This document provides information on safely managing common medical conditions during pregnancy and lactation. It discusses medication classification systems and factors affecting drug transfer across the placenta and into breastmilk. Guidelines are presented for treating depression, diabetes, thyroid disorders, infections, pain, nausea, and other issues. Many prescription and over-the-counter drugs are deemed safe to use when necessary, such as most antibiotics, acetaminophen, ranitidine, and antidepressants. Untreated medical conditions pose greater risks than potential side effects of approved medications. Resources for further information and guidance are also referenced.
1. Treat the Patient, not the
Pregnancy:
Susan McLellan, BSc. Pharm
Safe and Effective Medication use
in Pregnancy and Lactation
April 25, 2015
2. Objectives:
• Appropriate medication therapy during
pregnancy and lactation for the treatment of
depression, diabetes, and thyroid disorders
• Recommend safe non-prescription options
for select conditions.
• How to assess a drug for potential safety and
toxicity during pregnancy and lactation,
including key references.
3. Outline:
1. Classification Systems for drugs in
pregnancy and lactation
2. Resources – professional and patient
friendly
3. Therapeutics of selected conditions: Rx
and OTC
5. Old FDA classifications:
• Category A Controlled studies in women fail to
demonstrate a risk to the fetus in the first
trimester (and there is no evidence of risk in later
trimesters), and the possibility of fetal harm
appears remote.
• Category B Either animal reproduction studies
have not demonstrated a fetal risk but there are
no controlled studies in pregnant women, or
animal reproduction studies have shown an
adverse effect (other than a decrease in fertility)
that was not confirmed in controlled studies in
women in the first trimester (and there is no
evidence of risk in later trimesters).
6. Old FDA Classifications:
• Category C Either studies in animals have revealed adverse effects
on the fetus (teratogenic or embryocidal or other) and there are no
controlled studies in women, or studies in women and animals are
not available. Drugs should be given only if the potential benefit
justifies the potential risk to the fetus.
• Category D There is positive evidence of human fetal risk, but
the benefits from use in pregnant women may be acceptable
despite the risk (e.g., if the drug is needed in a life-threatening
situation or for a serious disease in which safer drugs cannot be
used or are ineffective).
• Category X Studies in animals or human beings have demonstrated
fetal abnormalities or there is evidence of fetal risk based on human
experience, and the risk of the use of the drug in pregnant women
clearly outweighs any possible benefit. The drug is
contraindicated in women who are or may become pregnant.
8. New FDA Labeling:
• Pregnancy and Lactation Labeling
Rule « PLLR »
• In both Pregnancy and Lactation:
– Risk summary
– Clinical considerations
– Data (human and animal, pregnancy drug
registries)
• In Reproductive Potential:
– Contraception
– Infertility
– Pregnancy testing
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm425317.htm
12. Drug Transport across
Placenta:
• Drugs more likely to cross have:
• Lower molecular weight
• Higher maternal blood concentration
• High lipid solubility
• Decreased protein binding
• Decreased ionization at physiological
pH
• Maternal Factors:
• Placental blood flow
• Placental surface area (related to
gestational age)
Drugs in Pregnancy and Lactation: A Reference Guide to
Fetal and Neonatal Risk. Briggs, et al. Lippincott Williams.
2011.
13. Factors affecting drug
levels in lactation:
• Drugs more likely to enter breast milk have:
– Increased half life
– Decreased protein binding
– Decreased molecular weight
– High bioavailability
– High CMax (maximum concentration)
– High volume of distribution (Vd)
– High milk : plasma ratio
http://www.medsmilk.com/pages/how_to_read_drug_entries (Hale’s
Medications and Mothers’ Milk)
25. Print and e-Resources:
• RxFiles
• Hale’s Medications and
Mother’s Milk
• Briggs Drugs in Pregnancy and
Lactation
• Lexicomp application
• Micromedex application
26.
27. Contra-indications to
breastfeeding:
• Active HIV or anti-retroviral therapy
• Amiodarone
• Antineoplastic agents
• Lithium
• Radiopharmaceuticals (temporary)
• Retinoids
Medications and Mother’s Milk. Hale, Thomas, PhD. 13th Edition. 2008.
28.
29. Depression in Pregnancy:
• 25% (1 in 4) Women will suffer from
depression while pregnant!
