Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3361
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Ortho Evra (Patch, Extended Release)
|
| dailymed-instance:dosage |
To achieve maximum contraceptive effectiveness, ORTHO
EVRA must be used exactly as directed. Complete
instructions to facilitate patient counseling on proper system usage may be
found in the Detailed Patient Labeling.<br/>Transdermal Contraceptive System Overview: ORTHO EVRA is a combination transdermal
contraceptive that contains 6.00 mg norelgestromin (NGMN) and 0.75mg ethinyl
estradiol (EE). Systemic exposures (as measured by AUC and C)
of NGMN and EE during use of ORTHO EVRA are higher and peak
concentrations (C) are lower than those produced by an oral
contraceptive containing norgestimate 250��g / EE 35��g. (See BOLDED WARNING; CLINICAL PHARMACOLOGY, Transdermal
versus Oral Contraceptives). This
system uses a 28-day (four-week) cycle. A new patch is applied each week for
three weeks (21 total days). Week Four is patch-free. Withdrawal bleeding
is expected during this time. Every new patch
should be applied on the same day of the week. This day is known as the "Patch
Change Day." For example, if the first patch is applied on a Monday, all subsequent
patches should be applied on a Monday. Only one patch should be worn at a
time. The ORTHO EVRA patch
should not be cut, damaged or altered in any way. If the ORTHO EVRA patch
is cut, damaged or altered in size, contraceptive efficacy may be impaired. On the day after Week Four ends a new four-week cycle is
started by applying a new patch. Under no circumstances should there be more
than a seven-day patch-free interval between dosing cycles. If the ORTHO EVRA patch becomes
partially or completely detached and remains detached, insufficient drug delivery
occurs. If
a patch is partially or completely detached: A patch should not be re-applied if it is no longer
sticky, if it has become stuck to itself or another surface, if it has other
material stuck to it or if it has previously become loose or fallen off. If
a patch cannot be re-applied, a new patch should be applied immediately. Supplemental
adhesives or wraps should not be used to hold the ORTHO EVRA patch
in place. If
the woman forgets to change her patch Week Four (Day 22): If the woman forgets to remove
her patch, she should take it off as soon as she remembers. The next cycle
should be started on the usual "Patch Change Day," which is the day after
Day 28. No back-up contraception is needed. Under no circumstances should there be more
than a seven-day patch-free interval between cycles. If there are
more than seven patch-free days, THE WOMAN MAY NOT BE PROTECTED FROM PREGNANCY
and back-up contraception, such as condoms, spermicide, or diaphragm, must
be used for seven days. As with combined oral contraceptives, the risk of
ovulation increases with each day beyond the recommended drug-free period.
If coital exposure has occurred during such an extended patch-free interval,
the possibility of fertilization should be considered.<br/>Change Day Adjustment: If the woman wishes to change her Patch Change Day
she should complete her current cycle, removing the third ORTHO EVRA patch
on the correct day. During the patch-free week, she may select an earlier
Patch Day Change by applying a new ORTHO EVRA patch on the
desired day. In no case should there be more than 7 consecutive patch-free
days.<br/>Switching From an Oral Contraceptive: Treatment with ORTHO EVRA should
begin on the first day of withdrawal bleeding. If there is no withdrawal bleeding
within 5 days of the last active (hormone-containing) tablet, pregnancy must
be ruled out. If therapy starts later than the first day of withdrawal bleeding,
a non-hormonal contraceptive should be used concurrently for 7 days. If more
than 7 days elapse aftertaking the last active oral contraceptive tablet,
the possibility of ovulation and conception should be considered.<br/>Use After Childbirth: Women who elect not to breast-feed should start
contraceptive therapy with ORTHO EVRA no sooner than 4 weeks
after childbirth. If a woman begins using ORTHO EVRA postpartum,
and has not yet had a period, the possibility of ovulation and conception
occurring prior to use of ORTHO EVRA should be considered,
and she should be instructed to use an additional method of contraception,
such as condoms, spermicide, or diaphragm, for the first seven days. (See Precautions: Nursing
Mothers, and Warnings: Thromboembolic and Other Vascular Problems.)<br/>Use After Abortion or Miscarriage: After an abortion or miscarriage that occurs in
the first trimester, ORTHO EVRA may be started immediately.
