OBAT-OBAT

TERATOGENIK
 PENDAHULUAN

Pemberian obat-obatan kepada ibu

hamil  perubahan-perubahan
fisiologik N  pe volume
plasma, perubahan motilitas
gastrointestinal dan perubahan-
perubahan dlm komponen plasma,
fungsi ginjal
Prinsip R/ obat selama kehamilan :
• Hindari pemberian obat pada
trimester I kehamilan.
• Mempertimbangkan
kermungkinan terjadi kehamilan.
• R/ jangka panjang  konseling.
• R/ penting / dibutuhkan tdk
dihentikan.
• Efek obat mengalami perubahan
selama kehamilan.
• R/ tunggal & jangka pendek
daripada R/ jangka panjang /
kombinasi.
• Gunakan dosis efektif terendah
jika tersedia.
• Gunakan obat hanya jika
manfaat lebih besar daripada
risikonya.
• Gunakan cara pemberian
alternatif.
• Pilih obat tanpa ES.
• Gunakan dosis lebih rendah
TERATOGENESIS

Defek  fetus, malformasi,

deformasi, disrupsi.

Malformasi  perubahan
embrionik dlm morfogénesis 
disebabkan proses
perkembangan intrinsik abN.
Defek deformasi  bentuk,
kondisi atau posisi dari bagian
tubuh abN  kekuatan mekanik
ekstrinsik.

Disrupsi  kekuatan ekternal yg

merubah jar. sebelumnya N.
Teratogen  bahan, organisme,
bahan fisik / keadaan defisiensi 
menginduksi fungsi / struktur abN
postnatal.

Bahan teratogen  infeksi, radiasi,

pestisida, metal, bahan organik,
peny. kronik dari ibu & obat-
obatan.
Tabel 1. FDA pregnancy drug risk categories

DRUG RISK DEFINITION

CATEGORIY
 Contraindicated in pregnancy
X  There is no reason to risk use of the drug in pregnancy

 Positive evidence for risk to human fetus

D  However, benefits may outweigh risk of the drug

 Risk cannot be ruled out-human studies are lacking

C  Animal studies may or may, not show risk
 Potentials benefits may justify potential risk

 No risk to human fetus despite posible animal risk

B  Or, no risk in animal studies and human studies have not
been does

A  Controlled studies show no fetal risk

Unrated  No pregnancy category has been assigned

Tabel 2. Drug with minimal risk to mother and
fetus during pregnancy – cont’d

ANTIVIRAL AGENTS  Ayclovir

(restrict use to  Famcyclovir
treatment of severe  Vala\cyclovir
herpesvirus infections)
 Oral : avoid high doses first
CORTICOSTEROISD trimester
 Topical : avoid high doses long term
MISCELLANEOUS-  Benzoyl peroxide
OTHER DRUGS  Tretinoin (except first trimester)
 Calcipotriene – topical (low doses)
MISCELLANEOUS-  Dapsone (except close to term)
TOPICAL ANTIACNE  Hydroquinone – topical
PRODUCTS  Methoxsalen – topical
Tabel 3. Drug with minimal risk to mother and
fetus during Lactation

 Acetaminophen
 Codeine (low dose)
 Meperidine (low dose)
ANALGESICS  Morphine (low dose)
 Oxycodone (low dose)
 Pentazocine (low dose)
 Propoxyphene (low dose)
ANESTHETICS  Bupivacaine (low strength)
 Lidocaine
 Lidocaine with epinephrine
 Lidocaine-prilocaine
 Mepivacaine
  Bacitracin-topical
 Cephalosporins
 Erythromycins
 Erythromycin-topical
ANTIBACTERIAL AGENTS  Penicillins
 Sulfur-topical
 Sulfur with resorcinol-topical
 Tetracycline-topical

 Butoconazole-topical
 Ciclopirox-topical
 Clotrimazole-topical
ANTIFUNGAL AGENTS  Econazole-topical
 Miconazole-topical
 Naftifine-topical
 Nystatin-oral and topical

