Lo Ovral

Smoking can increase your risk of blood clots, stroke, or heart attack caused by birth control pills, especially if you are older than 35.

This medication will not protect you from sexually transmitted diseases--including HIV and AIDS. Using a condom is the only way to protect yourself from these diseases.

Rx only

Patients should be counseled that oral contraceptives do not protect against transmission of HIV (AIDS) and other sexually transmitted diseases (STDs) such as chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis.

Oral contraceptives are indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception.

Oral contraceptives are highly effective. Table I 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, the IUD, and implants depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates.

Table I: Percentage Of Women Experiencing An Unintended Pregnancy During The First Year Of Typical Use And The First Year Of Perfect Use Of Contraception And The Percentage Continuing Use At The End Of The First Year. United States.

	% of Women Experiencing an Unintended Pregnancy within the First Year of Use		% of Women Continuing Use at One Year 3
Method (1)	Typical Use 1 (2)	Perfect Use 2 (3)	(4)
Lactation Amenorrhea Method: LAM is a highly effective, temporary method of contraception.9
Source: Trussell J. Contraceptive efficacy. In: Hatcher RA, Trussell J, Stewart F, Cates W, Stewart GK, Kowel D, Guest F. Contraceptive Technology: Seventeenth Revised Edition. New York NY: Irvington Publishers; 1998.
1. 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.
2. 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.
3. Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year.
4. The percents 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.
5. Foams, creams, gels, vaginal suppositories, and vaginal film.
6. Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases.
7. With spermicidal cream or jelly.
8. Without spermicides.
9. 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.
Chance 4	85	85
Spermicides 5	26	6	40
Periodic abstinence	25		63
Calendar		9
Ovulation Method		3
Sympto-Thermal 6		2
Post-Ovulation		1
Cap 7
Parous Women	40	26	42
Nulliparous Women	20	9	56
Sponge
Parous Women	40	20	42
Nulliparous Women	20	9	56
Diaphragm 7	20	6	56
Withdrawal	19	4
Condom 8
Female (Reality)	21	5	56
Male	14	3	61
Pill	5		71
Progestin only		0.5
Combined		0.1
IUD
Progesterone T	2.0	1.5	81
Copper T380A	0.8	0.6	78
LNg 20	0.1	0.1	81
Depo-Provera®	0.3	0.3	70
Levonorgestrel Implants (Norplant®)	0.05	0.05	88
Female Sterilization	0.5	0.5	100
Male Sterilization	0.15	0.10	100

Combination oral contraceptives should not be used in women with any of the following conditions:

  Thrombophlebitis or thromboembolic disorders   A past history of deep-vein thrombophlebitis or thromboembolic disorders   Cerebral-vascular or coronary-artery disease (current or history)   Thrombogenic valvulopathies   Thrombogenic rhythm disorders   Major surgery with prolonged immobilization   Diabetes with vascular involvement   Headaches with focal neurological symptoms   Uncontrolled hypertension   Known or suspected carcinoma of the breast or personal history of breast cancer   Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia   Undiagnosed abnormal genital bleeding   Cholestatic jaundice of pregnancy or jaundice with prior pill use   Hepatic adenomas or carcinomas, or active liver disease, as long as liver function has not returned to normal   Known or suspected pregnancy   Hypersensitivity to any of the components of Lo/Ovral

An increased risk of the following serious adverse reactions (see WARNINGS section for additional information) has been associated with the use of oral contraceptives:

Thromboembolic and thrombotic disorders and other vascular problems (including thrombophlebitis and venous thrombosis with or without pulmonary embolism, mesenteric thrombosis, arterial thromboembolism, myocardial infarction, cerebral hemorrhage, cerebral thrombosis), carcinoma of the reproductive organs and breasts, hepatic neoplasia (including hepatic adenomas or benign liver tumors), ocular lesions (including retinal vascular thrombosis), gallbladder disease, carbohydrate and lipid effects, elevated blood pressure, and headache including migraine.