An additional method of contraception is not needed if ORTHO EVRA is
started immediately. If use of ORTHO EVRA is not started
within 5 days following a first trimester abortion, the woman should follow
the instructions for a woman starting ORTHO EVRA for the
first time. In the meantime she should be advised to use a non-hormonal contraceptive
method. Ovulation may occur within 10 days of an abortion or miscarriage. ORTHO EVRA should be started no earlier
than 4 weeks after a second trimester abortion or miscarriage. When ORTHO
EVRA is used postpartum or postabortion, the increased risk
of thromboembolic disease must be considered. (See CONTRAINDICATIONS and WARNINGS concerning
thromboembolic disease. See PRECAUTIONS for "Nursing Mothers".)<br/>Breakthrough Bleeding or Spotting: In the event of breakthrough bleeding or spotting
(bleeding that occurs on the days that ORTHO EVRA is worn),
treatment should be continued. If breakthrough bleeding persists longer than
a few cycles, a cause other than ORTHO EVRA should be considered. In the event of no withdrawal bleeding (bleeding that should
occur during the patch-free week), treatment should be resumed on the next
scheduled Change Day. If ORTHO EVRA has been used correctly,
the absence of withdrawal bleeding is not necessarily an indication of pregnancy.
Nevertheless, the possibility of pregnancy should be considered, especially
if absence of withdrawal bleeding occurs in 2 consecutive cycles. ORTHO EVRA should
be discontinued if pregnancy is confirmed.<br/>In Case of Vomiting or Diarrhea: Given the nature of transdermal application, dose
delivery should be unaffected by vomiting.<br/>In Case of Skin Irritation: If patch use results in uncomfortable irritation,
the patch may be removed and a new patch may be applied to a different location
until the next Change Day. Only one patch should be worn at a time.
|
| dailymed-instance:descripti... |
ORTHO EVRA is a combination transdermal
contraceptive patch with a contact surface area of 20 cm. It contains
6.00 mg norelgestromin (NGMN) and 0.75 mg ethinyl estradiol (EE). Systemic
exposures (as measured by area under the curve [AUC] and steady state concentration
[C]) of NGMN and EE during use of ORTHO EVRA are
higher and peak concentrations (C) are lower than those produced
by an oral contraceptive containing norgestimate 250��g / EE 35��g.
(See BOLDED
WARNING; CLINICAL
PHARMACOLOGY, Transdermal versus Oral Contraceptives). ORTHO EVRA is a thin, matrix-type transdermal
contraceptive patch consisting of three layers. The
backing layer is composed of a beige flexible film consisting of
a low-density pigmented polyethylene outer layer and a polyester inner layer.
It provides structural support and protects the middle adhesive layer from
the environment. The middle layer contains
polyisobutylene/polybutene adhesive, crospovidone, non-woven polyester fabric
and lauryl lactate as inactive components. The active components in this layer
are the hormones, norelgestromin and ethinyl estradiol. The
third layer is the release liner, which protects the adhesive layer
during storage and is removed just prior to application. It is a transparent
polyethylene terephthalate (PET) film with a polydimethylsiloxane coating
on the side that is in contact with the middle adhesive layer. The outside of the backing layer is heat-stamped "ORTHO EVRA". The structural formulas of the components are: norelgestromin ethinyl
estradiol Molecular
weight, norelgestromin: 327.47Molecular weight, ethinyl estradiol: 296.41Chemical name for norelgestromin: 18, 19-dinorpregn-4-en-20-yn-3-one,
13 ethyl- 17-hydroxy-, 3-oxime, (17��)Chemical name for ethinyl estradiol: 19-Norpregna-1, 3, 5 (10)-trien-20-yne-3,
17-diol, (17��)
|
| dailymed-instance:clinicalP... |
Pharmacodynamics: Norelgestromin is the active progestin largely responsible
for the progestational activity that occurs in women following application
of ORTHO EVRA. Norelgestromin is also the primary active
metabolite produced following oral administration of norgestimate (NGM), the
progestin component of the oral contraceptive products ORTHO-CYCLEN and
ORTHO TRI-CYCLEN. 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). Receptor and human sex hormone-binding globulin (SHBG) binding
studies, as well as studies in animals and humans, have shown that both NGM
and NGMN exhibit high progestational activity with minimal intrinsic androgenicity.
