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Prevention of calcium nephrolithiasis with low-dose thiazide, amiloride and allopurinol
KlOlRIX@ (POWSHIM CHLORIDEj
SLO~RELEASE TABLETS 10mtq OESCRlPTlON KLOTRIX IS a ftlm-coated (not enterrc-coated) tablet contarnrng 750 mg potassrum chlorrde fequrvalent to 10 rnEq) MI a wax matrrx Thts farmulatron IS Mended to provrde a controlled release of ootassrum from the matrrx to minrmrze the lrkelrhood of producrnR high localized concentratt~ns of potassrum wtthrn the gastrorntestrnai tract ” _ iNDlCAliONS-BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AN0 BLEEDING WITH SLOW-RELEASE POTASSIUM CHLORIOE PREPARATIONS, THESE DRUGS
SNDULD BE RESERVED FOR 1HOSE PAllENlS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIPUIO OR EFFERVESCENT PDBSSIUM PREPARRIONS OR FOR PATIENTS IN WHOM THERE IS A PRDDLEM OF COMPLIANCE WtlH THESE PREPARATIONS.
I For th~apeutrc use m patrents with hypokalemra with or without metabolr~ alkalosrs. in drgrtalis rntoxrcatron and rn patrents with hypokalemrc famriral perrodrc paralyses 2 For preventron of patassrum depletron when the dretary Intake of potassrum IS Inadequate rrl the followrng condrtrons Patrents recervrng drgrtalrs and druretrcs for congestrve heart farlure: hepatrc crrrhosrs wtth ascrtes; states of aldosterone excess wrth normal renal functron: potassrum-losing nephropathy, and certain diarrhea1 states. 3 The use of potassium salts rn patre~ts receivrng druretrcs for uncomplicated essentrai hypwtensron IS often unnecessary when such patrents have a normal dretary pattern Serum potassium should be checked periodically. however, and, if hypokalemta occurs, dretary supplementatron wrth potassrum-contarmngfoods may be adequate to control molder cases In more severe cases supplementatton wrth potassium salts may be rndrcated. CONTR~NDlCAnONS In patients wrth hyperkatemta, since a fu~her Increase rn serum potassium concentratr~ in such patients can produce cardiac arrest Hyperkaiemia may compileate any of thefollowrngcondrtrons: chronic renal farlure. systemrc acrdosrs such as drabetrc acidosis. acute dehydratron. extensrve tissue breakdown as rn severe burns, adrenal tnsufhcrency, or the admrnrstratron of a potassium-sparrng druretrc leg. sprronolactone, trramterenel Wax-matrrx potasstum chloride preparations have produced esophageal ulceratron rn certarn cardiac patients with esophageal compressIon due to enlarge left airrum All soled dosage forms of potassium supplements are contrar~r~ated m any patrent m whom there IS cause for arrest or delay rn tablet passage through the G.I tract In these instances, potassrum supplementatron should be wrth a Irqurd preparatron. WARNINGS Hyperkalemia: In patrents wrth rmparred mechamsms for excretrng potassrum, admrmstratron of potassrum salts can produce hyperkaiemta and cardrac arrest Thus occurs most commonly m patrents grven potassium intravenously but may also occur when given orally Potentially fatal hyperkalemra can develop rapidly and be asymplomatrc Use of potassium salts tn patrents wrth chrome renal drsease, or any other condrtron whrch Impairs potasstum excretion requires partrcularly careful momtorrng of the serum potassium concentratton and appropriate dosage adfustment Interaction with potassium-sparinf diuretics: Hypokalemra should nof be treated by the concomrtant admrnlstration of potassrum salts and a potassium-s~rrng druretrc (eg, sprronolactone or triamterene). since the slmultane~s admrnrstratron of these agents can produce severe hyperkalemra Gastrointestinal lesions: Potassium chloride tablets have produced stenotrc and/or ulcerative lessons of the small bowel and deaths. These lesions arecaused by a high localtzed concentratton of potassrum ion rn the regron of a raprdry drssolvrng tablet, whrch rnfures the bowet wall and Ihereby pr~uces obstructran, hemorrhage, or peroration KLOIRIX IS a wax-matrix tablet formulated to provrde a controlled rate of release of potassium chloride and thus to mrntmrze the posscbtlrty of a hrgh lcoal concqntratron oi potassium ton near the bowel wall. Whrle the reported frequency of small-bowel lessons IS much less with wax-matrix tablets (less than