Microgestin 24 FE

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using this medicine and call your doctor at once if you have:

• signs of a stroke--sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance;
• signs of a blood clot--chest pain, sudden cough, wheezing, coughing up blood, swelling or warmth in one or both legs;
• heart attack symptoms--chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;
• vision changes;
• a change in the pattern or severity of migraine headaches;
• swelling in your hands, ankles, or feet;
• a breast lump; or
• symptoms of depression--sleep problems, weakness, tired feeling, mood changes.

Common side effects may include:

• nausea, vomiting;
• breast tenderness or swelling;
• freckles or darkening of facial skin, increased hair growth, loss of scalp hair;
• changes in weight or appetite;
• problems with contact lenses;
• vaginal itching or discharge; or
• changes in your menstrual periods, decreased sex drive.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Coughing up blood.
• Shortness of breath.
• Chest pain or pressure.
• Very bad dizziness or passing out.
• Very upset stomach or throwing up.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Swelling, warmth, numbness, change of color, or pain in a leg or arm.
• Very bad headache.
• Low mood (depression).
• Feeling very tired or weak.
• Very bad belly pain.
• Swelling.
• Not able to pass urine or change in how much urine is passed.
• A lump in the breast, breast soreness, or nipple discharge.
• Vaginal itching or discharge.
• Spotting or vaginal bleeding that is very bad or does not go away.
• Bulging eyes.
• Change in eyesight.
• Change in how contact lenses feel in the eyes.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Feeling more or less hungry.
• Dizziness.
• Weight gain.
• Headache.
• Upset stomach or throwing up.
• Stomach cramps.
• Bloating.
• Enlarged breasts.
• Breast soreness.
• Hair loss.
• Lowered interest in sex.
• This medicine may cause dark patches of skin on your face. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.
• Period (menstrual) changes. These include lots of bleeding, spotting, or bleeding between cycles.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Protect from light.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Combination oral contraceptives act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation).

PHARMACOKINETICS

Absorption

Norethindrone acetate appears to be completely and rapidly deacetylated to norethindrone after oral administration, because the disposition of norethindrone acetate is indistinguishable from that of orally administered norethindrone. Norethindrone acetate and ethinyl estradiol are rapidly absorbed from Microgestin24 Fe tablets, with maximum plasma concentrations of norethindrone and ethinyl estradiol occurring 1 to 4 hours postdose. Both are subject to first-pass metabolism after oral dosing, resulting in an absolute bioavailability of approximately 64% for norethindrone and 43% for ethinyl estradiol.

The plasma norethindrone and ethinyl estradiol pharmacokinetics following single- and multiple-dose administrations of Microgestin 24 Fe tablets in 17 healthy female volunteers are provided in Figures 1 and 2, and Table 1.

Following multiple-dose administration of Microgestin 24 Fe tablets, mean maximum concentrations of norethindrone and ethinyl estradiol were increased by 95% and 27%, respectively, as compared to single-dose administration. Mean norethindrone and ethinyl estradiol exposures (AUC values) were increased by 164% and 51% respectively, as compared to single-dose administration of Microgestin 24 Fe tablets.

Steady-state with respect to norethindrone was reached by Day 17 and steady-state with respect to ethinyl estradiol was reached by Day 13.

Mean SHBG concentrations were increased by 150% from baseline (57.5 nmol/L) to 144 nmol/L at steady-state.

Figure 1.       Mean Plasma Norethindrone Concentration-Time Profiles Following Single- and Multiple-Dose Oral Administration of Microgestin 24 Fe Tablets to Healthy Female Volunteers under Fasting Condition (n = 17)

Figure 2.       Mean Plasma Ethinyl Estradiol Concentration-Time Profiles Following Single- and Multiple-Dose Oral Administration of Microgestin 24 Fe Tablets to Healthy Female Volunteers under Fasting Condition (n = 17)

Effect of Food: Microgestin 24 Fe tablets may be administered without regard to meals. A single-dose administration of Microgestin 24 Fe tablet with food decreased the maximum concentration of norethindrone by 11% and increased the extent of absorption by 27% and decreased the maximum concentration of ethinyl estradiol by 30% but not the extent of absorption.

