Estrogen-Progestin Combinations

Class: Contraceptives
VA Class: GU400
CAS Number: 57-63-6
Brands: Alesse, Apri, Aviane, Brevicon, Cryselle, Cyclessa, Demulen, Desogen, Enpresse, Estrostep, Femcon, Kariva, Lessina, Levlen, Levlite, Levora, Lo/Ovral, Loestrin, LoSeasonique, Low-Ogestrel, Lybrel, Microgestin, Mircette, Modicon, MonoNessa, Necon, Nelova, Nordette, Norinyl, Nortrel, NuvaRing, Ogestrel, Ortho Evra, Ortho Tri-Cyclen, Ortho-Cept, Ortho-Cyclen, Ortho-Novum, Ovcon, Ovral, Portia, Seasonale, Seasonique, Sprintec, Tri-Levlen, Tri-Norinyl, Triphasil, Tri-Spintec, Trivora, Yasmin, Yaz, Zovia

Special Alerts:

ISSUE: FDA is aware of two newly published studies that evaluated the risk of venous thromboembolism (VTE) in women who use birth control pills that contain drospirenone. The two recently published studies looked at whether there is a higher risk of blood clots in women taking birth control pills containing the progestin drospirenone when compared to similar women taking birth control pills containing a different progestin called levonorgestrel. These two new studies reported that there is a greater risk of VTE associated with birth control pills that contain drospirenone. This risk is reported to be up to 2 to 3 times greater than the risk of VTE associated with using levonorgestrel-containing pills. Other studies have not reported an increase in risk. The FDA is currently evaluating the conflicting results from these studies and will look at all currently available information to fully assess the risks and benefits of drospirenone-containing birth control pills. FDA will continue to communicate any new safety information to the public as it becomes available. Read the drug safety communication for more information on these studies.

BACKGROUND: Drospirenone is a type of female sex hormone called a progestin. Most birth control pills contain two types of hormones--estrogen and progestin. Birth control pills work by preventing the release of eggs from the ovaries (ovulation) and changing the cervical mucus and the lining of the uterus to prevent pregnancy. Brand names of drospirenone-containing products include Yaz (generics Gianvi and Loryna), Yasmin (generics Ocella, Syeda, and Zarah), Beyaz, and Safyral.

RECOMMENDATION: If your birth control pill contains drospirenone, do not stop taking it without first talking to your healthcare professional. Contact your healthcare professional immediately if you develop any symptoms of blood clots, including persistent leg pain, severe chest pain, or sudden shortness of breath. If you smoke and are over 35 years of age, you should not take combination oral contraceptives because they increase the risk that you could experience serious cardiovascular events, including blood clots. For more information visit the FDA website at: and .

• 
  

  Cigarette smoking during oral contraceptive use increases the risk of serious adverse cardiovascular effects.^a This risk increases with age and with heavy smoking (≥15 cigarettes daily) and is markedly greater in women >35 years of age.^a Women who use oral contraceptives should be strongly advised not to smoke.^a

  
  

Introduction

Contraceptive combinations containing estrogenic and progestinic steroids.^a

Uses for Estrogen-Progestin Combinations

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Contraception

Prevention of conception in women.^a

Postcoital Contraception

Prevention of conception after unprotected intercourse (including known or suspected contraceptive failure) as an emergency contraceptive† (“morning-after” pills).^{254 255 257 258 259 261 262 264 265 345 346 347 348 349} Postcoital (emergency) contraceptive regimens are not as effective as most other forms of long-term contraception and should not be used as routine forms of contraception.^{345 346}

An emergency contraceptive regimen employing a progestin alone (levonorgestrel) appears to be more effective and better tolerated than a common estrogen-progestin emergency contraceptive (“Yuzpe”) regimen when the regimens are initiated within 72 hours of unprotected intercourse, and therefore, generally is preferred when readily available.^{345 346 347 348}

