Microgestin 1.5/30 - Norethindrone Acetate/Ethinyl Estradiol prescribing information
Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke.
INDICATIONS AND USAGE
Microgestin 1.5/30 is indicated for the prevention of pregnancy in women who elect to use oral contraceptives as a method of contraception.
Oral contraceptives are highly effective. Table 1 lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates.
DOSAGE AND ADMINISTRATION
The compact tablet dispenser has been designed to make oral contraceptive dosing as easy and as convenient as possible. The tablets are arranged in three rows of seven tablets each, with the days of the week appearing on the compact tablet dispenser above the first row of tablets.
Note: Each compact tablet dispenser has been preprinted with the days of the week, starting with Sunday, to facilitate a Sunday-Start regimen. Six different day label stickers have been provided with the Detailed Patient & Brief Summary Patient Package Insert in order to accommodate a Day-1 Start regimen. If the patient is using the Day-1 Start regimen, she should place the self-adhesive day label sticker that corresponds to her starting day over the preprinted days.
Important: The patient should be instructed to use an additional method of protection until after the first week of administration in the initial cycle when utilizing the Sunday-Start regimen.
The possibility of ovulation and conception prior to initiation of use should be considered.
Dosage and Administration for 21-Day Dosage Regimen
To achieve maximum contraceptive effectiveness, Microgestin 1.5/30 should be taken exactly as directed and at intervals not exceeding 24 hours. Microgestin 1.5/30 provides the patient with a convenient tablet schedule of "3 weeks on-1 week off". Two dosage regimens are described, one of which may be more convenient or suitable than the other for an individual patient. For the initial cycle of therapy, the patient begins her tablets according to the Day 1 Start or Sunday-Start regimen. With either regimen, the patient takes one tablet daily for 21 consecutive days followed by one week of no tablets.
A. Sunday-Start Regimen: The patient begins taking tablets from the top row of the dispenser (labeled Sunday) on the first Sunday after menstrual flow begins. When the menstrual flow begins on Sunday, the first tablet is taken on the same day. The last tablet in the dispenser will be taken on a Saturday, followed by no tablets for a week (7 days). For all subsequent cycles, the patient then begins a new 21-tablet regimen on the eighth day, Sunday, after taking her last tablet. Following this regimen, of 21 days on-7 days off, the patient will start all subsequent cycles on a Sunday.
B. Day-1 Start Regimen: The first day of menstrual flow is Day 1. The patient places the self-adhesive day label sticker that corresponds to her starting day over the preprinted days on the tablet dispenser. She starts taking one tablet daily, beginning with the first tablet in the top row. The patient completes her 21-tablet regimen when she has taken the last tablet in the tablet dispenser. She will then take no tablets for a week (7 days). For all subsequent cycles, the patient begins a new 21-tablet regimen on the eighth day after taking her last tablet, again starting with the first tablet in the top row after placing the appropriate day label sticker over the preprinted days on the tablet dispenser. Following this regimen of 21 days on--7 days off, the patient will start all subsequent cycles on the same day of the week as the first course. Likewise, the interval of no tablets will always start on the same day of the week.
Tablets should be taken regularly with a meal or at bedtime. It should be stressed that efficacy of medication depends on strict adherence to the dosage schedule.
Special Notes on Administration
Menstruation usually begins two or three days, but may begin as late as the fourth or fifth day, after discontinuing medication. If spotting occurs while on the usual regimen of one tablet daily, the patient should continue medication without interruption.
If the patient forgets to take one or more tablets, the following is suggested:
One tablet is missed
● take tablet as soon as remembered
● take next tablet at the regular time
Two consecutive tablets are missed (week 1 or week 2)
● take two tablets as soon as remembered
● take two tablets the next day
● use another birth control method for seven days following the missed tablets
Two consecutive tablets are missed (week 3)
Sunday-Start Regimen:
● take one tablet daily until Sunday
● discard remaining tablets
● start new pack of tablets immediately (Sunday)
● use another birth control method for seven days following the missed tablets
Day-1 Start Regimen:
● discard remaining tablets
● start new pack of tablets that same day
● use another birth control method for seven days following the missed tablets
Three (or more) consecutive tablets are missed
Sunday-Start Regimen:
● take one tablet daily until Sunday
● discard remaining tablets
● start new pack of tablets immediately (Sunday)
● use another birth control method for seven days following the missed tablets
Day-1 Start Regimen:
● discard remaining tablets
● start new pack of tablets that same day
● use another birth control method for seven days following the missed tablets
The possibility of ovulation occurring increases with each successive day that scheduled yellow tablets are missed. While there is little likelihood of ovulation occurring if only one yellow tablet is missed, the possibility of spotting or bleeding is increased. This is particularly likely to occur if two or more consecutive yellow tablets are missed.
In the rare case of bleeding which resembles menstruation, the patient should be advised to discontinue medication and then begin taking tablets from a new compact tablet dispenser on the next Sunday or the first day (Day-1), depending on her regimen. Persistent bleeding which is not controlled by this method indicates the need for reexamination of the patient, at which time nonfunctional causes should be considered.
Use of Oral Contraceptives in the Event of a Missed Menstrual Period
1. If the patient has not adhered to the prescribed dosage regimen, the possibility of pregnancy should be considered after the first missed period and oral contraceptives should be withheld until pregnancy has been ruled out.
2. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.
After several months on treatment, bleeding may be reduced to a point of virtual absence. This reduced flow may occur as a result of medication, in which event it is not indicative of pregnancy.
