(nabumatone)
Tablets
DESCRIPTION
CLINICAL PHARMACOLOGY
CLINICAL TRIALS
INDIVIDUALIZATION OF DOSING
INDICATIONS AND USAGE
CONTRAINDICATIONS
WARNINGS
PRECAUTIONS
ADVERSE REACTIONS
OVERDOSAGE
DOSAGE AND ADMINISTRATION
HOW SUPPLIED
Relafen (nabumetone) is a naphthylalkanone designated chemically as 4-(6-methoxy-2-naphthalenyl)-2-butanone. It has the following structure:
nabumetone
Nabumetone is a white to off-white crystalline substance with a molecular weight of 228.3 It is
nonacidic and practically insoluble in water, but soluble in alcohol and most organic solvents. It
has an n-octanol:phosphate buffer partition coefficient of 2400 at pH 7.4.
Tablets for Oral Administration: Each oval-shaped, film-coated tablet contains 500 mg or 750
mg of nabumetone. Inactive ingredients consist of hydroxypropyl methylcellulose,
microcrystalline cellulose, polyethylene glycol, polysorbate 80, sodium lauryl sulfate, sodium
starch glycolate and titanium dioxide. The 750 mg tablets also contain iron oxides.
Relafen is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory,
analgesic and antipyretic properties in pharmacologic studies. As with other nonsteroidal anti-
inflammatory agents, its mode of action is not known. However, the ability to inhibit
prostaglandin synthesis may be involved in the anti-inflammatory effect.
The parent compound is a prodrug, which undergoes hepatic biotransformation to the active
component, 6-methoxy-2-naphthylacetic acid (6MNA), that is a potent inhibitor of prostaglandin
synthesis.
It is acidic and has an n-octonal:phosphate buffer partition coefficient of 0.5 at pH 7.4.
Pharmcokinetics
After oral administration, approximately 80% of a radiolabelled dose of nabumetone is found in
the urine, indicating that nabumetone is well absorbed from the gastrointestinal tract.
Nabumetone itself is not detected in the plasma because, after absorption, it undergoes rapid
biotransformation to the principal active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA).
Approximately 35% of a 1000 mg oral dose of nabumetone is converted to 6MNA and 50% is
converted into unidentified metabolites which are subsequently excreted in the urine. Following
oral administration of Relafen, 6MNA exhibits pharmacokinetic characteristics that generally
follow a one-compartment model with first order input and first order elimination.
6MNA is more than 99% bound to plasma proteins. The free fraction is dependent on total
concentration of 6MNA and is proportional to dose over the range of 1000 mg to 2000 mg. It is
0.2% to 0.3% at concentrations typically achieved following administration of Relafen 1000 mg
and is approximately 0.6% to 0.8% of the total concentrations at steady state following daily
administration of 2000 mg.
Steady-state plasma concentrations of 6MNA are slightly lower than predicted from single-dose
data. This may result from the higher fraction of unbound 6MNA which undergoes greater
hepatic clearance.
Coadministration of food increases the rate of absorption and subsequent appearance of 6MNA
in the plasma but does not affect the extent of conversion of nabumetone into 6MNA. Peak
plasma concentrations of 6MNA are increased by approximately one third.
Coadministration with an aluminum-containing antacid had no significant effect on the
bioavailability of 6MNA.
active metabolite (6MNA) at steady state following oral administration of 1000 mg or 2000 mg
doses of Relafen (nabumetone)
Young Adult Young Adults Elderly
Mean +/-SD Mean +/-SD Mean +/-SD
Abbreviation 1000 mg 2000 mg 1000 mg
(units) n=31 n=12 n=27
tmax (hours) 3.0 (1.0 to 12.0) 2.5(1.0 to 8.0) 4.0(1.0 to 10.0)
t1/2 (hours) 22.5 +/- 3.7 26.2 +/- 3.7 29.8 +/- 8.1
CLss/F(mL/min.) 26.1 +/- 17.3 21.0 +/- 4.0 18.6 +/- 13.4
Vdss/F(L) 55.4 +/- 26.4 53.4 +/- 11.3 50.2 +/- 25.3
The simulated curves in the graph below illustrate the range of active metabolite plasma
concentrations that would be expected from 95% of patients following 1000 mg to 2000 mg
doses to steady state. The cross-hatched area represents the expected overlap in plasma
concentrations due to intersubject variation following oral administration of 1000 mg to 2000 mg
of Relafen.
at Steady State Following One-Daily Dosing of Nabumetone
1000 mg (n=31) 2000 mg (n=12)
6MNA undergoes biotransformation in the liver, producing inactive metabolites that are
eliminated as both free metabolites and conjugates. None of the known metabolites of 6MNA
has been detected in plasma. Preliminary in vivo and in vitro studies suggest that unlike other
NSAIDs, there is no evidence of enterohepatic recirculation of the active metabolite.
