LATHAM & WATKINS SV
`
`1111111111111111111111111111111111111111111111111111111111111111
`
`Ex. 1121-0001
`
`

`
`y
`MAY 1 9 2D05
`LATHAM & WATKINS
`SILICON VALLEY, CA
`
`PHVSCANS'
`DESK
`REFERENCE.
`
`Publisher • EDWARD R. BARNHART
`
`Director of Production
`MARY TRELEWICZ
`Managing Editor
`BARBARA B. HUFF
`Medical Consultant
`NATHAN W.NEMIROFF, M.D.
`Manager of Production Services
`ELIZABETH H. CARUSO
`Traffic Coordinator
`CARRIE HENWOOp
`Index Editor
`ADELE L. DOWD
`Editorial Assistants
`JOAN AKERLIND
`DONNA CAMPAGNA
`WILLIAM A. GANZENMULLER
`Editorial Consultant
`DAVID W. SIFTON
`Administrative-Assistants
`ROSEMARIE MCGREGOR
`MARGARET SIEKMANN
`Design Director
`JOHN NEWCOMB
`
`Director of Manufacturing
`RALPH G. PELUSO
`Group Production Director
`RICHARD BIELAWSKI
`Marketing and Circulation Director
`THOMAS C. MILLER
`Assistant Circulation Director
`ANNETTE G. VERNON
`Professional Relations Manager
`ANNA E. BARBAGALLO
`Circulation Coordinator
`MARY J. CADLEY
`Senior Research Associate
`MARY BARRETT
`National Sales Manager
`SHAWN MEEHAN
`Account Managers
`JEFFERY J. BONISTALLI
`PAULL. SCALITI
`DANIEL W. STEEL
`
`~ Copyright "'i 1988 and published by Medical Economics Company Inc., at Oradell, N.J. 07649. All rights reserved. None of the content of this publication may be reproduced,
`• • stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying, or otherwise) without the prior written permission of the
`publisher. PHYSICIANS' DESK REFERENCE®, PDR®, PDR For Ophthalmology and PDR For Nonprescription Drugs® are trademarks of Medical Economics Company Inc.,
`registered in the United States Patent and Trademark Office.
`
`President and Chief Executive Officer. Thomas J. McGill; Senior Vice Presidents; Jack E. Angel , Howard C. Clutterbuck ;
`Officers of Medical Economics Company Inc.:
`Senior Vice PresidenUSecretary, Stephen J. Sorkenn; Vice Presidents: Edward R. Barnhart, Jeffrey M. Fass, James H. Jenkins, Williams J. Reynolds, Lewis A. Scaliti.
`
`ISBN 0-87489-844-7
`
`Ex. 1121-0002
`
`

`
`742
`
`Boots-Cont.
`
`' .
`
`nal irritat10n, undiluted large single doses (more than a ta(cid:173)
`blespoonful or 15 ml) of TWIN-K-Cl are to be avoided.
`To minimize gastrointestinal irritation, it is recommended
`that TWIN-K-Cl be taken with meals or diluted with water
`. or fruit juice. A tablespoonful (15 ml) in 8 ounces of water is
`· approximately isotonic. More than a single tablespoonful
`should not be taken without prior dilution.
`Deviations from this schedule may be indicated, since no
`average total daily dose can be defmed, but must be governed
`by close observation for clinical effects.
`HOWSUPPUED
`Bottles of 1 pint (16 fl. oz.)
`NDC 0524-0022-16
`Caution: Federal law prohibits dispensing without pre(cid:173)
`scription.
`
`Manufactured and Distributed by
`Boots Pharmaceuticals, Inc.
`Shreveport. Louisiana 71106 U.S.A.
`
`Rev. 11/83
`
`0022-02
`
`ZORprln®
`(aspirin)
`(Zero-Order Release)
`
`DESCRIPTION
`Each capsule-shaped tablet of WRPRIN contains 800 mg of
`aspirin, formulated in a special matrix to control the release
`of aspirin after ingestion. The in vitro release of aspirin from
`the tablet matrix is linear and independent of the concentra(cid:173)
`tion of the drug.
`The structural formula of aspirin is
`
`CLINICAL PHARMACOLOGY
`Aspirin, as contained in WRPRIN, is a salicylate that has
`demonstrated anti-inflammatory and analgesic activity. Its
`mode of action as an anti-inflammatory and analgesic agent
`may be due to the inhibition of synthesis of prostaglandins,
`although its exact mode of action is not known.