CONTRAINDICATIONS
Oral contraceptives should not be used in women who currently have the following conditions:
● Thrombophlebitis or thromboembolic disorders
● A past history of deep vein thrombophlebitis or thromboembolic disorders
● Cerebral vascular or coronary artery disease
● Known or suspected carcinoma of the breast
● 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
● Known or suspected pregnancy
● Are receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations (see Warnings , RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT ).
ADVERSE REACTIONS
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, although additional confirmatory studies are needed:
● 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
● Melasma which may persist
● Breast changes: tenderness, enlargement, secretion
● Change in weight (increase or decrease)
● Change in cervical erosion and secretion
● Diminution in lactation when given immediately postpartum
● Cholestatic jaundice
● Rash (allergic)
● Mental depression
● Reduced tolerance to carbohydrates
● Vaginal candidiasis
● Change in corneal curvature (steepening)
● Intolerance to contact lenses
The following adverse reactions have been reported in users of oral contraceptives and the association has been neither confirmed nor refuted:
● Pre-menstrual syndrome
● Cataracts
● Changes in appetite
● Cystitis-like syndrome
● Headache
● Nervousness
● Dizziness
● Hirsutism
● Loss of scalp hair
● Erythema multiforme
● Erythema nodosum
● Hemorrhagic eruption
● Vaginitis
● Porphyria
● Impaired renal function
● Hemolytic uremic syndrome
● Budd-Chiari syndrome
● Acne
● Changes in libido
● Colitis
DESCRIPTION
Microgestin 1.5/30 is a progestogen-estrogen combination.
Microgestin 1.5/30 provides a continuous dosage regimen consisting of 21 yellow oral contraceptive tablets.
Each yellow tablet contains norethindrone acetate (17 alpha-ethinyl-19-nortestosterone acetate), 1.5 mg; ethinyl estradiol (17 alpha-ethinyl-1,3,5(10)-estratriene-3, 17 beta-diol), 30mcg. Also contains polyvinyl alcohol, titanium dioxide, talc, macrogol/polyethylglycol 3350 NF, lecithin (soya), iron oxide yellow, FD&C Blue No.2 Aluminum Lake, D&C Yellow No.10 Aluminum Lake, FD&C Yellow No.6 Aluminum Lake, lactose, magnesium stearate and pregelatinized corn starch.
The structural formulas are as follows:
CLINICAL PHARMACOLOGY
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).
Pharmacokinetics
The pharmacokinetics of Microgestin 1.5/30 has not been characterized; however, the following pharmacokinetic information regarding norethindrone acetate and ethinyl estradiol is taken from the literature.
Absorption
Norethindrone acetate appears to be completely and rapidly deacetylated to norethindrone after oral administration, since the disposition of norethindrone acetate is indistinguishable from that of orally administered norethindrone (1) . Norethindrone acetate and ethinyl estradiol are subject to first-pass metabolism after oral dosing, resulting in an absolute bioavailability of approximately 64% for norethindrone and 43% for ethinyl estradiol (1 to 3).
Distribution
Metabolism
Norethindrone undergoes extensive biotransformation, primarily via reduction, followed by sulfate and glucuronide conjugation. The majority of metabolites in the circulation are sulfates, with glucuronides accounting for most of the urinary metabolites (5) . A small amount of norethindrone acetate is metabolically converted to ethinyl estradiol. Ethinyl estradiol is also extensively metabolized, both by oxidation and by conjugation with sulfate and glucuronide. Sulfates are the major circulating conjugates of ethinyl estradiol and glucuronides predominate in urine. The primary oxidative metabolite is 2-hydroxy ethinyl estradiol, formed by the CYP3A4 isoform of cytochrome P450. Part of the first-pass metabolism of ethinyl estradiol is believed to occur in gastrointestinal mucosa. Ethinyl estradiol may undergo enterohepatic circulation (6) .
Excretion
Special Population
Race:
The effect of race on the disposition of Microgestin 1.5/30 has not been evaluated.
Renal Insufficiency
The effect of renal disease on the disposition of Microgestin 1.5/30 has not been evaluated. In premenopausal women with chronic renal failure undergoing peritoneal dialysis who received multiple doses of an oral contraceptive containing ethinyl estradiol and norethindrone, plasma ethinyl estradiol concentrations were higher and norethindrone concentrations were unchanged compared to concentrations in premenopausal women with normal renal function.
Hepatic Insufficiency
The effect of hepatic disease on the disposition of Microgestin 1.5/30 has not been evaluated. However, ethinyl estradiol and norethindrone may be poorly metabolized in patients with impaired liver function.
Drug-Drug Interactions
Numerous drug-drug interactions have been reported for oral contraceptives. A summary of these is found under PRECAUTIONS, Drug Interactions.
HOW SUPPLIED
Microgestin 1.5/30 is available in dispensers (NDC 51862-872-01) each containing 21 yellow tablets. Each yellow, biconvex, round tablet debossed with "L3" on one side contains 1.5mg of norethindrone acetate and 30 mcg of ethinyl estradiol.
Microgestin 1.5/30 Tablets are available in the following configurations:
Carton of 1 NDC 51862-872-02
Carton of 3 NDC 51862-872-03
Carton of 6 NDC 51862-872-06
Store at 20 ˚C ~ 25 ˚C (68 ˚F~77 ˚F) [See USP Controlled Room Temperature].
