Pregnancy & Breastfeeding

Dosage
Dr Dhanuja Bhowmick
Mensural cycle
• It consists of natural changes that occur in a woman’s body every
month in preparation for pregnancy. Menstruation starts at puberty
and ends at menopause.
• Phases: Menstruation, Follicular phase, Ovulation & Luteal phase
• The menstrual cycle is under the control of three sets of hormones:
1) Gonadotrophin releasing hormones
2) Gonadotrophins - luteinising hormone (LH) and follicle stimulating
hormone (FSH) from the pituitary gland
3) Ovarian hormones - oestrogen and progesterone
Pregnancy
• It is a unique period in a women’s life. During 40 weeks many changes occur
that affect the pharmacology of medicines. (ie) Increased cardiac output,
Increased gastric PH, Decreased motility, Increased maternal plasma
volume, Increase in Progesterone and estradiol levels, Increased GFR.
• The placenta allows exchange of nutrients and medications to the fetus. The
fetus is generally at the greatest risk of developing teratogenic effects from
medications during the first trimester, but it is drug specific.
• All efforts should be made to optimize the risk benefit ratio.
• Drugs with low molecular weight, low maternal protein binding, low
ionization, and high lipophilicity are more likely to cross the placenta and
cause pharmacologic affects.
• The developing fetus’s body systems are not mature; therefore, the fetus
may lack the ability to metabolize medications causing teratogenic effects.
PHYSIOLOGICAL CHANGES IN
PREGNANCY
• Pregnancy occurs when a sperm penetrates an egg (fertilization) and usually
takes place in the woman's fallopian tube. The fertilized egg immediately begins
to divide into a growing cluster of cells. Between 5-7 days after ovulation the
fertilized egg implants into the wall of uterus and starts forming the placenta.
fetus.
• As the fetus and placenta grows, phenomenal alterations in metabolism occur.
The most obvious physical changes are weight gain and altered body shape.
• How a drug affects the fetus depends on the fetus's stage of development and
the strength and dose of the drug
• The effect of a medication also depends on the dose that reaches the fetus. This
dose is affected by the maternal dose, distribution of the drug in maternal blood
stream, placental function, maternal and fetal genetic and physiologic status as
well as exposure to other drugs, chemicals or environmental hazards
Impact of Physiologic Changes During
Pregnancy on Pharmacokinetics
Absorption
Drug absorption is affected in several ways during pregnancy, and it is difficult to predict the final repercussion on drug
efficacy. Decreased GI transit can result in a delay in drug peak effect, prolonging the time of contact of drugs with the
intestinal mucosa, and possibly enhancing absorption of certain drugs. The higher gastric pH may affect the absorption of
weak bases or acids. Skin, tissue, and lung absorption might also be increased by physiologic changes during pregnancy.
Distribution
The volume of distribution increases for most drugs during pregnancy due to plasma volume expansion and the presence of
amniotic fluid, the placenta, and the fetus. This results in a decrease in maximal concentrations of drugs and in their half-life.
In addition, hypoalbuminemia and decreased protein binding of drugs increases free fraction of some medications.
Metabolism
During pregnancy the activity of some isoenzymes is increased (e.g., CYP3A4, CYP2A6, CYP2D6, CYP2C9), and the activity of
others is decreased (e.g., CYP1A2, CYP2C19). It is difficult to predict the net impact on drug effect since there is a wide
interindividual variability and since some drugs are metabolized by several isoenzymes. The activity of uridine diphosphate
glucuronosyltransferase (UGT) is also increased during pregnancy.
Renal Elimination
Renal blood flow and glomerular filtration are increased significantly during pregnancy. The impact of this increase is more
important for drugs that are eliminated unchanged in the urine.
Embryonic development
PLACENTAL TRANSFER OF DRUGS
• The placenta is the product of conception.
• It is the functional unit between fetal blood and maternal blood.
• In order for a drug to cause a teratogenic or pharmacological effect on the fetus, it must cross
from maternal circulation to fetal circulation through the placenta by diffusion.
• During pregnancy maternal plasma albumin decreases while fetal albumin increases. As a
result the concentration of free drug increases which crosses the placenta to reach the fetus.
• Fetal pH is slightly more acidic than maternal pH and so weak bases are more likely to cross
the placenta.
• Moderately lipid soluble drugs can easily diffuse across the placental membrane. Drugs with
low molecular weight (<500 g/mol) diffuse freely across the placenta. Drugs with a higher
molecular weight (between 500-1000 g/mol) cross the placenta less easily, while a few drugs
with a high molecular weight (>1000 g/mol) do not cross the placental membrane.
• Transplacental transfer of drugs increases in the third trimester due to increased maternal
and placental blood flow, decreased thickness and increased surface area of the placenta
• Study 1: Information from one population-based study conducted during 1998 to 2002 found
that although the prevalence of medication use decreased from 72% before pregnancy to
56% during pregnancy, it returned to 78% in the postpartum period. The most commonly
used medications during pregnancy in this population included antibiotics (75%), oral
contraceptives (45%), and nonsteroidal anti-inflammatory drugs (NSAIDs; 17%). In the
postpartum period, the most commonly used medications were NSAIDs (56%), oral
contraceptives (53%), and antidepressants (13%). Another study has indicated that
antiemetics, tranquilizers, antihistamines, and diuretics are additional frequently used
medications during pregnancy.