Acne Vulgaris

Ortho Tri-Cyclen, Estrostep: Treatment of moderate acne vulgaris in females ≥15 years of age who have no known contraindications to oral contraceptive therapy, desire contraception, have achieved menarche, and are unresponsive to topical anti-acne medication.^{299 321} Estrostep should be used for the treatment of acne vulgaris only in women who desire oral contraception and plan to take the drug for at least 6 months.²⁹⁹

Premenstrual Dysphoric Disorder

Yaz: Management of premenstrual dysphoric disorder in women who desire oral contraception.^{333 338 341}

Estrogen-Progestin Combinations Dosage and Administration

Administration

Administered orally, intravaginally, or percutaneously by topical application of a transdermal system to the skin.^a

Oral Administration

Contraception

Take as near as possible to the same time each day (i.e., at regular 24-hour intervals) to ensure maximum contraceptive efficacy.^a

Take with or after the evening meal or at bedtime to minimize nausea.^a

Vomiting or diarrhea may decrease absorption of oral contraceptives and potentially result in treatment failures; in such instances, use a back-up method of contraception (e.g., condoms, foam, sponge) until the next clinician contact.^{295 296 298 299 301}

Chewable tablets may be swallowed whole or chewed and consumed with 240 mL of liquid.³³⁷

Available in a mnemonic dispensing package designed to aid the user in complying with the prescribed dosage schedule.^a

Postcoital Contraception

Administer first contraceptive dose as soon as possible but preferably within 72 hours following unprotected sex; repeat dose 12 hours later.^{254 255 257 258 260 261 262 264 265 345 346 347} Schedule first dose as conveniently as possible so that the likelihood of missing the second dose 12 hours later is minimized (e.g., if the first dose were taken at 3 p.m., the second dose would need to be taken at 3 a.m., which might pose a problem of compliance for heavy sleepers).^{265 275 282 284}

Most data support administration of the first dose up to 120 hours after unprotected intercourse if necessary, but efficacy decreases as initiation of contraception becomes more remote from unprotected intercourse.^{345 346 347} Efficacy not established if administered >120 hours after unprotected intercourse.^{345 346}

Consider use of an antiemetic 1 hour before the first dose.^{254 255 257 258 259 260 261 262 264 265 282 284 285 286 345} The high dosage in the combination regimens may cause severe nausea and vomiting.^{254 255 257 258 260 261 262 264 265 285} Food not effective in reducing adverse GI effects (i.e., nausea).^{345 346}

Consider repeating a dose if breakthrough vomiting occurs within 2 hours after administration.³⁴⁵

Vaginal Administration

The vaginal contraceptive ring (NuvaRing) is inserted into the vagina by the patient; the exact position of the ring inside the vagina is not critical for its proper functioning.³⁰⁹

If the ring is accidentally expelled, rinse with cool or lukewarm water and reinsert it or, if necessary, insert a new ring as soon as possible; in either case, the administration schedule employed should be continued.³⁰⁹

If the contraceptive ring is removed from the vagina for longer than 3 hours, use a back-up method of contraception (e.g., condoms, spermicides) until the ring has been used continuously for 7 days.³⁰⁹

Topical Administration

Apply transdermal system to a clean and dry area of intact skin on the buttock, abdomen, upper outer arm, or upper torso by firmly pressing the system with the adhesive side touching the skin.³⁰⁸ Press system firmly in place with the palm of the hand for about 10 seconds; ensure good contact, especially around the edges.³⁰⁸ Do not apply to sites that are oily, damaged, or irritated.³⁰⁸ Do not apply transdermal system to the breasts or to areas where tight clothing may cause the system to be rubbed off.³⁰⁸

If the system inadvertently gets detached and is removed for less than one day, reapply the system or, if necessary, apply a new system (if the system is no longer sticky); in either case, the application schedule employed should be continued.³⁰⁸

If the system is removed for longer than 1 day or for an unknown duration, apply a new system immediately and start a new 4-week cycle; use a back-up method of contraception (e.g., condoms, spermicides, diaphragm) for the first week of the new cycle.³⁰⁸