Distribution

Volume of distribution of norethindrone and ethinyl estradiol ranges from 2 to 4 L/kg. Plasma protein binding of both steroids is extensive (>95%); norethindrone binds to both albumin and SHBG, whereas ethinyl estradiol binds only to albumin. Although ethinyl estradiol does not bind to SHBG, it induces SHBG synthesis.

Metabolism

Norethindrone undergoes extensive biotransformation, primarily via reduction, followed by sulfate and glucuronide conjugation. The majority of metabolites in the circulation are sulfates, with glucuronides accounting for most of the urinary metabolites.

Ethinyl estradiol is also extensively metabolized, both by oxidation and by conjugation with sulfate and glucuronide. Sulfates are the major circulating conjugates of ethinyl estradiol and glucuronides predominate in urine. The primary oxidative metabolite is 2-hydroxy ethinyl estradiol, formed by the CYP3A4 isoform of cytochrome P450. Part of the first-pass metabolism of ethinyl estradiol is believed to occur in gastrointestinal mucosa. Ethinyl estradiol may undergo enterohepatic circulation.

Excretion

Norethindrone and ethinyl estradiol are excreted in both urine and feces, primarily as metabolites. Plasma clearance values for norethindrone and ethinyl estradiol are similar (approximately 0.4 L/hr/kg). Steady-state elimination half-lives of norethindrone and ethinyl estradiol following administration of Microgestin 24 Fe tablets are approximately 8 hours and 14 hours, respectively.

Special Populations

Race. The effect of race on the disposition of norethindrone and ethinyl estradiol after Microgestin 24 Fe administration has not been evaluated.

Renal Insufficiency. The effect of renal disease on the disposition of norethindrone and ethinyl estradiol after Microgestin 24 Fe administration has not been evaluated. In premenopausal women with chronic renal failure undergoing peritoneal dialysis who received multiple doses of an oral contraceptive containing ethinyl estradiol and norethindrone, plasma ethinyl estradiol concentrations were higher and norethindrone concentrations were unchanged compared to concentrations in premenopausal women with normal renal function.

Hepatic Insufficiency. The effect of hepatic disease on the disposition of norethindrone and ethinyl estradiol after Microgestin 24 Fe administration has not been evaluated. However, ethinyl estradiol and norethindrone may be poorly metabolized in patients with impaired liver function.

Drug-Drug Interactions

See PRECAUTIONS sectionDRUG INTERACTIONS

The following noncontraceptive health benefits related to the use of oral contraceptives are supported by epidemiological studies which largely utilized oral-contraceptive formulations containing doses exceeding 0.035 mg of ethinyl estradiol or 0.05 mg of mestranol.

Effects on menses:

• Increased menstrual cycle regularity
  
• Decreased blood loss and decreased incidence of iron-deficiency anemia
  
• Decreased incidence of dysmenorrhea

Effects related to inhibition of ovulation:

• Decreased incidence of functional ovarian cysts
  
• Decreased incidence of ectopic pregnancies

Effects from long-term use:

• Decreased incidence of fibroadenomas and fibrocystic disease of the breast
  
• Decreased incidence of acute pelvic inflammatory disease
  
• Decreased incidence of endometrial cancer
  
• Decreased incidence of ovarian cancer

To achieve maximum contraceptive effectiveness, Microgestin 24 Fe should be taken exactly as directed and at intervals not exceeding 24 hours. Microgestin 24 Fe tablets may be administered without regard to meals.

Microgestin 24 Fe provides a regimen consisting of 24 white active tablets of Microgestin 24 Fe and 4 brown non-hormonal (placebo) tablets of ferrous fumarate. The ferrous fumarate tablets do not serve any therapeutic purpose.

During the first cycle of use:
The possibility of ovulation and conception prior to initiation of medication should be considered. The patient is instructed to begin taking Microgestin 24 Fe on either Day 1 of menstruation (Day 1 Start) or the first Sunday after the onset of menstruation (Sunday Start). If menstruation begins on a Sunday, the first tablet (white) is taken that day. One white tablet should be taken daily for 24 consecutive days followed by one brown tablet daily for 4 consecutive days. Withdrawal bleeding should usually occur within three days following discontinuation of white tablets and may not have finished before the next pack is started. During the first cycle with a Sunday start, contraceptive reliance should not be placed on Microgestin 24 Fe until a white tablet has been taken daily for 7 consecutive days and a non-hormonal back-up method of birth control (such as condoms or spermicide) should be used during those 7 days.

