Drospirenone and Ethinyl Estradiol Tablets

Dosage Forms And Strengths

Lo-Zumandimine (drospirenone and ethinyl estradiol tablets, USP) are available in blister packs.

Each blister pack (28 tablets) contains in the following order:

• 24 light pink to pink tablets each containing 3 mg drospirenone USP (DRSP) and 0.02 mg ethinyl estradiol USP (EE)
• 4 green inert tablets

Storage And Handling

Lo-Zumandimine (drospirenone and ethinyl estradiol tablets, USP) are available in Blister Pack Containing 28 tablets in the following order.

Each blister pack (28 tablets) contains in the following order:

• 24 active light pink to pink, round, flat faced, beveled-edge tablets, debossed with “S” on one side and “77” on other side
• 4 inert green, round, mottled, flat faced beveled-edge, uncoated tablets, debossed with “S” on one side and “37” on other side.

The blister packs are available in the following packages:

• The Blister Packs are packed in Pouches and the pouches are packaged in cartons

Carton of 1 Pouch .. NDC 59651-029-87
Carton of 3 Pouches .. NDC 59651-029-88

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Manufactured by: Aurobindo Pharma Limited. Hyderabad-500 038, India. Revised: Mar 2018.

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

• Serious cardiovascular events and stroke [see BOX WARNING and WARNINGS AND PRECAUTIONS]
• Vascular events [see WARNINGS AND PRECAUTIONS]
• Liver disease [see WARNINGS AND PRECAUTIONS]

Adverse reactions commonly reported by COC users are:

• Irregular uterine bleeding
• Nausea
• Breast tenderness
• Headache

Clinical Trials Experience

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

The data provided reflect the experience with the use of Lo-Zumandimine in the adequate and wellcontrolled studies for contraception (N=1,056) and for moderate acne vulgaris (N=536).

For contraception, a Phase 3, multicenter, multinational, open-label study was conducted to evaluate safety and efficacy up to one year in 1,027 women aged 17 to 36 who took at least one dose of Lo- Zumandimine. A second Phase 3 study was a single center, open-label, active-controlled study to evaluate the effect of 7 28-day cycles of Lo-Zumandimine on carbohydrate metabolism, lipids and hemostasis in 29 women aged 18 to 35. For acne, two multicenter, double-blind, randomized, placebocontrolled studies, in 536 women aged 14 to 45 with moderate acne vulgaris who took at least one dose of Lo-Zumandimine, evaluated the safety and efficacy during up to 6 cycles.

The adverse reactions seen across the 2 indications overlapped, and are reported using the frequencies from the pooled dataset. The most common adverse reactions (≥ 2% of users) were: headache/migraine (6.7%), menstrual irregularities (including vaginal hemorrhage [primarily spotting] and metrorrhagia (4.7%), nausea/vomiting (4.2%), breast pain/tenderness (4%) and mood changes (mood swings, depression, depressed mood and affect lability) (2.2%).

Safety data from trials for the indication of PMDD are reported separately due to differences in study design and setting in the Contraception and Acne studies as compared to the PMDD clinical program.

Two (one parallel and one crossover designed) multicenter, double-blind, randomized, placebocontrolled trials for the secondary indication of treating the symptoms of PMDD evaluated safety and efficacy of Lo-Zumandimine during up to 3 cycles among 285 women aged 18 to 42, diagnosed with PMDD and who took at least one dose of Lo-Zumandimine.

Common adverse reactions (≥ 2% of users) were: menstrual irregularities (including vaginal hemorrhage [primarily spotting] and metrorrhagia) (24.9%), nausea (15.8%), headache (13.0%), breast tenderness (10.5%), fatigue (4.2%), irritability (2.8%), decreased libido (2.8%), increased weight (2.5%), and affect lability (2.1%).

Of 1,056 women, 6.6% discontinued from the clinical trials due to an adverse reaction; the most frequent adverse reactions leading to discontinuation were headache/migraine (1.6%) and nausea/vomiting (1.0%).