The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug related (alphabetically listed):

  Acne   Amenorrhea   Anaphylactic/anaphylactoid reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms   Breakthrough bleeding   Breast changes: tenderness, pain, enlargement, secretion   Budd-Chiari syndrome   Cervical erosion and secretion, change in   Cholestatic jaundice   Chorea, exacerbation of   Colitis   Corneal curvature (steepening), change in   Diminution in lactation when given immediately postpartum   Dizziness   Edema/fluid retention   Erythema multiforme   Erythema nodosum   Gastrointestinal symptoms (such as abdominal pain, cramps, and bloating)   Hirsutism   Intolerance to contact lenses   Libido, changes in   Loss of scalp hair   Melasma/chloasma which may persist   Menstrual flow, change in   Mood changes, including depression   Nausea   Nervousness   Pancreatitis   Porphyria, exacerbation of   Rash (allergic)   Serum folate levels, decrease in   Spotting   Systemic lupus erythematosus, exacerbation of   Temporary infertility after discontinuation of treatment   Vaginitis, including candidiasis   Varicose veins, aggravation of   Vomiting   Weight or appetite (increase or decrease), change in  
The following adverse reactions have been reported in users of oral contraceptives:
  Cataracts   Cystitis-like syndrome   Dysmenorrhea   Hemolytic uremic syndrome   Hemorrhagic eruption   Optic neuritis, which may lead to partial or complete loss of vision   Porphyria   Premenstrual syndrome   Renal function, impaired

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

Lo/Ovral-28 can cause birth defects. Do not use if you are pregnant. Tell your doctor right away if you become pregnant, or if you miss two menstrual periods in a row. If you have recently had a baby, wait at least 4 weeks before taking Lo/Ovral-28. You should not take Lo/Ovral-28 if you have:

• untreated or uncontrolled high blood pressure;

• heart disease (coronary artery disease, uncontrolled heart valve disorder, history of heart attack, stroke, or blood clot);

• a blood-clotting disorder or circulation problems;

• problems with your eyes, kidneys or circulation caused by diabetes;

• a history of hormone-related cancer such as breast or uterine cancer;

• unusual vaginal bleeding that has not been checked by a doctor;

• liver disease or liver cancer;

• severe migraine headaches (with aura, numbness, weakness, or vision changes), especially if you are older than 35;

• a history of jaundice caused by pregnancy or birth control pills; or

• if you smoke and are over 35 years old.

To make sure you can safely take Lo/Ovral-28, tell your doctor if you have any of these other conditions:

• high blood pressure, varicose veins;

• high cholesterol or triglycerides, or if you are overweight;

• a history of depression;

• underactive thyroid;

• gallbladder disease;

• diabetes;

• seizures or epilepsy;

• a history of irregular menstrual cycles;

• tuberculosis; or

• a history of fibrocystic breast disease, lumps, nodules, or an abnormal mammogram.

The hormones in Lo/Ovral-28 can pass into breast milk and may harm a nursing baby. Lo/Ovral-28 may also slow breast milk production. Do not use if you are breast feeding a baby.

Get emergency medical help if you have any of these signs of an allergic reaction to Lo/Ovral-28: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using Lo/Ovral-28 and call your doctor at once if you have a serious side effect such as:

• sudden numbness or weakness, especially on one side of the body;

• sudden and severe headache, confusion, problems with vision, speech, or balance;

• chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;

• sudden cough, wheezing, rapid breathing, coughing up blood;

• pain, swelling, warmth, or redness in one or both legs;

• a change in the pattern or severity of migraine headaches;

• nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• swelling in your hands, ankles, or feet;

• a breast lump; or

• symptoms of depression (sleep problems, weakness, tired feeling, mood changes).

Less serious Lo/Ovral-28 side effects may include:

• mild nausea (especially when you first start taking this medicine), vomiting, bloating, stomach cramps;

• breast tenderness or swelling, nipple discharge;

• 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.

Some drugs can make Lo/Ovral-28 less effective, which may result in pregnancy. Before using Lo/Ovral-28, tell your doctor if you are using any of the following drugs:

• bosentan (Tracleer);

• an antibiotic or tuberculosis medication;

• drugs to treat hepatitis C, HIV, or AIDS;

• phenobarbital (Solfoton) and other barbiturates;

• St. John's wort; or

• seizure medications.

Tell your doctor about all other medicines you use, especially:

• dantrolene (Dantrium);

• tizanidine (Zanaflex); or

• tranexamic acid (Cyklokapron, Lysteda).

This list is not complete and other drugs may interact with Lo/Ovral-28. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Applies to ethinyl estradiol / norgestrel: oral tablet

Other

Many of the adverse effects experienced by women on oral contraceptive combination products are related to a relative excess or deficiency of the estrogen and progestin components of these formulations. The following categorizes many of the frequent adverse effects by relative excess or deficiency of these components.

