Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1776
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Triphasil-21 (Kit)
|
| dailymed-instance:dosage |
To achieve maximum contraceptive effectiveness, Triphasil-21
Tablets (levonorgestrel and ethinyl estradiol tablets���triphasic regimen)
must be taken exactly as directed and at intervals not exceeding 24 hours. Triphasil-21
Tablets are a three-phase preparation. The dosage of Triphasil-21 Tablets
is one tablet daily for 21 consecutive days per menstrual cycle in the following
order: 6 brown tablets (phase 1), followed by 5 white tablets (phase 2), and
then followed by the last 10 light-yellow tablets (phase 3), according to
the prescribed schedule. Tablets are then discontinued for 7 days (three weeks
on, one week off). It is recommended that Triphasil-21 Tablets be taken at
the same time each day, preferably after the evening meal or at bedtime. During
the first cycle of medication, the patient should be instructed to take one
Triphasil-21 Tablet daily in the order of 6 brown, 5 white and, finally, 10
light-yellow tablets, for twenty-one (21) consecutive days, beginning on day
one (1) of her menstrual cycle. (The first day of menstruation is day one.)
The tablets are then discontinued for one week (7 days). Withdrawal bleeding
usually occurs within 3 days following discontinuation of Triphasil-21 Tablets
and may not have finished before the next pack is started. (If Triphasil-21
Tablets are first taken later than the first day of the first menstrual cycle
of medication or postpartum, contraceptive reliance should not be placed on
Triphasil-21 Tablets until after the first 7 consecutive days of administration
and a nonhormonal back-up method of birth control should be used during those
7 days. The possibility of ovulation and conception prior to initiation of
medication should be considered.) When switching from
another oral contraceptive, Triphasil-21 Tablets should be started on the
first day of bleeding following the last active tablet taken of the previous
oral contraceptive. The patient may switch any day from a progestin-only pill
and should begin Triphasil-21 the next day. If switching from an implant or
injection, the patient should start Triphasil-21 on the day of implant removal
or, if using an injection, the day the next injection would be due. In switching
from a progestin-only pill, injection, or implant, the patient should be advised
to use a nonhormonal back-up method of birth control for the first 7 days
of tablet-taking. The patient begins her next and all
subsequent 21-day courses of Triphasil-21 Tablets on the same day of the week
that she began her first course, following the same schedule: 21 days on���7 days off. She begins taking her brown tablets on the 8th day after discontinuance,
regardless of whether or not a menstrual period has occurred or is still in
progress. Any time a subsequent cycle of Triphasil-21 Tablets is started later
than the 8th day, the patient should be protected by another means of contraception
until she has taken a tablet daily for seven consecutive days. 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 physician. Although the occurrence of pregnancy
is highly unlikely if Triphasil-21 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 before
the medication is resumed. If the patient has adhered to the prescribed regimen
and misses two consecutive periods, pregnancy should be ruled out before continuing
the contraceptive regimen. The risk of pregnancy increases
with each tablet missed. For additional patient instructions regarding missed
pills, see the���WHAT TO DO IF YOU MISS PILLS���section
in the DETAILED PATIENT LABELING below. If
breakthrough bleeding occurs following missed tablets, it will usually be
transient and of no consequence. Triphasil-21 may be
initiated no earlier than day 28 postpartum in the non-lactating mother or
after a second trimester abortion due to the increased risk for thromboembolism
(see���Contraindications,������Warnings,���and���Precautions���concerning thromboembolic disease). The patient should be advised
to use a nonhormonal back-up method for the first 7 days of tablet-taking.