`WRPRIN dissolution is pH dependent. In vitro studies have
`shown very little aspirin to be released in acidic solutions;
`whereas, WRPRIN releases the majority of its aspirin (90%)
`in a zero-order mode at a neutral to alkaline pH. It is this pH
`dependence of WRPRIN that reduces direct contact be(cid:173)
`tween aspirin and the gastric mucosa, resulting in a reduc(cid:173)
`tion of its gastrointestinal sidiH!ffect potential.
`Bioavailability data for WRPRIN have confirmed that
`plasma levels of salicylic acid and acetylsalicylic acid can be
`measured 24 hours after a single oral dose. This substanti(cid:173)
`ates a twice daily dose regimen. Multiple dose bioavailability
`studies showed similar steady-i!tate salicylate levels for WR(cid:173)
`PRIN as for conventional release aspirin using the same
`total daily dose. Long-term monitoring of salicylate levels
`showed no signs of accumulation once steady-state levels
`were reached (4--6 days).
`Studies of in vivo prostaglandin levels (PGE2) have shown
`WRPRIN plasma levels of salicylic acid and acetylsalicylic
`acid to reduce PGE2 levels 14 hours after a single oral 800
`mg dose while an equivalent dose of aspirin produced a re(cid:173)
`duction of PGE2 levels only through six hours. WRPRIN's
`effect on other prostaglandins than PGE2 has not been deter(cid:173)
`mined.
`Salicylates are excreted mainly by the kidney, and from
`studies in humans it appears that salicylate is excreted in
`the urine as free salicylic acid (10%); salicyluric acid (75%);
`salicylic phenolic (10%); acyl glucuronides (5%) and gentisic
`acid (<1%).
`INDICATIONS & USAGE
`WRPRIN is indicated for the treatment of rheumatoid ar(cid:173)
`thritis and osteoarthritis. The safety and efficacy of WR(cid:173)
`PRIN have not been established in those rheumatoid ar(cid:173)
`thritic patients who are designated by the American Rheu,
`matism Association as Functional Class IV (incapacitated,
`largely or wholly bedridden, or confined to wheelchair, little
`or no self-care).
`In patients treated with WRPRIN for rheumatoid arthritis
`and osteoarthritis, the anti-inflammatory action of WR(cid:173)
`PRIN has been shown by reduction in pain, morning stiff(cid:173)
`ness and disease activity as assessed by both the investiga(cid:173)
`tors and patients.
`In clinical studies in patients with rheumatoid arthritis and
`osteoarthritis, WRPRIN has been shown to be comparable
`to conventional release aspirin in controlling the aforemen(cid:173)
`tioned signs and symptoms of disease activity and to be asso(cid:173)
`ciated with a statistically significant reduction in the milder
`gastrointestinal side effects (see ADVERSE REACTIONS).
`WRPRIN may be well tolerated in some patients who have
`
`Product Information
`
`had gastrointestinal side effects with conventional release
`aspirin, but these patients when treated with WRPRIN
`should be carefully followed for signs and symptoms of gas(cid:173)
`trointestinal bleeding and ulceration.
`Since there have been no controlled trials to demonstrate
`whether or not there is any beneficial effect or harmful in(cid:173)
`teraction with the use of WRPRIN in conjunction with
`other nonsteroidal anti-inflammatory agents (NSAI), the
`combination cannot be recommended (see Drug Interac(cid:173)
`tions).
`Because of its relatively long onset of action, ZORPRIN is not
`recommended for antipyresis or for short-term analgesia.
`CONTRAINDICATIONS
`WRPRIN should not be used in patients known to be hyper(cid:173)
`sensitive to salicylates or in individuals with the syndrome of
`nasal polyps, angioedema, bronchospastic reactivity to aspi(cid:173)
`rin, renal or hepatic insufficiency, hypoprothrombinemia or
`other bleeding disorders. WRPRIN is not recommended for
`children under 12 years of age; it is contraindicated in all
`children with fever accompanied by dehydration.
`WARNINGS
`WRPRIN should be used with caution when anticoagulants
`are prescribed concurrently, since aspirin may depress plate(cid:173)
`let aggregation and increase bleeding time. Large doses of
`salicylates may have hypoglycemic action and enhance the
`effect of the oral hypoglycemics; concomitant use therefore is
`not recommended. However, if such use is necessary, dosage
`of the hypoglycemic agent must be reduced. The hypoglyce(cid:173)
`mic action of the salicylates may also necessitate adjustment
`of the insulin requirements of diabetics.