Dosage

The smallest dosage of estrogen and progestin compatible with a low failure rate and the individual needs of the woman should be used.^a

In establishing an oral contraceptive dosage cycle, the menstrual cycle is usually considered to be 28 days. The first day of bleeding is counted as the first day of the cycle.^a

Estrogen-progestin oral contraceptives are usually classified according to their formulation:

• 
  

  those monophasic preparations containing 50 mcg of estrogen,

  
  


• 
  

  those monophasic preparations containing <50 mcg of estrogen (usually 20–35 mcg),

  
  


• 
  

  those containing <50 mcg of estrogen with 2 sequences of progestin doses (biphasic),

  
  


• 
  

  those containing <50 mcg of estrogen with 3 sequences of progestin doses (triphasic), and

  
  


• 
  

  those containing 3 sequences of estrogen (e.g., 20, 30, 35 mcg) with a fixed dose of progestin (estrophasic).

  
  

Oral contraceptives usually are described in terms of their estrogen content, although the progestin content of the formulations also varies.^a The estrogenic and progestinic dominance of oral contraceptives depends mainly on the amount of estrogen and the amount and specific progestin contained in the formulation.^a The estrogenic or progestinic dominance of an oral contraceptive may contribute to hormone-related adverse effects and may be useful in selecting an alternate formulation when unacceptable adverse effects occur with a given formulation.^a

Biphasic oral contraceptives contain 2 sequentially administered, fixed combinations of hormones per dosage cycle.^a The first sequence consists of tablets containing a fixed combination of low-dose estrogen and low-dose progestin, and the second sequence consists of tablets containing a fixed combination of low-dose estrogen and higher-dose progestin.^a Biphasic oral contraceptives are not the same as previously available “sequential” oral contraceptives, which consisted of an estrogen alone for the first sequence.^a

Triphasic oral contraceptives contain graduated sequences of progestin or estrogen per dosage cycle.^{294 299} With most commercially available triphasic oral contraceptives, each dosage cycle consists of 3 sequentially administered fixed combinations of the hormones in which the ratio of progestin to estrogen progressively increases with each sequence.^a The first sequence consists of tablets containing a fixed combination of low-dose estrogen and low-dose progestin, the second sequence consists of tablets containing a fixed combination of low-dose or low but slightly higher-dose estrogen and higher-dose progestin, and the third sequence consists of tablets containing low-dose estrogen and either an even higher-dose progestin or low-dose progestin.^a

Estrophasic oral contraceptives are triphasic preparations in which the estrogen component progressively increases with each sequence.^{294 299}

Fixed-combination, conventional-cycle oral contraceptives are available as 21- or 28-day dosage preparations.^a Some 28-day preparations contain 21 hormonally active tablets and 7 inert or ferrous fumarate-containing tablets.^a Other 28-day preparations contain 24 hormonally active tablets and 4 inert or ferrous fumarate-containing tablets.^{332 333}

One monophasic, fixed-combination, extended-cycle oral contraceptive (e.g., Seasonale) is available as a 91-day dosage preparation containing 84 hormonally active tablets and 7 inert tablets.³²² Other extended-cycle oral contraceptive preparations (e.g., LoSeasonique, Seasonique) are available as 91-day preparations with 84 hormonally active tablets containing estrogen/progestin and 7 tablets containing low-dose estrogen.^{331 354}

One fixed-combination, continuous-regimen (noncyclic) oral contraceptive (i.e., Lybrel) is available as a 28-day dosage preparation containing 28 hormonally active tablets.³³⁹

The transdermal system (Ortho Evra) is applied topically in a cyclic regimen using a 28-day cycle.³⁰⁸

The vaginal contraceptive ring (NuvaRing) is intended to be used for 1 cycle, which consists of a 3-week period of continuous use of the ring followed by a 1-week ring-free period.³⁰⁹

Adults

Contraception

Oral (21- or 28-day conventional-cycle preparations)

Start on the first Sunday after or on which menstrual bleeding begins or on the first day of the menstrual cycle.^a

