Drug Therapy during Pregnancy and BreastFeeding Drug Therapy

Drug Therapy during Pregnancy and Breast-Feeding

Drug Therapy during Pregnancy and Breast-Feeding • Purpose of this lecture is to introduce concepts and to promote critical thinking among students • Disclaimer: This lecture is introductory in nature and does not attempt to comprehensively address all clinically relevant and important considerations. • Review of Burchum, J. R. , & Rosenthal, L. D. (2016). Drug Therapy during Pregnancy and Breast-Feeding In Lehne’s Pharmacology for Nursing Care, 9 th edition (pp. 81 -87). St. Louis, Missouri: Elsevier Saunders. • Lecture adapted by M Pinson, Winter 2016 from powerpoint supplied by Elsevier Saunders. • Sources of supplemental material are noted when 2 relevant.

3

Learning Objectives 1. Purpose: to introduce basic concepts r/t pregnancy and breastfeeding, and promote critical thinking among nursing students. 2. Understand therapeutic goal and clinical challenges of drug therapy during pg/BF. 3. Identify several reasons for medication use during pregnancy 4. Become familiar with general approach to drug therapy during pg/BF 5. Become familiar with some chronic health conditions that pose significant risk to the fetus if not managed properly. 6. Learn major physiologic changes of pregnancy that impact maternal pharmacokinetics and may warrant dose adjustments. 7. Become familiar with types of drug-related Adverse Effects during pregnancy 8. Define teratogenesis and teratogen. Describe dose/response relationship, and significance of stage of fetal development and effects of teratogen exposure. 9. Understand the purpose and limitations of FDA Pregnancy Risk Categories.

Learning Objectives, cont’d 10. Describe the basic approach and principles of drug therapy during breastfeeding. 11. Describe several strategies for minimizing infant exposure to drug in breast milk.

Drug Therapy during Pregnancy and Breast-Feeding Clinical Goal: Provide effective treatment for mother while avoiding harm to fetus and/or nursing infant Clinical Challenge: How to provide safe and effective treatment when there is limited data on drug use during pregnancy and breast-feeding?

Limited research data on drugs during pregnancy and breast-feeding • Women of reproductive age, infants and children were historically excluded from drug research trials • Data from adult men had to be “translated” or “extrapolated” to pregnant/ nursing women as well as children • In the 1990’s, research standards shifted 7

Medication use during pregnancy is common • Pregnant and breast-feeding women use medications for a variety of reasons • Certain health conditions in the mother may be (are) more dangerous to the fetus than drug(s) used to control the condition • Conditions that threaten the mother’s health may well impact the fetus/baby as well 8

Certain health conditions and/or risk factors that may pose significant risks to woman and/or fetus. • • Asthma Advanced maternal age Anemia/ blood disorder lifestyle choices Diabetes Epilepsy Mother’s personal medical history Hypertension infection Mother’s family history pre-existing obesity underlying mental health conditions http: //www. cdc. gov/reproductivehealth/maternalinfanthealth/pregcomplications. htm 9 http: //contemporaryobgyn. modernmedicine. com/contemporary-obgyn/news/sickle-celldisease-pregnancy? page=full

Example • Uncontrolled asthma doubles the incidence of stillbirth among women with asthma who did not take medications to control asthma • Rule: avoid unnecessary drugs during pg/BF, but all drug therapy cannot and should not be avoided 10

Severe maternal morbidity (SMM) increasing in the United States • “Maternal morbidity” includes physical and psychologic conditions that result from pregnancy, or are aggravated by pregnancy, and have an adverse effect on a woman’s health. • The most severe complications of pregnancy, generally referred to as severe maternal morbidity (SMM), affect more than 50, 000 women in the United States every year. Based on recent trends, this burden has been steadily increasing. • Downloaded December 12, 2016 from http: //www. cdc. gov/reproductivehealth/maternalinfanthealth/pregcomplicatio ns. htm 11

