Jencycla Description

Each tablet contains 0.35 mg norethindrone. Inactive ingredients include D&C yellow No. 10, FD&C blue No. 1, lactose anhydrous, magnesium stearate, povidone and sodium starch glycolate.

The chemical name of norethindrone is 17-hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one. It has a molecular formula of C20H26O2 and a molecular weight of 298.4. It has the following structural formula:

Jencycla - Clinical Pharmacology

Jencycla progestin-only oral contraceptives prevent conception by suppressing ovulation in approximately half of users, thickening the cervical mucus to inhibit sperm penetration, lowering the midcycle LH and FSH peaks, slowing the movement of the ovum through the fallopian tubes, and altering the endometrium.

2. Pharmacokinetics

Serum progestin levels peak about two hours after oral administration, followed by rapid distribution and elimination. By 24 hours after drug ingestion, serum levels are near baseline, making efficacy dependent upon rigid adherence to the dosing schedule. There are large variations in serum levels among individual users. Progestin-only administration results in lower steady-state serum progestin levels and a shorter elimination half-life than concomitant administration with estrogens.

Indications and Usage for Jencycla

Progestin-only oral contraceptives are indicated for the prevention of pregnancy.

2. Efficacy

If used perfectly, the first-year failure rate for progestin-only oral contraceptives is 0.3%. However, the typical failure rate is estimated to be closer to 9%, due to late or omitted pills. Table 1 lists the pregnancy rates for users of all major methods of contraception.

Contraindications

• Known or suspected pregnancy
• Known or suspected carcinoma of the breast
• Undiagnosed abnormal genital bleeding
• Hypersensitivity to any component of this product
• Benign or malignant liver tumors
• Acute liver disease

Warnings

Jencycla does not contain estrogen and, therefore, this insert does not discuss the serious health risks that have been associated with the estrogen component of combined oral contraceptives (COCs). The healthcare professional is referred to the prescribing information of combined oral contraceptives for a discussion of those risks. The relationship between progestin-only oral contraceptives and these risks is not fully defined. The healthcare professional should remain alert to the earliest manifestation of symptoms of any serious disease and discontinue oral contraceptive therapy when appropriate.

1. Ectopic Pregnancy

The incidence of ectopic pregnancies for progestin-only oral contraceptive users is 5 per 1000 woman-years. Up to 10% of pregnancies reported in clinical studies of progestin-only oral contraceptive users are extrauterine. Although symptoms of ectopic pregnancy should be watched for, a history of ectopic pregnancy need not be considered a contraindication to use of this contraceptive method. Healthcare professionals should be alert to the possibility of an ectopic pregnancy in women who become pregnant or complain of lower abdominal pain while on progestin-only oral contraceptives.

2. Delayed Follicular Atresia/Ovarian Cysts

If follicular development occurs, atresia of the follicle is sometimes delayed and the follicle may continue to grow beyond the size it would attain in a normal cycle. Generally these enlarged follicles disappear spontaneously. Often they are asymptomatic; in some cases they are associated with mild abdominal pain. Rarely they may twist or rupture, requiring surgical intervention.

3. Irregular Genital Bleeding

Irregular menstrual patterns are common among women using progestin-only oral contraceptives. If genital bleeding is suggestive of infection, malignancy or other abnormal conditions, such nonpharmacologic causes should be ruled out. If prolonged amenorrhea occurs, the possibility of pregnancy should be evaluated.

4. Carcinoma of the Breast and Reproductive Organs

Some epidemiological studies of oral contraceptive users have reported an increased relative risk of developing breast cancer, particularly at a younger age and apparently related to duration of use. These studies have predominantly involved combined oral contraceptives and there is insufficient data to determine whether the use of POPs similarly increases the risk.

A meta-analysis of 54 studies found a small increase in the frequency of having breast cancer diagnosed for women who were currently using combined oral contraceptives or had used them within the past ten years.

