Androderm

Store testosterone at room temperature.

Keep this and all medicines out of the reach of children.

Used pumps, packets, or storage containers for this medication should be disposed of in household trash in a manner that prevents accidental application or ingestion by children or pets.

Follow all directions on your prescription label. Never use testosterone topical in larger amounts, or for longer than prescribed.

Misuse of testosterone can cause dangerous or irreversible effects, such as enlarged breasts, small testicles, infertility, high blood pressure, heart attack, stroke, liver disease, bone growth problems, addiction, and mental effects such as aggression and violence.

Do not share this medicine with another person.

Different brands of testosterone topical have different instructions for use. Not every brand of this medicine is used on the same skin areas. Some brands are applied to the shoulder, upper arm, or stomach. Other brands are applied to the thighs or to the underarms. Carefully follow the patient instructions provided with your medicine.

Do not apply testosterone topical to your penis or scrotum. Some brands of this medicine should also not be applied to the back, chest, or stomach areas. Apply this medicine only to the skin areas recommended for your specific brand of testosterone topical.

Apply testosterone gel to dry skin after showering or bathing. Allow the medicine to dry for at least 5 minutes before you dress.

Wash your hands with soap and water after applying the gel.

Cover treated skin areas with clothing to keep from getting this medicine on other people. If someone else does come into contact with a treated skin area, they must wash the contact area right away with soap and water.

Apply the transdermal skin patch to a flat, clean, dry, and undamaged area of skin on your back, stomach, upper arm, or thigh. Wear the patch for 24 hours and then replace it with a new patch. Choose a different skin area each time you put on a new patch. Do not use the same skin area twice in a 7-day period.

While using testosterone topical, you may need frequent blood tests.

Use testosterone topical regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Store at room temperature away from moisture and heat.

Keep each skin patch in the foil pouch until you are ready to use it. Do not use a skin patch that has been cut or damaged After removing a skin patch, fold it closed with the sticky side in, and throw it away in a place where pets and children cannot reach it.

Apply the gel or skin patch as soon as you remember. Skip the missed dose if it is almost time to apply your next dose. Do not use extra patches or gel to make up the missed dose.

If a skin patch falls off in the morning, reapply it. If it does not stick well, apply a new patch. If the patch falls off in the afternoon and cannot be reapplied, wait until your regular patch replacement time in the evening before putting on a new patch.

Testosterone transdermal patch is used for the treatment of males whose bodies do not make enough natural testosterone, a condition called hypogonadism. Testosterone is a male hormone responsible for the growth and development of the male sex organs and maintenance of secondary sex characteristics.

This medicine is available only with your doctor's prescription.

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and check for any problems or unwanted effects that may be caused by this medicine. Blood tests will be needed to check for unwanted effects.

This medicine should not be used by women who are pregnant or might become pregnant. Testosterone may cause birth defects if a pregnant woman comes in contact with the patch or medicine. Make sure your doctor knows if your sexual partner is pregnant. If a pregnancy occurs while you are using this medicine, tell your doctor right away.

If a woman comes in contact with the patch, wash the skin area right away with soap and water to remove all the medicine. If the patch sticks to a woman, remove the patch right away and wash her skin thoroughly with soap and water.

If your female partner starts to have male-like changes such as unusual hair growth or increased acne, check with your doctor.

This medicine may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose. Call your doctor for instructions.

This medicine may increase the risk of prostate cancer, especially in older men. Make sure your doctor knows if you have prostate cancer, or if anyone in your family has prostate cancer.

This medicine may cause blood clotting problems. Tell your doctor right away if you have pain, redness, or swelling in the arm or leg, shortness of breath, sharp pains in the chest, or trouble breathing.

This medicine may increase your risk of having heart or blood vessel problems, including a heart attack or stroke. Tell your doctor right away if you have chest pain that may spread to your arms, jaw, back, or neck, faintness, headache, nausea, vomiting, trouble breathing, trouble seeing or speaking, or unusual sweating.

In some cases, this medicine may decrease the amount of sperm men make and affect their ability to have children. If you plan to have children, talk with your doctor before using this medicine.

Tell your doctor if you experience too frequent erection of the penis, nausea, vomiting, yellowing of your skin or the whites of your eyes, or swelling of the ankle.

This medicine may cause swelling of the breasts (gynecomastia) and breast pain in some patients. If you have questions about this, talk to your doctor.

This medicine may cause changes in the level of cholesterol and fats in your blood. If this condition occurs, your doctor may give you a medicine to adjust the cholesterol and fats. Talk to your doctor if you have concerns.

