Estandron Prolongado

Estradiol Benzoate:

• Estandron Prolongado information
• Estandron Prolongado indications
• Estandron Prolongado warnings
• Estandron Prolongado intake guidelines
• Estandron Prolongado dosage
• Estandron Prolongado overdose
• Estandron Prolongado missed dose
• Estandron Prolongado side effects
• Estandron Prolongado drug reactions
• Estandron Prolongado (Estradiol Benzoate) reviews

Estandron Prolongado information

Estandron Prolongado (Estradiol Benzoate) is a female sex hormone that regulates many functions in the female organism. This medicine is currently available under the form of tablets in two concentrations - 1 mg and 2 mg, respectively.

Estandron Prolongado indications

Estandron Prolongado (Estradiol Benzoate) is used for the treatment of menopausal symptoms such as vaginal dryness, irritation or burning, or hot flushes - other symptoms that are not listed here may be treated with this medicine as well. Also, this pharmaceutical preparation can be used as a prophylactic agent for the prevention of a medical condition known as osteoporosis in both female and male patients. In some cases, this medicine may also be employed in conjunction with other drugs as part of the treatment for certain types of cancer, both in the case of women and men.

There may be other uses for Estandron Prolongado (Estradiol Benzoate), which are not covered in this leaflet. If you are interested to find out more about the possible uses of this product, it is recommended that you consult with a pharmacist or a specialized physician.

Estandron Prolongado warnings

Estandron Prolongado (Estradiol Benzoate) should not be administered to patients that are suffering from any type of disorder involving blood clots, or from circulatory / cardiac disorders. Patients who present an undiagnosed, abnormal vaginal bleeding may not start taking this medicine until they undergo medical examination and receive their physician's approval. Also, patients that have uterine cancer, breast cancer or any type of hormone-dependant cancer may not start a treatment with Estandron Prolongado (Estradiol Benzoate).

Before you start a therapy course with this drug, it is strongly advised to inform your personal physician of any health problems you may be suffering from. In particular, affections such as hypertension, heart disease, angina, high triglyceride / cholesterol levels, renal or hepatic disease, asthma, migraines, epilepsy (or any other disorder involving seizures), diabetes or gallbladder disease should be mentioned, as well as past surgical procedures such as a hysterectomy. Patients suffering from these conditions may require special dosage adjustments or monitoring during the treatment.

Estandron Prolongado (Estradiol Benzoate) may not be administered during pregnancy. Also, for the duration of the therapy you will need to employ an effective, non-hormonal contraceptive method.

Pharmaceutical products based on Estradiol (including Estandron Prolongado (Estradiol Benzoate)) increase the patients' risk of developing an affection known as endometrial hyperplasia. This can be countered by administration of progestin medication. It is recommended that you consult with your doctor for more information.

Estandron Prolongado intake guidelines

You need to take Estandron Prolongado (Estradiol Benzoate) exactly as directed by your health care specialist. You may take the tablets with a glass of water or with food to reduce stomach upset; however you may not chew, crush or break the tablets.

While following a treatment course with Estandron Prolongado (Estradiol Benzoate) you will need to undergo regular medical examination, typically on a monthly basis. Also, you will need to regularly self-examine your breasts for the presence of lumps.

Estandron Prolongado dosage

Your health care specialist will determine the Estandron Prolongado (Estradiol Benzoate) dosage appropriate for your case by taking into consideration a number of factors, most of which are characteristic to you; as such, your medication dosage is very likely to be different from that of other patients'. Because of that, you should never use the Estandron Prolongado (Estradiol Benzoate) dosage that has been prescribed to another patient - you may not obtain the desired results unless you employ the medication dosage best suited for your situation.

At the same time, your physician will inform you regarding the duration of the Estandron Prolongado (Estradiol Benzoate) therapy and the number of daily intakes. Make sure that you understand all of his or her indications. If you have trouble understanding or remembering any of the dosage directions, you should ask your physician to assist you by providing additional information.

Estandron Prolongado overdose

If an overdose with Estandron Prolongado (Estradiol Benzoate) is suspected, immediately contact the nearest hospital as the patient may need emergency medical assistance. The most common signs of an overdose are vaginal bleeding, nausea and vomiting.

Estandron Prolongado missed dose

In the event that you miss taking one of your Estandron Prolongado (Estradiol Benzoate) doses, take it when you remember before returning to your normal dosing schedule. However, you should skip taking the missed dose if it is almost time for another dose of the medicine. Consult with your physician if you have missed two or more intakes.

