Norethindrone Tablets Usp

Cigarette smoking greatly increases the possibility of suffering heart attacks and strokes. Women who use oral contraceptives are strongly advised not to smoke.

1. Indications

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 0.5%. However, the typical failure rate is estimated to be closer to 5%, due to late or omitted pills. The following table lists the pregnancy rates for users of all major methods of contraception.

To achieve maximum contraceptive effectiveness, norethindrone tablets must be taken exactly as directed. One tablet is taken every day, at the same time. Administration is continuous, with no interruption between pill packs. See PATIENT LABELING for detailed instructions.

Progestin-only oral contraceptives (POPs) should not be used by women who currently have the following conditions:

• •
  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

• •
  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.

Norethindrone Tablets USP containing 0.35 mg of norethindrone, are yellow coloured, round flat face beveled edge tablets debossed with "LU" on one side and "J22" on the other side.

Norethindrone Tablets USP are available in 28-tablet wallets. One such wallet is packed in a bag.

They are supplied as follows:

NDC 82804-175-28                                  28 tablets blister strips

STORAGE

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

Each yellow norethindrone tablet USP provides a continuous oral contraceptive regimen of 0.35 mg norethindrone daily, and the inactive ingredients include D&C Yellow No. 10, FD&C Yellow No. 6, lactose anhydrous, lactose monohydrate, corn starch, povidone and magnesium stearate.

The chemical name for norethindrone is 17-Hydroxy-19-Nor-17α-pregn-4-en-20-yn-3-one. The structural formula follows:

0.35 mg

Rx only

Patients should be counseled that oral contraceptives do not protect against transmission of HIV (AIDS) and other sexually transmitted diseases (STDs) such as chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis.

There have been no reports of serious ill effects from overdosage, including ingestion by children.

1. General

Patients should be counseled that oral contraceptives do not protect against transmission of HIV (AIDS) and other sexually transmitted diseases (STDs) such as chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis.

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 clinician.

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 no effect on total cholesterol, HDL₃, LDL, or VLDL.

4. Drug Interactions

Change in contraceptive effectiveness associated with co-administration of other products:

a.           Anti-infective agents and anticonvulsants.

Contraceptive effectiveness may be reduced when hormonal contraceptives are co-administered with antibiotics, anticonvulsants, and other drugs that increase the metabolism of contraceptive steroids. This could result in unintended pregnancy or breakthrough bleeding. Examples include rifampin, barbiturates, phenylbutazone, phenytoin, carbamazepine, felbamate, oxcarbazepine, topiramate, and griseofulvin.

b.           Anti-HIV protease inhibitors.

Several of the anti-HIV protease inhibitors have been studied with co-administration of oral contraceptives; significant changes (increase and decrease) in the plasma levels of the estrogen and progestin have been noted in some cases. The safety and efficacy of OC products may be affected with the co-administration of anti-HIV protease inhibitors. Health care providers should refer to the label of the individual anti-HIV protease inhibitors for further drug-drug interaction information.

c.           Herbal products.

Herbal products containing St. John's Wort (hypericum perforatum) may induce hepatic enzymes (cytochrome P450) and p-glycoprotein transporter and may reduce the effectiveness of contraceptive steroids. This may also result in breakthrough bleeding.

5. Interactions with laboratory tests

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).

6. Carcinogenesis

See WARNINGS section.

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

Small amounts of progestin pass into the breast milk, resulting in steroid levels in infant plasma of 1-6% of the levels of maternal plasma.⁶ However, isolated post-market cases of decreased milk production have been reported in POPs. Very rarely, adverse effects in the infant/child have been reported, including jaundice.

9. Fertility following discontinuation

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

10. Headache/Migraine

If you have a headache or a worsening migraine headache with a new pattern that is recurrent, persistent, or severe, this requires discontinuation of oral contraceptives and evaluation of the cause.

11. Gastrointestinal

Diarrhea and/or vomiting may reduce hormone absorption resulting in decreased serum concentrations.

12. Pediatric Use

Safety and efficacy of norethindrone 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.

