LO/OVRAL- norgestrel and ethinyl estradiol tablet
Wyeth Pharmaceuticals Company
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs are contraindicated in women who are over 35 years of age and smoke [see Contraindications].
LO/OVRAL-28 is a combination oral contraceptive containing the progestational compound norgestrel and the estrogenic compound ethinyl estradiol. Norgestrel is designated as (2) (±)-13-Ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one and ethinyl estradiol is designated as (19-nor-17α-pregna-1,3,5 (10)-trien-20-yne-3,17-diol). Each white active LO/OVRAL tablet contains 0.3 mg norgestrel and 0.03 mg ethinyl estradiol and inert ingredients.
Each pink placebo tablet contains only inert ingredients:
Inert ingredients: cellulose, D&C Red 30, lactose, magnesium stearate, and polacrilin potassium.
Each pill pack contains 21 white active tablets and 7 pink inert tablets.
|C21H28O2 M.W. 312.45||C20H24O2 M.W. 296.40|
LO/OVRAL-28 is indicated for use by females of reproductive potential to prevent pregnancy.
In a study of 1,287 women with a total of 11,085 cycles or 852.7 women-years of usage, the pregnancy rate in women age 15–40 years was approximately 1 pregnancy per 100 women-years of use.
Do not prescribe LO/OVRAL-28 to women who are known to have any of the following conditions:
Combination oral contraceptives should not be used in women who are receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations (see Warnings, Risk of liver enzyme elevations with concomitant hepatitis c treatment).
Do not use LO/OVRAL-28 in women with liver disease, such as acute viral hepatitis or severe (decompensated) cirrhosis of the liver [see Contraindications]. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded. Discontinue LO/OVRAL-28 if jaundice develops.
LO/OVRAL-28 is contraindicated in women with benign and malignant liver tumors [see Contraindications]. Hepatic adenomas are associated with COC use. An estimate of the attributable risk is 3.3 cases/100,000 users. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage.
Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) COC users. However the risk of liver cancers in COC users approaches less than one case per million users.
During clinical trials with the Hepatitis C combination drug regimen that contains ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN), including some cases greater than 20 times the ULN, were significantly more frequent in women using ethinyl estradiol-containing medications such as COCs. Discontinue LO/OVRAL-28 prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see Contraindications]. LO/OVRAL-28 can be restarted approximately 2 weeks following completion of treatment with the combination drug regimen.
LO/OVRAL-28 is contraindicated in women with uncontrolled hypertension or hypertension with vascular disease [see Contraindications]. For women with well-controlled hypertension, monitor blood pressure and stop LO/OVRAL-28 if blood pressure rises significantly.
An increase in blood pressure has been reported in women taking COCs, and this increase is more likely in older women with extended duration of use. The incidence of hypertension increases with increasing quantities of progestin.
Studies suggest a small increased relative risk of developing gallbladder disease among COC users. Use of COCs may worsen existing gallbladder disease. A past history of COC-related cholestasis predicts an increased risk with subsequent COC use. Women with a history of pregnancy-related cholestasis may be at an increased risk for COC related cholestasis.
Carefully monitor prediabetic and diabetic women who take LO/OVRAL-28. COCs may decrease glucose tolerance.
Consider alternative contraception for women with uncontrolled dyslipidemia. A small proportion of women will have adverse lipid changes while on COCs.
Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs.
If a woman taking LO/OVRAL-28 develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue LO/OVRAL-28 if indicated.
Consider discontinuation of LO/OVRAL-28 in the case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event).
Unscheduled (breakthrough or intracyclic) bleeding and spotting sometimes occur in patients on COCs, especially during the first three months of use. If bleeding persists or occurs after previously regular cycles, check for causes such as pregnancy or malignancy. If pathology and pregnancy are excluded, bleeding irregularities may resolve over time or with a change to a different contraceptive product.
In 1,287 patients (pooled data from a number of studies), unscheduled bleeding was recorded in 15% of first cycles and by Cycle 12 was 5%. In total, 23% of subjects reported spotting, 20% reported unscheduled bleeding, and 2% reported change in menstrual flow at some point in the studies.
In the studies, 1.2% discontinued use of the product due to breakthrough bleeding and 1% discontinued due to spotting.
Women who use LO/OVRAL-28 may experience amenorrhea. A total of 9% of subjects in the studies reported amenorrhea in one or more cycles.
Some women may experience amenorrhea or oligomenorrhea after discontinuation of COCs, especially when such a condition was pre-existent.
If scheduled (withdrawal) bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy.