`While salicylates in large doses have a uricosuric effect,
`smaller amounts may reduce urate excretion and increase
`serum uric acid.
`Although ZORPRIN is not Indicated for the treatment of
`chicken pox or flu, nor for use in children under the age of
`twelve, children and teenagers, before using this product for
`or while suffering from chicken pox, influenza or flu symp.
`toms, should consult a doctor. Aspirin may increase the risk
`of developing Reye's Syndrome, a rare but serious illness.
`USE IN PREGNANCY: Aspirin can harm the fetus when
`administered to pregnant women. Aspirin interferes with
`maternal and infant hemostasis and may lengthen the dura(cid:173)
`tion of pregnancy and parturition. Aspirin has produced
`teratogenic effects and increases the incidence of stillbirths
`and neonatal deaths in animals.
`If this drug is used during pregnancy, or if the patient
`becomes pregnant while taking this drug, the patient should
`be apprised of the potential hazard to the fetus.
`Aspirin should not be taken during the last 3 months of preg(cid:173)
`nancy.
`PRECAUTIONS
`Appropriate precautions should be 'taken in prescribing
`WRPRIN for patients who are known to be sensitive to aspi(cid:173)
`rin or salicylates. Particular care should be used when pre(cid:173)
`scribing this medication for patients with erosive gastritis,
`peptic ulcer, mild diabetes or gout. As with all salicylate
`drugs, caution should be exercised in prescribing WRPRIN
`for those patients with bleeding tendencies or those on anti(cid:173)
`coagulants. ·
`In order to avoid exacerbation of disease or adrenal insuffi(cid:173)
`ciency, patients who have been on prolonged corticosteroid
`therapy should have their therapy tapered slowly rather
`than discontinued abruptly when WRPRIN is made a part
`of the treatment program.
`Patients receiving large doses of aspirin and/ or prolonged
`therapy may develop mild salicylate intoxication (salicylism)
`that may be reversed by dosage reduction.
`Saiicylates can produce changes in thyroid function tests.
`Salicylates should be used with caution in patients with se(cid:173)
`vere hepatic damage, preexisting hypoprothrombinemia,
`Vitamin K deficiency and in those undergoing surgery.
`Since aspirin release from WRPRIN® (aspirin) is pH de(cid:173)
`pendent, it may change in those conditions where the gastric
`pH has been increased as a result of antacids, gastric secre(cid:173)
`tion inhibitors or surgical procedures.
`Drug Interactions: (See WARNINGS) Aspirin may inter(cid:173)
`fere with some anticoagulant and antidiabetic drugs. Drugs
`which lower serum uric acid by increasing uric acid excre(cid:173)
`tion (uricosurics) may be antagonized by the concomitant use
`of aspirin, particularly in doses less than 2.0 grams/ day.
`Nonsteroidal anti-inflammatory drugs may be competitively
`displaced from their albumin binding sites by aspirin. This
`effect may negate the clinical efficacy of both drugs. Also, the
`gastrointestinal inflammatory potential of nonsteroidal
`anti-inflammatory drugs may be potentiated by aspirin. The
`combination of alcohol and aspirin may increase the risk of
`gastrointestinal bleeding.
`Aspirin may enhance the activity of methotrexate and in-
`crease its toxicity.
`,
`Sodium excretion produced by spironolactone may be de(cid:173)
`creased in the presence of salicylates. Concomitant adminis(cid:173)
`tration of other anti-inflammatory drugs may increase the
`risk of gastrointestinal ulceration. Urinary alkalinizers de(cid:173)
`crease aspirin's effectiveness by increasing the rate of sali-
`
`cylate renal excretion. Phenobarbital decreases
`effectiveness by enzyme induction.
`Pregnancy Category D. See WARNINGS Section.
`Nursing Mothers: Salicylates have been detected
`breast milk of nursing mothers. Because of the
`serious adverse reactions in nursing infants
`decision should be made whether to discotttiime
`discontinue the drug, taking into account the ~•••u""''•
`drug to the mother.
`ADVERSE REACTIONS
`Hematologic: Aspirin interferes with hemostasis.
`with a history of blood coagulation defects or recetVtn•-·•
`coagulant drugs or with severe anemia
`PRIN. Aspirin used chronically may cause a l''"nnstent Ul
`deficiency anemia.