This increase in the frequency of breast cancer diagnosis, within ten years of stopping use, was generally accounted for by cancers localized to the breast. There was no increase in the frequency of having breast cancer diagnosed ten or more years after cessation of use.

Women with breast cancer should not use oral contraceptives because the role of female hormones in breast cancer has not been fully determined.

Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors. There is insufficient data to determine whether the use of POPs increases the risk of developing cervical intraepithelial neoplasia.

5. Hepatic Neoplasia

Benign hepatic adenomas are associated with combined oral contraceptive use, although the incidence of benign tumors is rare in the United States. Rupture of benign, hepatic adenomas may cause death through intra-abdominal hemorrhage.

Studies have shown an increased risk of developing hepatocellular carcinoma in combined oral contraceptive users. However, these cancers are rare in the U.S. There is insufficient data to determine whether POPs increase the risk of developing hepatic neoplasia.

Precautions

Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

2. Physical Examination and Follow up

It is considered good medical practice for sexually active women using oral contraceptives to have annual history and physical examinations. The physical examination may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the healthcare professional.

3. Carbohydrate and Lipid Metabolism

Some users may experience slight deterioration in glucose tolerance, with increases in plasma insulin but women with diabetes mellitus who use progestin-only oral contraceptives do not generally experience changes in their insulin requirements. Nonetheless, prediabetic and diabetic women in particular should be carefully monitored while taking POPs.

Lipid metabolism is occasionally affected in that HDL, HDL2, and apolipoprotein A-I and A-II may be decreased; hepatic lipase may be increased. There is usually no effect on total cholesterol, HDL3 , LDL, or VLDL.

4. Drug Interactions

Consult the labeling of 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

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 women 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 HCs:

Co-administration of certain HCs and strong or moderate CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase the systemic concentrations of progestins, including norethindrone.

Human Immunodeficiency Virus (HIV)/Hepatitis C Virus (HCV) protease inhibitors and nonnucleoside reverse transcriptase inhibitors:

Significant decreases in systemic concentrations of progestin have been noted in cases of co- administration with some HIV protease inhibitors (e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir), some HCV protease inhibitors (e.g., boceprevir and telaprevir), and some non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine, efavirenz).

In contrast, significant increases in systemic exposure of the progestin have been noted in cases of co-administration with certain other HIV protease inhibitors (e.g., indinavir and atazanavir/ritonavir) and with other non-nucleoside reverse transcriptase inhibitors (e.g., etravirine).

These changes may be clinically relevant in some cases.

Consult the prescribing information of anti-viral and anti-retroviral concomitant medications to identify potential interactions.

• Effects of Hormonal Contraceptives on Other Drugs

• Interactions between ulipristal and hormonal contraceptives

The following endocrine tests may be affected by progestin-only oral contraceptive use:

• Sex hormone-binding globulin (SHBG) concentrations may be decreased.
• Thyroxine concentrations may be decreased, due to a decrease in thyroid binding globulin (TBG).

See WARNINGS .

7. Pregnancy

Many studies have found no effects on fetal development associated with long-term use of contraceptive doses of oral progestins. The few studies of infant growth and development that have been conducted have not demonstrated significant adverse effects. It is nonetheless prudent to rule out suspected pregnancy before initiating any hormonal contraceptive use.

8. Nursing Mothers

In general, no adverse effects have been found on breastfeeding performance or on the health, growth, or development of the infant. However, isolated post-marketing cases of decreased milk production have been reported. Small amounts of progestins pass into the breast milk of nursing mothers, resulting in detectable steroid levels in infant plasma.

9. Pediatric Use

Safety and efficacy of Jencycla tablets have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated.

10. Fertility Following Discontinuation

The limited available data indicate a rapid return of normal ovulation and fertility following discontinuation of progestin-only oral contraceptives.

11. Headache

The onset or exacerbation of migraine or development of severe headache with focal neurological symptoms which is recurrent or persistent requires discontinuation of progestin-only contraceptives and evaluation of the cause.

