Drugs in lactation and pregnancy

By : Dr. Mohammad Baghaei ,Cosmetic scientist, Pharmacist ,Facedoux1
In the name of God
The Safety of Dermatological Drugs
During Pregnancy & Lactation
Dr.Mohammad Baghaei (Pharm .D), Dr. Hamidreza Zolfaghari(MD),
Dr. Hamidreza Mohseni (MD), Dr.Aliasghar Aliyari (MD),
Dr. Ali Abedi (Pharm .D), Dr. Alireza Khosravi (MD)

INCLUDES:
 Introduction
 Dermatological drugs during Pregnancy
 FDA category
 Dermatological drugs during Lactation
 References

Introduction
Treatment of many dermatologic conditions is elective. Some drugs which used by the
dermatologist for the patient who is pregnant or lactating may have potentially harmful
effects on the mother and fetus or nursing infant. Likewise, not every pregnancy (in the
absence of drug therapy) results in the delivery of a perfectly healthy baby, and physicians
are anxious to have litigation about prescribe a medication that might possibly have
contributed to the problem. For this reason, a general reluctance exists among physicians
to prescribe medications during pregnancy and lactation. There are, however, drugs for
which use during pregnancy and lactation have no apparent contraindication. It may be
have both interest and comfort to the clinician and patient to become familiar with this
select list of drugs.
This book identifies contraindications of various drugs with the possible extent information which
currently available.

Pregnancy:
During the first trimester drugs may produce congenital malformations (teratogenesis),
and the period of greatest risk is from the third to the eleventh week of pregnancy. During
the 2nd and 3rd trimesters drugs may affect the growth and functional development of the
fetus or have toxic effects on fetal tissues. Drugs given shortly before term or during
labour may have adverse effects on labour or on the neonate after delivery.
The natural occurrence of fetal abnormalities in 1-2% of human pregnancies makes
interpretation of case reports difficult. Data from animal teratogenicity studies are
extremely valuable; however, they are not always applicable to humans. Drugs that are
teratogenic in animals may be safe in humans and versa. One factor which makes the
gathering of appropriate information on the effect of drugs in pregnancy very difficult is
that the manufacturers of many of the drugs carry a blanket warning on use in pregnancy
in their product information literature.
If treatment is clearly indicated and the patient is willing to accept potential risks but the
safety of the treatment in pregnancy has not been established, then the first approach
should be topical therapy when possible.

The term "Pregnancy Risk Factor" followed by letter A, B, C, D or X signifies a pregnancy
category. The FDA established these five categories to indicate the potential of a systemically
absorbed drug for causing birth defects. The categories are determined by the reliability of
documentation and the risk to benefit (risk: benefit) ratio.
Pregnancy category X is particularly distinguished in that if any data exists that may
implicate a drug as a teratogen (potentially causing birth defects) and the risk to benefit ratio
is clearly negative, the drug is contraindicated (prohibited from use) during pregnancy.
Sometimes a drug taken by a woman during pregnancy may enter a fetus, causing damage or
birth defects. The risk of damage to the fetus is the greatest in the first few weeks of
pregnancy, when major organs are developing. However, researchers do not know if taking
medicines during pregnancy may also have negative effects on the baby later on.
Introduced in 1979, the pregnancy category of a pharmaceutical agent is an assessment of the
risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during
pregnancy. It does not include any risks given by pharmaceutical agents or their metabolites
that are present in breast milk.

The FDA requires a relatively large amount of high-quality data on a pharmaceutical for it to
be defined as pregnancy category A. As a result of this, many drugs that would be considered
pregnancy category A in other countries are allocated to category C by the FDA.
FDA CATEGORIES
Category A: Controlled studies in pregnant women fail to demonstrate a risk to the fetus in the
first trimester with no evidence of risk in later trimesters. The possibility of fetal harm appears
unlikely.
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 a risk in later trimesters.
Category C: Either studies in animals have revealed adverse effects on the fetus (teratogenic or
embryocidal effects 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 benefits justify 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 for 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, or both, 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.