Transdermally-administered norelgestromin, in combination with ethinyl estradiol,
does not counteract the estrogen-induced increases in SHBG, resulting in lower
levels of free testosterone in serum compared to baseline. One clinical trial assessed the return of hypothalamic-pituitary-ovarian
axis function post-therapy and found that FSH, LH, and Estradiol mean values,
though suppressed during therapy, returned to near baseline values during
the 6 weeks post therapy.<br/>Pharmacokinetics:<br/>Absorption: Following a single application of ORTHO EVRA,
both NGMN and EE reach a plateau by approximately 48 hours. Pooled data from
the 3 clinical studies have demonstrated that steady state is reached within
2 weeks of application. The mean steady state Cconcentrations
ranged from 0.305-1.53 ng/mL for NGMN and from 11.2-137 pg/mL for EE. Absorption of NGMN and EE following application of ORTHO
EVRA to the buttock, upper outer arm, abdomen and upper torso
(excluding breast) was examined. While absorption from the abdomen was slightly
lower than from other sites, absorption from these anatomic sites was considered
to be therapeutically equivalent. The mean
(%CV) pharmacokinetic parameters Cand AUCfor
NGMN and EE following a single buttock application of ORTHO EVRA are
summarized in Table
1. In multiple dose
studies, AUCfor NGMN and EE was found to increase over time
(Table 1). In a three-cycle study, these pharmacokinetic parameters reached
steady-state conditions during Cycle 3 (Figures 1 and 2). Upon removal of the patch,
serum levels of EE and NGMN reach very low or non-measurable levels within
3 days. The absorption of NGMN and EE following application of ORTHO
EVRA was studied under conditions encountered in a health
club (sauna, whirlpool and treadmill) and in a cold water bath. The results
indicated that for NGMN there were no significant treatment effects on Cor
AUC when compared to normal wear. For EE, increased exposures were observed
due to sauna, whirlpool and treadmill. There was no significant effect of
cold water on these parameters. Results from
a study of consecutive ORTHO EVRA wear for 7 days and 10
days indicated that serum concentrations of NGMN and EE dropped slightly during
the first 6 hours after the patch replacement, and recovered within 12 hours.
By Day 10 of patch administration, both NGMN and EE concentrations had decreased
by approximately 25% when compared to Day 7 concentrations.<br/>Metabolism: Since ORTHO EVRA is applied transdermally,
first-pass metabolism (via the gastrointestinal tract and/or liver) of NGMN
and EE that would be expected with oral administration is avoided. Hepatic
metabolism of NGMN occurs and metabolites include norgestrel, which is highly
bound to SHBG, and various hydroxylated and conjugated metabolites. Ethinyl
estradiol is also metabolized to various hydroxylated products and their glucuronide
and sulfate conjugates.<br/>Distribution: NGMN and norgestrel (a serum metabolite of NGMN)
are highly bound (>97%) to serum proteins. NGMN is bound to albumin and not
to SHBG, while norgestrel is bound primarily to SHBG, which limits its biological
activity. Ethinyl estradiol is extensively bound to serum albumin and induces
an increase in the serum concentrations of SHBG (See CLINICAL PHARMACOLOGY, Transdermal versus Oral Contraceptives,
Table 3).<br/>Elimination: Following removal of patches, the elimination
kinetics of NGMN and EE were consistent for all studies with half-life values
of approximately 28 hours and 17 hours, respectively. The metabolites of NGMN
and EE are eliminated by renal and fecal pathways.<br/>Transdermal versus Oral Contraceptives: The ORTHO EVRA transdermal patch
was designed to deliver EE and NGMN over a seven-day period while oral contraceptives
(containing NGM 250��g / EE 35��g) are administered on a daily basis. Figures 3 and 4 present
mean pharmacokinetic (PK) profiles for EE and NGMN following administration
of an oral contraceptive (containing NGM 250��g / EE 35��g) compared
to the 7-day transdermal ORTHO EVRA patch (containing NGMN
6.0 mg / EE 0.75 mg) during cycle 2 in 32 healthy female volunteers. Table
2 provides the mean (%CV) for NGMN and EE pharmacokinetic
(PK) parameters. In general, overall exposure for NGMN and EE (AUC
and C) was higher in subjects treated with ORTHO EVRA for
both Cycle 1 and Cycle 2, compared to that for the oral contraceptive, while
Cvalues were higher in subjects administered the oral contraceptive.
