Penggunaan Obat

dalam kehamilan

By Muh Muhlis
 Background

• Topik Keamanan penggunaan obat selama

kehamilan" berhubungan dengan
kehamilan, janin atau neonatus, dan efek
dari kehamilan atas disposisi/ terpapar
obat.
• Hampir semua obat/racun melintasi
plasenta sampai taraf tertentu dan boleh
jadi beresiko kepada janin yang sedang
berkembang
• Pemakaian obat oleh ibu hamil biasanya
meningkat tajam, disebabkan oleh gangguan
yang dialami ibu hamil.
• Mulai dari mual, muntah, nyeri punggung , nyeri
ulu hati yang biasa dikira gastritis, ingin BAK
terus, hingga gatal-gatal di perut samping (karena
peregangan kulit perut dengan makin besarnya
janin). resiko hipertensi karena tingginya kadar
protein dalam urin (preeklamsi/eklamsi) dan
munculnya diabetes karena ketidaknormalan
The effect of drugs on the pregnancy, foetus
or neonate :
Teratogenicity : pada trimester pertama,
paparan obat memberikan resiko yang lebih
besar untuk menyebabkan teratogenik,
Idealnya harus ada penghentian
penggunaan obat pada fase ini (pasca
konsepsi)
 pre-embryonic, embryonic and
foetal stages:
1. Pre-embryonic (days 0 – 17 post-
conception): Paparan obat pada periode
ini biasanya tidak menimbulkan resiko
malformasi,
tetapi perlu dipertimbangkan untuk
beberapa obat yang memiliki waktu paruh
yang lama.
2. Embryonic (days 18 – 56 post-conception):
This is the most important time in terms of risk
of foetal malformations
3.Foetal period (days 56 – term): The risk of
malformations is lower,
Tetapi beberapa ketidak normalan mungkin
terjadi sebab masa ini adalah masa
pembentukan organ/jaringan juga the central
nervous system, teeth and genitalia
• For example, ethanol exposure may affect
central nervous system development, and
tetracyclines may adversely discolour
deciduous teeth and suppress bone growth
• Bila obat menembus placenta, maka
kemungkinan obat akan menimbulkan efek
samping ke janin akan semakin meningkat.
• Terjadinya efek samping obat tsb (ESO)
tergantung dari :
1. keadaan genetic ibu dan janin.pada
individu tertentu, keadaan genetiknya
membuat sensitivitas terhadap obat
meningkat, sehingga terjadinya ESO juga
makin mungkin terjadi.
2. masa konsumsi obat terkait dengan fase
perkembangan janin. Tiap fase dalam
perkembangan janin akan memberikan
ESO yang berbeda
3. dosis obat yang dikonsumsi. Makin besar
dosis obat yang dikonsumsi, makin parah
ESO yang terjadi.
4. interaksi obat dengan bahan lain yang
dikonsumsi
Minggu ke- Fase ESO yang mungkin
(trimester) perkembangan terjadi
janin
1-8 Konsepsi, nidasi Abortus berulang