If the first dose is on the first Sunday on or after menstrual bleeding starts, use a back-up method of contraception (e.g., condoms, foam, sponge) for 7 days following initiation of oral contraceptive therapy.^{236 298 295 296 298 299 301 332 333 337} If the first dose is on the first day of the menstrual cycle, a back-up method of contraception is not necessary.^{236 298 295 296 298 299 301}

With 21-day conventional-cycle preparations, take 1 estrogen/progestin tablet once daily for 21 consecutive days, followed by 7 days without tablets.^a Begin repeat dosage cycles on the eighth day after the last hormonally active tablet (i.e., on the same day of the week as the initial cycle).^a

With 28-day conventional-cycle preparations containing 21 hormonally active tablets, take 1 estrogen/progestin tablet once daily for 21 consecutive days, followed by inert tablets or ferrous fumarate tablets for 7 days.^a Begin repeat dosage cycles on the eighth day after the last hormonally active tablet (i.e., on the same day of the week as the initial cycle).^a

With 28-day conventional-cycle preparations containing 24 hormonally active tablets, take 1 estrogen/progestin tablet once daily for 24 consecutive days, followed by inert tablets or ferrous fumarate tablets for 4 days.^{332 333} Begin repeat dosage cycles on the fifth day after the last hormonally active tablet (i.e., on the same day of the week as the initial cycle).^{332 333}

When 1 estrogen/progestin tablet of a conventional-cycle oral contraceptive is missed, take the missed tablet as soon as it is remembered, followed by resumption of the regular schedule.^a Additional contraceptive methods are not necessary if only 1 tablet is missed.^{295 296 298 299 301 321 332 333 337}

When 2 estrogen/progestin tablets are missed during the first 1 or 2 weeks of the cycle, take the 2 missed tablets as soon as they are remembered, take 2 tablets the next day, then resume the regular schedule.^{295 296 298 299 301 321 332 333 337} If 2 consecutive estrogen/progestin tablets are missed during the third or fourth week of a dosage cycle that was initiated on the first day of the menstrual cycle, discard the remainder of the tablets in the pack for that cycle and start a new dosage cycle the same day.^{295 296 298 299 301 321 332 333 337} If 2 consecutive estrogen/progestin tablets are missed during the third or fourth week of a dosage cycle that was initiated on the first Sunday on or after menstruation started, continue to take 1 tablet daily until Sunday, then discard the remainder of the tablets for that cycle and start a new dosage cycle that same day.^{295 296 298 299 301 321 332 333 337} When 2 or more estrogen/progestin tablets are missed on consecutive days, a back-up method of contraception should be used for each sexual encounter until a hormonally active tablet has been taken for 7 consecutive days.^{321 332 333 337}

If 3 or more consecutive estrogen/progestin tablets are missed during a dosage cycle that was initiated on the first day of the menstrual cycle, discard the remainder of the tablets in that cycle and start a new dosage cycle the same day.^{295 296 298 299 301 321 332 333 337} If 3 or more consecutive estrogen/progestin tablets are missed during a dosage cycle that was initiated on the first Sunday on or after menstruation started, take 1 tablet daily until Sunday, then discard the remainder of the tablets for that cycle and start a new dosage cycle that same day.^{295 296 298 299 301 321 332 333 337} A back-up method of contraception should be used for each sexual encounter until a hormonally active tablet has been taken for 7 consecutive days.^{321 332 333 337}

During week 4 of a 28-day dosage cycle, any inactive or ferrous fumarate tablets that are missed should be discarded; continue to take the remaining tablets until the cycle is finished.^{295 296 298 299 301 332 333 337} A back-up contraceptive method is not required during the fourth week as a result of missed inactive or ferrous fumarate tablets.^{295 296 298 299 301 332 333 337}

With 28-day contraceptive cycles, a new cycle of tablets should be started the day after taking the last tablet of the previous 28-day dosage cycle (i.e., no days without tablets).^{295 296 298 299 301 332 333 337}

