RESEARCH*-*-*0000000

Ms Tanguay is a third-year medical student andDr McBean, a Fellow ofthe College, is an AssistantProfessor in the Department ofFamily Medicine, both at theUniversity of Calgary.DrJain is an InternationalBoard Certified LactationConsultant and is MedicalDirector of the CalgaryBreas{feeding Clinic.

Nipple candidiasis amongbreastfeeding mothersCase-control study ofpredisposing_factorsKAREN E. TANGUAY, MSCMARY R. MCBEAN, MD, CCFPEVELYNJAIN, MD, CCFP

OBJECTIVE To investigate factors that predispose breastfeediing mothers to nipple candidiasis.DESIGN A retrospective case-control study ofwomen attending the Calgary Breastfceding Clinic.SETTING Ambulatory breastfeeding referral centre.

PARTICIPANTS All women (105) who attended the clinic during a 3.5-month study period. All werereferred for problems with breastfceding; 27 (the case group) had positive diagnostic criteria fornipple candidiasis. The other 78 formed a control group.MAIN OUTCOME MEASURE A patient information sheet, completed while taking a medical history,recorded the presence or absence of four possible predisposing factors. Two infant variables werealso noted on physical examination. Patients were diagnosed as having or not having nipplccandidiasis on the basis of specific clinical criteria, and statistics on other variables werecompared for those with positive and with negative diagnoses.RESULTS A statistically significant correlation (P < 0.05) was found between nipple candidiasis andthree factors: vaginal candidiasis (P = 0.001), previous antibiotic use (P = 0.036), and nippletrauma (P= 0.001).CONCLUSIONS Further research is required to establish clear causality. However, we recommendthat physicians be suspicious of nipple candidiasis; avoid antibiotics or use the shortest effectivecourse; treat yeast vaginitis during the third trimester and after delivery aggressively; and treatmothers for nipple yeast if babies have oral or diaper candidiasis. Breastfeeding mothers can alsobe counseled in preventive measures.

OBJECTIF Investiguer les facteurs qui pr6disposent les meres allaitantes A la candidose dumammelon.

CONCEPTION Etude retrospective de cas-temoins aupres des femmes frequentant la cliniqued'allaitement de Calgary.CONTEXTE Centre ambulatoire de reference pour l'allaitement.PARTICIPANTES Toutes les femmes (105) qui ont frequente la clinique pendaint les 3,5 mois de laperiode d'etude. Elles avaient toutes ete referees pour des problemes d'allaitement. Parmi cclles-ci, 27 (le groupe de cas) repondaient aux criteres diagnostiques positifs d'une candidose dumammelon. Les 78 autres ont constitue le groupe temoin.PRINCIPALES MESURES DES RESULTATS Sur une feuille de renseignements concernant la patiente, oninscrivait la presence ou l'absence de quatre facteurs pr6disposants potentiels. A l'examenphysique, on notait egalement deux variables reliees au nourrisson. Le diagnostic positif ounegatif de candidose du mammelon reposait sur quatre criteres cliniques specifiques. On acompare les statistiques concernant les autres variables entre les diagnostics positifs et lesdiagnostics negatifs.RESULTATS L'analyse a revel une correlation statistiquement significativc (p < 0,05) entre lacandidose du mammelon et trois facteurs: candidose vaginale (p = 0,001), antibiotherapieanterieure (p = 0,036) et traumatisme du mammelon (p = 0,001).CONCLUSIONS I1 est necessaire de poursuivre les recherches pour etablir clairement un lien decausalite. Nous recommandons toutefois d'etre vigilants face A la candidose du mammelon:eviter les antibiotiques ou utiliser le traitement efficace le plus court possible, traiteragressivement la candidose vaginale pendant le troisieme trimestre ou apres l'accouchcment ettraiter les meres contre la candidose du mammelon si les nourrissons presentent une candidoseorale ou un erytheme fessier A champignons. On peut 6galement donner des conscils sur lesmesures preventives aux meres qui allaitent.

Can Fam Physician 1994;40:1407-1413.