Of 536 women, 5.4% discontinued from the clinical trials due to an adverse reaction; the most frequent adverse reaction leading to discontinuation was menstrual irregularities (including menometrorrhagia, menorrhagia, metrorrhagia and vaginal hemorrhage) (2.2%).

Of 285 women, 11.6% discontinued from the clinical trials due to an adverse reaction; the most frequent adverse reactions leading to discontinuation were: nausea/vomiting (4.6%), menstrual irregularity (including vaginal hemorrhage, menorrhagia, menstrual disorder, menstruation irregular and metrorrhagia) (4.2%), fatigue (1.8%), breast tenderness (1.4%), depression (1.4%), headache (1.1%), and irritability (1.1%).

Contraception Clinical Trials: migraine and cervical dysplasia Acne Clinical Trials: none reported in the clinical trials PMDD Clinical Trials: cervical dysplasia

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Lo-Zumandimine. 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.

Adverse reactions are grouped into System Organ Classes, and ordered by frequency.

Venous and arterial thromboembolic events (including pulmonary emboli, deep vein thrombosis, cerebral thrombosis, retinal thrombosis, myocardial infarction and stroke), hypertension (including hypertensive crisis)

Gallbladder disease, liver function disturbances, liver tumors Immune system disorders: Hypersensitivity (including anaphylactic reaction)

Hyperkalemia, hypertriglyceridemia, changes in glucose tolerance or effect on peripheral insulin resistance (including diabetes mellitus)

Chloasma, angioedema, erythema nodosum, erythema multiforme Gastrointestinal disorders: Inflammatory bowel disease

Systemic lupus erythematosus

Included as part of the "PRECAUTIONS" Section

WARNING TO WOMEN WHO SMOKE

Do not use Lo-Zumandimine if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects (heart and blood vessel problems) from birth control pills, including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you smoke.

Birth control pills help to lower the chances of becoming pregnant when taken as directed. They do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

What is Lo-Zumandimine?

Lo-Zumandimine is a birth control pill. It contains two female hormones, a synthetic estrogen called ethinyl estradiol and a progestin called drospirenone.

The progestin drospirenone may increase potassium. Therefore, you should not take Lo-Zumandimine if you have kidney, liver or adrenal disease because this could cause serious heart and health problems. Other drugs may also increase potassium. If you are currently on daily, long-term treatment for a chronic condition with any of the medications below, you should consult your healthcare provider about whether Lo-Zumandimine is right for you, and during the first month that you take Lo- Zumandimine, you should have a blood test to check your potassium level.

• NSAIDs (ibuprofen [Motrin, Advil], naproxen [Aleve and others] when taken long-term and daily for treatment of arthritis or other problems)
• Potassium-sparing diuretics (spironolactone and others)
• Potassium supplementation
• ACE inhibitors (Capoten, Vasotec, Zestril and others)
• Angiotensin-II receptor antagonists (Cozaar, Diovan, Avapro and others)
• Heparin
• Aldosterone antagonists

Lo-Zumandimine may also be taken to treat premenstrual dysphoric disorder (PMDD) if you choose to use the Pill for birth control. Unless you have already decided to use the Pill for birth control, you should not start Lo-Zumandimine to treat your PMDD because there are other medical therapies for PMDD that do not have the same risks as the Pill. PMDD is a mood disorder related to the menstrual cycle. PMDD significantly interferes with work or school, or with usual social activities and relationships with others. Symptoms include markedly depressed mood, anxiety or tension, mood swings, and persistent anger or irritability. Other features include decreased interest in usual activities, difficulty concentrating, lack of energy, change in appetite or sleep, and feeling out of control. Physical symptoms associated with PMDD may include breast tenderness, headache, joint and muscle pain, bloating and weight gain.

These symptoms occur regularly before menstruation starts and go away within a few days following the start of the period. Diagnosis of PMDD should be made by healthcare providers.

You should only use Lo-Zumandimine for treatment of PMDD if you:

• Have already decided to use oral contraceptives for birth control, and
• Have been diagnosed with PMDD by your healthcare provider.