The estrogen component of COCs may raise the serum concentrations of thyroxine-binding globulin, sex hormone-binding globulin, and cortisol-binding globulin. The dose of replacement thyroid hormone or cortisol therapy may need to be increased.
In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.
Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while taking LO/OVRAL-28.
Consult the labeling of all concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.
Do not co-administer LO/OVRAL-28 with HCV drug combinations containing ombitasvir/ paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations (see Warnings, Risk of liver enzyme elevations with concomitant hepatitis c treatment).
Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of COCs and potentially diminish the effectiveness of COCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate rifabutin, rufinamide, aprepitant, and products containing St. John's wort. Interactions between hormonal contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with COCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability.
Co-administration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20–25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. Concomitant administration of CYP3A4 inhibitors such as itraconazole, fluconazole, grapefruit juice or ketoconazole may increase plasma hormone concentrations.
Significant changes (increase or decrease) in the plasma concentrations of the estrogen and/or progestin have been noted when COCs are co-administered with some HIV protease inhibitors (decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir], or increase [e.g., indinavir and atazanavir/ritonavir] HCV protease inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]).
COCs containing EE may inhibit the metabolism of other drugs (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations. COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in the plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary.
Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentration of thyroid-binding globulin increases with use of COCs.
The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.
There is little or no increased risk of birth defects in women who inadvertently use COCs during early pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb reduction defects) following exposure to low dose COCs prior to conception or during early pregnancy.
Discontinue LO/OVRAL-28 use if pregnancy is confirmed.
Do not administer COCs to induce withdrawal bleeding as a test for pregnancy. Do not use COCs during pregnancy to treat threatened or habitual abortion.
Advise the nursing mother to use other forms of contraception, when possible, until she has weaned her child. COCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women. Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk.
Safety and efficacy of LO/OVRAL-28 tablets have been established in women of reproductive age. Efficacy is expected to be the same for post-pubertal adolescents under the age of 16 and for users 16 years and older. Use of LO/OVRAL-28 before menarche is not indicated.
LO/OVRAL-28 has not been studied in postmenopausal women and is not indicated in this population.
Counsel patients about the following information:
An increased risk of the following serious adverse reactions (see Warnings section for additional information) has been associated with the use of oral contraceptives:
Adverse reactions commonly reported by COC users are:
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 rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety of LO/OVRAL-28 was evaluated in 1,343 healthy women of child-bearing potential who participated in 9 clinical trials and received at least one dose of LO/OVRAL-28 for contraception. Subjects were exposed for a total of 11,085 cycles, with 429 women completing one year of exposure. Subjects ranged in age from 15–40 years. Demographics were 69% Caucasian, 28% Black, and 3% other.
Common Adverse Reactions (≥ 2% of women):
A total of 8% of subjects discontinued the trials prematurely due to an adverse reaction, most commonly due to unscheduled bleeding, spotting, headache (including migraine), nausea, acne, changes in menstrual flow, weight increase, nervousness, high blood pressure, and depression.
The following additional adverse drug reactions have been reported from worldwide postmarketing experience with LO/OVRAL-28. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Arterial Events: Arterial thromboembolism, Myocardial infarction, Cerebral hemorrhage
Eye Disorder: Optic neuritis, which may lead to partial or complete loss of vision, Intolerance to contact lenses, Change (steepening) in corneal curvature
Gastrointestinal Disorders: Colitis, Nausea, Pancreatitis
Hepatobiliary Disorders: Gallbladder disease, Cholestatic jaundice, Budd-Chiari syndrome
Immune System Disorders: Anaphylactic/anaphylactoid reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms
Metabolism and Nutrition Disorders: Carbohydrate and lipid effects, Porphyria, exacerbation of Porphyria
Neoplasms, Benign, Malignant, and Unspecified: Carcinoma of the reproductive organs and breasts, Hepatic neoplasia (including hepatic adenomas or benign liver tumors)
Psychiatric Disorders: Mood changes
Reproductive System and Breast Disorders: Temporary infertility after discontinuation of treatment, Changes in libido, Vaginitis, including candidiasis; Breast secretion
Skin and Subcutaneous Tissue Disorders: Melasma/chloasma, which may persist; Erythema multiforme, Erythema nodosum, Hemorrhagic eruption, Hirsutism
Vascular Events: Venous thrombosis, Pulmonary embolism, Cerebral thrombosis, Mesenteric thrombosis, Retinal vascular thrombosis
There have been no reports of serious ill effects from overdosage of oral contraceptives, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea.
