Drug Therapy in the Pregnant Drug Therapy in the Pregnant Dental PatientDental Patient

Doreen Matsui MD, FRCPCDoreen Matsui MD, FRCPCAssociate Professor, Associate Professor, Department of PaediatricsDepartment of Paediatrics

Children’s Hospital of Western OntarioChildren’s Hospital of Western Ontario

ObjectivesObjectives

• To review general To review general principles principles regarding drugs in pregnancyregarding drugs in pregnancy

• To describe effects of drugs To describe effects of drugs commonly used in dentistrycommonly used in dentistry

• To briefly overTo briefly overview use of drugs view use of drugs during breastfeedingduring breastfeeding

Drug Use in PregnancyDrug Use in Pregnancy(Larimore WL et al. Prim Care 2000;27:35-53)(Larimore WL et al. Prim Care 2000;27:35-53)

• 1991 WHO International Survey of Drug 1991 WHO International Survey of Drug Utilization in PregnancyUtilization in Pregnancy

• 86% of women took medication during 86% of women took medication during pregnancypregnancy

• Average of 2.9 prescriptionsAverage of 2.9 prescriptions• Despite this high rate of medication intake, Despite this high rate of medication intake,

most drugs are not labeled for use during most drugs are not labeled for use during pregnancypregnancy

Inadvertent ExposureInadvertent Exposure

• 1/2 of pregnancies unplanned1/2 of pregnancies unplanned

• Teratogenic potential should be Teratogenic potential should be considered and explained to women of considered and explained to women of childbearing age at time drug is childbearing age at time drug is prescribedprescribed– <50% of women know they are pregnant by 4<50% of women know they are pregnant by 4thth

week and ~20% still don’t know by 8week and ~20% still don’t know by 8thth week week

Drug Use in PregnancyDrug Use in Pregnancy(Van Trigt AM et al. Pharm World Sci 1994;16:254-9)(Van Trigt AM et al. Pharm World Sci 1994;16:254-9)

• Women interviewed within 2 weeks after Women interviewed within 2 weeks after deliverydelivery

40% had had one or more questions about 40% had had one or more questions about drugs during their pregnancydrugs during their pregnancy

• Similar proportion said that during pregnancy Similar proportion said that during pregnancy important to consult a health professional important to consult a health professional before using any medicationbefore using any medication

• Safety was issue that raised the most questionsSafety was issue that raised the most questions

ComplianceCompliance

• Pregnant women tend to comply Pregnant women tend to comply less than optimally with drug less than optimally with drug therapytherapy

• MisinformationMisinformation• 39% of women reported 39% of women reported

noncompliance predominantly due noncompliance predominantly due to hesitation to use drugs during to hesitation to use drugs during pregnancy (Van Trigt AM et al. pregnancy (Van Trigt AM et al. Pharm World Sci1994;16:254-9)Pharm World Sci1994;16:254-9)

Perception of Teratogenic RiskPerception of Teratogenic Risk(Am J Obstet Gynecol 1989;160;1190-4)(Am J Obstet Gynecol 1989;160;1190-4)

• Women exposed to nonteratogens Women exposed to nonteratogens assigned a risk of 24% for major assigned a risk of 24% for major malformationsmalformations

• Risk in general population 5.6%Risk in general population 5.6%• May be important factor in May be important factor in

decision to terminate pregnancydecision to terminate pregnancy

Perception of Teratogenic RiskPerception of Teratogenic Risk(Sanz E et al. Eur J Obstet Gynecol Reprod Biol (Sanz E et al. Eur J Obstet Gynecol Reprod Biol

2001;95:127-31)2001;95:127-31)

• Perception of risk related to medication used in Perception of risk related to medication used in pregnancy higher than the recognized risk in a pregnancy higher than the recognized risk in a group of 15 GPs, 10 gynaecologists, 106 pre-group of 15 GPs, 10 gynaecologists, 106 pre-clinical medical students, 150 medical students clinical medical students, 150 medical students in clinical training, 81 pregnant women and 63 in clinical training, 81 pregnant women and 63 non-pregnant womennon-pregnant women

General ConsiderationsGeneral Considerations• Almost all drugs cross the Almost all drugs cross the

placenta to some extentplacenta to some extent• Majority of drugs have not Majority of drugs have not

been associated with been associated with adverse effects when taken adverse effects when taken during pregnancyduring pregnancy

