Women should be observed for signs of virilization (deepening of the voice,
hirsutism, acne and clitoromegaly). To prevent irreversible change, drug therapy
must be discontinued when mild virilism is first detected. Such virilization
is usual following androgenic anabolic steroid use at high doses. Some virilizing
changes in women are irreversible even after prompt discontinuance of therapy
and are not prevented by concomitant use of estrogens. Menstrual irregularities,
including amenorrhea, may also occur.
The insulin or oral hypoglycemic dosage may need adjustment in diabetic patients
who receive anabolic steroids.
Anabolic steroids may cause suppression of clotting factors II, V, VII and
X, and an increase in prothrombin time.
Women with disseminated breast carcinoma should have frequent determination
of urine and serum calcium levels during the course of androgenic anabolic steroid
therapy (see WARNINGS).
Because of the hepatoxicity 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 prepubertal patients to determine the rate of bone maturation and
the effects of androgenic anabolic steroid therapy on the epiphyseal centers.
Anabolic steroids have been reported to lower the level of high-density lipoproteins
and raise the level of low-density lipoproteins. These changes usually revert
to normal on discontinuation of treatment. Increased low-density lipoproteins
and decreased high-density lipoproteins are considered cardiovascular risk factors.
Serum lipids and high-density lipoprotein cholesterol should be determined periodically.
Hemoglobin and hematocrit should be checked periodically for polycythemia in
patients who are receiving high doses of anabolics.
Because iron deficiency anemia has been observed in some patients treated with
oxymetholone, periodic determination of the serum iron and iron binding capacity
is recommended. If iron deficiency is detected, it should be appropriately treated
with supplementary iron.
Oxymetholone has been shown to decrease 17-ketosteroid excretion.
Carcinogenesis, Mutagenesis, Impairment of Fertility
A two-year carcinogenicity study in rats given oxymetholone orally was conducted
under the auspices of the US National Toxicology Program (NTP). A wide spectrum
of neoplastic and non-neoplastic effects was observed. In male rats, no effects
were classified as neoplastic in response to doses up to 150 mg/kg/day (5 times
therapeutic exposures with 5 mg/kg based on body surface area). Female rats
given 30 mg/kg/day (1 fold the maximum recommended clinical dose of 5 mg/kg/day
based on the body surface area) had increased incidences of lung alveolar/bronchiolar
adenoma and adenoma or carcinoma combined. At 100 mg/kg/day (about 3 fold the
maximum recommended clinical dose of 5 mg/kg/day based on BSA), female rats
had increased incidences of hepatocellular adenoma and adenoma or carcinoma
combined; the combined incidence of squamous cell carcinoma and carcinoma of
the sweat glands also was increased.
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 of developing
prostatic hypertrophy and prostatic carcinoma although conclusive evidence to
support this concept is lacking.
In studies conducted under the auspices of the US National Toxicology Program,
no evidence of genotoxicity was found using standard assays for mutagenicity,
chromosomal aberrations, or induction of micronuclei in erythrocytes.
Impairment of fertility was not tested directly in animal species. However,
as noted below under ADVERSE REACTIONS, oligospermia
in males and amenorrhea in females are potential adverse effects of treatment
with ANADROL Tablets. Therefore, impairment of fertility is a possible outcome
of treatment with ANADROL Tablets.
Pregnancy category X (see CONTRAINDICATIONS).
It is not known whether anabolics are excreted in human milk. Because of the
potential for serious adverse reactions in nursed infants from anabolics, women
who take oxymetholone should not nurse.
Anabolic/androgenic steroids should be used very cautiously in children and
only by specialists who are aware of their effects on bone maturation.
Anabolic agents may accelerate epiphyseal maturation more rapidly than linear
growth in children, and the effect may continue for 6 months after the drug
has been stopped. Therefore, therapy should be monitored by x-ray studies at
6-month intervals in order to avoid the risk of compromising the adult height.
Clinical studies of ANADROL Tablets did not include sufficient numbers of subjects
aged 65 and over to determine whether they respond differently from younger
subjects. Other reported clinical experience has not identified differences
in responses between the elderly and younger patients. In general, dose selection
for an elderly patient should be cautious, usually starting at the low end of
the dosing range, reflecting the greater frequency of decreased hepatic, renal,
or cardiac function, and of concomitant disease or other drug therapy.