However, if intercourse has already occurred, pregnancy should be excluded
before the start of combined oral contraceptive use or the patient must wait
for her first menstrual period. In the case of first-trimester abortion, if
the patient starts Triphasil-21 immediately, additional contraceptive measures
are not needed. It is to be noted that early resumption of ovulation may occur
if Parlodel (bromocriptine mesylate) has been used for the
prevention of lactation.
|
| dailymed-instance:descripti... |
Each Triphasil cycle of 21 tablets consists of three different
drug phases as follows: Phase 1 comprised of 6 brown tablets, each containing
0.050 mg of levonorgestrel (d (-)-13
beta-ethyl-17-alpha-ethinyl-17-beta-hydroxygon-4-en-3-one), a totally synthetic
progestogen, and 0.030 mg of ethinyl estradiol (19-nor-17��-pregna-1,3,5(10)-trien-20-yne-3,
17-diol); phase 2 comprised of 5 white tablets, each containing 0.075 mg
levonorgestrel and 0.040 mg ethinyl estradiol; and phase 3 comprised
of 10 light-yellow tablets, each containing 0.125 mg levonorgestrel and
0.030 mg ethinyl estradiol. The inactive ingredients present are cellulose,
iron oxides, lactose, magnesium stearate, polacrilin potassium, polyethylene
glycol, titanium dioxide, and hydroxypropyl methylcellulose.
|
| dailymed-instance:clinicalP... |
Combination oral contraceptives primarily 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).<br/>PHARMACOKINETICS:<br/>Absorption: Levonorgestrel is rapidly and completely absorbed after oral
administration (bioavailability about 100%). Levonorgestrel is not subject
to first-pass metabolism or enterohepatic circulation and therefore does not
undergo variations in absorption after oral administration. Ethinyl estradiol
is rapidly and almost completely absorbed from the gastrointestinal tract
but,due to first-pass metabolism in gut mucosa and liver, the bioavailability
of ethinyl estradiol is between 38% and 48%. There
have been no formal multiple-dose studies conducted using Triphasil. However,
a multiple-dose study was done in 22 women using a monophasic, low dose combination
of 0.10 mg levonorgestrel and 0.02 mg ethinyl estradiol. Maximum
serum concentrations of levonorgestrel were found to be 2.8��0.9 ng/mL
(mean��SD) at 1.6��0.9 hours after a single dose, reaching a steady
state at day 19. Observed levonorgestrel concentrations increased from day
1 to days 6 and 21 by 34% and 96%, respectively. Unbound levonorgestrel concentrations
subsequently increased from day 1 to days 6 and 21 by 25% and 83%, respectively,
however, the accumulation of unbound levonorgestrel was approximately 14%
less than total levonorgestrel accumulation. The kinetics of total levonorgestrel
were non-linear due to an increase in binding of levonorgestrel to SHBG, which
is attributedto increased SHBG levels that are induced by the daily administration
of ethinyl estradiol. Ethinyl estradiol reached maximum serum concentrations
of 62��21 pg/mL at 1.5��0.5 hours after a single dose, reaching
steady state at day 6. Ethinyl estradiol concentrations increased by 19% from
days 1 to 21 consistent with an elimination half-life of 18 hours. Single-dose
studies with Triphasil have been conducted with the following data reported
below in Table I. Plasma concentrations have
been corrected below to reflect single tablet dosing/day.<br/>Distribution: Levonorgestrel is bound to SHBG and albumin. Levonorgestrel
has high binding affinity for SHBG that is 60% of that of testosterone. Ethinyl
estradiol is about 97% bound to plasma albumin. Ethinyl estradiol does not
bind to SHBG, but will induce SHBG synthesis.<br/>Metabolism: Levonorgestrel: The
most important metabolic pathway occurs in the reduction of the��4-3-oxo
group and hydroxylation at positions 2��, 1��, and 16��, followed
by conjugation. Most of the metabolites that circulate in the blood are sulfates