Dermatological drugs in pregnancy:
1. Analgesics, Narcotics & Antipyretics, Anesthetics
General & Local
2. Anthelmintics
3. Anti-Acne products topical
4. Antiamoebics
5. Antibacterials
6. Antidepressants,Antipsychotics,Anxiolytics,Hypnotics
Sedatives
7. Antifungals
8. Antihistamines
9. Anti-mycobacterial
10.Antirheumatic,anti-inflammatory
11.Antiscabietics and Pediculicides
12.Antituberculous Agents
13.Antivirals
14.Contraceptive Agents

15.Cytotoxic Drugs
16.Hormones
17.Vaccines (Live)
18.Vitamins and Minerals
19.Miscellaneous

Analgesics,Narcotics & Antipyretics, Anasethetic General & Local
Adverse effectsFDATrimester of riskDrugsGroups
categories
With large doses, neonatal respiration depression, hypotonia and bradycardiaB3Lidocaeine(topical)
after paracervical or epidural block neonatal methaemoglobinaemia with prilocaineB3Lidocaeine-H(topical)
B3Lidocaeine-p(topical)Anasethetic
Neonatal methaemoglobinaemiaB3Prilocaine-FGeneral & Local
C3Codein
C3Morphine
Respiratory depression in newborns, withdrawal symptoms in neonates ofC3Meperidine
dependent mothersC3OxycodoneNarcotics
C3Diphenoxylate
Closure of fetal ductus arteriosus in utero and possibly persistent pulmonaryD1,3Aspirin,Salicylates
hypertension of the newborn (occurs with high regular doses) Delayed onset and
increased duration of labour with increased blood loss. Impaired platelet function
and risk of haemorrhage both in newborn and in the mother. kernicterus in
jaundiced neonates.
B3AcetaminophenNSAIDS
Regular use results in closure of fetal ductus arteriosus in utero and possiblyB1,3Naproxen
persistent pulmonary hypertension of the newborn. Prolong labour and delay inB1,3Ibuprofen
parturition.C1,3Celeoxib
D1,3Indomethacine

Antihelminitics
categories
C1Albendazole
Teratogenic in animal studiesC1MebendazoleAntihelminitics
C1Thiabendazole
Anti- acne Topical
categories
It has not shown mutagenicity, teratogenicity, or embryotoxicity in animal butBAzelaic Acid
experience is too limited to assess safety of the drug.Anti-acne
The medication may be systemically absorbed with topical use. Studies inCBenzoyl peroxidetopical
human have not been done . Use during pregnancy is not contraindicated.
A congential anomaly involving the eye has been reported.CAdapalene
It has been associated in case reports with teratogenicity when used during the first trimesterC1,2,3Tretinoin
It has caused retinoid-like anomalies.X1,2,3Tazarotene

Antiamoebics
categories
Manufacturer advises avoidance of short, high dosage regimensBMetronidazole (ALL FORMS)Antiamoebics

Antibacterial
categories
Avoid, 8th cranial nerve damage. Risk higher with streptomycin, kanamycin thanC2, 3Gentamycin
gentamicin, tobramycin. Potentially nephrotoxic and ototoxic to fetus.D2, 3StreptomycinAminoglycosides
D2, 3Kanamycin
D2, 3Tobramycin
CCiprofloxacin
Congenital anomailis are inconsistC1,2,3OfloxacinFlouroquinolones
CLomefloxacin
CNalidixic Acid
Maternal hepatotoxicity with large parenteral doses, bone growth disturbance,D2, 3Tetracycline
May induce hypoplasia of the enamel and discoloration of the teeth.D2, 3MinocyclineTetracyclines
D2, 3Doxycycline
BPenicillin G
BPenicillin VPenicillins
Have not been associated with an increased risk of congenital anomaliesBAmoxicillin
BAmpicillin
BCloxacillin
Possible teratogenic risk (folate antagonist).CTrimethoprimTrimethoprim
A large survillance study found an association between congenitalB1Cephalexin
malformationsand use of cephalexin ,cefaclor & cephradine during the firstB1Cefaclor
trimester of pregnancybut similar findings did not occur with cefadroxil.B1Cephradine
BCefradoxilCephalosporines
BCefexim
BCefotaxime
BCeftizoxime
BCeftazidime
BCeftriaxone
BCefuroxime

Antibacterial(cont)
categories
Toxicities that may be observed in the newborn includeC3SulfamethoxazoleSulfonamides
jaundice and hemolytic anemia.B3Sulfadiazine
C3Sulfacetamide
It has not been associated with a reported risk .BAzithromycinAzithromycin
It has not been associated with a reported risk .BErythromycinMacrolides
It has not been associated with a reported risk .BErythromycinTopical antibacterial
It has not been associated with a reported risk .BMupirocinAgents
It has not been associated with a reported risk .BClindamycin
It has not been associated with a reported risk .BPolymixin B
It has not been associated with a reported risk .BNeomycin
It is thought to pose a potential risk for Kernictures and hemorrhage inBSilver Sulfadiazine
the premature infant or infant with glucose-6-phosphate
dehydrogenes (G6PD)Deficiency.