Lo-Zumandimine has not been shown to be effective for the treatment of premenstrual syndrome (PMS), a less serious set of symptoms occurring before menstruation. If you or your healthcare provider believe you have PMS, you should take Lo-Zumandimine only if you want to prevent pregnancy; and not for the treatment of PMS.

Lo-Zumandimine may also be taken to treat moderate acne if all of the following are true:

• Your healthcare provider says it is safe for you to use Lo-Zumandimine.
• You are at least 14 years old.
• You have started having menstrual periods.
• You want to use a birth control pill to prevent pregnancy.

How Well Does Lo-Zumandimine Work?

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 one clinical study, 1 to 2 women out of 100 women, may get pregnant during the first year they use Lo-Zumandimine.

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.

How Do I Take Lo-Zumandimine?

1. Be sure to read these directions before you start taking your pills or anytime you are not sure what to do.
2. The right way to take the pill is to take one pill every day at the same time in the order directed on the package. Preferably, take the pill after the evening meal or at bedtime, with some liquid, as needed. Lo- Zumandimine can be taken without regard to meals.

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. See “WHAT TO DO IF YOU MISS PILLS” below.

3. Many women have spotting or light bleeding at unexpected times, or may feel sick to their stomach during the first 1 to 3 packs of pills.

If you do 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 does not go away, check with your healthcare provider.

4. Missing pills can also cause spotting or light bleeding, even when you make up these missed pills. On the days you take two 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 and some herbal products such as St. John's Wort, your pills may not work as well.

Use a back-up method (such as condoms and spermicides) 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.

Before You Start Taking Your Pills

1. Decide What Time of Day You Want to Take Your Pill It is important to take Lo-Zumandimine in the order directed on the package at the same time every day, preferably after the evening meal or at bedtime, with some liquid, as needed. Lo-Zumandimine can be taken without regard to meals.
2. Look at Your Pill Pack – It has 28 Pills The Lo-Zumandimine-pill pack has 24 light pink to pink pills (with hormones) to be taken for 24 days, followed by 4 green pills (without hormones) to be taken for the next four days.
3. Also look for:
   1. Where on the pack to start taking pills,
   2. In what order to take the pills (follow the arrows)

4. Be sure you have ready at all times (a) another kind of birth control (such as condoms and spermicides) to use as a back-up in case you miss pills, and (b) an extra, full pill pack.

When To Start the First Pack of Pills

You have a choice for 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 which will be easy to remember.

Day 1 Start:

1. Take the first light pink to pink pill of the pack during the first 24 hours of your period.
2. 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. However, if you start Lo-Zumandimine later than the first day of your period, you should use another method of birth control (such as a condom and spermicide) as a back-up method until you have taken 7 light pink to pink pills.

Sunday Start:

1. Take the first light pink to pink pill of the 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 (such as a condom and spermicide) as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days). This also applies if you start Lo-Zumandimine after having been pregnant, and you have not had a period since your pregnancy.

When You Switch From a Different Birth Control Pill

When switching from another birth control pill, Lo-Zumandimine should be started on the same day that a new pack of the previous birth control pill would have been started.

When You Switch From Another Type of Birth Control Method

When switching from a transdermal patch or vaginal ring, Lo-Zumandimine should be started when the next application would have been due. When switching from an injection, Lo-Zumandimine should be started when the next dose would have been due. When switching from an intrauterine contraceptive or an implant, Lo-Zumandimine should be started on the day of removal.

What to Do During the Month

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 pills, start the next pack on the day after your last green pill. Do not wait any days between packs.

What to Do if You Miss Pills

If you miss 1 light pink to pink pill of your pack:

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

If you miss 2 light pink to pink pills in a row in Week 1 or Week 2 of your pack:

1. Take two pills on the day you remember and two pills the next day.
2. Then take one pill a day until you finish the pack.
3. You could become pregnant if you have sex in the 7 days after you restart your pills. You must use another birth control method (such as a condom and spermicide) as a back-up for those 7 days.