one per 100.000 patrent-years) than wrth enterrc-coated potassrum chlortde tablets (40-50 per 100.000 patrent-y~rs) cases assocrated wrth wax-matrix tablets have been reported both rn foretgn countrres and in the United States In addrtron, perhaps because the wax -matrix preparatrons are not entwrc-coated and release potassrum rn the stomach, there have been reports of upper gastrotntestrnal bleeding assocrated wrth these products The total number of gastrorntestlnal lessons remarns less than one per 100.000 patrent-years. KLOTRIX should be drscontrnued rmmedrately and the possrbrlrty of bowel obstruction or perforatron considered If severe vomrtrng. abdomrnal parn, dtstentron, or gastrorntestrnal bleeding occurs Me~akoljc acidosis: Hypokalemia in palrents wrth metabolrc ~c/~os;s should be treated with an aikalrmzrng potassrum salt such as potasscum bicarbonate. potassium crtrate, or potassrum acetate. PRECAUTIONS Potassrum depletion IS ordrnarrly diagnosed by demonstratrng hypokalemra in 3 patrent wrth a clrnrcal hrstory suggesting some cause for potassium depletron In interpreting the serum potassrum level. the physictan should bear tn mrnd that acute alkalosrs per se can produce hypokalemra in the absence of a deficit rn tolat body potassum. while acute acidosis pef se can increase the serum potassium concentratr~ into the normal range even in the presence of a reduced total body potassium Treatment of potassium depletron particularly rn presence of cardrac drsease. renal disease. or acrdosts. requrres careful attention to acid-base balance and approprcate monrtorrng of serum electrolyles. electrocardrogram and clrnrcal status of patrent Caronogenesrs No data are avarlable on long-term potential for carctnogentcrty In ammats or humans Piegfrancy Klotrrx IS not expected to cause fetal harm when admInIstered m dosages which WI!/ not result in hy~rkalemra ~urs/~g ~of~efs Although no studies have been done it IS presumed that potassmm chloride !s excreted rn human milk. Caution should be exercrsed when Klotrrx IS admtnrstered to a nursing woman F’ediatffc use: Safety and effectrveness in children have not been established ADVERSE REACTIONS Most common to oral potassium salts nausea. vomrttng. abdomrnal drs~omfort. and diarrhea These symptoms are due to rrritatron 01 the gastrorntestrnal tract and are best managed by drlutrng the preparatron further taking the dose with meats. or :educrng the dose One of the most severe adverse effects IS hyperkaiemra isee Gontratndicatrons and Warrnngs) There also have been reports of upper and lower gastrointestinal condrtrons rncludtng obstructron, bleeding. ulceratron and perforation (see Contrarndrcatrons and Warnrngs), other factors known to be assoctated wrth such condrtrons were present in many of these patrents Skin rash has been reported rarely DOSAGE AND ADMINISTRATIDN bsuai dietary intake potassrum by the average adult 1s 40 to 80 mZq per day Potassium depletron sufficient to cause hypokalemra usually requires loss of 200 or more mEq of potassrum from the total body store Dosage must be adjusted to the rndrvrdual needs of each patrent but IS typically in tile range of 20 mtq per day for preventton of hypokalemra to 40-100 mfq per day or more for treatment of potassrum dep~etron Note: KLO~RIX slow-release tablets must be swallowed whole and never crushed or chewed HOW SUPPLIEO Bottles of 100 1000 and Umt Dose cartons of 100
MMJKlWll
PHARMACEUTICAL
DIVISION
MJL 0 4587
SLO~RELEASE TABLETS 10mtq OESCRlPTlON KLOTRIX IS a ftlm-coated (not enterrc-coated) tablet contarnrng 750 mg potassrum chlorrde fequrvalent to 10 rnEq) MI a wax matrrx Thts farmulatron IS Mended to provrde a controlled release of ootassrum from the matrrx to minrmrze the lrkelrhood of producrnR high localized concentratt~ns of potassrum wtthrn the gastrorntestrnai tract ” _ iNDlCAliONS-BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AN0 BLEEDING WITH SLOW-RELEASE POTASSIUM CHLORIOE PREPARATIONS, THESE DRUGS
SNDULD BE RESERVED FOR 1HOSE PAllENlS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIPUIO OR EFFERVESCENT PDBSSIUM PREPARRIONS OR FOR PATIENTS IN WHOM THERE IS A PRDDLEM OF COMPLIANCE WtlH THESE PREPARATIONS.