Antidepressants, Antipsychotics,Anxiolytics&Hypnotics Sedatives
categories
AVOID, withdrawal effectsin neonates, post partumhemorrhage and hemorrhagicD1,2,3BarbituratesAntidepressants
disease of the newborn, hypotension, reduced respiratory function and hypothermiaAntipsychotics
Neonatal drowsiness, hypotonia and withdrawal symptoms,D1,3BenzodiazepinesAnxiolytics
avoid large doses and regular use.Hypnotics Sedatives
Extrapyramidal effects in neonate occasionally reported.C3Phenothiazines(Trifluprazine)
Occasionally, tachycardia, irritability, muscle spasms, convulsions,D3Tricyclics (Amitriptyline)
urinary retention, withdrawal effects in neonate
Antifungal Drugs
categories
Adverse fetal effects seen in animals at high doses.C1,2,3Fluconazole
Fetotoxicity and teratogenic in animals.Unrated1,2,3Griseofulvin
Abnormalities of fetal development when given at high doses to pregnant ratsC1,2,3Itraconazole
and mice No data available in human pregnancy.
Induces syndactylismin rats at a dose of 80 mg/kgC1,2,3KetoconazoleAntifungal Drugs
May be absorbed if used over large areas of the body.1,2,3Seleniumsulfide, topical
It has not been associated with a reported risk .BNystatin
Animal studies evaluating oral terbinafin in pregnancy showed production of benign tumors in rats.BTerbinafin
It is a known teratogen and should be avoided during pregnancy .DVoriconazol
Clotrimazole used during the first trimester of pregnancy as an oral topical treatmentB1Clotrimazol (topical)
of vaginitis has been associated ith a slightly increased risk of congenital
defects in humans in one study.
It has been associated with animal fetotoxicityC1,2,3miconazole

Antihistamins
categories
It has not been associated with a reported risk .BCetrizine
It has not been associated with a reported risk .BCyproheptadine
It has not been associated with a reported risk .BDiphenhydramine
UnratedDoxepinAntihistamins
Fexofenadine has no human data,and notes that animal studies have shownC1,2,3Fexofenadine
toxicity to the embryo and fetus.
UnratedHydroxyzine
It has been associated with a few adverse outcomes during pregnancy includingB1,2,3Loratidine
cleft palate, microtia, microphthalmia,deafness,dysmorphia and diaphragmatic hernia.
Anti-mycobacterial
categories
Associated with pigmentation of infant's skinC1,2,3ClofazimineAnti-mycobacterial

Antiscabietics and Pediculicides
categories
Absorption in humans has not been studied.CCrotamitonAntiscabietics
Use of lindane has been controversial, with some reports discouragingandBLindaneandPediculicides
the use of lindane in pregnancy .
It has not shown teratogenicity in animals.BMalathion
It has not shown teratogenicity in animals.BPermethrin
Antirheumatic,Anti-inflammatory
categories
Avoid if possibleD1,2,3PenicillamineAntirheumatic,
anti-inflammatory

Antivirals
categories
It has not shown teratogenicity in animals, but causes fetal death, growthBAcyclovir
retardation, and malformations in rats at maternotoxic dose. Use in human
pregnancies has not been associated with adverse fetal effects.
It has not shown teratogenicity in animals, but causes benign tumors in rats.BFamciclovirAntivirals
It has not shown teratogenicity in animals.Bvalacyclovir
Avoid, teratogenic in animal studies Manufacturer recommends avoid unless compelling reasons.C1,3Idoxuridine
Avoid, teratogenic in animal studies Manufacturer recommends avoid unless compelling reasons.C1,3Interferon
Antituberculous Agents
categories
Embryotoxicity in animals. Increased risk at neonatal bleeding - if given in 3rdC1,2,3RifampicinAntituberculous
trimester. Prophylactic Vitamin K is recommended for mother and newborn infant
if used during the last few weeks of pregnancy

Contraceptives
categories
Epidemiological evidence suggests no harmful effects on fetus.X1,2,3Oral contraceptivesContraceptives
Cytotoxic Drugs
categories
Most are teratogenicX1,2,3Cytotoxic DrugsCytotoxic Drugs