If you miss 2 light pink to pink 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 one 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 could become pregnant if you have sex in the 7 days after you restart your pills. You must use another birth control method (such as a condom and spermicide) as a back-up for those 7 days.
3. You may not have your period this month but this is expected. However, if you miss your period two months in a row, call your healthcare provider because you might be pregnant.

If you miss 3 or more light pink to pink pills in a row during any week:

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 could become pregnant if you have sex in the 7 days after you restart your pills. You must use another birth control method (such as condoms and spermicides) as a back-up for those 7 days.
3. Call your healthcare provider if you miss your period, because you might be pregnant.

If you miss any of the 4 green pills in Week 4:

Throw away the pills you missed.

Keep taking one pill each day until the pack is empty.

You do not need a back-up method.

Finally, if you are still not sure what to do about the pills you have missed:

Use a back-up method (such as condoms and spermicides) anytime you have sex. Contact your healthcare provider and continue taking one active light pink to pink pill each day until otherwise directed.

WHO SHOULD NOT TAKE LO-ZUMANDIMINE?

Your healthcare provider will not give you Lo-Zumandimine if you:

• Ever had blood clots in your legs (deep vein thrombosis), lungs (pulmonary embolism), or eyes (retinal thrombosis)
• Ever had a stroke
• Ever had a heart attack
• Have certain heart valve problems or heart rhythm abnormalities that can cause blood clots to form in the heart
• Have an inherited problem with your blood that makes it clot more than normal
• Have high blood pressure that medicine can’t control
• Have diabetes with kidney, eye, nerve, or blood vessel damage
• Ever had certain kinds of severe migraine headaches with aura, numbness, weakness or changes in vision
• Ever had breast cancer or any cancer that is sensitive to female hormones
• Have liver disease, including liver tumors
• 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.
• Have kidney disease
• Have adrenal disease

Also, do not take birth control pills if you:

• Smoke and are over 35 years old
• Are or suspect you are pregnant

Birth control pills may not be a good choice for you if you have ever had jaundice (yellowing of the skin or eyes) caused by pregnancy (also called cholestasis of pregnancy).

Tell your healthcare provider if you have ever had any of the above conditions (your healthcare provider can recommend another method of birth control).

What Else Should I Know about Taking Lo-Zumandimine?

Birth control pills do not protect you against any sexually transmitted disease, including HIV, the virus that causes AIDS.

Do not skip any pills, even if you do not have sex often.

If you miss a period, you could be pregnant. However, some women miss periods or have light periods on birth control pills, even when they are not pregnant. Contact your healthcare provider for advice if you:

• Think you are pregnant
• Miss one period and have not taken your birth control pills every day
• Miss two periods in a row

Birth control pills should not be taken during pregnancy. However, birth control pills taken by accident during pregnancy are not known to cause birth defects.

You should stop Lo-Zumandimine at least four weeks before you have major surgery and not restart it until at least two weeks after the surgery due to an increased risk of blood clots.

If you are breastfeeding, consider another birth control method until you are ready to stop breastfeeding. Birth control pills that contain estrogen, like Lo-Zumandimine, may decrease the amount of milk you make. A small amount of the pill's hormones pass into breast milk.

If you have vomiting or diarrhea, your birth control pills may not work as well. Use another birth control method, like condoms and a spermicide, until you check with your healthcare provider.

If you are scheduled for any laboratory tests, tell your doctor you are taking birth-control pills. Certain blood tests may be affected by birth-control pills.

Tell your healthcare provider about all the medicines you take, including prescription and over-thecounter medicines, vitamins and herbal supplements.

Lo-Zumandimine may affect the way other medicines work, and other medicines may affect how well Lo-Zumandimine works. Know the medicines you take.

Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

What are the Most Serious Risks of Taking Birth Control Pills ?

Like pregnancy, birth control pills increase the risk of serious blood clots (see following graph), especially in women who have other risk factors, such as smoking, obesity, or age greater than 35. This increased risk is highest when you first start taking birth control pills and when you restart the same or different birth control pills after not using them for a month or more. Women who use birth control pills with drospirenone (like Lo-Zumandimine) may have a higher risk of getting a blood clot. Some studies reported that the risk of blood clots was higher for women who use birth control pills that contain drospirenone than for women who use birth control pills that do not contain drospirenone.

