21647 Vioxx Lbl

This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
9556415
VIOXX®
(rofecoxib tablets and oral suspension)
DESCRIPTION
VIOXX* (rofecoxib) is described chemically as 4-[4-(methylsulfonyl)phenyl]-3-phenyl-2(5H)-furanone. It

has the following chemical structure:
O
S
H3 C
O
Rofecoxib is a white to off-white to light yellow powder. It is sparingly soluble in acetone, slightly soluble
in methanol and isopropyl acetate, very slightly soluble in ethanol, practically insoluble in octanol, and
insoluble in water. The empirical formula for rofecoxib is C17H14O4S, and the molecular weight is 314.36.
Each tablet of VIOXX for oral administration contains either 12.5 mg, 25 mg, or 50 mg of rofecoxib and
the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, lactose, magnesium
stearate, microcrystalline cellulose, and yellow ferric oxide. The 50 mg tablets also contain red ferric oxide.
Each 5 mL of the oral suspension contains either 12.5 or 25 mg of rofecoxib and the following inactive
ingredients: citric acid (monohydrate), sodium citrate (dihydrate), sorbitol solution, strawberry flavor, xanthan
gum, and purified water. Added as preservatives are sodium methylparaben 0.13% and sodium
propylparaben 0.02%.
CLINICAL PHARMACOLOGY
Mechanism of Action
VIOXX is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and
antipyretic activities in animal models. The mechanism of action of VIOXX is believed to be due to inhibition
of prostaglandin synthesis, via inhibition of cyclooxygenase-2 (COX-2). At therapeutic concentrations in
humans, VIOXX does not inhibit the cyclooxygenase-1 (COX-1) isoenzyme. Studies to elucidate the
mechanism of action of VIOXX in the acute treatment of migraine have not been conducted.
Pharmacokinetics
Absorption
The mean oral bioavailability of VIOXX at therapeutically recommended doses of 12.5, 25, and 50 mg is
approximately 93%. The area under the curve (AUC) and peak plasma level (Cmax ) following a single 25-mg
dose were 3286 (±843) ng•hr/mL and 207 (±111) ng/mL, respectively. Both Cmax and AUC are roughly dose
proportional across the clinical dose range. At doses greater than 50 mg, there is a less than proportional
increase in Cmax and AUC, which is thought to be due to the low solubility of the drug in aqueous media.
The plasma concentration-time profile exhibited multiple peaks. The median time to maximal concentration
(Tmax ), as assessed in nine pharmacokinetic studies, is 2 to 3 hours. Individual Tmax values in these studies
ranged between 2 to 9 hours. This may not reflect rate of absorption as Tmax may occur as a secondary
peak in some individuals. With multiple dosing, steady-state conditions are reached by Day 4. The AUC0-24hr
and Cmax at steady state after multiple doses of 25 mg rofecoxib was 4018 (±1140) ng•hr/mL and
321 (±104) ng/mL, respectively. The accumulation factor based on geometric means was 1.67.
*Registered trademark of MERCK & CO., Inc., Whitehouse Station, New Jersey, USA
COPYRIGHT  MERCK & CO., Inc., 1998, 2002
All rights reserved
1
VIOXX (rofecoxib tablets and oral suspension) 9556415
VIOXX Tablets 12.5 mg and 25 mg are bioequivalent to VIOXX Oral Suspension 12.5 mg/5 mL and
25 mg/5 mL, respectively.
Food and Antacid Effects
Food had no significant effect on either the peak plasma concentration (Cmax ) or extent of absorption
(AUC) of rofecoxib when VIOXX Tablets were taken with a high fat meal. The time to peak plasma
concentration (Tmax ), however, was delayed by 1 to 2 hours. The food effect on the suspension formulation
has not been studied. VIOXX tablets can be administered without regard to timing of meals.
There was a 13% and 8% decrease in AUC when VIOXX was administered with calcium carbonate
antacid and magnesium/aluminum antacid to elderly subjects, respectively. There was an approximate 20%
decrease in Cmax of rofecoxib with either antacid.
Distribution
Rofecoxib is approximately 87% bound to human plasma protein over the range of concentrations of 0.05
to 25 mcg/mL. The apparent volume of distribution at steady state (V dss) is approximately 91 L following a
12.5-mg dose and 86 L following a 25-mg dose.
Rofecoxib has been shown to cross the placenta in rats and rabbits, and the blood-brain barrier in rats.
Metabolism
Metabolism of rofecoxib is primarily mediated through reduction by cytosolic enzymes. The principal
metabolic products are the cis-dihydro and trans-dihydro derivatives of rofecoxib, which account for nearly
56% of recovered radioactivity in the urine. An additional 8.8% of the dose was recovered as the glucuronide
of the hydroxy derivative, a product of oxidative metabolism. The biotransformation of rofecoxib and this
metabolite is reversible in humans to a limited extent (<5%). These metabolites are inactive as COX-1 or
COX-2 inhibitors.
Cytochrome P450 plays a minor role in metabolism of rofecoxib. Inhibition of CYP 3A activity by
administration of ketoconazole 400 mg daily does not affect rofecoxib disposition. However, induction of
general hepatic metabolic activity by administration of the non-specific inducer rifampin 600 mg daily
produces a 50% decrease in rofecoxib plasma concentrations. (Also see Drug Interactions.)
Excretion
Rofecoxib is eliminated predominantly by hepatic metabolism with little (<1%) unchanged drug recovered
in the urine. Following a single radiolabeled dose of 125 mg, approximately 72% of the dose was excreted
into the urine as metabolites and 14% in the feces as unchanged drug.
The plasma clearance after 12.5- and 25-mg doses was approximately 141 and 120 mL/min,
respectively. Higher plasma clearance was observed at doses below the therapeutic range, suggesting the
presence of a saturable route of metabolism (i.e., non-linear elimination). The effective half-life (based on
steady-state levels) was approximately 17 hours.
Special Populations
Gender
The pharmacokinetics of rofecoxib are comparable in men and women.
Geriatric
After a single dose of 25 mg VIOXX in elderly subjects (over 65 years old) a 34% increase in AUC was
observed as compared to the young subjects. Dosage adjustment in the elderly is not necessary; however,
therapy with VIOXX should be initiated at the lowest recommended dose.
Pediatric
VIOXX has not been investigated in patients below 18 years of age.
Race
Meta-analysis of pharmacokinetic studies has suggested a slightly (10-15%) higher AUC of rofecoxib in
Blacks and Hispanics as compared to Caucasians. No dosage adjustment is necessary on the basis of
race.
Hepatic Insufficiency
A single-dose pharmacokinetic study in mild (Child-Pugh score ≤6) hepatic insufficiency patients
indicated that rofecoxib AUC was similar between these patients and healthy subjects. A pharmacokinetic
study in patients with moderate (Child-Pugh score 7-9) hepatic insufficiency indicated that mean rofecoxib
plasma concentrations were higher (mean AUC: 55%; mean Cmax : 53%) relative to healthy subjects. Since
patients with hepatic insufficiency are prone to fluid retention and hemodynamic compromise, the maximum
recommended chronic dose of VIOXX for patients with moderate hepatic insufficiency is 12.5 mg daily. (See
2
PRECAUTIONS, Hepatic Effects and DOSAGE AND ADMINISTRATION, Hepatic Insufficiency.) Patients
with severe hepatic insufficiency have not been studied.
Renal Insufficiency
In a study (N=6) of patients with end stage renal disease undergoing dialysis, peak rofecoxib plasma
levels and AUC declined 18% and 9%, respectively, when dialysis occurred four hours after dosing. When
dialysis occurred 48 hours after dosing, the elimination profile of rofecoxib was unchanged. While renal
insufficiency does not influence the pharmacokinetics of rofecoxib, use of VIOXX in advanced renal disease
is not recommended. (See WARNINGS, Advanced Renal Disease.)
Drug Interactions (Also see PRECAUTIONS, Drug Interactions.)
General
In human studies the potential for rofecoxib to inhibit or induce CYP 3A4 activity was investigated in
studies using the intravenous erythromycin breath test and the oral midazolam test. No significant difference
in erythromycin demethylation was observed with rofecoxib (75 mg daily) compared to placebo, indicating no
induction of hepatic CYP 3A4. A 30% reduction of the AUC of midazolam was observed with rofecoxib
(25 mg daily). This reduction is most likely due to increased first pass metabolism through induction of
intestinal CYP 3A4 by rofecoxib. In vitro studies in rat hepatocytes also suggest that rofecoxib might be a
mild inducer for CYP 3A4.
Drug interaction studies with the recommended doses of rofecoxib have identified potentially significant
interactions with rifampin, theophylline, and warfarin. Patients receiving these agents with VIOXX should be
appropriately monitored. Drug interaction studies do not support the potential for clinically important
interactions between antacids or cimetidine with rofecoxib. Similar to experience with other nonsteroidal
anti-inflammatory drugs (NSAIDs), studies with rofecoxib suggest the potential for interaction with ACE
inhibitors. The effects of rofecoxib on the pharmacokinetics and/or pharmacodynamics of ketoconazole,
prednisone/prednisolone, oral contraceptives, and digoxin have been studied in vivo and clinically important
interactions have not been found.
CLINICAL STUDIES
Osteoarthritis (OA)
VIOXX has demonstrated significant reduction in joint pain compared to placebo. VIOXX was evaluated for
the treatment of the signs and symptoms of OA of the knee and hip in placebo- and active-controlled clinical
trials of 6 to 86 weeks duration that enrolled approximately 3900 patients. In patients with OA, treatment
with VIOXX 12.5 mg and 25 mg once daily resulted in improvement in patient and physician global
assessments and in the WOMAC (Western Ontario and McMaster Universities) osteoarthritis questionnaire,
including pain, stiffness, and functional measures of OA. In six studies of pain accompanying OA flare,
VIOXX provided a significant reduction in pain at the first determination (after one week in one study, after
two weeks in the remaining five studies); this continued for the duration of the studies. In all OA clinical
studies, once daily treatment in the morning with VIOXX 12.5 and 25 mg was associated with a significant
reduction in joint stiffness upon first awakening in the morning. At doses of 12.5 and 25 mg, the
effectiveness of VIOXX was shown to be comparable to ibuprofen 800 mg TID and diclofenac 50 mg TID for
treatment of the signs and symptoms of OA. The ibuprofen studies were 6-week studies; the diclofenac
studies were 12-month studies in which patients could receive additional arthritis medication during the last
6 months.
Rheumatoid Arthritis (RA)
VIOXX has demonstrated significant reduction of joint tenderness/pain and joint swelling compared to
placebo. VIOXX was evaluated for the treatment of the signs and symptoms of RA in two 12-week placebo-
and active-controlled clinical trials that enrolled a total of approximately 2,000 patients. VIOXX was shown to
be superior to placebo on all primary endpoints (number of tender joints, number of swollen joints, patient
and physician global assessments of disease activity). In addition, VIOXX was shown to be superior to
placebo using the American College of Rheumatology 20% (ACR20) Responder Index, a composite of
clinical, laboratory, and functional measures of RA. VIOXX 25 mg once daily and naproxen 500 mg twice
daily showed generally similar effects in the treatment of RA. A 50-mg dose once daily of VIOXX was also
studied; however, no additional efficacy was seen compared to the 25-mg dose.
Analgesia, including Dysmenorrhea
In acute analgesic models of post-operative dental pain, post-orthopedic surgical pain, and primary
dysmenorrhea, VIOXX relieved pain that was rated by patients as moderate to severe. The analgesic effect
3
(including onset of action) of a single 50-mg dose of VIOXX was generally similar to 550 mg of naproxen
sodium or 400 mg of ibuprofen. In single-dose post-operative dental pain studies, the onset of analgesia with
a single 50-mg dose of VIOXX occurred within 45 minutes. In a multiple-dose study of post-orthopedic
surgical pain in which patients received VIOXX or placebo for up to 5 days, 50 mg of VIOXX once daily was
effective in reducing pain. In this study, patients on VIOXX consumed a significantly smaller amount of
additional analgesic medication than patients treated with placebo (1.5 versus 2.5 doses per day of
additional analgesic medication for VIOXX and placebo, respectively).
Migraine with or without aura
The efficacy of VIOXX in the acute treatment of migraine headaches was demonstrated in two double-
blind, placebo-controlled, outpatient trials. Doses of 25 and 50 mg were compared to placebo in the
treatment of one migraine attack. A second dose of VIOXX was not allowed in either trial. In these controlled
short-term studies, patients were predominantly female (88%) and Caucasian (84%), with a mean age of 40
years (range 18 to 78). Patients were instructed to treat a moderate to severe headache. Headache relief,
defined as a reduction in headache severity from moderate or severe pain to mild or no pain, was assessed
up to 2 hours after dosing. Associated symptoms such as nausea, photophobia, and phonophobia were also
assessed. Maintenance of relief was assessed for up to 24 hours postdose. Other medication, with the
exception of NSAIDs (including COX-2 inhibitors) or combination medications that contained NSAIDs, was
permitted from 2 hours after the dose of study medication. The frequency and time to use of additional
medications were also recorded.
In both placebo-controlled trials, the percentage of patients achieving headache relief 2 hours after
treatment was significantly greater among patients receiving VIOXX at all doses compared to those who
received placebo (Table 1). There were no statistically significant differences between the 25- and the 50-mg
dose groups in either trial.
Table 1
Percentage of Patients with Headache Relief (Mild or No Headache)
2 hours Following Treatment
Trial VIOXX 25 mg VIOXX 50 mg Placebo