`Gastrointestinal: Aspirin may potentiate peptic
`cause stomach distress or heartburn. Aspirin
`increase in occult bleeding and in some
`gastrointestinal bleeding. However, the greatest
`active drug from WRPRIN is designed to occur in
`intestine over a period of time. This has resulted in
`symptomatic gastrointestinal side effects.
`Allergic: Allergic and anaphylactic reactions have
`noted when hypersensitive individuals have taken
`Fatal anaphylactic shock, while not common, has beea
`ported.
`Respiratory: Aspirin intolerance, manifested by
`tion of bronchospasm and rhinitis, may occur
`with a history of nasal polyps, asthma, or rhinitis.
`anism of this intolerance is unknown but may be
`aspirin-induced shunting of prostaglandin
`lipoxygenase pathway and the liberation of leukotri!IU
`e.g., slow-reacting substance of anaphylaxis.
`Dermatologic: Hives, rashes, and angioedema may
`especially in patients suffering from chronic
`Central Nervous System: Taken in nv••r<los.,..
`vides stimulation which may be manifested by WllJmu•,.u
`. lowing initial stimulation, depression of the central
`system may be noted.
`Renal: Aspirin rarely may aggravate chronic
`ease.
`Hepatic: High doses of aspirin have been reported
`duce reversible hepatic dysfunction.
`· OVERDOSAGE
`Overdosage, if it occurs would produce the usual
`of salicylism: tinnitus, vertigo, headache,
`ness, sweating, hyperventilation, vomiting
`Plasma salicylate levels in adults may range
`mg/ dl in the mildly intoxicated patient to 110
`in the severely intoxicated patient. An arterial
`7.1 may indicate serious poisoning. The
`ates in children is much slower than
`receive due consideration when aspirin ove)'([OSl!U!eBOOIIIIR
`infants; salicylate half-lives of 30 hours have
`in infants 4--6 months old. Treatment for
`·
`should include emptying the stomach with an emetJC;CII'I•
`tric lavage with 5% sodium bicarbonate. Incliviidwllls 1111111•
`ing from severe intoxication should, in
`diuresis by intravenous infusions of sodium hi~arboDBI~••
`dextrose or sodium lactate. In extreme cases, he•nocliall . . B
`peritoneal dialysis may be required.
`('A plasma salicylate level of 160 mg/ dl in an
`ally considered lethal.)
`DOSAGE & ADMINISTRATION
`In orikr to achieve a zero-orikr release, the tablets
`PRIN should be swallowed intact.
`Breaking the tablets or disrupting the structure will
`release profile of the drug.
`It is recommended that WRPRIN be taken with
`. J,d
`quantities of fluids (8 oz. or more).
`Adult Dosage: For mild to moderate pain assoclll
`rheumatoid arthritis and osteoarthritis, the ...,.,ntJDI!Il•
`initial dose of WRPRIN is 1800 mg (2-800 mg _, _,_,,. .. .,
`day. Because ofWRPRIN's prolonged
`the bloodstream, the tablets may be taken
`Further adjustment of the dosage should
`the physician, based upon the patient's
`Since it will take ~ days to reach Rt..cRd'•-state
`cylic acid with WRPRIN, it is rec:ommecnd•~
`given for at least one week before further
`general, patients with rheumatoid arthritis
`higher doses of WRPRIN than do patients witb
`tis.
`ZORPRIN is not recommended for children beloW
`12.
`HOWSUPPUED
`ZORPRIN Tablets 800 mg; plain, white ""'"'ulle-51lllr'
`lets.
`·thotJI
`Bottles of 100 Tablets--NDC 0524-0057 .{)1
`Caution: Federal law prohibits dispensing WI
`scription.
`
`Ex. 1121-0003
`
`

`
`revisions
`
`t No 4,308,251
`paten soOTS PHARMACEUTICALS. INC.
`Shreveport. Louisiana 71106 USA
`0057.{)8
`. "--'uct Identiftcaticn Section, page 406
`.... :J.81
`.,.. ShoWn Ill rrvu
`
`-----!"" & Company
`sox :o ARROYO PARKWAY
`
`:~~ADENA. CA 91105
`
`~® FORTE SYRUP
`1J111 SOlution
`
`,_oDUCI' oVERVIEW
`JIY ~A~yruJ) is a unique combination of two antihista(cid:173)
`::. :Ud a proven antitussive in a sodium free, pleasant
`lllliD' vehicle.