Progestin Excess:

Acne, oily skin
Breast tenderness
Depression
Tiredness, fatigue
Hair loss
Hypertension
Increased appetite
Weight gain
Cholestatic jaundice

Progestin Deficiency:

Late breakthrough bleeding
Amenorrhea
Hypermenorrhea

Estrogen Excess:

Nausea
Headache
Melasma
Hypertension
Breast tenderness
Edema

Estrogen Deficiency:

Early/mid-cycle breakthrough bleeding
Increased spotting
Hypomenorrhea[Ref]

General

Women taking oral contraceptive combinations experience several non-contraceptive health benefits. These benefits include protection against two malignant neoplasms (endometrial carcinoma and ovarian cancer). In addition, use of oral contraceptive combinations decreases the frequency of benign breast tumors, ovarian cysts, ectopic pregnancy, menstrual irregularity, iron deficiency anemia, dysmenorrhea, and pelvic inflammatory disease.[Ref]

A number of studies have suggested that use of oral contraceptives decreases the risk of ovarian cancer. Specifically, the risk of epithelial ovarian cancers is decreased by 40%. The protection against ovarian cancer may last for 10 to 15 years after discontinuation of oral contraceptives. After long term use (12 years), the risk of ovarian cancer is decreased by as much as 80%.

The risk of endometrial cancer is decreased by approximately 50%. Protection may last for 15 years after discontinuation and may be greatest for nulliparous women who may be at higher risk for endometrial carcinoma than other women.

The incidence of hospitalization for pelvic inflammatory disease is approximately 50% lower in women taking oral contraceptives. The reason for the decrease in the frequency (or severity) of pelvic inflammatory disease in women taking oral contraceptives has not been fully elucidated.

Some recent studies have suggested that the decrease in frequency of functional ovarian cysts reported with some older formulations may not occur in women taking newer low dose formulations.

One recent study (The Nurses' Health Study) has suggested that long term use of oral contraceptives is safe and does not adversely affect long term risk for mortality.[Ref]

Gastrointestinal

Cases of oral contraceptive-induced esophageal ulceration and geographic tongue have been reported rarely.

More recent studies have suggested that the risk of gallbladder disease is minimal.[Ref]

A relatively common gastrointestinal side effect is nausea, which occurs in approximately 10% of treated women and may be more frequent during the first cycles of therapy. Some early reports suggested an association between oral contraceptive use and gallbladder disease.[Ref]

Oncologic

The World Health Organization committee also noted that some studies "have found a weak association between long-term use of oral contraceptives and breast cancer diagnosed before the age of 36, and perhaps up to the age 45....It is unclear whether this observed association is attributable to bias, the development of new cases of cancer, or accelerated growth of existing cancers."

The World Health Organization committee further concluded that there is no increased risk of breast cancer in women over the age of 45 who have previously taken oral contraceptives. In addition, studies suggest that use of oral contraceptives does not place specific groups of women (like those with a family history of breast cancer) at higher or lower risk, and variations in the hormonal content of oral contraceptives do not influence the risk of breast cancer.

In general, studies evaluating the potential risk of cervical cancer in patients taking oral contraceptives have been complicated by the large number of confounding factors which make investigations into the epidemiology of this neoplasm difficult. Some studies have suggested that women taking oral contraceptives are at increased risk of dysplasia, epidermoid carcinoma, and adenocarcinoma of the cervix. However, other studies have not found such an association.[Ref]

Oral contraceptive combinations have been studied extensively for oncologic side effects. A number of studies have examined a possible relationship between the use of oral contraceptives and the development of breast cancer. Many of the studies have reported conflicting results. A committee of the World Health Organization evaluated these studies and the risks of breast cancer and concluded that: "Numerous studies have found no overall association between oral contraceptive use and risk of breast cancer." In addition, the same committee also examined a possible relationship between oral contraceptive use and neoplasms of the uterine cervix and concluded that: "There are insufficient data to draw any firm conclusions regarding the effects of combined oral contraceptives on the risk of cervical adenocarcinoma."[Ref]

Cardiovascular

Cardiovascular side effects of the estrogen component of this combination drug may be significant and include hypertension. However, significant blood pressure increases generally occur only in women receiving high-dose estrogen products (50 mcg or more of ethinyl estradiol or equivalent daily). Estrogens have also been associated with edema. In addition, exogenous estrogens may exert cardio-protective effects by causing favorable changes in lipid profiles. These beneficial effects, however, may be partially or completely offset by alterations in lipid profiles induced by exogenous progestins.[Ref]

Detailed information concerning the effects of oral contraceptive therapy on lipid metabolism is available in the Endocrine paragraph of this side effect monograph.

Some early investigations of women taking high dose estrogen combinations (50 mcg or more of ethinyl estradiol or equivalent daily) suggested that such women may be at increased risk of cardiovascular complications (myocardial infarction, stroke, and vascular thrombosis, including venous thromboembolism). However, more recent large investigations of women taking low dose estrogen combinations have suggested that oral contraceptive use is not associated with an increased risk of serious cardiovascular complications in healthy non smoking women up to the age of 45. (For women aged 35 to 44 who smoke or who have preexisting systemic diseases that may affect the cardiovascular system, use of oral contraceptives is not recommended.)