Approximately 75% of a radiolabelled dose was recovered in urine in 48 hours. Approximately
80% was recovered in 168 hours. A further 9% appeared in the feces. In the first 48 hours,
metabolites consisted of:
-nabumetone, unchanged not detectable
-6-methoxy-2-naphthylacetic acid < 1%
(6MNA), unchanged
-6MNA, conjugated 11%
-6-hydroxy-2-naphthylacetic acid 5%
-(6HNA), unchanged
-6HNA, conjugated 7%
-4-(6-hydroxy-2-naphthyl)-butan-2-ol, 9%
conjugated
-O-desmethyl-nabumetone,
conjugated 7%
-unidentified minor metabolites 34%
------------
Total % Dose: 73%
Following oral administration of dosages of 1000 mg to 2000 mg to steady state, the mean
plasma clearance of 6MNA is 20 to 30 mL/min. and the elimination half-life is approximately 24
hours.
Elderly patients: Steady-state plasma concentrations in elderly patients were generally higher
than in young healthy subjects. (See Table 1 for summary of pharmacokinetic parameters.)
Renal Insufficiency: In studies of patients with renal insufficiency, the mean terminal half-life of
6MNA was increased in patients with severe renal dysfunction (creatinine clearance < 30 mL/min./1.73 m2). In patients undergoing hemodialysis, steady-state plasma concentrations
of the active metabolite were similar to those observed in healthy subjects. Due to extensive
protein-binding, 6MNA is not dialyzable.
Hepatic Impairment: Data in patients with severe hepatic impairment are limited.
Biotransformation of nabumetone to 6MNA and the further metabolism of 6MNA to inactive
metabolites is dependent on hepatic function and could be reduced in patients with severe
hepatic impairment (history of or biopsy-proven cirrhosis).
Special Studies
Gastrointestinal: Relafen (nabumetone) was compared to aspirin in inducing gastrointestinal
blood loss. Food intake was not monitored. Studies utilizing 51Cr-tagged red blood cells in
healthy males showed no difference in fecal blood loss after 3 or 4 weeks’ administration of
Relafen 1000 mg or 2000 mg daily when compared to either placebo-treated or nontreated
subjects. In contast, aspirin 3600 mg daily produced an increase in fecal blood loss when
compared to the Relafen-treated, placebo-treated or nontreated subjects. The clinical relevance
of the data is unknown.
The following endoscopy trials entered patients who had been previously treated with NSAIDs.
These patients had varying baseline scores and different courses of treatment. The trials were
not designed to correlate symptoms and endoscopy scores. The clinical relevance of these
endoscopy trials, i.e. either G.I. symptoms or serious G.I. events, is not known.
Ten endoscopy studies were conducted in 488 patients who had baseline and post-treatment
endoscopy. In 5 clinical trials that compared a total of 194 patients on Relafen 1000 mg daily or
naproxen 250 mg or 500 mg twice daily for 3 to 12 weeks. Relafen treatment resulted in fewer
patients with endoscopically detected lesions (> 3mm). In 2 trials a total of 101 patients on
Relafen 1000 mg or 2000 mg daily or piroxicam 10 mg to 20 mg for 7 to 10 days, there were
fewer Relafen patients with endoscopically detected lesions. In 3 trials of a total of 47 patients
on Relafen 1000 mg daily or indomethacin 100 mg to 150 mg daily for 3 to 4 weeks, the
endoscopy scores were higher with indomethacin. Another 12-week trial in a total of 171 patients
compared the results of treatment with Relafen 1000 mg/day to ibuprofen 2400 mg/day plus
misprostol 800 mcg/day. The results showed that patients treated with Relafen had a lower
number of endoscopically detected lesions (> 5 mm) than patients treated with ibuprofen alone
but comparable to the combination of ibuprofen plus misoprostol. The results did not correlate
with abdominal pain.