`... _tOR USES
`-
`F rte baa been used successfully for many yeara to
`~ 0cough suppressant action where a narcotic antitus-
`1""'!""7 di~ted or where the cough is caused by a histamine
`ift tiiD -
`IIIPCJDII!·
`8AfETY INFORMATION
`atra Forte is contraindicated in patients with allergies ~
`formula ingredients and should be used With caution m
`~ts with hypertension, cardiac disease, diabetes or hy(cid:173)
`;.rt~tyroidism.
`PBJ!SCIUBING INFORMATION
`CITfiA® FORTE SYRUP
`0111 Solution
`ooMPOSITION
`ea. 5 ml
`~~~~~~~~~ .. ~~~~~~~~.~~:. .. ~ ..................... 5 mg
`
`=~~:~~ .. :::::::::::::::::::::::::::::::::::::::::::::::::::3~3~ ::::
`
`Akabol2% in a pleasant flavored syrup base with Ascorbic
`Add 30 mg and Potassium Citrate 150 mg.
`ACI'ION AND lJSES
`arRA FORTE SYRUP: Antitussive, Expectorant, Antihis(cid:173)
`tlminic, Provides effective cough suppressant action sodium
`he. Two antihistamines to help control allergic reactions.
`ADMINISTRATION AND DOSAGE
`arRA FORTE SYRUP: Usual Adult Dose. -One or two tea(cid:173)
`.,onfuls every 3 or 4 houra. Children (6-12l--<>ne-half adult
`'-'ce· Children under 6 years-according to standard
`.elhod of calculation.
`PRECAUTIONS
`l'llients should be advised to avoid using machinery or driv(cid:173)
`llc until response to antihistamines is established. Use with
`• lion in patients with idiosyncrasies to formula ingredi(cid:173)
`- CITRA FORTE should be used with caution in patients
`'Iiiii hypertension, cardiac disease, diabetes or hyperthyroi(cid:173)
`ilm.
`BOW SUPPilED
`aTRA FORTE SYRUP in pints and gallons.
`Clution: Federal (USA) law prohibits dispensing without
`Pftleription.
`
`1'111VA® DOUCHE POWDER
`fOR VAGINAL USE ONLy
`
`l'RODUCI' OVERVIEW
`IIYFACI'S
`;r~der .effectively treats Monilial and Trichomonal
`friet mf~tions as well as non-specific Vulvovaginitis.
`ment IS antiseptic as well as symptomatic.
`IIA.Joa USES
`~Used as directed as a douche, chronic, stubborn cases of
`1111 be and Trichomonas occurring separately or together
`eradtcated along with symptoms.
`~~~MATION
`1'!it8 .onally Irntation occurs at the onset of treatment.
`IIUla ~ cont;aindicated in patients with allergies to the for-
`mgrechents.
`~lNG INFORMATION
`~VA® DOUCHE POWDER
`VAGINAL USE ONLy
`!!.IIPosiTION
`~~~he Powder contains (per 3 g packet)_:
`~I ~IS Benzoate .......................................... 60 mg (2%)
`ulfonate ............................................ 1.05 g (35%)
`
`Product Information
`Disoclium Edetate ............................................... 10 mg (0.33%)
`Sodium Sulfate .................................................... 1.59 g (52.5%)
`Lactose (dispersant) ......................................... 290 mg (9.67%)
`ACTION AND USES
`TRIV A DOUCHE POWDER effectively treats Monilial and
`Trichombnal as well as Non-specific Vulvovaginitis. Chronic,
`stubborn cases as well as Monilia and Trichomonas occur(cid:173)
`ring together can be successfully treated. Organisms are
`eradicated along with symptoms. Vaginal flora and pH re(cid:173)
`turn to normal spontaneously. Trichomonacidal, bacterici(cid:173)
`dal, detergent and chelating agents are provided for a safe,
`simple, patient-administered treatment without need for
`restraints on patient's activities. Flushing and detergent
`action of the douche quickly destroys the infection and stops
`the symptoms.
`Effectiveness of TRIV A DOUCHE POWDER has been dem(cid:173)
`onstrated by clinical tests. Both diagnosis and cure were es(cid:173)
`tablished by the use of special Papanicolaou smear and Sab(cid:173)
`ouraud culture.
`ADMINISTRATION AND DOSAGE
`TRIV A DOUCHE POWDER (individual packet dissolved in
`1 qt water) is effective in most cases of Monilial, Trichomonal
`and Non-specific Vulvovaginitis. It provides rapid relieffrom
`symptoms. Particularly useful in pre- and pos~perative and
`post-partum care. May be used adjunctively with oral treat(cid:173)
`ment for Trichomonas.
