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1. Estrogen Tembakau/Rokok

Studi epidemiologis menunjukkan bahwa bahaya efek kardiovaskuler seperti stroke, infark

miokardial dan thromboembolisme yang dikaitkan dengan penggunaan kontrasepsi oral (pil

KB) jauh lebih besar pada seorang perokok daripada bukan perokok. Risiko ini meningkat

dengan umur serta jumlah rokok yang diisap seharinya. Mekanisme pasti dari interaksi inimasih kurang jelas. Bagaimana pun, wanita yang sedang ber-KB dengan Pil KB seharusnya

tidak merokok karena asap rokok dapat mengurangi kadar estrogen dalam darah. Dan kalau

wanita ini tidak mau menghentikan rokoknya, maka dia harus memakai cara kontrasepsi yang

lain, misalnya kondom.

c.Benzodiazepinpil KB

Efek pil KB dapat berkurang. Akibatnya : resiko hamil meningkat kecuali jika

digunakan cara kontrasepsi lain. Perdarahan sekonyong-konyong adalah gejala

kemungkinan terjadi interaksi.

Efek beberapa trankulansia dapat meningkat (klordiazepoksid, diazepam); efek

trankulansi benzodiazepine lainnya dapat berkurang.

Pil kb-fenitoin, barbiturat

Hormonal contraceptives are less reliable during the use of phenytoin and barbiturates such as

phenobarbital and primi-done. Intermenstrual breakthrou gh bleeding and spotting can take place,

and pregnancies have occurred. Controlled studies have shown that phenytoin and phenobarbitalcan reduce contra-ceptive steroid levels.

Co ntraceptives + barbiturat

Combined hormonal contraceptives and possibly progestogen only oral contraceptives are less

reliable during treatment with phenobarbital. Inter-menstrual break -through bleedin gand spotting

can take place, and pregnancies have occurred.

Controlled studies have shown that phenobarbital can reduce contraceptive steroid

levels. Similarly, emergency hormonal contraceptives are considered to be less

effectiv e in those taking phenobarbital. Note that primidone is metabolised to

phenobarbital and therefore may interact similarly.

The increase in failure rate appears small , but be cause of the consequences of an

unwanted pregnancy, especially with drugs that may cause foetal abnormalities,

adjustments should be made. If possible , change to an other suitable , non inter acting antiepileptic

. For additional advice on the use of enzyme inducers, such as

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phenobarbital, and contraceptives, see co ntr ace pt ive s, pa ge 19 9. Reliable contraception in most

patients is said to be achievable with 80 to 100 micrograms of ethinylestradiol daily . Additional

barrier methods are considered the most appropriate option for the short-term use of enzyme -

inducing antiepileptics

KB+TETRASIKLIN

Contraceptive failure has been attr ibuted to doxycycline, lymecy-cline, minocycline, oxytetracycline

and tetracycline in about 40 reported cases, 7 of which specified long-term antibacterial use, but the

interaction (if such it is) appears to be rare. Control-led studies have not shown any effect of

tetracycline or doxycy-cline on contraceptive steroid levels.

Mechanism

Not understood. If an interaction occurs, suppression of intestinal bacteria resulting in a fall in

enterohepatic r ecirculation of ethinylestradiol is the usual suggested explanation, but there is no

evidence that this is clinically important. For a full discussion of th is mechanism, see Hormonal

contra-ceptives + Antibacterials; Penicillins, p.981.

Importance and management

The interactions between the oral contraceptives and tetracyclines summa-rised here are all that

have been identified in the literature. Much of the ev-idence is anecdotal with insufficient controls

(if any). These interactions are not adequately established and the whole issue remains ontroversial.

Bearing in mind the extremely wide use of both drugs, any increase in the incidence of contraceptive

failure above the accepted failure rate is clearly very low indeed. On the other hand, the personal

and ethical consequences of an unwanted pregnancy can be very serious. For this reason, the

Faculty of Family Planning and Reproductive Health Care (FFPRHC) Clinical Effectiveness Unit

recommends that an additional form of contraception, such as condoms, should be used while

taking a short course of antibacte-rials that do not induce liver enzymes, and for 7 days after the

antibacterial has been stopped. See Hormonal contraceptives + Antibacterials; Peni-cillins, p.981,

for more detailed info rmation on how to manage this inter-action.

In the case of long-term use of tetracyclines for acne, at least 7 cases of contraceptive failure have

been reported. Nevertheless, in statistical terms the only well-designed case-controlle d study in

dermatological practice indicated that the incidence of contraceptive failure due to this interaction

could not be distinguished from the general and recognised failure rate of oral contraceptives.

