FARMAKOTERAPI PADA KEHAMILAN DAN LAKTASI

Welly Ratwita, dr., MKes. Lab Farmakologi FK Unjani

 Teratologi
Mempelajari malformasi kongenital yang dapat diamati saat kelahiran dan diinduksi oleh agen eksogen selama periode organogenesis

Dismorfisme
Abnormalitas fungsional dan struktural pada fetus

 Thalidomide Tragedy Akhir 1950-Awal 1960 thalidomide dianggap aman pada kehamilan

Penelitian pada hewan belum sempurna

Amelia, phocomelia, abnormalitas jantung, defek pada mata

Mekanisme Dismorfogenitas
1. Efek Langsung Obat pada Fetus
Dipengaruhi oleh: Distribusi obat ke plasenta
aliran darah maternal & uterus

Struktur & biokimia plasenta Komponen obat (BM <<, larut lemak, unionised)

2. Efek Obat pada Fungsi Plasenta Biotransformasi obat pada plasenta dapat mempengaruhi fungsi plasenta melalui kompetisi enzimatik, produksi hormon & inhibisi transpor energi
Rokok: Mengganggu nutrisi dan oksigenasi fetal, resistensi vaskular, benzopiren hidroksilase plasenta

3. Efek Obat terhadap Metabolisme Maternal

Misal: Efek hipotensi yang diinduksi anestesi spinal 4. Tahapan Perkembangan Fetus All or none pada awal kehamilan Diferensiasi & Organosintesis Hambatan pertumbuhan, gangguan fungsi, pada periode fetogenik

5. Genetik
6. Metabolisme Obat Cyt P450 mempengaruhi metabolisme obat, keseimbangan hormonal yang

dapat mempengaruhi viabilitas fetus

Guidelines for Prescribing

1. Penggunaan obat esensial yang memiliki efek dismorfogenik harus dibatasi pada WUS, atau berikan dengan disertai kontrasepsi adekuat & tes kehamilan secara teratur

2. Penggunaan obat esensial dengan

komplikasi (-) pada fetus diberikan

dengan dosis rendah dan waktu singkat

3. Jika memungkinkan ganti dengan obat lain. Misal: OHO Insulin

4. Apabila tidak ada obat pengganti, pertimbangkan risiko & keuntungan. Biarkan pasien mengambil keputusan.

Klasifikasi keamanan Obat pada Kehamilan (FDA): Category A: Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and there is no evidence of a risk in later trimesters), and the possibility of fetal harm appears remote.

 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, 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 benefit justifies 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 lifethreatening 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.

Key: ++++ +++

++
+ -

: Contraindicated : Avoid in preference for safer categories : Use cautiously, weighing risk and benefits : Seems safe but information limited : Proven safe in pregnancy

Antiulcer Drugs Week

Antasid
Mg++

12

24 term

++
++ ++ ++

1 st suggest malform
Large, frequent dose: neuromusc, CVS, renal damage Large dose: metabolic acidosis 1 case report: no ADR 17-24w

Bicarbonat

++ ++

++ ++

++ ++

Simetidin

Analgetik
Week Codein Aspirin ++ ++ 0 12 24 term ++ ++++
Withdrawal effects 3rd: impaired platelet func, haemorrhage, kernicterus No evidence effect on organogenesis. Premature closure of ductus arteriosus, pulmonary HT

NSAIDs +

++

++++

PCT

Anti TBC

Week
Rifampicin

12

24 term
Neonatal bleeding, suggested embryotoxicity, IUFD, malformation Theoretical malformation, no evidence of damage Pyridoxine 10 mg should accompany each Isoniazid dose to prevent fetal neural damage

+++ +++ +++ ++ ++ ++ ++ ++ ++

Ethambuthol

Isoniazid

Anti-Infectives

Week
Aminoglikosid Sulfonamid Penisilin Cefalosporin Kloramfenikol

24 term ++++ ++++ ++++ ++ ++ +++

12

Ototoxicity, renal damage Haemolysis in G6PD def., kernicterus No reported fetal rx No reported fetal rx

++++

Grey syndrome, CVS collaps, +

Tetrasiklin
Cotrimoksazol

++++ ++++ ++++

++ ++ +++

Dental discolourisation, bone growth disturb.

Risk of kernicterus

DRUGS IN LACTATION
Endocrine System
Contraindicated Corticosteroid Betamethasone Prednisone Prednisolon CS inhalated, low dose Insignificant amounts in milk Caution May be pescribed Comments

Cortisone
Dexa Hydrocortison (systemic) Methylprednisolon

Triamcinolone

Hypoglycaemic agents
Contraindicated Caution May be precribed Comments OHO-theoritical risk of infant hypoglicaemia. Monitor Chlorpropramide Exreted in milk. Effects on infant unknown

Glibenclamide

Metformin
Tolazamide Tobutamide Infant dose 18 % maternal dose. Avoid in neonatal period

GIT
Contraindicated Caution Antacids Al+3, Mg +2 Not absorbed May be prescribed Comments

Cimetidine
Nizatidine Ranitidine Sucralfat Bisacodyl Loperamide

Infant dose 5 % maternal dose. Avoid in prematurity

Secreted & cocentrated in milk (rats) Exreted in milk. ADRR (-) but long term effect?

Infection
Contraindicated Caution May be prescribed
Amoxycillin Chloramphenicol Cotrimoxazole Sulphonamide

Comments
Insignificant amount in milk. Gray syndrome. Theoritical risk of blood dyscrasia Minimal risk from sulpha component. No ADRR May cause diarrhoea, rash, kernicterus

Cephalosporin Insignificant amount in milk. No ADRR

Tetracycline

Probable negligible abs. in infant due to chelation w/ Ca in mik. Remote possibility of toth staining/bone growth abn.
Infant dose 50 % maternal. Theoritical risk of convulsion and neuopathy. Avoid in newborn Pennicillin No ADRR, possibility of hypersensitivity in infant

Ethambuthol Isoniazid