Yasmin (Page 6 of 6)

13 NONCLINICAL TOXICOLOGY

13.1 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.

14 CLINICAL STUDIES

In the clinical efficacy studies of up to 2 years duration, 2,629 subjects completed 33,160 cycles of use without any other contraception. The mean age of the subjects was 25.5 ± 4.7 years. The age range was 16 to 37 years. The racial demographic was: 83% Caucasian, 1% Hispanic, 1% Black, <1% Asian, <1% other, <1% missing data, 14% not inquired and <1% unspecified. Pregnancy rates in the clinical trials were less than one per 100 woman-years of use.

15 REFERENCES

1. Dinger JC, Heinemann LAJ, et al: The safety of a drospirenone-containing oral contraceptive: final results from the European active surveillance study on oral contraceptives based on 142,475 women-years of observation. Contraception 2007;75:344-354.

2. Seeger JD, Loughlin J, Eng PM, et al: Risk of thromboembolism in women taking ethinyl estradiol/drospirenone and other oral contraceptives. Obstetrics & Gynecology 2007;110(3):587-593.

3. van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, et al: The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ 2009;339:b2921.

4. Lidegaard O, Lokkegaard E, Svendsen AL, et al: Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ 2009; 339:b2890.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Yasmin (drospirenone/ethinyl estradiol) tablets are available in blister packs (54868-4590-0).

The film-coated tablets are rounded with biconvex faces, one side is embossed with a regular hexagon shape with DO or DP.

Each blister pack contains 28 film-coated tablets in the following order:

21 round, biconvex, yellow, film-coated tablets with embossed “DO” in a regular hexagon on one side each containing 3 mg drospirenone and 0.03 mg ethinyl estradiol

7 round, biconvex, white, film-coated tablets with embossed “DP” in a regular hexagon on one side

16.2 Storage

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

17 PATIENT COUNSELING INFORMATION

See “FDA-approved patient labeling (Patient Information).”

• Counsel patients that cigarette smoking increases the risk of serious cardiovascular events from COC use, and that women who are over 35 years old and smoke should not use COCs.
• Counsel patients that the increased risk of VTE compared to non-users of COCs is greatest after initially starting a COC or restarting (following a 4-week or greater pill-free interval) the same or a different COC.
• Counsel patients that Yasmin does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
• Counsel patients on Warnings and Precautions associated with COCs.
• Counsel patients that Yasmin contains DRSP. Drospirenone may increase potassium. Patients should be advised to inform their healthcare provider if they have kidney, liver or adrenal disease because the use of Yasmin in the presence of these conditions could cause serious heart and health problems. They should also inform their healthcare provider if they are currently on daily, long-term treatment (NSAIDs, potassium-sparing diuretics, potassium supplementation, ACE inhibitors, angiotensin-II receptor antagonists, heparin or aldosterone antagonists) for a chronic condition.
• Inform patients that Yasmin is not indicated during pregnancy. If pregnancy occurs during treatment with Yasmin, instruct the patient to stop further intake.
• Counsel patients to take one tablet daily by mouth at the same time every day. Instruct patients what to do in the event pills are missed. See “What to Do if You Miss Pills” section in FDA-Approved Patient Labeling .
• Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with COCs.
• Counsel patients who are breastfeeding or who desire to breastfeed that COCs may reduce breast milk production. This is less likely to occur if breastfeeding is well established.
• Counsel any patient who starts COCs postpartum, and who has not yet had a period, to use an additional method of contraception until she has taken a yellow tablet for 7 consecutive days.

• Counsel patients that amenorrhea may occur. Rule out pregnancy in the event of amenorrhea in two or more consecutive cycles.

Manufactured for Bayer HealthCare Pharmaceuticals Inc.

Wayne, NJ 07470

Manufactured in Germany

©2012 Bayer HealthCare Pharmaceuticals Inc. All Rights Reserved

Bayer HealthCare Pharmaceuticals Inc.

Additional barcode labeling by:
Physicians Total Care, Inc.
Tulsa, Oklahoma 74146

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

PLACE DAY LABEL HERE

START

YASMIN^® 28

3 MG/0.03 MG

(DROSPIRENONE & ETHINYL ESTRADIOL TABLETS)

Package/Label Principal Display Panel

NDC 54868-4590-0

1 Unit

YASMIN

(drospirenone and ethinyl estradiol tablets) 3 mg/0.03 mg

This product (like all oral contraceptives) is

intended to prevent pregnancy. It does not

protect against HIV infection (AIDS) and other

sexually transmitted diseases.

Store at 25°C with excursions permitted between

15–30°C. [See USP Controlled Room Temperature].

To the Dispenser: This unit contains two pieces of

information intended for the patient, which are

combined in a single booklet. This informational

piece is to be provided to the patient with each

prescription.

Rx only

image of package label

YASMIN drospirenone and ethinyl estradiol kit

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:54868-4590(NDC:50419-402)

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:54868-4590-0 1 BLISTER PACK in 1 PACKAGE contains a BLISTER PACK 1 1 KIT in 1 BLISTER PACK This package is contained within the PACKAGE (54868-4590-0)

Quantity of Parts Part # Package Quantity Total Product Quantity Part 1 21 Part 2 7

Part 1 of 2 YASMIN drospirenone and ethinyl estradiol tablet, film coated

Product Information Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength DROSPIRENONE (DROSPIRENONE) DROSPIRENONE 3 mg ETHINYL ESTRADIOL (ETHINYL ESTRADIOL) ETHINYL ESTRADIOL 0.03 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN FERRIC OXIDE YELLOW HYPROMELLOSES LACTOSE MONOHYDRATE POLYETHYLENE GLYCOL 6000 MAGNESIUM STEARATE POVIDONE K25 TALC TITANIUM DIOXIDE

Product Characteristics Color yellow (YELLOW) Score no score Shape ROUND (ROUND) Size 6mm Flavor Imprint Code Contains

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021098 01/15/2002

Part 2 of 2 INERT inert tablet, film coated

Product Information Route of Administration ORAL DEA Schedule

Inactive Ingredients Ingredient Name Strength STARCH, CORN HYPROMELLOSES LACTOSE MONOHYDRATE MAGNESIUM STEARATE POVIDONE K25 TALC TITANIUM DIOXIDE

Product Characteristics Color white (WHITE) Score no score Shape ROUND (ROUND) Size 6mm Flavor Imprint Code Contains

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021098 01/15/2002

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021098 01/15/2002

Labeler — Physicians Total Care, Inc. (194123980)

Establishment
Name	Address	ID/FEI	Operations
Physicians Total Care, Inc.		194123980	relabel

Revised: 03/2012 Physicians Total Care, Inc.