ORAL CONTRACEPTIVES

Presented by: Pauline Teo

Pharmacy Department, Hospital Miri

8th July, 2009

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OUTLINE Contraceptive methods Menstrual cycle Mechanisms of action Type of OCPs Non-contraception benefits of OCPs Adverse effects Contraindications Drug interactions Counseling

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CONTRACEPTION METHODS Hormonal methods Mechanical/Barrier methods Natural methods Sterilization Emergency contraception

Oral contraceptives

Oral contraceptives

Combined oral contraceptives (COC)

Emergencycontraception

Progestin-only pills (mini-pill)

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THE MENSTRUAL CYCLE

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THE ESTROGENS

Estrogens

Natural• estradiol• estrone• estriol

Semi-synthetic• ethinyl estradiol

Synthetic• mestranol

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THE PROGESTOGENS Progesterone – most important natural

progestogens Examples of Progestogen:

Medroxyprogesterone, Dyhydrogesterone, Gestodene, Levonorgestrel, Cyproterone acetate, Desogestrel, Drospirenone, Norethisterone, Norgestimate

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ORAL CONTRACEPTIVES: Mechanisms of action

Estrogen

inhibit secretion of FSH & thus preventing the development of a dominant follicle

Progestogen

suppress LH & thus prevent ovulation

cause atrophy of endometrium

alter fallopian tube secretion

thicken cervical mucus which interferes with sperm transport

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MECHANISMS OF ACTION

Suppress ovulation

Change endometrium making implantation less likely

Thicken cervical mucus (preventing sperm

penetration)

Reduce sperm transport in upper genital tract

(fallopian tubes)

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COMBINED ORAL CONTRACEPTIVES (COC)

Estrogen + Progestogen Estrogen content: 20-40 ug 21 days of active (hormone-containing)

pills followed by either 7 days of placebo pills or instructions of not to take pills for 7 days

Menstrual bleeding usually begins 1 to 4 days after cessation of a 21-day cycle of COCs or during placebo tablets of 28-day pack

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COC (con’t)

COC

Monophasic Biphasic Triphasic

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COC (con’t) Monophasic: contain a fixed ratio of estrogen &

progestin given daily for 21 days Eg:

Marvelon®, Regulon® (Desogestrel 150ug, EE 30ug) Microgynon 30®, Nordette®, Rigevidon® (Levonogestrel 150ug, EE 30ug) Diane 35®, Estelle-35® (Cryproterone acetate 2mg, EE 35ug) Meliane® (Gestodene 75ug, EE 20ug) Mercilon®, Novynette® (Desogestrel 150ug, EE 20ug) Loette® (Levonogestrel 100ug, EE 20ug) Gynera®, Minulet® (Gestodene 75ug, EE 30ug) Yasmin® (Drospirenone 3mg, EE 30ug)

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Biphasic: contain a fixed dose of estrogen (days 1-21) with a lower progestin dose on days 1 to 10 than on days 11 to 21

1st half: the progestin/estrogen ratio is lower to allow the endometrium to thicken as it normally does.

2nd half: the progestin/estrogen ratio is higher to allow normal shedding of the lining of the uterus to occur

COC (con’t)

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Triphasic: have constant or changing estrogen concentrations and varying progestin concentrations throughout the cycle

Eg: Trinordiol® 6 brown tabs (EE 30ug, Levonogestrel 50ug) + 5 white tabs (EE 40ug, Levonogestrel 75ug) + 10 yellow tabs (EE 30ug, Levonogestrel 125ug)

COC (con’t)

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PROGESTIN-ONLY PILLS Contain no estrogen Given for 28 days continuously A good choice in lactating women

efficacy is increased as a result of the combined effect of prolactin-induced suppression of ovulation does not adversely affect milk volume & infant growth

Alternative for those who are unable to take estrogens

Less effective than COC Eg: Noriday® (norethisterone 0.35mg)

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EMERGENCY CONTRACEPTION

Used only when there is an episode of unprotected sex or there is potential contraceptive failure

Synonyms: “morning-after pill”, “post-coital contraception”

Should be taken within 72 hours If vomiting occurs within 2 hours after drug

intake, dose should be repeated

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Progestogen only emergency contraception (POEC)

0.75mg levonorgestrel (Madonna®, Postinor-2®)

2nd dose: 12 hours later (not >16 hours)

1.5mg levonorgestrel (Escapelle®)

s/e: nausea (20%), vomiting (5%)

EMERGENCY CONTRACEPTION(con’t)

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NON-CONTRACEPTION BENEFITS OF OCPs

Improves menstrual disorders ↓ in dysmenorrhea prevent ectopic pregnancy ↓ risk of pelvic infection ↓ in functional ovarian cysts ↓ risk of loss of bone density ↓ incidence of ovarian cancer ↓ incidence of endometrial cancer Improvement in acne & hirsutism

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ADVERSE EFFECTS Breakthrough bleeding/ spotting Amenorrhea Nausea, vomiting, anorexia Breast tenderness Headache Depression Weight gain Change in BP Acne Chloasma

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CONTRAINDICATIONS Smokers aged ≥ 35 years Hypertension Myocardial infarct Stroke Thrombosis Severe migraine Poorly controlled diabetes Severe obesity Gall bladder disease or liver tumours Known or suspected pregnancy Unexplained vaginal bleeding

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DRUG INTERACTIONS ↓ effectiveness of OCP

Rifampicin Antifungal Barbiturates Phenytoin Certain antibiotics Activated charcoal Laxatives St John’s wort

Requirement for oral antidiabetics & insulin can change

The actions of TCAs, theophylline, diazepam are potentiated by OCP

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COUNSELING Daily, same time each day Take with food or immediately after food If you vomit within 4 hours of taking pill, repeat the dose Start 1st day of menstrual cycle protection starts from

the very 1st pill Start on other time in menstrual cycle must use a

different form of contraception for 7 days (COC) or 48 hours (POP)

Do not protect against STDs (eg: HIV/AIDS) If you miss 2 or more menstrual periods, should check

for pregnancy If you become sick and have severe diarrhea or

vomiting for several days, you should use another method of contraception until you next period

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IF COCs ARE MISSED A pill is regarded as missed if it is >12hours late If you forget to take 1 pill, take it as soon as you

remember, even if it means taking 2 pills on 1 day.

Missed 2 or more pills Take a pill at once:

- If 7 or more pills left, take the rest of the pills as usual

- If < 7 pills left, take the rest of the pills as usual and omit the pill-free interval

Additional contraceptive for the next 7 days

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IF POPs ARE MISSED A pill is regarded as missed if it is >3 hours

late The missed pill should be taken as soon as

one remembers The next pill should be taken at the usual

time Avoid sexual activity If sexual activity cannot be avoided, use

additional contraception for 48 hours.

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REFERENCES Milton SW Lum 2003. Contraception. Malaysia: Kuala Lumpur Blackburn RD, Cunkelman JA & Zlidar VM 2000. Oral

Contraceptives-An Update. Population Reports: Series A, Number 9

Zlidar VM 2000. Helping Women Use the Pill. Population Reports: Series A, Number 10

MyHEALTH for life. Reproductive Health: Family Planning. Adapted from http://www.myhealth.gov.my

British National Formulary (BNF), Issue 54, September 2007. RPS Publishing

MedlinePlus Drug Information: Estrogen and Progestin (Oral Contraceptives). American Society of Health-System Pharmacists, Inc. Adapted from http://www.nlm.nih.gov/medlineplus/druginfo/meds/a601050.html [27 April 2009]

Roberts H 2008. Combined oral contraceptives: Issues for current users. BPJ:12:21-29.