Nor-QD

Nor-QD® (norethindrone) tablets are available in 28-tablet dispensers.

Storage

Store at controlled room temperature 15 - 25°C (59 - 77°F).

Revised: MARCH 2006. Address medical inquires to: WATSON PHARMA, INC., Medical Communications, P.O. Box 1953, Morristown, NJ 07962-1953. 800-272-5525. Mfg. for: WATSON PHARMA, INC., A subsidiary of Watson Pharmaceuticals, Inc., Corona, CA 92880 USA. FDA revision date: 10/20/2005

Mode of Action

Nor-QD (norethindrone) ® 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.

Pharmacokinetics

Absorption: Norethindrone is rapidly absorbed with maximum plasma concentrations occurring within 1 to 2 hours after Nor-QD® 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 Nor-QD (norethindrone) ® Administration.

Peak plasma concentrations occur approximately 1 hour after administration (mean Tmax 1.2 hours). The mean (SD) Cmax 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) Cavg 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 Nor-QD (norethindrone) ® administration.

Table 1: Mean ± SD Pharmacokinetic Parameters Following Single Dose Administration of Nor-QD (norethindrone) ® in 12 Healthy Female Subjects Under Fasting Conditions

The food effect on the rate and extent of norethindrone absorption after Nor-QD (norethindrone) ® administration has not been evaluated.

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.

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.

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 Nor-QD (norethindrone) ® is approximately 8 hours.

Nor-QD is part of the drug class:

• Estren derivatives

Norethindrone is a form of progesterone, a female hormone. Norethindrone prevents ovulation (the release of an egg from an ovary). This medication also causes changes in your cervical mucus and uterine lining, making it harder for sperm to reach the uterus and harder for a fertilized egg to attach to the uterus.

Norethindrone is used for birth control (contraception) to prevent pregnancy. Norethindrone is also used to treat menstrual disorders, endometriosis, or abnormal vaginal bleeding caused by a hormone imbalance.

Norethindrone may also be used for other purposes not listed in this medication guide.

This medication can cause birth defects. Do not use if you are pregnant. Tell your doctor right away if you become pregnant.

Do not use this medication if you are allergic to norethindrone, or if you have:

• a history of a stroke, blood clot, or circulation problems;

• breast cancer;

• abnormal vaginal bleeding; or

• if you have recently had an incomplete miscarriage or abortion.

Before using norethindrone, tell your doctor if you have any of the following conditions. You may need a dose adjustment or special tests to safely take norethindrone.

• high blood pressure or a history of heart disease;

• migraines;

• kidney disease;

• liver disease or liver cancer;

• a history of depression or mental illness;

• high cholesterol or triglycide (fatty acid) levels in your blood;

• asthma; or

• seizures or epilepsy.

Norethindrone can pass into breast milk. Make sure your doctor knows if you are breast-feeding a baby while taking this medication.

Taking hormones can increase your risk of blood clots, stroke, or heart attack, especially if you smoke and are older than 35.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using this medication and call your doctor at once if you have any of these serious side effects:

• sudden numbness or weakness, especially on one side of the body;

• sudden headache, confusion, pain behind the eyes, problems with vision, speech, or balance;

• pain or swelling in one or both legs;

• migraine headache;

• swelling in your hands or feet, rapid weight gain;

• symptoms of depression (sleep problems, weakness, mood changes);

• severe pelvic pain;

• chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling; or

• nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

• mild nausea, vomiting, bloating, stomach cramps;

• breast pain, swelling, or tenderness;

• dizziness;

• freckles or darkening of facial skin;

• increased acne or hair growth;

• changes in weight;

• vaginal itching or discharge;

• skin itching or rash;

• changes in your menstrual periods, decreased sex drive; or

• mild headache.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

In the U.S.