1 54%* (n=176) 57%* (n=187) 34% (n=175)
2 60%* (n=187) 62%* (n=188) 30% (n=187)
*p<0.0001 vs. placebo
Note that, in general, comparisons of results obtained in different clinical studies conducted under different conditions by
different investigators with different samples of patients are ordinarily unreliable for purposes of quantitative comparison.
The estimated probability of achieving initial headache relief within 2 hours following treatment is depicted
in Figure 1.
Figure 1
Estimated Probability of Achieving Initial Headache Relief within 2 Hours
4
100% 100%
Estimated Probability of Headache Relief
90% 90%
80% 80%
Placebo
70% VIOXX 25 mg 70%
VIOXX 50 mg
60% 60%
50% 50%
40% 40%
30% 30%
20% 20%
10% 10%
0% 0%
0.0 0.5 1.0 1.5 2.0
Hours Post-Dose
Figure 1 shows the Kaplan-Meier plot of the probability over time of obtaining headache relief (no or mild pain) following treatment with VIOXX or
placebo. The plot is based on pooled data from the 2 placebo-controlled, outpatient trials in adults providing evidence of efficacy. Patients taking
additional medication or not achieving headache relief prior to 2 hours were censored at 2 hours.
5
There was a decreased incidence of migraine-associated nausea, photophobia and phonophobia in

VIOXX treated patients compared to placebo. The estimated probability of taking other medication for
migraine over the 24 hours following initial dose of study treatment is summarized in Figure 2.
Figure 2
Estimated Probability of Patients Taking Additional Medication for Migraines
over the 24 Hours Following the Initial Dose of Study Treatment
100% 100%
90% Placebo 90%

Estimated Probability of Additional Medication
VIOXX 25 mg
VIOXX 50 mg
80% 80%
70% 70%
60% 60%
50% 50%
40% 40%
30% 30%
20% 20%
10% 10%
0% 0%
0 2 4 6 12 18 24
Hours Post-Dose
This Kaplan-Meier plot is based on pooled data obtained in 2 placebo-controlled outpatient trials. Patients not using additional medications were
censored at 24 hours. The plot includes both patients who had headache relief at 2 hours and those who had no response to the initial dose.
Additional medication was not allowed within 2 hours postdose.
VIOXX was effective regardless of presence of aura, gender, race, age, presence of menses or
dysmenorrhea. Similarly, the concomitant use of common migraine prophylactic drugs (e.g., beta-blockers,
calcium channel blockers, tricyclic antidepressants) or oral contraceptives did not affect efficacy. VIOXX was
also effective whether or not there was a history of prior response to NSAIDs.
Special Studies
The following special studies were conducted to evaluate the comparative safety of VIOXX.
VIOXX GI Clinical Outcomes Research (VIGOR Study)
Study Design
The VIGOR study was designed to evaluate the comparative GI safety of VIOXX 50 mg once daily (twice
the highest dose recommended for chronic use in OA and RA) versus naproxen 500 mg twice daily
(common therapeutic dose). The general safety and tolerability of VIOXX 50 mg once daily versus naproxen
500 mg twice daily was also studied. VIGOR was a randomized, double-blind study (median duration of
9 months) in 8076 patients with rheumatoid arthritis (RA) requiring chronic NSAID therapy (mean age
58 years). Patients were not permitted to use concomitant aspirin or other antiplatelet drugs. Patients with a
recent history of myocardial infarction or stroke and patients deemed to require low-dose aspirin for
cardiovascular prophylaxis were to be excluded from the study. Fifty-six percent of patients used
concomitant oral corticosteroids. The GI safety endpoints (confirmed by a blinded adjudication committee)
included:
PUBs-symptomatic ulcers, upper GI perforation, obstruction, major or minor upper GI bleeding.
Complicated PUBs (a subset of PUBs)-upper GI perforation, obstruction or major upper GI bleeding.
Study Results
Gastrointestinal Safety in VIGOR
The VIGOR study showed a significant reduction in the risk of development of PUBs, including
complicated PUBs in patients taking VIOXX compared to naproxen (see Table 2).
6
Table 2
VIGOR-Summary of Patients with Gastrointestinal Safety Events1
COMPARISON TO NAPROXEN
VIOXX 50 mg Naproxen Relative Risk of

GI Safety Endpoints daily 1000 mg daily VIOXX compared 95% CI5
(N=4047)2 (N=4029)2 to naproxen5
3
n3 (Cumulative n (Cumulative
Rate 4) Rate 4)
PUBs 56 (1.80) 121 (3.87) 0.46* (0.33, 0.64)
Complicated PUBs 16 (0.52) 37 (1.22) 0.43* (0.24, 0.78)