`TRIV A DOUCHE POWDER, sig, douche (1 packet in 1 qt
`water) morning and night for 12 days.
`IMPORTANT: During menstruation, continue treatment as
`instructed.
`PRECAUTIONS
`Occasionally, irritation occurs at the onset "Of treatment. In
`such cases it is recommended that the douche be prescribed
`in one-half or less than usual strength for a day or two, then
`treatment resumed as directed.
`SIDE EFFECTS
`None.
`CONTRAINDICATIONS
`Allergy or hypersensitivity to any ingredient.
`HOW SUPPLIED
`TRIV A DOUCHE POWDER- 24 individual 3 G packets.
`
`Braintree Laboratories, Inc.
`285 WASHINGTON STREET
`BRAINTREE, MA 02184
`
`GoLYTELY®
`.
`[go-lft'le]
`PEG-3350 and Electrolytes For Oral Solution
`
`DESCRIPTION
`A white powder for reconstitution containing 236 g polyethy(cid:173)
`lene glycol 3350, 22.7 4 g sodium sulfate, 6. 7 4 g sodium bicar(cid:173)
`bonate, 5.86 g sodium chloride, and 2.97 g potassium chlo(cid:173)
`ride. When dissolved in water to a volume of 4 litera,
`GoL YTEL Y is an isosmotic solution having a mildly salty
`taste. GoL YTEL Y is administered orally or via nasogastric
`tube.
`CLINICAL PHARMACOLOGY
`GoL YTEL Y induces a diarrhea which rapidly cleanses the
`bowel, usually within four houra. The osmotic activity of
`polyethylene glycol 3350 and the electrolyte concentration
`result in virtually no net absorption or excretion of ions or
`water. Accordingly, large volumes may be administered
`without significant changes in fluid or electrolyte balance.
`INDICATIONS AND USAGE
`GoL YTEL Y is indicated for bowel cleansing prior to colonos(cid:173)
`copy and barium enema x-ray examination.
`CONTRAINDICATIONS
`GoL YTEL Y is contraindicated in patients with gastrointesti(cid:173)
`nal obstruction, gastric retention, bowel perforation, toxic
`colitis, toxic megacolon or ileus.
`WARNINGS
`No additional ingredients, e.g. flavorings, should be added to
`the solution. GoL YTEL Y should be used with caution in pa(cid:173)
`tients with severe ulcerative colitis.
`PRECAUTIONS
`General: Patients with impaired gag reflex, unconscious or
`semiconscious patients, and patients prone to regurgitation
`or aspiration, should be observed during the administration
`of GoL YTEL Y, especially if it is administered via nasogastric
`tube. If a patient experiences severe bloating, distention or
`abdominal pain, administration should be slowed or tempo(cid:173)
`rarily discontinued until the symptoms abate. If gastrointes(cid:173)
`tinal obstruction or perforati011' is suspected, appropriate
`studies should be performed to rule out these conditions be(cid:173)
`fore administration of GoLYTELY.
`
`743
`
`Information for patients: GoLYTELY produces a watery
`stool which cleanses the bowel before examination. Prepare
`the solution according to the instructions on the bottle. It is
`more palatable if chilled. For best results, no solid food
`should be consumed during the 3 to 4 hour period before
`drinking the solution, but in no case should solid foods be
`• '
`eaten within 2 houra of taking GoL YTELY.
`Drink 240 ml (8 oz.) every 10 minutes. Rapid drinking of each
`portion is better than drinking small amounts continuously.
`The firat bowel movement should occur approximately one
`hour after the start of GoL YTEL Y administration. You may
`experience some abdominal bloating and distention before
`the bowels start to move. If severe discomfort or distention
`occur, stop drinking temporarily or drink each portion at
`longer intervals until these symptoms disappear. Continue
`drinking until the watery stool is clear and free of solid mat(cid:173)
`ter. This usually requires at least 3 litera and it is best to
`drink all of the solution. Any unused portion should be dis(cid:173)
`carded.
`Drug Interactions: Oral medication administered within
`one hour of the start of administration of GoL YTEL Y may be
`flushed from the gastrointestinal tract and not absorbed .
`Carcinogenesis, Mutagenesis, Impairment of Fertility:
`Carcinogenic and reproductive studies with animals have
`not been performed.
