Testosterone products

INDICATIONS AND USAGE:
ANDRODERM is an androgen indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone (1):

Primary hypogonadism (congenital or acquired)
Hypogonadotropic hypogonadism (congenital or acquired)

Important limitations of use: Safety and efficacy of ANDRODERM in males less than 18 years old have not been established.

DOSAGE AND ADMINISTRATION:
The recommended starting dose is one ANDRODERM 4 mg/day system (not two 2 mg/day systems) applied nightly for 24 hours, delivering approximately 4 mg of testosterone per day.

To ensure proper dosing, approximately 2 weeks after starting therapy, the early morning serum testosterone concentration should be measured following system application in the previous evening.

Serum testosterone concentrations measured in the early morning outside the range of 400 - 930 ng/dL require increasing the daily dose to 6 mg (i.e., one 4 mg/day and one 2 mg/day system) or decreasing the daily dose to 2 mg (i.e., one 2 mg/day system), maintaining nightly application.

Patients currently maintained on ANDRODERM 2.5 mg/day systems applied once daily may be switched to ANDRODERM 2 mg/day systems applied once daily in the evening at the next scheduled dose.

Patients currently maintained on ANDRODERM 5 mg/day systems applied once daily may be switched to ANDRODERM 4 mg/day systems applied once daily in the evening at the next scheduled dose.

Patients currently maintained on ANDRODERM 7.5 mg (2.5 mg/day and 5 mg/day systems) applied once daily may be switched to ANDRODERM 6 mg (2 mg/day and 4 mg/day systems) applied once daily in the evening at the next scheduled dose.

To ensure proper dosing, approximately 2 weeks after switching therapy an early morning serum testosterone concentration should be measured following system application the previous evening.

CONTRAINDICATIONS:
Men with carcinoma of the breast or known or suspected carcinoma of the prostate.
Pregnant or breastfeeding women. Testosterone may cause fetal harm.

WARNINGS AND PRECAUTIONS

• Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH.
• Avoid exposure of women or children to ANDRODERM.
• Exogenous administration of testosterone may lead to azoospermia.
• Edema with or without congestive heart failure, may be a complication in patients with pre-existing cardiac, renal, or hepatic disease.
• Sleep apnea may occur in those with risk factors.
• Monitor serum testosterone, prostate specific antigen (PSA), liver function, lipid concentrations, hematocrit and hemoglobin periodically.
• Skin burns have been reported at the application site in patients wearing an aluminized transdermal system during a magnetic resonance imaging scan (MRI). Because ANDRODERM contains aluminum, it is recommended to remove the system before undergoing an MRI.

ADVERSE REACTIONS:
The most common adverse reactions (incidence > 3%) are application site reactions, and back pain.

To report SUSPECTED ADVERSE REACTIONS, contact Watson Laboratories, Inc. at 1-800-272-5525 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

• Androgens may decrease blood glucose and insulin requirement in diabetic patients.
• Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of International Normalized Ratio (INR) and prothrombin time is recommended.
• Use of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease.

USE IN SPECIFIC POPULATIONS:
There are insufficient long-term safety data in geriatric patients using ANDRODERM to assess the potential risks of cardiovascular disease and prostate cancer.

Review PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

DOSAGE FORMS AND STRENGTHS:
Transdermal system: 2 mg/day and 4 mg/day.

SOURCE:
Package insert data:
Watson Laboratories, Inc.
Salt Lake City, UT 84108 USA
Revised 04/2012

INDICATIONS AND USAGE:
AndroGel 1% is an androgen indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone:

• Primary hypogonadism (congenital or acquired).
• Hypogonadotropic hypogonadism (congenital or acquired).

Important limitations of use:

• Safety and efficacy of AndroGel 1% in males less than 18 years old have not been established.
• Topical testosterone products may have different doses, strengths or application instructions that may result in different systemic exposure.

DOSAGE AND ADMINISTRATION:

• Dosage and Administration for AndroGel 1% differs from AndroGel 1.62 %. For dosage and administration of AndroGel 1.62%  (outside link) refer to its full prescribing information.
• Starting dose of AndroGel 1% is 50 mg of testosterone (4 pump actuations, two 25 mg packets, or one 50 mg packet), applied once daily in the morning.
• Apply to clean, dry, intact skin of shoulders and upper arms and/or abdomen. Do NOT apply AndroGel 1% to any other parts of the body including the genitals, chest or back.
• Dose adjustment: AndroGel 1% can be dose adjusted using 50 mg, 75 mg, or 100 mg of testosterone on the basis of total serum testosterone concentration. The dose should be titrated based on the serum testosterone concentration. Additionally, serum testosterone concentration should be assessed periodically.
• Patients should wash hands immediately with soap and water after applying AndroGel 1% and cover the application site(s) with clothing after the gel has dried. Wash the application site thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated.

CONTRAINDICATIONS:
Men with carcinoma of the breast or known or suspected prostate cancer.
Pregnant or breastfeeding women. Testosterone may cause fetal harm.

WARNINGS AND PRECAUTIONS::

• Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH.
• Avoid unintentional exposure of women or children to AndroGel 1%. Secondary exposure to testosterone can produce signs of virilization. AndroGel 1% should be discontinued until the cause of virilization is identified.
• Exogenous administration of androgens may lead to azoospermia.
• Edema, with or without congestive heart failure (CHF), may be a complication in patients with preexisting cardiac, renal, or hepatic disease.
• Sleep apnea may occur in those with risk factors.
• Monitor serum testosterone, prostate specific antigen (PSA), hemoglobin, hematocrit, liver function tests, and lipid concentrations periodically.
• AndroGel 1% is flammable until dry.

ADVERSE REACTIONS:
Most common adverse reactions (incidence ≥ 5%) are acne, application site reaction, abnormal lab tests, and prostatic disorders.