1
As confirmed by an independent committee blinded to treatment, 2N=Patients randomized, 3n=Patients with events,
4
Kaplan-Meier cumulative rate at end of study when at least 500 patients remained (approx. 10 1/2 months),
5
Based on Cox proportional hazard model
*p-value ≤0.005 for relative risk compared to naproxen
The risk reduction for PUBs and complicated PUBs for VIOXX compared to naproxen (approximately
50%) was maintained in patients with or without the following risk factors for developing a PUB (Kaplan-
Meier cumulative rate of PUBs at approximately 10 1/2 months, VIOXX versus naproxen, respectively): with
a prior PUB (5.12, 11.47); without a prior PUB (1.54, 3.27); age 65 or older (2.83, 6.49); or younger than 65
years of age (1.48, 3.01). A similar risk reduction for PUBs and complicated PUBs (approximately 50%)
was also maintained in patients with or without Helicobacter pylori infection or concomitant corticosteroid
use.
Other Safety Findings: Cardiovascular Safety
The VIGOR study showed a higher incidence of adjudicated serious cardiovascular thrombotic events in
patients treated with VIOXX 50 mg once daily as compared to patients treated with naproxen 500 mg twice
daily (see Table 3). This finding was largely due to a difference in the incidence of myocardial infarction
between the groups. (See Table 4.) (See PRECAUTIONS, Cardiovascular Effects.) Adjudicated serious
cardiovascular events (confirmed by a blinded adjudication committee) included: sudden death, myocardial
infarction, unstable angina, ischemic stroke, transient ischemic attack and peripheral venous and arterial
thromboses.
Table 3
VIGOR-Summary of Patients with Serious Cardiovascular
Thrombotic Adverse Events1 Over Time
COMPARISON TO NAPROXEN
Treatment Group Patients 4 Months 2 8 Months 3 10 ½ months 4

Randomized
Total number of 17 29 45
VIOXX 50 mg 4047 events
Cumulative Rate† 0.46% 0.82% 1.81%*
Total number of 9 15 19
Naproxen 4029 events
1000 mg
Cumulative Rate† 0.23% 0.43% 0.60%
1 2
Confirmed by blinded adjudication committee, Number of patients remaining after 4 months were
3405 and 3395 for VIOXX and naproxen respectively, 3Number of patients remaining after 8
months were 2806 and 2798 for VIOXX and naproxen respectively, 4Number of patients remaining
were 531 and 514 for VIOXX and naproxen respectively.
†Kaplan-Meier cumulative rate.
* p-value <0.002 for the overall relative risk compared to naproxen by Cox proportional hazard
model
7
8
Table 4
VIGOR- Serious Cardiovascular
Thrombotic Adverse Events 1
VIOXX 50 m g Naproxen
N2=4047 1000 mg
n3 N2=4029
n3
Any CV thrombotic event 45 * 19
Cardiac events 28** 10
Fatal MI/Sudden death 5 4
Non-fatal MI 18** 4
Unstable angina 5 2
Cerebrovascular 11 8
Ischemic stroke 9 8
TIA 2 0
Peripheral 6 1
1
Confirmed by blinded adjudication committee, 2N=Patients randomized, 3n=Patients with events
* p-value <0.002 and ** p-value ≤0.006 for relative risk compared to naproxen by Cox proportional
hazard model
For cardiovascular data from 2 long-term placebo-controlled studies, see PRECAUTIONS, Cardiovascular
Effects.
Upper Endoscopy in Patients with Osteoarthritis and Rheumatoid Arthritis
The VIGOR study described above compared clinically relevant outcomes. Several studies summarized
below have utilized scheduled endoscopic evaluations to assess the occurrence of asymptomatic ulcers in
individual patients taking VIOXX or a comparative agent. The results of outcomes studies, such as VIGOR,
are more clinically relevant than the results of endoscopy studies (see CLINICAL STUDIES, Special
Studies, VIGOR).
Two identical (U.S. and Multinational) endoscopy studies in a total of 1516 patients were conducted to
compare the percentage of patients who developed endoscopically detectable gastroduodenal ulcers with
VIOXX 25 mg daily or 50 mg daily, ibuprofen 2400 mg daily, or placebo. Entry criteria for these studies
permitted enrollment of patients with active Helicobacter pylori infection, baseline gastroduodenal erosions,
prior history of an upper gastrointestinal perforation, ulcer, or bleed (PUB), and/or age ≥65 years. However,
patients receiving aspirin (including low-dose aspirin for cardiovascular prophylaxis) were not enrolled in
these studies. Patients who were 50 years of age and older with osteoarthritis and who had no ulcers at
baseline were evaluated by endoscopy after weeks 6, 12, and 24 of treatment. The placebo-treatment group
was discontinued at week 16 by design.
Treatment with VIOXX 25 mg daily or 50 mg daily was associated with a significantly lower percentage of
patients with endoscopic gastroduodenal ulcers than treatment with ibuprofen 2400 mg daily. See Figures 3
and 4 for the results of these studies.
9
Figure 3
COMPARISON TO IBUPROFEN
Life -Table Cumulative Incidence Rate of Gastroduodenal

Ulcers ≥ 3 mm** (Intention-to-Treat)
Cumulative Incidence Rate

50
U.S. Study
45.8
40
30 27.7
(%)
18.8
20
14.7†
9.9† 9.6†
10 7.3†
4.7 4.1†
3.4 2.9
0
6-Week 12-Week*** 24-Week
Time by Treatment
Placebo (N=158)
Rofecoxib 25mg (N=186)
Ibuprofen 2400 mg (N=167)
† p < 0.001 versus ibuprofen 2400 mg

** Results of analyses using a ≥ 5mm gastroduodenal ulcer endpoint were consistent.
*** The primary endpoint was the cumulative incidence of gastroduodenal ulcer at 12 weeks.
10
Figure 4
COMPARISON TO IBUPROFEN
Life -Table Cumulative Incidence Rate of Gastroduodenal

Ulcers ≥ 3 mm** (Intention-to-
Multinational Study
Cumulative Incidence Rate 50 46.8
40
29.2
30
(%)
20.2
20
12.4†
8.8† 9.9†
10 6.9
5.1† 5.3†
3.4
0.00
0
6-Week 12-Week*** 24-Week
Time by Treatment
Placebo (N=182)
Ibuprofen 2400 mg (N=187)
Treat)
† p < 0.001 versus ibuprofen 2400 mg
** Results of analyses using a ≥ 5mm gastroduodenal ulcer endpoint were consistent.
*** The primary endpoint was the cumulative incidence of gastroduodenal ulcer at 12 weeks.
In a similarly designed 12-week endoscopy study in RA patients treated with VIOXX 50 mg once daily
(twice the highest dose recommended for chronic use in OA and RA) or naproxen 1000 mg daily (common
therapeutic dose), treatment with VIOXX was associated with a significantly lower percentage of patients
with endoscopic gastroduodenal ulcers than treatment with naproxen.
A similarly designed 12-week endoscopy study was conducted in OA patients treated with low-dose
enteric coated aspirin 81 mg daily, low-dose enteric coated aspirin 81 mg plus VIOXX 25 mg daily, ibuprofen
2400 mg daily, or placebo. There was no difference in the cumulative incidence of endoscopic
gastroduodenal ulcers in patients taking low-dose aspirin plus VIOXX 25 mg as compared to those taking
ibuprofen 2400 mg daily alone. Patients taking low-dose aspirin plus ibuprofen were not studied. (See
PRECAUTIONS, Drug Interactions, Aspirin.)
Serious clinically significant upper GI bleeding has been observed in patients receiving VIOXX in
controlled trials, albeit infrequently (see WARNINGS, Gastrointestinal (GI) Effects - Risk of GI Ulceration,
Bleeding, and Perforation).
Assessment of Fecal Occult Blood Loss in Healthy Subjects
Occult fecal blood loss associated with VIOXX 25 mg daily, VIOXX 50 mg daily, ibuprofen 2400 mg per
day, and placebo was evaluated in a study utilizing 51Cr-tagged red blood cells in 67 healthy males. After 4
weeks of treatment with VIOXX 25 mg daily or VIOXX 50 mg daily, the increase in the amount of fecal blood
loss was not statistically significant compared with placebo-treated subjects. In contrast, ibuprofen 2400 mg
per day produced a statistically significant increase in fecal blood loss as compared with placebo-treated
subjects and VIOXX-treated subjects. The clinical relevance of this finding is unknown.
Platelets
Multiple doses of VIOXX 12.5, 25, and up to 375 mg administered daily up to 12 days had no effect on
bleeding time relative to placebo. There was no inhibition of ex vivo arachidonic acid- or collagen-induced
platelet aggregation with 12.5, 25, and 50 mg of VIOXX.
11
Because of its lack of platelet effects, VIOXX is not a substitute for aspirin for cardiovascular
prophylaxis. (See PRECAUTIONS, Cardiovascular Effects.)
INDICATIONS AND USAGE