Pre-pregnancy patient education on cdc. gov “…If you are receiving treatment for a health problem, your health care provider might want to change the way your health problem is managed. For example, some medicines used to treat health problems could be harmful if taken during pregnancy. At the same time, stopping medicines that you need could be more harmful than the risks posed should you become pregnant…” http: //www. cdc. gov/reproductivehealth/maternalinfanthealth/pregcomplicati ons. htm 12

Questions so far? 13

Review of Terms ■ Pharmacokinetics: —Absorption —Distribution —Metabolism —Excretion MPinson_wi_16 14

Review of Terms ■ ADME: ■ Determine the concentration of a drug at its site(s) of action. ■ The concentration of drug at its sites of action determines the intensity and duration of the response. MPinson_wi_16 15

Review of Terms ■ Characteristics that allow molecules to cross membranes more readily ■ ? ■ These characteristics determine how readily a drug crosses membranes: ■ such as crossing into the placenta, entering the fetus ■ or crossing the blood-brain barrier (BBB), entering the CNS ■ Or crossing into breast-milk and being ingested by a baby MPinson_wi_16 16

Basic approach to drug therapy during Pregnancy and Breast-Feeding ● Decide: should mother’s health condition be managed with medications or not? Risk vs benefit ● Rule: Avoid drug therapy when reasonably appropriate ● Use non-pharmacological measures to promote health when applicable/appropriate: nutrition/ fiber/ water, physical activity, sleep, emotional support, physical assistance, etc ● If drug therapy is indicated, then choose the drug/ regimen with the least risk of causing harm ● Some conditions may require temporary use of a “lowest risk” med during pg/BF, then mother can resume use of a 17 different med after pg/BF if desired

Physiologic changes during pregnancy impact pharmacokinetics. Dose adjustments of maternal medications may be necessary. • Blood volume: By the third trimester, blood volume doubles, thereby reducing the plasma concentration of drug. • RBF: By the third trimester, renal blood flow doubles, thereby more rapidly eliminating renal-excreted drugs. • Liver: For some drugs, hepatic metabolism increases (enzyme induction), thereby decreasing amount of drug. • Bowel: Tone & motility decrease, thereby prolonging transit time. Increased time in the bowel allows greater drug absorption and enterohepatic cycling to occur. 18

Placental circulation: anatomic diagram MOM FETUS 19 For practical purposes, the clinician should assume any drug taken during pregnancy will reach the fetus

Placental drug transfer • Essentially, all drugs can cross the placenta, but the degree to which specific drugs enter the placenta varies • Factors that determine drug passage into the placenta are the same factors that determine drug passage across all other membranes • For practical purposes, assume that any drug taken during pregnancy will reach the fetus 20

Drug-related Adverse Effects during pregnancy 1 - Pregnant women are subject to the same adverse effects as non-pregnant women 2 - The physiologic state of being pregnant may itself impose additional issues for mother 3 - Potential adverse effects to: ● Reproductive structures (uterus, cervix, placenta) ● Fetus (organogenesis, functional development) 21

Examples of drug impacts on reproductive anatomy or fetus • Drugs may affect uterine contractions: – Cocaine and prostaglandins stimulate contractions • thereby may induce abortion (ex misoprostol) or early labor – Aspirin can suppress contractions in labor, but increases the risk of serious bleeding • Drugs may cause bleeding: • Dependence-producing drugs: babies may experience withdrawal (abstinence syndrome) and require careful weaning off the drug (Ex: cocaine, heroin, opiates)22

Prevent Pre-term Labor 23

24

Baby born prematurely 25

26

27

Drugs given to a pregnant women near term/ or near delivery • Maternal drug history is important to ongoing infant care in the mother/baby unit or in the Neonatal Intensive Care Unit • Medications are sometimes given near term/ preterm to the mother to intentionally induce fetal effects –Ex: mothers who will give birth prematurely (particularly prior to 36 weeks’ gestation) may be given corticosteroids to induce more rapid maturation of the fetal lungs – surfactant given post-partum to baby • By contrast, giving corticosteroids to a baby after birth is losing favor among experts 28

