How to Take DROSPERT Chewable Tablets

Chew DROSPERT Chewable Tablets (white active and green inert chewable tablets) completely before swallowing. Do not swallow whole. DROSPERT Chewable Tablets can be taken with or without water and food. Take one chewable tablet daily for 28 consecutive days; one white active chewable tablet daily during the first 24 days and one green inert chewable tablet daily during the 4 following days. Chewable tablets must be taken every day at about the same time of the day so that the interval between two tablets is always 24 hours.

 1.1              Missed Doses

Table 2: Instructions for Missed DROSPERT Chewable Tablets

WARNINGS AND PRECAUTIONS

HOW SUPPLIED/STORAGE AND HANDLING

Clinical Trial 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 safety of DROSPERT Chewable Tablets has been established from studies of DROSPERT tablets [see Clinical Studies (14)]. The data described below reflect exposure to DROSPERT tablets.

Four clinical studies including Study CF111/303 [see Clinical Studies (14)] in females of reproductive potential desiring to prevent pregnancy were conducted. The mean time of DROSPERT exposure ranged from 197 to 328 days. The demographic profile for the pooled study data was: mean age 28 years; mean BMI 25 kg/m²; racial distribution was 83% White; 14% Black; 1% Asian and 2% Other.

Table 3: Adverse Reactions Occurring in ≥ 1% of Females Receiving DROSPERT Tablets in Four Pooled Studies

PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved Patient Labeling (Patient Information and Instructions for Use).

DROSPERT Chewable Tablets and Dosing InstructionsAdvise females on proper daily use of DROSPERT Chewable Tablets and what to do if she misses a pill [see Dosage and Administration (2)]. Inform patient that amenorrhea may occur and instruct patient to check for pregnancy if she misses two consecutive periods.

Counsel patients on the following information:

Recommendation to check serum potassium levels during the first treatment cycle in females receiving daily, long-term treatment for chronic conditions of diseases with medications that may increase serum potassium concentrations.

Sexually Transmitted Infections

DROSPERT Chewable Tablets does not protect against HIV-infection (AIDS) and other sexually transmitted infections.

Use During Pregnancy

DROSPERT Chewable Tablets is not to be used during pregnancy; instruct the patient to stop use if pregnancy is confirmed during treatment [see Use in Specific Populations (8.1)].

Drug Interactions

Advise females to inform their healthcare provider if they take herbal supplements such as St. John’s wort [see Drug Interactions (7.1)].

Distributed by: Exeltis USA, Inc. Florham Park, NJ 07932

Manufactured by: Laboratorios León Farma, S.A., Navatejera, Spain 24008

 

Step 2.

 

Place the day label strip (see Figure B) that starts with the first day of your period (Day 1) on top of the blister pack over “Place the label here”. See Figure C. For example, if your period begins on Monday, place the day label strip with Monday as the first day on the top of your blister pack. See Figure C.

 

FIGURE B

 

 

 

FIGURE C

 

Step 3.

Remove the white pill by pressing the pill through the foil in the bottom of the blister pack. Continue taking the white pills for 24 days.

Step 4.

In the middle of Week 4 start taking the green pills. Take the green pill for 4 days. Your period should start during this time.

Step 5.

When you have taken all of the green pills in your blister pack, get a new blister pack and start taking the white pills from the new blister pack at your usual time the following day, starting with the Day 1 pill.

For a Day 1 start:

·         Begin your next blister pack on the same day of the week as your first cycle blister pack.

What should I do if I miss any DROSPERT Chewable Tablets? If you miss 1 white pill (active pills):

·         Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day.

·         Then continue taking 1 pill every day until you finish the blister pack.

·         You do not need to use a back-up birth control method if you have sex.

If you miss 2 or more white pills (active pills), follow these steps:

·         Take the last missed pill as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day.

·         Then continue to take 1 pill every day until you finish the blister pack (this will mean 1 or more missed white pills will remain in the blister pack).

·         Use a non-hormonal birth control method (such as a condom or spermicide) as a back-up if you have sex during the first 7 days after missing your pills.

If you miss 1 or more green pills (inactive pill):

·         You do not need to take 1 or more missed green pills. Take the next green pill at your regular time, every day until you finish the blister pack (this means 1 or more missed green pills will remain in the blister pack).

If you have any questions or are unsure about the information in this leaflet, call your healthcare provider. You can ask your healthcare provider or pharmacist for information about DROSPERT Chewable Tablets that is written for health professionals.