of 3��,5��-tetrahydro-levonorgestrel, while excretion occurs predominately
in the form of glucuronides. Some of the parent levonorgestrel also circulates
as 17��-sulfate. Metabolic clearance rates may differ among individuals
by several-fold, and this may account in part for the wide variation observed
in levonorgestrel concentrations among users. Ethinyl estradiol: Cytochrome P450 enzymes (CYP3A4)
in the liver are responsible for the 2-hydroxylation that is the major oxidative
reaction. The 2-hydroxy metabolite is further transformed by methylation and
glucuronidation prior to urinary and fecal excretion. Levels of Cytochrome
P450 (CYP3A) vary widely among individuals and can explain the variation in
rates of ethinyl estradiol 2-hydroxylation. Ethinyl estradiol is excreted
in the urine and feces as glucuronide and sulfate conjugates, and undergoes
enterohepatic circulation.<br/>Excretion: The elimination half-life for levonorgestrel is approximately
36��13 hours at steady state. Levonorgestrel and its metabolites are
primarily excreted in the urine (40% to 68%) and about 16% to 48% are excreted
in the feces. The elimination half-life of ethinyl estradiol is 18��4.7 hours at steady state.<br/>SPECIAL POPULATIONS:<br/>Hepatic Insufficiency: No formal studies have evaluated the effect of hepatic disease
on the disposition of Triphasil. However, steroid hormones may be poorly metabolized
in patients with impaired liver function.<br/>Renal Insufficiency: No formal studies have evaluated the effect of renal disease
on the disposition of Triphasil.<br/>Drug-Drug Interactions: See���Precautions���section���DRUG
INTERACTIONS.
|
| dailymed-instance:contraind... |
Combination oral contraceptives should not be used in women
with any of the following conditions:
|
| dailymed-instance:supply |
Triphasil-21 Tablets (levonorgestrel and
ethinyl estradiol tablets���triphasic regimen), NDC 0008-2535, are
available in packages of 3 dial dispensers. Each cycle contains 21 round,
coated tablets as follows: NDC 0008-0641, six
brown tablets marked���W���and���641���, each containing 0.050 mg levonorgestrel and 0.030 mg
ethinyl estradiol; NDC 0008-0642, five white to
off-white tablets marked���W���and���642���, each containing 0.075 mg levonorgestrel
and 0.040 mg ethinyl estradiol; and NDC 0008-0643,
ten light-yellow tablets marked���W���and���643���, each containing 0.125 mg levonorgestrel
and 0.030 mg ethinyl estradiol. Store
at controlled room temperature 20��to
25��C (68��to 77��F). References available upon request.
|
| dailymed-instance:boxedWarn... |
Cigarette smoking increases the
risk of serious cardiovascular side effects from oral-contraceptive use. This
risk increases with age and with the extent of smoking (in epidemiologic studies,
15 or more cigarettes per day was associated with a significantly increased
risk) and is quite marked in women over 35 years of age. Women who use oral
contraceptives should be strongly advised not to smoke.
|
| dailymed-instance:inactiveI... |
dailymed-ingredient:cellulose,
dailymed-ingredient:hydroxypropyl_methylcellulose,
dailymed-ingredient:iron_oxides,
dailymed-ingredient:lactose,
dailymed-ingredient:magnesium_stearate,
dailymed-ingredient:polacrilin_potassium,
dailymed-ingredient:polyethylene_glycol,
dailymed-ingredient:titanium_dioxide
|
| dailymed-instance:precautio... |
1. GENERAL: Patients should be counseled that
this product does not protect against HIV infection (AIDS) and other sexually
transmitted diseases.<br/>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 withparticular
care.<br/>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,���1d.) 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.<br/>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.<br/>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.<br/>6. EMOTIONAL DISORDERS: 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.<br/>7. CONTACT LENSES: Contact-lens wearers who develop visual changes or changes