Under steady-state conditions, AUCand Cfor
EE were approximately 55% and 60% higher, respectively, for the transdermal
patch, and the Cwas about 35% higher for the oral contraceptive,
respectively. Inter-subject variability (%CV) for the PK parameters following
delivery from ORTHO EVRA was higher relative to the variability
determined from the oral contraceptive. The mean pharmacokinetic profiles
are different between the two products and caution should be exercised when
making a direct comparison of these PK parameters. In Table 3,
percent change in concentrations (%CV) of markers of systemic estrogenic activity
(Sex Hormone Binding Globulin [SHBG] and Corticosteroid Binding Globulin [CBG])
from Cycle 1 Day 1 to Cycle 1 Day 22 is presented. Percent change in SHBG
concentrations was higher for ORTHO EVRA users compared to
women taking the oral contraceptive; percent change in CBG concentrations
were similar for ORTHO EVRA and oral contraceptive users.
Within each group, the absolute values for SHBG were similar for Cycle 1,
Day 22 and Cycle 2, Day 22.<br/>Special Populations:<br/>Effects of Age, Body Weight, Body Surface Area and Race:: The effects of age, body weight, body surface
area and race on the pharmacokinetics of NGMN and EE were evaluated in 230
healthy women from nine pharmacokinetic studies of single 7-day applications
of ORTHO EVRA. For both NGMN and EE, increasing age, body
weight and body surface area each were associated with slight decreases in
Cand AUC values. However, only a small fraction (10-25%) of
the overall variability in the pharmacokinetics of NGMN and EE following application
of ORTHO EVRA may be associated with any or all of the above
demographic parameters. There was no significant effect of race with respect
to Caucasians, Hispanics and Blacks.<br/>Renal and Hepatic Impairment: No formal studies were conducted with ORTHO EVRA to
evaluate the pharmacokinetics, safety, and efficacy in women with renal or
hepatic impairment. Steroid hormones may be poorly metabolized in patients
with impaired liver function .<br/>Drug Interactions: The metabolism of hormonal contraceptives may be
influenced by various drugs. Of potential clinical importance are drugs that
cause the induction of enzymes that are responsible for the degradation of
estrogens and progestins, and drugs that interrupt entero-hepatic recirculation
of estrogen (e.g. certain antibiotics). The
proposed mechanism of interaction of antibiotics is different from that of
liver enzyme-inducing drugs. Literature suggests possible interactions with
the concomitant use of hormonal contraceptives and ampicillin or tetracycline.
In a pharmacokinetic drug interaction study, oral administration of tetracyclineHCl, 500 mg q.i.d. for 3 days prior to and 7 days during wear ofORTHO EVRA did
not significantly affect the pharmacokinetics of NGMN or EE. The major target for enzyme inducers is the hepatic microsomal
estrogen-2-hydroxylase (cytochrome P450 3A4). See also PRECAUTIONS,
Drug Interactions.<br/>Patch Adhesion: In the clinical trials with ORTHO EVRA,
approximately 2% of the cumulative number of patches completely detached.
The proportion of subjects with at least 1 patch that completely detached
ranged from 2% to 6%, with a reduction from Cycle 1 (6%) to Cycle 13 (2%).
For instructions on how to manage detachment of patches, refer to the DOSAGE AND ADMINISTRATION section.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:supply |
Each beige ORTHO EVRA patch contains
6.00 mg norelgestromin and 0.75 mg EE. Each patch
surface is heat stamped with ORTHO EVRA. Each patch is packaged
in a protective pouch. ORTHO EVRA is
available in folding cartons of 1 cycle each (NDC # 0062-1920-15); each cycle
contains 3 patches. ORTHO EVRA is
available for clinic usage in folding cartons of 1 cycle each (NDC# 0062���1920���24);
each cycle contains 3 patches. ORTHO EVRA is
also available in folding cartons containing a single patch (NDC # 0062-1920-01),
intended for use as a replacement in the event that a patch is inadvertently
lost or destroyed.<br/>Special Precautions for Storage and Disposal: Store at 25��C (77��F); excursions permitted
to 15-30��C (59-86��F). Store patches
in their protective pouches. Apply immediately upon removal from the protective
pouch. Do not store in the refrigerator or
freezer. Used patches still contain some active
hormones. The sticky sides of the patch should be folded together and the
folded patch placed in a sturdy container, preferably with a child-resistant
cap, and the container thrown in the trash. Used patches should not be flushed
down the toilet.
|
| dailymed-instance:boxedWarn... |
Cigarette smoking increases
the risk of serious cardiovascular side effects from hormonal 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
hormonal contraceptives, including ORTHO EVRA, should be
strongly advised not to smoke.
|
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... | |
| dailymed-instance:overdosag... |
Serious ill effects have not been reported following
accidental ingestion of large doses of hormonal contraceptives. Overdosage
may cause nausea and vomiting, and withdrawal bleeding may occur in females.