Distributed by: Exeltis USA, Inc. Florham Park, NJ 07932

Manufactured by: Laboratorios León Farma, S. A., Navatejera, Spain 24008

4780101-01

This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.

Issued: 06/2022

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of DROSPERT. 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:

Immune System Disorders: Hypersensitivity reactions, including rash, urticaria, pruritis, and angioedema

USE IN SPECIFIC POPULATIONS

DOSAGE AND ADMINISTRATION

DROSPERT Chewable Tablets is dispensed in a blister card. DROSPERT Chewable Tablets should be started using a Day 1 start.

Table 1: Instructions for Starting or Switching DROSPERT Chewable Tablets

DESCRIPTION

DROSPERT Chewable Tablets is an oral contraceptive. DROSPERT Chewable Tablets is supplied in a blister card with 28 round, film-coated and unscored chewable tables in the following order:

·      24 white active chewable tablets each containing 3.5 mg of DROSPERT debossed with a “C” on one side and a “D” on the other side

·      4 green inert chewable tablets debossed with a “E” on one side and a “C” on the other side

DROSPERT is a white to almost white or slightly yellow crystalline powder. It is a progestin and neutral molecule with slight solubility in water. DROSPERT is chemically described as (6R,7R,8R,9S,10R,13S,14S,15S,16S,17S)-1,3’,4’,6,6a,7,8,9,10,11, 12,13,14,15,15a,16-

hexadecahydro10,13-dimethylspiro-[17H-dicyclopropa- [6,7:15,16]cyclopenta[a]phenanthrene- 17,2’(5’H)-furan]-3,5’(2H)-dione). It has a molecular weight of 366.49, a molecular formula of C24H30O3, and the structural formula below:

The active chewable tablet is a 5 mm, round, unscored, film-coated, white chewable tablet that contains 3.5 mg of DROSPERT as the active ingredient, and the following inactive ingredients: microcrystalline cellulose, anhydrous lactose, colloidal silicon dioxide, and magnesium stearate. The white film coating is comprised of polyvinyl alcohol-partially hydrolyzed, polyethylene glycol (Macrogol) 3350, talc, and titanium dioxide. The peppermint flavor contains peppermint oil, maltodextrin and modified starch (E 1450).

The inert chewable tablet is a 5 mm, round, unscored, film-coated, green chewable tablet that does not contain DROSPERT. Each inert green chewable tablet contains the following inactive ingredients: lactose monohydrate, colloidal silicon dioxide, corn starch, magnesium stearate, and povidone K 30. The peppermint flavor contains peppermint oil, maltodextrin and modified starch (E 1450). The green film coating consists of FD&C blue 2 aluminum lake, ferric oxide yellow, hypromellose 2910, polysorbate 80, titanium dioxide, and triacetin.

INDICATIONS AND USAGE

DROSPERT Chewable Tablets is a progestin indicated for use by females of reproductive potential to prevent pregnancy.

Advice in Case of Gastrointestinal Disturbances

If vomiting or diarrhea occurs within 3-4 hours after taking chewable tablet, the new chewable tablet (scheduled for the next day) should be taken as soon as possible. The new chewable tablet should be taken within 12 hours of the usual time of tablet-taking if possible. If more than two chewable tablets are missed, the advice concerning missed tablets, including using backup non- hormonal contraception, given above (Table 2) is applicable

CLINICAL PHARMACOLOGY

DOSAGE FORMS AND STRENGTHS

DROSPERT Chewable Tablets is supplied in a blister card with 28 round, film-coated and unscored chewable tablets in the following order:

·      24 white active chewable tablets each containing 3.5 mg of DROSPERT debossed with a “C” on one side and a “D” on the other side

·      4 green inert chewable tablets debossed with a “E” on one side and a “C” on the other side

CONTRAINDICATIONS

DROSPERT Chewable Tablets is contraindicated in females with the following conditions:

·         Renal impairment [see Warnings and Precautions (5.1) and Use in Specific Populations (8.7)]

·         Adrenal insufficiency [see Warnings and Precautions (5.1)]

·         Presence or history of cervical cancer or progestin sensitive cancers [see Warnings and Precautions (5.4)]

·         Liver tumors, benign or malignant, or hepatic impairment [see Warnings and Precautions (5.5) and Use in Specific Populations (8.6)]

·         Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.8)]