Talk with your healthcare provider about your risk of getting a blood clot before deciding which birth control pill is right for you.

It is possible to die or be permanently disabled from a problem caused by a blood clot, such as a heart attack or a stroke. Some examples of serious clots are blood clots in the:

• Legs (deep vein thrombosis or DVT)
• Lungs (pulmonary embolus or PE)
• Eyes (loss of eyesight)
• Heart (heart attack)
• Brain (stroke)

To put the risk of developing a blood clot into perspective: If 10,000 women who are not pregnant and do not use birth control pills are followed for one year, between 1 and 5 of these women will develop a blood clot. The figure below shows the likelihood of developing a serious blood clot for women who are not pregnant and do not use birth control pills, for women who use birth control pills, for pregnant women, and for women in the first 12 weeks after delivering a baby.

Likelihood of Developing a Serious Blood Clot

A few women who take birth control pills may get:

Figure 2: Likelihood of Developing a VTE

*Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy duration is nine months, the rate is 7 to 27 per 10,000 WY.

A few women who take birth control pills may get:

• High blood pressure
• Gallbladder problems
• Rare cancerous or noncancerous liver tumors

All of these events are uncommon in healthy women.

Call your healthcare provider right away if you have:

• Persistent leg pain
• Sudden shortness of breath
• Sudden blindness, partial or complete
• Severe pain in your chest
• Sudden, severe headache unlike your usual headaches
• Weakness or numbness in an arm or leg, or trouble speaking
• Yellowing of the skin or eyeballs

What are the Common Side Effects of Birth Control Pills ?

The most common side effects of birth control pills are:

• Spotting or bleeding between menstrual periods
• Nausea
• Breast tenderness
• Headache

These side effects are usually mild and usually disappear with time.

Less common side effects are:

• Acne
• Less sexual desire
• Bloating or fluid retention
• Blotchy darkening of the skin, especially on the face
• High blood sugar, especially in women who already have diabetes
• High fat (cholesterol; triglyceride) levels in the blood
• Depression, especially if you have had depression in the past. Call your healthcare provider immediately if you have any thoughts of harming yourself.
• Problems tolerating contact lenses
• Weight changes

This is not a complete list of possible side effects. Talk to your healthcare provider if you develop any side effects that concern you. You may report side effects to the FDA at 1-800-FDA-1088.

No serious problems have been reported from a birth control pill overdose, even when accidentally taken by children.

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 Should I Know about My Period when Taking Lo-Zumandimine?

Irregular vaginal bleeding or spotting may occur while you are taking Lo-Zumandimine. Irregular bleeding may vary from slight staining between menstrual periods to breakthrough bleeding, which is a flow much like a regular period. Irregular bleeding occurs most often during the first few months of oral contraceptive use, but may also occur after you have been taking the pill for some time. Such bleeding may be temporary and usually does not indicate any serious problems. It is important to continue taking your pills on schedule. If the bleeding occurs in more than one cycle, is unusually heavy, or lasts for more than a few days, call your healthcare provider.

Some women may not have a menstrual period but this should not be cause for alarm as long has you have taken the pills according to direction.

What if I Miss My Scheduled Period when Taking Lo-Zumandimine?

It is not uncommon to miss your period. However, if you miss two periods in a row or miss one period when you have not taken your birth control pills according to directions, call your healthcare provider. Also notify your healthcare provider if you have symptoms of pregnancy such as morning sickness or unusual breast tenderness. It is important that your healthcare provider checks you to find out if you are pregnant. Stop taking Lo-Zumandimine if you are pregnant.

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

• Serious cardiovascular events and stroke [see BOX WARNING and WARNINGS AND PRECAUTIONS]
• Vascular events [see WARNINGS AND PRECAUTIONS]
• Liver disease [see WARNINGS AND PRECAUTIONS]

Adverse reactions commonly reported by COC users are:

• Irregular uterine bleeding
• Nausea
• Breast tenderness
• Headache

Clinical Trials Experience

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

The data provided reflect the experience with the use of Lo-Zumandimine in the adequate and wellcontrolled studies for contraception (N=1,056) and for moderate acne vulgaris (N=536).