DRUG INTERACTIONS:

• Androgens may decrease blood glucose and insulin requirement in diabetic patients.
• Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of International Normalized Ratio (INR) and prothrombin time is recommended.
• Use of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease.

USE IN SPECIFIC POPULATIONS:
There are insufficient long-term safety data in geriatric patients using AndroGel 1% to assess the potential risks of cardiovascular disease and prostate cancer.

Review PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

DOSAGE FORMS AND STRENGTHS:
AndroGel (testosterone gel) 1% for topical use is available as follows:

Metered-dose pump that delivers 12.5 mg of testosterone per actuation.
Packets containing 25 mg of testosterone.
Packets containing 50 mg of testosterone.

SOURCE:
PaPackage insert data:
Abbott Laboratories
North Chicago, IL 60064, U.S.A.
Rev: September 2012

1] Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range.

2] Hypogonadotropic hypogonadism (congenital or acquired): idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations, but have gonadotropins in the normal or low range.

Important limitations of use: Safety and efficacy of AndroGel 1.62% in males < 18 years old have not been established

DOSAGE AND ADMINISTRATION:
Dosage and Administration for AndroGel 1.62% differs from AndroGel 1%. For dosage and administration of AndroGel 1% refer to its full prescribing information.

Dosing and Dose Adjustment
The recommended starting dose of AndroGel 1.62% is 40.5 mg of testosterone (2 pump actuations) applied topically once daily in the morning to the shoulders and upper arms.

The dose can be adjusted between a minimum of 20.25 mg of testosterone (1 pump actuation) and a maximum of 81 mg of testosterone (4 pump actuations). To ensure proper dosing, the dose should be titrated based on the pre-dose morning serum testosterone concentration from a single blood draw at approximately 14 days and 28 days after starting treatment or following dose adjustment. In addition, serum testosterone concentration should be assessed periodically thereafter. Table 1 describes the dose adjustments required at each titration step.

Table 1: Dose Adjustment Criteria

The application site and dose of AndroGel 1.62% are not interchangeable with other topical testosterone products.
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Administration Instructions
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AndroGel 1.62% should be applied to clean, dry, intact skin of the upper arms and shoulders. Do not apply AndroGel 1.62% to any other parts of the body, including the abdomen or genitals [see CLINICAL PHARMACOLOGY]. Area of application should be limited to the area that will be covered by the patient's short sleeve t-shirt. Patients should be instructed to use the palm of the hand to apply AndroGel 1.62% and spread across the maximum surface area as directed in Table 2 and in Figure 1.

Table 2: Application Sites for AndroGel 1.62%

The prescribed daily dose of AndroGel 1.62% should be applied to the right and left upper arms and shoulders as shown in the shaded areas in Figure 1.
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Figure 1: Application Sites for AndroGel 1.62%
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Once the application site is dry, the site should be covered with clothing [see CLINICAL PHARMACOLOGY]. Wash hands thoroughly with soap and water. Avoid fire, flames or smoking until the gel has dried since alcohol based products, including AndroGel 1.62%, are flammable.

The patient should avoid swimming or showering or washing the administration site for a minimum of 2 hours after application [see CLINICAL PHARMACOLOGY].

To obtain a full first dose, it is necessary to prime the canister pump. To do so, with the canister in the upright position, slowly and fully depress the (actuator) three times. Safely discard the gel from the first three actuations. It is only necessary to prime the pump before the first dose.

After the priming procedure, fully depress the actuator once for every 20.25 mg of AndroGel 1.62%. AndroGel 1.62% should be delivered directly into the palm of the hand and then applied to the application sites. Alternatively, AndroGel 1.62% can be applied directly to the application sites.

Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from AndroGel 1.62%-treated skin:

• Children and women should avoid contact with unwashed or unclothed application site(s) of men using AndroGel 1.62%.
• AndroGel 1.62% should only be applied to the upper arms and shoulders. The area of application should be limited to the area that will be covered by a short sleeve t-shirt.
• Patients should wash their hands with soap and water immediately after applying AndroGel 1.62%.
• Patients should cover the application site(s) with clothing (e.g., a t-shirt) after the gel has dried.
• Prior to situations in which direct skin-to-skin contact is anticipated, patients should wash the application site(s) thoroughly with soap and water to remove any testosterone residue.
• In the event that unwashed or unclothed skin to which AndroGel 1.62% has been applied comes in direct contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible.

CONTRAINDICATIONS:
AndroGel 1.62% is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see package insert for WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].
AndroGel 1.62% is contraindicated in women who are or may become pregnant, or who are breastfeeding. AndroGel 1.62% may cause fetal harm when administered to a pregnant woman.

AndroGel 1.62% may cause serious adverse reactions in nursing infants. Exposure of a fetus or nursing infant to androgens may result in varying degrees of virilization. Pregnant women or those who may become pregnant need to be aware of the potential for transfer of testosterone from men treated with AndroGel 1.62%. If a pregnant woman is exposed to AndroGel 1.62%, she should be apprised of the potential hazard to the fetus [see package insert for WARNINGS AND PRECAUTIONS and Use In Specific Populations].

DOSAGE FORMS AND STRENGTHS:
AndroGel (testosterone gel) 1.62% for topical use only, is supplied in a metered-dose pump. One pump actuation delivers 20.25 mg of testosterone.
Storage And Handling

AndroGel 1.62% is supplied in a metered-dose pump that delivers 20.25 mg of testosterone per complete pump actuation. The pump is composed of plastic and stainless steel and an LDPE/aluminum foil inner liner encased in rigid plastic with a polypropylene cap. The metered-dose pump is capable of dispensing 60 metered pump actuations. One pump actuation delivers 1.25 g of gel.

