Case Study: USFDA approval of Exeltis’s Slynd, an oral contraceptive tablet

Exeltis USA, Inc. a division of the global pharmaceutical group Insud Pharma, announced that the US Food and Drug Administration (FDA) has approved the new drug application (NDA) for Slynd containing drospirenone 4 mg, an oral contraceptive tablet for pregnancy prevention.

Features:

• Slynd, a progestin-only oral contraceptive, lowers the risk of becoming pregnant primarily by suppressing ovulation.
• It contains the synthetic progestin drospirenone in a 4mg dosage strength that is given in a 24/4 dose regimen.
• Drospirenone is a spironolactone analogue with antimineralocorticoid and antiandrogenic activity.
• Slynd, a progestin-only pill (POP) is a novel estrogen-free oral contraceptive that is intended as a 24 active with 4 inactive tablet dosing regimen and also allows a 24-hour missed pill window. This not only can mean favorable safety and efficacy but an improved bleeding profile and contraceptive efficacy for up to 24 hours in the event of a delayed or missed dose.

Packaging:

SLYND (drospirenone) is for use as an oral contraceptive. It is supplied as clear to a slightly opaque PVC-PVDC/Aluminum blister cards, each holding of 24 white tablets each containing 4 mg of drospirenone, a synthetic progestational compound and 4 green inert tablets.

The active tablet is a 5 mm, round, unscored, film-coated, white tablet that contains 4mg of drospirenone as the active ingredient, and microcrystalline cellulose NF, anhydrous lactose NF, colloidal silicon dioxide NF, magnesium stearate NF, polyvinyl alcohol partially hydrolyzed NF, talc NF, titanium dioxide NF, and polyethylene glycol NF as the inactive ingredients. Each tablet is debossed with the letter “E” on one side and the letter “D” on the other sides.

The inert tablet is a 5 mm, round, unscored, film-coated, green tablet that does not contain drospirenone. Each inert green tablet contains the following inactive ingredients: Lactose monohydrate NF, corn starch NF, povidone 30000 NF, colloidal silicon dioxide NF, magnesium stearate NF, hypromellose NF, talc NF, titanium dioxide USP, polysorbate 2910 NF, triacetin NF, FD&C blue 2 aluminum lake and yellow ferric oxide.

Clinical Basis of approval:

In clinical trials, Slynd (a synthetic form of progesterone that has a similar pharmacological profile to the natural hormone progesterone) showed no instances of thromboembolic events experienced by some women taking COCs, which by definition contain estrogen. In addition, the safety of Slynd™ is supported by its approval with no black box warning unlike other combined oral contraceptives. But for females with conditions that predispose to hyperkalemia (e.g. renal impairment, hepatic impairment and adrenal insufficiency), Slynd is contraindicated due to its anti-mineralocorticoid activity