Canadian Family Plysician VOI, 40: August 1994 1407

RESEARCH

Nipple candidiasis amongbreosifeeding mothersCase-control study ofpredisposing factors

Table 1. Patient data

Have you had a previousvaginal yeast infection?

Have you been takingantibiotics?

* During pregnancy? Whatwas the reason and thetiming?

* At delivery? What was thereason and the timing?

* After delivery? What was

the reason and the timing?

Have you had any injury to

your nipple whileestablishing breastfeeding?

Do you have diabetes(gestational,insulin-dependent, or

non-insulin-dependent)?Has anyone in your familyhad diabetes?

What have you been eating?Have you had any changes to

your diet? What do you feedyour infant? Have there beenany changes to the diet?

*I ANDIDA INFEC'ITIONS HAVI' BEENreported in virtually everytissue in the human body,although by far the most

common manifestations of candidiasisare superficial lesions, especially infec-tions of the mucous surfaces of themouth and vagina.' Candida does notusually colonize healthy glabrous skin,such as the nipple. It can do so, howev-er, during lactation, causing pain anderythema.

Nipple candidiasis is characterizedby severe burning pain, as well as stab-bing pain, which often radiatesthroughout the breast and is typicallyworse after feedings.2b6 Pain and dis-comfort can lead to the early cessationof breastfeeding if the infection is notrecognized promptly and treatedappropriately.

Few researchers have investigatedthe factors that predispose nursingmothers to nipple candidiasis, althoughan association between oral thrush ininfants and nipple thrush in mothershas been reported.2'78 Early studiesshowed that cases of oral infection interm babies within the first few days oflife are caused primarily by maternalcontamination of the newborn duringdelivery.8 Candida can be present inthe mother's vagina either symptomati-cally or asymptomatically. Vaginalyeast infection has been shown toincrease during pregnancy. "

It is probable, however, that someother factor alters the host's defencesand allows yeast to colonize the nippleat pathological levels. Several condi-tions have been suggested, includingnipple trauma, diet, diabetes, cortico-steroids, and antibiotic therapy.'2 Forexample, several reports have describedcolonization of nipple fissures byCandida.ji3"4 But much of the literatureis anecdotal; very few studies haveexamined which of these factors corre-late with nipple yeast.

The most complete study to date isby Amir,'2 who attempted to identifypredisposing factors among womenattending the Family PlanningAssociation in Victoria, Australia.

Amir's findings suggested a correlationbetween nipple candidiasis and severalfactors, primarily nipple damage inearly lactation, use of antibiotics afterdelivery, previous long-term antibioticuse, and previous vaginal yeast infec-tion. The study lacked clear diagnosticcriteria, however, and the cases andcontrols were recruited from differentpatient populations. Further researchis thus required to confirm Amir'sfindings.

Our study aimed to investigate fac-tors that could predispose breastfeed-ing mothers to nipple candidiasis.Women attending the CalgaryBreastfeeding Clinic were surveyed atthe time of consultation. The patientsattending the clinic had all beenreferred because they were havingproblems with breastfeeding. This pop-ulation, therefore, had a high concen-tration of nipple candidiasis: 250%. Theretrospective case-control approachyielded a larger number of cases thanwould have been available in aprospective study.

METHODS

Sample populationInformation was gathered from allpatients attending the Calgary Breast-feeding Clinic from the beginning ofJanuary to mid-April, 1992. Thewomen were asked by the nurse lacta-tion consultant in the clinic whetherthey would like to participate in thestudy; all 105 of them signed the con-sent form.

Patients had been referred by theirprimary care physicians. The provin-cial health insurance plan covered allthe services. The main reason forattending the clinic was painful breast-feeding. Other reasons included latch-ing difficulties, inverted nipples, infantsfailing to thrive, and problems withmilk supply. The case group was com-prised of all the women (n = 27) whofulfilled the diagnostic criteria for nip-ple candidiasis. The control group wasmade up of all the women attending

1408 Canadian Fanily Physician \VOL 10: August 1994

the clinic during the study period whodid not meet the criteria for nipplecandidiasis (n = 78).