Other: In 1-week repeat-dose studies in healthy volunteers, Relafen 1000 mg daily had little
effect on collagen-induced platelet aggregation and no effect on bleeding time. In comparison,
naproxen 500 mg daily suppressed collagen-induced platelet aggregation and significantly
increased bleeding time.
Osteoarthritis: The use of Relafen in relieving the signs and symptoms of osteoarthritis was
assessed in double-blind controlled trials in which 1,047 patients were treated for 6 weeks to 6
months. In these trials, Relafen, in a dose of 100 mg/day administered at night was comparable
to naproxen 500 mg/day and to aspirin 3600 mg/day.
Rheumatoid Arthritis: The use of Relafen in relieving the signs and symptoms of rheumatoid
arthritis was assessed in double-blind, randomized, controlled trials in which 770 patients were
treated for 3 weeks to 6 months. Relafen, in a dose of 1000 mg/day administered at night was
comparable to naproxen 500/mg/day and to aspirin 3600 mg/day.
In controlled clinical trials of rheumatoid arthritis patients, Relafen has been used in combination
with gold, d-penicillamine and corticosteroids.
There is considerable interpatient variation in response to Relafen. Therapy is usually initiated at
a Relafen dose of 1000 mg daily, then adjusted, if needed, based on clinical response.
In clinical trials with osteoarthritis and rheumatoid arthritis patients, most patients responded to
Relafen in doses of 1000 mg/day administered nightly; total daily dosages up to 2000 mg were
used. In open-labeled studies, 1,490 patients were permitted dosage increases and were
followed for approximately 1 year (mode). Twenty percent of patients (n=294) were withdrawn
for lack of effectiveness during the first year of these open-labeled studies. The following table
provides patient-exposure to doses used in the U.S. clinical trials:
Relafen (nabumetone) in osteoarthritis and rheumatoid arthritis
Mean/Mode Number of Duration of Patients Treatment (yrs.) Relafen Dose OA RA OA RA
500 mg 17 6 0.4/- 0.2/- 1000 mg 917 701 1.2/1 1.4/1 1500 mg 645 224 2.3/1 1.7/1 2000 mg 15 100 0.6/1 1.3/1
As with other NSAIDs, the lowest dose should be sought for each patient. Patients weighing
under 50 kg may be less likely to require dosages beyond 1000 mg. Therefore, after observing
the response to initial therapy, the dose should be adjusted to meet individual patients’
requirements.
Relafen is indicated for acute and chronic treatment of signs and symptoms of osteoarthritis and
rheumatoid arthritis.
Relafen is contraindicated in patients who have previously exhibited hypersensitivity to it.
Relafen is contraindicated in patients in whom Relafen, aspirin or other NSAIDs induce asthma,
urticaria or other allergic-type reactions. Fatal asthmatic reactions have been reported in such
patients receiving NSAIDs.
Risk of G.I. Ulceration, Bleeding and Perforation with NSAID Therapy: Serious gastrointestinal
toxicity such as bleeding, ulceration and perforation can occur at any time, with or without
warning symptoms, in patients treated chronically with NSAID therapy. Although minor upper
gastrointestinal problems, such as dyspepsia, are common, usually developing early in therapy,
physicians should remain alert for ulceration and bleeding in patients treated chronically with
NSAIDs even in the absence of previous G.I. tract symptoms.
In controlled clinical trials involving 1,677 patients treated with Relafen (1,140 followed for 1 year
and 927 for 2 years), the cumulative incidence of peptic ulcers was 0.3% (95% CI: 0%, 0.6%) at
3 to 6 months, 0.5% (95% CI; 0.1%, 0.9%), at 3 to 6 months, 0.5% (95% CI; 0.1%, 0.9%) at 1
year and 0.8% (95% CI, 0.3%, 1.3%) at 2 years. Physicians
should inform patients about the
signs and symptoms of serious G.I. toxicity and what steps to take if they occur. In patients with
active peptic ulcer, physicians must weigh the benefits of Relafen (nabumetone) therapy against
possible hazards, institute an appropriate ulcer treatment regimen and monitor the patients’
progress carefully.