The patient begins her next and all subsequent 28-day courses of tablets on the same day of the week on which she began her first course, following the same schedule: 24 days on white tablets4 days on brown tablets. If in any cycle the patient starts tablets later than the proper day, she should protect herself against pregnancy by using a non-hormonal back-up method of birth control until she has taken a white tablet daily for 7 consecutive days.

Switching from another hormonal method of contraception:
When the patient is switching to Microgestin 24 Fe after completing a 21-day regimen of oral contraceptive tablets, transdermal patches, or a vaginal ring, she should wait 7 days after her last tablet, patch, or ring before she starts Microgestin 24 Fe. She will probably experience withdrawal bleeding during that week. She should be sure that no more than 7 days pass after her previous 21-day regimen. When the patient is switching to Microgestin 24 Fe after completing a 28-day regimen of oral contraceptive tablets, she should start her first pack of Microgestin 24 Fe on the day after her last tablet. She should not wait any days between packs. The patient may switch any day from a progestin-only pill and should begin Microgestin 24 Fe the next day. If switching from an implant or injection, the patient should start Microgestin 24 Fe on the day of implant removal or, if using an injection, the day the next injection would be due.

If spotting or breakthrough bleeding occurs:
The patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance; however, if the bleeding is persistent or prolonged, the patient is advised to consult her healthcare provider. Although pregnancy is unlikely if Microgestin 24 Fe is taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (missed one or more tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out. Hormonal contraceptives should be discontinued if pregnancy is confirmed.

For additional patient instructions regarding missed pills:
See the “WHAT TO DO IF YOU MISS PILLS” section in the DETAILED PATIENT LABELING. Any time the patient misses two or more white tablets, she should also use another method of non-hormonal back-up contraception until she has taken a white tablet daily for seven consecutive days. If the patient misses one or more brown tablets, she is still protected against pregnancy provided she begins taking the active white tablets again on the proper day. If breakthrough bleeding occurs following missed white tablets, it will usually be transient and of no consequence. The possibility of ovulation increases with each successive day that scheduled white tablets are missed. Therefore, the risk of pregnancy increases with each active (white) tablet missed.

Use after pregnancy, abortion or miscarriage:
Microgestin 24 Fe should be initiated no earlier than 28 days postpartum in the nonlactating mother due to the increased risk for thromboembolism. When the tablets are administered in the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered (see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS concerning thromboembolic disease). The patient should be advised to use a non-hormonal back-up method for the first 7 days of tablet taking. However, if intercourse has already occurred, the possibility of ovulation and conception prior to initiation of medication should be considered.

Microgestin 24 Fe may be initiated after a first-trimester abortion or miscarriage; if the patient starts Microgestin 24 Fe immediately, additional contraceptive measures are not needed.

For additional patient instructions regarding complete dosing instructions, see the “HOW TO TAKE THE PILL” section in the DETAILED PATIENT LABELING.

Microgestin 24 Fe is available in blister cards (dispensers) containing 24 white active tablets and 4 brown placebo tablets. Each white, round tablet contains 1 mg of norethindrone acetate and 20 mcg of ethinyl estradiol and is imprinted with WC on one side and 530 on the other. Each brown, round tablet contains 75 mg ferrous fumarate.

N 52544-167-41        One blister card (28 tablets)

N 52544-167-31        Cartons of 3 blister cards (3 X 28 tablets)

Rx only

Keep this drug and all drugs out of the reach of children.

Store at 25º C (77º F); excursions permitted to 15-30º C (59-86º F) [see USP Controlled Room Temperature].

References are available upon request.

PATIENT BRIEF SUMMARY

This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Oral contraceptives, also known as "birth control pills" or "the pill", are taken to prevent pregnancy, and when taken correctly without missing any pills, have a failure rate of about 1% per year (1 pregnancy per 100 women per year of use). The typical failure rate of pill users is 5% (5 pregnancies per 100 women per year of use) when women who miss pills are included.

