BTG PHARMACEUTICALS
OXANDRIN®
(oxandrolone tablets, USP)
Revised; Aug. 30, 1996
G
DESCRIPTION
Oxandrin® oral tablets contain 2,5 mg of the anabolic steroid
oxandrolone. Oxandrolone is 17p-hydroxy-17a-methyl-2-oxa-5a-
androstan-3-one with the following structural formula:
OH
Inactive ingredients include cornstarch, lactose, magnesium
stearate, and hydroxypropyl methylcellulose.
CLINICAL PHARMACOLOGY
Anabolic steroids are synthetic derivatives of testosterone. Cer
tain clinical effects and adverse reactions demonstrate the
androgenic properties of this class of drugs. Complete disso
ciation of anabolic and androgenic effects has not been
achieved. The actions of anabolic steroids are therefore simi
lar to those of male sex hormones with the possibility of caus
ing serious disturbances of growth and sexual development if
given to young children. Anabolic steroids suppress the
gonadotropic functions of the pituitary and may exert a direct
effect upon the testes.
During exogenous administration of anabolic androgens,
endogenous testosterone release is inhibited through inhibition
of pituitary luteinizing hormone (LH). At large doses, sper
matogenesis may be suppressed through feedback inhibition
of pituitary follicle-stimulating hormone (FSH).
Anabolic steroids have been reported to increase low-den
sity lipoproteins and decrease high-density lipoproteins. These
levels revert to normal on discontinuation of treatment.
INDICATIONS AND USAGE
Cxandrin is indicated as adjunctive therapy to promote weight
gain after weight loss following extensive surgery, chronic infec
tions, or severe trauma, and in some patients who without def
inite pathophysiologic reasons fail to gain or to maintain normal
weight, to offset the protein catabolism associated with pro
longed administration of corticosteroids, and for the relief of
the bone pain frequently accompanying osteoporosis (See
DOSAGE AND ADMINISTRATION).
DRUG ABUSE AND DEPENDENCE
Oxandrolone is classified as a controlled substance under the
Anabolic Steroids Control Act of 1990 and has been assigned
to Schedule III (non-narcotic).
CONTRAINDICATIONS
1. Known or suspected carcinoma of the prostate or the
male breast.
2. Carcinoma of the breast in females-with hypercalcemia
(androgenic anabolic steroids may stimulate osteolytic
bone resorption).
3. Pregnancy, because of possible masculinization of the
fetus. Oxandrin has been shown to cause embryotoxic-
ity, fetotoxici^, infertility, and masculinization of female
animal offspring when given in doses 9 times the human
dose.
4. Nephrosis, the nephrotic phase of nephritis.
5. Hypercalcemia.
WARNINGS
PELIOSIS HEPATIS, A CONDITION IN WHICH LIVER AND
■SOMETIMES SPLENIC TISSUE IS REPLACED WITH
BLOOD-FILLED CYSTS, HAS BEEN REPORTED IN
PATIENTS RECEIVING ANDROGENIC ANABOLIC
STEROID THERAPY. THESE CYSTS ARE SOMETIMES
PRESENT WITH MINIMAL HEPATIC DYSFUNCTION, BUT
AT OTHER TIMES THEY HAVE BEEN ASSOCIATED
WITH LIVER FAILURE. THEY ARE OFTEN NOT RECOG
NIZED UNTIL LIFE-THREATENING LIVER FAILURE OR
INTRA-ABDOMINAL HEMORRHAGE DEVELOPS. WITH
DRAWAL OF DRUG USUALLY RESULTS IN COMPLETE
DISAPPEARANCE OF LESIONS.
LIVER CELL TUMORS ARE ALSO REPORTED. MOST
OFTEN THESE TUMORS ARE BENIGN AND ANDRO
GEN-DEPENDENT, BUT FATAL MALIGNANT TUMORS
HAVE BEEN REPORTED. WITHDRAWAL OF DRUG
OFTEN RESULTS IN REGRESSION OR CESSATION OF
PROGRESSION OF THE TUMOR. HOWEVER, HEPATIC
TUMORS ASSOCIATED WITH ANDROGENS OR ANA
BOLIC STEROIDS ARE MUCH MORE VASCULAR THAN
OTHER HEPATIC TUMORS AND MAY BE SILENT UNTIL
LIFE-THREATENING INTRA-ABDOMINAL HEMOR
RHAGE DEVELOPS. BLOOD LIPID CHANGES THAT ARE
KNOWN TO BE ASSOCIATED WITH INCREASED RISK
OF ATHEROSCLEROSIS ARE SEEN IN PATIENTS
TREATED WITH ANDROGENS OR ANABOLIC
STEROIDS. THESE CHANGES INCLUDE DECREASED
HIGH-DENSITY LIPOPROTEINS AND SOMETIMES
INCREASED LOW-DENSITY LIPOPROTEINS. THE
CHANGES MAY BE VERY MARKED AND COULD HAVE
A SERIOUS IMPACT ON THE RISK OF ATHEROSCLE
ROSIS AND CORONARY ARTERY DISEASE.