If unsure of what drug regimen to take as a result of missed tablets, use a back-up method of contraception for each sexual encounter and take 1 estrogen/progestin tablet daily until the next clinician contact.^{295 296 298 299 301 321 332 333 337}

Oral (91-day extended-cycle preparations)

Start on the first Sunday after or on which bleeding begins.^{322 331 354} Use a back-up method of contraception (e.g., condom, spermicide) for 7 days following initiation of therapy.^{322 331 354}

Take 1 estrogen/progestin tablet daily for 84 days, followed by inert tablets or tablets containing 10 mcg of estrogen for 7 days.^{322 331 354} Repeat dosage cycles begin on the same day of the week (Sunday) as the initial cycle.^{322 331 354} If a repeat cycle is started later than the scheduled day, use a back-up method of contraception until an estrogen/progestin tablet has been taken for 7 consecutive days.^{322 331 354}

When 1 estrogen/progestin tablet is missed, take the missed tablet as soon as it is remembered, followed by resumption of the regular schedule.^{322 331 354} Additional contraceptive measures are not necessary if only one tablet is missed.^{322 331 354}

When 2 estrogen/progestin tablets are missed, take the 2 missed tablets as soon as they are remembered, 2 tablets the next day, then resume the regular cycle.^{322 331 354} Use a back-up method of contraception until an estrogen/progestin tablet has been taken for 7 consecutive days.^{322 331 354}

When 3 or more consecutive estrogen/progestin tablets are missed, continue to take 1 tablet daily; the missed tablets should be discarded.^{322 331 354} Use a back-up method of contraception until an estrogen/progestin tablet has been taken for 7 consecutive days.^{322 331 354}

If unsure of what drug regimen to take as a result of missed tablets, use a back-up method of contraception for each sexual encounter, and take 1 tablet daily until the next clinician contact.^{322 331 354}

Discard inert tablets or estrogen-containing tablets that are missed; continue to take the remaining tablets until the cycle is finished.^{322 331 354} If inert tablets or estrogen-containing tablets are missed, a back-up contraceptive method is not required.^{322 331 354}

Oral (continuous-regimen [noncyclic] preparation)

Women who did not use hormonal contraception in the preceding month: Start on the first day of the menstrual cycle.³³⁹ If the first dose is on the first day of the menstrual cycle, a back-up method of contraception is not necessary.³³⁹

Women switching from cyclic estrogen-progestin oral contraceptives: Start on the first day of withdrawal bleeding, within 7 days of the last hormonally active tablet.³³⁹ A back-up method of contraception is not needed.³³⁹

Women switching from progestin-only oral contraceptives: Start on the day after the last progestin tablet.³³⁹ Use a back-up method of contraception (e.g., condom, spermicide) until an estrogen/progestin tablet has been taken for 7 consecutive days.³³⁹

Women switching from a progestin-only implant: Start on the day that the implant is removed.³³⁹ Use a back-up method of contraception until an estrogen/progestin tablet has been taken for 7 consecutive days.³³⁹

Women switching from a progestin-only contraceptive injection: Start on the day that the next contraceptive injection would have been due.³³⁹ Use a back-up method of contraception until an estrogen/progestin tablet has been taken for 7 consecutive days.³³⁹

Take 1 estrogen/progestin tablet each day and continue daily without interruption.³³⁹

When 1 tablet is missed, take the missed tablet as soon as it is remembered, then resume the regular schedule (2 tablets may be taken on the same day).³³⁹ Use a back-up method of contraception until an estrogen/progestin tablet has been taken for 7 consecutive days.³³⁹

When 2 tablets are missed and the missed doses are remembered on the day of the second missed dose, take the 2 missed tablets as soon as remembered, then resume the regular schedule.³³⁹ When the 2 tablets are missed and the missed doses are remembered on the day after the second missed dose, take the 2 missed tablets as soon as remembered, take 2 tablets the next day, then resume the regular schedule.³³⁹ Use a back-up method of contraception until an estrogen/progestin tablet has been taken for 7 consecutive days.³³⁹

