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
Defek fetus, malformasi,
deformasi, disrupsi.

Malformasi perubahan
embrionik dlm morfognesis
disebabkan proses
perkembangan intrinsik abN.
TERATOGENESIS
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
CATEGORIY
DEFINITION
X
Contraindicated in pregnancy
There is no reason to risk use of the drug in pregnancy
D
Positive evidence for risk to human fetus
However, benefits may outweigh risk of the drug
C
Risk cannot be ruled out-human studies are lacking
Animal studies may or may, not show risk
Potentials benefits may justify potential risk
B
No risk to human fetus despite posible animal risk
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 contd
ANTIVIRAL AGENTS
(restrict use to
treatment of severe
herpesvirus infections)
Ayclovir
Famcyclovir
Vala\cyclovir
CORTICOSTEROISD
Oral : avoid high doses first
trimester
Topical : avoid high doses long term
MISCELLANEOUS-
OTHER DRUGS
Benzoyl peroxide
Tretinoin (except first trimester)
MISCELLANEOUS-
TOPICAL ANTIACNE
PRODUCTS
Calcipotriene topical (low doses)
Dapsone (except close to term)
Hydroquinone topical
Methoxsalen topical
Tabel 3. Drug with minimal risk to mother and
fetus during Lactation
ANALGESICS
Acetaminophen
Codeine (low dose)
Meperidine (low dose)
Morphine (low dose)
Oxycodone (low dose)
Pentazocine (low dose)
Propoxyphene (low dose)
ANESTHETICS Bupivacaine (low strength)
Lidocaine
Lidocaine with epinephrine
Lidocaine-prilocaine
Mepivacaine




ANTIBACTERIAL AGENTS
Bacitracin-topical
Cephalosporins
Erythromycins
Erythromycin-topical
Penicillins
Sulfur-topical
Sulfur with resorcinol-topical
Tetracycline-topical



ANTIFUNGAL AGENTS
Butoconazole-topical
Ciclopirox-topical
Clotrimazole-topical
Econazole-topical
Miconazole-topical
Naftifine-topical
Nystatin-oral and topical
ANTIFUNGAL AGENTS
contd
Oxiconazole-topical
Sulconazole-topical
Terbinafine-topical

ANTIHISTAMINES
Concern for all antihistamines regarding
inhibition of milk production and
infantile irritability
ANTIVIRAL AGENTS Acyclovir
Valacyclovir
ANTISCABETIC
AGENTS
Crotamiton-topical

CORTICOSTEROIDS
Oral : use prednisolone, avoid nursing
for 4 hours after use
Topical : aoid use of nipple or areola
MISCELLNEOUS-
TOPICAL ANTIACNE
Azelaic acid
Benzoyl peroxide
Tretinoid

MISCELLANEOUS-
OTHER DRUGS
Allopurinol
Calcipotriene-topical
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
ANALGESICS
Acetaminophen
Aspirin - low dose (avoid third trimester)
Codeine (low dose)
Ibuproven - low dose (avoid third trimester)
Meperidine - low dose
Oxycodone -low dose
Pentazocine - low dose
Propoxyphene - low dose


ANESTHETICS
Bupivacaine
Lidocaine
Lidocaine with epinephrine
Lidocaine-prilocaine
Mepivacaine






ANTIBACTERIAL
AGENTS
Bacitracin-topical
Clindamycin-topical
Erythromycin (except estolate)
Erythromycin-topical
Metronidazole-topical
Mupirocin-topical
Neomycin-topical
Penicillins
Polymyxin B-topical
Sulfonamides (except third
trimester)
Sulfur-topical
Sulfur with resorcinol-topical
Tetracycline-topical
ANTIFUNGAL AGENTS
(avoid vaginal use after
membrane rupture)
Butoconazole-topical
Ciclopirox-topical





ANTIFUNGAL
AGENTS contd
Clotrimazole-topical (except first trimester)
Econazole-topical (except first trimester)
Fluconazole single dose
Ketokonazole-topical
Miconazole-topical (except first trimester)
Naftifine-topical
Nystatin-oral and topical
Oxiconazole-topical
Sulconazole-topical
Terbinafine-topical
Terconazole-topical (except first trimester)
Tioconazole-topical
ANTIHISTAMINES
(avoid lat 2 weeks
of pregnancy if
fetus is premature)
Brompheniramine (except first trimester)
Cetirizine (except first trimester)
Chlorpheniramine
Cyproheptadine
Diphenhydramine
Hydroxyzine (except first trimester)

ANTIMALARIALS
Chloroquine (approved for use during
pregnancy only for hepatic amebiasis or
malaria)
ANTIPROTOZOAL
AGENTS
Metronidazole (except first trimester)