Hyperkalemia

DROSPERT Chewable Tablets contains DROSPERT, a progestin, which has anti- mineralocorticoid activity, including the potential for hyperkalemia in high-risk females, comparable to a 25 mg dose of spironolactone. DROSPERT Chewable Tablets is contraindicated in females with conditions that predispose to hyperkalemia (e.g., renalimpairment, hepatic impairment, and adrenal insufficiency). Females receiving daily, long-term treatment for chronic conditions or diseases with medications that may increase serum potassium concentration should have their serum potassium concentration checked prior to starting treatment and during the first treatment cycle. Consider monitoring serum potassium concentration in females at increased risk for hyperkalemia i.e., those females who take a strong CYP3A4 inhibitor long-term and concomitantly with DROSPERT Chewable Tablets. Strong CYP3A4 inhibitors include azole antifungals (e.g., ketoconazole, itraconazole, voriconazole), HIV/HCV protease inhibitors (e.g., indinavir, boceprevir), and clarithromycin [see Drug Interactions (7)]. Monitor females taking DROSPERT Chewable Tablets who later develop medical conditions and/or begin medication that put them at an increased risk for hyperkalemia.

Most females with hyperkalemia in the clinical development studies of DROSPERT had mild potassium elevations and/or isolated increases that returned to normal while still on study medication. No concurrent adverse reactions were attributed to hyperkalemia. In the pivotal trial with DROSPERT, two females (0.2%) with persistent potassium elevations discontinued DROSPERT.

Thromboembolic Disorders

Epidemiological studies have not indicated an association between progestin-only preparations and an increased risk of myocardial infarction, cerebral thromboembolism, or venous thromboembolism.

Combined oral contraceptives containing DROSPERT and ethinyl estradiol may be associated with a higher risk of venous thromboembolism (VTE) than those containing some other progestins in combination with ethinyl estradiol. It is unknown whether the risk of VTE is increased with DROSPERT alone; however, if there is a risk, it is expected to be lower than that of DROSPERT in combination with ethinyl estradiol.

When prescribing DROSPERT Chewable Tablets, consider the increased risk of thromboembolism inherent in the postpartum period and in females with a history of thromboembolism.

Discontinue DROSPERT Chewable Tablets if arterial or venous thromboembolic events occur. Consider discontinuing DROSPERT Chewable Tablets, if feasible, in case of prolonged immobilization due to surgery or illness.

Bone Loss

Treatment with DROSPERT Chewable Tablets leads to decreased estradiol serum levels. It is unknown if this may cause a clinically relevant loss of bone mineral density.

Cervical Cancer

Some studies suggest that use of combination hormonal contraceptives containing progestin and estradiol has been associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors.

Pharmacokinetics

The pharmacokinetic parameters after a single dose administration of DROSPERT Chewable Tablets under fasting condition in healthy female subjects are summarized in Table 4.

Table 4: Pharmacokinetic Parameters After Single Dose Administration of DROSPERT Chewable Tablets Under Fasting Condition

SD = Standard Deviation

^*Tmax values are median with range between parentheses

Absorption

The pharmacokinetics of oral DROSPERT is dose-proportional following single doses ranging from 1-10 mg. During a treatment cycle, maximum steady-state concentrations of DROSPERT are reached after about 10 days of treatment. Plasma DROSPERT Cmax and area under the curve (AUC) accumulate by a factor of about 1.5 to 2 following multiple dose administration.

Effect of Food

A food-effect study involving administration of DROSPERT Chewable Tablets to healthy volunteers under fasting conditions and with a high-fat-high-calorie meal (i.e., 894 calorie meal in which 57% of calories are derived from fat) indicated that the Cmax was decreased approximately 10% while the AUC remained unchanged. This decrease in exposure is not clinically significant, and therefore DROSPERT Chewable Tablets can be taken without regards to meals.

Distribution

DROSPERT is 95% to 97% bound to serum albumin and does not bind to sex hormone binding globulin (SHBG) or corticosteroid binding globulin (CBG). The apparent volume of distribution of DROSPERT is approximately 4 L/kg.

Elimination

Metabolism

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

Excretion

DROSPERT serum concentrations are characterized by a terminal disposition phase half-life of approximately 30 hours after both single and multiple dose regimens. Excretion of DROSPERT

 was nearly complete after ten days and amounts excreted were slightly higher in feces compared to urine. DROSPERT was extensively metabolized and only trace amounts of unchanged DROSPERT were excreted in urine and feces.