SOURCE:
Package insert data:
Abbott Laboratories, North Chicago, IL, 60064, U.S.A.
Revised: 04/2011

INDICATIONS AND USAGE:
AXIRON® is an androgen indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone:

1] Primary hypogonadism (congenital or acquired)
2] Hypogonadotropic hypogonadism (congenital or acquired)

Important limitations of use: Safety and efficacy of AXIRON in males <18 years old have not been established

DOSAGE AND ADMINISTRATION:

• Starting AXIRON dose is 60 mg of testosterone (1 pump actuation of 30 mg of testosterone to each axilla), applied once daily, at the same time each morning.
• Apply to clean, dry intact skin of the axilla, not to any other parts of the body including the abdomen or genitals
• Dose adjustment: The dose of testosterone may be decreased from 60 mg (2 pump actuations) to 30 mg (1 pump actuation) or increased from 60 mg to 90 mg (3 pump actuations) or from 90 mg to 120 mg (4 pump actuations) based on the serum testosterone concentration from a single blood draw 2 - 8 hours after applying AXIRON and at least 14 days after starting treatment or following dose adjustment.
• Patients should wash hands immediately with soap and water after applying AXIRON and cover the application site with clothing after the solution has dried. Wash the application site thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated.
• The application site and dose of AXIRON are not interchangeable with other topical testosterone products.

CONTRAINDICATIONS:
Men with carcinoma of the breast or known or suspected prostate cancer.
Pregnant or breastfeeding women. Testosterone may cause fetal harm.

WARNINGS AND PRECAUTIONS:

• Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH
• Avoid unintentional exposure of women or children to AXIRON. Secondary exposure to testosterone can produce signs of virilization. AXIRON should be discontinued until the cause of the virilization is identified
• Exogenous administration of testosterone may lead to azoospermia
• Edema with or without congestive heart failure, may be a complication in patients with preexisting cardiac, renal, or hepatic disease
• Sleep apnea may occur in those with risk factors
• Monitor serum testosterone, prostate specific antigen (PSA), liver function, lipid concentrations, hematocrit and hemoglobin periodically
• AXIRON is flammable until dry

ADVERSE REACTIONS:
Most common adverse reactions (incidence >4%) are skin application site reactions, increased hematocrit, headache, diarrhea, vomiting, and increased serum PSA

To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS:

• Androgens may decrease blood glucose and insulin requirement in diabetic patients.
• Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of International Normalized Ratio (INR) and prothrombin time is recommended.
• Use of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease.

USE IN SPECIFIC POPULATIONS:
There are insufficient long-term safety data in geriatric patients using Axiron to assess the potential risks of cardiovascular disease and prostate cancer.
Review PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

DOSAGE FORMS AND STRENGTHS:
AXIRON (testosterone) topical solution is available as a metered-dose pump. One pump actuation delivers 30 mg of testosterone. Each metered-dose pump is supplied with an applicator.

SOURCE:
Package insert data:
revised December 2011
Marketed by: Lilly USA, LLC Indianapolis, IN 46285, USA
Copyright © 2010, 2011, Eli Lilly and Company. All rights reserved.

U.S. Approval:  2014.

Mechanism of Action: Endogenous androgens, including testosterone and dihydrotestosterone (DHT) 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 facial, pubic, chest, and axillary hair; laryngeal enlargement, vocal cord thickening, and alterations in body musculature and fat distribution.

Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter’s syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

INDICATIONS AND USAGE:
Aveed (testosterone undecanoate) injection is an androgen indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone:

o Primary hypogonadism (congenital or acquired)
o Hypogonadotropic hypogonadism (congenital or acquired)

Aveed should only be used in patients who require testosterone replacement therapy and in whom the benefits of the product outweigh the serious risks of pulmonary oil microembolism and anaphylaxis (1).

Limitations of use:
Safety and efficacy of Aveed in men with "age-related hypogonadism" have not been established .
Safety and efficacy of Aveed in males less than 18 years old have not been established.

HOW SUPPLIED: 750 mg/3 mL (250 mg/mL) testosterone undecanoate sterile injectable solution is provided in an amber glass, single use vial with silver-colored crimp seal and gray plastic cap

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 growth and maturation of prostate, seminal vesicles, penis, and scrotum; development of male hair distribution, such as beard, pubic, chest, and axillary hair; laryngeal enlargement; vocal chord thickening; alterations in body musculature; and fat distribution.

Androgens also cause retention of nitrogen, sodium, potassium, and 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 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 the 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.
INDICATIONS AND USAGE:
Males
DELATESTRYL® (Testosterone Enanthate Injection, USP) is indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone.

Primary hypogonadism (congenital or acquired) - Testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, or orchidectomy.

Hypogonadotropic hypogonadism (congenital or acquired) - Idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation. (Appropriate adrenal cortical and thyroid hormone replacement therapy are still necessary, however, and are actually of primary importance.)

If the above conditions occur prior to puberty, androgen replacement therapy will be needed during the adolescent years for development of secondary sexual characteristics. Prolonged androgen treatment will be required to maintain sexual characteristics in these and other males who develop testosterone deficiency after puberty.

Delayed puberty - DELATESTRYL® (Testosterone Enanthate Injection, USP) 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 obtained every six months to assess the effect of treatment on the epiphyseal centers (see WARNINGS).

Females
Metastatic mammary cancer - DELATESTRYL® (Testosterone Enanthate Injection, USP) may be used secondarily in women with advancing inoperable metastatic (skeletal) mammary cancer who are one to five years postmenopausal. Primary goals of therapy in these women include ablation of the ovaries. Other methods of counteracting estrogen activity are adrenalectomy, hypophysectomy, and/or antiestrogen therapy. This treatment has also been used in premenopausal women with breast cancer who have benefited from oophorectomy and are considered to have a hormone-responsive tumor. Judgment concerning androgen therapy should be made by an oncologist with expertise in this field.
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DOSAGE AND ADMINISTRATION:
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Dosage and duration of therapy with DELATESTRYL® (Testosterone Enanthate Injection, USP) will depend on age, sex, diagnosis, patient’s response to treatment, and appearance of adverse effects. When properly given, injections of DELATESTRYL are well tolerated. Care should be taken to slowly inject the preparation deeply into the gluteal muscle, being sure to follow the usual precautions for intramuscular administration, such as the avoidance of intravascular injection (see PRECAUTIONS).

