PRINCIPIOS DE FARMACOLOGIA

NOTE: Nandrolone decanoate is a schedule C-III controlled substance. Description: Nandrolone decanoate is a parenteral anabolic steroid. It is used to manage the anemia of chronic renal failure and for osteoporosis. This agent will increase hemoglobin and red cell mass. With the development of recombinant human erythropoietin, nandrolone decanoate use in anemia associated with chronic renal failure has declined. Data on the effects of combining nandrolone decanoate and epoetin alfa are lacking. Anabolic steroids also promote body tissue-building processes and reverse catabolic or tissue-depleting processes. They have also been the subject of drug misuse and abuse, often producing adverse effects such as changes in libido, hepatotoxicity, increased risk of cardiovascular disease, and antisocial behavior. Some of the masculinizing effects in women can be irreversible. When using androgens and anabolic steroids, it is important to provide adequate calorie and protein intake to maintain a positive nitrogen balance. Nandrolone decanoate was approved by the FDA in 1983. Mechanism of Action: Nandrolone decanoate shares the actions of endogenous androgens such as testosterone. Exogenous androgens such as nandrolone decanoate promote protein anabolism and stimulate appetite which results in a reversal of catabolic processes and negative nitrogen balance. Increases in lean body mass in patients with cachexia (e.g., malnourished dialysis patients) and decreased bone resorption and increased bone density in patients with osteoporosis are often noted. Blood glucose, erythrocyte production, and the balance of calcium are also affected by androgens. Increased erythrocyte production is apparently due to enhanced production of erythropoietic stimulating factor. Patients with anemia associated with renal disease will have increases in red blood cell volume and hemoglobin after receiving nandrolone decanoate. Since nandrolone decanoate has actions similar to endogenous androgens, administration of nandrolone decanoate has the possibility of causing serious disturbances of growth and sexual development if given to young children and causing unwanted adverse effects in women. Exogenous androgens suppress gonadotropin-releasing hormone, thereby reducing the gonadotropic function of the pituitary through a negative-feedback mechanism. This results in a reduction of endogenous testosterone, luteinizing hormone, and follicle-stimulating hormone. Exogenous androgens may also have a direct effect on the testes. Reversible increases in low-density lipoproteins (LDL) and decreases in high-density lipoproteins (HDL) also occur. Pharmacokinetics: Nandrolone decanoate is administered intramuscularly. Following intramuscular injection, the drug is slowly released from the intramuscular depot at a relatively constant rate over approximately 4 days. A 100-mg dose produces peak serum concentrations in 3—6 days. In the systemic circulation, nandrolone decanoate is rapidly hydrolyzed to free nandrolone by plasma esterases. Nandrolone has high lipid solubility and can rapidly diffuse into cells. Nandrolone is subsequently metabolized in the liver via reduction and oxidation which is similar to the metabolism of testosterone. Data on the excretion of the parent compound and metabolites are lacking. The plasma clearance of nandrolone is approximately 1.6 L/hour/kg and the elimination half-life of the parent compound is 6 to 8 days.

Indications...Dosage For the treatment of anemia associated with chronic renal failure: NOTE: When given at 3—4 week intervals, therapy may be continued for up to 12 weeks. If necessary, the cycle may be repeated if the second-course is preceded by a 4-week rest period. Adequate iron intake is required for a maximal response. Therapy should be discontinued if no hematologic improvement is seen within the first six months. Intramuscular dosage: Adult and adolescent males >= 14 years of age: The recommended dose is 50—200 mg IM at one- to four-week intervals. Adult and adolescent females >= 14 years of age: The recommended dose is 50—100 mg IM at one- to four-week intervals. Children 2—13 years: The recommended dose is 25—50 mg IM every 3 to 4 weeks. Children up to 2 years: Dosage has not been established. For increasing peripheral and axial bone mass in postmenopausal women with osteoporosis†: Intramuscular dosage: Adults: A dose of 50 mg IM every 3—4 weeks has been studied. In one study, standard therapies for osteoporosis (e.g., estradiol, calcitonin, sodium fluoride plus calcium) were compared with nandrolone decanoate 50 mg IM every 3 weeks. Nandrolone decanoate had similar effectiveness to standard therapies in inhibiting bone resorption and increasing bone density, but exhibited less desireable adverse reactions (e.g., virilization).[2381] Another study reported that nandrolone decanoate 50 mg IM every 3—4 weeks for 6 months produced significant increases in bone mineral density at the proximal and distal radius, and in some patients at the lumbar spine. Therapy was not without adverse effects. Approximately 50% of patients experienced virilization and 9% dropped out due to virilization. The author of this study recommends that nandrolone decanoate be prescribed for this use only in patients > 65—75 years of age in order to minimize the occurrence of clinical adverse effects and to increase tolerability. Data were insufficient to determine nandrolone's effect on fracture rates.[2382] For promoting lean body mass development in dialysis patients with cachexia†: Intramuscular dosage: Adults: In a randomized double-blind, placebo-controlled study, 29 patients undergoing dialysis with evidence of malnutrition or poor quality of life were randomly assigned to receive nandrolone decanoate 100 mg IM or a placebo IM once a week for 6 months. Epoetin alfa therapy was not used concurrently. Compared to patients treated with placebo, nandrolone decanoate-treated patients had significant increases in lean body mass and an overall improvement in quality of life.[2383] Patients with renal impairment: Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. †non-FDA-approved indication

Administration Intramuscular administration •Inject IM deeply into the upper outer quadrant of the gluteal muscles. Aspirate prior to injection to avoid injection into a blood vessel.

