수유 중 약물 복용의 상담 원칙 2016

단국대학교 의과대학 제일병원 한국마더세이프안현경

수유 중 약물 복용의 상담 원칙

젖의 장점

Mother

Reduced risk of fracture/

osteoporosis

Reduced risk of cancer

Emotional

Convenience

Cost

Baby

Reduced risk of infection

Reduced risk of SIDS

Reduced risk of many im-

mune mediated diseases

Emotional/Bonding

모유수유의 장점

수유아

1970 1982 1985 1988 1997 2000 2002 2005 2007 20090.0

20.0

40.0

60.0

80.0

100.0 99.7

68.9 59.0

36.4

14.1 10.2 6.5 12.7

37.4 46.0

모유수유율

90%

10%

모유수유계획분유수유계획

임신 중 모유수유 계획 율- 제일병원

• 의료인의 권유

• 젖이 모자라서

• 함몰 유두• 젖을 못 빨아서• 물 젖이어서• 유두가 아파서• 기타

37.1%18.8%

12.1%10.5%

7.0%6.1%8.4% 이승주 등 . 소아과 40: 1336

모유수유 중단요인

90% of women: medication in first week postpartum

Mothers worry about effect of medication on nursing infant Non compliance

Weaning

Aavoidance of breastfeeding

50% of mothers more reluctant to take a medication while

nursing than during pregnancy

수유 중 약물복용

Nearly all drugs pass into human milk

Almost all medication appears in small amounts, usu-

ally less than 1% of the maternal dose

Very few drugs are contraindicated for nursing moth-

ers

수유 중 약물복용

Mother HIV + (in USA)

Use of illegal drugs by mother

Certain medications

Active, untreated TB in mother

Galactosemia in baby

Mother HTLV +

Herpes on breast

모유수유금기 (AAP 2005)

Pharmacokinetic factors

Factors which govern drug transfer across membranes

into breast milk as well as the metabolism of the drug

in mother and infant

약물 선택시 고려사항

Passive diffusion

Molecular weight

Protein binding

Lipid solubility

Half life

Oral bioavailability

PHARMACOKINETIC FACTORS

PASSIVE DIFFUSION

Drugs move in and out of breast milk

High to low

With time direction may shift

Example: alcohol

High molecular weight limits movement into breast

milk

MW >500 daltons does not enter breast milk

MOLECULAR WEIGHT

Insulin: MW > 6,000 daltons

Heparin: MW 40,000 daltons

Ethanol: MW 200

MOLECULAR WEIGHT: EXAMPLES

Medications circulate in maternal circulation bound or

unbound to albumin

Only unbound drug gets into maternal milk

Definition of good protein binding > 90%

PROTEIN BINDING

High protein binding

Propranolol 90%

L2

Diazepam 99% L3

Low protein binding

Lithium 0% L3

PROTEIN BINDING

Drugs that are very lipid soluble penetrate into breast

milk in higher concentration

Drugs that are active in the CNS are drugs with high

lipid solubility

LIPID SOLUBILITY

Short half life drugs

Alcohol 24 min

Keflex 50 min

Ibuprofen 120 min

General anesthesia

Long half life drugsProzac 216 hours

HALF LIFE

Amount of drug that is absorbed from the gut into the blood stream

ORAL BIOAVAILABILITY

Drug

Maternal gut and liver

Maternal plasma

Infant gut

Infant plasma

Oral bioavailability variesHigh (>90%) Low (<50%)Acetaminopen Acyclovir Lo-razepam AzithromycinMetronidazole BudesonideMinoxidil Sulfasalazine

Dilution of all drugs leads to low concentrations in mother’s plasma

Only drugs are not protein-bound can pass into milkDrug protein bindingHigh LowBepridil >99% Bisoprolol 30%Diazepam 99% Cyclophosphamide 13%Diclofenac >99% Ranitidine 15%Propranolol 90% Primidone <20%Oral bioavailiability varies

Usually very low levels (often undetectable)