When 3 or more tablets are missed, contact clinician and continue to take 1 tablet daily until clinician contact.³³⁹ Use a back-up method of contraception until an estrogen/progestin tablet has been taken for 7 consecutive days.³³⁹

If unsure of what drug regimen to take as a result of missed tablets, use a back-up method of contraception for each sexual encounter.³³⁹

Nonlactating postpartum women may start the fixed-combination, continuous-regimen oral contraceptive no earlier than 28 days after delivery; a back-up method of contraception is needed until an estrogen/progestin tablet has been taken for 7 consecutive days.³³⁹

Women may start the continuous regimen immediately after a complete first-trimester abortion; a back-up method of contraception is not needed.³³⁹

Women may start the continuous regimen no earlier than 28 days after a second-trimester abortion; a back-up method of contraception is needed until an estrogen/progestin tablet has been taken for 7 consecutive days.³³⁹

Vaginal

To initiate therapy in women who did not use hormonal contraception in the preceding month, insert the vaginal contraceptive ring (NuvaRing) on or before day 5 of the cycle.³⁰⁹ During the first cycle, use a back-up method of contraception (e.g., condom, spermicide) until the vaginal ring has been used continuously for 7 days.³⁰⁹

After 3 weeks, remove the vaginal ring on the same day of the week as it was inserted and at about the same time of day.³⁰⁹ For contraceptive effectiveness, insert a new vaginal ring 1 week after the previous vaginal ring is removed even if menstrual bleeding is not finished.³⁰⁹

Women switching from estrogen-progestin oral contraceptives: Insert the vaginal ring within 7 days of the last hormonally active tablet and no later than the day that a new oral contraceptive cycle would have been started; a back-up method of contraception is not needed.³⁰⁹

Women switching from progestin-only oral contraceptives: Insert the vaginal ring on any day of the month (without skipping any day between receiving the last progestin oral contraceptive and the initial administration of the vaginal ring).³⁰⁹ Use a back-up method of contraception until the vaginal ring has been used continuously for 7 days.³⁰⁹

Women switching from a progestin-only contraceptive injection: Insert the vaginal ring on the same day as the next contraceptive injection would have been due.³⁰⁹ Use a back-up method of contraception until the vaginal ring has been used continuously for 7 days.³⁰⁹

Women who are switching from a progestin-only implant or a progestin-containing intrauterine device: Insert the vaginal ring on the same day as the implant or intrauterine device is removed.³⁰⁹ Use a back-up method of contraception until the vaginal ring has been used continuously for 7 days.³⁰⁹

If a woman forgets to insert a new vaginal ring at the start of any cycle, insert the ring as soon as remembered; use a back-up method of contraception until the ring has been used continuously for 7 days.³⁰⁹ If the vaginal ring is left in place for up to 1 extra week (up to 4 weeks total), remove the ring and insert a new ring after a 1-week drug-free interval.³⁰⁹ If the ring is left in place for longer than 4 weeks, rule out pregnancy and use a back-up method of contraception until a new ring has been used continuously for 7 days.³⁰⁹

Women may start using the vaginal contraceptive ring in the first 5 days following a complete first-trimester abortion; a back-up method of contraception is not needed in these women.³⁰⁹ If the contraceptive ring is not used within the first 5 days, follow the general instructions for women who did not use hormonal contraception in the preceding month.³⁰⁹

If a nonlactating woman chooses to initiate contraception postpartum with the contraceptive vaginal ring before menstruation has started, consider the possibility that ovulation and conception may have occurred prior to initiation of contraceptive therapy; use a back-up method of contraception for the first 7 days.³⁰⁹

Topical

To initiate therapy, start on the first day of the menstrual cycle or on the first Sunday after menstrual bleeding has started.³⁰⁸ Use a back-up method of contraception (condom, spermicide, diaphragm) for the first 7 days if therapy is started after day 1 of the menstrual cycle.³⁰⁸ A back-up method of contraception is not needed if the first system is applied on the first day of the menstrual cycle.³⁰⁸