In general, total doses above 400 mg per month are not required because of the prolonged action of the preparation. Injections more frequently than every two weeks are rarely indicated. NOTE: Use of a wet needle or wet syringe may cause the solution to become cloudy; however this does not affect the potency of the material. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. DELATESTRYL is a clear, colorless to pale yellow solution.

Male hypogonadism: As replacement therapy, i.e., for eunuchism, the suggested dosage is 50 to 400 mg every 2 to 4 weeks.

In males with delayed puberty: Various dosage regimens have been used; some call for lower dosages initially with gradual increases as puberty progresses, with or without a decrease to maintenance levels. Other regimens call for higher dosage to induce pubertal changes and lower dosage 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. Dosage is within the range of 50 to 200 mg every 2 to 4 weeks for a limited duration, for example, 4 to 6 months. X-rays should be taken at appropriate intervals to determine the amount of bone maturation and skeletal development (see INDICATIONS AND USAGE, and WARNINGS).

Palliation of inoperable mammary cancer in women: A dosage of 200 to 400 mg every 2 to 4 weeks is recommended. Women with metastatic breast carcinoma must be followed closely because androgen therapy occasionally appears to accelerate the disease.

CONTRAINDICATIONS:
Androgens are contraindicated in men with carcinomas of the breast or with known or suspected carcinomas of the prostate and in women who are or may become pregnant. When administered to pregnant women, androgens cause virilization of the external genitalia of the female fetus. This 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 androgens, she should be apprised of the potential hazard to the fetus.

This preparation is also contraindicated in patients with a history of hypersensitivity to any of its components.

WARNINGS:
In patients with breast cancer and in immobilized patients, androgen therapy may cause hypercalcemia by stimulating osteolysis. In patients with cancer, hypercalcemia may indicate progression of bony metastasis. If hypercalcemia occurs, the drug should be discontinued and appropriate measures instituted.

Prolonged use of high doses of androgens has been associated with the development of peliosis hepatis and hepatic neoplasms including hepatocellular carcinoma (see PRECAUTIONS, Carcinogenesis). Peliosis hepatis can be a life-threatening or fatal complication.

If cholestatic hepatitis with jaundice appears or if liver function tests become abnormal, the androgen should be discontinued and the etiology should be determined. Drug-induced jaundice is reversible when the medication is discontinued.

Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hypertrophy and prostatic carcinoma.

Due to sodium and water retention, edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required. If the administration of testosterone enanthate is restarted, a lower dose should be used.

Gynecomastia frequently develops and occasionally persists in patients being treated for hypogonadism.

Androgen therapy should be used cautiously in healthy males with delayed puberty. The effect on bone maturation should be monitored by assessing bone age of the wrist and hand every six months. In children, androgen treatment may accelerate bone maturation without producing compensatory gain in linear growth. This adverse effect may result in compromised adult stature. The younger the child the greater the risk of compromising final mature height.

PRECAUTIONS
General
Women should be observed for signs of virilization (deepening of the voice, hirsutism, acne, clitoromegaly, and menstrual irregularities). Discontinuation of drug therapy at the time of evidence of mild virilism is necessary to prevent irreversible virilization. Such virilization is usual following androgen use at high doses and is not prevented by concomitant use of estrogens. A decision may be made by the patient and the physician that some virilization will be tolerated during treatment for breast carcinoma.

Because androgens may alter serum cholesterol concentration, caution should be used when administering these drugs to patients with a history of myocardial infarction or coronary artery disease. Serial determinations of serum cholesterol should be made and therapy adjusted accordingly. A causal relationship between myocardial infarction and hypercholesterolemia has not been established.

Information for Patients
Male adolescent patients receiving androgens for delayed puberty should have bone development checked every six months.

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.
Women - hoarseness, acne, changes in menstrual periods, or more facial hair.
All patients - any nausea, vomiting, changes in skin color, or ankle swelling.

Geriatric Use
Clinical studies of DELATESTRYL did not include sufficient numbers of subjects, aged 65 and older, to determine whether they respond differently from younger subjects. Testosterone replacement is not indicated in geriatric patients who have age-related hypogonadism only (“andropause”), because there is insufficient safety and efficacy information to support such use. Current studies do not assess whether testosterone use increases risks of prostate cancer, prostate hyperplasia, and cardiovascular disease in the geriatric population.

Drug/Laboratory Test Interferences
Androgens may decrease levels of thyroxine-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.

Carcinogenesis
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 the liver in rats.

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.

DRUG INTERACTIONS:

• Androgens may decrease blood glucose and insulin requirement in diabetic patients.
• Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of International Normalized Ratio (INR) and prothrombin time is recommended.
• Use of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease.

USE IN SPECIFIC POPULATIONS:
Review PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

DOSAGE FORMS AND STRENGTHS:
DELATESTRYL® (Testosterone Enanthate Injection, USP) is available in 5 mL (200 mg/mL) multiple dose vials.

STORAGE
DELATESTRYL® (Testosterone Enanthate Injection, USP) should be stored at room temperature. Warming and rotating the vial between the palms of the hands will redissolve any crystals that may have formed during storage at low temperatures.

SOURCE:
Package insert data:
Manufactured for:
Indevus Pharmaceuticals, Inc.
Lexington, MA 02421

Manufactured by:
SAB-Pharma Inc.
Boucherville, QC, Canada J4B 7K8

Revised: July 2007

1. Primary hypogonadism (congenital or acquired)-testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy.

2. Hypogonadotropic hypogonadism (congenital or acquired)-idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation.

DOSAGE AND ADMINISTRATION:
DEPO-Testosterone Injection is for intramuscular use only.