For the majority of women, oral contraceptives can be taken safely. But for some women oral contraceptive use is associated with certain serious medical problems that can be life-threatening or may cause temporary or permanent disability or death. The risks associated with taking oral contraceptives increase significantly if you:

• Smoke
  
• Have high blood pressure, diabetes, high cholesterol, or are obese
  
• Have or have had clotting disorders, heart attack, stroke, angina pectoris (severe chest pains), cancer of the breast or sex organs, jaundice, or malignant or benign liver tumors

You should not take the pill if you are pregnant or have unexplained vaginal bleeding.

Although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy, non-smoking women (even with the newer low-dose formulations), there are also greater potential health risks associated with pregnancy in older women.

Most side effects of the pill are not serious. The most common are nausea, vomiting, bleeding or spotting between menstrual periods, weight gain, breast tenderness, and difficulty wearing contact lenses. These side effects, especially nausea and vomiting, may decrease or subside within the first three months of use.

The serious side effects of the pill occur very infrequently, especially if you are in good health and do not smoke. However, you should know that the following medical conditions have been associated with or made worse by the pill:

1. Blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), stoppage or rupture of a blood vessel in the brain (stroke), blockage of blood vessels in the heart (heart attack or angina pectoris), or other organs of the body. As mentioned above, smoking increases the risk of heart attacks and strokes and subsequent serious medical consequences. Women with migraine headaches also may be at increased risk of stroke when taking the pill.

2. Liver tumors, which may rupture and cause severe bleeding. A possible but not definite association has been found with the pill and liver cancer. However, liver cancers are extremely rare. The chance of developing liver cancer from using the pill is thus even rarer.

3. High blood pressure, although blood pressure usually returns to normal when the pill is stopped.

The symptoms associated with these serious side effects are discussed in the DETAILED PATIENT INFORMATION leaflet given to you with your supply of pills. Notify your healthcare provider if you notice any unusual physical disturbances while taking the pill. In addition, drugs such as rifampin, as well as some anticonvulsants and some antibiotics, and herbal preparations containing St. John's Wort (hypericum perforatum), may decrease oral contraceptive effectiveness.

Breast cancer has been diagnosed slightly more often in women who use the pill than in women of the same age who do not use the pill. This very small increase in the number of breast cancer diagnoses gradually disappears during the 10 years after stopping use of the pill. It is not known whether the difference is caused by the pill. It may be that women taking the pill are examined more often, so that breast cancer is more likely to be detected. You should have regular breast examinations by a healthcare provider and examine your own breasts monthly. Tell your healthcare provider if you have a family history of breast cancer or if you have had breast nodules or an abnormal mammogram. Women who currently have or have had breast cancer should not use hormonal contraceptives because breast cancer is usually a hormone-sensitive tumor.

Some studies have found an increase in the incidence of cancer or precancerous lesions of the cervix in women who use the pill. However, this finding may be related to factors other than the use of the pill. 

Taking the combination pill provides some important noncontraceptive health benefits. These include less painful menstruation, less menstrual blood loss and anemia, fewer pelvic infections, and fewer cancers of the ovary and the lining of the uterus.

Be sure to discuss any medical condition you may have with your healthcare provider. Your healthcare provider will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the healthcare provider believes that it is a good medical practice to postpone it. You should be reexamined at least once a year while taking oral contraceptives. The DETAILED PATIENT INFORMATION leaflet gives you further information which you should read and discuss with your healthcare provider.

DOSAGE AND ADMINISTRATION

HOW TO TAKE Microgestin 24 Fe

BEFORE YOU START TAKING YOUR PILLS:

1. BE SURE TO READ THESE DIRECTIONS:
   • Before you start taking your pills
   • Anytime you are not sure what to do
   
2. TAKE ONE PILL EVERY DAY AT THE SAME TIME. If you miss pills you could get pregnant. This includes starting the pack late. The more pills you miss, the more likely you are to get pregnant.
   
3. MANY WOMEN HAVE SPOTTING OR LIGHT BLEEDING, OR MAY FEEL SICK TO THEIR STOMACH WHILE TAKING THE FIRST 1 to 3 PACKS OF PILLS.
   If you have spotting or light bleeding or feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If it doesn't go away, check with your healthcare provider.
   