1. Mode of Action

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

2. Pharmacokinetics

Absorption

Norethindrone is rapidly absorbed with maximum plasma concentrations occurring within 1 to 2 hours after norethindrone tablet administration (see Table 1). Norethindrone appears to be completely absorbed following oral administration; however, it is subject to first pass metabolism resulting in an absolute bioavailability of approximately 65%.

Figure 1: Mean ± SD Norethindrone Plasma Concentrations Following Norethindrone Tablets Administration.

Peak plasma concentrations occur approximately 1 hour after administration (mean T_max 1.2 hours). The mean (SD) C_max was 4816.8 (1532.6) pg/mL and generally occurred within 1 hour (mean) of tablet administration, ranging from 0.5 to 2 hours. The mean (SD) C_avg was 885 (250) pg/mL, however, the mean concentration at 24 hrs was 130 (47) pg/mL.

Table 1 provides summary statistics of the pharmacokinetic parameters associated with single dose norethindrone tablets administration.

The food effect on the rate and extent of norethindrone absorption after norethindrone tablet administration has not been evaluated.

Distribution

Following oral administration, norethindrone is 36% bound to sex hormone-binding globulin (SHBG) and 61% bound to albumin. Volume of distribution of norethindrone is approximately 4 L/kg.

Metabolism

Norethindrone undergoes extensive biotransformation, primarily via reduction, followed by sulfate and glucuronide conjugation; less than 5% of a norethindrone dose is excreted unchanged; greater than 50% and 20-40% of a dose is excreted in urine and feces, respectively. The majority of metabolites in the circulation are sulfate, with glucuronides accounting for most of the urinary metabolites.

Excretion

Plasma clearance rate for norethindrone has been estimated to be approximately 600 L/day. Norethindrone is excreted in both urine and feces, primarily as metabolites. The mean terminal elimination half-life of norethindrone following single dose administration of norethindrone tablet is approximately 8 hours.

Norethindrone Tablets USP

0.35 mg

Rx Only

NDC 82804-175-28

Bag Label: 1 Wallet, 28 Tablets Each

28 Day Regimen

www.birthcontrolhealth.com

Cigarette smoking greatly increases the possibility of suffering heart attacks and strokes. Women who use oral contraceptives are strongly advised not to smoke.

0.35 mg

Rx only

Patients should be counseled that oral contraceptives do not protect against transmission of HIV (AIDS) and other sexually transmitted diseases (STDs) such as chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis.

There have been no reports of serious ill effects from overdosage, including ingestion by children.

Each yellow norethindrone tablet USP provides a continuous oral contraceptive regimen of 0.35 mg norethindrone daily, and the inactive ingredients include D&C Yellow No. 10, FD&C Yellow No. 6, lactose anhydrous, lactose monohydrate, corn starch, povidone and magnesium stearate.

The chemical name for norethindrone is 17-Hydroxy-19-Nor-17α-pregn-4-en-20-yn-3-one. The structural formula follows:

1. General

Patients should be counseled that oral contraceptives do not protect against transmission of HIV (AIDS) and other sexually transmitted diseases (STDs) such as chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis.

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 clinician.

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 no effect on total cholesterol, HDL₃, LDL, or VLDL.

4. Drug Interactions

Change in contraceptive effectiveness associated with co-administration of other products:

a.           Anti-infective agents and anticonvulsants.

Contraceptive effectiveness may be reduced when hormonal contraceptives are co-administered with antibiotics, anticonvulsants, and other drugs that increase the metabolism of contraceptive steroids. This could result in unintended pregnancy or breakthrough bleeding. Examples include rifampin, barbiturates, phenylbutazone, phenytoin, carbamazepine, felbamate, oxcarbazepine, topiramate, and griseofulvin.

b.           Anti-HIV protease inhibitors.

Several of the anti-HIV protease inhibitors have been studied with co-administration of oral contraceptives; significant changes (increase and decrease) in the plasma levels of the estrogen and progestin have been noted in some cases. The safety and efficacy of OC products may be affected with the co-administration of anti-HIV protease inhibitors. Health care providers should refer to the label of the individual anti-HIV protease inhibitors for further drug-drug interaction information.

c.           Herbal products.

