Testopel

Mechanism of Action

Endogenous androgen; promotes growth and development of male sex organs and maintains secondary sex characteristics in androgen-deficient males

Absorption

Bioavailability: IM, slowly absorbed

Duration: 2-4 wk (IM)

Peak plasma time: 24 hr (IM)

Distribution

Protein bound: 98%

Vd: 75-122 L/kg

Metabolism

Metabolized in liver to glucuronic and sulfuric acid conjugates

Metabolites: Testosterone glucuronic conjugate (activity unknown), testosterone sulfuric acid conjugate (activity unknown), testosterone-19-d3

Elimination

Half-life: 10-100 min

Renal clearance: 2 L/min

Excretion: Urine (90%), feces (6%)

Topical:

Testosterone is a prescription medication used to treat low testosterone levels in men who do not produce enough natural testosterone.

Injectable:

Testosterone is a prescription medication used to treat low testosterone levels in men who do not produce enough natural testosterone. Injectable forms of testosterone may also be used to treat delayed puberty in adolescent males. Testosterone may also be administered to women to treat certain types of cancer.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with testosterone. See the “Testosterone Precautions” section.

Topical:

Common side effects of topical testosterone include the following:

• Breast enlargement
• Decreased sexual desire
• Acne
• Hair loss
• Hot flashes
• Depression
• Changes in mood
• Nervousness
• Headache
• Weakness
• Insomnia
• Dry skin
• Changes in the ability to taste or smell
• Skin irritation at the site of application

Injectable:

Common side effects of injectable testosterone include the following:

• Nausea and vomiting
• Changes in skin color
• Ankle swelling
• Increased calcium levels in the blood
• Enlarged breasts
• Enlarged prostate in men
• Deepening of the voice, the appearance of facial hair, and acne in women

This is not a complete list of testosterone side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Testosterone falls into category X. It has been shown that women taking testosterone during pregnancy may have babies born with problems. There are no situations where the benefits of the medication for the mother outweigh the risks of harm to the baby. Testosterone should never be used by pregnant women.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your age
• your gender

Topical:

The recommended dose of testosterone gel for the treatment of hypogonadism in males is 50 to 100 mg daily applied to the skin. The recommended dose of the nasal formulation of testosterone is 11 mg daily. The recommended dose of the buccal system of testosterone is 30 mg twice daily. The recommended dose of the testosterone transdermal patch is 4 to 6 mg daily.

Injectable:

The recommended dose of testosterone for the treatment of hypogonadism in males is 50 to 400 mg every 2 to 4 weeks.

The recommended dose of testosterone for the treatment of delayed puberty in adolescent males is 50 to 200 mg every 2 to 4 weeks for 4 to 6 months.

Testopel® (testosterone pellets) are cylindrically shaped pellets 3.2mm (1/8 inch) in diameter and approximately 9mm in length. Each sterile pellet weighs approximately 78mg (75mg testosterone) and is ready for implantation.

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

Structural formula for testosterone follows:

INGREDIENTS

Each Testopel® (testosterone pellets) for subcutaneous implantation contains 75mg testosterone. In addition each pellet contains the following inactive ingredients: stearic acid NF 0.97mg and polyvinylpyrrolidone USP 2mg.

Testopel® (testosterone pellets) consist of crystalline testosterone. When implanted subcutaneously, the pellets slowly release the hormone for a long acting androgenic effect.

MALES

Androgens are indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone.

• a.Primary hypogonadism (congenital or acquired) - testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testes syndrome; or orchiectomy.
• b.Hypogonadotropic hypogonadism (congenital or acquired) - gonadotropic LHRH deficiency, or pituitary - hypothalamic injury from tumors, trauma or radiation.

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

Safety and efficacy of Testopel® (testosterone pellets) in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.

• c.Androgens may be used to stimulate puberty in carefully selected males with clearly delayed puberty. These patients usually have a familial pattern of delayed puberty that is not secondary to a pathological disorder; puberty is expected to occur spontaneously at a relatively late date. Brief treatment with conservative doses may occasionally be justified in these patients if they do not respond to psychological support. The potential adverse effect on bone maturation should be discussed with the patient and parents prior to androgen administration. An x-ray of the hand and wrist to determine bone age should be taken every 6 months to assess the effect of treatment on epiphyseal centers (see WARNINGS).

