Document
DailyMed Label: Testopel
Title
DailyMed Label: Testopel
Date
2024
Document type
DailyMed Prescription
Name
Testopel
Generic name
testosterone
Manufacturer
ENDO USA, Inc.
Product information
NDC: 66887-004
Product information
NDC: 66887-004
Description
TESTOPEL ®
(testosterone pellets) are cylindrically shaped pellets 3.2mm (1/8 inch) in
diameter and approximately 9mm in length. Each sterile pellet weighs
approximately 78mg (75mg testosterone) and is ready for implantation.
Androgens are steroids that develop and maintain primary and
secondary male sex characteristics. Testosterone is a member of this
class.
Structural formula for testosterone follows:
INGREDIENTS
Each TESTOPEL ®
(testosterone pellets) for subcutaneous implantation contains 75mg
testosterone. In addition each pellet contains the following inactive
ingredients: stearic acid NF 0.97mg and polyvinylpyrrolidone USP 2mg.
TESTOPEL ®
(testosterone pellets) consist of crystalline testosterone. When implanted
subcutaneously, the pellets slowly release the hormone for a long acting
androgenic effect.
stucture
Indications
MALES
Androgens are indicated for replacement therapy in conditions
associated with a deficiency or absence of endogenous testosterone.
a. Primary hypogonadism (congenital or acquired)
- testicular failure due to cryptorchidism, bilateral torsion,
orchitis, vanishing testes syndrome; or orchiectomy.
b. Hypogonadotropic hypogonadism (congenital or
acquired) - gonadotropic LHRH deficiency, or pituitary
- hypothalamic injury from tumors, trauma or radiation.
If the above conditions occur prior to puberty, androgen
replacement therapy will be needed during the adolescent years for
development of secondary sex characteristics. Prolonged androgen
treatment will be required to maintain sexual characteristics in these
and other males who develop testosterone deficiency after puberty.
Safety and efficacy of TESTOPEL ® (testosterone pellets) in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.
c. Androgens may be used to stimulate puberty in
carefully selected males with clearly delayed puberty. These
patients usually have a familial pattern of delayed puberty that is
not secondary to a pathological disorder; puberty is expected to
occur spontaneously at a relatively late date. Brief treatment with
conservative doses may occasionally be justified in these patients
if they do not respond to psychological support. The potential
adverse effect on bone maturation should be discussed with the
patient and parents prior to androgen administration. An x-ray of
the hand and wrist to determine bone age should be taken every 6
months to assess the effect of treatment on epiphyseal centers (see
WARNINGS ).
Dosage
Prior to initiating, TESTOPEL ® (testosterone pellets) confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range.
The suggested dosage for androgens varies depending on the age,
and diagnosis of the individual patient. Dosage is adjusted according to
the patient’s response and the appearance of adverse reactions. The
dosage guideline for the testosterone pellets for replacement therapy in
androgen-deficient males is 150mg to 450mg subcutaneously every 3 to 6
months. Various dosage regimens have been used to induce pubertal
changes in hypogonadal males; some experts have advocated lower doses
initially, gradually increasing the dose as puberty progresses, with or
without a decrease in maintenance levels. Other experts emphasize that
higher dosages are needed to induce pubertal changes and lower dosages
can be used for maintenance after puberty. The chronological and
skeletal ages must be taken into consideration, both in determining the
initial dose and in adjusting the dose.
Dosages in delayed puberty generally are in the lower range of
that listed above and, for a limited duration, for example 4 to 6
months.
The number of pellets to be implanted depends upon the minimal
daily requirements of testosterone propionate determined by a gradual
reduction of the amount administered parenterally. The usual dosage is
as follows: implant two 75mg pellets for each 25mg testosterone
propionate required weekly. Thus when a patient requires injections of
75mg per week, it is usually necessary to implant 450mg (6 pellets).
With injections of 50mg per week, implantation of 300mg (4 pellets) may
suffice for approximately three months. With lower requirements by
injection, correspondingly lower amounts may be implanted. It has been
found that approximately one-third of the material is absorbed in the
first month, one-fourth in the second month and one-sixth in the third
month. Adequate effect of the pellets ordinarily continues for three to
four months, sometimes as long as six months.
Contraindications
Androgens are contraindicated in men with carcinomas of the
breast or with known or suspected carcinomas of the prostate. If
administered to pregnant women, androgens cause virilization of the
external genitalia of the female fetus. The virilization includes
clitoromegaly, abnormal vaginal development, and fusion of genital folds
to form a scrotal-like structure. The degree of masculinization is
related to the amount of drug given and the age of the fetus, and is
most likely to occur in the female fetus when the drugs are given in the
first trimester. If the patient becomes pregnant while taking these
drugs she should be apprised of the potential hazard to the
fetus.
Precautions
GENERAL
Pellet implantation is much less flexible for dosage adjustment
than is oral administration of or intramuscular injections of oil
solutions or aqueous suspensions. Therefore, great care should be used
when estimating the amount of testosterone needed.
In the face
of complications where the effects of testosterone should be
discontinued, the pellets would have to be removed.
INFORMATION FOR THE PATIENT
The physician should instruct patients to report any of the
following side effects of androgens:
Adult or adolescent males: Too frequent or persistent erections
of the penis. Any nausea, vomiting, changes in skin color, ankle
swelling.
Implantation site infection and/or pellet extrusion can occur and may be associated with implant site induration, inflammation, fibrosis, bleeding, bruising, wound drainage, pain, itching, and pellet extrusion. (see WARNINGS and ADVERSE REACTIONS).
Any male adolescent patient receiving androgens for delayed
puberty should have bone development checked every 6 months.
LABORATORY TESTS
Because of the hepatotoxicity associated with
the use of 17-alpha-alkylated androgens, liver function tests should
be obtained periodically.