One transdermal system (containing ethinyl estradiol 0.75 mg and norelgestromin 6 mg) is applied once weekly (same day each week) for 3 weeks, followed by a 1-week drug-free interval (drug-free interval should not exceed 7 days); the regimen is then repeated.³⁰⁹

Women switching from estrogen-progestin oral contraceptives: Apply the transdermal system on the first day of withdrawal bleeding.³⁰⁸ If there is no withdrawal bleeding within 5 days of the last hormonally active tablet, rule out pregnancy.³⁰⁹ If therapy with the transdermal system is initiated after the first day of bleeding, use a back-up method of contraception for 7 days.³⁰⁸ If more than 7 days elapse after receiving the last hormonally active tablet, consider the possibility of ovulation and conception.³⁰⁹

When a woman has not adhered to the prescribed transdermal contraceptive regimen by not applying the estrogen and progestin-containing system at the initiation of any cycle (i.e., day 1/first week), apply the system as soon as it is remembered and start a new dosage cycle the same day; use a back-up method of contraception for the first 7 days of the new cycle.³⁰⁸

If, in the middle of the cycle (i.e., on day 8/week 2 or day 15/week 3), the transdermal system has not been changed for 1–2 days (<48 hours), apply a new system as soon as it is remembered and continue the application schedule employed; back-up contraception is not needed.³⁰⁸ If, in the middle of the cycle the transdermal system has not been changed for more than 2 days (≥48 hours), start a new dosage cycle; use a back-up method of contraception for the first 7 days of the new cycle.³⁰⁸

When the transdermal system is not removed at the end of the application schedule (i.e., on day 22/week 4), remove the system as soon as it is remembered and continue the application schedule employed (i.e., apply system on day 28); back-up contraception is not needed.³⁰⁸

Women may start using the transdermal contraceptive system immediately after a first-trimester abortion; a back-up method of contraception is not needed.³⁰⁸ If the contraceptive preparation is not used within 5 days of a first-trimester abortion, follow instructions as if initiating transdermal contraception for the first time.³⁰⁸

Postcoital Contraception

Oral

“Yuzpe” regimen†: Take 100 mcg of ethinyl estradiol and 1 mg of norgestrel within 72 hours after unprotected intercourse, repeating the dose 12 hours later.^{254 255 257 258 259 261 262 264 265 275 282 284 345}

Other regimens†: Take 100–120 mcg of ethinyl estradiol and 1.2 mg of norgestrel or 0.5–0.6 mg of levonorgestrel within 72 hours after intercourse, repeating the dose 12 hours later.^{264 265 275 282 284 345}

If necessary, the first dose can be administered up to 120 hours after unprotected intercourse, but efficacy decreases the longer initiation of contraception is delayed.^{345 346 347}

Repeated postcoital (emergency) contraception use indicates need for counseling about other contraceptive options.^{345 350} Safety of recurrent use not established but risk appears low, even within same menstrual cycle.^{345 350} Consider possibility that risk of adverse effects may be increased with frequently repeated postcoital contraception.³⁵⁰