Hormones
categories
Possibility of suppression of the adrenal cortexin the newborn after tong termC2, 3Corticosteroids,oral
treatment ,in animal studies during pregnancy has been associated with an
increased risk of cleft palate, placental insufficiency, spontaneous abortion
, and growth retardation in utero.
Avoid superpotents, avoid occlusion, avoid large areasC2, 3Corticosteroids,topicalHormones
Avoid, virilisation of female fetusD1,2,3Androgens(Testosterone)
Avoid, high doses may be teratogenic. Animal studies have shown that high dosesx1Progestogens
of progestogens can cause masculinisation of female fetus.
Vaccines (Live)
categories
Theoretical risk of congenital malformationsUnrated1Vaccines (Live)Vaccines (Live)

Vitamins and Minerals
categories
Excessive doses may be teratogenicB(D,X)Vitamin A
May produce neonatal hemolysis, risk of kernicterus in jaundiced infants especially if prematureCVitamin K analogues
CVitamin B- complex
CVitamin B12Vitamins and
CVitamin B1Minerals
CVitamin B2
CVitamin C
Excessive doses may be teratogenicAVitamin D
AVitamin E
Miscellaneous
categories
May be small risk of teratogenesis including increased risk of neural tube defectsD1Carbamazepine
High doses cause neurological disturbances in the fetusC1,2,3Chloroquine,Hydroxychloroquine
Teratogenic in animalsCColchicine
Neonatal haemolysis and methaemoglobinaemiaC3DapsoneMiscellaneous
Neonatal hirsutismreportedC3Minoxidil
May inhibit labour, teratogenic in animalsC3Nifedipine
AVOID, Neonatal death and embryotoxicity have been reportedX1,2,3Podophyllin,topical
Avoid, may cause hypothyroidismD2, 3Potassiumiodide,oral
Possible skin absorption of sufficient iodine to affect the fetal thyroidCPovidone-iodine,topical
It is a known carcinogen and mutagen , no studies have been done in human .CCoal Tar
It was embryotoxic, fetotoxic, and carcinogenic in some animal studies.CCyclosporine

Lactation:
Most drugs taken by the nursing mother will be excreted in her milk. Usually the amount is
negligible and the effect on the infant insignificant rarely is it necessary to stop breast feeding due
to the mother's medications.
A good rule to follow is if the drug can safely be given directly to the infant, it is generally safe to
give to the mother during lactation.
To minimize the amount likely to be excreted in breast milk and ingested by the infant, it is
recommended that the dose of a drug is taken 15 minutes after feeding, or 3-4 hours before the
next feed.
Drugs with short acting characteristics or with short elimination half lives are obviously less likely
to cause problems and once or twice daily dosage is preferable to more frequent administration.
All breast fed infants should be monitored for adverse effects of drugs ingested by the mother.

Dermatological drugs during lactation:
1- Analgesic & antipyretic
2- Antihelmintics
3- Antibacterials
4- Antidepressants/Antipsychotics/ Anxiolytics/Hypnotics/Sedatives
5- Antifungals
6- Antiscabetics
7- Antituberculous agents
8- Contraceptives
9- Cytotoxic drugs
10- Hormones
11- Immunosuppressants
12- Vitamins & minerals
13- Miscellaneous

Analgesics & Antipyretics
Adverse effectsDrugsGroups
AVOID -possible risk of Reye's Syndrome. Regular use of high doses could impair platelet function andAspirin
produce hypoprothrombinaemia if neonatal vitamin K stores are low.Analgesics
Milk levels are similar to maternal plasma levels. One case report of possible indomethacin inducedIndomethacin& Antipyretics
seizures in a breast-fed infant.
Regular use of high doses can produce dependence and withdrawal effects.Narcotic analgesics
Antibacterials
Excreted into breast milkClindamycin
Significant amount in milk, may give bitter taste to milk.Metronidazole
Risk of haemolytic anaemia in G6PD deficient babies. Small risk of kernicterus in jaundiced infants.SulfonamidesAntibacterials
& Co-trimoxazole
Remote theoretical possibility of dental staining and inhibition of bone growth.Tetracycline

Antidepressants / Antipsychotics/ Anxiolytics / Hypnotics / Sedatives
AVOID large doses and regular use; drowsiness, lethargy and failure to thrive have been reportedBenzodiazepinesAntidepressants
DrowsinessChloral hydrateAntipsychotics
Monitor infant for excessive drowsiness and for normal growth and developmentPhenothiazinesAnxiolytics /
Hypnotics / Sedatives