Estandron Prolongado side effects

Side effects of a treatment with Estandron Prolongado (Estradiol Benzoate) include nausea and vomiting, loss of appetite, swelling of the breasts, sex drive changes, impotence (in the case of men), abnormal vaginal bleeding, vaginal dryness, discomfort or pain, break-through bleeding, menstrual period changes, jaundice, sudden weakness or numbness, breast lumps. These are not all the signs and symptoms that may appear. It is best that you check with your doctor at any point during the course of your therapy if anything unusual occurs.

Although uncommon, allergic reactions to Estandron Prolongado (Estradiol Benzoate) are possible. It is strongly recommended that you cease taking the medicine and contact your personal health care provider if you begin experiencing any of the characteristic symptoms - breathing difficulties, swelling of the throat, lips, tongue or face, rashes and hives.

Estandron Prolongado drug reactions

Estandron Prolongado (Estradiol Benzoate) may interact with Phenobarbital, Phenytoin, Ritonavir, Cimetidine, Carbamazepine, Rifampin, blood thinning agents such as Warfarin or with antibiotics (Clarithromycin, Erythromycin, Ketoconazole or Itraconazole). Also, this product may interact with the herbal remedy St. John's wort. These are not all the possible drug reactions; it is best that you tell your prescriber about any other drugs you are currently taking prior to starting your treatment. In most cases, an adjustment to the medication dosage will ensure the safety of the treatment, reducing the risk of accidental interactions.

Testosterone Propionate:

• Warning: serious pulmonary oil microembolism (pome) reactions and anaphylaxis
• Recent major changes
• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Drug abuse and dependence
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Estandron Prolongado (Testosterone Propionate) reviews

WARNING: SERIOUS PULMONARY OIL MICROEMBOLISM REACTIONS AND ANAPHYLAXIS

• Serious POME reactions, involving urge to cough, dyspnea, throat tightening, chest pain, dizziness, and syncope; and episodes of anaphylaxis, including life-threatening reactions, have been reported to occur during or immediately after the administration of Estandron Prolongado (Testosterone Propionate) undecanoate injection. These reactions can occur after any injection of Estandron Prolongado (Testosterone Propionate) undecanoate during the course of therapy, including after the first dose [see Warnings and Precautions (5.1)].
• Following each injection of Estandron Prolongado (Testosterone Propionate), observe patients in the healthcare setting for 30 minutes in order to provide appropriate medical treatment in the event of serious POME reactions or anaphylaxis .
• Because of the risks of serious POME reactions and anaphylaxis, Estandron Prolongado (Testosterone Propionate) is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Estandron Prolongado (Testosterone Propionate) REMS Program [see Warnings and Precautions (5.2)].

WARNING: SERIOUS PULMONARY OIL MICROEMBOLISM (POME) REACTIONS AND ANAPHYLAXIS

See full prescribing information for complete boxed warning

• Serious POME reactions, involving urge to cough, dyspnea, throat tightening, chest pain, dizziness, and syncope; and episodes of anaphylaxis, including life-threatening reactions, have been reported to occur during or immediately after the administration of Estandron Prolongado (Testosterone Propionate) undecanoate injection. These reactions can occur after any injection of Estandron Prolongado (Testosterone Propionate) undecanoate during the course of therapy, including after the first dose (5.1).
• Following each injection of Estandron Prolongado (Testosterone Propionate), observe patients in the healthcare setting for 30 minutes in order to provide appropriate medical treatment in the event of serious POME reactions or anaphylaxis (5.1).
• Estandron Prolongado (Testosterone Propionate) is available only through a restricted program called the Estandron Prolongado (Testosterone Propionate) REMS Program (5.2).

RECENT MAJOR CHANGES

Warnings and Precautions (5.7) 10/2016

1 INDICATIONS AND USAGE

Estandron Prolongado (Testosterone Propionate) is indicated for Estandron Prolongado (Testosterone Propionate) replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous Estandron Prolongado (Testosterone Propionate).

• 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 Estandron Prolongado (Testosterone Propionate) concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [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 Estandron Prolongado (Testosterone Propionate) serum concentrations but have gonadotropins in the normal or low range.

Estandron Prolongado (Testosterone Propionate) should only be used in patients who require Estandron Prolongado (Testosterone Propionate) replacement therapy and in whom the benefits of the product outweigh the serious risks of pulmonary oil microembolism and anaphylaxis.