• Aygestin
• Camila
• Errin
• Jolivette
• Lyza
• My Way
• Next Choice
• Nora-BE
• Nor-QD
• Ovrette
• Plan B
• Plan B One-Step
• Provera

In Canada

• Option 2

Available Dosage Forms:

• Tablet

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Chest pain or pressure.
• Shortness of breath.
• Coughing up blood.
• Swelling, warmth, numbness, change of color, or pain in a leg or arm.
• Very bad headache.
• Very upset stomach or throwing up.
• Very bad belly pain.
• Very bad dizziness or passing out.
• Bulging eyes.
• Change in eyesight.
• Loss of eyesight.
• A lump in the breast, breast soreness, or nipple discharge.
• Breast pain.
• Vaginal itching or discharge.
• Vaginal bleeding that is not normal.
• Low mood (depression).
• Mood changes.
• Swelling in the feet or hands.

Each yellow Nor-QD® tablet 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, magnesium stearate, povidone, and starch.

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

norethindrone

Therapeutic class = oral contraceptive.

Applies to norethindrone: compounding powder, oral tablet

General

The most commonly reported side effects included cycle irregularity, spotting/breakthrough bleeding, and temporary amenorrhea.[Ref]

Genitourinary

Common (1% to 10%): Uterine/vaginal bleeding and spotting/breakthrough bleeding, short-lasting amenorrhea
Uncommon (0.1% to 1%): Breast discomfort
Frequency not reported: Irregular/increased/decreased bleeding/delayed menstruation, change in menstrual flow, menorrhagia, vaginal hemorrhage, cervical secretion alteration, cervical erosions, prolonged anovulation, suppressed lactation, galactorrhea, mastodynia, breast tenderness/enlargement, genital discharge, withdrawal bleeding (on treatment discontinuation), premenstrual-type depression, changes in cervical squamocolumnar junction and secretions[Ref]

Nervous system

Common (1% to 10%): Dizziness, headache
Frequency not reported: Drowsiness, somnolence, concentration loss, migraine, tremor, cerebral thrombosis and embolism[Ref]

Local

Common (1% to 10%): Injection site reaction, local skin reaction[Ref]

Gastrointestinal

Common (1% to 10%): Nausea
Uncommon (0.1% to 1%): Bloating
Frequency not reported: Vomiting, abdominal pain, gastrointestinal disturbance[Ref]

Dermatologic

Common (1% to 10%): Skin disorder
Frequency not reported: Angioedema, acne, hirsutism, alopecia, rash, pruritus, pruritic rash, melasma, chloasma, urticaria, exacerbation of existing skin conditions, sweating, allergic rash with and without pruritus[Ref]

Metabolic

Common (1% to 10%): Increased weight
Frequency not reported: Increased fasting insulin levels, Cushing's syndrome, decreased glucose tolerance, exacerbation of diabetes mellitus, glycosuria, weight gain/change, change in appetite, fluid retention, increased serum calcium and potassium levels, altered serum lipid and lipoprotein levels (e.g., decreased HDL, increased LDL/HDL ratio)[Ref]

Hypersensitivity

Common (1% to 10%): Hypersensitivity reaction
Frequency not reported: Anaphylaxis/anaphylactoid reactions[Ref]

Psychiatric

Uncommon (0.1% to 1%): Depressed mood/depression/clinical depression/metal depression
Frequency not reported: Insomnia, nervousness, libido change, mood swings[Ref]

Respiratory

Frequency not reported: Urge to cough, paroxysmal cough, respiratory distress, dyspnea, pulmonary embolism, voice deepening[Ref]

Ocular

Frequency not reported: Retinal thrombosis, diabetic cataract, vision disorders, visual disturbance, contact lens intolerance, optic neuritis (may lead to partial or complete vision loss)[Ref]

Cardiovascular

Frequency not reported: Circulatory irregularity, thromboembolic disorders, thrombophlebitis, increased blood pressure/hypertension, edema[Ref]

Hepatic

Frequency not reported: Cholestatic liver changes/cholestatic jaundice, hepatitis, disturbed liver function, transient liver test abnormalities (e.g., AST, ALT, bilirubin)[Ref]

Other

Frequency not reported: Fever, hyperpyrexia, fatigue, extremity pain[Ref]

Hematologic

Frequency not reported: Increased white cell and platelet counts[Ref]

Endocrine

Frequency not reported: Masculinization of the female fetus[Ref]

Some side effects of Nor-QD may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.