• Weigh therapeutic benefits Weigh therapeutic benefits of drug to mother against of drug to mother against its risk potential to its risk potential to developing fetusdeveloping fetus

Adverse EffectsAdverse Effects• Spontaneous abortionSpontaneous abortion• Fetal growth retardationFetal growth retardation• TeratogenicityTeratogenicity• Direct drug toxicityDirect drug toxicity• Neonatal drug withdrawalNeonatal drug withdrawal• Long term effects on neurobehavioral Long term effects on neurobehavioral

developmentdevelopment• CarcinogenesisCarcinogenesis

Teratogenic RiskTeratogenic Risk(Lo et al. Obstet Gynecol 2002;100:465-73)(Lo et al. Obstet Gynecol 2002;100:465-73)

• Standard clinical teratology databasesStandard clinical teratology databases

• 485 drugs approved by FDA 1980 - 2000485 drugs approved by FDA 1980 - 2000

• Treatment with only small fraction (2.4%) Treatment with only small fraction (2.4%) has been associated with substantial has been associated with substantial teratogenic riskteratogenic risk

• Took on average 6.0 ± 4.1 years after Took on average 6.0 ± 4.1 years after approval to determine risk approval to determine risk

Known TeratogensKnown Teratogens

• Alcohol (Ethanol)Alcohol (Ethanol)• CarbamazepineCarbamazepine• Cytotoxic Cytotoxic

chemotherapychemotherapy• DESDES• Isotretinoin and Isotretinoin and

EtretinateEtretinate• LithiumLithium

• MethimazoleMethimazole• MisoprostolMisoprostol• PhenytoinPhenytoin• ThalidomideThalidomide• TrimethoprimTrimethoprim• Valproic AcidValproic Acid• WarfarinWarfarin

Baseline RiskBaseline Risk• Risk of major malformation (cosmetic or Risk of major malformation (cosmetic or

functional significance) = 3% at birthfunctional significance) = 3% at birth

• Assessment of magnitude of increase in Assessment of magnitude of increase in risk above baseline is importantrisk above baseline is important

• Need to put risk in perspectiveNeed to put risk in perspective

Important FactorsImportant Factors

• Timing of exposure (sensitive period)Timing of exposure (sensitive period)– ““All-or-none” periodAll-or-none” period– *Organogenesis**Organogenesis*

• ““Avoid drug administration, if at all possible Avoid drug administration, if at all possible during 1st trimester”during 1st trimester”

– Brain developmentBrain development

• Dose of drug (threshold, dose-Dose of drug (threshold, dose-response)response)

• Genetic susceptibilityGenetic susceptibility

Associated FactorsAssociated Factors• Role of underlying maternal Role of underlying maternal

diseasedisease

• Other exposures such as Other exposures such as alcohol and cigarette alcohol and cigarette smokingsmoking

General RecommendationsGeneral Recommendations

• Minimize use of medications to those Minimize use of medications to those which are necessary and for shortest which are necessary and for shortest duration possibleduration possible

• Effective drugs that have been in use Effective drugs that have been in use for long periods preferable to newer for long periods preferable to newer alternativesalternatives

Evaluating Risk - Drug StudiesEvaluating Risk - Drug Studies

• Manufacturer almost never tests Manufacturer almost never tests product in pregnant women prior to product in pregnant women prior to marketingmarketing

• Evidence from large clinical trials does Evidence from large clinical trials does not existnot exist

• Reproductive toxicology studies in Reproductive toxicology studies in animals - extrapolation?animals - extrapolation?

Animals vs HumansAnimals vs Humans• 40-50 chemical and physical agents probably 40-50 chemical and physical agents probably

human developmental toxicantshuman developmental toxicants• >1200 produce developmental defects in >1200 produce developmental defects in

experimental animalsexperimental animals• >80% of agents known to produce defects in >80% of agents known to produce defects in

humans also cause defects in at least one humans also cause defects in at least one test animaltest animal

““CPS”CPS”

• Majority of drugs not labeled for use Majority of drugs not labeled for use during pregnancyduring pregnancy

• ““Safety of Drug X in pregnancy has not Safety of Drug X in pregnancy has not been established. Drug X should not be been established. Drug X should not be used during pregnancy unless the used during pregnancy unless the potential benefit to the patient outweighs potential benefit to the patient outweighs the possible risk to the fetus.”the possible risk to the fetus.”