Research protocolDuring the medical history, a patientinformation sheet containing questionson the presence or absence of severalvariables was completed (Table 1).

Four different categories of putativepredisposing factors were investigated:previous yeast infection, antibiotic useduring the pregnancy or during thepostnatal period, nipple trauma, andgestational diabetes. Patients were thengiven a physical examination and diag-nosed as positive or negative for nipplecandidiasis.

Criteria for diagnosisNipple candidiasis was diagnosed sole-ly on clinical grounds. A clinical diag-nosis was chosen over culture becauseit has been demonstrated that, forCandida infections of the vagina, norelation is found between the numberof C(andida organisms isolated and thepresence of vaginal symptoms, 15

whereas aggregate symptoms had ahigh sensitivity, specificity, and predic-tive value.'" Extensive clinical experi-ence of one of the authors suggestedthat the same held true for nipple can-didiasis.

Patients were diagnosed with nipplecandidiasis if they presented with allthree of the following2'':* Severe, burning nipple and areolarpain that is worse after feedings andlasts for at least 15 minutes or for theentire period between feedings.Onset is later than the first postpar-tum week. If yeast infection super-venes in a mother with painfulnipples resulting from trauma causedby poor latching of the baby, thenature of the pain will change to thedistinct pattern of burning pain afterfeeding. Pain from candidiasis, unlikepain from trauma, does not respondto improving the nursing technique;

* Deep, shooting pains radiating intothe breast tissue, which occur duringand between feedings; and

* Red or purple discoloration of thenipple and proximal areola.

Other signs that occur frequently, butthat we did not use as diagnostic crite-ria, include a sheen on the affectedareola, mild edema of the areola, andfine circumferential cracks around thenipple. An infrequent finding is whitespots on the nipple that appear curdy,like cottage cheese.

RESEARCH

Nipple (andidiasis amongbreastfeeding mothersCase-control study ofpredisposing facors

Candidiasis infectionin the infantData were also collected on two othervariables that are reported to be associ-ated with nipple candidiasis: the pres-ence of oral thrush and Candida diaper

Table 2. Factors that could predispose women to nipplecandidiasis

PREDISPOSINGFACTOR CASES (N = 27) CONTROLS (N = 78) P LEVEL*

Vaginal 22 (81%) 35 (45%) 0.001candidiasis

Previous 14 (52%) 23 (29%) 0.036antibiotics........................................................................................I.............. ............................... ............

Nipple trauma 19 (70%) 24 (31 %) 0.001

*% analysis.

rash in the infant (at the time of physi-cal examination in the clinic).

EthicsProcedures were in accordance withthe ethical standards of the MedicalEthics Committee of the University ofCalgary.

StatisticsPercentages, X2, and probabilities werecalculated using Mystat (Systat, Inc,Evanston, Ill). The required level forstatistical significance was P < 0.05.

RESULTS

A statistically significant correlation(P < 0.05) was found between nipplecandidiasis and three of the putative

Canadian Famij Physlican voL 40n August 1994 1409

RESEARCH. . *. *....... * * .

predisposing factors: vaginal candidia-sis, nipple trauma, and previous use ofantibiotics (Table 2). The prevalence ofgestational diabetes was too low tomake any reliable deductions. Dietaryfactors were too complex to permit any

conclusions to be drawn.

TIME BEFORE DIAGNOSIS CASES CONTROLS

Durinig pregniancy 3 1 2.................................................................... .................................................................................

After delivery................................................. .......................................................-........................................

* <2 weeks 1 5

...............................-.............. ...................................I....................................................................

* 2-4 weeks 8 3.................................I.............................I..................................................................I.....................

* >4weeks 1 1

........................... ....................... ........................................................ .....................................

