Syeda

Name: Syeda

Manufacturer

  • Sandoz Inc.

What is the most important information I should know about Syeda (drospirenone and ethinyl estradiol)?

Do not use birth control pills if you are pregnant or if you have recently had a baby.

You should not take birth control pills if you have any of the following conditions: uncontrolled high blood pressure, heart disease, a blood-clotting disorder, circulation problems, diabetic problems with your eyes or kidneys, unusual vaginal bleeding, liver disease or liver cancer, severe migraine headaches, if you smoke and are over 35, or if you have ever had breast or uterine cancer, jaundice caused by birth control pills, a heart attack, a stroke, or a blood clot.

Taking birth control pills can increase your risk of blood clots, stroke, or heart attack, especially if you have certain other conditions, or if you are overweight.

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

What happens if I overdose?

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

Syeda Side Effects

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:

More common
  • 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
Less common
  • Longer or heavier menstrual periods
  • unusual tiredness or weakness
  • vomiting
Incidence not known
  • 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:

Less common
  • 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.

How is this medicine (Syeda) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Follow how to use as you have been told by the doctor or read the package insert.
  • Take Syeda at the same time of day.
  • Take with or without food. Take with food if it causes an upset stomach.
  • If you drink grapefruit juice or eat grapefruit often, talk with your doctor.
  • Do not skip doses, even if you do not have sex very often.
  • If you throw up or have diarrhea, this medicine may not work as well to prevent pregnancy. Use an extra form of birth control, like condoms, until you check with your doctor.
  • If you miss 2 periods in a row, take a pregnancy test before starting a new cycle.

What do I do if I miss a dose?

  • If a dose is missed, check the package insert or call the doctor to find out what to do. If using Syeda to prevent pregnancy, another form of birth control may need to be used for some time to prevent pregnancy.

What are some side effects that I need to call my doctor about right away?

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

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

Adverse Reactions

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

• Serious cardiovascular events and stroke [see BOXED WARNING AND WARNINGS AND PRECAUTIONS (5.1)] • Vascular events [see WARNINGS AND PRECAUTIONS (5.1)] • Liver disease [see WARNINGS AND PRECAUTIONS (5.4)]   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, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in practice.

The data provided reflect the experience with the use of drospirenone and ethinyl estradiol (3 mg DRSP/0.03 mg EE) in the adequate and well-controlled studies for contraception (N=2,837). The US pivotal clinical study (N=326) was a multicenter, open-label trial in healthy women aged 18 to 35 who were treated for up to 13 cycles. The second pivotal study (N=442)was a multicenter, randomized, open-label comparative European study of drospirenone and ethinyl estradiol vs. 0.150 mg desogestrel/0.03 mg EE conducted in healthy women aged 17 to 40 who were treated for up to 26 cycles.

The most common adverse reactions (≥ 2% of users) were: premenstrual syndrome (13.2%), headache/migraine (10.7%), breast pain/tenderness/discomfort (8.3%), nausea/vomiting (4.5%) abdominal pain/discomfort/tenderness (2.3%) and mood changes (depression, depressed mood, irritability, mood swings, mood altered and affect lability (2.3%).

Adverse Reactions (≥ 1%) Leading to Study Discontinuation

Of 2,837 women, 6.7% discontinued from the clinical trials due to an adverse reaction; the most frequent adverse reaction leading to discontinuation was headache/migraine (1.5%).

Serious Adverse Reactions

Depression, pulmonary embolism, toxic skin eruption, and uterine leiomyoma.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of drospirenone and ethinyl estradiol. 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, including fatalities, are grouped into System Organ Classes and ordered by frequency.

Vascular disorders: Venous and arterial thromboembolic events (including pulmonary emboli, deep vein thrombosis, intracardiac thrombosis, intracranial venous sinus thrombosis, sagittal sinus thrombosis, retinal vein occlusion, myocardial infarction and stroke), hypertension

Hepatobiliary disorders: Gallbladder disease

Immune system disorders: Hypersensitivity

Metabolism and nutrition disorders: Hyperkalemia

Skin and subcutaneous tissue disorders: Chloasma

Syeda - Clinical Pharmacology

Mechanism of Action

COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation.