Studies to date have not identified any subset of patients not at risk of developing peptic
ulceration and bleeding. Except for a prior history of serious G.I. events and other risk factors
known to be associated with peptic ulcer disease, such as alcoholism, smoking, etc., no risk
factors (e.g., age, sex) have been associated with increased risk. Elderly or debilitated patients
seem to tolerate ulceration or bleeding less well than other individuals and most spontaneous
reports of fatal G.I. events are in this population.
High doses of any NSAID probably carry a greater risk of these reactions, although controlled
clinical trials showing this do not exist in most cases. In considering the use of relatively large
doses (within the recommended dosage range), sufficient benefit should be anticipated to offset
the potential increased risk of G.I. toxicity.
General
Renal Effects: As a class, NSAIDs have been associated with renal papillary necrosis and other
abnormal renal pathology during long-term administration to animals.
A second form of renal toxicity often associated with NSAIDs is seen in patients with conditions
leading to a reduction in renal blood flow or blood volume, where renal prostaglandins have a
supportive role in the maintenance of renal perfusion. In these patients, administration of an
NSAID results in a dose-dependent decrease in prostaglandin synthesis and, secondarily, in a
reduction of 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 the elderly. Discontinuation of NSAID therapy is
typically followed by recovery to the pretreatment state.
Because nabumetone undergoes extensive hepatic metabolism, no adjustment of Relafen
dosage is generally necessary in patients with renal insufficiency. However, as with all NSAIDs,
patients with impaired renal function should be monitored more closely than patients with normal
renal function (see CLINICAL PHARMACOLOGY, Special Studies). The oxidized and
conjugated metabolites of 6MNA are eliminated primarily by the kidneys. The extent to which
these largely inactive metabolites may accumulate in patients with renal failure has not been
studied. As with other drugs whose metabolites are excreted by the kidneys, the possibility that
adverse reactions (not listed in ADVERSE REACTIONS) may be attributable to these
metabolites should be considered.
Hepatic Function: As with other NSAIDs, borderline elevations of one or more liver function
tests may occur in up to 15% of patients. These abnormalities may progress, may remain
essentially unchanged, or may return to normal with continued therapy. The ALT (SGPT) test is
probably the most sensitive indicator of liver dysfunction. Meaningful (3 time the upper limit of
normal) elevation of ALT (SGPT) or AST (SGOT) have occurred in controlled clinical trials of
Relafen (nabumetone) in less than 1% of patients. A patient with symptoms and/or signs
suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be
evaluated for evidence of the development of a more severe hepatic reaction while on Relafen
therapy. Severe hepatic reactions, including jaundice and fatal hepatitis, have been reported
with other NSAIDs. Although such reactions are rare, if abnormal liver tests persist or worsen, if
clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations
occur (e.g., eosinophilia, rash, etc.), Relafen should be discontinued. Because nabumetone’s
biotransformation to 6MNA is dependent upon hepatic function, the biotransformation could be
decreased in patients with severe hepatic dysfunction. Therefore, Relafen should be used with
caution in patients with severe hepatic impairment (see Pharmacokinetics, Hepatic Impairment).
Fluid Retention and Edema: Fluid retention and edema have been observed in some patients
taking Relafen. Therefore, as with other NSAIDs, Relafen should be used cautiously in patients
with a history of congestive heart failure, hypertension or other conditions predisposing to fluid
retention.
Photosensitivity: Based on U.V. light photosensitivity testing, Relafen may be associated with
more reactions to sun exposure than might be expected based on skin tanning types.
Information for Patients: Relafen, like other drugs of its class, is not free of side effects. The
side effects of these drugs can cause discomfort and rarely, there are more serious side effects,
such as gastrointestinal bleeding, which may result in hospitalization and even fatal outcome.
NSAIDs are often essential agents in the management of arthritis, but they also may be
commonly employed for conditions which are less serious. Physicians may wish to discuss with
their patients the potential risks (see WARNINGS, PRECAUTIONS and ADVERSE
REACTIONS) and likely benefits of NSAID treatment, particularly when the drugs are used for
less serious conditions where treatment without NSAIDs may represent an acceptable alternative
to both the patient and the physician.