* Uniknown 1 2.....................................................................................................................................................TOTAL 14 23

Table 4. Concomitant Candida infection in the infant

INFECTION IN THE INFANT CASES (N = 27) CONTROLS (N = 78)

Visible oral thrush 9 (3300) 0 (000)

Diaper candidiasis 13 (4800) 0 (000)

Vaginal candidiasisAlthough many of the women in bothgroups reported previous vaginal yeastinfections at some time in their lives, a

significantly higher percentage of thegroup with nipple candidiasis reportedprevious vaginal yeast infections(P= 0.001).

Nipple traumaThere was also a strong associationbetween nipple trauma and the subse-quent development of nipple yeastinfection. Seventy percent of the case

group reported sore, cracked nipplesbefore developing the distinct symp-

toms of nipple candidiasis as comparedwith only 310% of the control group

(P< 0.001).

Use of antibioticsOf the 105 women participating in thestudy, 37 reported taking antibiotics atsome time during the prenatal or post-natal periods. Antibiotics had beentaken for several reasons, including uri-nary tract infections, upper respiratorytract infections, mastitis, and acne. Asignificantly higher percentage ofwomen in the case group than in thecontrol group had taken antibiotics(P = 0.036). Nineteen percent of thecase group and 6% of the controlgroup reported taking antibiotics formastitis. The timing of antibiotic use

was even more suggestive: 410% of thecases had received antibiotics in thepostnatal period compared with 14%of the control subjects. Of women tak-ing antibiotics after delivery, 73% ofthe case group reported taking antibi-otics within 2 to 4 weeks of being diag-nosed with nipple candidiasis (8/1 1,Table 3) whereas only 27% (3/1 1) ofthe women in the control group fellinto the same time interval.

Candida in infantsNone of the infants in the controlgroup had a clinical diagnosis of oralthrush or diaper candidiasis, whereas48% of the infants in the case group

had diaper yeast and 33% had visibleoral thrush (Table 4).

DISCUSSION

Validity ofthe studyMisclassification of the subjects into"case" and "control" groups has beenminimized by defining, a priori, strictclinical criteria for the diagnosis of nip-ple candidiasis. In contrast to Amir'sstudy,'2 we gathered data directlythrough in-person questionnaires fromboth the case and control groups.

Moreover, all the control subjectsattended the same clinic as the cases.

The very high rate of consent probablyreflects the strong motivation of thesewomen. While, by definition, they rep-

resent a statistically select group, thisshould not detract from the validity of

1410 (,ianadian Fanily Plysician \XLso(): August 1994

Nipple candidiusis amongbreasifeeding mothersCase-control study ofpredisposing factors

Table 3. Temporal relationship between antibiotic use andnipple candidiasis

the study because the cases and con-trols came from the same pool ofwomen. Furthermore, we surmise thatinfected women who do not receiveappropriate treatment are likely to stopbreastfeeding, often without an estab-lished diagnosis.We are reasonably confident that

the correlations between nipple Candidainfection and these predisposing fac-tors reflect the situation in the popula-tion at large. Our findings substantiatepreliminary data presented by Amir''and provide strong, statistically rele-vant evidence that these factors predis-pose to nipple candidiasis.

Antibiotic useThe most important finding of thisstudy- important because it relatesto a potentially modifiable factor - isthe association between antibioticsand nipple candidiasis. Antibioticsare reported to predispose to Candidainfections at other sites."',7 When theantibiotics eliminate or reduce theresident bacteria that normally com-pete with yeast for nutrients, the yeastare able to multiply more readily, andtheir overgrowth can lead to invasiveinfection.Do our data support the idea that

antibiotics also predispose to nippleyeast? It is important to establishwhether an appropriate temporal rela-tionship exists between the use ofantibiotics and the onset of nipple can-didiasis. We found that 73% of thewomen in the case group reported tak-ing antibiotics 2 to 4 weeks beforediagnosis, a period consistent with acausal relationship. Although ourstudy does not prove a link betweenantibiotics and nipple candidiasis, itdoes provide substantial evidence tosupport one.

