Zenchent FE

Zenchent Fe is part of the drug class:

• Combination Progesterone and Estrogen Contraceptives

Zenchent FE™ Norethindrone and ethinyl estradiol tablets, chewable and ferrous fumarate tablets provide a regimen for oral contraception derived from 21 light yellow tablets composed of norethindrone and ethinyl estradiol followed by 7 natural brown ferrous fumarate (placebo) tablets. The chemical name for norethindrone is 17-hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one and for ethinyl estradiol the chemical name is 19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol. The molecular weights for norethindrone and ethinyl estradiol are 298.42 and 296.40, respectively. The structural formulas are:

The active light yellow norethindrone and ethinyl estradiol tablets contain 0.4 mg norethindrone and 0.035 mg ethinyl estradiol, and the following inactive ingredients: dicalcium phosphate dihydrate, lactose monohydrate, magnesium stearate, maltodextrin, povidone, D&C yellow #10 (15% to 20%), natural spearmint and sucralose.

The inert natural brown tablets contain 75 mg ferrous fumarate and compressible sugar, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, and sucralose. The ferrous fumarate tablets do not serve any therapeutic purpose. Ferrous fumarate tablets are not USP for dissolution and assay.

Combination oral contraceptives act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation).

Combination oral contraceptives should not be used in women who currently have the following conditions:

• Thrombophlebitis or thromboembolic disorders
  
• History of deep vein thrombophlebitis or thromboembolic disorders
  
• Cerebrovascular or coronary artery disease (current or history)
  
• Valvular heart disease with thrombogenic complications
  
• Uncontrolled hypertension
  
• Diabetes with vascular involvement
  
• Headaches with focal neurological symptoms, such as aura
  
• Major surgery with prolonged immobilization
  
• Known or suspected carcinoma of the breast or personal history of breast cancer
  
• Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia
  
• Undiagnosed abnormal genital bleeding
  
• Cholestatic jaundice of pregnancy or jaundice with prior pill use
  
• Hepatic adenomas or carcinomas, or active liver disease
  
• Known or suspected pregnancy
  
• Hypersensitivity to any component of this product

1. SEXUALLY TRANSMITTED DISEASES

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

A periodic personal and family medical history and complete physical examination are appropriate for all women, including women using oral contraceptives. The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care.

3. LIPID DISORDERS

Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult. (See WARNINGS 1.d.).

In patients with familial defects of lipoprotein metabolism receiving estrogen-containing preparations, there have been case reports of significant elevations of plasma triglycerides leading to pancreatitis.

4. LIVER FUNCTION

If jaundice develops in any woman receiving such drugs, the medication should be discontinued. Steroid hormones may be poorly metabolized in patients with impaired liver function.

5. FLUID RETENTION

Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention.

6. EMOTIONAL DISORDERS

Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree. Patients becoming significantly depressed while taking oral contraceptives should stop the medication and use an alternate method of contraception in an attempt to determine whether the symptom is drug related. Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree.

7. CONTACT LENSES

Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.

8. DRUG INTERACTIONS

Changes in contraceptive effectiveness associated with coadministration of other products:

a. Anti-infective agents and anticonvulsants

Contraceptive effectiveness may be reduced when hormonal contraceptives are coadministered 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. Several cases of contraceptive failure and breakthrough bleeding have been reported in the literature with concomitant administration of antibiotics such as ampicillin and tetracyclines. However, clinical pharmacology studies investigating drug interaction between combined oral contraceptives and these antibiotics have reported inconsistent results.

b. Anti-HIV protease inhibitors

Several of the anti-HIV protease inhibitors have been studied with coadministration of oral combination hormonal 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 combination oral contraceptive products may be affected with coadministration of anti-HIV protease inhibitors. Healthcare 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.

Increase in plasma levels of estradiol associated with coadministered drugs:

Coadministration of atorvastatin and certain combination oral contraceptives 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.

Changes in plasma levels of coadministered drugs:

Combination hormonal contraceptives containing some synthetic estrogens (e.g., ethinyl estradiol) may inhibit the metabolism of other compounds. Increased plasma concentrations of cyclosporin, prednisolone, and theophylline have been reported with concomitant administration of combination oral contraceptives. Decreased plasma concentrations of acetaminophen and increased clearance of temazepam, salicylic acid, morphine and clofibric acid, due to induction of conjugation have been noted when these drugs were administered with combination oral contraceptives.

9. INTERACTIONS WITH LABORATORY TESTS

Certain endocrine and liver function tests and blood components may be affected by oral contraceptives:

1. Increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability.
   
2. Increased thyroid-binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 by column or by radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG, free T4 concentration is unaltered.
   
3. Other binding proteins may be elevated in serum.
   
4. Sex hormone binding globulins are increased and result in elevated levels of total circulating sex steroids and corticoids; however, free or biologically active levels remain unchanged.
   