8-12 (I) Pembentukan organ Cacad/tak terbentuk organ

vital vital
12-24 (II) Penyempurnaan fisik Gangguan motorik organ
organ
24-36 atau Terbentuk fungsi Gangguan
lbh (III) organ behaviour/down syndrom
 Bagaimana obat dapat menyebabkan
teratogenik
• 1. merusak plasenta
• 2. Menghambat aliran darah ke janin
• 3. merusak endometrium
• 4. langsung mengganggu pertumbuhan
janin
Table I: Drugs considered to be human
teratogens (not exhaustive/tdk mutlak)
ACE inhibitors
androgens
antineoplastics (some)
carbamazepine
carbimazole
danazol
diethylstilboestrol
ethanol
lithium
misoprostil
penicillamine
phenytoin
tetracyclines
thalidomide
valproic acid
vitamin A & derivatives e.g. isotretinoin
warfarin
FDA pregnancy categories
A - controlled studies show no rise
C - risk cannot be ruled out
D - positive evidence of risk
X - contraindicated in pregnancy
 Category Meaning Safe Examples
A -controlled studies show NO risk Yes -vitamins
1% of meds -adequate, well controlled studies in PG wmn have -minerals
failed to demonstrate risk to the fetus -levothyroxine
-maybe insulin
B -no evidence of risk in humans Yes -acetaminophen
19% of meds -either animal findings do not, or if no adequate -Insulin
human studies have been done, animal findings are -cimetidine
negative -amoxicillin
-erythromycin
C -risk cannot be ruled out Maybe, weigh -tons
66% of meds -human studies are lacking & animal studies are benefits vs. risks
either positive for fetal risk or lacking as well; -most drugs are
however, potential benefits may outweigh risks "C" b/c not
enough studies are
done
D -positive evidence of risk Caution -phenytoin
7% of meds -investigational or post-marketing data show risk to -narcotic analgesics
the fetus; potential benefits MUST outweigh the @ high doses
risks (i.e. drugs needed for a life-threatening -NSAIDs @ high
situation or for a serious dis for which safer drugs doses for long period
cannot be used or are infective) of time
X -contraindicated in pregnancy Avoid! -thalidamide
7% of meds -studies in animal or humans, or investigational or -accutane
post-marketing reports, have shown fetal risk which -ACE/ARBs
clearly outweighs any possible benefit to the -Warfarin
patient -Methotrexate
Drugs Used in the Management of Nausea
and Vomiting During Pregnancy
Drug Pregnancy
Risk
Category
Metoclopramide (Reglan®) B
Cyclizine (Marezine®) B
Ondansetron (Zofran®) B
Promethazine (Phenergan®) C
Prochlorperazine (Compazine®) C

Chlorpromazine (Thorazine®) C
 Drugs Used for the Management of
Hypertension During Pregnancy

Drug Example Pregnancy Comment

Class Risk
Category
Central Methyldopa (Aldomet®) C Drug of choice by the
ΰ-agonist NHBPEP* Working Group
α-Blockers Atenolol (Tenormin®) C  
Metoprolol (Lopressor®)
C
Labetolol (ΰ and α)
(Normodyne®) C
Calcium Diltiazem (Cardizem® CD, C Potential synergism with
Dilacor® XR, Trizac®)
antagonists   magnesium sulfate may lead
Verapamil (Calan®,
Covera-HS®, Verelan®) C to precipitous hypotension

NHBPEP: National High Blood Pressure Education Program

ACE inhibitors Captopril (Capoten®)
Angiotensin Enalapril (Vasotec®)
Lisinopril (Prinivil,
IIReceptor
Zestril®)
blockers Losarten (Cozaar®)
Valsarten (Diovan®)
Diuretics Bumetanide (Bumex®)
Frosemide (Lasix®)
Hydrochlorothiazide
(HydroDIURIL®)
Indapamide (Lozol®)
Spironolactone
(Aldactone®)
Triamterine (Dyrenium®)
Directvasodilators Hydralazine (Apresoline®)
Minoxidil (Loniten®)
D Fetal abnormalities including
death, can be caused, and
should not be used in
pregnancy
D  
D
D
D
D Recommended for chronic
C hypertension if prescribed
C before gestation or if patients
are salt-sensitive. Not
D recommended in preclampsia
D
B
C Hydralazine is parenteral drug
C of choice vased on its long
history of safety and efficacy
Table 4: Drugs Used in the Treatment of Migraines during Pregnancy

Drug Pregnancy
Risk
Category
Acetominophen (Tylenol®) B
Ibuprofen (Motrin®) B
Ergotamine tartrate D
(Ergotrate®)
Dihydroergotamine X
(Migranal®)
Prochlorperazine C
(Compazine®)
Sumatriptan (Imitrex®) C
Naratriptan (Amerge®) C
Zolmitriptan (Zomig®) C
 Obat yang beredar di Indonesia yg sering digunakan dan
penggolongan serta kemungkinan ESO