This medicine contains aluminum that may cause skin burns at the patch site if you have a procedure called a magnetic resonance imaging (MRI) scan while you are wearing the patch. You must remove the patch before your MRI to prevent skin burns.

Check with your doctor immediately if mild, burn-like skin blisters, redness, itching, or swelling occurs at the site of application during or after treatment.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Pimples (acne).
• Loose stools (diarrhea).
• Emotional ups and downs.
• Change in sex interest.
• Change in sex ability.
• Feeling tired or weak.
• Not able to sleep.
• Irritation where this medicine is used.
• Back pain.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• Store at room temperature. Do not freeze.
• Store in a dry place. Do not store in a bathroom.
• Store in pouch until ready for use.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Androderm is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone.

• Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism,  bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter Syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (FSH, LH) above the normal range.
  
• Hypogonadotropic hypogonadism (congenital or acquired): 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.

Limitations of use

• Safety and efficacy of Androderm in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.
  
• Safety and efficacy of Androderm in males less than 18 years old have not been established [see Use  in Specific Populations (8.4)].

5.1 Worsening of Benign Prostatic Hyperplasia and Potential Risk of Prostate Cancer

• Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH.
  
• Patients treated with androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating treatment. It is appropriate to re-evaluate patients 3 to 6 months after initiation of treatment, and then in accordance with prostate cancer screening practices [see Contraindications (4)].

5.2 Polycythemia

Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating testosterone treatment. It is appropriate to re-evaluate the hematocrit 3 to 6 months after starting testosterone treatment, and then monitor annually. Discontinue testosterone therapy if the hematocrit becomes elevated. Testosterone therapy may be restarted when the hematocrit decreases to an acceptable level. An increase in red blood cell mass may increase the risk of thromboembolic events.

5.3 Venous Thromboembolism

There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products such as Androderm. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with Androderm and initiate appropriate workup and management [see Adverse Reactions (6.2)].

5.4 Cardiovascular Risk

Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE) such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use Androderm.

5.5 Abuse of Testosterone and Monitoring of Serum Testosterone Concentrations

Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions [see Drug Abuse and Dependence (9)].

If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events.

5.6 Use in Women and Children

Women and children should not use Androderm. Use in women and children has not been studied with Androderm.

Due to lack of controlled studies in women and potential virilizing effects, Androderm is not indicated for use in women and children [see Contraindications (4) and Use in Specific Populations (8.1, 8.3, 8.4)].

5.7 Potential for Adverse Effects on Spermatogenesis

At large doses of exogenous androgens, including Androderm, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH) that could lead to adverse effects on semen parameters including reduction of sperm count.

5.8 Hepatic Adverse Effects

Prolonged use of high doses of orally active 17-alpha-alkyl androgens (methyltestosterone) has 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 intramuscular testosterone enanthate has produced multiple hepatic adenomas. Androderm is not known to cause these adverse effects.

5.9 Edema

Androgens, including Androderm, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal, or hepatic disease [see Adverse Reactions (6)].

5.10 Gynecomastia

Gynecomastia may develop and persist in patients being treated with androgens, including Androderm, for hypogonadism.

5.11 Sleep Apnea

The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity and chronic lung disease.

5.12 Lipids

Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy.

5.13 Hypercalcemia

Androgens, including Androderm, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients.

5.14 Decreased Thyroxine-Binding Globulin

Androgens, including Androderm, may decrease concentrations of thyroxine-binding globulins, resulting in decreased total T4 serum concentration and increased resin uptake of T3 and T4. Free thyroid hormone concentration remains unchanged and there is no clinical evidence of thyroid dysfunction.

5.15 Magnetic Resonance Imaging (MRI)

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. 

12.1 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. Testosterone and DHT are necessary for the normal development of secondary sex characteristics.

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 Syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

12.2 Pharmacodynamics

No specific pharmacodynamic studies were conducted using Androderm.

12.3 Pharmacokinetics

Absorption

Androderm delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate the normal concentration range (300 - 1030 ng/dL) seen in healthy men. Androderm provides a continuous daily dose of testosterone in a self-contained transdermal system. Following Androderm application, testosterone is continuously absorbed during the 24-hour dosing period with a median (range) Tmax of 8 (4-12) hours.

Distribution

Circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free) and the rest is bound to albumin and other proteins.

Metabolism

Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are estradiol and dihydrotestosterone (DHT).

During steady-state pharmacokinetic studies in hypogonadal men treated with Androderm, the average DHT:T and E2:T ratios were approximately 1:10 and 1:200, respectively.

Excretion

There is considerable variation in the half-life of testosterone as reported in the literature, ranging from 10 to 100 minutes. About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver.