ANTIFUNGAL AGENTS –  Oxiconazole-topical

cont’d  Sulconazole-topical
 Terbinafine-topical
 Concern for all antihistamines regarding
ANTIHISTAMINES inhibition of milk production and
infantile irritability
ANTIVIRAL AGENTS  Acyclovir
 Valacyclovir
ANTISCABETIC  Crotamiton-topical
AGENTS
 Oral : use prednisolone, avoid nursing
CORTICOSTEROIDS for 4 hours after use
 Topical : aoid use of nipple or areola
MISCELLNEOUS-  Azelaic acid
TOPICAL ANTIACNE  Benzoyl peroxide
 Tretinoid
 Allopurinol
MISCELLANEOUS-  Calcipotriene-topical
OTHER DRUGS  Hydroquinone-topical
 Masoprocol-topical
 Methoxsalen-topical
 Tabel 4. Pregnancy category X-avoid in
pregnancy and lactation

Acitretin Flutamide
Estrogens Isotretinoin
Etretinate Methotrexate (both males and females
should avoid of pregnancy is
anticipoated)
Finasteride Stanozolol
Fluorouracil Thalidomide (both males and females
should avoid of pregnancy is
anticipoated)
 Tabel 5. Pregnancy category D or unrated –
drugs to avoid in pregnancy and lactation
DRUG CATEGORY D UNRATED
Aspirin (high-dose, extende-release 
form should be avoided)
Azathioprine 
Bleomycin 
Colchicines 
Cyclophosphamide 
Griseofulvin 
Hydroxyurea 
Mechlorethamine 
Penicillamine 
Potassium iodide 
Spironolactone 
Tetracycline 
Tabel 6. Drug with minimal risk to mother and
fetus during pregnancy

 Acetaminophen
 Aspirin - low dose (avoid third trimester)
 Codeine (low dose)
 Ibuproven - low dose (avoid third trimester)
ANALGESICS  Meperidine - low dose
 Oxycodone -low dose
 Pentazocine - low dose
 Propoxyphene - low dose

 Bupivacaine
 Lidocaine
ANESTHETICS  Lidocaine with epinephrine
 Lidocaine-prilocaine
 Mepivacaine
  Bacitracin-topical
 Clindamycin-topical
 Erythromycin (except estolate)
 Erythromycin-topical
 Metronidazole-topical
 Mupirocin-topical
ANTIBACTERIAL  Neomycin-topical
AGENTS  Penicillins
 Polymyxin B-topical
 Sulfonamides (except third
trimester)
 Sulfur-topical
 Sulfur with resorcinol-topical
 Tetracycline-topical
ANTIFUNGAL AGENTS  Butoconazole-topical
(avoid vaginal use after  Ciclopirox-topical
membrane rupture)
  Clotrimazole-topical (except first trimester)
 Econazole-topical (except first trimester)
 Fluconazole single dose
 Ketokonazole-topical
 Miconazole-topical (except first trimester)
ANTIFUNGAL  Naftifine-topical
AGENTS – cont’d  Nystatin-oral and topical
 Oxiconazole-topical
 Sulconazole-topical
 Terbinafine-topical
 Terconazole-topical (except first trimester)
 Tioconazole-topical

ANTIHISTAMINES  Brompheniramine (except first trimester)

(avoid lat 2 weeks  Cetirizine (except first trimester)
of pregnancy if  Chlorpheniramine
fetus is premature)  Cyproheptadine
 Diphenhydramine
 Hydroxyzine (except first trimester)
 Chloroquine (approved for use during
ANTIMALARIALS pregnancy only for hepatic amebiasis or
malaria)

ANTIPROTOZOAL  Metronidazole (except first trimester)