FDA ClassificationFDA Classification

• X, D, C, B, AX, D, C, B, A

• Little correlation with riskLittle correlation with risk

Sources of InformationSources of Information

• Reference TextbooksReference Textbooks– Drugs in Pregnancy and Lactation (Briggs)Drugs in Pregnancy and Lactation (Briggs)– Maternal-Fetal Toxicology (Koren)Maternal-Fetal Toxicology (Koren)

• Computer DatabasesComputer Databases– ReprotoxReprotox– TERISTERIS

• Teratogen Information ServicesTeratogen Information Services– Motherisk ProgramMotherisk Program– FRAME ProgramFRAME Program

The Pregnant Dental PatientThe Pregnant Dental Patient

• Elective vs urgentElective vs urgent

• 2nd trimester2nd trimester

• Eliminate source of infection or painEliminate source of infection or pain

• Usually short-term drug therapyUsually short-term drug therapy

PenicillinsPenicillins

• Collaborative Perinatal ProjectCollaborative Perinatal Project

• Frequency of congenital anomalies no Frequency of congenital anomalies no greater than expected among children greater than expected among children of 4,356 women treated with penicillin of 4,356 women treated with penicillin (or one of its derivatives) during 1(or one of its derivatives) during 1stst 4 4 lunar months of pregnancylunar months of pregnancy

Penicillins and CephalosporinsPenicillins and Cephalosporins

• Amoxicillin and cephalosporins also Amoxicillin and cephalosporins also considered safe to use during pregnancyconsidered safe to use during pregnancy

• No increased risk of malformations with No increased risk of malformations with amoxicillin/clavulanic acid (Clavulin) in 2 amoxicillin/clavulanic acid (Clavulin) in 2 studies (Br J Clin Pharmacol studies (Br J Clin Pharmacol 2004;58:298-2004;58:298-302 and Eur J Obstet Gynecol Reprod Biol 302 and Eur J Obstet Gynecol Reprod Biol 2001;97:188-92)2001;97:188-92)

ErythromycinErythromycin

• Surveillance study of Michigan Medicaid Surveillance study of Michigan Medicaid recipients (1985-1992)recipients (1985-1992)

• No association between drug and No association between drug and congenital malformations in 6,972 congenital malformations in 6,972 newborns exposed during 1newborns exposed during 1stst trimester trimester

• Avoid estolate form (cholestatic hepatitis)Avoid estolate form (cholestatic hepatitis)• Less but reassuring data with Less but reassuring data with

clarithromycin and azithromycinclarithromycin and azithromycin

ClindamycinClindamycin(Scand J Infect Dis 2000;32:579-80)(Scand J Infect Dis 2000;32:579-80)

• Hungarian Case-Control Surveillance Hungarian Case-Control Surveillance of Congenital Abnormalities (1980-of Congenital Abnormalities (1980-1996)1996)

• OR (95% CI) for clindamycin 1.2 (0.4-OR (95% CI) for clindamycin 1.2 (0.4-3.8) and for lincomycin 1.3 (0.3-5.1)3.8) and for lincomycin 1.3 (0.3-5.1)

• Limited numbersLimited numbers

MetronidazoleMetronidazole

• Mutagenic in bacteria and Mutagenic in bacteria and carcinogenic in animalscarcinogenic in animals

• Small number of reports raised Small number of reports raised suspicion of teratogenic effectsuspicion of teratogenic effect

MetronidazoleMetronidazole(Am J Obstet Gynecol 1995;172:525-9)(Am J Obstet Gynecol 1995;172:525-9)

• Outcome of interest = occurrence of Outcome of interest = occurrence of birth defects in live-born infantsbirth defects in live-born infants

• Overall weighted OR during the 1st Overall weighted OR during the 1st trimester calculated by meta-analysis trimester calculated by meta-analysis of 7 studies was 0.93 (95% CI 0.73-of 7 studies was 0.93 (95% CI 0.73-1.18)1.18)

FluoroquinolonesFluoroquinolones(Antimicrob Agents Chemother 1998;42:1336-9)(Antimicrob Agents Chemother 1998;42:1336-9)

• Arthropathy in weight-bearing joints of animalsArthropathy in weight-bearing joints of animals• 200 women exposed to fluoroquinolones during 200 women exposed to fluoroquinolones during

pregnancypregnancy• Rates of major malformations did not differ Rates of major malformations did not differ

between groups exposed to quinolones during between groups exposed to quinolones during 1st trimester (2.2%) and control group (2.6%)1st trimester (2.2%) and control group (2.6%)

