METABOLIC COMPLICATIONS OF ACUTE ARTERIAL OCCLUSIONS AND RELATED CONDITIONS

BRIEF SUMMARY OF PRESIRIBING

INFORMATION

T IMENTIN#{174} tIcrciII$n U U #{149} cIavvIaMW

disodlum for Intravenous potasslem Mmintstration INDICATIONS AND USAGE: TIMENTIN#{174} is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the conditions listed below: Septicemia: including bacteremia, caused by 8-lactamase producing strains of Kiebsiella spp. ‘, E. co/i’ , Staphylococcus aureus ‘ and Pseudomonas aeruginosa’ (and other Pseudomonas species’). Lower Respiratory Infections: caused by B’Iactamase producin strains of Staphylococcus aureus, Hemophilus influenzae ‘ an Kiebsiella spp’. Bone and Joint Infections: caused by 6-tactamase producing strains of Staphylococcus aureus. Skin and Skin Structure Iifections: caused by If-tactamase producing strains of Staphylococcus aureus, Kiebsiella spp. ‘. and E. coil.’ Urinary Tract ln1etiQn (complicated and uncomplicated): caused by 8-lactamase producing strains of E. coil, Kiebsiella spp., Pseudomonas aeruginosa ‘ (and other Pseudomonas spp. ‘), Citrobacter spp.’, Enterobacter cloacae ‘, Serratia marcescens ‘, and Staphylococcus aureus. ‘ Gynecologic Infections: Endometritis caused by B’ lactamase producing strains of 8. melaninogenscus’. Enterobacter spp. (including E. cloacae’), Escherichia coil. Kiebsiella pneumoniae’ , Staphylococcus aureus, and Staphylococcus epidermidis. Efficacy for this organism in this organ system was studied in fewer than 10 infections. While TIMENTIN 5 indicated only for the conditions listed above, infections caused by ticarciltin susceptible or9anisms are also amenable to TIMENTIN treatment due to its ticarcillin content. Therefore, mixed infections caused by ticarcillin susceptible organisms and 6-lactamase producing organisms susceptible to TIMENTIN should not require the addition of another antibiotic. ADVERSE REACTIONS: As with other penicillins, the following adverse reactions may occur: Hypersensitivity reactions: skin rash, pruritus, urticaria, arthralgia, myalgia, drug fever, chills, chest discomfort, and anaphylactic reactions. Central nervous system: headache, giddiness, neuromuscular hyperirritability or convulsive seizures. Gastrointestinal disturbances: disturbances of taste and smell, stomatitis, flatulence, nausea, vomiting and diarrhea, epigastric pain. Hemic and Lymphatic systems: thrombocytopenia, leukopenia,

neutropenia,

eosinophilia

and

reduction

of hemoglobin

or hematocrit. Prolongation of prothrombin time and bleeding time. Abnormalities of hepatic and renal function tests: elevation of serum aspartate aminotransferase (SGOT), serum alanine aminotransferase (SGPT), serum alkalIne phosphatase, serum LDH, serum bilirubin. Rarely, transient hepatitis and cholestatic jaundice-as with some other penicillins and some cephalosporins. Elevation of serum creatinine and/or BUN, hypernatremia. Reduction in serum potassium and uric acid. Local reactions: pain, burnin9, swelling and induration at the inlection site and thrombophlebitis with intravenous ‘administration Overdosage As with other penicilirns. TIMENTIN ri ‘o.verdosagei.has .the potential t#{231}i cause neuromuscular1 ,hypenrritability or convulsive seizures Ticarcilirn may be removed from”circulatron’by

p.pteinbrnding

hemodialysis

The molecular.weight

and pharmacokinetic

.

profile

,t#{246}gett’iir. ,wth information from a single insutticiency all suggest that this compound ‘by hemodialysis ‘ V’ I. “‘r‘‘w_J

degree

acid renal.

.

may also be removed _‘:‘i’

CONTRAINDICAT1ONS: TIMENTINis contrainclicated in patients with’ a hi tory of hypersensitivity reactiobs to any of the Denicillins “ WA NINGS: SERIIJUS AND OCCASIGNALLY FATAL ‘HYPERSENSITIVITY IANAPHYLACTOID REACTIONS HAVE BE REPORTED IN PATfENTS ON PENICiLLIN THERAPY. THE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVER ‘REACTIONS WHEN TREATED WITH CEPHALOSPORINS BEFOR INITIATING -THERAPY WITHTIMENTIN CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS CEPHALOSPORINS OR OTHER DRUGS IF AN ALLERGIC REAC’rION OCCURS TIMENTIN SHOULD BE DISCONTINUED AND THE APPROI’RIATE THERAPY INSTITUTED SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN INTRAVENOUS STEROIDS AND AiRWAY MANAGEMENT ELUDING INTUBATION, SHOUL,D ALSO BE PROVIDED AS NOICATED. ‘ ‘ PRECAUTIONS: While TIMENTIN possesses the characteristic low oxicity of the penicillin group ‘of antibiotics organ system functions should be assessed periodically during therapy Ble#{232}ding’manifestations have occurred in some patients receiving, It-lactam

