수유 중 약물 복용의 상담 원칙

안 현경

임신 중 모유수유 계획율

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

Healthy People 2010 Goals

• Increase to at least 75% the proportion of mothers

breastfeeding upon discharge and 50% still breast-

feeding when the infant is 6 months of age.

0102030405060708090

100

1970 1995 1998 2010Goal

Discharge

6 Months

모유수유 중단요인

• 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

Obstacles to Initiating and Continuing Breast-feeding

• Physician apathy and misinformation

• Insufficient pre-natal breastfeeding educa-

tion

• Distribution and promotion of infant formula

• Disruptive hospital policies

• Inappropriate interruptions of breastfeeding

• Early hospital discharge

• Lack of social support

Role of the Physician

• Establish positive attitudes in pregnancy

• Address medical issues/ physical obstacles

• Encourage nursing immediately after delivery

• Provide post-partum support

• Explain nutritional needs

• Assess substance use

• Discuss employment concerns

Establish Positive Attitudes

• Endorse and encourage breastfeeding because

it is best for mother and baby.

• Ask about previous experience

• Provide positive statements about breastfeeding

• Offer confirmatory words from all office staff

• Distribute appropriate education materials

• Be supportive no matter what the woman plans

General Benefits of Breastfeeding

• Maternal-infant bonding

• Inexpensive

• Convenient (no preparation)

• Perfect temperature

• Easily digested

• Immunological protection

• Allergy prophylaxis

Breastfeeding Advantages for Mothers

• May delay return of ovulation.

• Loss of pregnancy associated adipose tissue.

• Reduction in postpartum blood loss due to in-

creased oxytocin levels.

• Reduction in pre-menopausal breast cancer

and reduced risk of ovarian cancer.

• Improved bone remineralization postpartum.

Immunological Contents of Breast Milk

• Immunoglobulins– IgA, IgG, IgM, leukocytes, cytokines

• Host resistance factors – Complement macrophages, lymphocytes, lactoferrin

• Anti-inflammatory components– Enzymes: catalase, histaminase, lysozymes, lac-

toperoxidase– Antioxidants: acsorbic acid, alpha-tocopherol– Prostoglandins

• Interleukin-6– Stimulates an increase in mononuclear cells in

breast milk.

Breastfeeding Advantages for Baby

• Decreased incidence and/or severity of otitis media, diarrhea, lower respiratory infections, bacteremia, bacterial meningitis, botulism, uri-nary tract infections, and necrotizing enterocol-itis.

• Less hospitalization in first 6 months.

• Possible protective effect against sudden infant death syndrome, type 1 diabetes, Crohn’s dis-ease, ulcerative colitis, lymphoma, allergies, and chronic digestive diseases.

Drugs in Breastfeeding

• Healthcare professionals should always encourage

breastfeeding

• Most drugs excreted into breast milk but usually in

small amounts

• Few drugs are absolutely contra-indicated

• Some drugs may increase or decrease milk yield.

Background - Mothers

• 90% of women are prescribed a medication in

first week postpartum

• Mothers worry about effect of medication on nurs-

ing infant

• Leads to: non compliance, weaning, avoidance of

breastfeeding

• 50% of mothers more reluctant to take a medica-

tion while nursing than during pregnancy

Seven contraindications to breastfeeding (AAP 2005)

• 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

How to decide if a medication or drug is ok?

• Pharmacokinetic factors

• Factors which govern drug transfer across mem-

branes into breast milk as well as the metabolism

of the drug in mother and infant

Pharmacokinetic factors

1. Passive diffusion

2. Molecular weight

3. Protein binding

4. Lipid solubility

5. Half life

6. Oral bioavailability

Passive diffusion

• Drugs move in and out of

breast milk

• High to low

• With time direction may

shift

• Example: alcohol

Molecular weight

• High molecular weight limits movement into

breast milk

• MW >500 daltons does not enter breast milk

Molecular weight: examples

• Insulin: MW > 6,000 daltons

• Heparin: MW 40,000 daltons

• Ethanol: MW 200

Protein binding

• 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

Lipid solubility

• 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

Half life

Short half life drugs• Alcohol 24 min• Keflex 50 min• Ibuprofen 120 min• General anesthesia