For contraception, a Phase 3, multicenter, multinational, open-label study was conducted to evaluate safety and efficacy up to one year in 1,027 women aged 17 to 36 who took at least one dose of Lo- Zumandimine. A second Phase 3 study was a single center, open-label, active-controlled study to evaluate the effect of 7 28-day cycles of Lo-Zumandimine on carbohydrate metabolism, lipids and hemostasis in 29 women aged 18 to 35. For acne, two multicenter, double-blind, randomized, placebocontrolled studies, in 536 women aged 14 to 45 with moderate acne vulgaris who took at least one dose of Lo-Zumandimine, evaluated the safety and efficacy during up to 6 cycles.

The adverse reactions seen across the 2 indications overlapped, and are reported using the frequencies from the pooled dataset. The most common adverse reactions (≥ 2% of users) were: headache/migraine (6.7%), menstrual irregularities (including vaginal hemorrhage [primarily spotting] and metrorrhagia (4.7%), nausea/vomiting (4.2%), breast pain/tenderness (4%) and mood changes (mood swings, depression, depressed mood and affect lability) (2.2%).

Safety data from trials for the indication of PMDD are reported separately due to differences in study design and setting in the Contraception and Acne studies as compared to the PMDD clinical program.

Two (one parallel and one crossover designed) multicenter, double-blind, randomized, placebocontrolled trials for the secondary indication of treating the symptoms of PMDD evaluated safety and efficacy of Lo-Zumandimine during up to 3 cycles among 285 women aged 18 to 42, diagnosed with PMDD and who took at least one dose of Lo-Zumandimine.

Common adverse reactions (≥ 2% of users) were: menstrual irregularities (including vaginal hemorrhage [primarily spotting] and metrorrhagia) (24.9%), nausea (15.8%), headache (13.0%), breast tenderness (10.5%), fatigue (4.2%), irritability (2.8%), decreased libido (2.8%), increased weight (2.5%), and affect lability (2.1%).

Of 1,056 women, 6.6% discontinued from the clinical trials due to an adverse reaction; the most frequent adverse reactions leading to discontinuation were headache/migraine (1.6%) and nausea/vomiting (1.0%).

Of 536 women, 5.4% discontinued from the clinical trials due to an adverse reaction; the most frequent adverse reaction leading to discontinuation was menstrual irregularities (including menometrorrhagia, menorrhagia, metrorrhagia and vaginal hemorrhage) (2.2%).

Of 285 women, 11.6% discontinued from the clinical trials due to an adverse reaction; the most frequent adverse reactions leading to discontinuation were: nausea/vomiting (4.6%), menstrual irregularity (including vaginal hemorrhage, menorrhagia, menstrual disorder, menstruation irregular and metrorrhagia) (4.2%), fatigue (1.8%), breast tenderness (1.4%), depression (1.4%), headache (1.1%), and irritability (1.1%).

Contraception Clinical Trials: migraine and cervical dysplasia Acne Clinical Trials: none reported in the clinical trials PMDD Clinical Trials: cervical dysplasia

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Lo-Zumandimine. 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.

Adverse reactions are grouped into System Organ Classes, and ordered by frequency.

Venous and arterial thromboembolic events (including pulmonary emboli, deep vein thrombosis, cerebral thrombosis, retinal thrombosis, myocardial infarction and stroke), hypertension (including hypertensive crisis)

Gallbladder disease, liver function disturbances, liver tumors Immune system disorders: Hypersensitivity (including anaphylactic reaction)

Hyperkalemia, hypertriglyceridemia, changes in glucose tolerance or effect on peripheral insulin resistance (including diabetes mellitus)

Chloasma, angioedema, erythema nodosum, erythema multiforme Gastrointestinal disorders: Inflammatory bowel disease

Systemic lupus erythematosus

Read the entire FDA prescribing information for Lo-Zumandimine (Drospirenone and Ethinyl Estradiol Tablets)