Adverse effects of aspirin, acetaminophen, and ibuprofen on immune function, viral shedding, and clinical status in rhinovirus-infected volunteers. Aspirin compared with acetaminophen in the treatment of fever and other symptoms of upper respiratory tract infection in adults: a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, single-dose, 6-hour dose-ranging study. Effectiveness of pseudoephedrine plus acetaminophen for treatment of symptoms attributed to the paranasal sinuses associated with the common cold.
A double-blind, placebo-controlled trial was conducted to study the effects of over-the-counter analgesic/antipyretic medications on virus shedding, immune response, and clinical status in the common cold. Sixty healthy volunteers were challenged intranasally with rhinovirus type 2 and randomized to one of four treatment arms: aspirin, acetaminophen, ibuprofen, or placebo. Fifty-six volunteers were successfully infected and shed virus on at least 4 days after challenge. Virus shedding, antibody levels, clinical symptoms and signs, and blood leukocyte levels were carefully monitored. Use of aspirin and acetaminophen was associated with suppression of serum neutralizing antibody response (P less than .05 vs. placebo) and increased nasal symptoms and signs (P less than .05 vs. placebo). A concomitant rise in circulating monocytes suggested that the suppression of antibody response may be mediated through drug effects on monocytes and/or mononuclear phagocytes. There were no significant differences in viral shedding among the four groups, but a trend toward longer duration of virus shedding was observed in the aspirin and acetaminophen groups. Aspirin (acetylsalicylic acid) and acetaminophen (paracetamol) are frequently used to treat fever and other symptoms of upper respiratory tract infection (URTI). Both are available over the counter for use at the standard recommended doses of 500 and 1000 mg per single use.
                This study investigated the efficacy, safety profiles, and tolerability of aspirin 500 and 1000 mg and acetaminophen 500 and 1000 mg compared with placebo in adult patients with acute febrile URTI of suspected viral origin.
                This was a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group trial conducted in Ukraine and Russia. Patients with URTI and acute fever of > or =38.5 degrees C received a single dose of aspirin 500 or 1000 mg, acetaminophen 500 or 1000 mg, or matching placebo. Oral body temperature was measured in the clinic at specified time points up to 6 hours after dosing. The intensity of other symptoms of URTI was rated by patients at baseline and at 2, 4, and 6 hours after dosing (scale from 0 = none to 10 = severe). The primary efficacy measure was the AUC for the change in orally measured body temperature from the time of treatment (baseline) to 4 hours after dosing. Secondary outcome measures included the change in body temperature from baseline to specified time points between 0.5 and 6 hours after dosing, the difference between baseline and the lowest measured body temperature, the time to the lowest measured body temperature, and the intensity of other symptoms of URTI (ie, headache, sinus sensitivity to percussion, sore throat, achiness, and feverish discomfort). Tolerability was monitored by recording of adverse events.
                Three hundred ninety-two patients were enrolled (78 in both aspirin groups, 79 in both acetaminophen groups, 78 in the placebo group). Demographic and baseline characteristics were comparable in the 5 groups; 51% of patients were male, with a mean age of 37.4 years and a mean body weight of 74.3 kg. The AUC values for the change in body temperature 0 to 4 hours after dosing were 3.18 (95% CI, 2.78-3.57) for aspirin 500 mg, 4.26 (95% CI, 3.84-4.68) for aspirin 1000 mg, 3.13 (95% CI, 2.77-3.49) for acetaminophen 500 mg, 4.11 (95% CI, 3.73-4.49) for acetaminophen 1000 mg, and 0.76 (95% CI, 0.38-1.13) for placebo. In terms of the primary efficacy variable, all active treatments were significantly superior to placebo (P < 0.001, 1-sided t test), with no significant differences between them. Reductions in body temperature were significantly greater with the 1000-mg doses of both active treatments compared with the 500-mg doses (P< 0.001, 1-sided t test). The mean maximum temperature reductions were 1.32 degrees C, 1.25 degrees C, 1.67 degrees C,1.71 degrees C, and 0.63 degrees C in the respective treatment groups. Significant reductions were seen in the mean intensity of headache, achiness, and feverish discomfort with all active treatments at most time points (P < 0.001), but not in sinus sensitivity to percussion or sore throat. All treatments were equally well tolerated, and no clinically significant adverse events occurred.
                In this single-dose study, aspirin 500 and 1000 mg and acetaminophen 500 and 1000 mg were more effective against fever and other symptoms of URTI than placebo. Both active treatments showed dose-related efficacy, and there was no significant difference between equal doses of the 2 agents. Safety profiles and tolerability were also comparable between treatments. Little data exist on the cause and treatment of subfacial pain and pressure and other discomfort attributed to the paranasal sinuses that develop early during the course of the common cold. The purpose of this study was to determine the efficacy of the combination of pseudoephedrine hydrochloride with acetaminophen for the treatment of early symptoms during colds, which are attributed by the patient to the sinuses.
                Four hundred thirty subjects (216, pseudoephedrine and acetaminophen recipients; 214, placebo recipients) with cold symptoms of 48 hours or less who reported overall "sinus" symptoms of at least moderate severity were enrolled in this randomized double-blind placebo-controlled 2-dose study. Self-reported symptoms were scored (0 to 4, absent to severe) before and at 2 hours after the first and second doses. The 2 primary were measured 2 hours after the second dose were the overall sinus symptom assessment and a weighted composite assessment of sinus pressure, pain, and congestion (sinus symptoms).
                Compared with baseline, 2 hours after the second dose, the mean +/- SEM overall sinus symptom assessment score had decreased by 1.30 +/- 0. 06 in the pseudoephedrine and acetaminophen-treated subjects compared with 0.93 +/- 0.06 in the placebo-treated subjects (P< or = .029). The mean +/- SEM weighted average of sinus symptoms 2 hours after the second dose of study medication had decreased by 1.14 +/- 0.06 in the pseudoephedrine and acetaminophen-treated subjects compared with 0.84 +/- 0.06 in the placebo-treated subjects (P< or = .029). Reductions in similar magnitude were also observed for each of the individual sinus symptoms, and headache and rhinorrhea. Nervousness occurred in 4% of the pseudoephedrine and acetaminophen recipients compared with 0% of placebo recipients (P =.007).
                Our results suggest that pseudoephedrine plus acetaminophen is effective for relief of symptoms attributable to the paranasal sinuses that may develop early in the course of a cold. Arch Fam Med. 2000;9:979-985
Acetaminophen may help relieve nasal obstruction and rhinorrhoea but does not appear to improve some other cold symptoms (including sore throat, malaise, sneezing and cough). However, two of the four included studies in this review were small and allocation concealment was unclear in all four studies. The data in this review do not provide sufficient evidence to inform practice regarding the use of acetaminophen for the common cold in adults. Further large-scale, well-designed trials are needed to determine whether this intervention is beneficial in the treatment of adults with the common cold.