in lens tolerance should be assessed by an ophthalmologist.<br/>8. GASTROINTESTINAL MOTILITY: Diarrhea and/or vomiting may reduce hormone absorption.<br/>9. DRUG INTERACTIONS: Interactions between ethinyl estradiol and other substances
may lead to decreased or increased serum ethinyl estradiol concentrations. Decreased
ethinyl estradiol plasma concentrations may cause an increased incidence of
breakthrough bleeding and menstrual irregularities and may possibly reduce
efficacy of the combination oral contraceptive. Reduced ethinyl estradiol
concentrations have been associated with concomitant use of substances that
induce hepatic microsomal enzymes, such as rifampin, rifabutin, barbiturates,
phenylbutazone, phenytoin sodium, griseofulvin, topiramate, some protease
inhibitors, modafinil, and possibly St. John's wort. Substances
that may decrease plasma ethinyl estradiol concentrations by other mechanisms
include any substance that reduces gut transit time and certain antibiotics
(eg, ampicillin and other penicillins, tetracyclines) by a decrease of enterohepatic
circulation of estrogens. During concomitant use of
ethinyl estradiol containing products and substances that may lead to decreased
plasma steroid hormone concentrations, it is recommended that a nonhormonal
back-up method of birth control be used in addition to the regular intake
of Triphasil. If the use of a substance which leads to decreased ethinyl estradiol
plasma concentrations is required for a prolonged period of time, combination
oral contraceptives should not be considered the primary contraceptive. After
discontinuation of substances that may lead to decreased ethinyl estradiol
plasma concentrations, use of a nonhormonal back-up method of birth control
is recommended for 7 days. Longer use of a back-up method is advisable after
discontinuation of substances that have led to induction of hepatic microsomal
enzymes, resulting in decreased ethinyl estradiol concentrations. It may take
several weeks until enzyme induction has completely subsided, depending on
dosage, duration of use, and rate of elimination of the inducing substance. Some
substances may increase plasma ethinyl estradiol concentrations. These include: Ethinyl estradiol may interfere with the mechanism of other
drugs by inhibiting hepatic microsomal enzymes or by inducing hepatic drug
conjugation, particularly glucuronidation. Accordingly, tissue concentrations
may be either increased (eg, cyclosporine, theophylline, corticosteroids)
or decreased. The prescribing information of concomitant
medications should be consulted to identify potential interactions.<br/>10. INTERACTIONS WITH LABORATORY TESTS: Certain endocrine- and liver-function tests and blood components
may be affected by oral contraceptives:<br/>11. CARCINOGENESIS: See���Warnings���section.<br/>12. PREGNANCY: Pregnancy Category X. See���Contraindications���and���Warnings���sections.<br/>13. 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, combination 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 combination
oral contraceptives but to use other forms of contraception until she has
completelyweaned her child.<br/>14. PEDIATRIC USE: Safety and efficacy of Triphasil (levonorgestrel
and ethinyl estradiol tablets���triphasic regimen) 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 users 16 and older. Use
of this product before menarche is not indicated.<br/>INFORMATION FOR THE PATIENT: See Patient Labeling Printed Below.
|
| dailymed-instance:overdosag... |
Serious ill effects have not been reported following acute
ingestion of large doses of oral contraceptives by young children. Overdosage
may cause nausea, and withdrawal bleeding may occur in females.