Long half life drugs• Prozac 216 hours

Oral bioavailability

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

Oral bioavailability

DrugMaternal GI TractMaternal Plasma

Breast Milk

Infant GI TractInfant Plasma

Oral bioavailability

• Low bioavailability may be due to – Reduced absorption in GI tract– Poor GI stability due to acidity– High first-pass uptake by liver

Poor oral bioavailability

• Gentamycin – <1% oral bioavailability

• Insulin (destroyed in gut)– 0% oral bioavailability

• Heparin (destroyed in gut)

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

In general, baby gets <1% of maternal dose

of drug

Choice of Drug

• Short acting

• Highly protein bound

• Low lipid solubility

• High molecular weight

• No active metabolites

• Low oral bioavailability

• Route of administration

Drugs in Lactation – Factors to consider

• Avoid unnecessary drug use and limit 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 chil-

dren• Drugs licensed for use in infants do not generally pose a hazard• Neonates (esp premature infants) are at greater risk from exposure

to drugs via breast milk• Route of administration (minimum amount of drug to the infant)• Avoid long-acting preparations• Monitor Infants exposed to drugs via breast milk for unusual signs/

symptoms• Avoid new drugs if possible

Drug transfer into the breast milk

• 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

Way to minimize infant drug exposure

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

• Withhold breastfeeding temporarily if the drug is only used for a short duration.

• Choose drugs for the mother that have known and estab-lished information about their pharmacokinetics and toxicity and have low concentrations in breast milk and low relative infant dose

• Choose drugs that can be locally rather than systemically administered

• In case of long-acting drugs, time the drug administration to a once-a-day dose just before the infant’s longest sleep period to lessen exposure.

Evaluation of the infant

• 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 recognized• Dose

– 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

Summary

• Nearly all drugs pass into human milk

• Almost all medication appears in small amounts, usually

less than 1% of the maternal dose

• Very few drugs are contraindicated for nursing mothers

LACTATION RISK CATEGORY BY THOMAS W HALE

• L1 safest

• L2 safer

• L3 moderately safe

• L4 possibly hazardous

• L5 contraindicated

DRUG CLASSIFICATION BY AAP

• Cytotoxic drugs

• Drugs of abuse for which adverse effects on the infant

• Radioactive compounds that require temporary cessation of

breastfeeding

• Drugs for which the effect on nursing infants in unknown

but may be concern

• Drugs that have been associated with significant effects on

some nursing infants and should be given to nursing moth-

ers with caution

• Maternal medication usually compatible with breastfeeding

상담 시 주지 사항 및 상담내용

• 약을 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 .

Reasons for using the telephone line in breastfeeding women

Hemorrhoid

CV disease

GI disease

Contraception

Hepatitis B

Respiratory disease

Others

Psychotic disease

Nutrition

Breast problem

Dental disease

Pain

Inflamation

Dermatologic disease

Thyroid disease

12.5%11%

9.6%

7.4%

Antihistamine

Regional agents

Miscellaneous

CV agents

Nutritional agents

Natural & Herbal pro

Endocrine agents

Respiratory agentsSystemic antibiotics

CNS agents & Analges

GI drugs

Drugs prescribed for breastfeeding women

Drugs to avoid in the newborn and in infants < 6months of age

• Beta-blocking agents– Acebutolol– Atenolol– Labetalol– Propranolol– Sotalol

• Salicylates• Lithium• Antineoplastic agents• Drugs of abuse

Cytotoxic drugs that may interfere with cellular metabolism of the nursing in-

fant

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 concern

Amphetamine Irritability, poor sleeping pattern

Cocain Cocaine intoxication: irritability, vomiting, di-arrhea, tremulousness. seizure