Pharmacodynamics

Drospirenone is a spironolactone analogue with anti-mineralocorticoid activity. The estrogen in SyedaTM is ethinyl estradiol (EE).

No specific pharmacodynamic studies were conducted with drospirenone and ethinyl estradiol

Pharmacokinetics

Absorption

The absolute bioavailability of DRSP from a single entity tablet is about 76%. The absolute bioavailability of EE is approximately 40% as a result of presystemic conjugation and first-pass metabolism. The absolute bioavailability of drospirenone and ethinyl estradiol, which is a combination tablet of DRSP and EE, has not been evaluated. Serum concentrations of DRSP and EE reached peak levels within 1 to 2 hours after administration of drospirenone and ethinyl estradiol.

The pharmacokinetics of DRSP are dose proportional following single doses ranging from 1 to 10 mg. Following daily dosing of drospirenone and ethinyl estradiol, steady state DRSP concentrations were observed after 8 days. There was about 2 to 3 fold accumulation in serum Cmax and AUC (0-24h) values of DRSP following multiple dose administration of drospirenone and ethinyl estradiol (see Table 2).

For EE, steady-state conditions are reported during the second half of a treatment cycle. Following daily administration of drospirenone and ethinyl estradiol serum Cmax and AUC (0-24h) values of EE accumulate by a factor of about 1.5 to 2 (see Table 2).

Table 2 Mean Pharmacokinetic Parameters Of Drospirenone And Ethinyl Estradiol (DRSP 3 mg and EE 0.03 mg )

DRSP
Mean (%CV) Values

Cycle / Day

No. of Subjects

Cmax (ng/mL)

Tmax (h)

AUC(0-24h) (ng•h/mL)

t1/2 (h)

1/1

12

36.9 (13)

1.7 (47)

288 (25)

NA

1/21

12

87.5 (59)

1.7 (20)

827 (23)

30.9 (44)

6/21

12

84.2 (19)

1.8 (19)

930 (19)

32.5 (38)

9/21

12

81.3 (19)

1.6 (38)

957 (23)

31.4 (39)

13/21

12

78.7 (18)

1.6 (26)

968 (24)

31.1 (36)

EE
Mean (%CV) Values

Cycle / Day

No. of Subjects

Cmax (pg/mL)

Tmax (h)

AUC(0-24h) (pg•h/mL)

t1/2 (h)

1/1

11

53.5 (43)

1.9 (45)

280 (87)

NA

1/21

11

92.1 (35)

1.5 (40)

461 (94)

NA

6/21

11

99.1 (45)

1.5 (47)

346 (74)

NA

9/21

11

87 (43)

1.5 (42)

485 (92)

NA

13/21

10

90.5 (45)

1.6 (38)

469 (83)

NA

N/A – Not available

Food Effect

The rate of absorption of DRSP and EE following single administration of a formulation similar to drospirenone and ethinyl estradiol was slower under fed (high fat meal) conditions with the serum Cmax being reduced about 40% for both components. The extent of absorption of DRSP, however, remained unchanged. In contrast, the extent of absorption of EE was reduced by about 20% under fed conditions.

Distribution

DRSP and EE serum concentrations decline in two phases. The apparent volume of distribution of DRSP is approximately 4 L/kg and that of EE is reported to be approximately 4 to 5 L/kg.

DRSP does not bind to sex hormone binding globulin (SHBG) or corticosteroid binding globulin (CBG) but binds about 97% to other serum proteins. Multiple dosing over 3 cycles resulted in no change in the free fraction (as measured at trough concentrations). EE is reported to be highly but non-specifically bound to serum albumin (approximately 98.5 %) and induces an increase in the serum concentrations of both SHBG and CBG. EE induced effects on SHBG and CBG were not affected by variation of the DRSP dosage in the range of 2 to 3 mg.

Metabolism

The two main metabolites of DRSP found in human plasma were identified to be the acid form of DRSP generated by opening of the lactone ring and the 4,5-dihydrodrospirenone-3-sulfate, formed by reduction and subsequent sulfation. These metabolites were shown not to be pharmacologically active. Drospirenone is also subject to oxidative metabolism catalyzed by CYP3A4.