|
| dailymed-instance:genericMe... |
Levonorgestrel and Ethinyl Estradiol
|
| dailymed-instance:fullName |
Triphasil-21 (Kit)
|
| dailymed-instance:adverseRe... |
An increased risk of the following serious adverse reactions
(see���Warnings���section for additional information) has been associated with the
use of oral contraceptives: The following adverse reactions have been reported in patients
receiving oral contraceptives and are believed to be drug related: The following adverse reactions have been reported in users
of oral contraceptives, and the association has been neither confirmed nor
refuted:
|
| dailymed-instance:warning |
Cigarette smoking increases the
risk of serious cardiovascular side effects from oral-contraceptive use. This
risk increases with age and with the extent of smoking (in epidemiologic studies,
15 or more cigarettes per day was associated with a significantly increased
risk) and is quite marked in women over 35 years of age. Women who use oral
contraceptives should be strongly advised not to smoke. The use of oral contraceptives is associated with increased
risks of several serious conditions including venous and arterial thrombotic
and thromboembolic events (such as myocardial infarction, thromboembolism,
and stroke), hepatic neoplasia, gallbladder disease, and hypertension, although
the risk of serious morbidity or mortality is very small in healthy women
without underlying risk factors. The risk of morbidity and mortality increases
significantly in the presence of other underlying risk factorssuch as certain
inherited or acquired thrombophilias, hypertension, hyperlipidemias, obesity,
and diabetes. Practitioners prescribing oral contraceptives
should be familiar with the following information relating to these risks. The
information contained in this package insert is based principally on studies
carried out in patients who used oral contraceptives with higher formulations
of estrogens and progestogens than those in common use today. The effect of
long-term use of the oral contraceptives with lower formulations of both estrogens
and progestogens remains to be determined. Throughout
this labeling, epidemiological studies reported are of two types: retrospective
or case control studies and prospective or cohort studies. Case control studies
provide a measure of the relative risk of disease, namely, a ratio of the
incidence of a disease among oral-contraceptive users to that among nonusers.
The relative risk does not provide information on the actual clinical occurrence
of a disease. Cohort studies provide a measure of attributable risk, which
is the difference in the incidence of disease between oral-contraceptive users
and nonusers. The attributable risk does provide information about the actual
occurrence of a disease in the population. For further information, the reader
is referred to a text on epidemiological methods.<br/>1. THROMBOEMBOLIC DISORDERS AND OTHER VASCULAR PROBLEMS:<br/>a. Myocardial infarction: An increased risk of myocardial infarction has been attributed
to oral-contraceptive use. This risk is primarily in smokers or women with
other underlying risk factors for coronary-artery disease such as hypertension,
hypercholesterolemia, morbid obesity, and diabetes. The relative risk of heart
attack for current oral-contraceptive users has been estimated to be two to
six. The risk is very low under the age of 30. Smoking
in combination with oral-contraceptive use has been shown to contribute substantially
to the incidence of myocardial infarctions in women in their mid-thirties
or older with smoking accounting for the majority of excess cases. Mortality
rates associated with circulatory disease have been shown to increase substantially
in smokers over the age of 35 and nonsmokers over the age of 40 (Table III) among women who use oral contraceptives. CIRCULATORY DISEASE MORTALITY RATES PER 100,000 WOMAN YEARS
BY AGE, SMOKING STATUS AND ORAL-CONTRACEPTIVE USE Oral contraceptives may compound the effects of well-known
risk factors, such as hypertension, diabetes, hyperlipidemias, age, and obesity.
In particular, some progestogens are known to decrease HDL cholesterol and
cause glucose intolerance, while estrogens may create a state of hyperinsulinism.
Oral contraceptives have been shown to increase blood pressure among users
(see section 9 in���Warnings���). Similar effects on risk factors have been associated with an
increased risk of heart disease. Oral contraceptives must be used with caution
in women with cardiovascular disease risk factors.<br/>b. Thromboembolism: An increased risk of venous thromboembolic and thrombotic
disease associated with the use of oral contraceptives is well established.