Antifungals
Excreted in breast milk. Manufacturer recommends that the mother should not breast feedItraconazoleAntifungals
Probably excreted in breast milk. May increase the risk of kernicterus in nursing infants.Ketoconazole
Antihelmintics
Excretion in breast milk is unknown, manufacturer recommends discontinuation of the drug or of nursing.ThiabendazoleAntihelmintics

Antimycobacterial
As clofazimine is excreted in breast milk, infant may have skin discoloration frombreast-feedingClafazimineAntimycobacterial
Antiscabetics
Amount too small to be harmful, avoidance of breast feeding for 2 days after lindane application.Lindane, topicalAntiscabetics
Excretion in milk is unknown, tumorigenic potential in some animal studiesPermethrin, topical

Antituberculous agent
Theoretical risk of convulsions and neuropathy. Prophylactic pyridoxine should be given to mother and babyIsoniazidAntituberculous agent
Contraceptives
AVOID combined oral contraceptives until weaning or for 6 months after birth. Progestogen-onlyOral ContraceptivesContraceptives
oral contraceptive do not appear to affect established milk flow adversely but may alter composition.
Cytotoxic Drugs
AVOID - probably some risk of toxicity with most cytotoxicsAllCytotoxic Drugs

Hormones
AVOID - may cause masculinisation in the female infant or precocious development in the male infant,Androgens
high doses suppress lactation
Should not be applied to the breasts prior to nursing.Corticosteroids, topHormones
Prolonged, continuous treatment with high doses (> lOmg prednisolone daily) could affect infant's adrenal functionCorticosteroids
Significant amounts in milk. Possible risk of anti-androgen effects on the infantCyproterone acetate
AVOID adverse effects on lactationOestrogens
Immunosuppressants
AVOID - excreted into breast milk and potentially toxicCyclosporinImmunosuppressants

Vitamins & Minerals
Theoretical risk of toxicity in infants of mothers taking large dosesVitamin A
Severely thiamine-deficient mothers should not breastfeed as toxic methylglyoxal excreted in milkVitamin Bi (Thiamine)
Very large doses have been reported to have a lactationinhibiting effect. Monitor infant growthVitamin B6 ( Pyridoxine)Vitamins & minerals
Chronic maternal ingestion of large doses may result in hypercalcaemia in infantVitamin D
Miscellaneous
AVOIDAcitretin/Etretinate
Isotretinoin
Caution because of cytotoxicityColchicine
Haemolytic anaemia; although significant amount in milk, risk to infant is very smallDapsoneMiscellaneous
AVOID - risk of toxicity in infantHydroxychloroquine
AVOID - concentrated in breast milk, may cause thyroid suppression, goitreIodides
AVOID - potential for production of benign mammary fibroadenomas in animal studiesPentoxifylline
Excretion in human milk is unknown. Manufacturer recommends discontinuation of the drug or of nursingPodophyllum, (top)
Sufficient iodine can be absorbed fromvaginal preparations to affect infant's thyroidPovidone iodine
Possible risk of haemolyticSulphasalazine

References:
1. Physician's desk reference. Montvale, NJ: Thomson Healthcare;2005
2. BriggsGG,Freeman RK,Yaffe SL.Drugs in pregnancy and lactation, 7th
ed. Baltimore,
MD: Lippincott William AND Wilkins;2005
3. FDA Consumer magazine Volume 35, Number 3 May-June 2001
4. Use of Dermatological Drugs in Pregnancy and Lactation. J Turkish German Gynecol
Assoc. 2004; 5(3): 203-207
5. Collaborative Group on Drug Use in Pregnancy. Medication during pregnancy: an
intercontinental cooperative study. Int J Gynaecol Obstet 39(3):185-96 (1992Nov).
6. Koren G, Pastuszak A, Ito S. Drugs in pregnancy. NEngl J Med 338(16):1128-37(1998
Apr).
7. Navarre-Belhassen C, Blanchet P, Hillaire-Buys D,Sarda P, Blayac JP. Multiple
congenital malformations associated with topical tretinoin. Ann Pharmacother32 (4):505-6
(1998 Apr).
8. Colley SM, Walpole I, Fabian VA, Kakulas BA. Topical tretinoin and fetal
malformations. Med J Aust 168(9):467 (1998 May).
9. Kallen BA, Otterblad Olausson P, Danielsson BR. Is erythromycin therapy teratogenic in
humans? Reprod Toxicol 20(2):209-14 (2005 Jul Aug).
10. Drug safety in lactation Website: May 2001 Prescriber Update No.21:10-23 Last accessed:
17/03/04 http://www.medsafe.govt.nz/Profs/PUarticles/lactation.htm

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