This possible link should be takeninto consideration before prescribingantibiotics for mastitis. Nineteen per-cent (5/27) of the case group had beenprescribed antibiotics for mastitis,compared with 6% (5/78) of the con-trol group. While antibiotics are an

alternative therapies, such as massage,rest, milk expression, and increasednursing on the affected breast, ofteneffectively resolve mastitiS.

Furthermore, the possibility of alink between mastitis, antibiotics, andthe subsequent development of nipplecandidiasis would be important toexamine in future studies. A prospec-tive study could follow women diag-nosed with mastitis who are giveneither antibiotics or alternative thera-pies to see what proportions of thetwo treatment groups develop nipplecandidiasis.

Nipple traumaThis study demonstrated a correlationbetween nipple damage and nippleyeast infection. Odds' described trau-ma or maceration as mechanical fac-tors that predispose to candidiasis.Trauma can provide a route of entryfor the microorganism. Although thisrationale makes implicit sense, otherpossible explanations for the associa-tion cannot be ruled out. For example,some of the women might have devel-oped cracked nipples as a result of theCandida infection and not vice versa.In this study, however, women in thecase group reported significantly morenipple trauma while establishingbreastfeeding than did women in thecontrol group.

It thus becomes important to pre-vent trauma and preserve nippleintegrity, which also reduces the likeli-hood of invasion by bacteria oryeast.'"2"'1 Proper positioning of theinfant at the breast and correctlatching technique are paramount.Moreover, good technique is basic tocomfortable, pain-free nursing. Andpain inhibits the milk ejection reflex,which could increase the incidence ofplugged ducts and mastitis. Thus, nec-essary antibiotic treatment could bereduced by giving mothers and babieswhatever early assistance they requireto establish effective and comfortablebreastfeeding. In addition, babies whoexhibit such conditions as ankyloglos-

accepted treatment for this condition, sia, nipple confusion, or incorrect

C,'anadian Family Physician VoLi-to: August 1994 1411

RESEARCH

Nipple candidiasis among'breasifeeding mothersCase-control study ofpredisposing fadors

RESEARCH

Nipple candidiasis amongbreostfeeding mothersCase-control study ofpredisposing factors

Table 5. Measures toprevent nipplecandidiasis

WHAT PHYSICIANS CAN DOPrevention* Avoid antibiotics unless

sound indication.* Use short courses of

antibiotics when needed.* Consider antifungal nipple

cream prophylactically foryeast-prone mother receiv-ing postpartum antibiotics.

Diagnosis* Diagnose yeast vaginitis if

symptoms are present, ifclinical appearance is sus-pect, or if culture is positive.

* Maintain high index ofsuspicion.

Treatment* Treat yeast vaginitis in

third trimester andpostpartum aggressivelyand prophylactically ifantibiotics have been usedand patient has a historyof yeast vaginitis.

* Treat mother for nippleyeast after delivery if babyhas oral or diapercandidiasis.

WHAT PATIENTS CAN DOPrenatally* Attend breastfeeding class.* Report symptoms of yeast

vaginitis to physician.

Postpartum* Seek early assistance in

latching.* Obtain help promptly for

nipple trauma.* Avoid disposable breast

pads, which can abradeand occlude.

* Reduce dietary sugar ifyeast vaginitis-prone.

* Avoid nipple infectionfrom vagina through goodhygiene.

* See physician if nipplepain appears after feeding.

sucking pattern should be identifiedearly so that steps can be taken toavoid nipple trauma.

Vaginal yeastAlthough a self-reported history ofprevious vaginal yeast infection wasfound to correlate well with the pres-ence of nipple candidiasis, it is difficultto draw firm conclusions because thedata on vaginal yeast infection includ-ed all cases, regardless of timing ofinfection; therefore we considered posthoc analysis to be of dubious value.Future studies will concentrate onestablishing the timing of the vaginalyeast infections and the other predis-posing factors in relation to the nippleCandida infection.