• Gross motor milestones did not differ between Gross motor milestones did not differ between children in 2 groupschildren in 2 groups

TetracyclineTetracycline

• Main risk is yellow-brown discoloration Main risk is yellow-brown discoloration of teethof teeth

• Risk only later than 4-5 months Risk only later than 4-5 months gestation when deciduous teeth begin gestation when deciduous teeth begin to calcifyto calcify

• No staining from doxycycline No staining from doxycycline documenteddocumented

• Effects on bone minimalEffects on bone minimal

Local Anesthetics - LidocaineLocal Anesthetics - Lidocaine

• Considered relatively safe for Considered relatively safe for use during pregnancyuse during pregnancy

EpinephrineEpinephrine

• Potential to compromise Potential to compromise uterine blood flowuterine blood flow

• Studies have failed to Studies have failed to demonstrate adverse fetal demonstrate adverse fetal effectseffects

• Low doses used in dentistryLow doses used in dentistry• Avoid inadvertent Avoid inadvertent

intravascular injectionintravascular injection

AcetaminophenAcetaminophen

• ““Analgesic of choice”Analgesic of choice”

• Occasional use at Occasional use at therapeutic dosestherapeutic doses

• Chronic use or overdoseChronic use or overdose

NSAIDSNSAIDS (including Aspirin)(including Aspirin)

• Increased risk of miscarriage? (BMJ Increased risk of miscarriage? (BMJ 2001;322:266-70)2001;322:266-70)

• Gastroschisis (abGastroschisis (abdominal wall defect) ???dominal wall defect) ???

• Avoid use during late pregnancy (3Avoid use during late pregnancy (3rdrd trimester)trimester) BleedingBleeding

– Inhibition of prostaglandin synthesisInhibition of prostaglandin synthesis• Prolonged labourProlonged labour

• Constriction of ductus arteriosusConstriction of ductus arteriosus

New COX-2 InhibitorsNew COX-2 Inhibitors(Am J Physiol Regul Integr Comp Physiol 2000;278:R1496-505)(Am J Physiol Regul Integr Comp Physiol 2000;278:R1496-505)

• Studies in fetal lambs demonstratedStudies in fetal lambs demonstrated– Celecoxib constricted isolated ductus in Celecoxib constricted isolated ductus in

vitrovitro

– Celecoxib produced both an increase in Celecoxib produced both an increase in pressure gradient and resistance across pressure gradient and resistance across the ductus in vivothe ductus in vivo

NarcoticsNarcotics(Codeine, Oxycodone, etc.)(Codeine, Oxycodone, etc.)

• Don’t appear to Don’t appear to risk of birth defects risk of birth defects

• Low dose short-term regimens Low dose short-term regimens acceptableacceptable

• Respiratory depressionRespiratory depression

• Neonatal withdrawalNeonatal withdrawal

CodeineCodeine• Unlikely to pose substantial teratogenic risk but Unlikely to pose substantial teratogenic risk but

data insufficient to state no risk (TERIS, 2002)data insufficient to state no risk (TERIS, 2002)• Associations between 1Associations between 1stst trimester use and trimester use and

congenital anomalies in case-control studies congenital anomalies in case-control studies although others have not confirmedalthough others have not confirmed

• Absence of consistent pattern and criticisms of Absence of consistent pattern and criticisms of possible bias in data make it unjustified to possible bias in data make it unjustified to consider codeine as causative of these consider codeine as causative of these malformationsmalformations

Nitrous Oxide (NNitrous Oxide (N22O) with OO) with O22

• Use during pregnancy somewhat controversialUse during pregnancy somewhat controversial• Inhibits methionine synthetase which can affect Inhibits methionine synthetase which can affect

DNA synthesisDNA synthesis• Teratogenic in animalsTeratogenic in animals• Single brief maternal exposure during Single brief maternal exposure during

pregnancy unlikely to pose a substantial pregnancy unlikely to pose a substantial teratogenic riskteratogenic risk

• Minimize prolonged use (< 30 minutes, at least Minimize prolonged use (< 30 minutes, at least 50% O50% O22))

Occupational Exposure to NOccupational Exposure to N22OO

risk of spontaneous risk of spontaneous abortion?abortion?