VIOXX is indicated:
For relief of the signs and symptoms of osteoarthritis.
For relief of the signs and symptoms of rheumatoid arthritis in adults.
For the management of acute pain in adults.
For the treatment of primary dysmenorrhea.
For the acute treatment of migraine attacks with or without aura in adults.
The safety and effectiveness of VIOXX have not been established for cluster headache, which is
present in an older, predominantly male, population.
CONTRAINDICATIONS
VIOXX is contraindicated in patients with known hypersensitivity to rofecoxib or any other component of
VIOXX.
VIOXX should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions
after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been
reported in such patients (see WARNINGS, Anaphylactoid Reactions and PRECAUTIONS, Preexisting
Asthma).
WARNINGS
Gastrointestinal (GI) Effects - Risk of GI Ulceration, Bleeding, and Perforation
Serious gastrointestinal toxicity such as bleeding, ulceration, and perforation of the stomach, small
intestine or large intestine, can occur at any time, with or without warning symptoms, in patients treated
with nonsteroidal anti-inflammatory drugs (NSAIDs). Minor upper gastrointestinal problems, such as
dyspepsia, are common and may also occur at any time during NSAID therapy. Therefore, physicians and
patients should remain alert for ulceration and bleeding, even in the absence of previous GI tract symptoms.
Patients should be informed about the signs and/or symptoms of serious GI toxicity and the steps to take if
they occur. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been
adequately assessed. Only one in five patients who develop a serious upper GI adverse event on NSAID
therapy is symptomatic. It has been demonstrated that upper GI ulcers, gross bleeding or perforation,
caused by NSAIDs, appear to occur in approximately 1% of patients treated for 3-6 months, and in about
2-4% of patients treated for one year. These trends continue thus, increasing the likelihood of developing a
serious GI event at some time during the course of therapy. However, even short-term therapy is not without
risk.
Although the risk of GI toxicity is not completely eliminated with VIOXX, the results of the VIOXX GI
outcomes research (VIGOR) study demonstrate that in patients treated with VIOXX, the risk of GI toxicity
with VIOXX 50 mg once daily is significantly less than with naproxen 500 mg twice daily. (See CLINICAL
STUDIES, Special Studies, VIGOR.)
NSAIDs should be prescribed with extreme caution in patients with a prior history of ulcer disease or
gastrointestinal bleeding. Most spontaneous reports of fatal GI events are in elderly or debilitated patients
and therefore special care should be taken in treating this population. To minimize the potential risk for
an adverse GI event, the lowest effective dose should be used for the shortest possible duration.
For high risk patients, alternate therapies that do not involve NSAIDs should be considered.
Previous studies have shown that patients with a prior history of peptic ulcer disease and/or
gastrointestinal bleeding and who use NSAIDs, have a greater than 10-fold higher risk for developing a GI
bleed than patients with neither of these risk factors. In addition to a past history of ulcer disease,
pharmacoepidemiological studies have identified several other co-therapies or co-morbid conditions that may
increase the risk for GI bleeding such as: treatment with oral corticosteroids, treatment with anticoagulants,
longer duration of NSAID therapy, smoking, alcoholism, older age, and poor general health status.
12
Anaphylactoid Reactions
As with NSAIDs in general, anaphylactoid reactions have occurred in patients without known prior
exposure to VIOXX. In post-marketing experience, rare cases of anaphylactic/anaphylactoid reactions and
angioedema have been reported in patients receiving VIOXX. VIOXX should not be given to patients with the
aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or
without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other
NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS, Preexisting Asthma). Emergency help should be
sought in cases where an anaphylactoid reaction occurs.
Advanced Renal Disease
Treatment with VIOXX is not recommended in patients with advanced renal disease. If VIOXX therapy
must be initiated, close monitoring of the patient's kidney function is advisable (see PRECAUTIONS,
Renal Effects).
Pregnancy
In late pregnancy VIOXX should be avoided because it may cause premature closure of the ductus
arteriosus.
PRECAUTIONS
General
VIOXX cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt
discontinuation of corticosteroids may lead to exacerbation of corticosteroid-responsive illness. Patients on
prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to
discontinue corticosteroids.
The pharmacological activity of VIOXX in reducing inflammation, and possibly fever, may diminish the
utility of these diagnostic signs in detecting infectious complications of presumed noninfectious, painful
conditions.
Cardiovascular Effects
The information below should be taken into consideration and caution should be exercised when VIOXX
is used in patients with a medical history of ischemic heart disease.
In VIGOR, a study in 8076 patients (mean age 58; VIOXX n=4047, naproxen n=4029) with a median
duration of exposure of 9months, the risk of developing a serious cardiovascular thrombotic event was
significantly higher in patients treated with VIOXX 50 mg once daily (n=45) as compared to patients treated
with naproxen 500 mg twice daily (n=19). In VIGOR, mortality due to cardiovascular thrombotic events (7 vs
6, VIOXX vs naproxen, respectively) was similar between the treatment groups. (See CLINICAL STUDIES,
Special Studies, VIGOR, Other Safety Findings: Cardiovascular Safety.) In a placebo-controlled database
derived from 2 studies with a total of 2142 elderly patients (mean age 75; VIOXX n=1067, placebo n=1075)
with a median duration of exposure of approximately 14 months, the number of patients with serious
cardiovascular thrombotic events was 21 vs 35 for patients treated with VIOXX 25 mg once daily versus
placebo, respectively. In these same 2 placebo-controlled studies, mortality due to cardiovascular
thrombotic events was 8 vs 3 for VIOXX versus placebo, respectively. The significance of the cardiovascular
findings from these 3 studies (VIGOR and 2 placebo-controlled studies) is unknown. Prospective studies
specifically designed to compare the incidence of serious CV events in patients taking VIOXX versus NSAID
comparators or placebo have not been performed.
Because of its lack of platelet effects, VIOXX is not a substitute for aspirin for cardiovascular
prophylaxis. Therefore, in patients taking VIOXX, antiplatelet therapies should not be discontinued and
should be considered in patients with an indication for cardiovascular prophylaxis. (See CLINICAL STUDIES,
Special Studies, Platelets; PRECAUTIONS, Drug Interactions, Aspirin.) Prospective, long-term studies on
concomitant administration of VIOXX and aspirin evaluating cardiovascular outcomes have not been
conducted.
Fluid Retention, Edema, and Hypertension
Fluid retention, edema, and hypertension have been reported in some patients taking VIOXX. In clinical
trials of VIOXX at daily doses of 25 mg in patients with rheumatoid arthritis the incidence of hypertension
was twice as high in patients treated with VIOXX as compared to patients treated with naproxen 1000 mg
daily. Clinical trials with VIOXX at daily doses of 12.5 and 25 mg in patients with osteoarthritis have shown
effects on hypertension and edema similar to those observed with comparator NSAIDs; these occurred with
an increased frequency with chronic use of VIOXX at daily doses of 50 mg. (See ADVERSE REACTIONS.)
13
VIOXX should be used with caution, and should be introduced at the lowest recommended dose in patients
with fluid retention, hypertension, or heart failure.
Renal Effects
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal
toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the
maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug
may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow,
which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with
impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the
elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Caution should be used when initiating treatment with VIOXX in patients with considerable dehydration. It
is advisable to rehydrate patients first and then start therapy with VIOXX. Caution is also recommended in
patients with pre-existing kidney disease (see WARNINGS, Advanced Renal Disease).
Hepatic Effects
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs, and
notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been
reported in approximately 1% of patients in clinical trials with NSAIDs. These laboratory abnormalities may
progress, may remain unchanged, or may be transient with continuing therapy. Rare cases of severe
hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure (some
with fatal outcome) have been reported with NSAIDs, including VIOXX. In controlled clinical trials of VIOXX,
the incidence of borderline elevations of liver tests at doses of 12.5 and 25 mg daily was comparable to the
incidence observed with ibuprofen and lower than that observed with diclofenac. In placebo-controlled trials,
approximately 0.5% of patients taking rofecoxib (12.5 or 25 mg QD) and 0.1% of patients taking placebo
had notable elevations of ALT or AST.
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has
occurred, should be monitored carefully for evidence of the development of a more severe hepatic reaction
while on therapy with VIOXX. The maximum recommended chronic daily dose in patients with moderate
hepatic insufficiency is 12.5 mg daily. Use of VIOXX is not recommended in patients with severe hepatic
insufficiency (see CLINICAL PHARMACOLOGY, Special Populations and DOSAGE AND
ADMINISTRATION, Hepatic Insufficiency). If clinical signs and symptoms consistent with liver disease
develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), VIOXX should be discontinued.
Hematological Effects
Anemia is sometimes seen in patients receiving VIOXX. In placebo-controlled trials, there were no
significant differences observed between VIOXX and placebo in clinical reports of anemia. Patients on
long-term treatment with VIOXX should have their hemoglobin or hematocrit checked if they exhibit any
signs or symptoms of anemia or blood loss. VIOXX does not generally affect platelet counts, prothrombin
time (PT), or partial thromboplastin time (PTT), and does not inhibit platelet aggregation at indicated
dosages (see CLINICAL STUDIES, Special Studies, Platelets).
Preexisting Asthma
Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with
aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross
reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has
been reported in such aspirin-sensitive patients, VIOXX should not be administered to patients with this form
of aspirin sensitivity and should be used with caution in patients with preexisting asthma.
Information for Patients
Physicians should instruct their patients to read the patient package insert before starting therapy with
VIOXX and to reread it each time the prescription is renewed in case any information has changed.
VIOXX can cause discomfort and, rarely, more serious side effects, such as gastrointestinal bleeding,
which may result in hospitalization and even fatal outcomes. Although serious GI tract ulcerations and
bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of
ulcerations and bleeding, and should ask for medical advice when observing any indicative signs or
symptoms. Patients should be apprised of the importance of this follow-up. For additional gastrointestinal
safety information see CLINICAL STUDIES, Special Studies, VIGOR and WARNINGS, Gastrointestinal (GI)
Effects - Risk of GI Ulceration, Bleeding and Perforation. Patients should be informed that VIOXX is not a
substitute for aspirin for cardiovascular prophylaxis because of its lack of effect on platelets. For additional
14
cardiovascular safety information see CLINICAL STUDIES, Special Studies, VIGOR and PRECAUTIONS,
Cardiovascular Effects.
Patients should promptly report signs or symptoms of gastrointestinal ulceration or bleeding, skin rash,
unexplained weight gain, edema or chest pain to their physicians.
Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue,
lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur,
patients should be instructed to stop therapy and seek immediate medical therapy.
Patients should also be instructed to seek immediate emergency help in the case of an anaphylactoid
reaction (see WARNINGS).
In late pregnancy VIOXX should be avoided because it may cause premature closure of the ductus
arteriosus.
Laboratory Tests
Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians
should monitor for signs or symptoms of GI bleeding.
Drug Interactions
ACE inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of Angiotensin
Converting Enzyme (ACE) inhibitors. In patients with mild to moderate hypertension, administration of 25 mg
daily of VIOXX with the ACE inhibitor benazepril, 10 to 40 mg for 4 weeks, was associated with an average
increase in mean arterial pressure of about 3 mm Hg compared to ACE inhibitor alone. This interaction
should be given consideration in patients taking VIOXX concomitantly with ACE inhibitors.
Aspirin: Concomitant administration of low-dose aspirin with VIOXX may result in an increased rate of GI
ulceration or other complications, compared to use of VIOXX alone. In a 12-week endoscopy study
conducted in OA patients there was no difference in the cumulative incidence of endoscopic gastroduodenal
ulcers in patients taking low-dose (81 mg) enteric coated aspirin plus VIOXX 25 mg daily, as compared to
those taking ibuprofen 2400 mg daily alone. Patients taking low-dose aspirin plus ibuprofen were not
studied. (See CLINICAL STUDIES, Special Studies, Upper Endoscopy in Patients with Osteoarthritis and
Rheumatoid Arthritis.)
At steady state, VIOXX 50 mg once daily had no effect on the anti-platelet activity of low-dose (81 mg
once daily) aspirin, as assessed by ex vivo platelet aggregation and serum TXB2 generation in clotting
blood. Because of its lack of platelet effects, VIOXX is not a substitute for aspirin for cardiovascular
prophylaxis. Therefore, in patients taking VIOXX, antiplatelet therapies should not be discontinued and
should be considered in patients with an indication for cardiovascular prophylaxis. (See CLINICAL STUDIES,
Special Studies, Platelets and PRECAUTIONS, Cardiovascular Effects.) Prospective, long-term studies on
concomitant administration of VIOXX and aspirin have not been conducted.
Cimetidine: Co-administration with high doses of cimetidine [800 mg twice daily] increased the Cmax of
rofecoxib by 21%, the AUC0-120hr by 23% and the t1/2 by 15%. These small changes are not clinically
significant and no dose adjustment is necessary.
Digoxin: Rofecoxib 75 mg once daily for 11 days does not alter the plasma concentration profile or renal
elimination of digoxin after a single 0.5 mg oral dose.
Furosemide: Clinical studies, as well as post-marketing observations, have shown that NSAIDs can
reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed
to inhibition of renal prostaglandin synthesis.
Ketoconazole: Ketoconazole 400 mg daily did not have any clinically important effect on the
pharmacokinetics of rofecoxib.
Lithium: NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium
clearance. In post-marketing experience there have been reports of increases in plasma lithium levels. Thus,
when VIOXX and lithium are administered concurrently, subjects should be observed carefully for signs of
lithium toxicity.
Methotrexate: VIOXX 12.5, 25, and 50 mg, each dose administered once daily for 7 days, had no effect
on the plasma concentration of methotrexate as measured by AUC0-24hr in patients receiving single weekly
methotrexate doses of 7.5 to 20 mg for rheumatoid arthritis. At higher than recommended doses, VIOXX
75 mg administered once daily for 10 days increased plasma concentrations by 23% as measured by AUC0-
24hr in patients receiving methotrexate 7.5 to 15 mg/week for rheumatoid arthritis. At 24 hours postdose, a
similar proportion of patients treated with methotrexate alone (94%) and subsequently treated with
methotrexate co-administered with 75 mg of rofecoxib (88%) had methotrexate plasma concentrations below
15
the measurable limit (5 ng/mL). Standard monitoring of methotrexate-related toxicity should be continued if
VIOXX and methotrexate are administered concomitantly.
Oral Contraceptives: Rofecoxib did not have any clinically important effect on the pharmacokinetics of
ethinyl estradiol and norethindrone.
Prednisone/prednisolone: Rofecoxib did not have any clinically important effect on the pharmacokinetics
of prednisolone or prednisone.
Rifampin: Co-administration of VIOXX with rifampin 600 mg daily, a potent inducer of hepatic metabolism,
produced an approximate 50% decrease in rofecoxib plasma concentrations. Therefore, a starting daily dose
of 25 mg of VIOXX should be considered for the treatment of osteoarthritis when VIOXX is co-administered
with potent inducers of hepatic metabolism.
Theophylline: VIOXX 12.5, 25, and 50 mg administered once daily for 7 days increased plasma
theophylline concentrations (AUC(0-∞)) by 38 to 60% in healthy subjects administered a single 300-mg dose
of theophylline. Adequate monitoring of theophylline plasma concentrations should be considered when
therapy with VIOXX is initiated or changed in patients receiving theophylline.
These data suggest that rofecoxib may produce a modest inhibition of cytochrome P450 (CYP) 1A2.
Therefore, there is a potential for an interaction with other drugs that are metabolized by CYP 1A2 (e.g.,
amitriptyline, tacrine, and zileuton).
Warfarin: Anticoagulant activity should be monitored, particularly in the first few days after initiating or
changing VIOXX therapy in patients receiving warfarin or similar agents, since these patients are at an
increased risk of bleeding complications. In single and multiple dose studies in healthy subjects receiving
both warfarin and rofecoxib, prothrombin time (measured as INR) was increased by approximately 8% to
11%. In post-marketing experience, bleeding events have been reported, predominantly in the elderly, in
association with increases in prothrombin time in patients receiving VIOXX concurrently with warfarin.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Rofecoxib was not carcinogenic in mice given oral doses up to 30 mg/kg (male) and 60 mg/kg (female)
(approximately 5- and 2-fold the human exposure at 25 and 50 mg daily based on AUC0-24) and in male and
female rats given oral doses up to 8 mg/kg (approximately 6- and 2-fold the human exposure at 25 and
50 mg daily based on AUC0-24) for two years.
Rofecoxib was not mutagenic in an Ames test or in a V-79 mammalian cell mutagenesis assay, nor
clastogenic in a chromosome aberration assay in Chinese hamster ovary (CHO) cells, in an in vitro and an
in vivo alkaline elution assay, or in an in vivo chromosomal aberration test in mouse bone marrow.
Rofecoxib did not impair male fertility in rats at oral doses up to 100 mg/kg (approximately 20- and 7-fold
human exposure at 25 and 50 mg daily based on the AUC0-24) and rofecoxib had no effect on fertility in
female rats at doses up to 30 mg/kg (approximately 19- and 7-fold human exposure at 25 and 50 mg daily
based on AUC0-24).
Pregnancy
Teratogenic effects: Pregnancy Category C.
Rofecoxib was not teratogenic in rats at doses up to 50 mg/kg/day (approximately 28- and 10-fold human
exposure at 25 and 50 mg daily based on AUC0-24). There was a slight, non-statistically significant increase
in the overall incidence of vertebral malformations only in the rabbit at doses of 50 mg/kg/day (approximately
1- or <1-fold human exposure at 25 and 50 mg daily based on AUC0-24). There are no studies in pregnant
women. VIOXX should be used during pregnancy only if the potential benefit justifies the potential risk to the
fetus.
Nonteratogenic effects
Rofecoxib produced peri-implantation and post-implantation losses and reduced embryo/fetal survival in
rats and rabbits at oral doses ≥10 and ≥75 mg/kg/day, respectively (approximately 9- and 3-fold [rats] and 2-
and <1-fold [rabbits] human exposure based on the AUC0-24 at 25 and 50 mg daily). These changes are
expected with inhibition of prostaglandin synthesis and are not the result of permanent alteration of female
reproductive function. There was an increase in the incidence of postnatal pup mortality in rats at
≥5 mg/kg/day (approximately 5- and 2-fold human exposure at 25 and 50 mg daily based on AUC0-24). In
studies in pregnant rats administered single doses of rofecoxib, there was a treatment-related decrease in
the diameter of the ductus arteriosus at all doses used (3-300 mg/kg: 3 mg/kg is approximately 2- and
<1-fold human exposure at 25 or 50 mg daily based on AUC0-24). As with other drugs known to inhibit
prostaglandin synthesis, use of VIOXX during the third trimester of pregnancy should be avoided.
16
Labor and delivery