• Risks of not treating depression during
pregnancy:
– miscarriage, perinatal complications, increased
risk of preeclampsia, low neonatal Apgar scores,
and increased admissions to neonatal intensive
care units
• Risks to Mom of stopping medication abruptly:
– withdrawal symptoms, including nausea and
vomiting, diarrhea, sweating, anxiety and panic
attacks, mood swings, and suicidal thoughts,
return of depression
http://www.motherisk.org/prof/updatesDetail.jsp?content_id=1075#1
30. Antidepressants:
Risks of some antidepressants to baby after birth:
– jitteriness; grasping muscle weakness; and respiratory difficulties that
sometimes require use of a ventilator
• The adverse effects on mothers and babies of untreated
depression during pregnancy … outweigh the risk of
transient poor neonatal adaptation in only a very few
neonates exposed to antidepressants during the third
trimester – August 2005
• “The risks of untreated moderate to severe depression far
outweigh the theoretical risks of taking selective serotonin
reuptake inhibitors.” – Dec 2014
• http://www.motherisk.org/prof/updatesDetail.jsp?content_id=1094
31. Antidepressants:
• All SSRIs considered safe
• Also SNRIs (Venlafaxine, Duloxetine)
• Buproprion, Mirtazapine
• Dosage requirements may increase in third
trimester, and return to baseline post-
partum. Monitored by symptom control.
• If discontinuing – go SLOWLY, under doctor’s
supervision - (decrease dose by 25% every 1-
2 weeks)
32. Antidepressants:
• Risks of congenital malformations with paroxetine:
conflicting data – recommend continuing if already stable.
• May be dose dependent (less than 25 mg/day has no
increased risk).
• Possible risk of persistent pulmonary hypertension in
newborn:
• Linked to SSRIs, but causality not proven. No cases of
PPHN have caused death.
33. Antidepressants:
• TCAs are safe:
• Desipramine
• Amitriptyline
• Nortiptyline
• Benzodiazepines:
– 1st
trimester: risk of oral cleft
malformation
– 3rd
trimester: lethargy, withdrawal
syndrome
– Not generally a good treatment for
depression/anxiety
34. Antidepressants:
• In Lactation:
• Same agents safe as during
pregnancy (SSRIs, SNRIs, TCAs)
• Lowest amount of drug found in
breastmilk:
– Sertraline
– Paroxetine
http://www.motherisk.org/women/updatesDetail.jsp?content_id=1000
35. Antidepressants:
• If treating for depression during
pregnancy, should NOT discontinue
postpartum.
–Treat at full dose for at least 6 – 12
months after remission
•Benzodiazepines: Generally safe in
breastfeeding.
–Lorazepam: short half life, low levels
in milk
36.
37. Diabetes:
– Risks to mother:
• retinopathy, nephropathy, hypertension, pre-
eclampsia, caesarean section
– Risks to infant:
• still birth, hypoglycemia, macrosomia, infant/childhood
obesity
– Glycemic targets for pre-existing and GDM:
38. Diabetes:
• Insulin in pregnancy:
– Regular and NPH insulin have most safety
evidence
– may use glargine and detemir
• Oral agents in pregnancy:
– metformin and glyburide are safe.
• Folic acid 5mg daily recommended.
RxFiles Diabetes and Pregnancy Q and A. March 2012.
39. Diabetes:
•Lactation:
•If GDM:
– no treatment needed post-partum
– But risk of developing DM
•Should screen with OGT between 6
weeks and 6 months postpartum.
•Same insulins and oral treatments
are safe in lactation.
– Others have unknown safety.
40. Hypothyroidism:
• Levothyroxine is safe in pregnancy and
lactation:
• Need for thyroid hormone goes up by 25-
50% during pregnancy
• Can take 2 extra pills per week (ex. 2 tabs
on Monday and Friday)
•Postpartum: return to pre-pregnancy dose
•Monitor TSH regularly
•Liothyronine also safe, but not preferred
45. Headache and Pain:
• Acetaminophen:
– Safe for all three trimesters and
lactation
– Maximum dose: 4000 mg per day
• Aspirin (Acetylsalicylic acid):
– avoid unless prescribed
46. Headache and Pain:
• NSAIDs:
– 1st
trimester: increased miscarriage
risk
– 3rd
trimester: premature PDA
closure, renal toxicity.
– Generally avoid in pregnancy!
• Lactation:
– Ibuprofen preferred
– Naproxen often used post-partum
47. Cough and Cold:
Cough:
• Honey, hot drinks, humidifier, raise
head of bed
• DM syrup safe, but no more effective
than honey
Sore throat:
• pain medication (Tylenol), hot drinks,
lozenges
48. Cough and Cold:
• Codeine: Risk of neonatal withdrawal if used
close to term
• May cause premature labour if stopped
abruptly
• Lactation: Risk of toxicity to baby in rapid
metabolizers.