Obat Golongan Kemungkinan ESO/saran

Accupril (quinopril HCl) C Resiko pada trimester 2 & 3
Alupent (metaproterenol C -
sulfat)
Amaryl (glimepirid) C Dapat menyebabkan penurunan
kadar gula darah bayi yang baru
lahir (syok hipoglikemi)
Amoksil (amoksisilin) B Keamanan belum terbukti
Ampicillin B Gunakan bila benar-benar
membutuhkan
Android / andro gel X Mengakibatkan maskulinisasi pada
(testosterone) bayi perempuan yang baru lahir
Anusol HC/supositoria C Jangan digunakan secara
berlebihan/lama
Aspirin C Hindari pemakaian pada trimester
3, menunda persalinan dan
memperlama pendarahan
Bactrim (cotrimoksasol) C Hindari pada trimester 1, mengganggu
metabolisme asam folat
Ergotamin cafein X Jangan digunakan
Captopril C/D Hindarkan selama kehamilan
ciprofloksasin C Gunakan bila benar-benar
membutuhkan
deksametason C Menyebabkan gangguan fungsi
kelenjar adrenalin pada bayi
Dietil stilbesterol/DES X Menyebabkan kanker organ reproduksi
bayi
Flagyl (metronidasol) B Jangan digunakan pada trimester 1
Lipitor X Jangan digunakan
Kontrasepsi oral X Jangan digunakan
Tamiflu (oseltamivir C Menunggu hasil penelitian lanjut
fosfat)=obat flu burung
Tetrasiklin B Menyebabkan kerapuhan gigi dan
pewarnaan gigi bayi
Voltaren (natrium B Tidak boleh digunakan pada trimester
diklofenak) 3, menunda persalinan, memperlama
pendarahan
Vitamin A dosis tinggi B Menyebabkan tak terbentuknya langit-
langit bayi
 Drugs that are CONTRAINDICATED
during breastfeeding:
• Antimetabolites: azathioprine,
cyclophosphamide, doxorubicin, MTX
• Ergot Alkaloids: bromocriptine, ergortamine
(for migraines)
• Iodine-containing compounds: amiodarone,
Potassium iodide
• Radiopharmaceuticals
• Recreational chemicals: amphetamines,
cocaine, heroin, merijuana, PCP, nicotine
 General principles
• Avoid all drugs in pregnancy where possible, especially in
the first-trimester.
• Herbal and other complementary therapies are often
perceived by the lay public as 'safe'. Unfortunately, data
on many of these products are very limited and insufficient
to determine their safety in pregnancy. In general, herbal
remedies should be avoided during pregnancy.
• Consider tapering and discontinuing unnecessary
pharmacotherapy prior to attempting conception.
Remember that some drugs or their metabolites may have
long half-life and persist for some time after stopping
therapy.
• Many conditions are self-limiting and do not
require drug treatment. Reassurance or
lifestyle measures (e.g. avoidance of
migraine triggers) may be sufficient.
• Where possible, delay treatment until after
results of laboratory testing (e.g. swabs), or
until after delivery (e.g. for treatment of
hypercholesterolaemia).
• If drug therapy is needed, select drugs with the most
established safety record. For example, amitriptyline
(or nortriptyline) or fluoxetine should be selected over
moclobemide or nefazodone for depression.
• Use the lowest effective dose for the shortest possible
time. Note: poor control of some maternal disease
states may carry significant risk to the development of
the foetus. In addition, the severity or frequency of
some maternal diseases (e.g. migraines) may improve
in pregnancy allowing a reduction in the dosage of
some drugs, or cessation of treatment.
• It is also important to realise that some
mothers may be very anxious about the
risks that their drug therapy poses to their
baby. This may lead to noncompliance with
drug therapy, or unnecessary pregnancy
terminations.