Specific Populations

Patients with Hepatic Impairment:

The mean exposure to DROSPERT in females with moderate liver impairment is approximately three times higher than the exposure in females with normal liver function. DROSPERT Chewable Tablets has not been studied in females with severe hepatic impairment [see Contraindications (4) and Warnings and Precautions (5.5)].

Patients with Renal Impairment:

The effect of renal impairment on the pharmacokinetics of DROSPERT (3 mg daily for 14 days) and the effect of DROSPERT on serum potassium concentrations were investigated in three separate groups of female subjects (n = 28, age 30–65). 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 DROSPERT treatment, the serum DROSPERT concentrations in the group with CLcr of 50–79 mL/min were comparable to those in the control group with CLcr ≥ 80 mL/min. The serum DROSPERT concentrations were on average 37% higher in the group with CLcr of 30–49 mL/min compared to those in the control group. DROSPERT 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 (5.1)].

Drug Interaction Studies:

In a clinical drug-drug interaction study conducted in 20 premenopausal females, co- administration of a combined oral contraceptive product containing DROSPERT (3 mg)/EE (0.02 mg) with the strong CYP3A4 inhibitor ketoconazole (200 mg twice daily) for 10 days increased the AUC(0-24h) and Cmax of DROSPERT by 2.68-fold (90% CI: 2.44, 2.95) and 1.97- fold (90% CI: 1.79, 2.17), respectively.

Liver Disease

Discontinue DROSPERT Chewable Tablets if jaundice or acute or chronic disturbances of liver function develop. Do not resume use until markers of liver function return to normal and DROSPERT Chewable Tablets causation has been excluded.

DROSPERT Chewable Tablets is contraindicated in females with liver tumors, benign or malignant, or hepatic impairment [see Use 

Ectopic Pregnancy

Be alert to the possibility of ectopic pregnancy in females who become pregnant or complain of lower abdominal pain while on DROSPERT Chewable Tablets

Risk of Hyperglycemia in Patients with Diabetes

Some patients receiving progestins, including DROSPERT Chewable Tablets, may exhibit a decrease in insulin sensitivity. Therefore, patients with diabetes may be at greater risk of hyperglycemia and may require additional medication adjustments or monitoring

Bleeding Irregularities and Amenorrhea

Females using DROSPERT Chewable Tablets may experience unscheduled (breakthrough or intracyclic) bleeding and spotting, especially during the first three months of use. Bleeding irregularities may resolve over time or by changing to a different contraceptive product. If bleeding persists or occurs after previously regular cycles, evaluate for causes such as pregnancy or malignancy.

Based on subject diaries from four clinical trials of DROSPERT, 64.4% of females experienced unscheduled bleeding at Cycle 1. This percentage decreased to 40.3% by Cycle 13.

A total of 91 out of 2593 subjects (3.5%) discontinued DROSPERT due to menstrual bleeding disorders including metrorrhagia, menstruation irregular, vaginal hemorrhage, menorrhagia, uterine hemorrhage, and amenorrhea.

If scheduled bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or two active chewable tablets or started taking them on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and perform appropriate diagnostic measures. If the patient has adhered to the prescribed dosing schedule and misses two consecutive periods, rule out pregnancy.

Depression

Carefully observe females for a history of depression and discontinue DROSPERT Chewable Tablets if depression recurs to a serious degree. Data on the association of progestin-only contraceptive products with onset of depression and exacerbation of depression are limited.
 

ADVERSE REACTIONS

1        The following clinically significant adverse reactions are described elsewhere in other sections of the labeling:

 The following clinically significant adverse reactions are described elsewhere in other sections of the labeling:

NONCLINICAL TOXICOLOGY

DRUG INTERACTIONS

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

Effects of Other Drugs on Hormonal Contraceptives

Substances decreasing the systemic concentrations of hormonal contraceptives (HCs) and potentially diminishing the efficacy of HCs:

Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the systemic concentrations of HCs and potentially diminish the effectiveness of HCs or increase breakthrough bleeding.

Some drugs or herbal products that may decrease the effectiveness of HCs include efavirenz, phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, rifabutin, rufinamide, aprepitant, and products containing St. John’s wort.

Interactions between HCs and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel females to use an alternative non-hormonal method of contraception or a back-up method when enzyme inducers are used with HCs, and to continue back-up non-hormonal contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability.