• Importance of scavenging Importance of scavenging equipmentequipment

BenzodiazepinesBenzodiazepines(BMJ 1998;317:839-43)(BMJ 1998;317:839-43)

• Meta-analysisMeta-analysis• Cohort studies showed no association Cohort studies showed no association

between fetal exposure to BZDs and risk for between fetal exposure to BZDs and risk for major malformations or oral cleftmajor malformations or oral cleft

• Case-control studies showed that risk for Case-control studies showed that risk for major malformations or oral cleft alone was major malformations or oral cleft alone was increasedincreased

• Use around delivery - “floppy infant”Use around delivery - “floppy infant”

RadiationRadiation• In most cases of diagnostic x-rays In most cases of diagnostic x-rays

the fetal radiation exposure is the fetal radiation exposure is much below the threshold dose of much below the threshold dose of 5 to 10 rad5 to 10 rad

Average Fetal Exposure DoseAverage Fetal Exposure Dose (mrad)(mrad)

CXR <5

Abdomen 200-289

UGI 48-360

IVP 358-880

Dental 0.01

• Fetal exposure dose from a full mouth series (18 films) or Fetal exposure dose from a full mouth series (18 films) or panoramic radiograph is <1/1000 value of concernpanoramic radiograph is <1/1000 value of concern• 40-fold < naturally occurring background radiation40-fold < naturally occurring background radiation

Antepartum Dental Radiography and Infant Antepartum Dental Radiography and Infant Low Birth WeightLow Birth Weight(JAMA 2004;291:1987-93)(JAMA 2004;291:1987-93)

• Population-based case-Population-based case-control studycontrol study

• Dental utilization data from Dental utilization data from Washington Dental ServiceWashington Dental Service

• Vital record birth Vital record birth certificates from certificates from Washington stateWashington state

Antepartum Dental Radiography and Infant Antepartum Dental Radiography and Infant Low Birth WeightLow Birth Weight(JAMA 2004;291:1987-93)(JAMA 2004;291:1987-93)

• When thyroid radiation dose was >0.4 When thyroid radiation dose was >0.4 mGy (40 mrad), adjusted OR for a term mGy (40 mrad), adjusted OR for a term low birth weight infant was 3.61 (95% CI low birth weight infant was 3.61 (95% CI 1.46-8.92) when compared with women 1.46-8.92) when compared with women with no known dental radiographwith no known dental radiograph

Dose to thyroid of dental radiograph 0.08 mGyDose to thyroid of dental radiograph 0.08 mGy

Antepartum Dental Radiography and Infant Antepartum Dental Radiography and Infant Low Birth WeightLow Birth Weight(JAMA 2004;291:1987-93)(JAMA 2004;291:1987-93)

• Weaknesses of study including chance finding Weaknesses of study including chance finding and missing dataand missing data

• Criticisms (JAMA 2004;292:1019-21)Criticisms (JAMA 2004;292:1019-21)– Confounding factorsConfounding factors– Dental pathologyDental pathology– Radiation dose was related to maternal smoking and Radiation dose was related to maternal smoking and

late prenatal carelate prenatal care– Large # of statistical tests (Type 1 error)Large # of statistical tests (Type 1 error)– Overestimation of radiation dosesOverestimation of radiation doses

American Dental AssociationAmerican Dental Association

• Abdominal exposure during dental Abdominal exposure during dental radiography is negligibleradiography is negligible

• Recommend that pregnant women Recommend that pregnant women postpone elective dental x-rays until after postpone elective dental x-rays until after delivery; however, there are times when delivery; however, there are times when an x-ray may be required during an x-ray may be required during pregnancy to help diagnose and treat oral pregnancy to help diagnose and treat oral disease (thyroid collar and apron)disease (thyroid collar and apron)

Drugs and Pregnancy - SummaryDrugs and Pregnancy - Summary

• List of drugs which have been associated List of drugs which have been associated with adverse effects when taken during with adverse effects when taken during pregnancy is relatively shortpregnancy is relatively short

• Teratogenic potential should be explained Teratogenic potential should be explained to women of childbearing age at time drug to women of childbearing age at time drug is prescribedis prescribed

• Lack of information but important to avoid Lack of information but important to avoid misinformationmisinformation

• Importance of baseline riskImportance of baseline risk

What is Baby Drinking?What is Baby Drinking?Drugs and the Nursing MotherDrugs and the Nursing Mother

Risk-Benefit RatioRisk-Benefit Ratio

• Benefits of continuing breastfeeding Benefits of continuing breastfeeding substantialsubstantial

• Convincing reason to justify cessation Convincing reason to justify cessation of breastfeeding requiredof breastfeeding required