Heroin Tremous, restlessness, vomiting, poor feeding

Marijuana 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 effect

Acebutolol Hypotension; bradycardia; tachycardia

5-aminosalicylic acid Diarrhea

Atenolol Cyanosis; bradycardia

Bromocriptin Suppresses lactation; may be hazardous to the mother

Aspirin Metabolic acidosis

Clemastine Drowsiness irritability, refusal to feed, high-pitched cry, neck stiffness

Ergotamine Vomiting, diarrhea, convulsions

Lithium One-third to one-half therapeutic blood concentration in infants

Phenindione Anticoagulant; increased prothrombin and partial thromboplastin time in 1 infant; not used in united states

Phenobarbital Sedation; infantile spasm after weaning from milk containing pheno-barbital

Primidone Sedation feeding problems

Slfasalazine Bloody diarrhea

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

Acetaminophen

Acetazolamide

Acitretin

Acyclovir

Alcohol (Ethanol)

Allopurinol

Amoxicilline

Antimony

Atropine

Azapropazone

Aztreonam

B1(Thiamin)

B6(Pyridoxine)

B12

Baclofen

Barbiturate

Bendroflumethiazide

Dicumarol

Bromide

Butorphanol

Caffeine

Captopril

Carbamazepine

Carbetocin

Carbimazole

Cascara

Cefadrxil

Cefazolin

Cefotaxime

AAP Clssification

Maternal medication usually compatible with breast-feeding

Cefoxetine

Cefprozil

Ceftazidime

Ceftriaxone

Chloral hydrate

Chloroform

Chloroquine

Chlorothiazide

Chlorothalidone

Cimetidine

Ciprofloxacin

Cisapride

Cisplatin

Clindamycin

Clogestone

Codeine

Colchicine

Oral contraceptive

pill with estr/proges

Cycloserine

D (vitamin)

Danthron

Dapson

Dexbrompheniramine

Diatrizoate

Digoxin

Diltiazem

Dipyrone

Disopyramide

Domperidone

Dyphylline

Enalpril

Erythromycin

Estradiol

Ethambutol

Ethosuximide

AAP Clssification

Maternal medication usually compatible with breast-feeding

Fentanyl

Fexofenadine

Flecainide

Fleroxacin

Fluconazole

Flufenamic acid

Fluorescein

Folic acid

Gadopentatic

Gentamicin

Gold salts

Halothane

Hydralazine

Hydrochlorothiazide

Hydroxychloroquine

Ibuprofen

Indomethacin

Iodides

Iodine

Iodine(Povidone-iodine)

Iohexol

Iopanoic acid

Isoniazid

Interferon

Ivermectine

K1(vitamin)

Kanamycin

Ketoconazole

Labetalol

Levonorgesterol

Lidocaine

Loperamide

Loratadine

Magnesium-

sulfate

AAP Clssification

Maternal medication usually compatible with reastfeed-ing

Medroxypro-

gesterone

Mefenamic acid

Meperidine

Methadone

Methimazole

Methohexital

Methyldopa

Methyprylon

Metoprolol

Metrizamide

Metrizoate

Mexiletine

Minoxidil

Morphine

Moxalactam

Nadolol

Nalidixic acid

Naproxen

Nefopam

Nifedipine

Nitrofurantoin

Norethynodrel

Norsteroids

Noscapine

Ofloxacin

Oxprenolol

Phenylbutazone

Phenytoin

Piroxicam

Prednisolone

Prednisone

Procainamide

Progesterone

Propoxyphene

Propranolol

AAP Clssification

Maternal medication usually compatible with breast-feeding

Propylthiouracil

Pseudoephedrine

Pyridostigmine

Pyrimethamine

Quinidine

Quinine

Riboflavin

Rifampin

Scopolamine

Secobarbital

Senna

Sotalol

Spironolactone

Streptomycin

Sulbactam

Sulfapyridine

Sulfisoxazole

Sumatriptan

Suprofen

Terbutaline

Terfenadine

Tetracycline

Theopylline

Thiopental

Thiouracil

Ticarcillin

Timolol

Tolbutamide

Tolmetin

Trimethprim/

Sulfamethoxazol

Triprolidine

Valproic acid

Verapamil

Warfarin

Zolpidem

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