Professional Information — Heather 28 Day

Indications and Usage

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.

Dosage and Administration

To achieve maximum contraceptive effectiveness, HEATHER 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.

Contraindications

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.

Adverse Reactions

• 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.

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.

Overdosage

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

Description

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

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

Norethindrone, USP

Therapeutic class = oral contraceptive

Clinical Pharmacology

1. Mode of Action

HEATHER 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 HEATHER 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%.

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 HEATHER administration.

The food effect on the rate and extent of norethindrone absorption after HEATHER 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 HEATHER is approximately 8 hours.

How Supplied / Storage and Handling

HEATHER (Norethindrone Tablets, USP 0.35 mg) is available in cartons (NDC 68462-303-29) of 3 blisters (NDC 68462-303-84) each containing 28 pale yellow, round, flat faced, beveled edged, uncoated tablets with ‘303’ debossed on one side and ‘G’ on the other side.

Patient Counseling Information

1. 1.See PATIENT LABELING for detailed information.
2. 2. Counseling issues.

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

3. The necessity of taking pills at the same time every day, including throughout all bleeding episodes.
4. The need to use a backup method such as condoms and spermicides for the next 48 hours whenever a progestin-only oral contraceptive is taken 3 or more hours late.
5. The potential side effects of progestin-only oral contraceptives, particularly menstrual irregularities.
6. The need to inform the clinician of prolonged episodes of bleeding, amenorrhea or severe abdominal pain.
7. 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.