• Monitor baby for breathing, feeding, limpness
• Simpler to avoid OTC codeine products!
49. Allergies/Sinus:
Rhinitis in pregnancy is common
All antihistamines safe in pregnancy and
lactation
• Diphenhydramine, Loratadine, Cetirizine
– 1st
generation drugs may decrease milk production
http://www.motherisk.org/prof/updatesDetail.jsp?content_id=927
50. Allergies/Sinus:
• Saline sprays and rinses are safe
• Intranasal conticosteroids are safe
• Topical decongestant sprays:
– watch for rebound congestion
• Pseudoephedrine:
– 1st trimester: may increase malformations
– Caution if hypertension
– Safe for short term use in later pregnancy and
lactation
51. Nausea:
• Hard candies
• Frequent small meals,
• Split prenatal vitamin, or take one without
iron
• Lots of fluids
• Popsicles, smoothies, Boost/Ensure
• Ginger – may be effective, not harmful
52. Nausea:
• Vitamin B6 – lollipops (B-Natal), tablets
– Watch maximum daily dose. (up to 150mg of Vitamin B6 per day is
safe)
• Diclectin – Rx
– Contains Vitamin B6 (10mg) and Doxylamine (10mg)
– Good first step for nausea and vomiting
– Side effects – drowsy, dry mouth
• Gravol – is safe, but should try Diclectin first
53. Heartburn:
• Elevate head of bed
• Avoid late night snacks
• Quit smoking
• Antacids (TUMS) – perfectly safe!
– May be constipating
• Anti-gas (Simethicone) –
– good for bloating, is safe
54. Heartburn:
• Ranitidine: safe in pregnancy and lactation
• PPIs safe – Omeprazole has most data
• Can take PRN, or regularly
55. Constipation:
• Fluids, fibre, and exercise
• May reduce/eliminate iron from prenatal if
early in pregnancy
• Metamucil
• Docusate
• Sennokot
• Lax-a-Day
56. Diarrhea:
• Lots of water
• Bananas – Rice – Applesauce - Toast
• Kaopectate – not absorbed into body,
therefore perfectly safe
• Loperamide – safe
• Pepto Bismol – not recommended
– Contains salicylate
57. Smoking cessation:
• Nicotine Replacement
– Good alternative if you can’t quit completely –
avoid the 4000 other chemicals from cigarettes
• Available as: gum, inhaler, lozenges, patches
• Either use the patch OR the gum/lozenges
58. Summary of Resources:
• RxFiles and Brigg’s Drugs in Pregnancy and
Lactation: online through SHIRP!
• Motherisk: http://www.motherisk.org/
• Lact Med:
http://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm
• Mother to Baby: http://mothertobaby.org
Interest in this topic, advising patients as community pharmacist. Previous presentations with Early Pregnancy Education program. Our reflex is to say no – but this does a disservice to women and children. “Holding” breastfeeding is not simple or often beneficial. What’s best for Mom is often what’s best for baby. (reference?)
Interest in this topic, advising patients as community pharmacist. Previous presentations with Early Pregnancy Education program. Our reflex is to say no – but this does a disservice to women and children. “Holding” breastfeeding is not simple or often beneficial. What’s best for Mom is often what’s best for baby. (reference?)
Pregnancy and Lactation Labeling Rule
The Pregnancy subsection will provide information relevant to the use of the drug in pregnant women, such as dosing and potential risks to the developing fetus, and will require information about whether there is a registry that collects and maintains data on how pregnant women are affected when they use the drug or biological product. Information in drug labeling about the existence of any pregnancy registries has been previously recommended but not required until now.
The Lactation subsection will provide information about using the drug while breastfeeding, such as the amount of drug in breast milk and potential effects on the breastfed child.
The Females and Males of Reproductive Potential subsection will include information about pregnancy testing, contraception and about infertility as it relates to the drug. This information has been included in labeling, but there was no consistent placement for it until now.
Good professional info, and patient friendly – disease states, drugs, exercise, nutrition, MotherNature (NHPs, CAM)
US content. Some drugs and conditions additional to Motherisk. Good printable patient resources.
A pregnancy exposure registry is a study that collects health information from women who take medicines or vaccines when they are pregnant. The FDA does not run pregnancy studies, but it keeps a list of registries. There may be a registry for the medicine you are taking.
