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수유 중 약물 복용의 상담 원칙 2016
- 1. 단국대학교 의과대학 제일병원 한국마더세이프 안현경 수유 중 약물 복용의 상담 원칙
- 2. 젖의 장점
- 4. 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 immune mediated diseases Emotional/Bonding 모유수유의 장점
- 5. 수유아
- 6. 99.7 68.9 59.0 36.4 14.1 10.2 6.5 12.7 37.4 46 0.0 20.0 40.0 60.0 80.0 100.0 1970 1982 1985 1988 1997 2000 2002 2005 2007 2009 모유수유율
- 7. 90% 10% 모유수유계획 분유수유계획 임신 중 모유수유 계획 율 - 제일병원
- 8. • 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
- 9. 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
- 10. 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 수유 중 약물복용
- 11. 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)
- 12. 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
- 13. Passive diffusion Molecular weight Protein binding Lipid solubility Half life Oral bioavailability PHARMACOKINETIC FACTORS
- 14. PASSIVE DIFFUSION Drugs move in and out of breast milk High to low With time direction may shift Example: alcohol
- 15. High molecular weight limits movement into breast milk MW >500 daltons does not enter breast milk MOLECULAR WEIGHT
- 16. Insulin: MW > 6,000 daltons Heparin: MW 40,000 daltons Ethanol: MW 200 MOLECULAR WEIGHT: EXAMPLES
- 17. 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
- 18. High protein binding Propranolol 90% L2 Diazepam 99% L3 Low protein binding Lithium 0% L3 PROTEIN BINDING
- 19. 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
- 20. Short half life drugs Alcohol 24 min Keflex 50 min Ibuprofen 120 min General anesthesia Long half life drugs Prozac 216 hours HALF LIFE
- 21. Amount of drug that is absorbed from the gut into the blood stream ORAL BIOAVAILABILITY
- 22. Drug Maternal gut and liver Maternal plasma Infant gut Infant plasma Oral bioavailability varies High (>90%) Low (<50%) Acetaminopen Acyclovir Lorazepam Azithromycin Metronidazole Budesonide Minoxidil Sulfasalazine Dilution of all drugs leads to low concentrations in mother’s plasma Only drugs are not protein-bound can pass into milk Drug protein binding High Low Bepridil >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
- 23. 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
- 24. Gentamycin <1% oral bioavailability Insulin (destroyed in gut) 0% oral bioavailability Heparin (destroyed in gut) POOR ORAL BIOAVAILABILITY
- 25. 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
- 26. IN GENERAL, BABY GETS <1% OF MATERNAL DOSE OF DRUG
- 27. 유아 고려사항 Age Body weight Health status 모성 고려사항 Dose Route of administration Health status 약물 선택 시 고려사항
- 28. 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 children Choose drugs for the mother that have known and established information 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 exposure to drugs via breast milk 약물 선택 시 일반적인 고려사항
- 29. Route of administration (minimum amount of drug to the infant) Choose medications : shortest T1/2 , 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. 약물 선택 시 일반적인 고려사항
- 30. Monitor Infants exposed to drugs via breast milk for unusual signs/symptoms feeding, 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 duration Advice the mother about milk expression & cup feeding instead of bottle feeding to avoid nipple confusion 약물 선택 시 일반적인 고려사항
- 31. L1 safest L2 safer L3 moderately safe L4 possibly hazardous L5 contraindicated LACTATION RISK CATEGORY BY THOMAS W HALE
- 32. 모유수유 중 약물 상담
- 33. (서울 콜센터 2014. 12) 상담종류별 상담건수 분포
- 34. 모유수유 상담 비율 모유수유 중 질병으로 인한 약물상담 89% 모유수유방법 관련상담 11% 모유수유 상담: 1,190건 생식발생독성정보활용화 연구 식약처 2008
- 35. 상담수유부의 질병 분류 생식발생독성정보활용화 연구 식약처 2008
- 36. 모유수유지속 81% 수유중단 10% 중단후 재수유 9% 약물 복용 후 모유수유 여부 생식발생독성정보활용화 연구 식약처 2008
- 37. 한국마더세이프전문상담센터 모유 수유중 다빈도 질문
- 38. SUMMARY Compatible Drug? Is a compatible Drug available? D/C drug & breastfeed Is therapy Necessary? Monitor nursling Monitor nursling Is there a non-drug Alternative That is compatible? Can therapy be Postponed? If acceptable pursue It & breastfeed Yes YesYes Yes No No No No
- 39. 감사합니다.