Potential impact of drugs on fetal growth and development • Teratogen = a medicine or other chemical capable of producing a permanent structural or functional birth defect, growth impairment, or fetal death • Teratogenesis = the process by which congenital malformations are produced in an embryo or fetus − greatest concern for many 29

Potential impact of drugs on fetal growth and development • Incidence of major structural abnormalities (ie life-threatening or require surgical correction) is between 1 -3% of births – half are identified at/near birth – half are identified later or on autopsy • Incidence of minor structural abnormalities is unknown • Incidence of functional abnormalities is unknown – Growth delays, learning/intellectual differences/ deficits, neurobehavioral and metabolic/ biochemical anomalies 30

Causes of birth anomalies • About 25% - genetic factors • Less than 1%- drugs • Significant but unknown %- environmental chemicals • Vast majority of birth defects have unidentified causes 31

Effects of teratogens at various stages of fetal development Stage of Fetal Development Effects of Teratogen Exposure Preimplantation conception – week 2 “All or nothing” Embryonic period week 3 – week 8 Gross malformations, anatomic abnormalities Fetal period week 9 – term Effects are usually functional (rather than anatomic structure) 32

Teratogenesis and Stage of Development Preimplantation Embryonic Period Fetal Period Figure 9 -1 Effects of teratogens at various stages of development of the fetus. (From Moore KL: The 33 Developing Human: Clinically Oriented Embryology, 5 th ed. Philadelphia: WB Saunders Company, 1993. With permission. )

Teratogens • Thought-provoking reasons why identifying teratogens in humans is challenging Lehne, page 82 • Minimizing the risk of teratogenesis – 50% of pregnancies are unintended – How can we minimize risk? • Responding to teratogen exposure – Informed response – Compassion 34

FDA pregnancy risk categories The FDA established five categories (A, B, C, D, and X) to indicate a drug's probable risk to the fetus (1979). A - Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester, and the possibility of fetal harm appears remote. B - Animal studies do not indicate a risk to the fetus and there are no controlled human studies, or animal studies do show an adverse effect on the fetus but well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus. C - Studies have’ shown that the drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women. D - Positive evidence of human fetal risk exists, but benefits in certain situations (e. g. , life-threatening situations or serious diseases for which safer drugs cannot be used or are ineffective) may make use of the drug acceptable despite its risks. X - Studies in animals or humans have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience, or both, and the risk 35 dearly outweighs any possible benefit. * This organizational schema is likely to be replaced by one that provides more detailed information.

Drugs that Should Be Avoided during pregnancy because of proven or strongly suspected teratogenicity. Table 9 -1 (p 84) 36

Questions? 37

Amena: example of approach to drug therapy in pregnant woman Case: Amena is a 28 year old Syrian refugee with a seizure disorder who is now pregnant. She seeks treatment to prevent seizures during the pregnancy. Decide: treat or not to treat? • Can the expectant woman safely go without medications to control the condition? – No, unsafe • Can the condition be safely managed without meds? -No • What med does she currently use to prevent seizures? – Carbamazepine (anticonvulsant, mood stabilizer) is in Pregnancy Category D, and listed on Table 9 -1 (p 84) “Drugs that Should Be Avoided during pregnancy because of proven or strongly suspected teratogenicity. ” 38

Amena, page 2 • Which AED (antiepileptic drug) is best for Amena? – Least teratogenic? And effective for her disorder? ● Research: Comparative safety of antiepileptic drugs during pregnancy. Neurology, 2012 May 22; 78(21): 1692 -9. http: //www. ncbi. nlm. nih. gov/pubmed/22551726 – Conclusions: AEDs such as valproate and phenobarbital were associated with a higher risk of major malformations than newer AEDs such as lamotrigine and levetiracetam. Topiramate was associated with an increased risk of cleft lip compared with that of a reference population. ● Lamotrigine = C, levetiracetam = C – Pregnancy Category C meds pose LESS risk to fetus than Pregnancy Category D. ● Nursing action: Discuss with provider and/or neurologist and arrange provider-patient counseling discussion. Obtain new 39 medication order as appropriate. Provide patient education.