Rofecoxib produced no evidence of significantly delayed labor or parturition in females at doses 15 mg/kg
in rats (approximately 10- and 3-fold human exposure as measured by the AUC0-24 at 25 and 50 mg). The
effects of VIOXX on labor and delivery in pregnant women are unknown.
Merck & Co., Inc. maintains a registry to monitor the pregnancy outcomes of women exposed to VIOXX
while pregnant. Healthcare providers are encouraged to report any prenatal exposure to VIOXX by calling the
Pregnancy Registry at (800) 986-8999.
Nursing mothers
Rofecoxib is excreted in the milk of lactating rats at concentrations similar to those in plasma. There
was an increase in pup mortality and a decrease in pup body weight following exposure of pups to milk from
dams administered VIOXX during lactation. The dose tested represents an approximate 18- and 6-fold
human exposure at 25 and 50 mg based on AUC0-24. It is not known whether this drug is excreted in human
milk. Because many drugs are excreted in human milk and because of the potential for serious adverse
reactions in nursing infants from VIOXX, a decision should be made whether to discontinue nursing or to
discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness in pediatric patients below the age of 18 years have not been evaluated.
Geriatric Use
Of the patients who received VIOXX in osteoarthritis clinical trials, 1455 were 65 years of age or older.
This included 460 patients who were 75 years or older, and in one of these studies, 174 patients who were
80 years or older. No substantial differences in safety and effectiveness were observed between these
subjects and younger subjects. Greater sensitivity of some older individuals cannot be ruled out. As with
other NSAIDs, including those that selectively inhibit COX-2, there have been more spontaneous post-
marketing reports of fatal GI events and acute renal failure in the elderly than in younger patients. Dosage
adjustment in the elderly is not necessary; however, therapy with VIOXX should be initiated at the lowest
recommended dose.
ADVERSE REACTIONS
Osteoarthritis
Approximately 3600 patients with osteoarthritis were treated with VIOXX; approximately 1400 patients
received VIOXX for 6 months or longer and approximately 800 patients for one year or longer. The following
table of adverse experiences lists all adverse events, regardless of causality, occurring in at least 2% of
patients receiving VIOXX in nine controlled studies of 6-week to 6-month duration conducted in patients with
OA at the therapeutically recommended doses (12.5 and 25 mg), which included a placebo and/or positive
control group.
Clinical Adverse Experiences occurring in
≥ 2.0% of Patients Treated with VIOXX in OA Clinical Trials
Placebo VIOXX Ibuprofen Diclofenac
12.5 or 25 mg 2400 mg 150 mg
daily daily daily
(N = 783) (N = 2829) (N = 847) (N = 498)
Body As A Whole/Site Unspecified
Abdominal Pain 4.1 3.4 4.6 5.8
Asthenia/Fatigue 1.0 2.2 2.0 2.6
Dizziness 2.2 3.0 2.7 3.4
Influenza-Like Disease 3.1 2.9 1.5 3.2
Lower Extremity Edema 1.1 3.7 3.8 3.4
Upper Respiratory Infection 7.8 8.5 5.8 8.2
Cardiovascular System
Hypertension 1.3 3.5 3.0 1.6
Digestive System
Diarrhea 6.8 6.5 7.1 10.6
Dyspepsia 2.7 3.5 4.7 4.0
Epigastric Discomfort 2.8 3.8 9.2 5.4
Heartburn 3.6 4.2 5.2 4.6
17
Naus ea 2.9 5.2 7.1 7.4