EE has been reported to be subject to significant gut and hepatic first-pass metabolism. Metabolism of EE and its oxidative metabolites occur primarily by conjugation with glucuronide or sulfate.

CYP3A4 in the liver is responsible for the 2-hydroxylation which is the major oxidative reaction. The 2-hydroxy metabolite is further transformed by methylation and glucuronidation prior to urinary and fecal excretion.

Excretion

DRSP serum concentrations are characterized by a terminal disposition phase half-life of approximately 30 hours after both single and multiple dose regimens. Excretion of DRSP was nearly complete after ten days and amounts excreted were slightly higher in feces compared to urine. DRSP was extensively metabolized and only trace amounts of unchanged DRSP were excreted in urine and feces. At least 20 different metabolites were observed in urine and feces. About 38 to 47% of the metabolites in urine were glucuronide and sulfate conjugates. In feces, about 17 to 20% of the metabolites were excreted as glucuronides and sulfates.

For EE the terminal disposition phase half-life has been reported to be approximately 24 hours. EE is not excreted unchanged. EE is excreted in the urine and feces as glucuronide and sulfate conjugates and undergoes enterohepatic circulation.

Use in Specific Populations

Pediatric Use:

Safety and efficacy of drospirenone and ethinyl estradiol has been established in women of reproductive age. Efficacy is expected to be the same for postpubertal adolescents under the age of 18 and for users 18 years and older. Use of this product before menarche is not indicated.

Geriatric Use:

Drospirenone and ethinyl estradiol has not been studied in postmenopausal women and is not indicated in this population.

Race:

No clinically significant difference was observed between the pharmacokinetics of DRSP or EE in Japanese versus Caucasian women (age 25 to 35) when 3 mg DRSP/0.02 mg EE was administered daily for 21 days. Other ethnic groups have not been specifically studied.

Renal Impairment:

Drospirenone and ethinyl estradiol is contraindicated in patients with renal impairment.

The effect of renal impairment on the pharmacokinetics of DRSP (3 mg daily for 14 days) and the effect of DRSP on serum potassium concentrations were investigated in three separate groups of female subjects (n=28, age 30 to 65). All subjects were on a low potassium diet. During the study, 7 subjects continued the use of potassium-sparing drugs for the treatment of their underlying illness. On the 14th day (steady-state) of DRSP treatment, the serum DRSP concentrations in the group with CLcr of 50 to 79 mL/min were comparable to those in a the control group with CLcr ≥ 80 mL/min. The serum DRSP concentrations were on average 37% higher in the group with CLcr of 30 to 49 mL/min compared to those in the control group. DRSP treatment did not show any clinically significant effect on serum potassium concentration. Although hyperkalemia was not observed in the study, in five of the seven subjects who continued use of potassium sparing drugs during the study, mean serum potassium concentrations increased by up to 0.33 mEq/L. [See CONTRAINDICATIONS (4) and WARNINGS AND PRECAUTIONS (5.2).]

Hepatic Impairment

Drospirenone and ethinyl estradiol is contraindicated in patients with hepatic disease.

The mean exposure to DRSP in women with moderate liver impairment is approximately three times higher than the exposure in women with normal liver function. Drospirenone and ethinyl estradiol has not been studied in women with severe hepatic impairment [see CONTRAINDICATIONS (4) and WARNINGS AND PRECAUTIONS (5.4)].

Drug Interactions

Consult the labeling of all concurrently used drugs to obtain further information about interactions with oral contraceptives or the potential for enzyme alterations.

Effects of Other Drugs on Combined Oral Contraceptives

Substances diminishing the efficacy of COCs

Drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease the effectiveness of COCs or increase breakthrough bleeding.

