Nikki

• Lupin Pharmaceuticals, Inc.

Drospirenone and ethinyl estradiol prevent ovulation (the release of an egg from an ovary) and also cause changes in your cervical and uterine lining, making it harder for sperm to reach the uterus and harder for a fertilized egg to attach to the uterus.

Drospirenone and ethinyl estradiol is a combination medicine used as contraception to prevent pregnancy. It is also used to treat moderate acne in women who are at least 14 years old and have started having menstrual periods.

This medicine is also used to treat the symptoms of premenstrual dysphoric disorder (PMDD), such as anxiety, depression, irritability, sleep or appetite changes, breast tenderness, headache, and weight gain.

Drospirenone and ethinyl estradiol may also be used for purposes not listed in this medication guide.

Taking birth control pills can increase your risk of blood clots, stroke, or heart attack. You are even more at risk if you have high blood pressure, diabetes, high cholesterol, or if you are overweight. Your risk of stroke or blood clot is highest during your first year of taking birth control pills. Your risk is also high when you restart birth control pills after not taking them for 4 weeks or longer.

Smoking can greatly increase your risk of blood clots, stroke, or heart attack. Your risk increases the older you are and the more you smoke. You should not take combination birth control pills if you smoke and are over 35 years old.

Do not use if you are pregnant. Stop taking this medicine and tell your doctor 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 birth control pills.

You should not take birth control pills 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, liver cancer, history of jaundice caused by pregnancy or birth control pills; or

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

To make sure birth control pills are safe for you, tell your doctor if you have:

• high blood pressure, varicose veins;

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

• an electrolyte imbalance (such as high levels of potassium in your blood);

• a history of depression;

• diabetes, underactive thyroid, gallbladder disease;

• seizures or epilepsy;

• tuberculosis; or

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

The hormones in birth control pills can pass into breast milk and may harm a nursing baby. This medicine may also slow breast milk production. Do not use if you are breast feeding.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended. You will take your first pill on the first day of your period or on the first Sunday after your period begins. You may need to use back-up birth control, such as condoms or a spermicide, when you first start using this medicine. Follow your doctor's instructions.

Take one pill every day, no more than 24 hours apart. When the pills run out, start a new pack the following day. You may get pregnant if you do not take one pill daily.

You may have breakthrough bleeding, especially during the first 3 months. Tell your doctor if this bleeding continues or is very heavy.

Use a back-up birth control if you are sick with severe vomiting or diarrhea.

If you need surgery or medical tests or if you will be on bed rest, you may need to stop using this medicine for a short time. Any doctor or surgeon who treats you should know that you are using birth control pills.

While taking birth control pills, you will need to visit your doctor regularly.

Store this medicine at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Overdose symptoms may include nausea, vomiting, and vaginal bleeding.

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly and does not cause unwanted effects. These visits will usually be every 6 to 12 months, but some doctors require them more often. Your doctor may also want to check your blood pressure while taking this medicine.

Although you are using this medicine to prevent pregnancy, you should know that using this medicine while you are pregnant could harm the unborn baby. If you think you have become pregnant while using the medicine, tell your doctor right away. Make sure your doctor knows if you have had a baby within 4 weeks before you start using this medicine.

Vaginal bleeding of various amounts may occur between your regular menstrual periods during the first 3 months of use. This is sometimes called spotting when slight, or breakthrough bleeding when heavier.

• If this should occur, continue with your regular dosing schedule.
• The bleeding usually stops within 1 week. Check with your doctor if the bleeding continues for more than 1 week.
• If the bleeding continues after you have been taking hormonal contraceptives on schedule and for more than 3 months, check with your doctor.

Check with your doctor right away if you miss a menstrual period. Missed periods may occur if you skip one or more tablets and have not taken your pills exactly as directed. If you miss two periods in a row, talk to your doctor. You might need a pregnancy test.

If you suspect that you may be pregnant, stop taking this medicine immediately and check with your doctor.