4. MISSING PILLS CAN ALSO CAUSE SPOTTING OR LIGHT BLEEDING, even if you take these missed pills. On the days you take 2 pills to make up for missed pills, you could also feel a little sick to your stomach.
   
5. IF YOU HAVE VOMITING (within 3 to 4 hours after you take your pill), you should follow the instructions for WHAT TO DO IF YOU MISS PILLS. IF YOU HAVE DIARRHEA or IF YOU TAKE CERTAIN MEDICINES, including some antibiotics, or the herbal supplement St. John’s Wort, your pills may not work as well. Use a back-up method of birth control (such as condoms or spermicide) until you check with your healthcare provider.
   
6. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your healthcare provider about how to make pill-taking easier or about using another method of birth control.
   
7. IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS LEAFLET, call your healthcare provider.

1. DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL.
   It is important to take it at about the same time every day.
   
2. LOOK AT YOUR PILL PACK:
   Microgestin 24 Fe contains 24 "active" WHITE PILLS (with hormones) for
   WEEKS 1, 2, 3 and the first part of WEEK 4, and 4 "reminder" BROWN
   PILLS (without hormones) for the last part of WEEK 4.

3. ALSO FIND:

• where on the pack to start taking pills,
  
• in what order to take the pills (follow the arrows), and
  
• the week numbers as shown in the picture above.

4. BE SURE YOU HAVE READY AT ALL TIMES:

• ANOTHER KIND OF BIRTH CONTROL (such as condoms or spermicide) to use as a back-up in case you miss pills.
  
• AN EXTRA, PILL PACK.

You have a choice of which day to start taking your first pack of pills. Decide with your healthcare provider which is the best day for you. Pick a time of day that will be easy to remember.

DAY-1 START:

1. Pick the day label strip that starts with the first day of your period. (This is the
   day you start bleeding or spotting, even if it is almost midnight when the bleeding begins.)
   
2. Place this day label strip on the tablet dispenser over the area that has the days of the week (starting with Sunday) printed on the plastic.
   
3. Take the first white pill of the first pack during the first 24 hours of your period.
   
4. You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period.

SUNDAY START:

1. Take the first white pill of the first pack on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the pack that same day.
   
2. Use another method of birth control as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days). Condoms or spermicide are good back-up methods of birth control.

WHEN YOU SWITCH FROM A DIFFERENT METHOD OF HORMONAL CONTRACEPTION

• If your previous method had 28 pills, finish taking all 28 pills, then start taking Microgestin 24 Fe on the day after the last pill.
  
• If your previous method had 21 pills, finish taking all 21 pills, and wait 7 days before starting Microgestin 24 Fe.
  
• When you switch from a vaginal ring or skin patch, finish the 21 days of use, and wait 7 days after removal of the ring or patch before starting Microgestin 24 Fe.
  
• When you switch from a progestin-only pill, you should start Microgestin 24 Fe the next day.
  
• When you switch from an implant or injectable contraceptive, you should start Microgestin 24 Fe on the day of implant removal or, if using an injectable contraceptive, the day on which the next injection would be due.

1. TAKE ONE PILL AT THE SAME TIME EVERY DAY UNTIL THE PACK IS EMPTY.
Do not skip pills even if you are spotting or bleeding between monthly periods or feel sick to your stomach (nausea).
Do not skip pills even if you do not have sex very often.

2. WHEN YOU FINISH A PACK OF YOUR Microgestin 24 Fe:
Start the next pack on the day after your last brown “reminder" pill. Do not wait any days between packs.

Birth control pills may not be as effective if you miss any white pills, and particularly if you miss the first few or the last few white pills in a pack.

If you MISS 1 white pill:

1. Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day.
   
2. You do not need to use a back-up birth control method if you have sex.

If you MISS 2 white pills in a row in WEEK 1 OR WEEK 2 of your pack:

1. Take 2 pills on the day you remember and 2 pills the next day.
   
2. Then take 1 pill a day until you finish the pack.
   
3. You COULD BECOME PREGNANT if you have sex during the 7 days after you restart your pills. You MUST use a non-hormonal birth control method (such as condoms or spermicide) as a back-up for those 7 days.

