Approved Drug Label (PDF)
4
Contraindications
(Additions and/or
revisions underlined)
LUPRON
DEPOT 11.25 mg is contraindicated in women with the following:
Hypersensitivity
to gonadotropin-releasing hormone (GnRH), GnRH agonist analogs, including leuprolide
acetate, or any of the excipients in LUPRON DEPOT 11.25 mg
Undiagnosed
abnormal uterine bleeding
Pregnancy
When
norethindrone acetate is administered with LUPRON DEPOT 11.25 mg, the contraindications
to the use of norethindrone acetate also apply to this
combination regimen. Refer to the norethindrone acetate prescribing information
for a list of contraindications for norethindrone acetate.
5
Warnings and Precautions
5.1 Loss of Bone Mineral Density
(Additions and/or
revisions underlined)
LUPRON
DEPOT 11.25 mg induces a hypoestrogenic state that results in loss of bone
mineral density (BMD), some of which may not be reversible after stopping
treatment. In women with major risk factors for decreased BMD such as chronic
alcohol use (> 3 units per day), tobacco use, strong family history of
osteoporosis, or chronic use of drugs that can decrease BMD, such as anticonvulsants
or corticosteroids, use of LUPRON DEPOT 11.25 mg may pose an additional risk.
Carefully weigh the risks and benefits of LUPRON DEPOT 11.25 mg use in these
populations.
The
duration of
LUPRON DEPOT 11.25 mg treatment is limited by the risk of loss of bone mineral
density.
When
using LUPRON DEPOT 11.25 mg for the management of endometriosis, combination
use of norethindrone acetate (add-back therapy) is effective in reducing the loss
of BMD that occurs
with leuprolide acetate. Do not retreat
with LUPRON DEPOT 11.25 mg without combination norethindrone acetate. Assess
BMD before retreatment.
5.2 Embryo-Fetal Toxicity
(Subsection title revised; Additions and/or
revisions underlined)
Based
on animal reproduction studies and the drug’s mechanism of action, LUPRON DEPOT
11.25
mg
may cause fetal harm if administered to a pregnant woman and is contraindicated
in pregnant women. Exclude pregnancy prior to initiating treatment with
LUPRON DEPOT 11.25 mg if clinically indicated. Discontinue LUPRON DEPOT 11.25
mg if the woman becomes pregnant during treatment and inform the woman of
potential risk to the fetus. Advise women to notify their healthcare provider if
they believe they may be pregnant.
When
used at the recommended dose and dosing interval, LUPRON DEPOT 11.25 mg usually
inhibits ovulation and stops menstruation. Contraception, however, is not ensured
by taking LUPRON DEPOT 11.25 mg. If contraception is indicated, advise women
to use non-hormonal methods of contraception while on treatment with LUPRON
DEPOT 11.25 mg.
5.3 Hypersensitivity Reactions
(Subsection title revised; Additions and/or
revisions underlined)
Hypersensitivity
reactions, including anaphylaxis, have been reported with LUPRON DEPOT use. LUPRON
DEPOT 11.25 mg is contraindicated in women with a history of hypersensitivity to
gonadotropin-releasing hormone (GnRH) or GnRH agonist analogs.
In
clinical trials of LUPRON DEPOT 11.25 mg, adverse events of asthma were reported
in women with pre-existing histories of asthma, sinusitis, and environmental or
drug allergies. Symptoms consistent with an anaphylactoid or asthmatic
process have been reported postmarketing.
5.5 Convulsions
(Additions and/or
revisions underlined)
There
have been postmarketing reports of convulsions in women on GnRH
agonists, including leuprolide acetate. These included women with
and without concurrent medications and comorbid conditions.
5.6 Clinical Depression
(Additions and/or
revisions underlined)
Depression
may occur or worsen during treatment with GnRH agonists including LUPRON DEPOT
11.25 mg. Carefully observe women for depression, especially those with
a history of depression and consider whether the risks of continuing LUPRON
DEPOT 11.25 mg outweigh the benefits. Women with new or worsening depression should
be referred to a mental health professional, as appropriate.