To achieve maximum contraceptive effectiveness, LO/OVRAL-28 (norgestrel and ethinyl estradiol tablets) must be taken exactly as directed and at intervals not exceeding 24 hours.
The dosage of LO/OVRAL-28 is one white tablet daily for 21 consecutive days, followed by one pink inert tablet daily for 7 consecutive days, according to prescribed schedule. It is recommended that LO/OVRAL-28 tablets be taken by mouth at the same time each day.
Consider the possibility of ovulation and conception prior to initiation of medication.
Instruct the patient to begin taking LO/OVRAL-28 on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, the first tablet (white) is taken that day. The patient should take one white tablet daily for 21 consecutive days followed by one pink inert tablet daily for 7 consecutive days. Withdrawal bleeding will usually occur within 3 days following discontinuation of white tablets and may not have finished before the next pack is started. During the first cycle, the patient should not rely on LO/OVRAL-28 for contraception until a white tablet has been taken daily for 7 consecutive days and she should use a non-hormonal back-up method of birth control during those 7 days.
The patient is to begin her next and all subsequent 28-day courses of tablets on the same day of the week (Sunday) on which she began her first course, following the same schedule: 21 days of white tablets, followed by 7 days of pink inert tablets. If in any cycle the patient starts tablets later than the proper day, instruct her to 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.
If spotting or breakthrough bleeding occurs, instruct the patient to continue on the same regimen. This type of bleeding is usually transient and without significance; however, advise the patient to consult her healthcare provider if the bleeding is persistent or prolonged.
The possibility of ovulation and pregnancy increases with each successive day that scheduled white tablets are missed. If withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (if she missed one or more tablets or started taking them on a day later than she should have), consider the probability of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy.
For additional patient instructions regarding missed tablets, see the WHAT TO DO IF YOU MISS PILLS section in FDA-Approved Patient Labeling below.
In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken. If vomiting or diarrhea occurs within 3 to 4 hours after taking an active tablet, handle this as a missed tablet [see FDA-Approved Patient Labeling].
LO/OVRAL-28 Tablets (0.3 mg norgestrel and 0.03 mg ethinyl estradiol) are available in packages of 6 PILPAK® dispensers, each containing 28 tablets as follows:
What is the most important information I should know about LO/OVRAL-28 ?
Do not use LO/OVRAL-28 if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects from hormonal birth control pills, including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you smoke.
What is LO/OVRAL-28?
LO/OVRAL-28 is a birth control pill (oral contraceptive) used by women to prevent pregnancy.
How does LO/OVRAL-28 work for contraception?
Your chance of getting pregnant depends on how well you follow the directions for taking your birth control pills. The better you follow the directions, the less chance you have of getting pregnant.
Based on the results of clinical studies, about 1 out of 100 women may get pregnant during the first year they use LO/OVRAL-28.
The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant.
Who should not take LO/OVRAL-28?
Do not take LO/OVRAL-28 if you:
You should not take the pill if you take any Hepatitis C drug combination containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. This may increase levels of the liver enzyme "alanine aminotransferase" (ALT) in the blood.
If any of these conditions happen while you are taking LO/OVRAL-28, stop taking LO/OVRAL-28 right away and talk to your healthcare provider. Use non-hormonal contraception when you stop taking LO/OVRAL-28.
What should I tell my healthcare provider before taking LO/OVRAL-28?
Tell your healthcare provider if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.
LO/OVRAL-28 may affect the way other medicines work, and other medicines may affect how well LO/OVRAL-28 works.
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
How should I take LO/OVRAL-28?
Read the Instructions for Use at the end of this Patient Information.
What are the possible serious side effects of LO/OVRAL-28?
Serious blood clots can happen especially if you smoke, are obese, or are older than 35 years of age. Serious blood clots are more likely to happen when you:
Call your healthcare provider or go to a hospital emergency room right away if you have:
Other serious side effects include:
What are the most common side effects of LO/OVRAL-28?
These are not all the possible side effects of LO/OVRAL-28. For more information, ask your healthcare provider or pharmacist.
You may report side effects to the FDA at 1-800-FDA-1088.
What else should I know about taking LO/OVRAL-28?
How should I store LO/OVRAL-28?
General information about the safe and effective use of LO/OVRAL-28:
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use LO/OVRAL-28 for a condition for which it was not prescribed. Do not give LO/OVRAL-28 to other people, even if they have the same symptoms that you have.