Eyes, Ears, Nose, And Throat
Sinusitis 2.0 2.7 1.8 2.4
Musculoskeletal System
Back Pain 1.9 2.5 1.4 2.8
Nervous System
Headache 7.5 4.7 6.1 8.0
Respiratory System
Bronchitis 0.8 2.0 1.4 3.2
Urogenital System
Urinary Tract Infection 2.7 2.8 2.5 3.6
In the OA studies, the following spontaneous adverse events occurred in >0.1% to 1.9% of patients
treated with VIOXX regardless of causality:
Body as a Whole: abdominal distension, abdominal tenderness, abscess, chest pain, chills, contusion,
cyst, diaphragmatic hernia, fever, fluid retention, flushing, fungal infection, infection, laceration, pain, pelvic
pain, peripheral edema, postoperative pain, syncope, trauma, upper extremity edema, viral syndrome.
Cardiovascular System: angina pectoris, atrial fibrillation, bradycardia, hematoma, irregular heartbeat,
palpitation, premature ventricular contraction, tachycardia, venous insufficiency.
Digestive System: acid reflux, aphthous stomatitis, constipation, dental caries, dental pain, digestive gas
symptoms, dry mouth, duodenal disorder, dysgeusia, esophagitis, flatulence, gastric disorder, gastritis,
gastroenteritis, hematochezia, hemorrhoids, infectious gastroenteritis, oral infection, oral lesion, oral ulcer,
vomiting.
Eyes, Ears, Nose, and Throat: allergic rhinitis, blurred vision, cerumen impaction, conjunctivitis, dry
throat, epistaxis, laryngitis, nasal congestion, nasal secretion, ophthalmic injection, otic pain, otitis, otitis
media, pharyngitis, tinnitus, tonsillitis.
Immune System: allergy, hypersensitivity, insect bite reaction.
Metabolism and Nutrition: appetite change, hypercholesterolemia, weight gain.
Musculoskeletal System: ankle sprain, arm pain, arthralgia, back strain, bursitis, cartilage trauma, joint
swelling, muscular cramp, muscular disorder, muscular weakness, musculoskeletal pain, musculoskeletal
stiffness, myalgia, osteoarthritis, tendinitis, traumatic arthropathy, wrist fracture.
Nervous System: hypesthesia, insomnia, median nerve neuropathy, migraine, muscular spasm,
paresthesia, sciatica, somnolence, vertigo.
Psychiatric: anxiety, depression, mental acuity decreased.
Respiratory System: asthma, cough, dyspnea, pneumonia, pulmonary congestion, respiratory infection.
Skin and Skin Appendages: abrasion, alopecia, atopic dermatitis, basal cell carcinoma, blister, cellulitis,
contact dermatitis, herpes simplex, herpes zoster, nail unit disorder, perspiration, pruritus, rash, skin
erythema, urticaria, xerosis.
Urogenital System: breast mass, cystitis, dysuria, menopausal symptoms, menstrual disorder, nocturia,
urinary retention, vaginitis.
The following serious adverse events have been reported rarely (estimated <0.1%) in patients taking
VIOXX, regardless of causality. Cases reported only in the post-marketing experience are indicated in
italics.
Cardiovascular: cerebrovascular accident, congestive heart failure, deep venous thrombosis, hypertensive
crisis, myocardial infarction, pulmonary edema, pulmonary embolism, transient ischemic attack, unstable
angina.
Gastrointestinal: cholecystitis, colitis, colonic malignant neoplasm, duodenal perforation, duodenal ulcer,
esophageal ulcer, gastric perforation, gastric ulcer, gastrointestinal bleeding, hepatic failure, hepatitis,
intestinal obstruction, jaundice, pancreatitis.
Hemic and lymphatic: agranulocytosis, aplastic anemia, leukopenia, lymphoma, pancytopenia,
thrombocytopenia.
Immune System: anaphylactic/anaphylactoid reaction, angioedema, bronchospasm, hypersensitivity
vasculitis.
Metabolism and nutrition: hyponatremia.
Nervous System: aseptic meningitis, epilepsy aggravated.
18
Psychiatric: confusion, hallucinations.