Case control studies have found the relative risk of users compared to nonusers
to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for
deep-vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing
conditions for venous thromboembolic disease. Cohort studies have shown the
relative risk to be somewhat lower, about 3 for new cases and about 4.5 for
new cases requiring hospitalization. The approximate incidence of deep-vein
thrombosis and pulmonary embolism in users of low dose (<50��g
ethinyl estradiol) combination oral contraceptives is up to 4 per 10,000
woman-years compared to 0.5-3 per 10,000 woman-years for nonusers. However,
the incidence is substantially less than that associated with pregnancy (6
per 10,000 woman-years). The risk of thromboembolic disease due to oral contraceptives
is not related to length of use and disappears after pill use is stopped. A
two- to four-fold increase in relative risk of postoperative thromboembolic
complications has been reported with the use of oral contraceptives. The relative
risk of venous thrombosis in women who have predisposing conditions is twice
that of women without such medical conditions. If feasible, oral contraceptives
should be discontinued at least four weeks prior to and for two weeks after
elective surgery of a type associated with an increase in risk of thromboembolism
and during and following prolonged immobilization. Since the immediate postpartum
period is also associated with an increased risk of thromboembolism, oral
contraceptives should be started no earlier than four to six weeks after delivery
in women who elect not to breast-feed, or a midtrimester pregnancy termination.<br/>c. Cerebrovascular diseases: Oral contraceptives have been shown to increase both the
relative and attributable risks of cerebrovascular events (thrombotic and
hemorrhagic strokes), although, in general, the risk is greatest among older
(>35 years), hypertensive women who also smoke. Hypertension was found to
be a risk factor for both users and nonusers, for both types of strokes, while
smoking interacted to increase the risk for hemorrhagic strokes. In
a large study, the relative risk of thrombotic strokes has been shown to range
from 3 for normotensive users to 14 for users with severe hypertension. The
relative risk of hemorrhagic stroke is reported to be 1.2 for nonsmokers who
used oral contraceptives, 2.6 for smokers who did not use oral contraceptives,
7.6 for smokers who used oral contraceptives, 1.8 for normotensive users,
and 25.7 for users with severe hypertension. The attributable risk is also
greater in older women. Oral contraceptives also increase the risk for stroke
in women with other underlying risk factors such as certain inherited or acquired
thrombophilias, hyperlipidemias, and obesity. Women
with migraine (particularly migraine with aura) who take combination oral
contraceptives may be at an increased risk of stroke.<br/>d. Dose-related risk of vascular disease from oral contraceptives: A positive association has been observed between the amount
of estrogen and progestogen in oral contraceptives and the risk of vasculardisease. A decline in serum high-density lipoproteins (HDL) has been reported
with many progestational agents. A decline in serum high-density lipoproteins
has been associated with an increased incidence of ischemic heart disease.
Because estrogens increase HDL cholesterol, the net effect of an oral contraceptive
depends on a balance achieved between doses of estrogen and progestogen and
the nature and absolute amount of progestogen used in the contraceptive. The
amount of both hormones should be considered in the choice of an oral contraceptive. Minimizing
exposure to estrogen and progestogen is in keeping with good principles of
therapeutics. For any particular estrogen/progestogen combination, the dosage
regimen prescribed should be one which contains the least amount of estrogen
and progestogen that is compatible with a low failure rate and the needs of
the individual patient. New acceptors of oral-contraceptive agents should
be started on preparations containing less than 50 mcg of estrogen.<br/>e. Persistence of risk of vascular disease: There are two studies which have shown persistence of risk
of vascular disease for ever-users of oral contraceptives. In a study in the
United States, the risk of developing myocardial infarction after discontinuing
oral contraceptives persists for at least 9 years for women 40 to 49 years
who had used oral contraceptives for five or more years, but this increased
risk was not demonstrated in other age groups. In another study in Great Britain,
the risk of developing cerebrovascular disease persisted for at least 6 years
after discontinuation of oral contraceptives, although excess risk was very
small. However, both studies were performed with oral-contraceptive formulations
containing 50 micrograms or higher of estrogens.<br/>2. ESTIMATES OF MORTALITY FROM CONTRACEPTIVE USE: One study gathered data from a variety of sources which have
estimated the mortality rate associated with different methods of contraception
at different ages (Table IV). These estimates
include the combined risk of death associated with contraceptive methods plus
the risk attributable to pregnancy in the event of method failure. Each method
of contraception has its specific benefits and risks. The study concluded
that with the exception of oral-contraceptive users 35 and older who smoke