`Pregnancy: Category C. Animal reproduction studies have
`not been conducted with GoLYTELY. It is also not known
`whether GoLYTELY can cause fetal harm when adminis(cid:173)
`tered to a pregnant woman or can affect reproductive capac(cid:173)
`ity. GoLYTELY should be given to a pregnant woman only if
`clearly needed.
`Pediatric Use: Safety and effectiveness in children have not
`been established.
`ADVERSE REACTIONS
`Nausea, abdominal fullness and bloating are the most com(cid:173)
`mon adverse reactions (occurring in up to 50% of patients) to
`administration ofGoLYTELY. Abdominal cramps, vomiting
`and anal irritation occur less frequently. These adverse reac(cid:173)
`tions are transient and subside rapidly. Isolated cases of urti(cid:173)
`caria, rhinorrhea and dermatitis have been reported which
`may represent allergic reactions.
`DOSAGE AND ADMINISTRATION
`The recommended dose for adults is 4 litera of GoL YTEL Y
`solution prior to gastrointestinal examination, as ingestion
`of this dose produces a satisfactory preparation in over 95%
`of patients. Ideally the patient should fast for approximately
`three or four houra prior to GoL YTEL Y administration, but
`in no case should solid food be given for at least two hours
`before the solution is given.
`GoL YTELY is usually administered orally, but may be given
`via nasogastric tube to patients who are unwilling or unable
`to drink the solution. Oral administration is at a rate of 240
`ml (8 oz.) every 10 minutes, until4litera are consumed or the
`rectal effluent is clear. Rapid drinking of each portion is pre(cid:173)
`ferred to drinking small amounts continuously. Nasogas(cid:173)
`tric tube administration is at the rate of 2Ch!O ml per min(cid:173)
`ute (1.2-1.8 liters per hour). The first bowel movement
`should occur approximately one hour after the start of
`GoL YTEL Y administration.
`Various regimens have been used. One method is to schedule
`patients for examination in midmorning or later, allowing
`the patients three houra for drinking and an additional one
`hour period for complete bowel evacuation. Another method
`is to administer GoL YTEL Yon the evening before the exam(cid:173)
`ination, particularly if the patient is to have a barium en(cid:173)
`ema.
`Preparation of the solution: GoL YTEL Y solution is pre(cid:173)
`pared by filling the container to the 4 liter mark with water
`and shaking vigorously several times to insure that the in(cid:173)
`gredients ate dissolved. Dissolution is facilitated by using
`lukewarm water. The solution is more palatable if chilled
`before administration. The reconstituted solution should be
`refrigerated and used within 48 hours. Discard any unused
`portion.
`HOW SUPPLIED
`In powdered form, for oral administration as a solution fol(cid:173)
`lowing reconstitution. Each disposable jug contains, in pow(cid:173)
`dered form: polyethylene glycol 3350 236 g, sodium sulfate
`22.74 g, sodium bicarbonate 6.74 g, sodium chloride 5.86 g,
`potassium chloride 2.97 g. When made up to 4litera volume
`with water, the solution contains PEG 3350 17.6 mmol/L,
`sodium 125 mmoi!L, sulfate 40 mmoi!L, chloride 35
`mmoi!L, bicarbonate 20 mmol/L and potassium 10 mmoi!L.
`CAUTION
`Federal law prohibits dispensing without prescription.
`STORAGE
`Store in sealed container at 59"-86"F. When reconstituted,
`keep solution refrigerated_ Use within 48 houra. Discard
`unused portion.
`
`Continued on next page
`
`Ex. 1121-0004
`
`

`
`1348
`
`Merck Sharp & Dohme-Cont.
`
`Hypokalemia may develop, especially with brisk diuresis,
`when severe cirrhosis is present, during concomitant use of
`corticosteroids or ACI'H, or after prolonged therapy.
`Interference with adequate oral electrolyte intake will con(cid:173)
`tribute to hypokalemia. Hypokalemia can sensitize or exag(cid:173)
`gerate the response of the heart to the toxic effects of digita(cid:173)
`lis (e.g., increased ventricular irritability). Hypokalemia
`may be avoided or treated by use of potassium supplements
`such as fo'ods with a high potassium content.
`Although any chloride deficit is generally mild and usually
`does not require specific treatment except under extraordi(cid:173)
`nary circumstances (as in liver disease or renal disease), chlo(cid:173)
`ride replacement may be required in the treatment of meta(cid:173)
`bolic alkalosis.