Infant infectionAnother important finding was thehigh incidence of oral and diaper can-didiasis among infants of mothers withnipple candidiasis. This concurrence ofCandida infection in mother and babyhas been documented previously,although anecdotally.,25",2 The genera-tion of statistically significant data, aspresented here, has important implica-tions for treating nipple and oral can-didiasis. It emphasizes the need to treatboth mother and infant with topicalantifungal agents even if only one isexhibiting symptoms. Equally impor-tant is the teaching of hygiene measuresto prevent infection being passed backand forth between mother and infant.In addition, approaches to prevent nip-ple yeast infection (Table 5) can decreasethe incidence of infant oral thrush.

ConclusionOur results suggest that the naturalhistory of nipple candidiasis, in at leasta subset of nursing mothers, involvesone or more of the associated predis-posing factors: antibiotics, vaginalyeast infection, and nipple trauma.However, further work in this area isrequired to obtain a clearer under-standing of the pathogenesis of nipplecandidiasis. Now that these factorshave been identified, we can focus on

changes in management of nursingmothers and their infants (Table 5) tosee whether the incidence of nipplecandidiasis can be reduced. R

AcknowledgmentsWe appreciate the valuable contribution ofDr R. Brant, who provided statistical advice andthe statistical software used in this study.Maureen Fjeld, Founder and Director of theCalgary Breastfeeding Clinic, was most helpfulin obtaining consent from the mothers in thestudy. We also thank Drs D. Hanley, P Sokol,and H. Bryantfor their critical review of the textand Mrs Sylvia Zuber for her assistance inpreparing the manuscript.

Requestsfor reprints to: Dr Evelyn _Jain,Calgary Breastfeeding Clinic, 6628 CrowchildTrail SW Calgary, AB T3E 5R8

References1. Odds FC. Factors that predispose the host tocandidiasis. In: Odds FC. Candida andcandidiasis: a review and bibliography. 2nd ed.Londoni: Bailliere Tindall, 1988:93-114.

2.Johnstone HA, MarcinakJE Candidiasis inthe breast feeding mother and infant.7 Obstet GynecolNAfeonatalNurs 1990; 19:171-3.

3. McGregorJA, Neifert MR. Maternal prob-lems in lactation. In: Neville MC, Neifert MR,editors. Lactation: plysiology, nutrition and breast-feeding. New York: Plenum Press, 1983:337.

4. Amir LH, Pakulas. Nipple pain, mastalgiaand candidiasis in the lactating breast.AustNKZJ Obstet Gynaecol 1991 ;3 1:378-40.

5. Lawrence RA. Medical complications of themother. In: Lawrence RA. Breas~feeding:a guidefor the medical profession. 3rd ed. St Louis:CV Mosby Co, 1989:392.

6. Burt A. Breast pain and candida: is there aconnection? Breas{feeding Rev 1988; 13:68.

7. Chetty GN, Selvi GS, Kamalan A,Thambian AS. Candidiasis in mother andchild. Mykosen (Berlin) 1980;23:580-2.

8. Mukherjee SC. Moniiasis breast.3 Indian Med Assoc 1964;43:536-8.

9. Kozinn PJ, Taschadjian CL, Wiener H.Incidence and pathogenesis of neonatal can-didiasis. Pediatrics 1958;21:421-9.

10. Von Maillot K, Rummel XA, Kleissl P.Candida mycosis in pregnant women andrelated risks to the newborn. A/Iykosen (Berlin)1978;1 (Suppl):246-51.

1412 C'anadian Family Physician VOL 40: August 1994

RESEARCH

11. Gillespie HL, Binmon WB, Slater V.Incidence of Candida in the vaginaduring pregnancy. Study utilizing thePagano-Levin culture medium.Obstet Gynecol 1960; 16:185-8.

12. Amir LH. Candida and the lactatingbreast: predisposing factors. 7 Hum Lact1991;7: 177-81.

13. Gunther M. Infantfeeding. Revised ed.London: Penguin Books, 1973: 10.

14. Minchin M. Breastfeeding matters: what weneed to know about infantfeeding. 2nd ed.Victoria, Australia: Alma Publications andAllen & Unwin, 1989:31-133.

