Get your patient on Slynd (Drospirenone)

SLYND is dispensed in a blister card. SLYND should be started using a Day 1 start.

SLYND (white active and green inert tablets) is swallowed whole once a day. Take one tablet daily for 28 consecutive days; one white active tablet daily during the first 24 days and one green inert tablet daily during the 4 following days. 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.

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

Safety and efficacy of SLYND have 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 SLYND 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.

SLYND has not been studied in postmenopausal females and is not indicated in this population.

SLYND is contraindicated in females with hepatic impairment [see Contraindications (4) , Warnings and Precautions (5.5) ]. The mean exposure to drospirenone in females with moderate liver impairment is approximately three times higher than the exposure in females with normal liver function. SLYND has not been studied in females with severe hepatic impairment [see Clinical Pharmacology (12.3) ] .

SLYND is contraindicated in females with renal impairment [see Contraindications (4) , Warnings and Precautions (5.1) ].

In subjects with creatinine clearance (CLcr) of 50–79 mL/min, serum DRSP levels were comparable to those in a control group with CLcr ≥ 80 mL/min. In subjects with CLcr of 30–49 mL/min, serum DRSP 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) ].

SLYND contains drospirenone, a progestin, which has anti-mineralocorticoid activity, including the potential for hyperkalemia in high-risk females, comparable to a 25 mg dose of spironolactone. SLYND is contraindicated in females with conditions that predispose to hyperkalemia (e.g. renal impairment, 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 SLYND. 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 SLYND 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 SLYND 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, two females (0.2%) with persistent potassium elevations discontinued SLYND.

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 drospirenone 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 drospirenone alone; however, if there is a risk, it is expected to be lower than that of drospirenone in combination with ethinyl estradiol.

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

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

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

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.

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

SLYND is contraindicated in females with liver tumors, benign or malignant, or hepatic impairment [see Use in Specific Populations (8.6) ].

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

Some patients receiving progestins, including SLYND, 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.

Females using SLYND 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 SLYND, 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 SLYND due to menstrual bleeding disorders including metrorrhagia, menstrual 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 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.

Carefully observe females for a history of depression and discontinue SLYND 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.

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

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

Drospirenone is a spironolactone analogue with anti-mineralocorticoid activity.

In a 24-month oral carcinogenicity study in mice with doses up to 10 mg/kg/day DRSP, 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 DRSP group. In a similar study in rats given doses up to 10 mg/kg/day DRSP, 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 DRSP group. Mutagenesis studies for DRSP were conducted in vivo and in vitro and no evidence of mutagenic activity was observed.

Pregnancy Prevention

The efficacy of SLYND was evaluated in Study CF111/303 (NCT02269241). This single arm multicenter, clinical trial was 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/m ² . 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.

Effect on Bleeding Patterns

The bleeding pattern with SLYND 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.

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. SLYND 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, two additional studies evaluated bleeding associated with SLYND. A total of 91 females (3.5%) from these four studies discontinued SLYND due to problems with irregular bleeding or amenorrhea.

SLYND (drospirenone) tablets is packaged in clear to a slightly opaque PVC-PVDC/Aluminum blister cards. Each blister card holds 24 white round active film-coated tablets, each containing 4mg of drospirenone and 4 green round inert film-coated tablets that do not contain drospirenone. SLYND is supplied in cardboard cartons containing a blister card of 28 tablets: NDC 0642-7470-01.

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