Limitations of use:

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

Estandron Prolongado (Testosterone Propionate) (testosterone undecanoate) injection is an androgen indicated for Estandron Prolongado (Testosterone Propionate) replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous Estandron Prolongado (Testosterone Propionate):

o Primary hypogonadism (congenital or acquired) (1)

o Hypogonadotropic hypogonadism (congenital or acquired) (1)

Estandron Prolongado (Testosterone Propionate) should only be used in patients who require Estandron Prolongado (Testosterone Propionate) 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 Estandron Prolongado (Testosterone Propionate) in men with “age-related hypogonadism” have not been established (1).
• Safety and efficacy of Estandron Prolongado (Testosterone Propionate) in males less than 18 years old have not been established (1, 8.4).

2 DOSAGE AND ADMINISTRATION

Prior to initiating Estandron Prolongado, confirm the diagnosis of hypogonadism by ensuring that serum Estandron Prolongado (Testosterone Propionate) concentrations have been measured in the morning on at least two separate days and that these serum Estandron Prolongado (Testosterone Propionate) concentrations are below the normal range.

• Prior to initiating Estandron Prolongado (Testosterone Propionate), confirm the diagnosis of hypogonadism by ensuring that serum Estandron Prolongado (Testosterone Propionate) has been measured in the morning on at least two separate days and that these concentrations are below the normal range (2).
• For intramuscular use only (2.1).
• 3 mL (750 mg) is to be injected intramuscularly at initiation, at 4 weeks, and every 10 weeks thereafter (2.1).
• Following each injection of Estandron Prolongado (Testosterone Propionate), observe patients in the healthcare setting for 30 minutes in order to provide appropriate medical treatment in the event of serious POME reactions or anaphylaxis (2.3).
• Inject Estandron Prolongado (Testosterone Propionate) deeply into the gluteal muscle following the usual precautions for intramuscular administration of oily solutions (2.3).

2.1 Dosage

Estandron Prolongado (Testosterone Propionate) is for intramuscular use only. Dosage titration is not necessary.

Inject Estandron Prolongado (Testosterone Propionate) deeply into the gluteal muscle following the usual precautions for intramuscular administration; care must be taken to avoid intravascular injection . Intravascular injection of Estandron Prolongado (Testosterone Propionate) may lead to pulmonary oil microembolism .

The recommended dose of Aveed is 3 mL (750 mg) injected intramuscularly, followed by 3 mL (750 mg) injected after 4 weeks, then 3 mL (750 mg) injected every 10 weeks thereafter.

2.2 Preparation Instructions

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Carefully remove the gray plastic cap from the top of the vial by lifting it up from the edges with your fingers or by pushing the bottom edge of the cap upward using the top of your thumb. Remove only the gray plastic cap while leaving the aluminum metal ring and crimp seal around the gray rubber stopper in place. To facilitate the removal of medication from the vial, you can draw 3 mL of air into the syringe and inject it through the gray rubber stopper into the vial to create positive pressure within the vial chamber.

Withdraw 3 mL of Estandron Prolongado (Testosterone Propionate) solution from the vial. Expel excess air bubbles from the syringe. Replace the syringe needle used to draw up the solution from the vial with a new intramuscular needle and inject. Discard any unused portion in the vial.

2.3 Administration Instructions

The site for injection for Estandron Prolongado (Testosterone Propionate) is the gluteus medius muscle site located in the upper outer quadrant of the buttock. Care must be taken to avoid the needle hitting the superior gluteal arteries and sciatic nerve. Between consecutive injections, alternate the injection site between left and right buttock.

Figure 1: Identifying the injection site

Following antiseptic skin preparation, enter the muscle and maintain the syringe at a 90° angle with the needle in its deeply imbedded position. Grasp the barrel of the syringe firmly with one hand. With the other hand, pull back on the plunger and aspirate for several seconds to ensure that no blood appears. If any blood is drawn into the syringe, immediately withdraw and discard the syringe and prepare another dose.

If no blood is aspirated, reinforce the current needle position to avoid any movement of the needle and slowly (over 60 to 90 seconds) depress the plunger carefully and at a constant rate, until all the medication has been delivered. Be sure to depress the plunger completely with sufficient controlled force. Withdraw the needle.

Immediately upon removal of the needle from the muscle, apply gentle pressure with a sterile pad to the injection site. If there is bleeding at the site of injection, apply a bandage.

Following each injection of Estandron Prolongado (Testosterone Propionate), observe patients in the healthcare setting for 30 minutes in order to provide appropriate medical treatment in the event of serious POME reactions or anaphylaxis (5.1).