I For th~apeutrc use m patrents with hypokalemra with or without metabolr~ alkalosrs. in drgrtalis rntoxrcatron and rn patrents with hypokalemrc famriral perrodrc paralyses 2 For preventron of patassrum depletron when the dretary Intake of potassrum IS Inadequate rrl the followrng condrtrons Patrents recervrng drgrtalrs and druretrcs for congestrve heart farlure: hepatrc crrrhosrs wtth ascrtes; states of aldosterone excess wrth normal renal functron: potassrum-losing nephropathy, and certain diarrhea1 states. 3 The use of potassium salts rn patre~ts receivrng druretrcs for uncomplicated essentrai hypwtensron IS often unnecessary when such patrents have a normal dretary pattern Serum potassium should be checked periodically. however, and, if hypokalemta occurs, dretary supplementatron wrth potassrum-contarmngfoods may be adequate to control molder cases In more severe cases supplementatton wrth potassium salts may be rndrcated. CONTR~NDlCAnONS In patients wrth hyperkatemta, since a fu~her Increase rn serum potassium concentratr~ in such patients can produce cardiac arrest Hyperkaiemia may compileate any of thefollowrngcondrtrons: chronic renal farlure. systemrc acrdosrs such as drabetrc acidosis. acute dehydratron. extensrve tissue breakdown as rn severe burns, adrenal tnsufhcrency, or the admrnrstratron of a potassium-sparrng druretrc leg. sprronolactone, trramterenel Wax-matrrx potasstum chloride preparations have produced esophageal ulceratron rn certarn cardiac patients with esophageal compressIon due to enlarge left airrum All soled dosage forms of potassium supplements are contrar~r~ated m any patrent m whom there IS cause for arrest or delay rn tablet passage through the G.I tract In these instances, potassrum supplementatron should be wrth a Irqurd preparatron. WARNINGS Hyperkalemia: In patrents wrth rmparred mechamsms for excretrng potassrum, admrmstratron of potassrum salts can produce hyperkaiemta and cardrac arrest Thus occurs most commonly m patrents grven potassium intravenously but may also occur when given orally Potentially fatal hyperkalemra can develop rapidly and be asymplomatrc Use of potassium salts tn patrents wrth chrome renal drsease, or any other condrtron whrch Impairs potasstum excretion requires partrcularly careful momtorrng of the serum potassium concentratton and appropriate dosage adfustment Interaction with potassium-sparinf diuretics: Hypokalemra should nof be treated by the concomrtant admrnlstration of potassrum salts and a potassium-s~rrng druretrc (eg, sprronolactone or triamterene). since the slmultane~s admrnrstratron of these agents can produce severe hyperkalemra Gastrointestinal lesions: Potassium chloride tablets have produced stenotrc and/or ulcerative lessons of the small bowel and deaths. These lesions arecaused by a high localtzed concentratton of potassrum ion rn the regron of a raprdry drssolvrng tablet, whrch rnfures the bowet wall and Ihereby pr~uces obstructran, hemorrhage, or peroration KLOIRIX IS a wax-matrix tablet formulated to provrde a controlled rate of release of potassium chloride and thus to mrntmrze the posscbtlrty of a hrgh lcoal concqntratron oi potassium ton near the bowel wall. Whrle the reported frequency of small-bowel lessons IS much less with wax-matrix tablets (less than one per 100.000 patrent-years) than wrth enterrc-coated potassrum chlortde tablets (40-50 per 100.000 patrent-y~rs) cases assocrated wrth wax-matrix tablets have been reported both rn foretgn countrres and in the United States In addrtron, perhaps because the wax -matrix preparatrons are not entwrc-coated and release potassrum rn the stomach, there have been reports of upper gastrotntestrnal bleeding assocrated wrth these products The total number of gastrorntestlnal lessons remarns less than one per 100.000 patrent-years. KLOTRIX should be drscontrnued rmmedrately and the possrbrlrty of bowel obstruction or perforatron considered If severe vomrtrng. abdomrnal parn, dtstentron, or gastrorntestrnal bleeding occurs Me~akoljc acidosis: Hypokalemia in palrents wrth metabolrc ~c/~os;s should be treated with an aikalrmzrng potassrum salt such as potasscum bicarbonate. potassium crtrate, or potassrum acetate. PRECAUTIONS Potassrum depletion IS ordrnarrly diagnosed by demonstratrng hypokalemra in 3 patrent wrth a clrnrcal hrstory suggesting some cause for potassium depletron In interpreting the serum potassrum level. the physictan should bear tn mrnd that acute alkalosrs per se can produce hypokalemra in the absence of a deficit rn tolat body potassum. while acute acidosis pef se can increase the serum potassium concentratr~ into the normal range even in the presence of a reduced total body potassium Treatment of potassium depletron particularly rn presence of cardrac drsease. renal disease. or acrdosts. requrres careful attention to acid-base balance and approprcate monrtorrng of serum electrolyles. electrocardrogram and clrnrcal status of patrent Caronogenesrs No data are avarlable on long-term potential for carctnogentcrty In ammats or humans Piegfrancy Klotrrx IS not expected to cause fetal harm when admInIstered m dosages which WI!/ not result in hy~rkalemra ~urs/~g ~of~efs Although no studies have been done it IS presumed that potassmm chloride !s excreted rn human milk. Caution should be exercrsed when Klotrrx IS admtnrstered to a nursing woman F’ediatffc use: Safety and effectrveness in children have not been established ADVERSE REACTIONS Most common to oral potassium salts nausea. vomrttng. abdomrnal drs~omfort. and diarrhea These symptoms are due to rrritatron 01 the gastrorntestrnal tract and are best managed by drlutrng the preparatron further taking the dose with meats. or :educrng the dose One of the most severe adverse effects IS hyperkaiemra isee Gontratndicatrons and Warrnngs) There also have been reports of upper and lower gastrointestinal condrtrons rncludtng obstructron, bleeding. ulceratron and perforation (see Contrarndrcatrons and Warnrngs), other factors known to be assoctated wrth such condrtrons were present in many of these patrents Skin rash has been reported rarely DOSAGE AND ADMINISTRATIDN bsuai dietary intake potassrum by the average adult 1s 40 to 80 mZq per day Potassium depletron sufficient to cause hypokalemra usually requires loss of 200 or more mEq of potassrum from the total body store Dosage must be adjusted to the rndrvrdual needs of each patrent but IS typically in tile range of 20 mtq per day for preventton of hypokalemra to 40-100 mfq per day or more for treatment of potassrum dep~etron Note: KLO~RIX slow-release tablets must be swallowed whole and never crushed or chewed HOW SUPPLIEO Bottles of 100 1000 and Umt Dose cartons of 100
MMJKlWll
PHARMACEUTICAL
DIVISION
MJL 0 4587