antibiotics

These

reactions

have

been

associated

with1

abnormalities of coagulation tests such as clotting time, platelet aggregation and prothrombin time and are more likely to occur in patients with renal impairment If bleeding manifestations appear, TIMENTIN treatment should be discontinued and appropnate therapy instituted. TIMENTIN has only rarely been reported to cause hypokalemia. Periodic monitoring of serum potassium may be advisable in patients receiving prolonged therapy. Pregnancy (Category B): Reproduction studies have been performed in rats given doses up to 1050 mg/kg/day and have revealed no evidence of impaired fertility or harm to the fetus due to TIMENTIN. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. DOSAGE AND ADMINISTRATION: TIMENTIN should be administered by intravenous infusion 3O mm.). Usual recommended dose for systemic and urinary tract infections for average (60 k9) adults is 3.1 Gm TIMENTIN (3.1 Gm vial containing 3 Gm ticarcillin and 100 mg clavulanic acid) given every 4 to 6 hours. For gynecologic infections TIMENTIN should be administered as follows: Moderate infections 200 mg/kg/day in divided doses every 6 hours and for severe infections 300 mg/kg/day, based on ticarcillin content, In divided doses every 4 hours. For patients weighing less than 60 kg, the recommended dosage is 200’300 mg/kg/day, based on ticarcillin content, given in divided doses every 4 to 6 hours. In urinary tract infections, a dosage of 3.2 Gm TIMENTIN (3.2 Gm vial containing 3 Gm ticarcillin and 200 mg clavulanic acid) given every 8 hours is adequate. Please see oflicial package insert for details on dosages for other patients, including those with renal insufficiency, and directions for use. tin vitroactivity does not necessarily imply in vivoethcacy. flabulated results of a retrospective review of 181 patients with lower respiratory tract infections enrolled in multicenter TIMENTIN#{174} clinical trial protocols, who would appear to be candidates for ORG 79frespiratory infection + inflammation, age >69, and/or CC.). REFERENCES: 7548/G-BS ©1988, Beecham Laboratories 1. Wise R: B’Lactamase inhibitors. JAntimicrob Chemotherl982;9 (suppl B):31-40. 2. Data on file, Medical Department, ham Beecham Laboratories. laboratories

A-28

Continuedfrorn LUNG TUMORS: WALL. Edited MARTINI, and

page

A-24

LUNG, MEDIASTINUM, PLEURA h’ B. HOOCSTRATF,N, B. J. ADDIS, H. S. G. SPIRO. Berlin: Springer-Verlag, 1988,

Tumors is the twelfth by the International

Lung sponsored

in a series on Union Against

Current Cancer

AND CHEST H. HANSEN, N. 272 pp. $59.50

Treatment (t’ICC).

of Cancer The book is

in two parts: part one covers lung tumors; part two. all other tumors of the mediastinum, pleura and chest wall. Epidemiology: hiolog screening and detection, pathology and clinical and diagnostic aspects. as well as treatments, are fully discussed. Contributors are authorities from three prestigious institutions: Memorial Sloan-Kettering. New York: Brompton Hospital, London: and Finsen Institute, Copenhagen. Each expresses his approach to treatment for lung tumors. There is a well-written chapter on malignant mesothelioma. Radioand chemotherapy ofall tumors are fully discussed. In general, the bOok S well-written and well-edited. However. quality is uneven from chapter to chapter. For example. chapter four by B. J. Addis, on the pathology of lung cancer and tumors of the pleura and chest wall, is superb with excellent illuStrations and well-researched references. Other chapters provide fes; if any, references. In a multi-author text, the material often is outdated; 1986. Similarly, staging method,

here, only two chapters provide the text does not mention magnetic use of neo-adjuvant chemotherapy.

references as recent as resonance imaging as a or combined radiation

and chemotherapy for non-small cell lung cancer. Also, recent mechanisms by which lung tumors produce paraneoplastic syndromes are not discussed. Nevertheless, Lung Tumors is a useful hok for students, for residents on oncology service rotation, for fellows, and for physicians treating these tumors.

I anardan

D. Kliaiidekar,

M.D. Illinois

ttr(ItlStOfl,

METABOLIC

COM

AND

RELATED

‘tork:

Futura

PLICATIONS CONDITIONS.

Publishing

Company

OF

ACUTE

B’

HENRa’

Inc.

1988,

ARTERIAL

OCCLUSIONS

HAISIovICI.

328

pp.

Mt.

Kisco,

New

$45.00

of

of clavulanic patient

with

meBooNslielt

It is a pleasure to read a scientific work by a single author. This one is also attractively bound in brilliant red, stamped with gold, and the cover graphically depicts an acute arterial occlusion causing the ischemia of skeletal muscle fibers, which is the subject ofthis text. As shown in this diagram. one can see myoglobin leaking into interstitial fluid spaces through sarcolemma, and

one can note sodium entering the cell while potassium passes outward. In an August 1988 1)blication, Robert Hobson said “the acutely ischemic extremity is one ofthe most common and serious problems that the vascular surgeon must manage.” Thus, this volume is tinsel’ and it is also informative. It is an extended essay describing the author long-term interest and intimate personal knowledge of the metabolic repercussions of acute skeletal muscle ischemia. The depth of Haimovicils interest is indicated by the topics encompassed. These include sections on basic considerations, clinical entities, unusual metabolic complications and management of rhabdomvolytic syndromes. This treatise in extc’n.so is, therefore, an invaluable reference to physicians and surgeons treating a variety of syndromes including traumatic crush injslry, arterial occlusion, and renal failure secondary to prolonged extremity ischemia. That the volume is up-to-date is indicated by the chapters on complications of thrombolytic agents, malignant hyperpyrexia. circulation i)f skeletal muscle free radicals during reperfstsion injury, and the role of scavenging agents. In the authoris epilogue, there is no hint that this is to he his last work on the subject. One would hope that even at age 81 he will continue to focus his massive intellect upon this and perhaps other challenging problems. Jolnj

Bergan,

M.D.,

F.C.C.P. Chicago