• Study 2: An assessment of prescription drug use in Hawaii from 2009 to 2011 surveyed
women with recent live births and found that 14.2% reported prescription drug use before
pregnancy and 17.6% reported prescription drug use during pregnancy. The most commonly
reported types of prescription medications used during pregnancy in this report were anti-
infectives, pain relievers, and gastrointestinal drugs. Of those women who reported
prescription use during pregnancy and attending prenatal care, 10.3% reported that they did
not receive counseling regarding safe medication use during their prenatal care.
Drugs of Concern During Breast-Feeding
The mammary tissue in the breast is composed of clusters of milk
producing alveolar cells surrounding a central lumen

• The effect of drugs on the nursing infant depends on

1) Transfer of drug into breast milk
2)The amount of breast milk consumed by the infant
3) The pharmacological activity of the drug: ADME by the infant
4) Condition of the infant: Premature, Compromised, Weak…
How drugs transfer into breast milk
• Ionization of drug: Non-protine bound and non-ionized drugs are
more likely to be transferred into breast milk
• Molecular weight of drug – Low mol. Wt drugs transfer easily
• Solubility of drugs in lipids and water
• Factors affecting drug transfer
1) Maternal serum drug concentration
2) Drugs protein binding, lipid solubility, molecular weight and
ionization
3) Milk composition
4) Age of Infant
Clinical Presentation and Diagnosis of
Pregnancy and Lactation
Hyperemesis gravidarum
Bacteriuria
Bacterial vaginosis
Vulvovaginal candidiasis
Chlamydia and gonorrhea
Genital herpes simplex virus
Pelvic inflammatory disease
Syphilis
Trichomoniasis
• Pre term labour
• Group B Streptococcus
• Mastitis
• Nipple candidiasis
• Gestational diabetes
• Hypertension (Chronic, Pre-eclampsia, Super imposed, Gestational,
Transient)
FDA Classification
Medications With Proven Teratogenic Effects
in Humans
Drug & Drug class Critical period
Alkylating agents Organogenesis
Amiodarone From 10th week post
conception
Androgens After first trimester
Angiotensin receptor After first trimester
antagonists
Anticonvulsants Organogenesis
Corticosteriods Organogenesis
Diethylstilbestrol First & second trimester
Fluconazole Throughout pregnancy
Vitamin A Organogenesis
Drug Critical period
Lithium Cardiac organogenesis
Methimazole/ Propyl Organogenesis
Methotrexate 2nd & 3rd trimester
Misoprostol Organogenesis
NSAID Third trimester
Penicillamine Not defined
Tetracycline 14 weeks post conception
Thalidomide 20 – 36 days after conception
Trimethoprim Organogenesis
Warfarin Between 4th & 7th week post conception
 Medication Dosing Recommendations During Pregnancy and Lactation
Drug Dosage Comments
Micro nutrients & Vitamins
Calcium 1000 – 1500 mg/day
Folic acid 4mcg/ day Higher dose in case of known H/O NTD
Iron 27 mg excess, upto 120mg daily Higher dose in case if IDA
Vitamin D 200 IU excess, 400 IU in BF infants
Nausea & Vomiting
Diphenhydramine 25 – 50 mg Q6H
Doxylamine 12.5 mg Q6H Can be taken with Pyridoxin 25 mg TDS
Metaclopramide 5 – 15 mg Q6H
Meclizine 12.5 – 50 mg OD
Heartburns
Liquid antacids 15 – 30 ml
Constipation
Polycarbophil, Psyilium, Docusate, Bisacodyl, Senna, Lactulose
Drugs Dosage Comments
Nasal Sprays & Cough
Oxymetazoline 2-3 sprays daily upto 5 Rebound congestion
days
Pseudoephedrine 60 mg every 4-6hrs Avoid In 1st trimester,
Use short term
CPM 4 mg every 4-6hrs
Cetirizine, Loratadine 10 mg
Budesonide 32 mcg (1-4 spray
daily)
Beclomethasone 50 – 100 mcg, BD
Fluticasone 100 mcg
Dextromethorphan 30 mg every 6-8 hrs
Codeine 10-20 mg every 6-8 hrs
Bacterial Vaginosis
Metranidazole 250 mg TDS x 7 days
(or) 500mg BD x 7 days
Clindamycin 300 mg BD x 7 days F/B Pregnancy – Oral, BF -
suppository HS Intravaginal
Drug Dosage Comments
Premature rupture of membranes
Ampicillin 2 g IV F/B 1g IV Q6H x 48 Can be used in
hrs, F/B Amoxicillin combination
Amoxicillin 250 – 500 mg x 5 days
Erythromycin 333 mg x 7 days
Fetal lung maturation
Betamethasone 12 mg IM OD x 2 doses
Dexamethasone 6 mg IM BD x 4 doses
Preterm Labour
Nifedipine 30mg p/o F/B 10 – 20 mg
Q4-6hr x 48 hrs
Magnesium Sulfate 4-6 g IV bolus over 20min
F/B 2-3 g/hr IV
Indomethacin 50 – 100 mg load F/B 25 –
50 mg P/O Q6H x 48 hrs
Terbutaline 0.25 mg S/C every 20min –
3 hrs
Glyceriltrinitrate 10 mg patch x 12 hrs upto
48 hrs
Antibiotics in Pregnancy
Drugs of choice
• Penicillin group : Ampicillin, Amoxicillin, Flucloxacillin, Penicillin V,
Propicillin
• Cephalosporins
• Macrolides: Erythromycin, Azithromycin
• Metronidazole
• Fosfomycin
Antidepressants
Drugs Effects