ROUTE OF DRUGS FROM MOTHER TO BABY VIA BREASTMILK

Low bioavailability may be due to

Reduced absorption in GI tract

Poor GI stability due to acidity

High first-pass uptake by liver

ORAL BIOAVAILABILITY

Gentamycin

<1% oral bioavailability

Insulin (destroyed in gut)

0% oral bioavailability

Heparin (destroyed in gut)

POOR ORAL BIOAVAILABILITY

Drugs transfer into human milk if they:

Attain high conc. in maternal plasma

Are small enough

Are non-protein bound

Are highly lipid soluble

Then once in breast milk:

Are affected by oral bioavailability in baby’s gut

SUMMARY

IN GENERAL, BABY GETS <1% OF MATERNAL DOSE OF DRUG

유아 고려사항

AgeBody weightHealth status

모성 고려사항

DoseRoute of administra-

tionHealth status

약물 선택 시 고려사항

Avoid unnecessary drug use and l imit use of OTC products Assess the benefit/risk ratio for both mother and infant Avoid use of drugs known to cause serious toxicity in adults or

children Choose drugs for the mother that have known and established in-

formation about their pharmacokinetics and toxicity and have low concentrations in breast milk and low relative infant dose

Avoid new drugs if possible Drugs licensed for use in infants do not generally pose a hazard Neonates (esp. premature infants) are at greater risk from expos -

ure to drugs via breast milk

약물 선택 시 일반적인 고려사항

Route of administration (minimum amount of drug to the infant)

Choose medications : shortest T 1/2 , highest protein binding ability, poorest oral absorption, lowest lipid solubility, well-studied in infants.

Avoid feeding the infant at the time of peak concentration of the drug in milk.

To minimize drug level in the milk administer the drug at / immediately after the infant feeds.

Avoid long-acting drug In case of no available alternative, medication is best

taken just prior to the longest sleep of the infant.


Monitor Infants exposed to drugs via breast milk for un-usual signs/symptomsfeeding, sedation, irritability, rash, etc

For some medications with potential harm, temporary suspension of breastfeeding may be necessary. Withhold breastfeeding temporarily if the drug is only

used for a short durationAdvice the mother about milk expression & cup feeding

instead of bottle feeding to avoid nipple confusion


L1 safest

L2 safer

L3 moderately safe

L4 possibly hazardous

L5 contraindicated

LACTATION RISK CATEGORY BY THOMAS W HALE

모유수유 중 약물 상담

( 서울 콜센터 2014. 12)

상담종류별 상담건수 분포

모유수유 상담 비율

모유수유 중 질병으로 인한 약물상담

89%

모유수유방법 관련상담11%

모유수유 상담 : 1,190 건

생식발생독성정보활용화 연구 식약처 2008

상담수유부의 질병 분류


모유수유지속81%

수유중단10%

중단후 재수유9%

약물 복용 후 모유수유 여부


한국마더세이프전문상담센터

모유 수유중 다빈도 질문

SUMMARY

CompatibleDrug?

Is a compatible Drug available?

D/C drug &breastfeed

Is therapyNecessary?

Monitor nursling

Monitor nursling

Is there a non-drug Alternative

That is compatible?

Can therapy bePostponed?

If acceptable pursue It & breast-

feed

Yes

YesYes

Yes

No

No

No

No

감사합니다 .

Reasons for using the telephone line in breastfeeding women

HemorrhoidCV diseaseGI diseaseContraceptionHepatitis BRespiratory disease

OthersPsychotic diseaseNutritionBreast problem

Dental diseasePain

Inflamation

Dermatologic diseaseThyroid disease

12.5%11%

9.6%

7.4%

AntihistamineRegional agents

Miscellaneous

CV agentsNutritional agentsNatural & Herbal proEndocrine agentsRespiratory agents Systemic antibiotics

CNS agents & Analges

GI drugs

Drugs prescribed for breastfeeding women

SUMMARY

Drugs transfer into human milk if they:Attain high conc in maternal plasmaAre small enoughAre non-protein boundAre highly lipid solubleThen once in breast milk:Are affected by oral bioavailability in baby’s gut

