1 INDICATIONS AND USAGE Tydemy is a combination of drospirenone, a progestin and ethinyl estradiol, an estrogen containing a folate, indicated for use by females of reproductive potential to: Prevent pregnancy.

( 1.1 ) Raise folate levels in females of reproductive potential who choose to use an oral contraceptive for contraception.

( 1.2 ) 1.1 Oral Contraceptive Tydemy TM is indicated for use by females of reproductive potential to prevent pregnancy.

1.2 Folate Supplementation Tydemy is indicated in females of reproductive potential who choose to use an oral contraceptive as their method of contraception, to raise folate levels for the purpose of reducing the risk of a neural tube defect in a pregnancy conceived while taking the product or shortly after discontinuing the product.

6 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 )] The most frequent adverse reactions (≥ 2%) in contraception and folate clinical trials are premenstrual syndrome (12.4%), headache/migraine (10.3%), breast pain/tenderness/discomfort (8.1%), nausea/vomiting (4.4%), mood changes (2.3%) and abdominal pain/tenderness/discomfort (2.2%).

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc.

at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 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.

Contraception and Folate Supplementation Clinical Trials The data provided reflect the experience with the use of Yasmin ® (3 mg DRSP/0.03 mg EE) in the adequate and well-controlled studies for contraception (N=2,837) and folate supplementation (N=172).

For contraception, the US pivotal clinical study (N=326) for the oral contraception indication for Yasmin ® was a multicenter, open-label trial in healthy women aged 18 to 35 who were treated with Yasmin ® for up to 13 cycles.

The second contraceptive pivotal study (N=442) was a multicenter, randomized, open-label comparative European study of Yasmin ® 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 primary efficacy study using drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets for folate supplementation was a randomized, single-center European trial in 172 healthy, female subjects aged 18 to 40 years comparing the pharmacodynamic effects of Yasmin ® + 0.451 mg levomefolate calcium to Yasmin ® co-administered with folic acid during 24 weeks of treatment followed by 20 weeks of open-label Yasmin ® .

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: premenstrual syndrome (12.4%), headache/migraine (10.3%), breast pain/tenderness/discomfort (8.1%), nausea/vomiting (4.4%), mood changes (depression, depressed mood, irritability, mood swings, mood altered and affect lability (2.3%), and abdominal pain/discomfort/tenderness (2.2%).

Adverse Reactions (≥ 1%) Leading to Study Discontinuation Contraception Clinical Trials 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%).

Folate Clinical Trial There were no subjects who discontinued due to an adverse reaction.

Serious Adverse Reactions: Contraception Clinical Trials : depression, pulmonary embolism, toxic skin eruption, and uterine leiomyoma.

Folate Supplementation Clinical Trial : none reported in the clinical trial 6.2 Postmarketing Experience Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 - 1.12 (Figure 3).

Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 3).

One of these studies reported no association between breast cancer risk and COC use.

The other two studies found an increased relative risk of 1.19 - 1.33 with current or recent use.

Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8-10 years of COC use.

Figure 3: Relative Studies of Risk of Breast Cancer with Combined Oral Contraceptives RR = relative risk; OR = odds ratio; HR = hazard ratio.

"ever COC" are females with current or past COC use; "never COC use" are females that never used COCs.

The following adverse reactions have been identified during post-approval use of Yasmin ® .

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 Image