Periodic (every 6 months) x-ray examinations
of the bone age should be made during treatment of prepubertal males
to determine the rate of bone maturation and the effects of androgen
therapy on the epiphyseal centers.
Hemoglobin and hematocrit should be checked
periodically for polycythemia in patients who are receiving high
doses of androgens.
DRUG INTERACTIONS
Anticoagulants. C-17 substituted derivatives
of testosterone, such as methandrostenolone have been reported to
decrease the anticoagulant requirements of patients receiving oral
anticoagulants. Patients receiving oral anticoagulant therapy
require close monitoring, especially when androgens are started or
stopped.
Oxyphenbutazone. Concurrent administration of
oxyphenbutazone and androgens may result in elevated serum levels of
oxyphenbutazone.
Insulin. In diabetic patients the metabolic
effects of androgens may decrease blood glucose and insulin
requirements.
DRUG/LABORATORY TEST
INTERFERENCES
Androgens may decrease levels of thyroxine-binding globulin,
resulting in decreased total T 4 serum levels and increased
resin uptake of T 3 and T 4 . Free thyroid hormone
levels remain unchanged, however, and there is no clinical evidence of
thyroid dysfunction.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF
FERTILITY
Animal Data. Testosterone has been tested by subcutaneous
injection and implantation in mice and rats. The implant induced
cervical-uterine tumors in mice, which metastasized in some cases. There
is suggestive evidence that injection of testosterone into some strains
of female mice increases their susceptibility to hepatoma. Testosterone
is also known to increase the number of tumors and decrease the degree
of differentiation of chemically induced carcinomas of liver in rats.
Human Data. There are rare reports of hepatocellular carcinoma in
patients receiving long-term therapy with androgens in high doses.
Withdrawal of the drugs did not lead to regression of the tumors in all
cases.
Geriatric patients treated with androgens may be at an increased
risk for the development of prostatic hypertrophy and prostatic
carcinoma.
PREGNANCY
Teratogenic Effects. Pregnancy Category X (see CONTRAINDICATIONS).
NURSING MOTHERS
It is not known whether androgens are excreted in human milk.
Because many drugs are excreted in human milk and because of the
potential for serious adverse reactions in nursing infants from
androgens, a decision should be made whether to discontinue nursing or
to discontinue the drug, taking into account the importance of the drug
to the mother.
PEDIATRIC USE
Androgen therapy should be used very cautiously in children and
only by specialists who are aware of the adverse effects on bone
maturation. Skeletal maturation must be monitored every 6 months by an
x-ray of the hand and wrist (see INDICATIONS
AND USAGE and WARNINGS ).
Adverse reactions
The following adverse reactions have been identified during post-approval use of testosterone replacement therapy, including TESTOPEL
How supplied
Testosterone pellets each containing 75mg testosterone. One pellet per vial in boxes of 10
(NDC: 66887-004-10) and 100 (NDC: 66887-004-20). Store at 25°C (77°F), excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature].
Rx Only
Manufactured for:
Endo USA
Malvern, PA 19355
© 2024 Endo, Inc. or one of its affiliates.
Revised 03/2024
Clinical pharmacology
Endogenous androgens are responsible for the normal growth and
development of the male sex organs and for maintenance of secondary sex
characteristics. These effects include the growth and maturation of
prostate, seminal vesicles, penis and scrotum; the development of male
hair distribution such as beard, pubic, chest and axillary hair,
laryngeal enlargements, vocal cord thickening, alterations in body
musculature and fat distribution. Drugs in this class can also cause
retention of nitrogen, sodium, potassium, phosphorus, and decreased
urinary excretion of calcium.
Androgens have been reported to increase protein anabolism and
decrease protein catabolism.
Nitrogen balance is improved only when there is sufficient intake
of calories and protein.
Androgens are responsible for the growth spurt of adolescence and
for the eventual termination of linear growth which is brought about by
the fusion of the epiphyseal growth centers. In children, exogenous
androgens accelerate linear growth rates, but may cause a
disproportionate advancement in bone maturation. Use over long periods
may result in fusion of the epiphyseal growth centers and termination of
growth process. Androgens have been reported to stimulate the production
of red blood cells by enhancing the production of erythropoietic
stimulating factor.
During exogenous administration of androgens, endogenous
testosterone release is inhibited through feedback inhibition of
pituitary luteinizing hormone (LH). At large doses of exogenous
androgens, spermatogenesis may also be suppressed through feedback
inhibition of pituitary follicle stimulating hormone (FSH).
There is a lack of substantial evidence that androgens are
effective in fractures, surgery, convalescence, and functional uterine
bleeding.
PHARMACOKINETICS
Testosterone in plasma is 98 percent bound to a specific
testosterone-estradiol binding globulin, and about 2 percent is free.
Generally, the amount of this sex-hormone binding globulin in the plasma
will determine the distribution of testosterone between the free and
bound forms, and the free testosterone concentration will determine its
half-life.
About 90 percent of a dose of testosterone is excreted as
glucuronic and sulfuric acid conjugates of testosterone and its
metabolites; about 6 percent of a dose is excreted in feces, mostly in
the unconjugated form. Inactivation of testosterone occurs primarily in
the liver. Testosterone is metabolized to various 17-keto steroids
through two different pathways. There are considerable variations of the
half-life as reported in the literature, ranging from 10-100 minutes.
In many tissues the activity of testosterone appears to depend on
reduction to dihydrotestosterone, which binds to cytosol receptor
proteins. The steroid-receptor complex is transported to the nucleus
where it initiates transcription events and cellular changes related to
androgen action.
Package label
Principal Display Panel – Vial Label
Vial label
1 organization
1 product
Product
Testosterone Gel, 1%Organization
ENDO USA, Inc.