Lo Simpesse

Do not prescribe Lo Simpesse to women who are known to have the following conditions:

• A high risk of arterial or venous thrombotic diseases. Examples include women who are known to:
  • Smoke, if over age 35
  • Have deep vein thrombosis or pulmonary embolism, now or in the past
  • Have cerebrovascular disease
  • Have coronary artery disease
  • Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation)
  • Have hypercoagulopathies
  • Have uncontrolled hypertension
  • Have diabetes with vascular disease
  • Have headaches with focal neurological symptoms or have migraine headaches with or without aura if over age 35
• Breast cancer or other estrogen- or progestin-sensitive cancer, now or in the past
• Liver tumors, benign or malignant, or liver disease
• Pregnancy, because there is no reason to use OCs during pregnancy
• Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations [see Warnings and Precautions (5.4)]. 

No formal drug-drug interaction studies were conducted with Lo Simpesse.

Changes in Contraceptive Effectiveness Associated with Co-Administration of Other Products

If a woman on hormonal contraceptives takes a drug or herbal product that induces enzymes, including CYP3A4, that metabolize contraceptive hormones, counsel her to use additional contraception or a different method of contraception. Drugs or herbal products that induce such enzymes may decrease the plasma concentrations of contraceptive hormones, and may decrease the effectiveness of hormonal contraceptives or increase breakthrough bleeding.  Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include:

• barbiturates
• bosentan
• carbamazepine 
• felbamate 
• griseofulvin
• oxcarbazepine
• phenytoin
• rifampin
• St. John’s wort
• topiramate

HIV protease inhibitors: Significant changes (increase or decrease) in the plasma levels of the estrogen and progestin have been noted in some cases of co-administration of HIV protease inhibitors.

Antibiotics: There have been reports of pregnancy while taking hormonal contraceptives and antibiotics, but clinical pharmacokinetic studies have not shown consistent effects of antibiotics on plasma concentrations of synthetic steroids.

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

Increase in Plasma Levels of Estradiol Associated with Co-Administered Drugs

Co-administration of atorvastatin and certain COCs containing ethinyl estradiol increase AUC values for ethinyl estradiol by approximately 20%. Ascorbic acid and acetaminophen may increase plasma ethinyl estradiol levels, possibly by inhibition of conjugation.  CYP3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels.

Concomitant Use with Hepatitis C Vaccine (HCV) Combination Therapy - Liver Enzyme Elevation

Do not co-administer Lo Simpesse with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions (5.4)].

Changes in Plasma Levels of Co-Administered Drugs

Combination OCs containing some synthetic estrogens (e.g., ethinyl estradiol) may inhibit the metabolism of other compounds. Combination OCs have been shown to significantly decrease plasma concentrations of lamotrigine likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Consult the labeling of the concurrently-used drug to obtain further information about interactions with COCs or the potential for enzyme alterations.

Pregnancy

There is little or no increased risk of birth defects in women who inadvertently use COCs during early pregnancy. 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 exposure to low dose COCs prior to conception or during early pregnancy.

The administration of COCs to induce withdrawal bleeding should not be used as a test for pregnancy. Combination OCs should not be used during pregnancy to treat threatened or habitual abortion.

Women who do not breastfeed may start COCs no earlier than four to six weeks postpartum.

Nursing Mothers

When possible, advise the nursing mother to use other forms of contraception until she has weaned her child. Estrogen-containing OCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well established; however, it can occur at any time in some women. Small amounts of estrogen and progestin from low dose COCs are present in breast milk, but these doses have not produced adverse effects in breastfeeding infants.

Pediatric Use

Safety and efficacy of Lo Simpesse have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 18 as for users 18 years and older. Use of this product before menarche is not indicated.

Geriatric Use

This product has not been studied in postmenopausal women and is not indicated in this population.

In a 12-month multicenter open-label clinical trial, 2,185 women aged 18 to 41 were studied to assess the safety and efficacy of Lo Simpesse, completing the equivalent of 20,937 28-day cycles of exposure. The racial demographic of those enrolled was: Caucasian (75%), African-American (12%), Hispanic (10%), Asian (2%), and Other (2%). There were no exclusions for body mass index (BMI) or weight. The weight range for those women treated was 87 to 381 lbs., with a mean weight of 159 lbs. Among the women in the trial, 59% were current or recent hormonal contraceptive users, 30% were prior users (had used hormonal contraceptives in the past but not in the 6 months prior to enrollment) and 11% were new starts. Of treated women, 14.2% were lost to follow-up, 11.6% discontinued due to an adverse event, and 10.3% discontinued by withdrawing their consent.

The pregnancy rate (Pearl Index [PI]) in women aged 18 to 35 years was 2.74 pregnancies per 100 women-years of use (95% confidence interval 1.92 to 3.78), based on 36 pregnancies that occurred after the onset of treatment and within 14 days after the last combination pill. Cycles in which conception did not occur, but which included the use of backup contraception, were not included in the calculation of the PI. The PI includes patients who did not take the drug correctly.

NDC 65862-866-95
Lo SimpesseTM
(Levonorgestrel and Ethinyl Estradiol
Tablets USP 0.1 mg/0.02 mg and
Ethinyl Estradiol Tablets USP 0.01 mg)
Rx only                                                    2 Extended-Cycle Wallets,
                                                                                91 Tablets each

Contains 2 Extended-Cycle Wallets, each containing 91 tablets: 84 light pink tablets,
each containing 0.1 mg levonorgestrel USP with 0.02 mg ethinyl estradiol USP,
and 7 light blue tablets, each containing 0.01 mg ethinyl estradiol USP.