5. Triglycerides may be increased and levels of various other lipids and lipoproteins may be affected.
   
6. Glucose tolerance may be decreased.
   
7. Serum folate levels may be depressed by oral contraceptive therapy. This may be of clinical significance if a woman becomes pregnant shortly after discontinuing oral contraceptives.

10. CARCINOGENESIS

See WARNINGS section.

11. PREGNANCY

Pregnancy Category X. See CONTRAINDICATIONS and WARNINGS sections.

12. NURSING MOTHERS

Small amounts of oral contraceptive steroids and/or metabolites have been identified in the milk of nursing mothers and a few adverse effects on the child have been reported, including jaundice and breast enlargement. In addition, oral contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk. If possible, the nursing mother should be advised not to use oral contraceptives but to use other forms of contraception until she has completely weaned her child.

13. PEDIATRIC USE

Safety and efficacy of Zenchent FE™ norethindrone and ethinyl estradiol tablets, chewable and ferrous fumarate tablets have been established in women of reproductive age. Safety and efficacy are expected to be the same in postpubertal adolescents under the age of 16 years and in users ages 16 years and older. Use of this product before menarche is not indicated.

14. GERIATRIC USE

This product has not been studied in women over 65 years of age and is not indicated in this population.

An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS section):

• Thrombophlebitis
  
• Arterial thromboembolism
  
• Pulmonary embolism
  
• Myocardial infarction
  
• Cerebral hemorrhage
  
• Cerebral thrombosis
  
• Hypertension
  
• Gallbladder disease
  
• Hepatic adenomas or benign liver tumors

There is evidence of an association between the following conditions and the use of oral contraceptives:

• Mesenteric thrombosis
  
• Retinal thrombosis

The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug related:

• Nausea
  
• Vomiting
  
• Gastrointestinal symptoms (such as abdominal cramps and bloating)
  
• Breakthrough bleeding
  
• Spotting
  
• Change in menstrual flow
  
• Amenorrhea
  
• Temporary infertility after discontinuation of treatment
  
• Edema/fluid retention
  
• Melasma/chloasma which may persist
  
• Breast changes: tenderness, pain, enlargement, and secretion
  
• Change in weight (increase or decrease)
  
• Change in cervical ectropion and secretion
  
• Possible diminution in lactation when given immediately postpartum
  
• Cholestatic jaundice
  
• Migraine headache
  
• Rash (allergic)
  
• Mood changes, including depression
  
• Vaginitis, including candidiasis
  
• Change in corneal curvature (steepening)
  
• Intolerance to contact lenses
  
• Decrease in serum folate levels
  
• Exacerbation of systemic lupus erythematosus
  
• Exacerbation of porphyria
  
• Exacerbation of chorea
  
• Aggravation of varicose veins
  
• Anaphylactic/anaphylactoid reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms

The following adverse reactions have been reported in users of oral contraceptives, and a causal association has been neither confirmed nor refuted:

• Premenstrual syndrome
  
• Cataracts
  
• Optic neuritis, which may lead to partial or complete loss of vision
  
• Cystitis-like syndrome
  
• Headache
  
• Nervousness
  
• Dizziness
  
• Hirsutism
  
• Loss of scalp hair
  
• Erythema multiforme
  
• Erythema nodosum
  
• Hemorrhagic eruption
  
• Impaired renal function
  
• Hemolytic uremic syndrome
  
• Budd-Chiari syndrome
  
• Acne
  
• Changes in libido
  
• Colitis
  
• Pancreatitis
  
• Dysmenorrhea

To achieve maximum contraceptive effectiveness, norethindrone and ethinyl estradiol tablets, chewable and ferrous fumarate tablets must be taken exactly as directed and at intervals not exceeding 24 hours. The dosage of norethindrone and ethinyl estradiol tablets, chewable and ferrous fumarate tablets is one light yellow tablet daily for 21 consecutive days, followed by one natural brown tablet, daily for 7 consecutive days. It is recommended that tablets be taken at the same time each day. The pill may be swallowed whole or chewed and swallowed. If the pill is chewed, the patient should drink a full glass (8 ounces) of liquid immediately after swallowing. During the first cycle of use, the patient is instructed to begin taking norethindrone and ethinyl estradiol tablets, chewable and ferrous fumarate tablets on either Day 1 or the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, the first tablet (light yellow) is taken that day. One light yellow tablet should be taken daily for 21 consecutive days followed by one natural brown tablet daily for 7 consecutive days. Withdrawal bleeding should usually occur within three days following discontinuation of light yellow tablets and may not have finished before the next pack is started. During the first cycle with a Sunday start, contraceptive reliance should not be placed on norethindrone and ethinyl estradiol tablets, chewable and ferrous fumarate tablets until a light yellow tablet has been taken daily for 7 consecutive days and a non-hormonal back-up method of birth control (such as condoms or spermicide) should be used during those 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

The patient begins her next and all subsequent 28-day courses of tablets on the same day of the week on which she began her first course, following the same schedule: 21 days on light yellow tablets - 7 days on natural brown tablets. If in any cycle the patient starts tablets later than the proper day, she should protect herself against pregnancy by using a non-hormonal back-up method of birth control until she has taken a light yellow tablet daily for 7 consecutive days.