Figure1

3 DOSAGE FORMS AND STRENGTHS

750 mg/3 mL (250 mg/mL) Estandron Prolongado (Testosterone Propionate) undecanoate sterile injectable solution is provided in an amber glass, single use vial with silver-colored crimp seal and gray plastic cap.

• 750 mg/3 mL (250 mg/mL) Estandron Prolongado (Testosterone Propionate) undecanoate sterile injectable solution is provided in an amber glass, single use vial with silver-colored crimp seal and gray plastic cap (3).

4 CONTRAINDICATIONS

Estandron Prolongado (Testosterone Propionate) should not be used in any of the following patients:

• Men with carcinoma of the breast or known or suspected carcinoma of the prostate .
• Women who are or may become pregnant, or who are breastfeeding. Estandron Prolongado (Testosterone Propionate) can cause fetal harm when administered to a pregnant woman. Estandron Prolongado (Testosterone Propionate) may cause serious adverse reactions in nursing infants. Exposure of a female fetus or nursing infant to androgens may result in varying degrees of virilization.
• Men with known hypersensitivity to Estandron Prolongado (Testosterone Propionate) or any of its ingredients (testosterone undecanoate, refined castor oil, benzyl benzoate).

• Men with carcinoma of the breast or known or suspected carcinoma of the prostate (4, 5.3).
• Pregnant or breastfeeding women. Testosterone may cause fetal harm (4, 8.1, 8.3).
• Known hypersensitivity to Estandron Prolongado (Testosterone Propionate) or its ingredients (testosterone undecanoate, refined castor oil, benzyl benzoate) (4).

5 WARNINGS AND PRECAUTIONS

• Monitor patients with benign prostatic hyperplasia for worsening of signs and symptoms of BPH (5.3).
• Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients using Estandron Prolongado (Testosterone Propionate) products. Evaluate patients with signs or symptoms consistent with DVT or PE. (5.5)
• Some postmarketing studies have shown an increased risk of myocardial infarction and stroke associated with use of Estandron Prolongado (Testosterone Propionate) replacement therapy. (5.6)
• Exogenous administration of androgens may lead to azoospermia (5.9).
• Edema with or without congestive heart failure may be a complication in patients with preexisting cardiac, renal, or hepatic disease (5.11).
• Sleep apnea may occur in those with risk factors (5.13).
• Monitor prostatic specific antigen (PSA), hemoglobin, hematocrit, and lipid concentrations periodically (5.3, 5.4, 5.14).

5.1 Serious Pulmonary Oil Microembolism (POME) Reactions and Anaphylaxis

Serious POME reactions, involving cough, urge to cough, dyspnea, hyperhidrosis, throat tightening, chest pain, dizziness, and syncope, have been reported to occur during or immediately after the injection of intramuscular Estandron Prolongado (Testosterone Propionate) undecanoate 1000 mg (4 mL). The majority of these events lasted a few minutes and resolved with supportive measures; however, some lasted up to several hours and some required emergency care and/or hospitalization. To minimize the risk of intravascular injection of Estandron Prolongado (Testosterone Propionate), care should be taken to inject the preparation deeply into the gluteal muscle, being sure to follow the recommended procedure for intramuscular administration .

In addition to serious POME reactions, episodes of anaphylaxis, including life-threatening reactions, have also been reported to occur following the injection of intramuscular Estandron Prolongado (Testosterone Propionate) undecanoate.

Both serious POME reactions and anaphylaxis can occur after any injection of Estandron Prolongado (Testosterone Propionate) undecanoate during the course of therapy, including after the first dose. Patients with suspected hypersensitivity reactions to Estandron Prolongado (Testosterone Propionate) should not be re-treated with Estandron Prolongado (Testosterone Propionate).

Following each injection of Estandron Prolongado (Testosterone Propionate), observe patients in the healthcare setting for 30 minutes in order to provide appropriate medical treatment in the event of serious POME reactions and anaphylaxis.

5.2 Estandron Prolongado Risk Evaluation and Mitigation Strategy (REMS) Program

Estandron Prolongado (Testosterone Propionate) is available only through a restricted program called the Estandron Prolongado (Testosterone Propionate) REMS Program because of the risk of serious POME and anaphylaxis.