Substances increasing the systemic concentrations of hormonal contraceptives (HCs):

In a clinical drug-drug interaction study conducted in premenopausal females, once daily

co-administration of DROSPERT 3 mg/ethinyl estradiol (EE) 0.02 mg containing tablets with strong CYP3A4 inhibitor, ketoconazole 200 mg twice daily for 10 days resulted in a moderate increase of DROSPERT systemic exposure.

Influence of DROSPERT Chewable Tablets on Other Medicinal Products

Based on in vitro studies and in vivo interaction studies in female volunteers using omeprazole, simvastatin and midazolam as marker substrate, an interaction of DROSPERT with the metabolism of other active substances is unlikely.

Potential to increase serum potassium concentration:

There is a potential for an increase in serum potassium concentration in females taking DROSPERT Chewable Tablets with other drugs that may increase serum potassium concentration (for example, ACE inhibitors, angiotensin-II receptor antagonists, potassium- sparing diuretics, potassium supplementation, heparin, aldosterone antagonists, and NSAIDS) [see Warnings and Precautions (5.1)].

Pregnancy

Risk Summary

Based on epidemiologic studies and meta-analyses, there is little or no increased risk of birth defects in the children of females who inadvertently use oral progestins during early pregnancy (See Data).

 Discontinue DROSPERT Chewable Tablets if pregnancy occurs, because there is no reason to use hormonal contraceptives during pregnancy

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively.

Data

Human Data

Epidemiologic studies and meta-analyses have not found an increased risk of genital or non- genital birth defects (including cardiac anomalies and limb-reduction defects) following maternal use of oral progestins before conception or during early pregnancy.

Lactation

Risk Summary

Negligible amounts of DROSPERT are excreted in the breast milk (see Data). Thus, at therapeutic doses of DROSPERT Chewable Tablets, no effects on breastfed newborns/infants are anticipated. In general, no adverse effects have been found on milk production or on the health, growth, or development of the infant with use of progestin-only pills (POPs).

Human Data

After daily administration of DROSPERT (4 mg tablets), the average DROSPERT concentration in breast milk over 24-hour period is 5.6 ng/mL. Based on this concentration, the estimated average infant daily dosages for an exclusively breastfed infant is 840 ng/kg/day (relative infant dose is 1.5%).

Pediatric Use

Safety and efficacy of DROSPERT tablets has been established in females of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and users 16 years and older.

Study CF111/304 evaluated the bleeding associated with DROSPERT in females ≥12 years of age. Bleeding data were generally consistent with those from Study CF111/303 in adult females [see Clinical Studies (14)].

Use of this product before menarche is not indicated.

Geriatric Use

DROSPERT Chewable Tablets has not been studied in postmenopausal females and is not indicated in this population.

CLINICAL STUDIES

The efficacy of DROSPERT Chewable Tablets has been established based upon studies of DROSPERT tablets. The data presented below reflect results from clinical studies of DROSPERT tablets.

The efficacy of DROSPERT tablets was evaluated in Study CF111/303 (NCT02269241), a single arm multicenter, clinical trial conducted in the U.S. The efficacy population consisted of 953 females ≤ 35 years of age with 5,547 evaluable cycles. The demographic profile for females was: mean age 26.4 years and mean BMI 28.5 kg/m². The racial distribution was 53.3% Caucasian; 38.5% African American; 2.2% Asian and 6% other. During these cycles, a total of 17 (1.8%) females reported pregnancy, leading to a Pearl Index (95% CI) of 4.0 (2.3, 6.4).

One female who became pregnant during the study was breastfeeding and not included in the Pearl Index (PI) calculation. The confidence interval for the PI was calculated assuming that events of pregnancy had a Poisson distribution.

Out of the 953 females evaluated for efficacy, 332 subjects had a baseline BMI ≥ 30 (35%) and 173 females had a baseline BMI ≥ 35 (18%). Data were insufficient to analyze PI by BMI subgroups.

Table 5: Pearl Index Based on Evaluable Cycles and Reported Pregnancies in Females

≤ 35 Years of Age in Study CF111/303

Effect on Bleeding Patterns

The bleeding pattern with DROSPERT tablets was assessed systematically using patient diaries in Study CF111/303 in adult females.

The percentage of females experiencing scheduled bleeding or unscheduled bleeding/spotting decreased over time. Overall, the percentage of females with scheduled bleeding or spotting decreased from 81% in Cycle 1 to 26% in Cycle 13. Similarly, the overall percentage of females with unscheduled bleeding or spotting decreased from 61% in Cycle 1 to 40% in Cycle 13. The percentages of females with scheduled and unscheduled bleeding or spotting generally decreased through Cycle 10 and were maintained at a consistent level thereafter.

