related to renal injury (i.e., acute renal failure) were identified during the study^10†

Pharmacotherapy, 1992 (Furey SA et al.)

• After non-prescription doses of ibuprofen, renal injury (i.e., acute renal failure or any renal injury) were not amongst the reported adverse effects^11†

AE = adverse event; CI = confidence interval; GI = gastrointestinal; NSAID = nonsteroidal anti-inflammatory drug; OTC = over the counter.

^† Garcia Rodriguez LA and colleagues conducted a retrospective cohort study with secondary case-control analysis. The study included 536 general practitioners' practices in England and Wales for the period October 1987 through August 1991. A total of 625,307 persons who received more than 2 million prescriptions for 1 of 12 NSAIDs, were followed up to estimate the risk of newly diagnosed acute liver injury. The incidence of acute liver injury was 3.7 per 100,000 NSAID users. Sulindac was the only NSAID with a substantially greater risk of acute liver injury than that for the overall NSAID group. The incidence of acute liver injury for indomethacin, diflunisal, tenoxicam, and fenoprofen was not provided. It was concluded that the risk of acute liver injury is sufficiently small as to be of minimal concern for most NSAIDs.

Moore N and colleagues conducted a review of available literature on the GI and hepatic safety of non-aspirin OTC analgesics, including NSAIDs (ibuprofen, ketoprofen, diclofenac, and naproxen) and acetaminophen. Safety in overdose was also reviewed. Articles describing clinical trials, meta-analyses, and epidemiological studies were evaluated for inclusion in the review, and focus was placed on studies discussing doses and durations of use consistent with OTC use. GI effects accounted for 75% of total AEs in the study. Across all studies reviewed here, the risk of serious GI toxicity, including upper GI bleeding and peptic ulcers, was low at OTC doses.

Griffin MR and colleagues is a nested case-control study using Tennessee Medicaid enrollees aged ≥65 years to determine the role of NSAIDs in acute deterioration of renal function. Cases included patients who had been hospitalized with community acquired acute renal failure. For ibuprofen, the odds ratio associated with dosages of ≤1200 mg/day was 0.94 (95% Cl: 0.58, 1.51) and increased as the dosage increased (>1200 to <2400 mg/day was 1.89 [95% Cl: 1.34, 2.67], while >2400 mg/day was 2.32 [95% Cl: 1.45, 3.71]). The researchers identified all prescriptions filled for these drugs in the 365 days before the index date (date of initial hospitalization for cases): 6% current NSAID users began in the past 30 days; 33% had less than 180 days’ use in the past year; 61% had more than 180 days’ use.

Pérez-Gutthann S and colleagues conducted a cohort study in the United Kingdom to evaluate the risk of a newly diagnosed episode of upper GI bleeding, acute liver and renal failure, agranulocytosis, aplastic anemia, severe skin disorders, and anaphylaxis occurring within 30 days after the first prescription for a low dose of oral diclofenac, naproxen, or ibuprofen. There was 22,146 persons using oral diclofenac (≤75 mg), 46,919 using naproxen (≤750 mg), and 54,830 using ibuprofen (≤1200 mg). Age, gender, and comorbidity were similar in the 3 cohorts and consisted of patients aged 15–85 (men and women). Of the 54,830 using ibuprofen (≤1200 mg/day) in the study, there were 2 cases of hepatic injury. A single case of potential renal failure for naproxen was reported and none for ibuprofen.

Furey SA and colleagues evaluated the safety of single doses of non-prescription strength ibuprofen by examining reported side effects from 15 double-blind, randomized, controlled trials conducted of the drug to treat various common painful conditions (e.g., headache, sore throat). All studies included placebo and another nonprescription analgesic, acetaminophen. A total of 878 subjects received ibuprofen 200 mg (n=171) or 400 mg (n=707), 849 subjects received acetaminophen 650 mg (n=237) or 1000 mg (n=612), and 852 subjects received placebo. Subjects were 16–79 years of age, had various pain conditions, but were otherwise in good health. Results indicated that no renal AEs were reported (side effects were predominantly related to the GI tract and the central nervous system).

^‡ Safety was demonstrated when ibuprofen was used as directed at a low dose (≤1200 mg/day) and for short term use. Advil should not be taken for fever for more than 3 days or for pain for more than 5 days, unless directed by a physician. Please consult the Product Monograph for complete dosing instructions and safety profile.

Like other NSAIDs, ibuprofen inhibits renal prostaglandin synthesis, which may decrease renal function and cause sodium retention. Renal blood flow and glomerular filtration rate decreased in patients with mild impairment of renal function who took 1200 mg/day of ibuprofen for 1 week. Patients at greatest risk of renal toxicity are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and the elderly. Use of ibuprofen in patients at risk of renal toxicity or with prerenal conditions should be approached with caution. For full safety information please refer to the warnings and precautions and adverse reactions of the product monograph.

Clinically proven to relieve mild to moderate pain symptoms due to the common cold and flu¹

Published studies have documented the efficacy of 200 mg doses and 400 mg doses of ibuprofen in treating mild to moderate pain including sore throat pain, headache and muscle aches in adults.¹

One Advil is often all it takes to relieve mild to moderate pain including:²

• Sore throat pain
• Headache & migraine
• Muscle aches
• Menstrual pain
• Toothache (dental pain)

Advil also reduces fever.