SUMMARY

DRUG CLASSIFICATION BY AAPCytotoxic drugs Drugs of abuse for which adverse effects on

the infantRadioactive compounds that require temporary

cessation of breastfeedingDrugs for which the effect on nursing infants in

unknown but may be concernDrugs that have been associated with signifi-

cant effects on some nursing infants and should be given to nursing mothers with cau-tion

Maternal medication usually compatible with breastfeeding

Maternal factor Dose and duration of therapy Route of administration Drug pharmacokinetics

Infant factor Infant’s ability to absorb, metabolize, and excrete the

drug Gestational age of infant and its postnatal age

DRUG TRANSFER INTO THE BREAST MILK

Infant age Premature and newborn infants are at somewhat

greater risk Infant stability

Unstable infants with poor GI stability may increase the risk of using medications

Pediatric approved drugs Generally are less hazardous if long-term history of

safety is recognizedDose

In a premature infant various doses may be more risky than in a 1 year old healthy infant

Drugs that alter milk production May be much more risky during neonatal period than

much later

EVALUATION OF THE INFANT

상담 시 주지 사항 및 상담내용약을 꼭 복용해야 하는지 평가한다 .젖을 빨리고 난 다음 약을 복용한다 .약물을 단기간 사용 할 경우에는 수유를 잠시 멈춘다 .정확한 정보가 있는 약으로 아이에게 영향이 적은 약을 선택하게 한다 .전신적으로 작용하는 약보다는 국소적으로 작용하는 약을 선택하게 한다 .

Beta-blocking agents Acebutolol Atenolol Labetalol Propranolol Sotalol

SalicylatesLithiumAntineoplastic agentsDrugs of abuse

DRUGS TO AVOID IN THE NEWBORN AND IN INFANTS < 6MONTHS OF AGE

CYTOTOXIC DRUGS THAT MAY IN-TERFERE

WITH CELLULAR METABOLISM OF THE NURSING INFANT

Cyclophosphamide Cycloserine Doxorubicin Methotrexate

DRUGS OF ABUSE FOR WHICH ADVERSE EFFECTS ON THE INFANT

DURING BREASTFEEDING HAVE BEEN REPORTED

Drug Reported effect or reasons for concernAmphetamine Irritability, poor sleeping patternCocain Cocaine intoxication: irritability, vomiting, di-

arrhea, tremulousness. seizureHeroin Tremous, restlessness, vomiting, poor feedingMarijuana Only 1 report in literature; no effect men-

tioned; very long half-life for some compo-nents

Phencyclidine Potent hallucinogen

AAP Clssification

RADIOACTIVE COMPOUNDS THAT REQUIRE TEMPORARY CESSATION

OF BREASTFEEDING

Copper 64 Gallium 67 Indium 111 Iodine 123 Iodine 125 Iodine 131 Technetium 99 Radioactive sodium

Anti-anxiety antidepressants antipsychotic Others

AlprazolamDiazepamLorazepamMidazolamPerphenazinePrazepamQuazepamTemazepam

AmitryptilineAmoxapineBupropionClomipramineDesipramineDothepineDoxepineFluoxetineFluvoxamineImipramineNortriptylineParoxetineSertralineTrazodone

ChloropromazineChlorprothixeneClozapineHaloperidolMesoridazineTrifluoperazine

AmiodaroneChloramphenicol ClofazimineLamotriginemetronidazoleMetoclopramideTinidazole

Drugs for which the effect on nursing infants is un-known but may be of concern

AAP Clssification

AAP Clssification

Drug Reported effectAcebutolol Hypotension; bradycardia; tachycardia5-aminosalicylic acid DiarrheaAtenolol Cyanosis; bradycardiaBromocriptin Suppresses lactation; may be hazardous to the motherAspirin Metabolic acidosisClemastine Drowsiness irritability, refusal to feed, high-pitched cry, neck stiffnessErgotamine Vomiting, diarrhea, convulsionsLithium One-third to one-half therapeutic blood concentration in infantsPhenindione Anticoagulant; increased prothrombin and partial thromboplastin time

in 1 infant; not used in united statesPhenobarbital Sedation; infantile spasm after weaning from milk containing pheno-

barbitalPrimidone Sedation feeding problemsSlfasalazine Bloody diarrhea

Drugs that have been association with significant ef -fects on some nursing infants and should be given to nursing mothers with caution

