Skyla IUD

Skyla is a LNG-releasing IUS consisting of a T-shaped polyethylene frame with a steroid reservoir containing a total of 13.5 mg LNG.

The following serious or otherwise important adverse reactions are discussed elsewhere in the labeling:

• Ectopic Pregnancy [see Warnings and Precautions (5.1)] • Intrauterine Pregnancy [see Warnings and Precautions (5.2)] • Group A Streptococcal Sepsis (GAS) [see Warnings and Precautions (5.3)] • Pelvic Inflammatory Disease [see Warnings and Precautions (5.4)] • Bleeding Pattern Alterations [see Warnings and Precautions (5.5)] • Perforation [see Warnings and Precautions (5.6)] • Expulsion [see Warnings and Precautions (5.7)] • Ovarian Cysts [see Warnings and Precautions (5.8)]

Clinical Trials 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 clinical practice.

The data described below reflect exposure to Skyla in 1,672 patients in two contraception studies, including 1,383 exposed for one year and 993 who completed the three year studies. The population was generally healthy, 18 to 40-year old females requesting contraception and predominately Caucasian (82.6%). The data cover more than 40,000 cycles of exposure. The frequencies of reported adverse drug reactions represent crude incidences.

Most common adverse reactions (occurring in ≥ 5% users) were increased bleeding (7.8%), vulvovaginitis (20.2%), abdominal/pelvic pain (18.9%), acne/seborrhea (15.0%), ovarian cyst (13.2%), headache (12.4%), dysmenorrhea (8.6%), breast pain/discomfort (8.6%) and nausea (5.5%).

In the contraception studies, 18% discontinued prematurely due to an adverse reaction. The most common adverse reactions leading to discontinuation (in >1% of users) were uterine bleeding complaints (4.6%), device expulsion (3.2%), acne/seborrhea (2.9%), abdominal pain (2.5%) dysmenorrhea/uterine spasms (2.0%) and pelvic pain (1.8%).

Other common adverse reactions (occurring in ≥ 1% users) by System Organ Class (SOC): The frequencies of adverse reactions observed in clinical trials are summarized in Table 3 by SOC (presented as crude incidences).

Table 3: Adverse reactions that occurred in at least 1% of Skyla users in clinical trials by SOC

* Ovarian cysts were reported as AEs if they were abnormal, non-functional cysts and/or had a diameter >3 cm on ultrasound examination † Not all bleeding alterations were captured as adverse reactions [see Warnings and Precautions (5.5)].
System Organ Class	Adverse Reaction	Incidence (%) (N=1,672)
Reproductive System and Breast Disorders	Vulvovaginitis	20.2
	Ovarian cyst*	13.2
	Dysmenorrhoea	8.6
	Increased bleeding†	7.8
	Breast pain/discomfort	5.3/3.3
	Genital discharge	4.2
	Device expulsion (complete and partial)	3.2
	Upper genital tract infection	1.4
Gastrointestinal Disorders	Abdominal pain/pelvic pain	12.7/6.2
	Nausea	5.5
Skin and Subcutaneous Tissue Disorders	Acne/Seborrhoea	13.6/1.4
	Alopecia	1.2
Nervous System Disorders	Headache	12.4
	Migraine	2.3
Psychiatric Disorders	Depression/ Depressed mood	3.8/0.5

Postmarketing Experience

The following adverse reactions have been identified during post approval use of a LNG-releasing IUS. 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.

• Arterial thrombotic and venous thromboembolic events, including cases of pulmonary emboli, deep vein thrombosis and stroke • Hypersensitivity including rash, urticaria, and angioedema • Device breakage

Carcinogenesis, Mutagenesis, Impairment of Fertility

[See Warnings and Precautions (5.9).]