15. Bro F The diagnosis of candida vagini-tis in general practice. ScandJ Prim HealthCare 1989;7:19-22.

16. Bluesein D, Rutledge C, Lumsden L.Predicting the occurrence of antibiotic-induced candidal vaginitis (AICV).Fam PractResj 1991;1 1:319-26.

17. Seelig MS. The role of antibiotics in thepathogenesis of Candida infections.Am7 Med 1966;40:887-917.

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and antipyretic effects of Naprosyn may mask the usual signsof infections. Periodic liver function tests and ophthalmicstudies are recommended for patients on chronic therapy.Caution should be exercised by patients whose activitiesrequire alertness if they experience drowsiness, dizziness,vertigo or depression during naproxen therapy. Naprosyn maydisplace other albumin-bound drugs from their binding sitesand may lead to drug interactions or interfere with certainlaboratory tests. See Product Monograph for further details.ADVERSE REACTIONS(1) Denotes incidence of reported reactions between 3% and9%. (2) Denotes incidence of reported reactions between 1%and 3%. See Product Monograph for reactions occurring inless than 1% of patients.Gastrointestinal: Heartburn(1), constipation(1), abdominalpain(1), nausea(1), diarrhea(2), dyspepsia(2), stomatitis(2),diverticulitis(2). Rectal burning(1) has been reportedoccasionally with the use of naproxen suppositories.Central Nervous System: Headache(1), dizziness(1),drowsiness(1), lightheadedness(2), vertigo(2), depression(2),and fatigue(2).Skin: Pruritus(1), ecchymoses(1), skin eruptions(1),sweating(2), and purpura(2).Cardiovascular: Dyspnea(1), peripheral edema(1), andpalpitations(2).Special Senses: Tinnitus(1), and hearing disturbances(2).Others: Thirst(2).Adverse reactions reported for SR tablets were similar tostandard tablets.DOSAGE AND ADMINISTRATIONAdult: Oral: The usual total daily dosage for osteoarthritis,rheumatoid arthritis and ankylosing spondylitis is 500 mg(20 mL, 4 teaspoons) a day in divided doses. It may be increasedgradually to 750 or 1000 mg or decreased depending on thepatient's response. Patients with rheumatoid arthritis orosteoarthritis maintained on a dose of 750 mg/day in divideddoses can be switched to a once daily dose of Naprosyn SR750 mg. The single daily dose of Naprosyn SR should not beexceeded and can be administered in the morning or evening.Naprosyn SR tablets should be swallowed whole.Rectal: Naprosyn Suppositories (500 mg) can replace one ofthe oral doses in patients receiving 1000 mg of Naprosyn daily.Juvenile Rheumatoid Arthritis: The recommended daily doseis approximately 10 mg/kg in two divided doses.AVAILABILITYNaprosyn is available as: 250 mg, 375 mg, and500 mg Tablets, as 250 mg, 375 mg and 500 mg Enteric CoatedTablets, as 750 mg Sustained-Release Tablets and 500 mgSuppositories. Suspension: Each 5 mL contains 125 mg ofnaproxen. Shake bottle gently before use. Pharmacists are toprovide the Naprosyn Patient Information leaflet whendispensing this drug. Product Monograph available to healthprofessionals upon request.References: 1. Bouchier-Hayes T. Practitioner Nov. 1979; 223:706-10. 2. Williams J. and Engler C. Rheumatol and Rehabil1977; 16: 265-9. 3. Kogstad 0. Scand J Rheumatology, Suppl2:159-163. 4. Gaismayer K. et al. Excerpta Medica 1980; 13-9.5. Vetter G. Brit J Clin Pract 1985;39: 276-281. 6. Schwartz etal. Data on File, Syntex Inc., 1993. 7. Navert H. Data on File,Document CL5131, Syntex Inc., 1990. 8. Data on File, SyntexInc., 9. Lizarazo H. et al. Curr Ther Res Oct. 1983; 34(4):701-7. 10. Schoen R. Vender R. Amer J Med 1989; 86: 449-56.

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Canadian Family Physician VOL 40: August 1994 1413