AcetaminophenAcetazolamideAcitretinAcyclovirAlcohol (Ethanol)AllopurinolAmoxicillineAntimonyAtropineAzapropazoneAztreonam

B1(Thiamin)B6(Pyridoxine)B12BaclofenBarbiturateBendroflumethiazideDicumarolBromideButorphanol

CaffeineCaptoprilCarbamazepineCarbetocinCarbimazoleCascaraCefadrxilCefazolinCefotaxime

AAP Clssification

Maternal medication usually compatible with breast-feeding

CefoxetineCefprozilCeftazidimeCeftriaxoneChloral hydrateChloroformChloroquineChlorothiazideChlorothalidoneCimetidineCiprofloxacinCisapride

CisplatinClindamycinClogestoneCodeineColchicineOral contraceptive pill with estr/progesCycloserineD (vitamin)DanthronDapsonDexbrompheniramine

DiatrizoateDigoxinDiltiazemDipyroneDisopyramideDomperidoneDyphyllineEnalprilErythromycinEstradiolEthambutolEthosuximide

AAP Clssification


FentanylFexofenadineFlecainideFleroxacinFluconazoleFlufenamic acidFluoresceinFolic acidGadopentaticGentamicinGold saltsHalothane

HydralazineHydrochlorothiazideHydroxychloroquineIbuprofenIndomethacinIodidesIodineIodine(Povidone-iodine)IohexolIopanoic acidIsoniazid

InterferonIvermectineK1(vitamin)KanamycinKetoconazoleLabetalolLevonorgesterolLidocaineLoperamideLoratadine Magnesium- sulfate

AAP Clssification

Maternal medication usually compatible with reastfeed-ing

Medroxypro- gesteroneMefenamic acidMeperidineMethadoneMethimazoleMethohexitalMethyldopaMethyprylonMetoprololMetrizamideMetrizoate

MexiletineMinoxidilMorphineMoxalactamNadololNalidixic acidNaproxenNefopamNifedipineNitrofurantoinNorethynodrelNorsteroids

NoscapineOfloxacinOxprenololPhenylbutazonePhenytoinPiroxicamPrednisolonePrednisoneProcainamideProgesteronePropoxyphenePropranolol

AAP Clssification


PropylthiouracilPseudoephedrinePyridostigminePyrimethamineQuinidineQuinineRiboflavinRifampinScopolamineSecobarbitalSennaSotalol

SpironolactoneStreptomycinSulbactamSulfapyridineSulfisoxazoleSumatriptanSuprofenTerbutalineTerfenadineTetracyclineTheopyllineThiopental

ThiouracilTicarcillinTimololTolbutamideTolmetinTrimethprim/SulfamethoxazolTriprolidineValproic acidVerapamilWarfarinZolpidem

AAP Clssification

Maternal medication usually compatible with breastfeeding

condition Recommended agents Use with caution

Allegic rhinitis BeclomethasoneFluticasone, cromolyn

Depression Sertraline, Paroxetine Fluoxetine,

Diabets Insulin, GlyburideTolbutamide

MetforminThiazolinediones

Asthma Cromolyn, Nedocromil

Pain Ibuprofen, Morphinacetaminophen

Naproxenmeperidine

Contraception Barrier method Estrogen-containing contraceptives

Epilepsy Phenytoin, Carbamazepine Phenobarbital

Chaves RG 2004

Medications commonly prescribed for maternal ailments during breastfeeding

Passive diffusionActive transport against a concentration gradientTranscellular diffusion

METHODS OF DRUG TRANSFER INTO MILK

1. Passive diffusion

2. Molecular weight

3. Protein binding

4. Lipid solubility

5. Half life

6. Oral bioavailability

약물 역동학적 인자

Short acting

Highly protein bound

Low lipid solubility

High molecular weight

No active metabolites

Low oral bioavailability

Route of administration

CHOICE OF DRUG

수유 중 약물 복용의 상담 원칙 2016

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