It should not be given intravenously. Intramuscular injections should be given deep in the gluteal muscle.

The suggested dosage for DEPO-Testosterone Injection varies depending on the age, sex, and diagnosis of the individual patient. Dosage is adjusted according to the patient's response and the appearance of adverse reactions.

Various dosage regimens have been used to induce pubertal changes in hypogonadal males; some experts have advocated lower dosages initially, gradually increasing the dose as puberty progresses, with or without a decrease to 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.

For replacement in the hypogonadal male, 50-400 mg should be administered every two to four weeks.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Warming and shaking the vial should redissolve any crystals that may have formed during storage at temperatures lower than recommended.

CONTRAINDICATIONS:

1. Known hypersensitivity to the drug
2. Males with carcinoma of the breast
3. Males with known or suspected carcinoma of the prostate gland
4. Women who are or who may become pregnant
5. Patients with serious cardiac, hepatic or renal disease

WARNINGS AND PRECAUTIONS:
WARNINGS
Hypercalcemia may occur in immobilized patients. If this occurs, the drug should be discontinued.

Prolonged use of high doses of androgens (principally the 17-a alkyl-androgens) has been associated with development of hepatic adenomas, hepatocellular carcinoma, and peliosis hepatis —all potentially life-threatening complications.

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.

Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal or hepatic disease.

Gynecomastia may develop and occasionally persists in patients being treated for hypogonadism.

This product contains benzyl alcohol. Benzyl alcohol has been reported to be associated with a fatal "Gasping Syndrome" in premature infants.

Androgen therapy should be used cautiously in healthy males with delayed puberty. The effect on bone maturation should be monitored by assessing bone age of the wrist and hand every 6 months. In children, androgen treatment may accelerate bone maturation without producing compensatory gain in linear growth. This adverse effect may result in compromised adult stature. The younger the child the greater the risk of compromising final mature height.

This drug has not been shown to be safe and effective for the enhancement of athletic performance. Because of the potential risk of serious adverse health effects, this drug should not be used for such purpose.

PRECAUTIONS
General
Patients with benign prostatic hypertrophy may develop acute urethral obstruction. Priapism or excessive sexual stimulation may develop. Oligospermia may occur after prolonged administration or excessive dosage. If any of these effects appear, the androgen should be stopped and if restarted, a lower dosage should be utilized.

Testosterone cypionate should not be used interchangeably with testosterone propionate because of differences in duration of action.

Testosterone cypionate is not for intravenous use.

Information for patients
Patients should be instructed to report any of the following: nausea, vomiting, changes in skin color, ankle swelling, too frequent or persistent erections of the penis.

Laboratory tests
Hemoglobin and hematocrit levels (to detect polycythemia) should be checked periodically in patients receiving long-term androgen administration.

Serum cholesterol may increase during androgen therapy.

Drug interactions
Androgens may increase sensitivity to oral anticoagulants. Dosage of the anticoagulant may require reduction in order to maintain satisfactory therapeutic hypoprothrombinemia.

Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone.

In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, insulin requirements.

Drug/Laboratory test Interferences
Androgens may decrease levels of thyroxine-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.

Carcinogenesis
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 the 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 of developing prostatic hypertrophy and prostatic carcinoma although conclusive evidence to support this concept is lacking.

Pregnancy
Teratogenic Effects
Pregnancy Category X. (See CONTRAINDICATIONS.)

Nursing mothers
DEPO-Testosterone is not recommended for use in nursing mothers.

Pediatric use
Safety and effectiveness in pediatric patients below the age of 12 years have not been established.

ADVERSE REACTIONS:
The following adverse reactions in the male have occurred with some androgens:

Endocrine and urogenital: Gynecomastia and excessive frequency and duration of penile erections. Oligospermia may occur at high dosages.

Skin and appendages: Hirsutism, male pattern of baldness, seborrhea, and acne.

Fluid and electrolyte disturbances: Retention of sodium, chloride, water, potassium, calcium, and inorganic phosphates.

Gastrointestinal: Nausea, cholestatic jaundice, alterations in liver function tests, rarely hepatocellular neoplasms and peliosis hepatis (see WARNINGS).

Hematologic: Suppression of clotting factors II, V, VII, and X, bleeding in patients on concomitant anticoagulant therapy, and polycythemia.

Nervous system: Increased or decreased libido, headache, anxiety, depression, and generalized paresthesia.

Allergic: Hypersensitivity, including skin manifestations and anaphylactoid reactions.

Miscellaneous: Inflammation and pain at the site of intramuscular injection.

USE IN SPECIFIC POPULATIONS:
Review PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

DOSAGE FORMS AND STRENGTHS:
DEPO-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate.

Each mL of the 100 mg/mL solution contains:
Testosterone cypionate................................................................................... 100 mg
Benzyl benzoate .............................................................................................. 0.1 mL
Cottonseed oil ................................................................................................ 736 mg
Benzyl alcohol (as preservative) ..................................................................... 9.45 mg

Each mL of the 200 mg/mL solution contains:
Testosterone cypionate .................................................................................. 200 mg
Benzyl benzoate .............................................................................................. 0.2 mL
Cottonseed oil ................................................................................................ 560 mg
Benzyl alcohol (as preservative) ..................................................................... 9.45 mg

DEPO-Testosterone Injection is available as follows:
200 mg/mL:
1 mL vials
10 mL vials

SOURCE:
Package insert data:
Physicians Total Care, Inc.
Tulsa, OK 74146
rev: September 2006

FIRST®- Testosterone in White Petrolatum Compounding Kit also contains 48 grams of white petrolatum for topical use. When compounded, the final product provides an homogeneous formulation
containing 2% testosterone.

