Gynophase

A synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception.

Gynophase is indicated for the prevention of pregnancy in women who elect to use oral contraceptives as a method of contraception.

Gynophase is indicated for the treatment of moderate acne vulgaris in females, ≥15 years of age, who have no known contraindications to oral contraceptive therapy, desire oral contraception, have achieved menarche, and are unresponsive to topical anti-acne medications. Gynophase should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control and plans to stay on it for at least 6 months.

Oral contraceptives are highly effective for pregnancy prevention. Table 2 lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates.

* Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason.

† Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason.

‡ Among couples attempting to avoid pregnancy, the percentage who continue to use a method for 1 year.

§ The percentages becoming pregnant in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% become pregnant within one year. This estimate was lowered slightly (to 85%) to represent the percent who would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether.

¶ Foams, creams, gels, vaginal suppositories, and vaginal film.

#Þ Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases.

ß With spermicidal cream or jelly.

à Without spermicides.

è The treatment schedule is one dose within 72 hours after unprotected intercourse, and a second dose 12 hours after the first dose. The Food and Drug Administration has declared the following brands of oral contraceptives to be safe and effective for emergency contraception: Ovral® (1 dose is 2 white pills), Alesse® (1 dose is 5 pink pills), Nordette® or Levlen® (1 dose is 4 light-orange pills), Lo/Ovral® (1 dose is 4 white pills), Triphasil® or Tri-Levlen® (1 dose is 4 yellow pills).

ð However, to maintain effective protection against pregnancy, another method of contraception must be used as soon as menstruation resumes, the frequency or duration of breastfeeds is reduced, bottle feeds are introduced, or the baby reaches 6 months of age.

Gynophase was evaluated for the treatment of acne vulgaris in two randomized, double-blind, placebo-controlled, multicenter, Phase 3, six (28-day) cycle studies. A total of 296 patients received Gynophase and 295 received placebo. Mean age at enrollment for both groups was 24 years. At six months each study demonstrated a statistically significant difference between Gynophase and placebo for mean change from baseline in lesion counts. Each study also demonstrated overall treatment success in the investigator’s global evaluation. Patients with severe androgen excess were not studied.

*Numbers rounded to nearest integer

† Limits for 95% Confidence Interval; not adjusted for baseline differences

Gynophase users who started with about 74 acne lesions had about 42 lesions after 6 months of treatment. Placebo users who started with about 72 acne lesions had about 49 lesions after the same duration of treatment.

Figure 2. Mean Percent Reduction in Total Lesion Counts From Baseline to Each 28-Day Cycle and Mean Total Lesion Counts at Each Cycle Following Administration of Gynophase and Placebo (Statistically significant differences were not found in both studies individually until cycle 6)

Ethinyl Estradiol (Gynophase) and Norethindrone (Gynophase) combination is used to prevent pregnancy. It is a birth control pill that contains two types of hormones, Ethinyl Estradiol (Gynophase) and Norethindrone (Gynophase), and when taken properly, prevents pregnancy. It works by stopping a woman's egg from fully developing each month. The egg can no longer accept a sperm and fertilization is prevented.

No contraceptive method is 100 percent effective. Birth control methods such as having surgery to become sterile or not having sex are more effective than birth control pills. Discuss your options for birth control with your doctor.

Ethinyl Estradiol (Gynophase) and Norethindrone (Gynophase) does not prevent HIV infection or other sexually transmitted diseases. It will not help as emergency contraception, such as after unprotected sexual contact.

Ethinyl Estradiol (Gynophase) and Norethindrone (Gynophase) is available only with your doctor's prescription.

How to Take Gynophase

To achieve maximum contraceptive effectiveness, Gynophase must be taken exactly as directed.​ Instruct patients to take one tablet by mouth at the same time every day. The tablet may be chewed and swallowed or swallowed whole. The patient should drink a full glass (8 ounces) of water immediately after the tablets are chewed or swallowed whole. Tablets must be taken in the order directed on the wallet pack. Tablets should not be skipped or taken at intervals exceeding 24 hours. For patient instructions for missed tablets,. Gynophase may be administered without regard to meals.

How to Start Gynophase

Instruct the patient to begin taking Gynophase either on the first day of her menstrual period (Day 1 Start) or on the first Sunday after the onset of her menstrual period (Sunday Start).