This Patient Information summarizes the most important information about LO/OVRAL-28. You can ask your pharmacist or healthcare provider for information about LO/OVRAL-28 that is written for health professionals.
For more information, call 1-800-438-1985.
Do birth control pills cause cancer?
Birth control pills do not seem to cause breast cancer. However, if you have breast cancer now, or have had it in the past, do not use birth control pills because some breast cancers are sensitive to hormones.
Women who use birth control pills may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as having more sexual partners.
What if I want to become pregnant?
You may stop taking the pill whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy checkup before you stop taking the pill.
What should I know about my period when taking LO/OVRAL-28?
Your periods may be lighter and shorter than usual. Some women may miss a period. Irregular vaginal bleeding or spotting may happen while you are taking LO/OVRAL-28, especially during the first few months of use. This usually is not a serious problem. It is important to continue taking your pills on a regular schedule to prevent a pregnancy.
What are the ingredients in LO/OVRAL-28?
Each white pill contains norgestrel and ethinyl estradiol.
White pills: cellulose, lactose, magnesium stearate, and polacrilin potassium.
Pink pills: cellulose, D&C Red 30, lactose, magnesium stearate, and polacrilin potassium.
Important Information about taking LO/OVRAL-28
BEFORE YOU START TAKING LO/OVRAL-28
WHEN TO START THE FIRST PACK OF PILLS
WHAT TO DO DURING THE MONTH
IF YOU SWITCH FROM ANOTHER BRAND OF COMBINATION PILLS:
If your previous brand had 21 pills: Wait 7 days to start taking LO/OVRAL. You will probably have your period during that week. Ideally, be sure that no more than 7 days pass between the 21-day pack and taking the first white LO/OVRAL pill ("active" with hormone). If you start LO/OVRAL more than 7 days after taking the last pill of your previous contraceptive, you must use a non-hormonal back-up method of birth control during the first 7 days of LO/OVRAL use.
If your previous brand had 28 pills: Start taking the first white LO/OVRAL pill ("active" with hormone) on the day after your last reminder pill. Ideally, do not wait any days between packs. If you do skip any days between the last pill of your previous contraceptive and starting LO/OVRAL, you must use a non-hormonal back-up method of birth control during the first 7 days of LO/OVRAL-28 use.
IF YOU SWITCH FROM ANOTHER TYPE OF BIRTH CONTROL METHOD:
If you were previously taking a progestin-only PILL: You may switch to LO/OVRAL on any day from a progestin-only pill and should start taking the first white LO/OVRAL pill ("active" with hormone) the day after you take your last progestin-only pill. In addition, use a non-hormonal back-up method of birth control for the first 7 days of tablet-taking.
If you are switching from a contraceptive vaginal ring or transdermal patch: Start taking the first white LO/OVRAL pill ("active" with hormone) on the day that you would have inserted a new ring or applied a new patch.
If you are switching from a contraceptive implant: Start taking the first white LO/OVRAL pill ("active" with hormone) on the day that the implant is removed.
If you are switching from a contraceptive injection: Start taking the first white LO/OVRAL pill ("active" with hormone) on the day that the next contraceptive injection is due.
If you are switching from an Intrauterine device (IUD) or Intrauterine system (IUS): Start taking the first white LO/OVRAL pill ("active" with hormone) on the day the IUD/IUS is removed. If your IUD/IUS is removed on the first day of your period you do not need to use an additional non-hormonal back up method of birth control. If the IUD/IUS is removed on any other day, use a non-hormonal back-up method of birth control for the first 7 days of tablet-taking.
LO/OVRAL-28 may not be as effective if you miss white "active" pills, and particularly if you miss the first few or the last few white "active" pills in a pack.
If you MISS 1 white "active" pill:
If you MISS 2 white "active" pills in a row in WEEK 1 OR WEEK 2 of your pack:
If you MISS 2 white "active" pills in a row in THE 3rd WEEK:
If you MISS 3 OR MORE white "active" pills in a row (during the first 3 weeks):
If you forget any of the 7 pink "reminder" pills in Week 4:
Throw away the pills you missed.
Keep taking 1 pill each day until the pack is empty.
You do not need a back-up non-hormonal birth control method if you start your next pack on time.
FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED
Use a back-up non-hormonal birth control method anytime you have sex.
Keep taking one pill each day until you can reach your healthcare provider.
|This product's label may have been revised after this insert was used in production. For further product information and current package insert, please-call our medical communications department toll-free at 1-800-438-1985.|
Wyeth Pharmaceuticals Inc.
Philadelphia, PA 19101