AGENTS

 Crotamiton-topical
 Lindane-topical (maximum twice during
pregnancy)
ANTISCABETIC  Malathion-topical
AGENTS  Permethrin-topical
 Precipitated sulfur-topical
Tabel 7. Examples of known human teratogens
CRITICAL
TERATOGEN ADVERSE EFFECTS
PERIOD
Maternal Conditions
Holoprosencephaly, pore cysts,
cardiac defects, sacral agenesis,
First
Diabetes caudal regression, laterally
trimester
defects, facial clefts, renal
defects
Hypothyroidism / Mental retardation (MR), Entire
Hyperthyroidism growth restriction pregnancy
MR, microcephaly, craniofacial
Phenylketonuria (PKU)
defects
Anencephaly / other neural
Hyperthermia 2-4 weeks
tube defects (NTDs)
Transient neonatal SLE,
Systemic lupus intrauterine growth restriction
erythematosus (SLE) (IUGR), prematurity,
congenital heart block
 CRITICAL
TERATOGEN ADVERSE EFFECTS
PERIOD
Nonprescription
Substance Use
Short palpebra fissures,
altered facies, prenatal and
Entire
Alcohol postnatal growth deficiency,
pregnancy
mild to moderate MR,
microcephaly
Low birth weight (LBW),
Tobacco Unknown
miscarriage
CNS (developmental delay,
Toluene Unknown
microcephaly, IUGR)
 CRITICAL
TERATOGEN ADVERSE EFFECTS
PERIOD

Medications

Aminopterin /
CNS, limb and skeletal defects 14-69 days
methotrexate

Second-third
Amiodarone Neonatal thyroid dysfunction
trimester

Oligohydramnios, renal
Second-third
ACE inhibitors dysplasia/failure, IUGR, joint
trimester
contractures, prenatal death

Spina bifida, hypoplasia of the

Carbamazepine 14-60 days
phalanges, IUGR
 CRITICAL
TERATOGEN ADVERSE EFFECTS
PERIOD

CNS defects, skeletal defects

(especially cranial and digits),
Cyclophosphamide 14-60 days
IUGR cleft palate, neonatal
death

Brachycephaly, abnormal facies,

Fluconazole (risk
abnormal calvarial
thought to be only with First
development, cleft palate,
high doses, especially trimester
cardiac defects, skeletal defects
parenteral)
(thinning)

Oligohydramnios, anuria,
necrotizing enterocolitis, Second-third
Indomethacin
premature ductus arteriosus trimester
closure
 CRITICAL
TERATOGEN ADVERSE EFFECTS
PERIOD

Cardiac defects (Ebstein

Lithium 14-60 days
anomaly)

Second
Methylene blue Jejunal atresia
trimester

Mobius anomaly, terminal

First-
transverse limb deficiency,
Misoprostol second
arthrogryposis multiplex
trimester
congenital, talipes equinovarus

Penicillamine Connective tissue abnormalities 14-60 days

 CRITICAL
TERATOGEN ADVERSE EFFECTS
PERIOD

CNS (structural and

development delay), facial
clefting, midface
Phenytoin 14-60 days
hypoplasia, cardiac
defects, digital nail
hypoplasia

CNS, ocular, cardiac, great

Retinoids vessel, and lib defects;
(isotretinoin, microtia, micrognathia, Unknown
acitretin) cleft lip/palate, thymic
deficiency

Selective serotonin Prenatal complication,

Third
reuptake inhibitors increase in minor
trimester
(SSRIs) anomalies
 CRITICAL
TERATOGEN ADVERSE EFFECTS
PERIOD

Second-
Staining of primary
Tetracycline third
dentition
trimester

Cranial nerve abnormalities,

limb shortening defects
(phocomelia), ocular and
Thalidomide 27-40 days
cardiac defects, oral/facial
anomalies, renal and
urogenital defects

NTDs, oral clefts,

First
Trimethoprim hypospadias, cardiovascular
trimester
defects
 CRITICAL
TERATOGEN ADVERSE EFFECTS
PERIOD
Medications-cont’d
CNS (development delay),
microcephaly, cleft lip/palate,
broad nasal brigde,
Trimethadione 14-60 days
genitourinary and
gastrointestinal defects, cardiac
defects
CNS defects (including
development delay),
brachycephaly, craniosynostosis,
Valproic acid microcephaly, ocular 14-60 days
hypertelorism, midface
hypoplasia, cleft lip/palate, limb
abnormalities, spina bifida
6-9 weeks; after
CNS and ocular defects, IUGR,
9 weeks, CNS,
neonatal hemorrhage, nasal
Warfarin ocular and
hypoplasia, vertebral anomalies,
disruptive
stippled epiphysis
defects