Clinical ImplicationsClinical Implications

• Majority of drugs cross from maternal Majority of drugs cross from maternal plasma into breast milkplasma into breast milk

• Most medications found in very small Most medications found in very small amounts in breast milk (<1% of maternal amounts in breast milk (<1% of maternal dose)dose)

• Risk of adverse effects in nursing infants Risk of adverse effects in nursing infants is negligible for most drugsis negligible for most drugs

Clinical ImplicationsClinical Implications• Reluctance to encourage Reluctance to encourage

continuation of breastfeedingcontinuation of breastfeeding– Pharmacological action of drug Pharmacological action of drug

suggests that a toxic effect may occursuggests that a toxic effect may occur– Adverse effects have previously been Adverse effects have previously been

noted in nursing infantsnoted in nursing infants

Clinical ImplicationsClinical Implications

• Experience with direct use of drug in Experience with direct use of drug in infants for therapy may provide infants for therapy may provide reassurancereassurance

• Infant’s age (< 6 months), clinical status Infant’s age (< 6 months), clinical status and frequency of feeding may be and frequency of feeding may be importantimportant

Clinical ImplicationsClinical Implications- Risk Assessment- Risk Assessment

• Arbitrarily define as safe a value of Arbitrarily define as safe a value of <10% of the therapeutic dose for <10% of the therapeutic dose for infants (or the adult dose standardized infants (or the adult dose standardized by weight)by weight)

Sources of InformationSources of Information

• Peer-reviewed literaturePeer-reviewed literature

• TextbooksTextbooks

• Committee on Drugs (AAP)Committee on Drugs (AAP)

• Computer DatabasesComputer Databases

• Teratogen Information ServicesTeratogen Information Services– FRAME Program (London)FRAME Program (London)– Motherisk Program (Toronto)Motherisk Program (Toronto)

MetronidazoleMetronidazole

• Use during lactation controversialUse during lactation controversial

• Excreted into breast milk in relatively large amountsExcreted into breast milk in relatively large amounts

• Concern expressed with respect to possible Concern expressed with respect to possible mutagenic effectsmutagenic effects

• No reports of adverse effects in nursing infantsNo reports of adverse effects in nursing infants

• In conventional doses compatible with In conventional doses compatible with breastfeedingbreastfeeding

• If taken in single large dose breastfeeding may be If taken in single large dose breastfeeding may be temporarily withheld for 12 to 24 hourstemporarily withheld for 12 to 24 hours

CodeineCodeine(Lancet 2006;368:704)(Lancet 2006;368:704)

• Full term healthy male infantFull term healthy male infant

• Intermittent difficulty Intermittent difficulty breastfeeding and lethargy breastfeeding and lethargy starting Day 7 and died Day 13starting Day 7 and died Day 13

• Blood morphine concentration Blood morphine concentration very highvery high

CodeineCodeine(Lancet 2006;368:704)(Lancet 2006;368:704)

• MotherMother– Taking acetaminophen/codeine preparation Taking acetaminophen/codeine preparation dose due to somnolence and constipationdose due to somnolence and constipation– Morphine [ ] of stored milk was very highMorphine [ ] of stored milk was very high– Ultra-rapid metabolizerUltra-rapid metabolizer

• Picture consistent with opioid toxicityPicture consistent with opioid toxicity• Careful follow-up of breastfeeding mothers Careful follow-up of breastfeeding mothers

using codeine and their infants (somnolence, using codeine and their infants (somnolence, poor feeding, etc.)poor feeding, etc.)

BenzodiazepinesBenzodiazepines

• Milk levels of benzodiazepines not Milk levels of benzodiazepines not excessive but rarely sedation has been excessive but rarely sedation has been reported in breastfed infantsreported in breastfed infants

• If sedative required, shorter half-life drugs If sedative required, shorter half-life drugs such as lorazepam and midazolam such as lorazepam and midazolam preferredpreferred

• Long term exposure not recommendedLong term exposure not recommended

Drugs and Breastfeeding - Drugs and Breastfeeding - SummarySummary

• Most medications found in very small Most medications found in very small amounts in breast milkamounts in breast milk

• Risk of adverse effects in nursing infants is Risk of adverse effects in nursing infants is negligible for most drugsnegligible for most drugs

• Consequences of misinformation Consequences of misinformation (medication noncompliance, breastfeeding (medication noncompliance, breastfeeding cessation) cessation) NB to consult appropriate NB to consult appropriate available sourcesavailable sources