Day 1 Start

During the first cycle of Gynophase use, instruct the patient to take one white Gynophase daily, beginning on Day one (1) of her menstrual cycle (the first day of menstruation is Day one). She should take one white Gynophase daily for 24 consecutive days, followed by one brown tablet daily on days 25 through 28. Gynophase should be taken in the order directed on the package at the same time each day. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days if she starts taking Gynophase on a day other than the first day of her menstrual cycle. The possibility of ovulation and conception prior to initiation of medication should be considered.

Sunday Start

During the first cycle of Gynophase use, instruct the patient to take one white Gynophase daily, beginning on the first Sunday after the onset of her menstrual period. She should take one white Gynophase daily for 24 consecutive days, followed by one brown tablet daily on days 25 through 28. Gynophase should be taken in the order directed on the package at the same time each day. Gynophase should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

The patient should begin her next and all subsequent 28-day regimens of Gynophase on the same day of the week that she began her first regimen, following the same schedule. She should begin taking her white Gynophase on the next day after ingestion of the last brown tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of Gynophase is started later than the day following administration of the last brown tablet, the patient should use another method of contraception until she has taken a white Gynophase daily for 7 consecutive days.

For postpartum women who do not breastfeed or after a second trimester abortion, start Gynophase no earlier than 4 weeks postpartum due to the increased risk of thromboembolism. If the patient starts on Gynophase postpartum and has not yet had a period, evaluate for possible pregnancy, and instruct her to use an additional method of contraception until she has taken Gynophase for 7 consecutive days.

Gynophase may be initiated immediately after a first-trimester abortion or miscarriage; if the patient starts Gynophase immediately, additional contraceptive measures are not needed.

Switching from another Hormonal Method of Contraception

If the patient is switching from a combination hormonal method such as:

○ Another pill

○ Vaginal ring

○ Patch

• Instruct her to take the first white Gynophase on the day she would have taken her next COC pill. She should not continue taking the tablets from her previous birth control pack, and should not skip any days between packs. If she does not have a withdrawal bleed, rule out pregnancy before starting Gynophase.
• If she previously used a vaginal ring or transdermal patch, she should start using Gynophase on the day she would have resumed the previous product.

If the patient is switching from a progestin-only method such as a:

○ Progestin-only pill

○ Implant

○ Intrauterine system

○ Injection

• She may switch any day from a progestin-only pill; instruct her to take the first white Gynophase on the day she would have taken her next progestin-only pill. She should use a non-hormonal method of contraception for 7 consecutive days.
• If switching from an implant or injection, start the first white Gynophase on the day her next injection would have been due or on the day of removal of her implant.
• If switching from an IUD, depending on the timing of removal, back-up contraception may be needed.

Advice in Case of Gastrointestinal Disturbances

If the patient vomits or has diarrhea (within 3 to 4 hours after she takes a white Gynophase tablets), she should follow the instructions in the "What to Do if You Miss Tablets" section.

See also:
What is the most important information I should know about Gynophase?

Do not prescribe Gynophase to women who are known to have the following:

• A high risk of arterial or venous thrombotic diseases. Examples include women who are known to:

  - Smoke, if over age 35

  - Have deep vein thrombosis or pulmonary embolism, now or in the past

  - Have cerebrovascular disease

  - Have coronary artery disease

  - Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation)

  - Have inherited or acquired hypercoagulopathies

  - Have uncontrolled hypertension

  - Have diabetes with vascular disease

  - Have headaches with focal neurological symptoms or have migraine headaches with or without aura if over age 35 ​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​

• Breast cancer or other estrogen- or progestin-sensitive cancer, now or in the past