How Supplied and Compounding Directions
Size (Net Weight) 60 grams
NDC# 65628-020-01
Testosterone Solution 12 mL (100 mg/mL)
White Petrolatum 48 grams
------------------------------------------------------
One 5 mL teaspoonful is approximately equivalent to 5.3 gm of
compounded product containing equivalent of 106 mg of testosterone.

1. FIRST®- Testosterone in White Petrolatum Compounding Kit contains pre-weighed white petrolatum in a mixing jar, premeasured testosterone solution, and a stirrer.

2. Important - Prior to dispensing, pour the entire contents of the bottle containing testosterone propionate in oil into white petrolatum.

3. Stir gently until homogeneous in appearance (2 to 3 minutes).

Prior to compounding, store FIRST®- Testosterone in White Petrolatum Compounding Kit at room temperature between 15°-30°C (59°-86°F). Also store final formulation at room temperature, 15°-30°C (59°-86°F).

FIRST®- Testosterone in White Petrolatum Compounding Kit components have a three-year expiration date.** Based on real time controlled room temperature and humidity testing,
compounded FIRST®- Testosterone in White Petrolatum is stable for at least six months.**
Each lot of FIRST®- Testosterone solution meets the requirements for total aerobic microbial count of not more than 100 cfu/mL, as well as for the absence of the specified microorganisms Escherichia
coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella spp. when tested as described in the current USP under <61> Microbial Enumeration Tests and <62> Tests for Specified
Microorganisms. FIRST®- Testosterone solution also meets the
requirements as described in the current USP under <51> Antimicrobial Effectiveness Testing for Category 2 products.
For external use only. Avoid contact with eyes. Keep container tightly closed. Keep out of the reach of children. Compounded product, as dispensed, is stable for at least 180 days at room temperature.
----------------

FIRST®- Testosterone MC
2% Testosterone MC in Moisturizing Cream
Base Compounding Kit
FOR PRESCRIPTION COMPOUNDING ONLY

DESCRIPTION
Each Testosterone MC in Moisturizing Cream Base Compounding Kit contains 1.4312 grams of micronized testosterone propionate USP (100 mg testosterone per mL) in solution* (total volume: 12 mL) with sesame oil NF, butylated hydroxytoluene NF, and benzyl alcohol NF.
Testosterone MC in Moisturizing Cream Base Compounding Kit also contains 48 grams of Moisturizing Cream Base for topical use. When compounded, the final product provides an homogeneous formulation containing 2% testosterone.

How Supplied and Compounding Directions
Size (Net Weight) 60 grams
NDC# 65628-021-01
Testosterone Solution 12 mL (100 mg/mL)
Moisturizing Cream Base 48 grams
-------------------------------------------------------------
One 5 mL teaspoonful is approximately equivalent to 6.1 gm of
compounded product containing equivalent of 122 mg of testosterone.

1. Testosterone MC in Moisturizing Cream Base Compounding Kit contains pre-weighed moisturizing cream base in a mixing jar, pre-measured testosterone solution, and a stirrer.

2. Important - Be careful not to spill the contents while mixing. Prior to dispensing, pour a few drops of the testosterone propionate in oil into moisturizing cream base.

3. Mix well to wet the base.

4. Continue to gradually add testosterone propionate in oil into moisturizing cream base and mix until all of the testosterone propionate in oil has been added to the moisturizing cream base

5 Continue stirring until homogeneous in appearance (2 to 3 minutes).

SOURCE:
Package insert data
https://www.cutispharma.com/products/topicals/testosterone/testosterone
https://www.cutispharma.com/products/topicals/testosterone/testosterone-mc

INDICATIONS AND USAGE:
FORTESTA is an androgen indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone:

Primary hypogonadism (congenital or acquired)
Hypogonadotropic hypogonadism (congenital or acquired)

Important limitations of use: Safety and efficacy of FORTESTA in males <18 years old have not been established

DOSAGE AND ADMINISTRATION:

CONTRAINDICATIONS:
Men with carcinoma of the breast or known or suspected prostate cancer.
Pregnant or breastfeeding women. Testosterone may cause fetal harm.

WARNINGS AND PRECAUTIONS:

• Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH
• Avoid unintentional exposure of women or children to FORTESTA. Secondary exposure to testosterone can produce signs of virilization. FORTESTA should be discontinued until the cause of virilization is identified
• Exogenous administration of androgens may lead to azoospermia
• Edema with or without congestive heart failure (CHF) may be a complication in patients with pre-existing cardiac, renal, or hepatic disease
• Sleep apnea may occur in those with risk factors
• Monitor serum testosterone, prostate specific antigen (PSA), hemoglobin, hematocrit, liver function tests and lipid concentrations periodically
• FORTESTA is flammable until dry

ADVERSE REACTIONS:
The most common adverse reaction (incidence ≥ 3%) is skin reactions at the application site (16.1%).

DRUG INTERACTIONS:

• Androgens may decrease blood glucose and insulin requirement in diabetic patients.
• Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of International Normalized Ratio (INR) and prothrombin time is recommended.
• Use of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease.

USE IN SPECIFIC POPULATIONS:
There are insufficient long-term safety data in geriatric patients using FORTESTA to assess the potential risks of cardiovascular disease and prostate cancer.

Review PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

DOSAGE FORMS AND STRENGTHS:
FORTESTA (testosterone) Gel is supplied as a metered-dose pump. One pump actuation delivers 10 mg of testosterone.

SOURCE:
Package insert data:
Manufactured by: Pharbil Waltrop GmbH, Im Wirrigen 25, 45731 Waltrop, Germany
Manufactured for: Endo Pharmaceuticals Inc., 100 Endo Boulevard, Malvern, PA 19355

© 2012 Endo Pharmaceuticals Inc. All rights reserved.
Rev: 12/2012

Striant® is a white to off-white colored, monoconvex, tablet-like, mucoadhesive buccal system. Striant® adheres to the gum tissue above the incisors, with the flat surface facing the cheek mucosa.