Upon removal of the Androderm systems, serum testosterone concentrations decrease with an apparent half-life of approximately 70 minutes. Hypogonadal concentrations are reached within 24 hours following system removal. There is no accumulation of testosterone during continuous treatment.

Effect of Showering

In a two-way crossover study, the effects of showering on the pharmacokinetics of total testosterone following a single application of Androderm 4 mg/day were assessed in 16 hypogonadal males. Showering 3 hours after application of Androderm increased Cavg by 0.5% and decreased Cmax by 0.4% respectively, as compared to not showering. The systemic exposure to Androderm was similar following applications with or without showering 3 hours after application.

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 Androderm) 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

Summary of Use during Lactation

Limited data indicate that a low-dose (100 mg) subcutaneous testosterone pellet given to a nursing mother appears not to increase milk testosterone levels markedly. Testosterone has low oral bioavailability because of extensive first-pass metabolism, so it is unlikely to affect the breastfed infant. One breastfed infant seemed not to be adversely affected by low-dose maternal testosterone therapy.

Drug Levels

Maternal Levels. A woman received testosterone for depressive symptoms sublingually (drops, dose unspecified), vaginally (cream, dose unspecified), and subcutaneously (pellet, 100 mg). Foremilk samples were obtained at various times over the first 24 hours after administration of the sublingual and vaginal administration and on days 2, 3 and 7 after the implanting of the testosterone pellet. The highest milk level recorded following the pellet implantation was 101 ng/L on day 7. Testosterone levels in breastmilk were not increased above baseline with any of these preparations.[1]

Infant Levels. After implantation of a 100 mg pellet of testosterone subcutaneously in a postpartum woman, serum levels of testosterone in her breastfed infant (extent and age not stated) were <100 mcg/L on days 2, 3 and 7, and at 5 months after the implanting of the testosterone pellet.[1]

Effects in Breastfed Infants

An infant (age not stated) was breastfed (extent not stated) after implantation of 100 mg of testosterone subcutaneously. No adverse effects were noted in the infant over a 5-month period.[1]

Effects on Lactation and Breastmilk

Supraphysiologic serum levels of testosterone, either from a tumor[2][3] or from exogenously administered testosterone,[4] reduces milk production in postpartum women. Testosterone alone reduces serum prolactin;[4] however, when given in combination with estrogen and progestin, serum prolactin levels are not markedly reduced.[5] Testosterone was previously used therapeutically to suppress lactation, usually in combination with an estrogen.[4][5][6][7][8][9][10]

References

1. Glaser RL, Newman M, Parsons M et al. Safety of maternal testosterone therapy during breast feeding. Int J Pharm Compound. 2009;13:314-7.

2. Betzold CM, Hoover KL, Snyder. Delayed lactogenesis II: a comparison of four cases. J Midwifery Womens Health. 2004;49:132-7. PMID: 15010666

3. Hoover KL, Barbalinardo LH, Platia MP. Delayed lactogenesis II secondary to gestational ovarian theca lutein cysts in two normal singleton pregnancies. J Hum Lact. 2002;18:264-8. PMID: 12192962

4. Weinstein D, Ben-David M, Polishuk WZ. Serum prolactin and the suppression of lactation. Br J Obstet Gynaecol. 1976;83:679-82. PMID: 788774

5. Welti H, Paiva F, Felber JP. Prevention and interruption of postpartum lactation with bromocriptine (Parlodel) and effect on plasma prolactin, compared with a hormonal preparation (Ablacton). Eur J Obstet Gynecol Reprod Biol. 1979;9:35-9. PMID: 570523

6. Schwartz DJ, Evans PC, Garcia CR et al. A clinical study of lactation suppression. Obstet Gynecol. 1973;42:599-606. PMID: 4582587

7. Ng KH, Lee KH. Inhibition of postpartum lactation with single-dose drugs. Aust N Z J Obstet Gynaecol. 1972;12:59-61. PMID: 4502478

8. McNicol E, Struthers JO. A combined/oestrogen/progestogen/testosterone agent for the inhibition of lactation. Br J Clin Pract. 1972;26:567-8. PMID: 4567863

9. Morris JA, Creasy RK, Hohe PT. Inhibition of puerperal lactation. Double-blind comparison of chlorotrianesene, testosterone enanthate with estradiol valerate and placebo. Obstet Gynecol. 1970;36:107-14. PMID: 4912251

10. Iliya FA, Safon L, O'Leary JA. Testosterone enanthate (180 mg.) and estradiol valerate (8 mg.) for suppression of lactation: a double-blind evaluation. Obstet Gynecol. 1966;27:643-5. PMID: 5949195