Herbal products containing St. John's Wort (hypericum perforatum) may induce hepatic enzymes (cytochrome P450) and p-glycoprotein transporter and may reduce the effectiveness of contraceptive steroids. This may also result in breakthrough bleeding.

5. Interactions with laboratory tests

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).

6. Carcinogenesis

See WARNINGS section.

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

Small amounts of progestin pass into the breast milk, resulting in steroid levels in infant plasma of 1-6% of the levels of maternal plasma.⁶ However, isolated post-market cases of decreased milk production have been reported in POPs. Very rarely, adverse effects in the infant/child have been reported, including jaundice.

9. Fertility following discontinuation

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

10. Headache/Migraine

If you have a headache or a worsening migraine headache with a new pattern that is recurrent, persistent, or severe, this requires discontinuation of oral contraceptives and evaluation of the cause.

11. Gastrointestinal

Diarrhea and/or vomiting may reduce hormone absorption resulting in decreased serum concentrations.

12. Pediatric Use

Safety and efficacy of norethindrone 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.

Norethindrone Tablets USP containing 0.35 mg of norethindrone, are yellow coloured, round flat face beveled edge tablets debossed with "LU" on one side and "J22" on the other side.

Norethindrone Tablets USP are available in 28-tablet wallets. One such wallet is packed in a bag.

They are supplied as follows:

NDC 82804-175-28                                  28 tablets blister strips

STORAGE

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

• •
  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.

Progestin-only oral contraceptives (POPs) should not be used by women who currently have the following conditions:

• •
  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

1. Mode of Action

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

2. Pharmacokinetics

Absorption

Norethindrone is rapidly absorbed with maximum plasma concentrations occurring within 1 to 2 hours after norethindrone tablet administration (see Table 1). Norethindrone appears to be completely absorbed following oral administration; however, it is subject to first pass metabolism resulting in an absolute bioavailability of approximately 65%.

Figure 1: Mean ± SD Norethindrone Plasma Concentrations Following Norethindrone Tablets Administration.

Peak plasma concentrations occur approximately 1 hour after administration (mean T_max 1.2 hours). The mean (SD) C_max was 4816.8 (1532.6) pg/mL and generally occurred within 1 hour (mean) of tablet administration, ranging from 0.5 to 2 hours. The mean (SD) C_avg was 885 (250) pg/mL, however, the mean concentration at 24 hrs was 130 (47) pg/mL.

Table 1 provides summary statistics of the pharmacokinetic parameters associated with single dose norethindrone tablets administration.

The food effect on the rate and extent of norethindrone absorption after norethindrone tablet administration has not been evaluated.

Distribution

Following oral administration, norethindrone is 36% bound to sex hormone-binding globulin (SHBG) and 61% bound to albumin. Volume of distribution of norethindrone is approximately 4 L/kg.

Metabolism

Norethindrone undergoes extensive biotransformation, primarily via reduction, followed by sulfate and glucuronide conjugation; less than 5% of a norethindrone dose is excreted unchanged; greater than 50% and 20-40% of a dose is excreted in urine and feces, respectively. The majority of metabolites in the circulation are sulfate, with glucuronides accounting for most of the urinary metabolites.

Excretion

Plasma clearance rate for norethindrone has been estimated to be approximately 600 L/day. Norethindrone is excreted in both urine and feces, primarily as metabolites. The mean terminal elimination half-life of norethindrone following single dose administration of norethindrone tablet is approximately 8 hours.

1. Indications

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 0.5%. However, the typical failure rate is estimated to be closer to 5%, due to late or omitted pills. The following table lists the pregnancy rates for users of all major methods of contraception.

Norethindrone Tablets USP

0.35 mg

Rx Only

NDC 82804-175-28

Bag Label: 1 Wallet, 28 Tablets Each

28 Day Regimen

www.birthcontrolhealth.com

To achieve maximum contraceptive effectiveness, norethindrone tablets must be taken exactly as directed. One tablet is taken every day, at the same time. Administration is continuous, with no interruption between pill packs. See PATIENT LABELING for detailed instructions.