- 41. 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%
- 42. Antihistamine Regional agents Miscellaneous CV agents Nutritional agents Natural & Herbal pro Endocrine agents Respiratory agents Systemic antibiotics CNS agents & Analges GI drugs Drugs prescribed for breastfeeding women
- 43. SUMMARY 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
- 44. SUMMARY
- 45. 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 mothers with caution Maternal medication usually compatible with breastfeeding
- 46. 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
- 47. 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 EVALUATION OF THE INFANT
- 48. 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 한 다. 전신적으로 작용하는 약보다는 국소적으로 작용하는 약을 선택하게 한다.
- 50. Beta-blocking agents Acebutolol Atenolol Labetalol Propranolol Sotalol Salicylates Lithium Antineoplastic agents Drugs of abuse DRUGS TO AVOID IN THE NEWBORN AND IN INFANTS < 6MONTHS OF AGE
- 51. CYTOTOXIC DRUGS THAT MAY INTERFERE WITH CELLULAR METABOLISM OF THE NURSING INFANT Cyclophosphamide Cycloserine Doxorubicin Methotrexate
- 52. 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, diarrhea, tremulousness. seizure Heroin Tremous, restlessness, vomiting, poor feeding Marijuana Only 1 report in literature; no effect mentioned; very long half-life for some components Phencyclidine Potent hallucinogen
- 53. 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
- 54. Anti-anxiety antidepressants antipsychotic Others Alprazolam Diazepam Lorazepam Midazolam Perphenazine Prazepam Quazepam Temazepam Amitryptiline Amoxapine Bupropion Clomipramine Desipramine Dothepine Doxepine Fluoxetine Fluvoxamine Imipramine Nortriptyline Paroxetine Sertraline Trazodone Chloropromazine Chlorprothixene Clozapine Haloperidol Mesoridazine Trifluoperazine Amiodarone Chloramphenicol Clofazimine Lamotrigine metronidazole Metoclopramide Tinidazole Drugs for which the effect on nursing infants is unknown but may be of concern AAP Clssification
- 55. 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 phenobarbital Primidone Sedation feeding problems Slfasalazine Bloody diarrhea Drugs that have been association with significant effects on some nursing infants and should be given to nursing mothers with caution
- 56. 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 breastfeeding
- 57. 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 breastfeeding
- 58. 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 reastfeeding
- 59. 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 breastfeeding
- 60. 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
- 61. condition Recommended agents Use with caution Allegic rhinitis Beclomethasone Fluticasone, cromolyn Depression Sertraline, Paroxetine Fluoxetine, Diabets Insulin, Glyburide Tolbutamide Metformin Thiazolinediones Asthma Cromolyn, Nedocromil Pain Ibuprofen, Morphin acetaminophen Naproxen meperidine Contraception Barrier method Estrogen-containing contraceptives Epilepsy Phenytoin, Carbamazepine Phenobarbital Chaves RG 2004 Medications commonly prescribed for maternal ailments during breastfeeding
- 62. Passive diffusion Active transport against a concentration gradient Transcellular diffusion METHODS OF DRUG TRANSFER INTO MILK
- 63. 1. Passive diffusion 2. Molecular weight 3. Protein binding 4. Lipid solubility 5. Half life 6. Oral bioavailability 약물 역동학적 인자
- 64. Short acting Highly protein bound Low lipid solubility High molecular weight No active metabolites Low oral bioavailability Route of administration CHOICE OF DRUG