SSRI’s Jitteriness, Irritability, Respiratory distress. Pulmonary

hypertension in rare cases

Paroxetine Cardiac defects,

Benzodiazepines Avoid: Tranquilizers for long term

Can use Lorazepam

Valporic acid NTD, Impaired cognitive development

Medication risks are typically not greater than those of untreated mental illness. “Switching a woman’s
medication is something that is to be done very carefully and reluctantly.”
Drugs of Concern During Breast-Feeding
Drugs Comments
Acebutolol Neonatal beta blockade reported
Amiodarone Accumulates due to longer ½ life,
Neonatal thyroid & CVS toxicities
Antineoplastics Neonatal myelosupression
Atenolol Neonatal beta blockade reported
Bromocriptine Supress lactation
Cabergoline Supress lactation
Ergotamine Ergotism, inhibit prolactin secreation
Lamotrigine Rash & CNS effects
Lithium Upto 50% maternal serum levels
reported in infants in case of toxicity
Radioactive Iodine Longer ½ life (21 – 42 days)
Tetracyclines Dental staining & decreased epiphyseal
bone growth
Illicit drugs Unknown contents & effects
Considerations in breast feeding

• With hold or delay treatment if possible

• Use of drugs with poor penetration into milk
• Use an alternative route of administration
• Avoid nursing at peak concentration
• Pump & dump milk
Summary
• Complex physiology surrounds the process of fertilization and pregnancy progression.
• Drug characteristics and physiologic changes modify drug pharmacokinetics during pregnancy,
including changes in absorption, protein binding, distribution, and elimination, requiring
individualized drug selection and dosing.
• Although drug-induced teratogenicity is a serious concern during pregnancy, most drugs required
by pregnant women can be used safely. Informed selection of drug therapy is essential.
• Health issues influenced by pregnancy, can be treated safely and effectively with non-
pharmacologic treatment or carefully selected drug therapy.
• Some acute and chronic illnesses pose additional risks during pregnancy, requiring treatment with
appropriately selected and monitored drug therapies to avoid harm to the woman and the fetus.
• Management of the pregnant woman during the peripartum period not only can encompass
uncomplicated pregnancies/deliveries, but can also include a wide variety of potential
complications that require use of evidence-based treatments to maximize positive maternal and
neonatal outcomes.
• Understanding the physiology of lactation and pharmacokinetic factors affecting drug distribution,
metabolism, and elimination can assist the clinician in selecting safe and effective medications
during lactation.