`Dilutional hyponatremia may occur in edematous patients
`in hot weather. Appropriate therapy is water restriction,
`rather than administration of salt, except in rare instances
`when the hyponatremia is life threatening. In actual salt
`depletion, appropriate replacement is the therapy of choice.
`Hyperuricemia may occur or acute gout may be precipitated
`in certain patients receiving thiazides.
`Insulin requirements in diabetic patients may be increased,
`decreased, or unchanged. Latent diabetes mellitus may be(cid:173)
`come manifest during thiazide therapy.
`Thiazides may increase the responsiveness to tubocurarine.
`In some patients, the administration of a non-steroidal anti(cid:173)
`inflammatory agent can reduce the diuretic, natriuretic, and
`antihypertensive effects of loop, potassium-sparing and thia(cid:173)
`zide diuretics. Therefore, when HYDROPRES and non-ste(cid:173)
`roidal anti-inflammatory agents are used concomitantly, the
`patient should be observed closely to determine if the desired
`effect of the diuretic is obtained.
`The antihypertensive effect of the drug may be enhanced in
`the postsympathectomy patient. Thiazides may decrease
`arterial responsiveness to norepinephrine. This diminution
`is not sufficient to preclude effectiveness of the pressor agent
`for therapeutic use.
`If progressive renal impairment becomes evident, consider
`withholding or discontinuing diuretic therapy.
`Thiazides may decrease serum PBI levels without signs of
`thyroid disturbance.
`Thiazides have been shoWn to increase the urinary excretion
`of magnesium; this may result in hypomagnesemia.
`Thiazides may decrease urinary calcium excretion. Thia(cid:173)
`zides may cause intermittent and slight elevation of serum
`calcium in the absence of known disorders of calcium metab(cid:173)
`olism. Marked hypercalcemia may be evidence of hidden
`hyperparathyroidism. Thiazides should be discontinued be(cid:173)
`fore carrying out tests for parathyroid function.
`Reserpine
`Since reserpine may increase gastric secretion and motility,
`it should be used cautiously in patients with a history of pep(cid:173)
`tic ulcer, ulcerative colitis, or other gastrointestinal disor(cid:173)
`der. This compound may precipitate biliary colic in patients
`with gallstones, or bronchial asthma in susceptible persons.
`Reserpine may cause hypotension including orthostatic hy(cid:173)
`potension.
`In hypertensive patients on reserpine therapy significant
`hypotension and bradycardia may" develop during surgical
`anesthesia. The anesthesiologist should be aware that reser(cid:173)
`pine has been taken, since it may be necessary to give vagal
`blocking agents parenterally to prevent or reverse hypoten(cid:173)
`sion and/ or bradycardia.
`Anxiety or depression, as well as psychosis, may develop
`during reserpine therapy. If depression is present when ther(cid:173)
`apy is begun, it may be aggravated. Mental depression is
`unusual with reserpine doses of 0.25 mg daily or less. In any
`case, HYDROPRES should be discontinued at the first sign
`.of depression. Extreme caution should be used in treating
`patients with a history of mental depression, and the possi(cid:173)
`bility of suicide should be kept in mind.
`As with most antihypertensive therapy, caution should be
`exercised when treating hypertensive patients with renal
`insufficiency, since they adjust poorly to lowered blood pres(cid:173)
`sure levels. Use reserpine cautiously with digitalis and quini(cid:173)
`dine; cardiac arrhythmias have occurred with reserpine
`preparations.
`When two or more antihypertensives are given, the individ(cid:173)
`ual dosages may have to be reduced to prevent excessive drop
`in blood pressure. In hypertensive patients with coronary
`artery disease, it is important to avoid a precipitous drop in
`blood pressure.
`Animal tumorigenicity: Rodent studies have shown that
`reserpine is an animal tumorigen, c~using an increased inci(cid:173)
`dence of mammary fibroadenomas in female mice, malig(cid:173)
`nant tumors of the seminal vesicles in male mice, and malig(cid:173)
`nant adrenal medullary tumors in male rats. These findings
`arose in 2 year studies in which the drug was administered in
`the feed at concentrations of 5 and 10 ppm-about 100 to 300
`times the usual human dose. The breast neoplasms are
`thought to be related to reserpine's prolactin-elevating ef(cid:173)
`fect. Several other prolactin-elevating drugs have also been
`
`Product Information
`
`Always consult
`
`associated with an increased incidence of mam