Notable requirements of the Estandron Prolongado (Testosterone Propionate) REMS Program include the following:

• Healthcare providers who prescribe Estandron Prolongado (Testosterone Propionate) must be certified with the REMS Program before ordering or dispensing Estandron Prolongado (Testosterone Propionate).
• Healthcare settings must be certified with the REMS Program and have healthcare providers who are certified before ordering or dispensing Estandron Prolongado (Testosterone Propionate). Healthcare settings must have on-site access to equipment and personnel trained to manage serious POME and anaphylaxis.

Further information is available at www. AveedREMS.com or call 1-855-755-0494.

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

Patients with BPH treated with androgens are at an increased risk of worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms.

Patients treated with androgens may be at an increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating and during treatment with androgens .

5.4 Polycythemia

Increases in hematocrit, reflective of increases in red blood cell mass, may require discontinuation of Estandron Prolongado.

Check hematocrit prior to initiating Estandron Prolongado (Testosterone Propionate) treatment. It would be appropriate to re-evaluate the hematocrit 3 to 6 months after starting Estandron Prolongado (Testosterone Propionate) treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable level. An increase in red blood cell mass may increase the risk of thromboembolic events.

5.5 Venous Thromboembolism

There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using Estandron Prolongado (Testosterone Propionate) products, such as Estandron Prolongado (Testosterone Propionate). 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 Estandron Prolongado (Testosterone Propionate) and initiate appropriate workup and management.

5.6 Cardiovascular Risk

Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of Estandron Prolongado 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 Estandron Prolongado (Testosterone Propionate) compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of Estandron Prolongado (Testosterone Propionate) replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use Estandron Prolongado (Testosterone Propionate).

5.7 Abuse of Estandron Prolongado (Testosterone Propionate) and Monitoring of SerumTestosterone Concentrations

Estandron Prolongado (Testosterone Propionate) 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 .

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

5.8 Use in Women

Due to lack of controlled evaluations in women and potential virilizing effects, Estandron Prolongado is not indicated for use in women.

5.9 Potential for Adverse Effects on Spermatogenesis

With large doses of exogenous androgens, including Estandron Prolongado (Testosterone Propionate), spermatogenesis may be suppressed through feedback inhibition of pituitary follicle- stimulating hormone (FSH) which could possibly lead to adverse effects on semen parameters including sperm count.

5.10 Hepatic Adverse Effects

Prolonged use of high doses of orally active 17-alpha-alkyl androgens 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 Estandron Prolongado (Testosterone Propionate) enanthate, which elevates blood levels for prolonged periods, has produced multiple hepatic adenomas. Estandron Prolongado (Testosterone Propionate) is not known to produce these adverse effects. Nonetheless, patients should be instructed to report any signs or symptoms of hepatic dysfunction (e.g., jaundice). If these occur, promptly discontinue Estandron Prolongado (Testosterone Propionate) while the cause is evaluated.

5.11 Edema

Androgens, including Estandron Prolongado (Testosterone Propionate), may promote retention of sodium and water. 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.

5.12 Gynecomastia

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

5.13 Sleep Apnea

The treatment of hypogonadal men with Estandron Prolongado (Testosterone Propionate) products may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases.

5.14 Lipids

Changes in serum lipid profile may require dose adjustment of lipid lowering drugs or discontinuation of Estandron Prolongado therapy.

5.15 Hypercalcemia

Androgens, including Estandron Prolongado (Testosterone Propionate), 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.

5.16 Decreased Thyroxine-binding Globulin

Androgens, including Estandron Prolongado (Testosterone Propionate), may decrease concentrations of thyroxine-binding globulin, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.

6 ADVERSE REACTIONS

The most commonly reported adverse reactions are acne, injection site pain, prostatic specific antigen (PSA) increased, estradiol increased, hypogonadism, fatigue, irritability, hemoglobin increased, insomnia, and mood swings (6.1).

To report SUSPECTED ADVERSE REACTIONS, contact Endo Pharmaceuticals at 1-800-462-3636 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Estandron Prolongado (Testosterone Propionate) was evaluated in an 84-week clinical study using a dose regimen of 750 mg (3 mL) at initiation, at 4 weeks, and every 10 weeks thereafter in 153 hypogonadal men. The most commonly reported adverse reactions (>2%) were: acne (5.2%), injection site pain (4.6%), prostate specific antigen increased (4.6%), hypogonadism (2.6%) and estradiol increased (2.6%).

Table 1 presents adverse reactions reported by ≥1% of patients in the 84-week clinical study.