Substances increasing the plasma concentrations of COCs

Co-administration of atorvastatin and certain COCs containing ethinyl estradiol increase AUC values for ethinyl estradiol by approximately 20%. Ascorbic acid and acetaminophen may increase plasma ethinyl estradiol concentrations, possibly by inhibition of conjugation. In a clinical drug-drug interaction study conducted in 20 premenopausal women, co-administration of a DRSP (3 mg)/EE (0.02 mg) COC with the strong CYP3A4 inhibitor ketoconazole (200 mg twice daily) for 10 days increased the AUC(0-24h) of DRSP and EE by 2.68-fold (90% CI: 2.44, 2.95) and 1.40-fold (90% CI: 1.31, 1.49), respectively. The increases in Cmax were 1.97-fold (90% CI: 1.79, 2.17) and 1.39-fold (90% CI: 1.28, 1.52) for DRSP and EE, respectively. Although no clinically relevant effects on safety or laboratory parameters including serum potassium were observed, this study only assessed subjects for 10 days. The clinical impact for a patient taking a DRSP-containing COC concomitantly with chronic use of a CYP3A4/5 inhibitor is unknown [see WARNINGS AND PRECAUTIONS (5.2)].

HIV/HCV protease inhibitors and non-nucleoside reverse transcriptase inhibitors

Significant changes (increase or decrease) in the plasma concentrations of estrogen and progestin have been noted in some cases of co-administration with HIV/HCV protease inhibitors or with non-nucleoside reverse transcriptase inhibitors.

Antibiotics

There have been reports of pregnancy while taking hormonal contraceptives and antibiotics, but clinical pharmacokinetic studies have not shown consistent effects of antibiotics on plasma concentrations of synthetic steroids.

Effects of Combined Oral Contraceptives on Other Drugs

COCs containing ethinyl estradiol may inhibit the metabolism of other compounds. COCs have been shown to significantly decrease plasma concentrations of lamotrigine, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Consult the labeling of the concurrently-used drug to obtain further information about interactions with COCs or the potential for enzyme alterations.

In vitro, EE is a reversible inhibitor of CYP2C19, CYP1A1 and CYP1A2 as well as a mechanism-based inhibitor of CYP3A4/5, CYP2C8, and CYP2J2. Metabolism of DRSP and potential effects of DRSP on hepatic CYP enzymes have been investigated in in vitro and in vivo studies. In in vitro studies DRSP did not affect turnover of model substrates of CYP1A2 and CYP2D6, but had an inhibitory influence on the turnover of model substrates of CYP1A1, CYP2C9, CYP2C19, and CYP3A4, with CYP2C19 being the most sensitive enzyme. The potential effect of DRSP on CYP2C19 activity was investigated in a clinical pharmacokinetic study using omeprazole as a marker substrate. In the study with 24 postmenopausal women [including 12 women with homozygous (wild type) CYP2C19 genotype and 12 women with heterozygous CYP2C19 genotype] the daily oral administration of 3 mg DRSP for 14 days did not affect the oral clearance of omeprazole (40 mg, single oral dose) and the CYP2C19 product 5-hydroxy omeprazole. Furthermore, no significant effect of DRSP on the systemic clearance of the CYP3A4 product omeprazole sulfone was found. These results demonstrate that DRSP did not inhibit CYP2C19 and CYP3A4 in vivo.

Two additional clinical drug-drug interaction studies using simvastatin and midazolam as marker substrates for CYP3A4 were each performed in 24 healthy postmenopausal women. The results of these studies demonstrated that pharmacokinetics of the CYP3A4 substrates were not influenced by steady state DRSP concentrations achieved after administration of 3 mg DRSP/day.

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.

Interactions With Drugs That Have the Potential to Increase Serum Potassium Concentration:

There is a potential for an increase in serum potassium concentration in women taking drospirenone and ethinyl estradiol with other drugs that may increase serum potassium concentration [see WARNINGS AND PRECAUTIONS (5.2)].

A drug-drug interaction study of DRSP 3 mg/estradiol (E2) 1 mg versus placebo was performed in 24 mildly hypertensive postmenopausal women taking enalapril maleate 10 mg twice daily. Potassium concentrations were obtained every other day for a total of 2 weeks in all subjects. Mean serum potassium concentrations in the DRSP/E2 treatment group relative to baseline were 0.22 mEq/L higher than those in the placebo group. Serum potassium concentrations also were measured at multiple time points over 24 hours at baseline and on Day 14. On Day 14, the ratios for serum potassium Cmax and AUC in the DRSP/E2 group to those in the placebo group were 0.955 (90% CI: 0.914, 0.999) and 1.010 (90% CI: 0.944, 1.08), respectively. No patient in either treatment group developed hyperkalemia (serum potassium concentrations > 5.5 mEq/L).