Do not use this medicine if you smoke cigarettes or if you are over 35 years of age. If you smoke while using birth control pills containing drospirenone, you increase your risk of having a blood clot, heart attack, or stroke. Your risk is even higher if you are over age 35, if you have diabetes, high blood pressure, high cholesterol, or if you are overweight. Talk with your doctor about ways to stop smoking. Keep your diabetes under control. Ask your doctor about diet and exercise to control your weight and blood cholesterol level.

Using this medicine may increase your risk of having blood clotting problems, especially in the first 6 months of use. This risk may be higher if you are using a birth control pill containing drospirenone and ethinyl estradiol. Stop using this medicine and check with your doctor right away if you have pain in the chest, groin, or legs, especially the calves, difficulty with breathing, a sudden, severe headache, slurred speech, a sudden, unexplained shortness of breath, a sudden loss of coordination, or vision changes while using this medicine.

Check with your doctor immediately if you wear contact lenses or if blurred vision, difficulty in reading, or any other change in vision occurs during or after treatment. Your doctor may want an eye doctor to check your eyes.

Stop using this medicine and check with your doctor right away if you have pain or tenderness in the upper stomach, dark urine or pale stools, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Check with your doctor before refilling an old prescription, especially after a pregnancy. You will need another physical examination and your doctor may change your prescription.

Make sure any doctor or dentist who treats you knows that you are using this medicine. The results of some medical tests may be affected by this medicine. You may also need to stop using this medicine at least 4 weeks before and 2 weeks after having major surgery.

This medicine may cause skin discoloration. Use a sunscreen when you are outdoors. Avoid sunlamps and tanning beds.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (e.g., St. John's wort) or vitamin supplements.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Breast pain or tenderness
• headache, severe and throbbing
• heavy non-menstrual vaginal bleeding
• irregular menstrual periods
• nausea
• normal menstrual bleeding occurring earlier, possibly lasting longer than expected

• Longer or heavier menstrual periods
• unusual tiredness or weakness
• vomiting

• Abdominal or stomach pain
• chills
• clay-colored stools
• dark urine
• difficulty with breathing
• dizziness
• fever
• headache
• itching
• loss of appetite
• pain in the chest, groin, or legs, especially the calves
• rash
• slurred speech
• sudden loss of coordination
• sudden, severe weakness or numbness in the arm or leg
• sudden, unexplained shortness of breath
• unpleasant breath odor
• unusual tiredness or weakness
• vision changes
• vomiting of blood
• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Crying
• decreased interest in sexual intercourse
• delusions of persecution, mistrust, suspiciousness, and/or combativeness
• false or unusual sense of well-being
• inability to have or keep an erection
• irritability
• loss in sexual ability, desire, drive, or performance
• mental depression
• quick to react or overreact emotionally
• rapidly changing moods
• weight gain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Nikki (drospirenone and ethinyl estradiol tablets USP), 3 mg/0.02 mg are available in wallet packs.

Each wallet pack (28 round, biconvex film-coated tablets) contains in the following order:

• 24 pink tablets each containing 3 mg drospirenone (DRSP) and 0.02 mg ethinyl estradiol (EE)
• 4 white to off-white inert tablets

How Supplied

Nikki (drospirenone and ethinyl estradiol tablets USP), 3 mg/0.02 mg is available in a wallet (NDC 68180-886-11) packed in a pouch (NDC 68180-886-11). Such three pouches are packaged in a carton (NDC 68180-886-13).

Each wallet pack (28 film-coated tablets) contains in the following order:

• 24 active pink, round, biconvex, film-coated tablets, debossed with "LU" on one side and "K31" on the other side each containing 3 mg drospirenone and 0.02 mg ethinyl Estradiol
• 4 inert white to off-white round, biconvex film-coated tablets debossed with "K33" on one side and "LU" on the other side.