and 40 and older who do not smoke, mortality associated with all methods of
birth control is less than that associated with childbirth. The observation
of a possible increase in risk of mortality with age for oral-contraceptive
users is based on data gathered in the 1970's���but not reported
until 1983. However, current clinical practice involves the use of lower estrogen
dose formulations combined with careful restriction of oral-contraceptive
use to women who do not have the various risk factors listed in this labeling. Because
of these changes in practice and, also, because of some limited new data which
suggest that the risk of cardiovascular disease with the use of oral contraceptives
may now be less than previously observed, the Fertility and Maternal Health
Drugs Advisory Committee was asked to review the topic in 1989. The Committee
concluded that although cardiovascular-disease risks may be increased with
oral-contraceptive use after age 40 in healthy nonsmoking women (even with
the newer low-dose formulations), there are greater potential health risks
associated with pregnancy in older women andwith the alternative surgical
and medical procedures which may be necessary if such women do not have access
to effective and acceptable means of contraception. Therefore,
the Committee recommended that the benefits of oral-contraceptive use by healthy
nonsmoking women over 40 may outweigh the possible risks. Of course, older
women, as all women who take oral contraceptives, should take the lowest possible
dose formulation that is effective.<br/>3. CARCINOMA OF THE REPRODUCTIVE ORGANS: A meta-analysis from 54 epidemiological studies reported
that there is a slightly increased relative risk (RR=1.24) of having breast
cancer diagnosed in women who are currently using combination oral contraceptives
compared to never-users. The increased risk gradually disappears during the
course of the 10 years after cessation of combination oral contraceptive use.
These studies do not provide evidence for causation. The observed pattern
of increased risk of breast cancer diagnosis may be due to earlier detection
of breast cancer in combination oral contraceptive users, the biological effects
of combination oral contraceptives, or a combination of both. Because breast
cancer is rare in women under 40 years of age, the excess number of breast
cancer diagnoses in current and recent combination oral contraceptive users
is small in relation to the lifetime risk of breast cancer. Breast cancers
diagnosed in ever-users tend to be less advanced clinically than the cancers
diagnosed in never-users. Some studies suggest that
oral-contraceptive use has been associated with an increase in the risk of
cervical intraepithelial neoplasia or invasive cervical cancer in some populations
of women. However, there continues to be controversy about the extent to which
such findings may be due to differences in sexual behavior and other factors. In
spite of many studies of the relationship between oral-contraceptive use and
breast and cervical cancers, a cause-and-effect relationship has not been
established.<br/>4. HEPATIC NEOPLASIA: Benign hepatic adenomas are associated with oral-contraceptive
use, although the incidence of benign tumors is rare in the United States.
Indirect calculations have estimated the attributable risk to be in the range
of 3.3 cases/100,000 for users, a risk that increases after four or more years
of use. Rupture of rare, benign, hepatic adenomas may cause death through
intra-abdominal hemorrhage. Studies from Britain have
shown an increased risk of developing hepatocellular carcinoma in long-term
(>8 years) oral-contraceptive users. However, these cancers are extremely
rare in the U.S., and the attributable risk (the excess incidence) of liver
cancers in oral-contraceptive users approaches less than one per million users.<br/>5. OCULAR LESIONS: There have been clinical case reports of retinal thrombosis
associated with the use of oral contraceptives that may lead to partial or
complete loss of vision. Oral contraceptives should be discontinued if there
is unexplained partial or complete loss of vision; onset of proptosis or diplopia;
papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic
measures should be undertaken immediately.<br/>6. ORAL-CONTRACEPTIVE USE BEFORE OR DURING EARLY PREGNANCY: Extensive epidemiological studies have revealed no increased
risk of birth defects in women who have used oral contraceptives prior to
pregnancy. Studies also do not suggest a teratogenic effect, particularly
insofar as cardiac anomalies and limb-reduction defects are concerned, when
taken inadvertently during early pregnancy (see���Contraindications���section). The
administration of oral contraceptives to induce withdrawal bleeding should
not be used as a test for pregnancy. Oral contraceptives should not be used
during pregnancy to treat threatened or habitual abortion. It
is recommended that for any patient who has missed two consecutive periods,
pregnancy should be ruled out before continuing oral-contraceptive use. If
the patient has not adhered to the prescribed schedule, the possibility of
pregnancy should be considered at the time of the first missed period. Oral-contraceptive
use should be discontinued if pregnancy is confirmed.<br/>7. GALLBLADDER DISEASE: Earlier studies have reported an increased lifetime relative
risk of gallbladder surgery in users of oral contraceptives and estrogens.