If you MISS 2 white pills in a row in WEEK 3 or WEEK 4 of your pack:

1. If you are a Day 1 Starter:
   THROW OUT the rest of the pill pack and start a new pack that same day.
   If you are a Sunday Starter:
   Keep taking 1 pill every day until Sunday.
   On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day.
   
2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your healthcare provider because you might be pregnant.
   
3. You COULD BECOME PREGNANT if you have sex during the 7 days after you restart your pills. You MUST use a non-hormonal birth control method (such as condoms or spermicide) as a back-up for those 7 days after you restart your pills.
   

If you MISS 3 OR MORE white pills in a row at any time:

1. If you are a Day 1 Starter:
   THROW OUT the rest of the pill pack and start a new pack that same day.
   If you are a Sunday Starter:
   Keep taking 1 pill every day until Sunday.
   On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day.
   
2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your healthcare provider because you might be pregnant.
   
3. You COULD BECOME PREGNANT if you have sex on the days when you missed pills or during the first 7 days after restarting your pills. You MUST use a non-hormonal birth control method (such as condoms or spermicide) as a back-up the next time you have sex and for the first 7 days after you restart your pills.

If you forget any of the 4 brown "reminder" pills in Week 4:

1. THROW AWAY the pills you missed.
   
2. Keep taking 1 pill each day until the pack is empty.
   
3. You do not need to use a back-up method of birth control.

FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED:

1. Use a BACK-UP METHOD of birth control anytime you have sex.
   
2. KEEP TAKING ONE WHITE PILL EACH DAY until you can reach your healthcare provider.

DETAILED PATIENT PACKAGE INSERT

Microgestin 24 Fe  

Rx only

This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

INTRODUCTION
Any woman who considers using oral contraceptives (the “birth control pill” or “the pill”) should understand the benefits and risks of using this form of birth control.

Although oral contraceptives have important advantages over other methods of contraception, they have certain risks that no other method has, and some of these risks may continue after you have stopped using the oral contraceptive. This leaflet will give you much of the information you will need to make this decision and will also help you determine if you are at risk of developing any of the serious side effects of the pill. It will tell you how to use Microgestin 24 Fe properly so that it will be as effective as possible. However, this booklet is not a replacement for a careful discussion between you and your healthcare provider. You should discuss the information provided in this booklet with your healthcare provider, both when you first start taking the pill and during your revisits. You should also follow your healthcare provider’s advice with regard to regular check-ups while you are on Microgestin 24 Fe.

EFFECTIVENESS OF ORAL CONTRACEPTIVES
Oral contraceptives or “birth control pill” or “the pill” are used to prevent pregnancy and are more effective than most other nonsurgical methods of birth control. The chance of becoming pregnant is approximately 1% per year (1 pregnancy per 100 women per year of use) when the pills are taken correctly, and no pills are missed. Typical failure rates are 5% per year when women who miss pills are included. The chance of becoming pregnant increases with each missed "active" hormonal pill during a 28-day cycle.

In comparison, typical failure rates for other methods of birth control during the first year of use are as follows:

No birth control methods: 85%
Vaginal sponge: 20 to 40%
Cervical cap: 20 to 40%
Spermicides alone: 26%
Periodic abstinence: 25%
Condom (female): 21%
Diaphragm with spermicides: 20%
Withdrawal: 19%
Condom (male): 14%
Female sterilization: less than 1%
IUD:  less than 1-2%
Injectable progestogen: less than 1%
Male sterilization: less than 1%
Norplant® system: less than 1%

WHO SHOULD NOT TAKE ORAL CONTRACEPTIVES

Some women should not use the pill. You should not use the pill if you have or have ever had any of the following conditions:

• A history of heart attack or stroke
  
• A history of blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), or eyes
  
• A history of blood clots in the deep veins of your legs
  
• Chest pain (angina pectoris)
  
• Known or suspected breast cancer or cancer of the lining of the uterus, cervix, vagina, or certain hormonally-sensitive cancers
  
• Unexplained vaginal bleeding (until a diagnosis is reached by your healthcare provider)
  
• Yellowing of the whites of the eyes or of the skin (jaundice) during pregnancy or during previous use of hormonal contraceptives of any type (the pill, patch, vaginal ring, injection, or implant)
  
• Liver tumor (benign or cancerous)
  
• Known or suspected pregnancy
  
• Heart valve or heart rhythm disorders that may be associated with formation of blood clots
  
• Diabetes with complications of the kidneys, eyes, nerves, or blood vessels
  
• Severe high blood pressure
  
• Active liver disease with abnormal liver function tests
  
• Allergy or hypersensitivity to any of the components of Microgestin 24 Fe
  
• A need for surgery with prolonged bedrest
  
• Headaches with neurological symptoms

Tell your healthcare provider if you have any of the above conditions. Your healthcare provider can recommend a safer method of birth control.