Contraindications Androgen therapy can result in loss of diabetic control and should be used with caution in patients with diabetes mellitus. Close monitoring of blood glucose is recommended. Nandrolone decanoate is absolutely contraindicated during pregnancy because of probable adverse effects on the fetus (FDA pregnancy category X). Androgenic anabolic steroids are known to cause embryotoxicity, fetotoxicity, and masculinization of female animal offspring. Nandrolone decanoate is contraindicated in females who are or may become pregnant. If nandrolone decanoate is used during pregnancy, or if the patient becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus. It is not known if anabolic steroids are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, alternative methods to breast-feeding are recommended in patients receiving nandrolone decanoate therapy. Use of androgens in children should be undertaken only with extreme caution. Androgens may accelerate bone maturation without stimulating compensatory linear growth, sometimes resulting in compromised adult stature. Radiographic examinations of the hand and wrist should be performed every 6 months to assess the rate of bone maturation and the effect of the drug on epiphyseal centers. Once the epiphyses have closed, growth is terminated. Even after discontinuation of treatment, epiphyseal closure can be enhanced for several months. Nandrolone decanoate can stimulate the growth of cancerous tissue and should not be used in male patients with prostate cancer or breast cancer. Patients with prostatic hypertrophy should be treated with caution because of the possible development of malignancy. Androgens can induce osteolysis and should be used with caution in patients with hypercalcemia. Androgen-induced hypercalcemia occurs especially in immobile patients and those with metastatic breast cancer. During treatment with androgens, edema occurs because of fluid retention in association with sodium retention. Nandrolone decanoate is therefore contraindicated in patients with severe cardiac disease, severe hepatic disease, or severe renal disease because of possible exacerbation of these conditions. In addition, patients with heart failure, nephrosis or nephrotic phase of nephritis, coronary artery disease, myocardial infarction, or existing edema should be treated with caution. Because androgenic anabolic steroids have been associated the development of peliosis hepatis and hepatomas, further cautions are warranted for patients with hepatic disease. Patients with hepatic disease or hepatic dysfunction also can be at risk of drug accumulation because of reduced clearance. Some commercial nandrolone decanoate products contain benzyl alcohol. Do not use these formulations in patients with benzyl alcohol hypersensitivity.

Interactions Nandrolone decanoate can enhance the effects of anticoagulants. Dosage of the anticoagulant may have to be decreased in order to maintain prothrombin time at the desired therapeutic level. When anabolic steroid or androgen therapy is started or stopped in patients on anticoagulant therapy, close monitoring is required. Additionally, nandrolone decanoate may generate a pharmacodynamic interaction with warfarin by independently affecting the activity of circulating coagulation proteins. Androgens reduce the amount or activity of circulating coagulant proteins thereby enhancing the anticoagulant effect of warfarin. The actions of androgens could be antagonized by finasteride and saw palmetto. Avoid concurrent use of androgens and saw palmetto, Serenoa repens. Administration of anabolic steroids or androgens to patients receiving oral antidiabetic agents can increase the risk of developing hypoglycemia by inhibiting the metabolism of oral antidiabetic agents. Some androgens can also lower blood glucose in diabetic patients. Interestingly, this blood glucose-lowering effect is not observed in non-diabetic patients. Androgens can also enhance the hypoglycemic effect of insulin. Patients receiving oral antidiabetic agents or insulin should be monitored closely for evidence of hypoglycemia if anabolic steroids or androgens are administered concomitantly. Androgens such as nandrolone decanoate can decrease the clearance of cyclosporine via inhibition of hepatic microsomal enzymes. Cyclosporine toxicity (e.g., nephrotoxicity, seizures) may result if androgens are added to cyclosporine therapy. Both androgens and fludrocortisone cause fluid retention and edema when administered alone. Concurrent use of androgens and fludrocortisone should be done cautiously. Goserelin and leuprolide inhibit steroidogenesis. Concomitant use of nandrolone decanoate with goserelin or leuprolide is relatively contraindicated and would defeat the purpose of goserelin or leuprolide therapy. Androgens are known to stimulate erythropoiesis. Despite the fact that endogenous generation of erythropoietin is depressed in patients with chronic renal failure, other tissues besides the kidney can synthesize erythropoietin, albeit in small amounts. Concurrent administration of androgens can increase the patient's response to epoetin alfa, reducing the amount required to treat anemia. Because adverse reactions to epoetin alfa have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.