More recent studies, however, have shown that the relative risk of developing
gallbladder disease among oral-contraceptive users may be minimal. The recent
findings of minimal risk may be related to the use of oral-contraceptive formulations
containing lower hormonal doses of estrogens and progestogens.<br/>8. CARBOHYDRATE AND LIPID METABOLIC EFFECTS: Oral contraceptives have been shown to cause glucose intolerance
in a significant percentage of users. Oral contraceptives containing greater
than 75 micrograms of estrogens cause hyperinsulinism, while lower doses of
estrogen cause less glucose intolerance. Progestogens increase insulin secretion
andcreate insulin resistance, this effect varying with different progestational
agents. However, in the nondiabetic woman, oral contraceptives appear to have
no effect on fasting blood glucose. Because of these demonstrated effects,
prediabetic and diabetic women should be carefully observed while taking oral
contraceptives. A small proportion of women will have
persistent hypertriglyceridemia while on the pill. As discussed earlier (see���Warnings,���1a. and 1d.), changes in serum triglycerides and lipoprotein levels have been
reported in oral-contraceptive users.<br/>9. ELEVATED BLOOD PRESSURE: An increase in blood pressure has been reported in women
taking oral contraceptives, and this increase is more likely in older oral-contraceptive
users and with continued use. Data from the Royal College of General Practitioners
and subsequent randomized trials have shown that the incidence of hypertension
increases with increasing quantities of progestogens. Women
with a history of hypertension or hypertension-related diseases, or renal
disease, should be encouraged to use another method of contraception. If women
with hypertension elect to use oral contraceptives, they should be monitored
closely, and if significant elevation of blood pressure occurs, oral contraceptives
should be discontinued (see���Contraindications���section). For most women, elevated blood pressure will return to
normal after stopping oral contraceptives, and there is no difference in the
occurrence of hypertension among ever- and never-users.<br/>10. HEADACHE: The onset or exacerbation of migraine or development of headache
with a new pattern that is recurrent, persistent, or severe requires discontinuation
of oral contraceptives and evaluation of the cause. (See���Warnings,���1c.)<br/>11. BLEEDING IRREGULARITIES: Breakthrough bleeding and spotting are sometimes encountered
in patients on oral contraceptives, especially during the first three months
of use. The type and dose of progestogen may be important. If bleeding persists
or recurs, nonhormonal causes should be considered and adequate diagnostic
measures taken to rule out malignancy or pregnancy in the event of breakthrough
bleeding, as in the case of any abnormal vaginal bleeding. If pathology has
been excluded, time or a change to another formulation may solve the problem.
In the event of amenorrhea, pregnancy should be ruled out if the oral contraceptive
has not been taken according to directions prior to the first missed withdrawal
bleed or if two consecutive withdrawal bleeds have been missed. Some
women may encounter post-pill amenorrhea or oligomenorrhea (possibly with
anovulation), especially when such a condition was preexistent.
|
| dailymed-instance:indicatio... |
Oral contraceptives are indicated for the prevention of pregnancy
in women who elect to use this product as a method of contraception. Oral
contraceptives are highly effective. Table II 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 and the IUD, depends upon the reliability with which
they are used. Correct and consistentuse of methods can result in lower failure
rates.<br/>Contraindications: Combination oral contraceptives should not be used in women
with any of the following conditions:
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Triphasil-21
|