However, some investigators have suggested that even the new low dose products may result in adverse effects on lipid metabolism and should prompt careful review of a woman's cardiovascular risk factors before a decision to use oral contraceptive combinations is made.

The frequency of both subarachnoid hemorrhage and thrombotic stroke has been reported by some investigators to be higher in women taking oral contraceptive hormones. However, other investigators have suggested that the risk of these effects for women using newer low dose formulations are very small for young women without underlying cardiovascular disease or other risk factors.[Ref]

Endocrine

Endocrine and metabolic effects include complex alterations in plasma lipid profiles and carbohydrate metabolism. In addition, oral contraceptive use has been reported to cause conception delay.[Ref]

All the progestins which occur in commercially available oral contraceptive combinations have adverse effects on lipid profiles. Specifically, these progestins exert antiestrogen and androgen effects and decrease HDL (and HDL2) cholesterol levels and increase LDL cholesterol levels. However, the estrogens in oral contraceptive combinations exert opposing effects. Consequently, alterations in lipid profiles are related to the relative amount and potency of the specific estrogen and progestin in a given product. (Norgestrel exerts potent progestin, antiestrogen and androgen effects.)

A number of investigations have suggested that oral contraceptive combinations may decrease glucose tolerance. However, some recent studies with low dose preparations have suggested that decreases in glucose tolerance due to oral contraceptive combinations are generally minimal.

Despite the potentially adverse effects of oral contraceptives on lipid levels and glucose tolerance, some investigators have suggested that young diabetic women without existing vascular disease or severe lipidemias may be candidates for low dose oral contraceptive combinations provided that they receive close monitoring for adverse metabolic effects.[Ref]

Hepatic

Hepatic side effects include focal nodular hyperplasia, intrahepatic cholestasis, liver cell adenomas, hepatic granulomas, hepatic hemangiomas and well-differentiated hepatocellular carcinomas, which have been reported rarely in association with estrogen therapy and therapy with oral contraceptive combinations.[Ref]

The rate of death due to hepatocellular carcinoma in the United States has not changed during the last 25 years (a time during which use of oral contraceptive hormones has increased dramatically).

A committee of the World Health Organization has reported that in developing countries where hepatitis B virus infection and hepatocellular carcinoma are common, "short term use of oral contraceptives does not appear to be associated with an increased risk. Data on the effects of long term use are scarce."

A recent Italian case-control study of women with hepatocellular carcinoma has suggested that the relative risk of hepatocellular carcinoma is 2.2 for oral contraceptive users compared to women who never used oral contraceptives.

A similar American case-control study from 1989 also reported a strong association between oral contraceptive use and hepatocellular carcinoma but concluded that: "If this observed association is causal, the actual number of cases of liver cancer in the United States attributable to oral contraceptive use is small. Therefore, these findings do not have public health importance in the United States and other Western nations."[Ref]

Hematologic

A hematologic concern is the risk of thromboembolism that is associated with the use of exogenous estrogens. However, because the dose of exogenous estrogens is low in most commercially available preparations, the risk of thromboembolism is minimal for most women (except women who are over age 35 and smoke and women with a history of previous thrombotic diseases).[Ref]

Cases of venous thrombosis, pulmonary embolism (sometimes fatal), and arterial thrombosis have been reported rarely.

Previous thrombotic disease is considered a contraindication to use of oral contraceptive combinations.[Ref]

Genitourinary

A common genitourinary side effect is breakthrough bleeding and spotting, especially during the first several cycles of oral contraceptive use. Non-hormonal causes of such bleeding should be excluded.[Ref]

Some women experience oligomenorrhea and amenorrhea following termination or oral contraceptive use.[Ref]

Psychiatric

Psychiatric side effects include depression and precipitation of panic disorder.[Ref]

Immunologic

Immunologic side effects include cases of oral contraceptive-induced systemic lupus erythematosus which have been reported rarely.[Ref]

Other

A case of fatal pulmonary venooclusive disease has been associated with oral contraceptive therapy.[Ref]

Nervous system

Nervous system side effects include chorea, which has been reported once in association with oral contraceptives.[Ref]

Ocular

Ocular side effects include cases of retinal thrombosis, which have been reported rarely. In addition, the manufacturers of oral contraceptive products report that some patients develop changes in contact lens tolerance.[Ref]

Some side effects of Lo / Ovral may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.