Table 6: Adult Females with Scheduled and Unscheduled Bleeding or Spotting: (Safety Set)

*Abbreviations: m = number of subjects with cycle data; n = number of subjects with bleeding or spotting.

In Study CF111/304 conducted in Europe in post-menarchal, female, adolescents (12 through 17 years of age), bleeding data were generally consistent with those from Study CF111/303 in adult females. DROSPERT tablets was associated with a decrease in the percentage of adolescent females experiencing bleeding or spotting over time. The percentage of adolescent females with scheduled bleeding or spotting decreased from 98.0% in Cycle 1 to 28.4% in Cycle 13. The percentage of adolescent females with scheduled bleeding or spotting generally decreased through Cycle 9 and was maintained at a consistent level thereafter. In contrast, the percentage of adolescent females with unscheduled bleeding or spotting was maintained at a relatively consistent level during the study (53.0% in Cycle 1 versus 52.2% in Cycle 13).

In addition to Studies CF111/303 and CF111/304, an additional two studies evaluated bleeding associated with DROSPERT tablets. A total of 91 females (0.4%) from these four studies discontinued DROSPERT tablets due to problems with irregular bleeding or amenorrhea.

Hepatic Impairment

DROSPERT Chewable Tablets is contraindicated in females with hepatic impairment [see Contraindications (4) and Warnings and Precautions (5.5)]. The mean exposure to DROSPERT in females with moderate liver impairment is approximately three times higher than the exposure

 in females with normal liver function. DROSPERT Chewable Tablets has not been studied in females with severe hepatic impairment [see Clinical Pharmacology (12.3)].

Renal Impairment

DROSPERT Chewable Tablets is contraindicated in females with renal impairment [see Contraindications (4) and Warnings and Precautions (5.1)].

In subjects with creatinine clearance (CLcr) of 50–79 mL/min, serum DROSPERT levels were comparable to those in a control group with CLcr ≥ 80 mL/min. In subjects with CLcr of 30–49 mL/min, serum DROSPERT concentrations were on average 37% higher than those in the control group. In addition, there is a potential to develop hyperkalemia in subjects with renal impairment whose serum potassium is in the upper reference range, and who are concomitantly using potassium sparing drugs [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)].

OVERDOSAGE

There have been no reports of serious deleterious effects from overdosage of DROSPERT Chewable Tablets. Symptoms that may occur include are nausea, vomiting, and vaginal bleeding. There are no antidotes and treatment should be to provide symptomatic support.

DROSPERT is a spironolactone analogue which has anti-mineralocorticoid properties. Therefore, serum potassium and sodium, and evidence of metabolic acidosis, should be monitored in cases of overdose.

Mechanism of Action

DROSPERT Chewable Tablets progestin-only oral contraceptive lowers the risk of becoming pregnant primarily by suppressing ovulation.

Pharmacodynamics

DROSPERT is a spironolactone analogue with anti-mineralocorticoid activity.

Laboratory Tests

The use of contraceptive steroids may influence the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, serum levels of (carrier) proteins, e.g., corticosteroid binding globulin and lipid/lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 24-month oral carcinogenicity study in mice with doses up to 10 mg/kg/day DROSPERT, equating to 2 times the maximum clinical exposure (based on AUC), there was an increase in carcinomas of the harderian gland in the high dose DROSPERT group. In a similar study in rats given doses up to 10 mg/kg/day DROSPERT, 10 times the maximum clinical exposure (based on AUC), there was an increased incidence of benign and total (benign and malignant) adrenal gland pheochromocytomas in the high dose DROSPERT group. Mutagenesis studies for DROSPERT were conducted in vivo and in vitro and no evidence of mutagenic activity was observed.

How Supplied

DROSPERT Chewable Tablets is packaged in clear to a slightly opaque PVC-PVDC/Aluminum blister cards. Each blister card holds 28 5-mm round, film-coated and unscored chewable tablets in the following order:

·      24 white active chewable tablets each containing 3.5 mg of DROSPERT debossed with a “C” on one side and a “D” on the other side

·      4 green inert chewable tablets debossed with a “E” on one side and a “C” on the other side

DROSPERT Chewable Tablets is supplied in cardboard carton containing a blister card of 28 chewable tablets: NDC 0642-7478-01

Storage and Handling

Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].