Laboratory Tests: Because severe G.I. tract ulceration and bleeding can occur without warning
symptoms, physicians should follow chronically treated patients for signs and symptoms of
ulceration and bleeding, and should inform them of the importance of this follow-up (see
WARNINGS, Risk of G.I. Ulceration, Bleeding and Perforation with NSAID Therapy).
Drug Interactions: In vitro studies have shown that, because of its affinity for protein, 6MNA may
displace other protein-bound drugs from their binding site. Caution should be exercised when
administering Relafen with warfarin since interactions have been seen with other NSAIDs.
Concomitant administration of an aluminum-containing antacid had no significant effect on the
bioavailability of 6MNA. When administered with food or milk, there is more rapid absorption;
however, the total amount of 6MNA in the plasma is unchanged (see Pharmacokinetics).
Carcinogenesis, Mutagenesis: In two-year studies conducted in mice and rats, nabumetone had
no statistically significant tumorigenic effect. Nabumetone did not show mutagenic potential in
the Ames test and mouse micronucleus test in vivo. However, nabumetone- and 6MNA-treated
lymphocytes in culture showed chromosomal aberrations at 80 mcg/mL and higher
concentrations (equal to the average human exposure to Relafen at the maximum
recommended dose).
Impairment of Fertility: Nabumetone did not impair fertility of male or female rats treated orally
at doses of 320 mg/kg/day (1888 mg/m X m) before mating.
Pregnancy: Teratogenic Effects. Pregnancy Category C. Nabumetone did not cause any
teratogenic effect in rats given up to 400 mg/kg (2360 mg/m2) orally. However, increased
post-implantation loss was observed in rats at 100 mg/kg (590 mg/m2) orally and at higher
doses (equal to the average human exposure to 6MNA at the maximum recommended human
dose). There are no adequate, well-controlled studies in pregnant women. This drug should be
used during pregnancy only if clearly needed.
Because of the known effect of prostaglandin-synthesis-inhibiting drugs on the human fetal
cardiovascular system (closure of ductus arteriosus), use of Relafen (nabumetone) during the
third trimester of pregnancy is not recommended.
Labor and Delivery: The effects of Relafen on labor and delivery in women are not known. As
with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia and
delayed parturition occurred in rats treated throughout pregnancy.
Nursing Mothers: Relafen is not recommended for use in nursing mothers because of the
possible adverse effects of prostaglandin-synthesis-inhibiting drugs on neonates. It is not known
whether nabumetone or its metabolites are excreted in human milk; however, 6MNA is excreted
in the milk of lactating rats.
Pediatric Use: Relafen is not recommended for use in children because the safety and efficacy
in children have not been established.
Geriatric Use: Of the 1,677 patients in the U.S. clinical studies who were treated with Relafen,
411 patients (24%) were 65 years of age or older; 22 patients (1%) were 75 years of age or
older. No overall differences in efficacy or safety were observed between these older patients
and younger ones. Similar results were observed in a 1-year, non-U.S. postmarketing
surveillance study of 10,800 Relafen patients, of whom 4,577 patients (42%) were 65 years of
age or older.
Adverse reaction information was derived from blinded-controlled and open-labeled clinical trials
and from worldwide marketing experience. In the description below, rates of the more common
events (greater than 1%) and many of the less common events (less than 1%) represent results
of U.S. clinical studies.
Of the 1,677 patients who received Relafen during U.S. clinical trials, 1,524 were treated for at
least 1 month, 1,327 for at least 3 months, 929 for at least a year and 750 for at least 2 years.
Over 300 patients have been treated for 5 years or longer.
The most frequently reported adverse reactions were related to the gastrointestinal tract. They
were diarrhea, dyspepsia and abdominal pain.
Gastrointestinal: Diarrhea (14%), dyspepsia (13%), abdominal pain (12%), constipation*,
flatulence*, nausea*, positive stool guaiac*, dry mouth, gastritis, stomatitis, vomiting.
Central Nervous System: Dizziness*, headache*, fatigue, increased sweating, insomnia,
nervousness, somnolence.
Dermatologic: Pruritus*, rash*.
Special Senses: Tinnitus*.
Miscellaneous: Edema*.
*Incidence of reported reaction between 3% and 9%. Reactions occurring in 1% to 3% of the
patients are unmarked.