TONS of information! Quick comparisons of drugs on each topic – great antibiotic summary of safety in each trimester.
Brigg’s Drugs in Pregnancy and Lactation – online with SHIRP
App for iPhone/iPad
Subscriptions required for apps
HIV may be transmitted by breastfeeding
Amiodarone – infant dose 4-6% of maternal, may accumulate, long t1/2, adverse cardiovascular and thyroid effects
Antineoplastics – bone marrow suppressions, damage to intestinal epithelial cells
Lithium – infant dose18-23% of maternal. Severe rash reported. Use with caution.
Radiopharm – see Hale’s for detailed info
Retinoids – highly lipid solube, mutagenic and carcinogenic
68% of women who stop their medication have recurrence of depression during pregnancy. Of these, 50% occurred in first trimester, and almost all (90%) by end of 2nd trimester.
Rate of relapse is 5 times higher in those who d/c meds vs. those who continued.
PPHN Absolute increased risk is from baseline of 0.1-0.2% to 0.3 -1.2%.
Postpartum depression can impact the mother’s ability to care for and bond with her child. [Incidence of 15% per Motherisk]
Infants are at a higher risk of irritability, inactivity, inattentiveness, and fewer facial expressions. They often have a similar
physiological profile as depressed mothers, such as cortisol, and peripheral levels of dopamine, serotonin & norepinephrine.
Cognitive, emotional and behavioural concerns can surface when an infant is exposed to a chronically depressed mother.
(same as general depression guidelines). (LactMed)
In older infants – may be able to time doses for after evening feed.
In infants, not likely to be possible.
Watch for sedation – more concern in premature or newborn infants than in older children.
From RxFiles
(20% over 9 years).
Hypothyroid: Levothyroxine safe in pregnancy and breastfeeding. Dose requirements will increase during pregnancy (up to 50%), patient can take 1 extra dose 2 days per week when pregnancy detected. LT3 (Liothyronine) is safe in pregnancy, and lactation, but not preferred agent. TSH should be checked when pregnancy detected and regularly during pregnancy. Postpartum: go back to pre-pregnancy dose, recheck TSH at postpartum visit.
Hyperthyroid: 1st trimester: Propylthiouracil preferred (MMI linked to cranial malformations), 2nd-3rd trimesters: Methimazole preferred – dose requirements may decrease in later pregnancy. (PTU has risk of hepatotoxicity). Lactation: MMI (doses under 30 mg) and PTU (doses under 300 mg) both safe
Remember: MMI is 10 times more potent than PTU.
Acetaminophen: safe in all trimesters and lactation
NSAIDS: 1st trimester – possible increased miscarriage risk, malformations. 3rd trimester: premature PDA closure, renal toxicity. Generally avoid in pregnancy!
Lactation: Ibuprofen preferred, Naproxen often used post-partum.
ASA: Avoid unless prescribed
NSAIDS: 1st trimester – possible increased miscarriage risk, malformations. 3rd trimester: premature PDA closure, renal toxicity. Generally avoid in pregnancy!
Lactation: Ibuprofen preferred, Naproxen often used post-partum.
Congestion: Saline sprays safe, topical decongestant sprays safe (but rebound congestion), Pseudoephedrine – 1st trimester use may increase malformations. Safe to use in short term (caution if hypertensive). Lactation: safe, but may decrease milk production.
Opioids:30 Codeine, tramadol; for other commonly used opioids. 3rd trimester
use may cause neonate depression & withdrawal. Abrupt D/C may cause premature
labour & spontaneous abortion. Taper to lowest effective dose.
Codeine – risk of morphine toxicity in ultrarapid CYP2D6 metabolizers. Limit
use to 4 days. Monitor baby for limpness, difficulty breathing/feeding, or sleep.
Rhinitis in pregnancy common due to: increased blood volume, vascular engorgement, hormonal increase in nasal secretions.
Antihistamines (Benadryl Cetirizine, Loratadine) safe in pregnancy and lactation, 1st generation drugs may decrease milk production
http://www.motherisk.org/prof/updatesDetail.jsp?content_id=927
Congestion: Saline sprays safe, topical decongestant sprays safe (but rebound congestion), Pseudoephedrine – 1st trimester use may increase malformations. Safe to use in short term (caution if hypertensive). Lactation: safe, but may decrease milk production.
Recall: Buproprion is safe in pregnancy
Champix not recommended