The FFPRHC advise that additional contraceptive protection is not re-quired in established users of

the combined hormonal contraceptive patch taking tetracycline. This is in line with the findings of

the study cited above. Note that antibacterials that do not induce liver enzymes do not affect the

reliability of the progestogen-only contraceptives, see Progestogen-only contraceptives +

Antibacterials, p.1007, or the progestogen-only emergency hormonal contraceptive, see Emergency

hormonal contra-ceptives + Antibacterials, p.977.

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KB+AMPISILIN

Combined oral contraceptive failure has been attributed to amp-icillin, amoxicillin, flucloxacil lin,

oxacillin, phenoxymethylpeni-cillin, pivampicillin and talampicillin. However, the interaction (if such

it is), appears to be very rare. Controlled studies have not shown any effect of ampicillin on

contraceptive steroid levels and ovarian suppression

MEKANISME: Not understood. The oestrogen component of the contraceptive undergoes

enterohepatic recirculation (i.e. it is repeatedly secreted in the bile as sul-fate and glucuronide

conjugates, which are hydrolysed by the gut bacteria

before reabsorption). One idea is that if these bacteria are suppressed by the use of an antibacterial,

the steroid conjugates are not hydrolysed and are therefore only poorly reabsorbed, resulting in

lower than normal concentrations of circulating oestr ogen in some women. This may result

in inadequate suppression of ovulation. However, although the penicil-lins reduce urinary oestriol

secretion in pregnant women,

15-19

no marked

changes in serum ethinylestradiol levels have been found in controlled studies in women taking an

oral contr aceptive with ampicillin or any other broad-spectrum antibacterial (see tetracyclines,

(p.983), macrolides, (p.979), quinolones, (p.982)). It may be that the enterohepatic recircula-tion

of ethinylestradiol is not clin ically important: note that women with an ileostomy have normal

serum contraceptive steroid levels. Alterna-tively, it may be that the proportion of women for

whom enterohepatic re-circulation is important is extremely small. The progestogens do not take

part in enterohepatic recirculation in their active forms.

Importance and management. The interaction between combined hormonal contraceptives and

penicil-lins is inadequately established and controversial. Almost all of the evi-dence is anecdotal

with no controls. The total number of failures is extremely small when viewed against the number of

women worldwide

using combined hormonal contraceptives (estimated at 70 million in 1996 by WHO 21 ), so most

women are apparently not at risk.

ASETAMINOFEN Mungkin menurunkan efek

penghilangan rasa sakit(

meningkatkan metabolisme)

Periksa respon penghilangan

rasa sakit

ALKOHOL Mungkin meningkatkan efek

alkohol

Gunakan dengan perhatian

AMPISILIN Penurunan efek kontrasepsi Kejadian rendah tapi tidak

dapat diprediksi,gunakan

metode kontrasepsi lain

ANTIKOAGULAN Penurunan efek antikoagulan Gunakan dengan perhatian

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(ORAL) periksa INR

ANTIKONVULSAN Mungkin menurunkan efek

kontrasepsi

Hindari penggunaan

serempak,gunakan metode

kontrasepsi lain untuk

penderita seizure

ANTIDEPRESAN Mungkin meningkatkan efekfarmakologi

Periksa efek samping

BENZODIAZEPIN Mungkin meningkatkan atau

menurunkan efek penenang

termasuk gangguan

psikomotorik

Gunakan dengan perhatian

gangguan terbesar pada

minggu pertama bebas obat

pada dosis KO

-bloker Mungkin meningkatkan atau

menurunkan efek

farmakologi -bloker

Periksa status kardiovaskular

KORTIKOSTEROID Mungkin meningkatkan

toksisitas kortikosteroid

Signifikansi klinik tidak ada

GRISEOVULVIN Menurunkan efek kontrasepsi Menggunakan metode

kontrasepsi lain

HIPOGLISEMIK Mungkin menurunkan efek

hipoglisemik

Periksa tekanan darah

METILDOPA Mungkin menurunkan efek

antihipertensi terutama KO

dosis besar

Periksa tekanan darah

INHIBITOR

TRANSKRIPTASE

BALIK NON-

NUKLEOSIDA

Penurunan efek kontrasepsi Menggunakan metode

kontrasepsi lain

FENITOIN Penurunan efek kontrasepsi

mungkin meningkat efek

fenitoin

Menggunakan metode

kontrasepsi lain,periksa kadar

fenitoin

PIOGLITAZON Penurunan efek kontrasepsi Menggunakan metode

kontrasepsi lain

INHIBITOR PROTEASE Penurunan efek kontrasepsi Menggunakan metode

kontrasepsi lain

RIFAMPICIN Penurunan efek kontrasepsi Menggunakan metode

kontrasepsi lain