Given the nature and design of the ORTHO EVRA patch, it is
unlikely that overdosage will occur. Serious ill effects have not been reported
following acute ingestion of large doses of oral contraceptives by young children.
In case of suspected overdose, all ORTHO EVRA patches should
be removed and symptomatic treatment given.
|
| dailymed-instance:genericMe... |
norelgestromin and ethinyl estradiol
|
| dailymed-instance:fullName |
Ortho Evra (Patch, Extended Release)
|
| dailymed-instance:adverseRe... |
The most common adverse events reported by 9 to 22%
of women using ORTHO EVRA in clinical trials (N= 3,330) were
the following, in order of decreasing incidence: breast symptoms, headache,
application site reaction, nausea, upper respiratory infection, menstrual
cramps, and abdominal pain. The most frequent adverse
events leading to discontinuation in 1 to 2.4% of women using ORTHO EVRA in
the trials included the following: nausea and/or vomiting, application site
reaction, breast symptoms, headache, and emotional lability. Listed
below are adverse events that have been associated with the use of combination
hormonal contraceptives. These are also likely to apply to combination transdermal
hormonal contraceptives such as ORTHO EVRA. An
increased risk of the following serious adverse reactions has been associated
with the use of combination hormonal contraceptives (see WARNINGS Section). There is evidence of an association between the following
conditions and the use of combination hormonal contraceptives: The following adverse reactions have been reported in users
of combination hormonal contraceptives and are believed to be drug related: The following adverse reactions have been reported in users
of combination hormonal contraceptives and a cause and effect association
has been neither confirmed nor refuted:
|
| dailymed-instance:indicatio... |
ORTHO EVRA is indicated for the prevention
of pregnancy in women who elect to use a transdermal patch as a method of
contraception. The pharmacokinetic profile for
the ORTHO EVRA transdermal patch is different from that of
an oral contraceptive. Healthcare professionals should balance the higher
estrogen exposure and the possible increase risk of venous thromboembolism
with ORTHO EVRA against the chance of pregnancy if a contraceptive
pill is not taken daily. (See BOLDED
WARNING; WARNINGS;
CLINICAL PHARMACOLOGY, Transdermal versus Oral Contraceptives). Like oral contraceptives, ORTHO EVRA is highly
effective if used as recommended in this label. In
3 large clinical trials in North America, Europe and South Africa, 3,330 women
(ages 18-45) completed 22,155 cycles of ORTHO EVRA use, pregnancy
rates were approximately 1 per 100 women-years of ORTHO EVRA use.
The racial distribution was 91% Caucasian, 4.9% Black, 1.6% Asian, and 2.4%
Other. With respect to weight, 5 of the 15 pregnancies
reported with ORTHO EVRA use were among women with a baseline
body weight���198 lbs. (90kg), which constituted<3% of the study
population. The greater proportion of pregnancies among women at or above
198 lbs. was statistically significant and suggests that ORTHO EVRA may
be less effective in these women. Health Care
Professionals who consider ORTHO EVRA for women at or above
198 lbs. should discuss the patient's individual needs in choosing the
most appropriate contraceptive option. Table 4 lists the accidental pregnancy rates for users of various methods
of contraception. The efficacy of these contraceptive methods, except sterilization,IUD, and Norplant depends upon the reliability with which they are used. Correct
and consistent use of methods can result in lower failure rates.<br/>Emergency Contraceptive Pills: Treatment initiated within 72 hours after unprotected
intercourse reduces the risk of pregnancy by at least 75%.<br/>Lactational Amenorrhea Method: LAM is highly effective, temporary
method of contraception. Source: Trussell J, Contraceptive efficacy. In Hatcher RA,
Trussell J, Stewart F, Cates W, Stewart GK, Kowal D, Guest F, Contraceptive
Technology: Seventeenth Revised Edition. New York NY: Irvington Publishers,
1998. ORTHO
EVRA has not been studied for and is not indicated for use
in emergency contraception.
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Ortho Evra
|