Adverse Reactions In females Menstrual irregularity can occur with nandrolone decanoate therapy in females. Disruption of the regular menstrual cycle secondary to nandrolone decanoate-induced suppression of gonadotropin secretion can lead to amenorrhea or oligomenorrhea. When androgens are given to women, virilization, manifested by acne, hirsutism, clitoromegaly, male pattern baldness, reduced breast size, and deepening of the voice or hoarseness, can occur. If treatment is discontinued when these symptoms first appear, they usually subside. Prolonged treatment can lead to irreversible masculinity, so the benefit of treatment should be measured against the risk. Androgens can cause teratogenesis. Androgens are classified as pregnancy category X, and are absolutely contraindicated during pregnancy because of probable adverse effects on the fetus. Androgenic anabolic steroids such as nandrolone decanoate are known to cause embryotoxicity, fetotoxicity, and masculinization of female animal offspring. Nandrolone decanoate is contraindicated in women who are or may become pregnant. In males Male patients can experience feminization during prolonged therapy with nandrolone decanoate, which is believed to result from inhibition of gonadotropin secretion and conversion of androgens to estrogens. These effects are more pronounced in patients with concurrent hepatic disease and include mastalgia and gynecomastia. Feminizing effects are generally reversible. Inhibition of testicular function, testicular atrophy, impotence, epididymitis, and bladder irritation can also occur. Priapism and excessive sexual stimulation, more common in geriatric males, are generally the effect of excessive nandrolone decanoate dosage. Oligospermia and decreased ejaculate volume may occur in patients receiving long-term therapy or excessive doses. Alopecia resembling male pattern baldness has also occurred. Prostate cancer as a secondary malignancy or prostatic hypertrophy can develop during prolonged therapy with nandrolone decanoate and are more likely to occur in elderly males. Signs of acute epididymitis (e.g., fever, chills, pain in the inguinal region) and/or urinary urgency should prompt withdrawal of the drug and reevaluation of dosage. In prepubescent males When androgens are used in the treatment of immature males, early virilism can be a disadvantage because it is accompanied by premature epiphyseal closure. Monitoring of skeletal maturation should be undertaken at about 6-month intervals. Once the epiphyses have closed, growth is terminated. Even after discontinuation of treatment, epiphyseal closure can be enhanced for several months. Penile enlargement and an increased frequency of erections can also occur. In males and females Peripheral edema can occur as the result of increased fluid retention (in association with sodium retention) and is manifested by weight gain. In the treatment of patients with impaired renal function or congestive heart failure, the fluid retention is of greater significance. Other serum electrolytes (i.e., calcium, chloride, phosphate, and potassium) are also retained. Androgen therapy is related to growth and secretion of the sebaceous glands, which can cause an acneiform rash indistinguishable from acne vulgaris. Hepatic dysfunction can occur from use of androgenic anabolic steroids and have been shown to be more significant with administration of the oral 17-alpha-alkylandrogens (e.g., methyltestosterone). Cholestatic jaundice with, rarely, hepatic necrosis and death have been reported. Elevated hepatic enzymes are more common than overt jaundice. The drug should be discontinued if cholestatic jaundice or hepatitis occurs. Peliosis hepatis, a condition characterized by splenic tissue being replaced by blood filled cysts, has occurred in patients receiving androgenic anabolic steroids. The cysts are sometimes present with minimal hepatic dysfunction, but may be associated with hepatic failure. They are often not noticeable until life-threatening hepatic failure or intra-abdominal hemorrhage develops. Discontinuation of steroid therapy usually results in complete disappearance of cysts. Hepatomas also occur rarely and are usually benign and androgen-dependent; life-threatening malignant hepatomas have been reported. Withdrawal of drug often results in regression or cessation of progression of the tumors. However, hepatomas associated with androgens or anabolic steroids are much more vascular than other hepatic tumors and may be undetected until life-threatening intra-abdominal hemorrhage develops. Androgen therapy has induced osteolysis and can exacerbate hypercalcemia. Androgen-induced hypercalcemia occurs especially in immobile patients and those with metastatic carcinoma of the breast. Observational studies in post-menopausal women, bodybuilders, and weightlifters using anabolic steroids have revealed "pro-atherogenic" changes in lipid profiles, including decreases in HDL concentrations and increases in LDL concentrations. Synthetic androgens may produce a greater lowering of the HDL-C:LDL-C ratio than does testosterone. Oral anabolic steroids (e.g., stanozolol) may produce greater changes than parenteral ones. Although the implications of androgen-induced hypercholesterolemia are unclear, caution should be exercised, particularly in patients predisposed to dyslipidemias or atherosclerosis. Androgen therapy can produce libido decrease or libido increase. Geriatric males have been found to be more likely to experience excessive sexual stimulation. Miscellaneous adverse reactions to nandrolone decanoate therapy have included decreased glucose tolerance, diarrhea, edema, excitability, habituation, increased CPK and creatinine, insomnia, mental depression, nausea/vomiting. Intramuscular administration of anabolic steroids can cause inflammation, urticaria, postinjection induration and furunculosis. Patients should be observed for any signs of an injection site reaction. Anabolic steroids may cause suppression of clotting factors II, V, VII, and X. Prolonged bleeding time may occur.

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