Cholestatic hepatitis and jaundice may occur with 17-alpha-
alkylated androgens at a relatively low dose. If cholestatic hepati
tis with jaundice appears or if liver function tests become
abnormal, oxandrolone should be discontinued and the etiol
ogy should.be determined. Drug-induced jaundice is reversible
when the medication is discontinued.
In patients with breast cancer, anabolic steroid therapy may
cause hypercalcemia by stimulating osteolysis. Oxandrolone
therapy should be discontinued if hypercalcemia occurs.
Edema with or without congestive heart failure may be a
serious complication in patients with pre-existing cardiac, renal,
or hepatic disease. Concomitant administration of adrenal cor
tical steroid or ACTH may increase the edema.
In children, androgen therapy may accelerate bone matura
tion without producing compensatory gain in linear growth. This
adverse effect results in compromised adult height. The younger
the child, the greater the risk of compromising final mature
height. The effect on bone maturation should be monitored by
assessing bone age of the left wrist and hand every 6 months
(See PRECAUTIONS: Laboratory tests).
Geriatric patients treated with androgenic anabolic steroids
may be at an increased risk for the development of prostatic
hypertrophy and prostatic carcinoma.
ANABOLIC STEROIDS HAVE NOT BEEN SHOWN TO
ENHANCE ATHLETIC ABILITY.
PRECAUTIONS
General:
Women should be observed for signs of virilization (deepen
ing of the voice, hirsutism, acne, clitoromegaly). Discontinua
tion of drug therapy at the time of evidence of mild virilism is
necessary to prevent irreversible virilization. Some virilizing
changes in women are irreversible even after prompt discon
tinuance of therapy and are not prevented by concomitant use
of estrogens. Menstrual irregularities may also occur.
Anabolic steroids may cause suppression of clotting factors
II, V, VII, and X, and an increase in prothrombin time.
Information for patients:
The physician should instruct patients to report any of the fol
lowing side effects of androgens:
Males: Too frequent or persistent erections .of the penis,
appearance or aggravation of acne.
Females: Hoarseness, acne, changes in menstrual periods,
or more facial hair.
All patients: Nausea, vomiting, changes in skin color, or ankle
swelling.
Laboratory tests:
Women with disseminated breast carcinoma should have fre.-
quent determination of urine and serum calcium levels during
the course of therapy (See WARNINGS).
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 bone age
should be made during treatment of children to determine the
rate of bone maturation and the effects of androgen therapy
on the epiphyseal centers.
Serum lipids and high-density lipoprotein cholesterol deter
minations should be done periodically as androgenic anabolic
steroids have been reported to increase low-density lipopro
teins. Serum cholesterol levels may increase during therapy.
Therefore, caution is required when administering these agents
to patients with a history of myocardial infarction or coronary
artery disease. Serial determinations of serum cholesterol should
be made and therapy adjusted accordingly.
Hemoglobin and hematocrit should be checked periodically
for polycythemia in patients who are receiving high doses of
anabolic steroids.
Drug interactions
Anticoagulants:
Anabolic steroids may increase sensitivity to oral anticoagu
lants. Dosage of the anticoagulant may have to be decreased
in order to maintain desired prothrombin time. Patients receiv
ing oral anticoagulant therapy require close monitoring, espe
cially when anabolic steroids are started or stopped.
Oral hypoglycemic agents:
Oxandrolone may inhibit the metabolism of oral hypoglycemic
agents.
Adrenal steroids or ACTH:
In patients with edema, concomitant administration with adrenal
cortical steroids or ACTH may increase the edema.
Drug/Laboratory test interactions:
Anabolic steroids may decrease levels of thyroxine-binding glob
ulin, resulting in decreased total T4 serum levels and increased
resin uptake of T3 and T4. Free thyroid hormone levels remain
unchanged. In addition, a decrease in PBI and radioactive iodine
uptake may occur.
Carcinogenesis, mutagenesis, impairment of fertility
Animal data:
Oxandrolone has not been tested in laboratory animals for car
cinogenic or mutagenic effects. In 2-year chronic oral rat stud
ies, a dose-related reduction of spermatogenesis and decreased
organ weights (testes, prostate, seminal vesicles, ovaries, uterus,
adrenals, and pituitary) were shown.