Patient Counseling Information

2. Counseling issues

The following points should be discussed with prospective users before prescribing progestin-only oral contraceptives:

• The necessity of taking pills at the same time every day, including throughout all bleeding episodes.
• The need to use a backup method such as condom and spermicide for the next 48 hours whenever a progestin-only oral contraceptive is taken 3 or more hours late.
• The potential side effects of progestin-only oral contraceptives, particularly menstrual irregularities.
• The need to inform the healthcare professional of prolonged episodes of bleeding, amenorrhea or severe abdominal pain.
• The importance of using a barrier method in addition to progestin-only oral contraceptives if a woman is at risk of contracting or transmitting STDs/HIV.

Adverse Reactions/Side Effects

• Menstrual irregularity is the most frequently reported side effect.
• Frequent and irregular bleeding are common, while long duration of bleeding episodes and amenorrhea are less likely.
• Headache, breast tenderness, nausea, and dizziness are increased among progestin-only oral contraceptive users in some studies.
• Androgenic side effects such as acne, hirsutism, and weight gain occur rarely.

Gastrointestinal Disorders:

vomiting, abdominal pain;

General Disorders and Administration Site Conditions:

fatigue, edema;

Psychiatric Disorders:

depression, nervousness;

Musculoskeletal and Connective Tissue Disorders:

pain in extremity;

Reproductive System and Breast Disorders:

genital discharge; breast pain, menstruation delayed, suppressed lactation, vaginal hemorrhage, menorrhagia, withdrawal bleed when product is stopped;

Immune System Disorders:

anaphylactic/anaphylactoid reaction, hypersensitivity;

Hepatobiliary Disorders:

hepatitis, jaundice cholestatic;

Skin and Subcutaneous Tissue Disorders:

alopecia, rash, rash pruritic.

Overdosage

Jencycla Dosage and Administration

How is Jencycla supplied

Jencycla Tablets are available in a blister (NDC 68180-877-71) containing 28 tablets. Such three blisters are packaged in a carton (NDC 68180-877-73).

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

Keep out of reach of children.

References

2. Van Giersbergen PLM, Halabi A, Dingemanse J. Pharmacokinetic interaction between bosentan and the oral contraceptives norethisterone and ethinyl estradiol. Int J Clin Pharmacol Ther 2006;44(3):113-118.

3. Truitt ST, Fraser A, Gallo ME, Lopez LM, Grimes DA and Schulz KF. Combined hormonal versus nonhormonal versus progestin-only contraception in lactation (Review). The Cochrane Collaboration. 2007, Issue 3.

4. Halderman, LD and Nelson AL. Impact of early postpartum administration of progestin-only hormonal contraceptives compared with nonhormonal contraceptives on short-term breast-feeding patterns. Am J Obstet Gynecol.; 186 (6):1250-1258.

5. Ostrea EM, Mantaring III JB, Silvestre MA. Drugs that affect the fetus and newborn infant via the placenta or breast milk. Pediatr Clin N Am; 51(2004): 539-579.

6. Cooke ID, Back DJ, Shroff NE: Norethisterone concentration in breast milk and infant and maternal plasma during ethynodiol diactetate administration. Contraception 1985; 31:611-21.

7. 2008 USPC Official:12/1/08-4/30/09, USP Monographs: Norethindrone Tablets (page 1 of 5).

Jencycla™ is a trademark of Lupin Pharmaceuticals, Inc.

The other brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products.

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States

Manufactured by:

Lupin Limited

Pithampur (M.P.) - 454 775

INDIA

Revised: April 2022

Jencycla™

(norethindrone tablets USP, 0.35 mg)

Rx Only

This product (like all oral contraceptives) is used to prevent pregnancy. It does not protect against HIV infection (AIDS) or other sexually transmitted diseases.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

(norethindrone tablets USP)

0.35 mg

Carton Pack:

NDC: 68180-877-73

3 Blisters of 28 Tablets Each

(norethindrone tablets USP)

0.35 mg

Blister Pack:

NDC: 68180-877-71

1 Blister of 28 Tablets