• Liver tumors, benign or malignant, or liver disease

• Undiagnosed abnormal uterine bleeding

• Pregnancy, because there is no reason to use COCs during pregnancy

Use Gynophase as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Gynophase. Talk to your pharmacist if you have questions about this information.
• Take Gynophase by mouth with or without food.
• Talk with your doctor about how you should start to take your first pack of Gynophase. If you begin to take Gynophase during the first 24 hours of your period, you do not need to use an extra form of birth control. If you begin to take Gynophase on the Sunday after your period starts, you will need to use an extra form of birth control for 7 days after you start taking Gynophase.
• If you are switching from another birth control pill to Gynophase, start Gynophase on the same day that you would have started a new pack of your previous birth control pills. If you are switching to Gynophase from another type of hormonal birth control (eg, patch, vaginal ring), ask your doctor or pharmacist about when to start taking Gynophase.
• Take Gynophase at the same time each day. Take the tablets in the order directed on the blister pack. After taking the last pill in the pack, start taking the first pill from the new pack the very next day.
• Severe vomiting or diarrhea may decrease Gynophase's effectiveness. Talk with your doctor about what to do if severe vomiting or diarrhea occurs while you take Gynophase. If you vomit or have diarrhea within 3 to 4 hours after you take Gynophase, this should be considered a missed dose.
• For Gynophase to be effective, it must be taken every day. Do not skip doses even if you do not have sex very often. Do not skip pills if you are spotting, bleeding, or nauseated. If you have these side effects and they do not go away, check with your doctor.
• On the days you take the brown tablets (iron), certain other medicines should not be taken at the same time. If you take antacids, bisphosphonates (eg, etidronate), cephalosporins (eg, cefdinir), methyldopa, quinolones (eg, ciprofloxacin), tetracyclines (eg, minocycline), thyroid hormones (eg, levothyroxine), or thrombopoietin mimetics (eg, eltrombopag), ask your doctor or pharmacist how to take them with the iron tablets.
• If you miss 1 dose of Gynophase, take it as soon as possible. Take your next dose at the regular time. This means you may take 2 doses on the same day. You do not need to use a backup form of birth control if you only miss 1 pill. If you miss more than 1 dose, read the extra patient leaflet that comes with Gynophase or contact your doctor for instructions. You must use a backup form of birth control (eg, condom, spermicide) if you miss more than 1 dose. If you are not sure how to handle missed doses, use an extra form of birth control (eg, condoms) and talk with your doctor.

Ask your health care provider any questions you may have about how to use Gynophase.

This combination hormone medication is used to prevent pregnancy. It contains 2 hormones: a progestin and an estrogen. It works mainly by preventing the release of an egg (ovulation) during your menstrual cycle. It also makes vaginal fluid thicker to help prevent sperm from reaching an egg (fertilization) and changes the lining of the uterus (womb) to prevent attachment of a fertilized egg. If a fertilized egg does not attach to the uterus, it passes out of the body.

Besides preventing pregnancy, birth control pills may make your periods more regular, decrease blood loss and painful periods, decrease your risk of ovarian cysts, and also treat acne.

Using this medication does not protect you or your partner against sexually transmitted diseases (such as HIV, gonorrhea, chlamydia).

How to use Gynophase (28)

Read the Patient Information Leaflet provided by your pharmacist before you start using this product and each time you get a refill. The leaflet contains very important information on when to take your pills and what to do if you miss a dose. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth as directed by your doctor, usually once daily. Pick a time of day that is easy for you to remember, and take your pill at the same time each day.

It is very important to continue taking this medication exactly as prescribed by your doctor. With certain brands of birth control pills, the amount of estrogen and progestin in each active tablet will vary at different times in the cycle. Therefore, it is very important that you follow the package instructions to find the first tablet, start with the first tablet in the pack, and take them in the correct order. Do not skip any doses. Pregnancy is more likely if you miss pills, start a new pack late, or take your pill at a different time of the day than usual.

Vomiting or diarrhea can prevent your birth control pills from working well. If you have vomiting or diarrhea, you may need to use a back-up birth control method (such as condoms, spermicide). Follow the directions in the Patient Information Leaflet and check with your doctor or pharmacist for more details.

Taking this medication after your evening meal or at bedtime may help if you have stomach upset or nausea with the medication. You may choose to take this medication at another time of day that is easier for you to remember. No matter what dosing schedule you use, it is very important that you take this medication at the same time each day, 24 hours apart. Ask your doctor or pharmacist if you have any questions.

Your pill pack contains 21 pills with active medication. It may also contain 7 reminder pills with no medication. Take one active pill (with hormones) once daily for 21 days in a row. If you are using a product with 28 tablets, take an inactive pill once daily for 7 days in a row after you have taken the last active pill unless otherwise directed by your doctor. If you are using a product with 21 tablets, do not take any tablets for 7 days unless otherwise directed by your doctor. You should have your period during the fourth week of the cycle. After you have taken the last inactive tablet in the pack or gone 7 days without taking an active tablet, start a new pack the next day whether or not you have your period. If you do not get your period, consult your doctor.