Skin and Skin Appendages: severe skin reactions, including Stevens-Johnson syndrome and toxic
epidermal necrolysis.
Urogenital System: acute renal failure, breast malignant neoplasm, hyperkalemia, interstitial nephritis,
prostatic malignant neoplasm, urolithiasis, worsening chronic renal failure.
In 1-year controlled clinical trials and in extension studies for up to 86 weeks (approximately 800 patients
treated with VIOXX for one year or longer), the adverse experience profile was qualitatively similar to that
observed in studies of shorter duration.
Rheumatoid Arthritis
Approximately 1,100 patients were treated with VIOXX in the Phase III rheumatoid arthritis efficacy
studies. These studies included extensions of up to 1 year. The adverse experience profile was generally
similar to that reported in the osteoarthritis studies. In studies of at least three months, the incidence of
hypertension in RA patients receiving the 25 mg once daily dose of VIOXX was 10.0% and the incidence of
hypertension in patients receiving naproxen 500 mg twice daily was 4.7%.
Analgesia, including primary dysmenorrhea
Approximately one thousand patients were treated with VIOXX in analgesia studies. All patients in
post-dental surgery pain studies received only a single dose of study medication. Patients in primary
dysmenorrhea studies may have taken up to 3daily doses of VIOXX, and those in the post-orthopedic
surgery pain study were prescribed 5 daily doses of VIOXX.
The adverse experience profile in the analgesia studies was generally similar to those reported in the
osteoarthritis studies. The following additional adverse experience, which occurred at an incidence of at
least 2% of patients treated with VIOXX, was observed in the post-dental pain surgery studies: post-dental
extraction alveolitis (dry socket).
Migraine with or without aura
Approximately 750 patients were treated with a single dose of VIOXX 25 mg or 50 mg in two single-
attack migraine studies. Approximately 460 patients in the 3-month extension phase of one study treated up
to 8 (average 3) migraine attacks per month. In single attack studies, the following adverse events were
more frequent in the VIOXX treatment groups (25 mg and 50 mg) compared to the placebo group, and
occurred at an incidence of at least 2% of patients treated: dizziness, nausea, somnolence and dyspepsia.
In the 3-month extension phase of one study, the following adverse events occurred at an incidence of at
least 2% of patients treated in the VIOXX treatment groups (25 mg and 50 mg): dizziness, dry mouth,
nausea, and vomiting.
Clinical Studies in OA and RA with VIOXX 50 mg (Twice the highest dose recommended for chronic
use)
In OA and RA clinical trials which contained VIOXX 12.5 or 25 mg as well as VIOXX 50 mg, VIOXX 50 mg
QD was associated with a higher incidence of gastrointestinal symptoms (abdominal pain, epigastric pain,
heartburn, nausea and vomiting), lower extremity edema, hypertension, serious* adverse experiences and
discontinuation due to clinical adverse experiences compared to the recommended chronic doses of 12.5
and 25 mg (see DOSAGE AND ADMINISTRATION).
OVERDOSAGE
No overdoses of VIOXX were reported during clinical trials. Administration of single doses of VIOXX
1000 mg to 6 healthy volunteers and multiple doses of 250 mg/day for 14 days to 75 healthy volunteers did
not result in serious toxicity.
In the event of overdose, it is reasonable to employ the usual supportive measures, e.g., remove
unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive
therapy, if required.
Rofecoxib is not removed by hemodialysis; it is not known whether rofecoxib is removed by peritoneal
dialysis.
*adverse experience that resulted in death, permanent or substantial disability, hospitalization, congenital
anomaly, or cancer, was immediately life threatening, was due to an overdose, or was thought by the
investigator to require intervention to prevent one of the above outcomes
19
DOSAGE AND ADMINISTRATION

VIOXX is administered orally. The lowest dose of VIOXX should be sought for each patient.
Osteoarthritis
The recommended starting dose of VIOXX is 12.5 mg once daily. Some patients may receive additional
benefit by increasing the dose to 25 mg once daily. The maximum recommended daily dose is 25 mg.
Rheumatoid Arthritis
The recommended dose is 25 mg once daily. The maximum recommended daily dose is 25 mg.
Management of Acute Pain and Treatment of Primary Dysmenorrhea
The recommended dose of VIOXX is 50 mg once daily. The maximum recommended daily dose is
50 mg. Use of VIOXX for more than 5 days in management of pain has not been studied. Chronic use of
VIOXX 50 mg daily is not recommended. (See ADVERSE REACTIONS, Clinical Studies in OA and RA with
VIOXX 50 mg).
Acute Treatment of Migraine Attacks with or without aura
The recommended starting dose of VIOXX is 25 mg once daily. Some patients may receive additional
benefit with 50 mg as compared to 25 mg. The maximum recommended daily dose is 50 mg. The safety of
treating more than 5 migraine attacks in any given month has not been established. Chronic daily use of
VIOXX for the acute treatment of migraine is not recommended.
Hepatic Insufficiency
Because of significant increases in both AUC and Cmax in patients with moderate hepatic impairment
(Child-Pugh score: 7-9), the maximum recommended chronic daily dose is 12.5 mg. (See CLINICAL
PHARMACOLOGY, Special Populations). The efficacy of 12.5 mg in rheumatoid arthritis patients with
moderate hepatic insufficiency has not been studied.
VIOXX Tablets may be taken with or without food.
Oral Suspension
VIOXX Oral Suspension 12.5 mg/5 mL or 25 mg/5 mL may be substituted for VIOXX Tablets 12.5 or
25 mg, respectively, in any of the above indications. Shake before using.
HOW SUPPLIED
No. 3810 — Tablets VIOXX, 12.5 mg, are cream/off-white, round, shallow cup tablets engraved MRK 74
on one side and VIOXX on the other. They are supplied as follows:
NDC 0006-0074-31 unit of use bottles of 30
NDC 0006-0074-28 unit dose packages of 100
NDC 0006-0074-68 bottles of 100
NDC 0006-0074-82 bottles of 1000
NDC 0006-0074-80 bottles of 8000.
No. 3834 — Tablets VIOXX, 25 mg, are yellow, round tablets engraved MRK 110 on one side and VIOXX
on the other. They are supplied as follows:
NDC 0006-0110-68 bottles of 100
NDC 0006-0110-82 bottles of 1000
NDC 0006-0110-80 bottles of 8000.
No. 3835 — Tablets VIOXX, 50 mg, are orange, round tablets engraved MRK 114 on one side and VIOXX
on the other. They are supplied as follows:
NDC 0006-0114-68 bottles of 100
NDC 0006-0114-74 bottles of 500
NDC 0006-0114-81 bottles of 4000.
No. 3784 — Oral Suspension VIOXX, 12.5 mg/5 mL, is an opaque, white to faint yellow suspension with
a strawberry flavor that is easily resuspended upon shaking.
NDC 0006-3784-64 unit of use bottles containing 150 mL (12.5 mg/5 mL).
No. 3785 — Oral Suspension VIOXX, 25 mg/5 mL, is an opaque, white to faint yellow suspension with a
strawberry flavor that is easily resuspended upon shaking.
20
NDC 0006-3785-64 unit of use bottles containing 150 mL (25 mg/5 mL).
Storage
VIOXX Tablets:
Store at 25°C (77°F), excursions permitted to 15-30°C (59-86°F). [See USP Controlled Room
Temperature.]
VIOXX Oral Suspension:
Store at 25°C (77°F), excursions permitted to 15-30°C (59-86°F). [See USP Controlled Room
Temperature.]
Rx only
Issued March 2004

Printed in USA
21
Patient Information about

VIOXX (rofecoxib tablets and oral suspension)
VIOXX (pronounced "VI-ox")
for Osteoarthritis, Rheumatoid Arthritis, Pain and Migraine Attacks
Generic name: rofecoxib ("ro-fa-COX-ib")
You should read this information before you start taking VIOXX*. Also, read the leaflet each time you refill
your prescription, in case any information has changed. This leaflet provides only a summary of certain
information about VIOXX. Your doctor or pharmacist can give you an additional leaflet that is written for
health professionals that contains more complete information. This leaflet does not take the place of careful
discussions with your doctor. You and your doctor should discuss VIOXX when you start taking your
medicine and at regular checkups.
What is VIOXX?
VIOXX is a prescription medicine called a COX-2 selective, nonsteroidal anti-inflammatory drug (NSAID).
VIOXX is used in adults for:
• relief of the pain and inflammation (swelling and soreness) of osteoarthritis (arthritis from wear and tear
on your bones and your joints)
• relief of the pain and inflammation of rheumatoid arthritis in adults (arthritis caused by a condition where
your immune system attacks your joints)
• management of short-term pain
• treatment of menstrual pain (pain during women’s monthly periods)
• treatment of migraine headache attacks with or without aura.
VIOXX has not been studied in children under the age of 18.
*Registered trademark of MERCK & CO., Inc.

COPYRIGHT © MERCK & CO., Inc., 1998, 2002
All rights reserved
1
Who should not take VIOXX?
Do not take VIOXX if you:

• have had an allergic reaction such as asthma attacks (wheezing), hives, or swelling of the throat and
face to aspirin or other medicines called non-steroidal anti-inflammatory drugs (NSAIDs). There are
many NSAID medicines. Ask your doctor or pharmacist for a list of medicines that contain NSAIDs if
you are not sure.
• are allergic to rofecoxib, the active ingredient of VIOXX, or to any other ingredients in VIOXX. See the
end of this leaflet for a complete list of ingredients in VIOXX.
What should I tell my doctor before and during treatment with VIOXX?
Tell your doctor about all your medical conditions including if you have or have had:
• an allergic reaction to aspirin or other NSAIDs
• asthma (a small number of patients with asthma have reactions to aspirin or other NSAIDs)
• stomach problems such as ulcers or bleeding
• kidney disease
• liver disease
• angina (chest pain), a heart attack, or a blocked artery in your heart
• heart failure
• high blood pressure
Tell your doctor if you are:

• pregnant or plan to become pregnant. VIOXX may harm your unborn baby if you take it in late
pregnancy. If you take VIOXX while you are pregnant, ask your doctor how you can be on the VIOXX
Pregnancy Registry.
• breast-feeding or plan to breast-feed. It is not known if VIOXX passes into your milk and if it can harm
your baby. You should discuss with your doctor whether or not to take VIOXX if you are breast-feeding.
2
Tell your doctor about:

• any other medical problems or allergies you have now or have had.
• all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal
supplements.
Tell your doctor right away if you develop:

• serious stomach problems such as ulcer or bleeding symptoms (for instance, stomach burning,
vomiting blood, or if there is blood in your bowel movement or it is black and sticky like tar, which are
signs of possible stomach bleeding).
• unexplained weight gain or swelling of the legs, feet, and/or hands.
• skin rash or allergic reactions. If you have a severe allergic reaction, get medical help right away.
How should I take VIOXX?
• Take VIOXX exactly as prescribed by your doctor. Your dose will depend on the condition being treated
and other medical problems you may have. Do not change your dose of VIOXX or take extra doses
unless your doctor has told you to.
• You can take VIOXX with or without food.
• If you miss a dose of VIOXX by a few hours, take it as soon as you remember. If it is close to your
next dose, do NOT take the missed dose.
• If you take too much VIOXX, call your doctor, pharmacist, or poison control center right away.
3
Can I take VIOXX with other medicines?
Tell your doctor about all of the other medicines you are taking or plan to take while you are on VIOXX, even
other medicines that you can get without a prescription, including vitamins and herbal supplements. VIOXX
and certain other medicines can affect each other causing serious side effects. Keep a list of the medicines
you take. Show the list to your doctors and pharmacists each time you get a new medicine. They will tell
you if it is safe to take VIOXX with other medicines. Your doctor may want to check that your medicines are
working properly together. Especially tell your doctor if you are taking:
• or have taken warfarin (Coumadin®) or any other similar blood thinner within the past 10 days
• theophylline (a medicine used to treat asthma)
• rifampin (an antibiotic)
• ACE inhibitors (medicines used for high blood pressure and heart failure)
• lithium (a medicine used to treat a certain type of depression).
VIOXX cannot take the place of aspirin for prevention of heart attack or stroke. If you take both aspirin and
VIOXX, you may have a higher chance of serious stomach problems than if you take VIOXX alone. If you are
taking aspirin for prevention of heart attack or stroke, you should not stop taking aspirin without talking to
your doctor.
4
What are the possible side effects of VIOXX?
Serious but rare side effects that have been reported in patients taking VIOXX and/or related medicines have
included:
• Serious allergic reactions including swelling of the face, lips, tongue, and/or throat which may cause
difficulty breathing or swallowing, hives, wheezing, or shock (loss of blood pressure and
consciousness) can occur. These may require treatment right away. Severe skin reactions have also
been reported.
• Serious stomach problems, such as stomach and intestinal bleeding, can occur with or without warning
symptoms. These problems, if severe, could lead to hospitalization or death. Although this happens
rarely, you should watch for signs (for instance, stomach burning, vomiting blood, or if there is blood in
your bowel movement or it is black and sticky like tar) that you may have this serious side effect and
tell your doctor right away.
• Heart attacks and other serious events, such as blood clots in your body, have been reported in
patients taking VIOXX.
• Serious kidney problems can occur, including acute (sudden) kidney failure and worsening of chronic
kidney failure.
• Severe liver problems, including hepatitis, jaundice and liver failure, can occur in patients taking
NSAIDs, including VIOXX. Tell your doctor if you develop symptoms of liver problems. These include
nausea, tiredness, itching, pain in the right upper abdomen, yellow skin or eyes, and flu-like
symptoms.
Your doctor may do blood tests and check you for problems that may happen during treatment with VIOXX.
5
In addition, the following side effects have been reported: anxiety, blurred vision, colitis, confusion,
constipation, decreased levels of sodium in the blood, depression, fluid in the lungs, hair loss,
hallucinations, increased levels of potassium in the blood, insomnia, low blood cell counts, menstrual
disorder, palpitations, pancreatitis, ringing in the ears, severe increase in blood pressure, tingling sensation,
unusual headache with stiff neck (aseptic meningitis), vertigo, worsening of epilepsy.
More common, but less serious side effects reported with VIOXX have included the following:
Respiratory infections
Headache
Dizziness
Diarrhea
Nausea, vomiting and upset stomach
Heartburn
Stomach pain
Swelling of the legs and/or feet
High blood pressure
Back pain
Tiredness
Urinary tract infection.
These are not all the side effects reported with VIOXX. Do not rely on this leaflet alone for information about
side effects. Your doctor or pharmacist can discuss with you a more complete list of side effects. Any time
you have a medical problem you think may be related to VIOXX, talk to your doctor.
How should I store VIOXX?
• Store VIOXX at room temperature, 59° to 86°F (15° to 30°C).

• Safely throw away VIOXX that is out of date or no longer needed.
• Keep VIOXX and all medicines out of the reach of children.
6
What else should I know about VIOXX?
This leaflet provides a summary of certain information about VIOXX. If you have any questions or concerns
about VIOXX, osteoarthritis, rheumatoid arthritis, pain or migraine attacks, talk to your health professional.
Your doctor or pharmacist can give you an additional leaflet that is written for health professionals. This
leaflet is also available at www.vioxx.com.
Medicines are sometimes prescribed for conditions other than those described in patient information
leaflets. Do not use VIOXX for a condition for which it was not prescribed. Do not give VIOXX to other people
even if they have the same symptoms you have. It may harm them.
What are the ingredients in VIOXX?
Active Ingredient: rofecoxib
Inactive Ingredients:
Oral suspension: citric acid (monohydrate), sodium citrate (dihydrate), sorbitol solution, strawberry flavor,
xanthan gum, sodium methylparaben, sodium propylparaben.
Tablets: croscarmellose sodium, hydroxypropyl cellulose, lactose, magnesium stearate, microcrystalline

cellulose, and yellow ferric oxide.
Rx Only
Issued
MERCK & CO., Inc.
Whitehouse Station, NJ 08889, USA

21647 Vioxx Lbl

Uploaded by

Copyright:

Available Formats

21647 Vioxx Lbl

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

21647 Vioxx Lbl

Uploaded by

Copyright:

Available Formats

This label may not be the latest approved by FDA.

For current labeling information, please visit https://www.fda.gov/drugsatfda

VIOXX* (rofecoxib) is described chemically as 4-[4-(methylsulfonyl)phenyl]-3-phenyl-2(5H)-furanone. It

VIOXX (rofecoxib tablets and oral suspension) 9556415

VIOXX (rofecoxib tablets and oral suspension) 9556415

VIOXX (rofecoxib tablets and oral suspension) 9556415

Trial VIOXX 25 mg VIOXX 50 mg Placebo

VIOXX (rofecoxib tablets and oral suspension) 9556415

0.0 0.5 1.0 1.5 2.0

VIOXX (rofecoxib tablets and oral suspension) 9556415

There was a decreased incidence of migraine-associated nausea, photophobia and phonophobia in

90% Placebo 90%

VIOXX (rofecoxib tablets and oral suspension) 9556415

VIOXX 50 mg Naproxen Relative Risk of

PUBs 56 (1.80) 121 (3.87) 0.46* (0.33, 0.64)

Complicated PUBs 16 (0.52) 37 (1.22) 0.43* (0.24, 0.78)

Treatment Group Patients 4 Months 2 8 Months 3 10 ½ months 4

VIOXX (rofecoxib tablets and oral suspension) 9556415

VIOXX (rofecoxib tablets and oral suspension) 9556415

VIOXX (rofecoxib tablets and oral suspension) 9556415

Life -Table Cumulative Incidence Rate of Gastroduodenal

Cumulative Incidence Rate

† p < 0.001 versus ibuprofen 2400 mg

VIOXX (rofecoxib tablets and oral suspension) 9556415

Life -Table Cumulative Incidence Rate of Gastroduodenal

VIOXX (rofecoxib tablets and oral suspension) 9556415

INDICATIONS AND USAGE

VIOXX (rofecoxib tablets and oral suspension) 9556415

VIOXX (rofecoxib tablets and oral suspension) 9556415

VIOXX (rofecoxib tablets and oral suspension) 9556415

VIOXX (rofecoxib tablets and oral suspension) 9556415

VIOXX (rofecoxib tablets and oral suspension) 9556415

Labor and delivery

VIOXX (rofecoxib tablets and oral suspension) 9556415

Naus ea 2.9 5.2 7.1 7.4

VIOXX (rofecoxib tablets and oral suspension) 9556415

Psychiatric: confusion, hallucinations.

VIOXX (rofecoxib tablets and oral suspension) 9556415

DOSAGE AND ADMINISTRATION

VIOXX (rofecoxib tablets and oral suspension) 9556415

Issued March 2004

Patient Information about

*Registered trademark of MERCK & CO., Inc.

Who should not take VIOXX?

Do not take VIOXX if you:

Tell your doctor if you are:

Tell your doctor about:

Tell your doctor right away if you develop:

How should I take VIOXX?

Can I take VIOXX with other medicines?

What are the possible side effects of VIOXX?

How should I store VIOXX?

• Store VIOXX at room temperature, 59° to 86°F (15° to 30°C).

What else should I know about VIOXX?

What are the ingredients in VIOXX?

Active Ingredient: rofecoxib

Tablets: croscarmellose sodium, hydroxypropyl cellulose, lactose, magnesium stearate, microcrystalline

You might also like