When the patient is switching from a 21-day regimen of tablets, she should wait 7 days after her last tablet before she starts norethindrone and ethinyl estradiol tablets, chewable and ferrous fumarate tablets. She will probably experience withdrawal bleeding during that week. She should be sure that no more than 7 days pass after her previous 21-day regimen. When the patient is switching from a 28-day regimen of tablets, she should start her first pack of norethindrone and ethinyl estradiol tablets, chewable and ferrous fumarate tablets on the day after her last tablet. She should not wait any days between packs. The patient may switch any day from a progestin-only pill and should begin norethindrone and ethinyl estradiol tablets, chewable and ferrous fumarate tablets the next day. If switching from an implant or injection, the patient should start norethindrone and ethinyl estradiol tablets, chewable and ferrous fumarate tablets on the day of implant removal or, if using an injection, the day the next injection would be due.

If spotting or breakthrough bleeding occurs, the patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance; however, if the bleeding is persistent or prolonged, the patient is advised to consult her healthcare provider. Although pregnancy is unlikely if norethindrone and ethinyl estradiol tablets, chewable and ferrous fumarate tablets are taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (missed one or more tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out. Hormonal contraceptives should be discontinued if pregnancy is confirmed.

For additional patient instructions regarding missed pills, see the “WHAT TO DO IF YOU MISS PILLS” section in the DETAILED PATIENT LABELING. Any time the patient misses two or more light yellow tablets, she should also use another method of non-hormonal back-up contraception until she has taken a light yellow tablet daily for seven consecutive days. If the patient misses one or more natural brown tablets, she is still protected against pregnancy provided she begins taking light yellow tablets again on the proper day. If breakthrough bleeding occurs following missed light yellow tablets, it will usually be transient and of no consequence. The possibility of ovulation increases with each successive day that scheduled light yellow tablets are missed. The risk of pregnancy increases with each active (light yellow) tablet missed.

Norethindrone and ethinyl estradiol tablets, chewable and ferrous fumarate tablets may be initiated no earlier than day 28 postpartum in the nonlactating mother due to the increased risk for thromboembolism. When the tablets are administered in the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered (see “CONTRAINDICATIONS,” “WARNINGS,” and “PRECAUTIONS” concerning thromboembolic disease). The patient should be advised to use a non-hormonal back-up method for the first 7 days of tablet-taking. However, if intercourse has already occurred, the possibility of ovulation and conception prior to initiation of medication should be considered. Norethindrone and ethinyl estradiol tablets, chewable and ferrous fumarate tablets may be initiated after a first-trimester abortion; if the patient starts norethindrone and ethinyl estradiol tablets, chewable and ferrous fumarate tablets immediately, additional contraceptive measures are not needed.

For additional patient instructions regarding complete dosing instructions, see “HOW TO TAKE THE PILL” section in the DETAILED PATIENT LABELING.

Applies to ethinyl estradiol / norethindrone: oral capsule liquid filled, oral tablet, oral tablet chewable

Other dosage forms:

• oral tablet, oral tablet chewable

Along with its needed effects, ethinyl estradiol / norethindrone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking ethinyl estradiol / norethindrone:

• Abdominal or stomach pain
• absent, missed, or irregular menstrual periods
• anxiety
• change in vision
• changes in skin color
• chest pain or discomfort
• chills
• clay-colored stools
• constipation
• cough
• dark urine
• diarrhea
• dizziness or lightheadedness
• fainting
• fast heartbeat
• fever
• headache
• hives or welts
• itching skin
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of appetite
• medium to heavy, irregular vaginal bleeding between regular monthly periods, which may require the use of a pad or a tampon
• nausea and vomiting
• pain or discomfort in the arms, jaw, back, or neck
• pain, tenderness, or swelling of the foot or leg
• pains in the chest, groin, or legs, especially in the calves of the legs
• pounding in the ears
• rash
• redness of the skin
• severe headaches of sudden onset
• slow or fast heartbeat
• sudden loss of coordination or slurred speech
• sudden onset of shortness of breath for no apparent reason
• sudden shortness of breath or troubled breathing
• sweating
• unusual tiredness or weakness
• vomiting of blood

Some side effects of ethinyl estradiol / norethindrone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abdominal or stomach cramps
• bloating
• blotchy spots on the exposed skin
• breast enlargement or tenderness
• discouragement
• feeling sad or empty
• irritability
• itching of the vagina or outside genitals
• loss of interest or pleasure
• pain during sexual intercourse
• thick, white curd-like vaginal discharge without odor or with mild odor
• tiredness
• trouble concentrating
• trouble sleeping
• trouble wearing contact lenses