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.

GENERAL

Pellet implantation is much less flexible for dosage adjustment than is oral administration of or intramuscular injections of oil solutions or aqueous suspensions. Therefore, great care should be used when estimating the amount of testosterone needed.

In the face of complications where the effects of testosterone should be discontinued, the pellets would have to be removed.

INFORMATION FOR THE PATIENT

The physician should instruct patients to report any of the following side effects of androgens:

Adult or adolescent males: Too frequent or persistent erections of the penis. Any nausea, vomiting, changes in skin color, ankle swelling.

Implantation site infection and/or pellet extrusion can occur and may be associated with implant site induration, inflammation, fibrosis, bleeding, bruising, wound drainage, pain, itching, and pellet extrusion. (see WARNINGS and ADVERSE REACTIONS).

Any male adolescent patient receiving androgens for delayed puberty should have bone development checked every 6 months.

LABORATORY TESTS

1. Because of the hepatotoxicity associated with the use of 17-alpha-alkylated androgens, liver function tests should be obtained periodically.
2. Periodic (every 6 months) x-ray examinations of the bone age should be made during treatment of prepubertal males to determine the rate of bone maturation and the effects of androgen therapy on the epiphyseal centers.
3. Hemoglobin and hematocrit should be checked periodically for polycythemia in patients who are receiving high doses of androgens.

DRUG INTERACTIONS

1. Anticoagulants. C-17 substituted derivatives of testosterone, such as methandrostenolone have been reported to decrease the anticoagulant requirements of patients receiving oral anticoagulants. Patients receiving oral anticoagulant therapy require close monitoring, especially when androgens are started or stopped.
2. Oxyphenbutazone. Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone.
3. Insulin. In diabetic patients the metabolic effects of androgens may decrease blood glucose and insulin requirements.

DRUG/LABORATORY TEST INTERFERENCES

Androgens may decrease levels of thyroxine-binding globulin, resulting in decreased total 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. The implant induced cervical-uterine tumors in mice, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of liver in rats.

Human Data. There are rare reports of hepatocellular carcinoma in patients receiving long-term therapy with androgens in high doses. Withdrawal of the drugs did not lead to regression of the tumors in all cases.

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

PREGNANCY

Teratogenic Effects. Pregnancy Category X (see CONTRAINDICATIONS).

NURSING MOTHERS

It is not known whether androgens are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from androgens, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

PEDIATRIC USE

Androgen therapy should be used very cautiously in children and only by specialists who are aware of the adverse effects on bone maturation. Skeletal maturation must be monitored every 6 months by an x-ray of the hand and wrist (see INDICATIONS AND USAGE and WARNINGS).

Applies to testosterone: buccal patch extended release

Other dosage forms:

• intramuscular injectable, intramuscular oil, intramuscular solution, intramuscular suspension
• nasal gel/jelly
• transdermal patch extended release

Along with its needed effects, testosterone (the active ingredient contained in Testopel) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking testosterone:

• Pain, redness, or swelling in the arm or leg
• trouble breathing

Get emergency help immediately if any of the following symptoms of overdose occur while taking testosterone:

• Blurred vision
• headache
• seizures
• slurred speech
• sudden and severe inability to speak
• temporary blindness
• weakness in the arm or leg on one side of the body, sudden and severe

Some side effects of testosterone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Gum or mouth irritation

• Bad, unusual, or unpleasant (after) taste
• bleeding gums
• blemishes on the skin
• breast pain
• change in taste
• cough
• crying
• depersonalization
• diarrhea
• discouragement
• dizziness
• dry mouth
• dysphoria
• enlarged breasts
• euphoria
• fear or nervousness
• feeling sad or empty
• gum pain or blisters
• hoarseness
• indigestion
• irritability
• itching skin
• loss of appetite
• loss of interest or pleasure
• lower back or side pain
• mouth ulcers
• nausea
• noisy breathing
• painful or difficult urination
• paranoia
• passing of gas
• pounding in the ears
• quick to react or overreact emotionally
• rapidly changing moods
• redness and swelling of the gums
• slow or fast heartbeat
• stinging of the lips
• stomach cramps, pain, fullness, or discomfort
• swelling of the gums
• swelling of the nose
• tiredness
• toothache
• trouble concentrating
• trouble sleeping
• unusual tiredness or weakness
• vomiting