OTHER CONSIDERATIONS BEFORE TAKING ORAL CONTRACEPTIVES

Tell your healthcare provider if you have or ever have had:

• Breast nodules, fibrocystic disease of the breast or an abnormal breast x-ray or mammogram
  
• Diabetes
  
• Elevated cholesterol or triglycerides
  
• High blood pressure
  
• Migraine or other headaches or epilepsy
  
• Depression
  
• Gallbladder, liver, heart, or kidney disease
  
• Scanty or irregular menstrual periods

Women with any of these conditions should be checked often by their healthcare provider if they choose to use oral contraceptives.

Talk to your healthcare provider about using Microgestin 24 Fe if you:

• Smoke
  
• Recently had a baby
  
• Recently had a miscarriage or abortion
  
• Are breastfeeding
  
• Are taking any other medications

RISKS OF TAKING ORAL CONTRACEPTIVES

1. Risk of developing blood clots

Blood clots and blockage of blood vessels are the most serious side effects of taking oral contraceptives and can cause death or serious disability. In particular, a clot in the legs can cause thrombophlebitis, and a clot that travels to the lungs can cause a sudden blocking of the vessel carrying blood to the lungs. Either of these can cause death or disability. Rarely, clots occur in the blood vessels of the eye and may cause blindness, double vision, or impaired vision.

If you take oral contraceptives and need elective surgery, need to stay in bed for a prolonged illness or injury, or have recently delivered a baby, you may be at risk of developing blood clots. You should consult your healthcare provider about stopping oral contraceptives four weeks before surgery and not taking oral contraceptives for two weeks after surgery or during bed rest. You should also not take oral contraceptives soon after delivery of a baby. It is advisable to wait for at least four weeks after delivery if you are not breastfeeding. If you are breastfeeding, you should wait until you have weaned your child before using the pill (see the section on breastfeeding in GENERAL PRECAUTIONS).

The risk of circulatory disease in oral contraceptive users may be higher in users of high-dose pills (containing 50 micrograms or higher of ethinyl estradiol) and may be greater with longer duration of oral contraceptive use. In addition, some of these increased risks may continue for a number of years after stopping oral contraceptives. The risk of abnormal blood clotting increases with age in both users and nonusers of oral contraceptives, but the increased risk from the oral contraceptive appears to be present at all ages. For women aged 20 to 44 it is estimated that about 1 in 2,000 using oral contraceptives will be hospitalized each year because of abnormal clotting. Among nonusers in the same age group, about 1 in 20,000 would be hospitalized each year. For oral contraceptive users in general, it has been estimated that in women between the ages of 15 and 34 the risk of death due to a circulatory disorder is about 1 in 12,000 per year, whereas for nonusers the rate is about 1 in 50,000 per year. In the age group 35 to 44, the risk is estimated to be about 1 in 2,500 per year for oral contraceptive users and about 1 in 10,000 per year for nonusers.

2. Heart attacks and strokes

Oral contraceptives may increase the tendency to develop strokes (stoppage or rupture of blood vessels in the brain) and angina pectoris and heart attacks (blockage of blood vessels in the heart). Any of these conditions can cause death or disability.

Smoking greatly increases the possibility of suffering heart attacks and strokes. Furthermore, smoking and the use of oral contraceptives greatly increase the chances of developing and dying of heart disease.

Women with migraine (especially migraine with aura) who take oral contraceptives also may be at higher risk of stroke.

3. Gallbladder disease

Oral contraceptive users probably have a greater risk than nonusers of having gallbladder disease, although this risk may be related to pills containing high doses of estrogens.