5.7 Risks Associated with Norethindrone Combination Treatment
(Newly added
subsection)
If
LUPRON DEPOT 11.25 mg is administered with norethindrone acetate, the warnings and
precautions for
norethindrone acetate apply to this regimen. Refer to the norethindrone
acetate prescribing information for a full list of the warnings and precautions
for norethindrone acetate.
6
Adverse Reactions
(Newly added
information))
The
following clinically significant adverse reactions are described elsewhere in
the labeling:
- Loss of Bone
Mineral Density
- Hypersensitivity
Reactions
- Initial Flare
of Symptoms with Management of Endometriosis
- Convulsions
- Clinical Depression
6.1 Clinical Trials Experience
(Extensive revisions;
please refer to label)
6.2 Postmarketing Experience
(Additions and/or
revisions underlined)
The
following adverse reactions have been identified during post-approval use of LUPRON
DEPOT monotherapy or LUPRON DEPOT with norethindrone acetate add-back therapy.
Because
these reactions are reported voluntarily from a population of uncertain size,
it is not always possible to reliably estimate their frequency or establish a
causal relationship to drug exposure.
During
postmarketing surveillance which includes other dosage forms and other
populations, the following adverse reactions were reported:
Body as a whole: Hypersensitivity reactions including
anaphylaxis, localized reactions including induration and abscess at the
site of injection
Nervous/Psychiatric
System -
Mood
swings, including depression; suicidal ideation and attempt; convulsion, peripheral
neuropathy, paralysis
Hepato-biliary
system -
Serious liver injury
Injury, poisoning
and procedural complications - Spinal fracture
Investigations - Decreased white blood
count
Musculoskeletal
and connective tissue system - Tenosynovitis-like symptoms
Vascular system - Hypotension, hypertension,
deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, transient
ischemic attack
Respiratory
system: Symptoms
consistent with an asthmatic process
- Multi-system
disorders- Symptoms
consistent with fibromyalgia (e.g., joint and muscle pain, headaches, sleep
disorders, gastrointestinal distress, and shortness of breath), individually and
collectively.
Pituitary
apoplexy
During
postmarketing surveillance, cases of pituitary apoplexy (a clinical syndrome secondary
to infarction of the pituitary gland) have been reported after the administration
of leuprolide acetate and other GnRH agonists. In a majority of these cases, a pituitary
adenoma was diagnosed, with a majority of pituitary apoplexy cases occurring
within 2 weeks of the first dose, and some within the first hour. In these cases,
pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia,
altered mental status, and sometimes cardiovascular collapse. Immediate medical
attention has been required.
7
Drug Interactions
(Additions and/or
revisions underlined)
No drug-drug interaction
studies have been conducted with LUPRON DEPOT 11.25 mg.
8
Use in Specific Populations
8.1 Pregnancy
(PLLR conversion)
Risk
Summary
LUPRON
DEPOT 11.25 mg is contraindicated in pregnancy.
LUPRON
DEPOT 11.25 mg may cause fetal harm based on findings from animal studies and
the drug’s mechanism of action. There
are limited human data on the use of LUPRON DEPOT in pregnant women. Based on animal
reproduction studies, LUPRON DEPOT 11.25 mg may be associated with an increased
risk of pregnancy complications, including early pregnancy loss and fetal harm.
In animal reproduction studies, subcutaneous administration of leuprolide
acetate to rabbits during the period of organogenesis caused embryo-fetal toxicity,
decreased fetal weights and a dose-dependent increase in major fetal abnormalities
in animals at doses less than the recommended human dose based on body surface
area using an estimated daily dose. A similar rat study also showed increased fetal
mortality and decreased fetal weights but no major fetal abnormalities at doses
less than the recommended human dose based on body surface area using an estimated
daily dose.