* Dose is administered initially and then repeated 12 hours later

Dosage of Estrogen-progestin Combinations for Postcoital Contraception

Estrogen-progestin Combination Formulation [Brand Name]	Number and Color of Tablets per Dose*
Ethinyl estradiol (50 mcg) with norgestrel (0.5 mg) [Ovral]	2 white tablets (any of 21 tablets)
Ethinyl estradiol (50 mcg) with norgestrel (0.5 mg) [Ovral-28]	2 white tablets (any of first 21 tablets)
Ethinyl estradiol (30 mcg) with norgestrel (0.3 mg) [Lo-Ovral]	4 white tablets (any of 21 tablets)
Ethinyl estradiol (30 mcg) with norgestrel (0.3 mg) [Lo-Ovral-28]	4 white tablets (any of first 21 tablets)
Ethinyl estradiol (30 mcg) with levonorgestrel (0.15 mg) [Nordette]	4 light-orange tablets (any of 21 tablets)
Ethinyl estradiol (30 mcg) with levonorgestrel (0.15 mg) [Nordette-28]	4 light-orange tablets (any of first 21 tablets)
Ethinyl estradiol (30 mcg) with levonorgestrel (0.15 mg) [Levlen 21]	4 light-orange tablets (any of 21 tablets)
Ethinyl estradiol (30 mcg) with levonorgestrel (0.15 mg) [Levlen 28]	4 light-orange tablets (any of first 21 tablets)
Ethinyl estradiol (30 mcg) with levonorgestrel (0.125 mg) [Tri-Levlen 21]	4 yellow tablets (any of last 10 tablets)
Ethinyl estradiol (30 mcg) with levonorgestrel (0.125 mg) [Tri-Levlen 28]	4 yellow tablets (any of tablets 12–21)
Ethinyl estradiol (30 mcg) with levonorgestrel (0.125 mg) [Tri-Phasil 21]	4 yellow tablets (any of last 10 tablets)
Ethinyl estradiol (30 mcg) with levonorgestrel (0.125 mg) [Tri-Levlen 28]	4 yellow tablets (any of tablets 12–21)
Ethinyl estradiol (20 mcg) with levonorgestrel (0.1 mg) [Lessina 28]	5 pink tablets (any of first 21 tablets)

Acne Vulgaris

Oral

Ortho Tri-Cyclen or Estrostep is used in the same dosage and administration (i.e., timing of initiation of therapy) as used in contraception.^a

Premenstrual Dysphoric Disorder

Oral

Yaz is used in the same dosage and administration (i.e., timing of initiation of therapy) as used in contraception.³³³ (See Oral [21- or 28-day conventional-cycle preparations] under Dosage and Administration.)

Cautions for Estrogen-Progestin Combinations

Contraindications

• 
  

  Hypersensitivity to the drug or any ingredient in the formulation.^a

  
  


• 
  

  Known or suspected pregnancy.^a

  
  


• 
  

  Undiagnosed abnormal genital bleeding.^a

  
  


• 
  

  Diplopia or any ocular lesion arising from ophthalmic vascular disease.^a

  
  


• 
  

  Classical migraine.^a

  
  


• 
  

  Active liver disease or history of cholestatic jaundice with pregnancy or with prior use of oral contraceptives.^a

  
  


• 
  

  Breast-feeding.^a

  
  


• 
  

  Thrombophlebitis or thromboembolic disorders.^a

  
  


• 
  

  Cerebrovascular disease or CAD (including MI).^a

  
  


• 
  

  Severe hypertension.^a

  
  


• 
  

  Diabetes with vascular involvement.^a

  
  


• 
  

  Known or suspected carcinoma of the breast.^a

  
  


• 
  

  Known or suspected estrogen-dependent neoplasia (e.g., carcinoma of the endometrium).^a

  
  


• 
  

  Benign or malignant liver tumor that developed during oral contraceptive or other estrogen use.^a

  
  


• 
  

  Oral contraceptives containing the progestin drospirenone are contraindicated in women with renal or hepatic impairment and in those with adrenal insufficiency.^{302 333}

  
  


• 
  

  Most experts state that there currently is no real contraindication to postcoital (emergency) contraception with the recommended regimens and that the benefits generally outweigh any theoretical or proven risk.^{345 346 350}

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Increased risk of several serious conditions, including thromboembolism, stroke, MI, liver tumor, gallbladder disease, visual disturbances, fetal abnormalities, and hypertension.^a However, risk of serious morbidity or mortality is very small in healthy women without underlying risk factors.^a

Ethinyl Estradiol/Norelgestromin Transdermal System

Overall exposure to ethinyl estradiol and norelgestromin is higher in women receiving Ortho Evra than in women receiving an oral contraceptive preparation containing ethinyl estradiol 35 mcg and norgestimate 0.25 mg.³⁰⁸ (See Absorption under Pharmacokinetics.)