Storage

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

Applies to drospirenone / ethinyl estradiol: oral tablet

General

The most common adverse events were irregular uterine bleeding, nausea, breast tenderness, and headache.[Ref]

Genitourinary

Very common (10% or more): Breast pain or discomfort (17.9%), menstrual disorders (17%), female genital tract bleeding (14%), premenstrual syndrome (13.2%)
Common (1% to 10%): Vaginal candidiasis, leukorrhea, intermenstrual bleeding, cystitis, unscheduled uterine bleeding/genital tract bleeding NOS, metrorrhagia, amenorrhea, breast tenderness, vaginal discharge, cervical polyp
Uncommon (0.1% to 1%): Vaginitis, pelvic pain, breast enlargement, fibrocystic breast, genital discharge, dysmenorrhea, hypomenorrhea, menorrhagia, vaginal dryness, Pap smear suspicious, breast hypertrophy
Rare (less than 0.1%): Dyspareunia, vulvovaginitis, postcoital bleeding, withdrawal bleeding, breast cyst, breast hyperplasia, endometrial atrophy, ovarian cyst, uterine enlargement, breast discharge
Frequency not reported: Cervical dysplasia[Ref]

Gastrointestinal

Gastrointestinal side effects have included 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. Abdominal pain and gastroenteritis have been reported in postmarketing experience.[Ref]

Cardiovascular

Uncommon (0.1% to 1%): Hypertension, hypotension, varicose vein
Rare (less than 0.1%): Venous and arterial thromboembolic events, tachycardia, vascular disorder, phlebitis[Ref]

Venous and arterial thromboembolic events includes peripheral deep vein occlusion, thrombosis and embolism/pulmonary vascular occlusion, thrombosis, embolism, infarction, intracardiac thrombosis, retinal vein occlusion, myocardial infarction, cerebral infarction, and stroke.[Ref]

Nervous system

Very common (10% or more): Headache (20%)
Common (1% to 10%): Dizziness, migraine
Uncommon (0.1% to 1%): Somnolence, dizziness, paresthesia, asthenia
Rare (less than 0.1%): Vertigo, tremor, syncope[Ref]

Psychiatric

Common (1% to 10%): Depression/depressive mood, nervousness, emotional lability, decrease and loss of libido, libido increased, affect lability
Rare (less than 0.1%): Anorgasmia, insomnia[Ref]

Other

Common (1% to 10%): Fatigue
Uncommon (0.1% to 1%): Weight gain, weight loss, hot flushes, edema (generalized)
Rare (less than 0.1%): Candidiasis, malaise, hypoacusis[Ref]

Dermatologic

Common (1% to 10%): Acne
Uncommon (0.1% to 1%): Pruritus, rash, increased sweating, eczema, alopecia
Rare (less than 0.1%): Chloasma, dermatitis acneiform, dry skin, erythema nodosum, erythema multiforme, hypertrichosis, skin disorder, skin striae, contact dermatitis, photosensitive dermatitis, skin nodule
Postmarketing reports: Angioedema[Ref]

Respiratory

Common (1% to 10%): Pharyngitis, sinusitis
Rare (less than 0.1%): Epistaxis, asthma[Ref]

Hypersensitivity

Rare (less than 0.1%): Hypersensitivity, allergic reaction[Ref]

Oncologic

Rare (less than 0.1%): Breast neoplasm, breast cancer, focal nodular hyperplasia
Frequency not reported: Uterine leiomyoma
Postmarketing reports: Liver tumors[Ref]

Hepatic

Rare (less than 0.1%): Biliary pain, cholecystitis acute
Postmarketing reports: Gallbladder disease, liver function disturbances[Ref]

Metabolic

Uncommon (0.1% to 1%): Fluid retention
Rare (less than 0.1%): Increased appetite, anorexia, hyperkalemia, hyponatremia[Ref]

Musculoskeletal

Uncommon (0.1% to 1%): Back pain, pain in extremity, muscle cramps
Postmarketing reports: Systemic lupus erythematosus[Ref]

Ocular

Rare (less than 0.1%): Conjunctivitis, dry eye, eye disorder, contact lens intolerance[Ref]

Hematologic

Rare (less than 0.1%): Anemia, thrombocythemia[Ref]

Endocrine

Rare (less than 0.1%): Endocrine disorder[Ref]

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