Gastrointestinal: Anorexia, cholestatic jaundice, duodenal ulcer, dysphagia, gastric ulcer,
gastroenteritis, gastrointestinal bleeding, increased appetite, liver function abnormalities,
melena.
Central Nervous System: Asthenia, agitation, anxiety, confusion, depression, malaise,
paresthesia, tremor, vertigo.
Dermatologic: Bullous eruptions, photosensitivity, urticaria, pseudoporphyria cutanea tarda,
toxic epidermal necrolosis.
Cardiovascular: Vasculitis.
Metabolic: Weight gain.
Respiratory: Dyspnea, eosinophilic pneumonia hypersensitivity pneumonitis.
Genitourinary: Albuminuria, azotemia, hyperuricemia, interstitial nephritis, nephrotic syndrome,
vaginal bleeding.
Special Senses: Abnormal vision.
Hypersensitivity: Anaphylactoid reaction, anaphylaxis, angioneurotic edema.
+Adverse reactions reported only in worldwide postmarketing experience or in the literature, not
seen in clinical trials, are considered rarer and are italicized.
Gastrointestinal: Bilirubinuria, duodenitis, eructation, gallstones, gingivitis, glossitis, pancreatitis,
rectal bleeding.
Central Nervous System: Nightmares.
Dermatologic: Acne, alopecia, erythema multiforme, Stevens-Johnson Syndrome.
Cardiovascular: Angina, arrhythmia, hypertension, myocardial infarction, palpitations, syncope,
thrombophlebitis.
Respiratory: Asthma, cough.
Genitourinary: Dysuria, hematuria, impotence, renal stones.
Special Senses: Taste disorder.
Body as a Whole: Fever, chills.
Hematologic/Lymphatic: Anemia, leukopenia, granulocytopenia, thrombocytopenia.
Metabolic/Nutritional: Hyperglycemia, hypokalemia, weight loss.
++Adverse reactions reported only in worldwide postmarketing experience or in the literature, not
seen in clinical trials, are considered rarer and are italicized.
Since only 1 case of Relafen (nabumetone) overdose has been reported, the experience is
limited. If acute overdose occurs, it is recommended that the stomach be emptied by vomiting
or lavage and general supportive measures be instituted, as necessary. In addition, the use of
activated charcoal, up to 60 grams, may effectively reduce nabumetone absorption.
Coadministration of nabumetone with charcoal to man has resulted in an 80% decrease in
maximum plasma concentrations of the active metabolite.
The 1 overdose occurred in a 17-year-old female patient who had a history of abdominal pain
and was hospitalized for increased abdominal pain following ingestion of 30 Relafen tablets (15
grams total). Stools were negative for occult blood and there was no fall in serum hemoglobin
concentration. The patient had no other symptoms. She was given an H2-receptor antagonist
and discharged from the hospital without sequelae.
Osteoarthritis and Rheumatoid Arthritis
The recommended starting dose is 1000 mg taken as a single dose with or without food. Some
patients may obtain more symptomatic relief from 1500 mg to 2000 mg per day. Relafen
(nabumetone) can be given in either a single or twice-daily dose. Dosages over 2000 mg per
day have not been studied. The lowest effective dose should be used for chronic treatment.
Tablets: Oval-shaped, film-coated: 500 mg-white, imprinted with the product name RELAFEN
and 500, in bottles of 100 and 500 and in Single Unit Packages of 100 (intended for institutional
use only). 750 mg-beige, imprinted with the product name RELAFEN and 750, in bottles of 100
and 500 and in Single Unit Packages of 100 (intended for institutional use only).
Store at controlled room temperature (59 degrees to 86 degrees Fahrenheit) in well-closed
container; dispense in light-resistant container.
500 mg 100’s: NDC 0029-4851-20
500 mg 500’s: NDC 0029-4851-25
500 mg SUP 100’s: NDC 0029-4851-21
750 mg 100’s: NDC 0029-4852-20
750 mg 500’s: NDC 0029-4852-25
750 mg SUP 100’s: NDC 0029-4852-21
DATE OF ISSUANCE AUG. 1994
©SmithKline Beecham, 1994
SmithKline Beecham Pharmaceuticals
Philadelphia, PA 19101
RL:L7 Printed in U.S.A.