Sherri Case Sherri - 28 y/o F. At primary care for referral to antepartum care. Positive home pregnancy test, LMP 6 weeks ago. • PMH: seasonal asthma, hypothyroidism, depression. • Medications: – Thyroid hormone, 125 mcg daily, for hypothyroid – Albuterol MDI, 1 -2 puffs PRN for asthma – Flovent (fluticasone) MDI, 1 puff/day for asthma – Zoloft (sertraline) 150 mg/d for depression – Ibuprofen, 400 mg, PRN, for headache 40

Questions? 41

42

Drug Therapy During Breast-Feeding “Breast milk is known to possess nutritional and immunologic properties superior to those found in infant formulas. An American Academy of Pediatrics position paper emphasizes breastfeeding as the best nutritional mode for infants for the first 6 months of life. In addition to those qualities, studies also suggest significant psychologic benefits of breastfeeding for both the mother and the infant. ” ~ Sumner J. Yaffe, MD, Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk 43

Drug Therapy During Breast-Feeding • Nearly all drugs can enter breast milk, but the extent of drug entry into breast milk varies greatly • “Fortunately, there are relatively few instances in which drugs secreted into breast milk have been found to cause injury to patients”… …For the few drugs that are absolutely contraindicated during lactation, equally effective and safer medications are usually available” (Adams, Holland & Urban, 2014, p 79. ) • If drug concentrations are high enough, the baby will experience a physiologic/pharmacologic effect, raising the possibility of harm 44 • Very little systematic research

Principles of Drug Therapy During Breastfeeding • Is the drug therapy necessary? • What is the safest option for the infant? • If there is the possibility of harm, monitor infant blood levels of the drug • Minimize infant exposure – American Academy of Pediatrics 45

Strategies to minimize infant exposure to drug • Postpone pharmacotherapy until the baby is weaned if possible; use nonpharm strategies when possible. • Although most maternal medications probably pose no harm to the breastfeeding infant, their effects have not been fully studied. • If drug needs to be used, then, when possible: – Mom should take the medication immediately AFTER feeding the baby… to reduce (if possible) the amount of drug in the breast milk – Avoid breast-feeding during peak effect – Avoid drugs with long half-life or active metabolites – Drugs that are highly protein-bound are preferred – Use caution if baby is severely ill; a neonate; or preterm. They may not have adequate drug metabolizing 46 enzymes

Drugs Associated with Serious Adverse Effects During Breast-Feeding • Insert AHU, Table p 80 • And lehne p 86 • Immune suppressants (e. g. , cyclosporine. methotrexate) • Amiodarone & antithyroid drugs • Benzodiazepines, anticonvulsants, antihistamine – watch for sedation • Caffeine – high infant exposure = irritability • All drugs of abuse, controlled substances 47

Resources for further Learning: Drugs • Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10 th edition by Gerald G. Briggs BPharm, FCCP, and Roger K. Freeman MD • www. hsl. uw. edu • Introduction to 9 th edition was written by Sumner J. Yaffe, MD: excellent, profound eye-opener. 48

Resources for further Learning: Herbs • HERBS TO BE AVOIDED DURING LACTATION Two popular herbal remedies for nursing mothers pose a health risk to their infants. – avoid fenugreek – comfrey is much more dangerous; banned in Canada. • Nursing mothers should be steered away from most herbs, but there are some teas. – Chicory, peppermint, orange spice and red bush tea are all fine. Rose hips is an especially good tea because it has a very high concentration of vitamin C. • www. micromedexsolutions. com 49

Resources for further Learning: OB and Lactation-Specific Resources § Association of Women's Health, Obstetric and Neonatal Nurses www. awhonn. org § NAACOG… NAACOG stands for Nurses' Association of the American College of Obstetricians and Gynecologists § Lactation training and certification programs § http: //iblce. org/ (? ) 50

Patient and family-centered care always important Maintaining/supporting the mental, emotional and physical well-being of the mother is critically important to promoting the overall welfare of the CHILD Fathers/partners have important roles also that need to be supported and affirmed 51

Questions? 52