ANTISCABETIC
AGENTS
Crotamiton-topical
Lindane-topical (maximum twice during
pregnancy)
Malathion-topical
Permethrin-topical
Precipitated sulfur-topical
Tabel 7. Examples of known human teratogens
TERATOGEN ADVERSE EFFECTS
CRITICAL
PERIOD
Maternal Conditions
Diabetes
Holoprosencephaly, pore cysts,
cardiac defects, sacral agenesis,
caudal regression, laterally
defects, facial clefts, renal
defects
First
trimester
Hypothyroidism /
Hyperthyroidism
Mental retardation (MR),
growth restriction
Entire
pregnancy
Phenylketonuria (PKU)
MR, microcephaly, craniofacial
defects
Hyperthermia
Anencephaly / other neural
tube defects (NTDs)
2-4 weeks
Systemic lupus
erythematosus (SLE)
Transient neonatal SLE,
intrauterine growth restriction
(IUGR), prematurity,
congenital heart block
TERATOGEN ADVERSE EFFECTS
CRITICAL
PERIOD
Nonprescription
Substance Use
Alcohol
Short palpebra fissures,
altered facies, prenatal and
postnatal growth deficiency,
mild to moderate MR,
microcephaly
Entire
pregnancy
Tobacco
Low birth weight (LBW),
miscarriage
Unknown
Toluene
CNS (developmental delay,
microcephaly, IUGR)
Unknown
TERATOGEN ADVERSE EFFECTS
CRITICAL
PERIOD
Medications
Aminopterin /
methotrexate
CNS, limb and skeletal defects 14-69 days
Amiodarone Neonatal thyroid dysfunction
Second-third
trimester
ACE inhibitors
Oligohydramnios, renal
dysplasia/failure, IUGR, joint
contractures, prenatal death
Second-third
trimester
Carbamazepine
Spina bifida, hypoplasia of the
phalanges, IUGR
14-60 days
TERATOGEN ADVERSE EFFECTS
CRITICAL
PERIOD
Cyclophosphamide
CNS defects, skeletal defects
(especially cranial and digits),
IUGR cleft palate, neonatal
death
14-60 days
Fluconazole (risk
thought to be only with
high doses, especially
parenteral)
Brachycephaly, abnormal facies,
abnormal calvarial
development, cleft palate,
cardiac defects, skeletal defects
(thinning)
First
trimester
Indomethacin
Oligohydramnios, anuria,
necrotizing enterocolitis,
premature ductus arteriosus
closure
Second-third
trimester
TERATOGEN ADVERSE EFFECTS
CRITICAL
PERIOD
Lithium
Cardiac defects (Ebstein
anomaly)
14-60 days
Methylene blue Jejunal atresia
Second
trimester
Misoprostol
Mobius anomaly, terminal
transverse limb deficiency,
arthrogryposis multiplex
congenital, talipes equinovarus
First-
second
trimester
Penicillamine Connective tissue abnormalities 14-60 days
TERATOGEN ADVERSE EFFECTS
CRITICAL
PERIOD
Phenytoin
CNS (structural and
development delay), facial
clefting, midface
hypoplasia, cardiac
defects, digital nail
hypoplasia
14-60 days
Retinoids
(isotretinoin,
acitretin)
CNS, ocular, cardiac, great
vessel, and lib defects;
microtia, micrognathia,
cleft lip/palate, thymic
deficiency
Unknown
Selective serotonin
reuptake inhibitors
(SSRIs)
Prenatal complication,
increase in minor
anomalies
Third
trimester
TERATOGEN ADVERSE EFFECTS
CRITICAL
PERIOD
Tetracycline
Staining of primary
dentition
Second-
third
trimester
Thalidomide
Cranial nerve abnormalities,
limb shortening defects
(phocomelia), ocular and
cardiac defects, oral/facial
anomalies, renal and
urogenital defects
27-40 days
Trimethoprim
NTDs, oral clefts,
hypospadias, cardiovascular
defects
First
trimester
TERATOGEN ADVERSE EFFECTS
CRITICAL
PERIOD
Medications-contd
Trimethadione
CNS (development delay),
microcephaly, cleft lip/palate,
broad nasal brigde,
genitourinary and
gastrointestinal defects, cardiac
defects
14-60 days
Valproic acid
CNS defects (including
development delay),
brachycephaly, craniosynostosis,
microcephaly, ocular
hypertelorism, midface
hypoplasia, cleft lip/palate, limb
abnormalities, spina bifida
14-60 days
Warfarin
CNS and ocular defects, IUGR,
neonatal hemorrhage, nasal
hypoplasia, vertebral anomalies,
stippled epiphysis
6-9 weeks; after
9 weeks, CNS,
ocular and
disruptive
defects