If this is the first time you are using this medication and you are not switching from another form of hormonal birth control (such as patch, other birth control pills), take the first tablet in the pack on the first Sunday following the beginning of your menstrual period or on the first day of your period. If your period begins on a Sunday, begin taking this medication on that day. For the first cycle of use only, use an additional form of non-hormonal birth control (such as condoms, spermicide) for the first 7 days to prevent pregnancy until the medication has enough time to work. If you start on the first day of your period, you do not need to use back-up birth control the first week.

Ask your doctor or pharmacist about how to switch from other forms of hormonal birth control (such as patch, other birth control pills) to this product. If any information is unclear, consult the Patient Information Leaflet or your doctor or pharmacist.

See also:
What other drugs will affect Gynophase?

No drug-drug interaction studies were conducted with Gynophase.

Changes In Contraceptive Effectiveness Associated With Co-Administration Of Other Products

If a woman on hormonal contraceptives takes a drug or herbal product that induces enzymes, including CYP3A4, that metabolize contraceptive hormones, counsel her to use additional contraception or a different method of contraception. Drugs or herbal products that induce such enzymes may decrease the plasma concentrations of contraceptive hormones, and may decrease the effectiveness of hormonal contraceptives or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include:

• barbiturates
• bosentan
• carbamazepine
• felbamate
• griseofulvin
• oxcarbazepine
• phenytoin
• rifampin
• St. John’s wort
• topiramate

HIV Protease Inhibitors And Non-Nucleoside Reverse Transcriptase Inhibitors

Significant changes (increase or decrease) in the plasma levels of the estrogen and progestin have been noted in some cases of co-administration of HIV protease inhibitors or of non-nucleoside reverse transcriptase inhibitors.

Antibiotics

There have been reports of pregnancy while taking hormonal contraceptives and antibiotics, but clinical pharmacokinetic studies have not shown consistent effects of antibiotics on plasma concentrations of synthetic steroids.

Consult the labeling of all concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.

Increase In Plasma Levels Of Ethinyl Estradiol (Gynophase) Associated With Co-Administered Drugs

Co-administration of atorvastatin and certain COCs containing Ethinyl Estradiol (Gynophase) increase AUC values for Ethinyl Estradiol (Gynophase) by approximately 20 percent. Ascorbic acid and acetaminophen may increase plasma Ethinyl Estradiol (Gynophase) levels, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels.

Changes In Plasma Levels Of Co-Administered Drugs

COCs containing some synthetic estrogens (for example, Ethinyl Estradiol (Gynophase)) may inhibit the metabolism of other compounds. COCs have been shown to significantly decrease plasma concentrations of lamotrigine, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Consult the labeling of the concurrently-used drug to obtain further information about interactions with COCs or the potential for enzyme alterations.

See also:
What are the possible side effects of Gynophase?

The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling:

• Serious cardiovascular events and smoking
• Vascular events
• Liver disease

Adverse reactions commonly reported by COC users are:

• Irregular uterine bleeding
• Nausea
• Breast tenderness
• Headache

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice.

A multicenter phase 3 clinical trial evaluated the safety and efficacy of Gynophase for pregnancy prevention. The study was a one year, open-label, single-arm, uncontrolled study. A total of 1,660 women aged 18 to 45 were enrolled and took at least one dose of Gynophase.

Common Adverse Reactions (≥ 2 percent of all Treated Subjects): The most common adverse reactions reported by at least 2 percent of the 1,660 women using Gynophase were the following in order of decreasing incidence: nausea/vomiting (7 percent), headache (7 percent), bleeding irregularities (including metrorrhagia, irregular menstruation, menorrhagia, vaginal hemorrhage and dysfunctional uterine bleeding) (5 percent), dysmenorrhea (4 percent), weight fluctuation (4 percent), breast tenderness (4 percent), acne (3 percent), abdominal pain (3 percent), anxiety (2 percent), and depression (2 percent).

Adverse Reactions Leading to Study Discontinuation: 10.7 percent of the women discontinued from the clinical trial due to an adverse reaction. Adverse reactions occurring in ≥1 percent of subjects leading to discontinuation of treatment were in decreasing order: menstrual irregularities (including metrorrhagia, irregular menstruation, menorrhagia and vaginal hemorrhage) (4 percent), headache/migraine (1 percent), mood disorder (including mood swings, depression, anxiety) (1 percent), and weight fluctuation (1 percent).

Serious Adverse Reactions: deep vein thrombosis, ovarian vein thrombosis, cholecystitis.