The active ingredient in Striant® is testosterone. Each buccal system contains 30 mg of testosterone. Testosterone USP is practically white crystalline powder chemically described as 17-beta hydroxyandrost-4-en-3one.

CLINICAL PHARMACOLOGY
Striant® delivers physiologic amounts of testosterone to the systemic circulation, thereby producing circulating testosterone concentrations in hypogonadal males that approximate physiologic levels seen in healthy young men (300 - 1050 ng/dL).

INDICATIONS AND USAGE:
Striant® is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone:

Primary hypogonadism (congenital or acquired) - testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchidectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone levels and gonadotropins (FSH, LH) above the normal range.

Hypogonadotropic hypogonadism (congenital or acquired) -- idiopathic gonadotropin or LHRH deficiency, or pituitary hypothalamic injury from tumors, trauma, or radiation. These patients have low serum testosterone levels but have gonadotropins in the normal or low range.

------------------------------------------------------------------------
DOSAGE AND ADMINISTRATION:
------------------------------------------------------------------------
The recommended dosing schedule for Striant® is the application of one buccal system (30 mg) to the gum region twice daily; morning and evening (about 12 hours apart). Striant® should be placed in a comfortable position just above the incisor tooth (on either side of the mouth). With each application, Striant® should be rotated to alternate sides of the mouth.

Upon opening the packet, the rounded side surface of the buccal system should be placed against the gum and held firmly in place with a finger over the lip and against the product for 30 seconds to ensure adhesion. Striant® is designed to stay in position until removed. If the buccal system fails to properly adhere to the gum or should fall off during the 12-hour dosing interval, the old buccal system should be removed and a new one applied. If the buccal system falls out of position within 4 hours prior to the next dose, a new buccal system should be applied and it may remain in place until the time of next regularly scheduled dosing.

Patients should take care to avoid dislodging the buccal system. Patients should check to see if Striant® is in place following toothbrushing, use of mouthwash and consumption of food or alcoholic/non-alcoholic beverages. Striant® should not be chewed or swallowed. To remove Striant®, gently slide it downwards from the gum towards the tooth to avoid scratching the gum.

CONTRAINDICATIONS:
Androgens are contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate.

Striant® is not indicated for use in women, and must not be used in women. Testosterone supplements may cause fetal harm.

Striant® should not be used in patients with known hypersensitivity to any of its ingredients, including testosterone USP that is chemically synthesized from soy.

WARNINGS AND PRECAUTIONS:
WARNINGS:

1. Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) have been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with testosterone enanthate, which elevates blood levels for prolonged periods, has produced multiple hepatic adenomas. Testosterone is not known to produce these adverse effects.
2. Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hyperplasia and prostatic carcinoma.
3. Geriatric patients and other patients with clinical or demographic characteristics that are recognized to be associated with an increased risk of prostate cancer should be evaluated for the presence of prostate cancer prior to initiation of testosterone replacement therapy. In men receiving testosterone replacement therapy, surveillance for prostate cancer should be consistent with current practices for eugonadal men
4. Edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required.
5. Gynecomastia frequently develops and occasionally persists in patients being treated for hypogonadism.
6. The treatment of hypogonadal men with testosterone esters may potentiate sleep apnea in some patients especially those with risk factors such as obesity or chronic lung diseases.

PRECAUTIONS:
Striant® is applied to the upper gum just above the incisor tooth on either side of the mouth. Long-term data on gum safety is available for 117 patients and 51 patients with at least 6 months and 1 year of exposure, respectively. While the available data supports the overall oral safety of Striant®, longer-term data is not currently available and studies continue. Until such longer-term data become available, it is recommended that patients regularly inspect their own gum region where Striant® is applied. Any abnormal finding should be brought promptly to the attention of the patient's physician. In such circumstances, dental consultation may be appropriate.

General
The physician should instruct patients to report any of the following:

Too frequent or persistent erections of the penis.
Any nausea, vomiting, changes in skin color, or ankle swelling.
Breathing disturbances, including those associated with sleep.

Information for Patients
Advise patients to carefully read the attached patient leaflet accompanying each carton of Striant® blister packaged tablets.

Advise patients to regularly inspect the gum region where they apply Striant® and to report any abnormality to their health care professional.

Laboratory Tests
Hemoglobin and hematocrit levels should be checked periodically (to detect polycythemia) in patients on long-term androgen therapy.
Liver function, prostate specific antigen (PSA), cholesterol and high-density lipoprotein should be checked periodically.
Serum total testosterone concentrations may be checked four to twelve weeks after initiating treatment with Striant®. To capture the maximum serum concentration, an early morning sample (just prior to applying the A.M. dose) is recommended. In the infrequent circumstance where the total testosterone concentration in this sample is excessive, therapy with Striant® should be discontinued and an alternative treatment considered.

Drug interactions
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 therefore, insulin requirements.

Corticosteroids
Concurrent administration of testosterone with ACTH or corticosteroids may enhance edema formation and should be administered cautiously, particularly in patients with cardiac or hepatic disease.

Drug/Laboratory Test Interactions
Androgens may decrease levels of thyroxin-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. 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. In mice, the implant induced cervical-uterine tumors, 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 the liver in rats.

Human data
There were 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.

Striant® has been evaluated in patients for 1 year without reports of cancer related to the product. However, safety in patients beyond 1 year has not been established.

Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hyperplasia and prostatic carcinoma.

Geriatric patients and other patients with clinical or demographic characteristics that are recognized to be associated with an increased risk of prostate cancer should be evaluated for the presence of prostate cancer prior to initiation of testosterone replacement therapy.

In men receiving testosterone replacement therapy, surveillance for prostate cancer should be consistent with current practices for eugonadal men.