4. Liver tumors

In rare cases, oral contraceptives can cause benign but dangerous liver tumors. These benign liver tumors can rupture and cause fatal internal bleeding. In addition, a possible, but not definite, association has been found with the pill and liver cancers in two studies, in which a few women who developed these very rare cancers were found to have used oral contraceptives for long periods. However, liver cancers in general are extremely rare, and the chance of developing liver cancer from using the pill is thus even rarer.

5. Cancer of the breast and reproductive organs

Breast cancer has been diagnosed slightly more often in women who use the pill than in women of the same age who do not use the pill. This small increase in the number of breast cancer diagnoses gradually disappears during the 10 years after stopping use of the pill. It is not known whether the difference is caused by the pill. It may be that women taking the pill are examined more often, so that breast cancer is more likely to be detected. You should have regular breast examinations by a healthcare provider and examine your own breasts monthly. Tell your healthcare provider if you have a family history of breast cancer or if you have had breast nodules or an abnormal mammogram.

Women who currently have or have had breast cancer should not use oral contraceptives because breast cancer is usually a hormone-sensitive tumor.

Some studies have found an increase in the incidence of cancer or precancerous lesions of the cervix in women who use oral contraceptives. However, this finding may be related to factors other than the use of oral contraceptives. There is insufficient evidence to rule out the possibility that the pill may cause such cancers.

6. Lipid metabolism and inflammation of the pancreas

In patients with inherited defects of lipid metabolism, there have been reports of significant elevations of plasma triglycerides during estrogen therapy. This has led to pancreatitis in some cases.

ESTIMATED RISK OF DEATH FROM A BIRTH CONTROL METHOD OR PREGNANCY

All methods of birth control and pregnancy are associated with a risk of developing certain diseases which may lead to disability or death. An estimate of the number of deaths associated with different methods of birth control and pregnancy has been calculated and is shown in the following table.

In the above table, the risk of death from any birth control method is less than the risk of childbirth, except for oral contraceptive users over the age of 35 who smoke and pill users over the age of 40 even if they do not smoke. It can be seen in the table that for women aged 15 to 39, the risk of death was highest with pregnancy (7 to 26 deaths per 100,000 women, depending on age). Among pill users who do not smoke, the risk of death was always lower than that associated with pregnancy for any age group less than 40. Over the age of 40, the risk increases to 32 deaths per 100,000 women, compared to 28 deaths associated with pregnancy in that age group. However, for pill users who smoke and are over the age of 35, the estimated number of deaths exceeds those associated with pregnancy. If a woman is over the age of 40 and smokes, her estimated risk of death is four times higher (117/100,000 women) than the estimated risk associated with pregnancy (28/100,000 women) in that age group.

The suggestion that women over 40 who don't smoke should not take oral contraceptives is based on information from older high-dose pills. An Advisory Committee of the FDA discussed this issue in 1989 and recommended that the benefits of oral contraceptive use by healthy, nonsmoking women over 40 years of age may outweigh the possible risks. Older women, as all women who take oral contraceptives, should take an oral contraceptive which contains the least amount of estrogen and progestin that is compatible with the individual patient needs.

WARNING SIGNALS

If any of these adverse conditions occur while you are taking oral contraceptives, call your healthcare provider immediately:

• Sharp chest pain, coughing of blood, or sudden shortness of breath (indicating a possible clot in the lung)
  
• Pain in the calf (indicating a possible clot in the leg)
  
• Crushing chest pain or heaviness in the chest (indicating a possible heart attack)
  
• Sudden severe headache or vomiting, dizziness or fainting, disturbances of vision or speech, weakness, or numbness in an arm or leg (indicating a possible stroke)
  
• Sudden partial or complete loss of vision (indicating a possible clot in the eye)
  
• Breast lumps (indicating possible breast cancer or fibrocystic disease of the breast; ask your healthcare provider to show you how to examine your breasts)
  
• Severe pain or tenderness in the stomach area (possibly indicating a ruptured liver tumor)
  
• Difficulty in sleeping, weakness, lack of energy, fatigue, or change in mood (possibly indicating severe depression)
  
• Jaundice or a yellowing of the skin or eyeballs, accompanied frequently by fever, fatigue, loss of appetite, dark-colored urine, or light-colored bowel movements (indicating possible liver problems)