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 24 month oral carcinogenicity study in mice dosed with 10 mg/kg/day DRSP alone or 1 + 0.01, 3 + 0.03 and 10 + 0.1 mg/kg/day of DRSP and EE, 0.1 to 2 times the exposure (AUC of DRSP) of women taking a contraceptive dose, there was an increase in carcinomas of the harderian gland in the group that received the high dose of DRSP alone. In a similar study in rats given 10 mg/kg/day DRSP alone or 0.3 + 0.003, 3 + 0.03 and 10 + 0.1 mg/kg/day DRSP and EE, 0.8 to 10 times the exposure of women taking a contraceptive dose, there was an increased incidence of benign and total (benign and malignant) adrenal gland pheochromocytomas in the group receiving the high dose of DRSP. Mutagenesis studies for DRSP were conducted in vivo and in vitro and no evidence of mutagenic activity was observed.

FDA Approved Patient Labeling

Guide for Using SyedaTM (Drospirenone and Ethinyl Estradiol Tablets, USP), 3 mg and 0.03 mg

(droh-SPYE-reh-none, ETH-in-il es-tra-DIE-ole)

WARNING TO WOMEN WHO SMOKE

Do not use SyedaTM 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 SyedaTM?

SyedaTM 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 SyedaTM 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 SyedaTM is right for you, and during the first month that you take SyedaTM, 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

How Well Does SyedaTM 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 two clinical studies, about 1 woman out of 100 women may get pregnant during the first year they use SyedaTM.

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 SyedaTM?

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. SyedaTM 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 SyedaTM 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. SyedaTM can be taken without regard to meals.

2. Look at Your Pill Pack – It has 28 Pills

The SyedaTM pill pack has 21 yellow pills (with hormones) to be taken for three weeks, followed by 7 white pills (without hormones) to be taken for one week.

3. Also look for:

a) Where on the pack to start taking pills,

b) 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 yellow 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, because you are starting the Pill at the beginning of your period. However, if you start SyedaTM 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 yellow pills.

Sunday Start:

1. Take the first yellow 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 SyedaTM 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, SyedaTM 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, SyedaTM should be started when the next application would have been due. When switching from an injection, SyedaTM should be started when the next dose would have been due. When switching from an intrauterine contraceptive or an implant, SyedaTM 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 white pill. Do not wait any days between packs.

What to Do if You Miss Pills

If you miss 1 yellow 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 yellow 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 yellow 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. 2. 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. 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. 4. 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 yellow 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. 2. 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. 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 condoms and spermicides) as a back-up for those 7 days. 4. 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 any of the 7 white 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 yellow pill each day until otherwise directed.

WHO SHOULD NOT TAKE SyedaTM?

Your healthcare provider will not give you SyedaTM 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 • 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 SyedaTM?

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 on time 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.

Due to an increased risk of blood clots, you should stop SyedaTM at least four weeks before you have major surgery and not restart it until at least two weeks after the surgery.

If you are breastfeeding, consider another birth control method until you are ready to stop breastfeeding. Birth control pills that contain estrogen, like SyedaTM, 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. Take another pill if you vomit within 3 to 4 hours after taking your pill, or 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-the-counter medicines, vitamins and herbal supplements.

SyedaTM may affect the way other medicines work, and other medicines may affect how well SyedaTM 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 Syeda™) 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.

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 SyedaTM?

Irregular vaginal bleeding or spotting may occur while you are taking SyedaTM. 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 as you have taken the pills regularly on time.

What if I Miss My Scheduled Period when Taking SyedaTM?

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 regularly on time, 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 SyedaTM if you are pregnant.

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.

General Advice about SyedaTM

Your healthcare provider prescribed SyedaTM for you. Please do not share SyedaTM with anyone else. Keep SyedaTM out of the reach of children.

If you have concerns or questions, ask your healthcare provider. You may also ask your healthcare provider for a more detailed label written for medical professionals.

SyedaTM is a trademark of Sandoz Inc.

The other brands listed are the registered trademarks of their respective owners and are not trademarks of Sandoz Inc.

Manufactured by Laboratorios Leon Farma S.A., Spain

For Sandoz Inc. Princeton, NJ 08540

Rev. March 2016

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