Pregnancy Category X

Teratogenic Effects
Striant® is not indicated for women and must not be used in women.

Labor and Delivery
Striant® is not indicated for women and must not be used in women.

Nursing Mothers
Striant® is not indicated for women and must not be used in women.

Pediatric Use
Safety and effectiveness in pediatric male patients below the age of 18 have not yet been established

Geriatric Use
Of the total number of subjects in clinical studies of Striant®, 51 patients (16.5 percent) were 65 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. However, in Study 1, in patients 65 years of age and older, the total testosterone C avg(0-24) value was higher by 12.7% compared to patients less than 65 years of age. In addition, the total T to DHT area-under-the curve ratio was lower in the older population compared to the younger population by 15.6%. These differences may not be clinically significant.

DOSAGE FORMS AND STRENGTHS:
Striant® (testosterone buccal system) is for buccal administration only. It contains testosterone, a Schedule III controlled substance as defined by the Anabolic Steroids Control Act.

Striant® is supplied in transparent blister packs containing 10 doses. It is white to off- white colored with a flat edge on one side and a convex surface on the other.

Each Striant® buccal system contains 30 mg of testosterone and is supplied as follows:
NDC Number    Strength     Package Size
55056-3060-1    30 mg        6 blister packs, 10 buccal systems per blister; 30 mg per buccal system

SOURCE:
Package insert data:
Manufactured by: Mipharm S.p.A, Milan, Italy
Manufactured for: Columbia Laboratories, Inc., Livingston, NJ 07039
© 2003 Columbia Laboratories, Inc.
Rev: 11/2009

One 5 g or two 5 g tubes of Testim® contains 50 mg or 100 mg of testosterone, respectively, to be applied daily to the skin’s surface. Approximately 10% of the applied testosterone dose is absorbed across skin of average permeability during a 24-hour period.

The active pharmacological ingredient in Testim® is testosterone.

INDICATIONS AND USAGE:
Testim® is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone:

1] Primary hypogonadism (congenital or acquired): testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone levels and gonadotropins (FSH, LH) above the normal range.

2] Hypogonadotropic hypogonadism (congenital or acquired): idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum levels but have gonadotropins in the normal or low range.

Testim® has not been clinically evaluated in males under 18 years of age.

DOSAGE AND ADMINISTRATION:
The recommended starting dose of Testim® is 5 g of gel (one tube) containing 50 mg of testosterone applied once daily (preferably in the morning) to clean, dry intact skin of the shoulders and/or upper arms (area of application should be limited to the area that will be covered by the patient’s short sleeve t-shirt). Morning serum testosterone levels should then be measured approximately 14 days after initiation of therapy to ensure proper serum testosterone levels are achieved. If the serum testosterone concentration is below the normal range, or if the desired clinical response is not achieved, the daily Testim® dose may be increased from 5 g (one tube) to 10 g (two tubes) as instructed by the physician.

Upon opening the tube the entire contents should be squeezed into the palm of the hand and immediately applied to the shoulders and/or upper arms (area of application should be limited to the area that will be covered by the patient’s short sleeve t-shirt). Application sites should be allowed to dry for a few minutes prior to dressing. Hands should be washed thoroughly with soap and water after Testim® has been applied.

In order to prevent transfer to another person, clothing should be worn to cover the application sites. If direct skin-to-skin contact with another person is anticipated, the application sites must be washed thoroughly with soap and water.

In order to maintain serum testosterone levels in the normal range, the sites of application should not be washed for at least two hours after application of Testim®.

Do not apply Testim® to the genitals or to the abdomen.

CONTRAINDICATIONS:
Androgens are contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate. Testim® is not indicated for use in women, has not been evaluated for use in women, and must not be used in women.

Pregnant and nursing women should avoid skin contact with Testim® application sites on men. Testosterone may cause fetal harm. Testosterone exposure during pregnancy has been reported to be associated with fetal abnormalities. In the event that unwashed or unclothed skin to which Testim® has been applied comes in direct contact with the skin of a pregnant or nursing woman, the general area of contact on the woman should be immediately washed with soap and water.

Testim® should not be used in patients with known hypersensitivity to any of its ingredients, including testosterone USP that is chemically synthesized from soy.

DOSAGE FORMS AND STRENGTHS:
Testim® contains testosterone, a Schedule III controlled substance as defined by the Anabolic Steroids Control Act. Testim® is supplied in unit-dose tubes in cartons of 30. Each tube contains 50 mg testosterone in 5 g of gel, and is supplied as follows:
NDC Number         Strength                  Package Size
54868-4989-0         1% (50 mg)                30 tubes: 5 g per tube

SOURCE:
Package insert data:
Manufactured for:
Auxilium Pharmaceuticals, Inc.
Malvern, PA 19355 USA
By: DPT Laboratories, Ltd.
San Antonio, TX 78215

Rev: September 2009

Androgens are steroids that develop and maintain primary and secondary male sex characteristics. Testosterone is a member of this class.

INDICATIONS AND USAGE:
MALES
Androgens are indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone.

1] Primary hypogonadism (congenital or acquired) - testicular failure due to cryptorchidism, bilateral torsion,orchitis, vanishing testes syndrome; or orchidectomy.

2] Hypogonadotrophic hypogonadism (congenital or acquired) - idiopathic or 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.

1] 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 package insert for WARNINGS).

DOSAGE AND ADMINISTRATION:
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.

WARNINGS AND PRECAUTIONS:
See package insert.

DOSAGE FORMS AND STRENGTHS:
Testosterone pellets of 75mg. One pellet per vial in boxes of 10 (NDC: 43773-1001-2) and 100 (NDC: 43773-1001-3). Store in a cool dry place.

SOURCE:
Package insert data:
Manufactured by Bartor Pharmacal
70 High St., Rye N.Y. 10580
Rev. 1/09