Human data:
Liver cell tumors have been reported in patients receiving long
term therapy with androgenic anabolic steroids in high doses
(See WARNINGS). Withdrawal of the drugs did not lead to
regression of the tumors in all cases.
Geriatric patients treated with androgenic anabolic steroids
may be at an increased risk for the development of prostatic
hypertrophy and prostatic carcinoma.
Pregnancy:
Teratogenic effects—Pregnancy Category X (See CONTRA
INDICATIONS).
Nursing mothers:
It is not known whether anabolic steroids are excreted in human
milk. Because of the potential of serious adverse reactions in
nursing infants from oxandrolone, 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:
Anabolic agents may accelerate epiphyseal maturation more
rapidly than linear growth in children and the effect may con
tinue for 6 months after the drug has been stopped. There
fore, therapy should be monitored by x-ray studies at 6-month
intervals in order to avoid the risk of compromising adult height.
Androgenic anabolic steroid therapy should be used very cau
tiously in children and only by specialists who are aware of
the effects on bone maturation (See WARNINGS).
ADVERSE REACTIONS
The following adverse reactions have been associated with use
of anabolic steroids: ,
Hepatic: Cholestatic jaundice with, rarely, hepatic necrosis and
death. Hepatocellular neoplasms and peliosis hepatis with long
term therapy (See WARNINGS). Reversible changes in liver
function tests also occur including increased bromsulfophthalein
(BSP) retention, and increases in serum bilirubin, aspartate
aminotransferase (AST, SGOT) and alkaline phosphatase.
In males:
Prepubertal: Phallic enlargement and increased frequency or
persistence of erections.
Postpubertal: Inhibition of testicular function, testicular atro
phy and oligospermia, impotence, chronic priapism, epi
didymitis, and bladder irritability.
In females:
Clitoral enlargement, menstrual irregularities.
CNS: Habituation, excitation, insomnia, depression, and
changes in libido.
Hematologic: Bleeding in patients on concomitant anticoagu
lant therapy.
Breast: Gynecomastia.
Larynx: Deepening of the voice in females.
Hair: Hirsutism and male pattern baldness in females.
Skin: Acne (especially in females and prepubertal males).
Skeletal: Premature closure of epiphyses in children (See PRE
CAUTIONS: Pediatric use).
Fluid and electrolytes: Edema, retention of serum electrolytes
(sodium chloride, potassium, phosphate, calcium).
Metabolic/Endocrine: Decreased glucose tolerance (See PRE
CAUTIONS: Laboratory tests), increased creatinine excretion,
increased serum levels of creatinine phosphokinase (CPK). Mas
culinization of the fetus. Inhibition of gonadotropin secretion.
OVERDOSAGE
No symptoms or signs associated with overdosage have been
reported. It is possible that sodium and water retention may
occur.
The oral LD50 of oxandrolone in mice and dogs is greater
than 5,000 mg/kg. No specific antidote is known, but gastric
lavage may be used.
DOSAGE AND ADMINISTRATION
Therapy with anabolic steroids is adjunctive to and not a
replacement for conventional therapy. The duration of therapy
with Oxandrin (oxandrolone) will depend on the response of the
patient and the possible appearance of adverse reactions. Ther
apy should be intermittent.
Adults: The usual adult dosage of Oxandrin is one 2.5-mg tablet
2 to 4 times daily. However, the resjDonse of individuals to ana
bolic steroids varies, and a daily dosage of as little as 2.5 mg
or as much as 20 mg may be required to achieve the desired
response. A course of therapy of 2 to 4 weeks is usually ade
quate. This may be repeated intemnittently as indicated.
Children: For children the total daily dosage of Oxandrin is 0.1
mg per kilogram body weight or 0.045 mg per pound of body
weight. This may be repeated intermittently as indicated.
HOW SUPPLIED
Oxandrin 2.5-mg tablets are oval, white, and scored with BTG
on one side and “11” on each side of the scoreline on the
other side; bottles of 100 (NDC 54396-111-11).
Caution: Federal law prohibits dispensing without prescription.
Revised: Aug. 30,1996
Manufactured for
BTG Pharmaceuticals by:
G.D. Searle & Co.
Chicago, IL 60680
Address medical inquiries to:
BTG Pharmaceuticals
Medical Affairs
70 Wood Avenue South
Iselin, NJ 08830
BTG PHARMACEUTICALS
©1996, BTG Pharmaceuticals Printed in USA
BTG PHARMACEUTICALS
OXANDRIN® §
(oxandrolone tablets, USP)