Data
Animal Data
When
administered on day 6 of pregnancy at test dosages of 0.00024 mg/kg, 0.0024 mg/kg,
and
0.024
mg/kg (1/300 to 1/3 of the human dose) to rabbits, leuprolide acetate produced
a dose- related increase in major fetal abnormalities. Similar studies in rats failed
to demonstrate an increase in fetal malformations. There was increased fetal
mortality and decreased fetal weights with the two higher doses of LUPRON DEPOT
in rabbits and with the highest dose (0.024 mg/kg) in rats.
8.2 Lactation
(PLLR conversion)
Risk
Summary
There are no data on
the presence of leuprolide acetate in either animal or human milk, the effects
on the breastfed infants, or the effects on milk production.
The
developmental and health benefits of breastfeeding should be considered along with
the mother’s clinical need for LUPRON DEPOT 11.25 mg and any potential adverse
effects on the breastfed infant from LUPRON DEPOT 11.25 mg or from the
underlying maternal condition.
8.3 Females and Males of Reproductive Potential
(PLLR conversion)
Pregnancy
Testing
Exclude
pregnancy in women of reproductive potential prior to initiating LUPRON DEPOT
11.25
mg if clinically indicated.
Contraception
Females
LUPRON
DEPOT 11.25 mg may cause embryo-fetal harm when administered during pregnancy. LUPRON
DEPOT 11.25 mg is not a contraceptive. If contraception is indicated, advise
females of reproductive potential to use a non-hormonal method of contraception
during treatment with LUPRON DEPOT 11.25 mg.
Infertility
Based
on its pharmacodynamic effects of decreasing secretion of gonadal steroids, fertility
is expected to be decreased while on treatment with LUPRON DEPOT 11.25 mg. Clinical
and pharmacologic studies in adults (>18 years) with leuprolide acetate and similar
analogs have shown reversibility of fertility suppression when the drug is discontinued
after continuous administration
for periods of up to 24 weeks.
There
is no evidence that pregnancy rates are affected following discontinuation of LUPRON
DEPOT 11.25 mg.
Animal
studies (prepubertal and adult rats and monkeys) with leuprolide acetate and
other GnRH analogs have shown functional recovery of fertility suppression.
8.4 Pediatric Use
(Additions and/or
revisions underlined)
Safety
and effectiveness of LUPRON DEPOT 11.25 mg for management of
endometriosis and the preoperative hematologic improvement of women with anemia
caused by fibroids have been established in females of reproductive age.
Efficacy is expected to be the same for postpubertal adolescents under the age of
18 as for users 18 years and older. The safety and effectiveness of LUPRON
DEPOT 11.25 mg for these indications have not been established in premenarcheal
pediatric patients.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
(Additions and/or
revisions underlined)
Loss
of Bone Density
Advise
patients about the risk of loss of bone mineral density and that treatment is limited. Advise patients about other
factors that can increase and decrease their risk of bone mineral density loss.
Embryo-Fetal
Toxicity
Advise
females of reproductive potential of the possible risk to a fetus. Advise
patients to inform healthcare provider of a known or suspected
pregnancy.
If contraception is indicated, advise females of reproductive
potential
to use non-hormonal contraception during treatment with LUPRON DEPOT 11.25
mg
Hypersensitivity
Reactions
Inform
patients that hypersensitivity reactions, including anaphylaxis, have been reported
with LUPRON DEPOT. Advise patients to seek appropriate medical care if symptoms
of hypersensitivity reactions occur.
Initial
Flare of Symptoms
Advise
patients that they may experience an increase in symptoms during the initial
days of therapy. Advise patients that these symptoms should dissipate with continued
therapy.
Convulsions
Inform
patients that convulsions have been reported in patients who have received LUPRON
DEPOT. Advise patients to seek medical attention in the event of a convulsion.
Clinical
Depression
Inform
patients that depression may occur or worsen during treatment with GnRH
agonists, including LUPRON DEPOT 11.25 mg, especially in patients with a history
of depression. Advise patients to immediately report thoughts and behaviors of concern
to healthcare providers.
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