Table 1

Adverse Reactions Reported in at Least 1% of Patients in the 84-Week Clinical Study of Estandron Prolongado (Testosterone Propionate)

* Prostate specific antigen increased defined as a serum PSA concentration >4 ng/mL.

In the 84-week clinical trial, 7 patients (4.6%) discontinued treatment because of adverse reactions. Adverse reactions leading to discontinuation included: hematocrit increased, estradiol increased, prostatic specific antigen increased, prostate cancer, mood swings, prostatic dysplasia, acne, and deep vein thrombosis.

During the 84-week clinical trial, the average serum PSA increased from 1.0 ± 0.8 ng/mL at baseline to 1.5 ± 1.3 ng/mL at the end of study. Fourteen patients (10.9%) in whom the baseline PSA was < 4 ng/mL had a post-baseline serum PSA of > 4 ng/mL during the 84-week treatment period.

A total of 725 hypogonadal men received intramuscular Estandron Prolongado (Testosterone Propionate) undecanoate in a total of 7 controlled clinical trials. In these clinical trials, the dose and dose frequency of intramuscular Estandron Prolongado (Testosterone Propionate) undecanoate varied from 750 mg to 1000 mg, and from every 9 weeks to every 14 weeks. Several of these clinical trials incorporated additional doses upon initiation of therapy (e.g., loading doses). In addition to those adverse reactions noted in Table 1, the following adverse events were reported by at least 3% of patients in these trials, irrespective of the investigator’s assessment of relationship to study medication: sinusitis, prostatitis, arthralgia, nasopharyngitis, upper respiratory tract infection, bronchitis, back pain, hypertension, diarrhea and headache.

Pulmonary Oil Microembolism (POME) and Anaphylaxis in Controlled Clinical Studies

Adverse events attributable to pulmonary oil microembolism and anaphylaxis were reported in a small number of patients in controlled clinical trials. In the 84-week clinical trial of Estandron Prolongado (Testosterone Propionate), 1 patient experienced a mild coughing fit lasting 10 minutes after his third injection, which was retrospectively attributed to POME. In another clinical trial of intramuscular Estandron Prolongado (Testosterone Propionate) undecanoate (1000 mg), a hypogonadal male patient experienced the urge to cough and respiratory distress at 1 minute after his tenth injection, which was also retrospectively attributed to POME.

During a review that involved adjudication of all cases meeting specific criteria, 9 POME events in 8 patients and 2 events of anaphylaxis among 3,556 patients treated with intramuscular Estandron Prolongado (Testosterone Propionate) undecanoate in 18 clinical trials were judged to have occurred.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Estandron Prolongado (Testosterone Propionate). Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Pulmonary Oil Microembolism (POME) and Anaphylaxis

Serious pulmonary oil microembolism (POME) reactions, involving cough, urge to cough, dyspnea, hyperhidrosis, throat tightening, chest pain, dizziness, and syncope, have been reported to occur during or immediately after the injection of intramuscular Estandron Prolongado (Testosterone Propionate) undecanoate 1000 mg (4 mL) in post-approval use outside the United States. The majority of these events lasted a few minutes and resolved with supportive measures; however, some lasted up to several hours and some required emergency care and/or hospitalization.

In addition to serious POME reactions, episodes of anaphylaxis, including life-threatening reactions, have also been reported to occur following the injection of intramuscular Estandron Prolongado (Testosterone Propionate) undecanoate in post-approval use outside of the United States.

Both serious POME reactions and anaphylaxis have been reported to occur after any injection of Estandron Prolongado (Testosterone Propionate) undecanoate during the course of therapy, including after the first dose.

Other Events

The following treatment emergent adverse events or adverse reactions have been identified during post-marketing clinical trials and during post-approval use of intramuscular Estandron Prolongado (Testosterone Propionate) undecanoate. In most cases, the dose being used was 1000 mg.

Blood and Lymphatic System Disorders: polycythemia, thrombocytopenia

Cardiac Disorders: angina pectoris, cardiac arrest, cardiac failure, coronary artery disease, coronary artery occlusion, myocardial infarction, tachycardia

Ear and Labyrinth Disorders: sudden hearing loss, tinnitus

Endocrine Disorders: hyperparathyroidism, hypoglycemia

Gastrointestinal Disorders: abdominal pain upper, diarrhea, vomiting

General Disorders and Administrative Site Conditions: chest pain, edema peripheral, injection site discomfort, injection site hematoma, injection site irritation, injection site pain, injection site reaction, malaise, paresthesia, procedural pain

Immune System Disorders: anaphylactic reaction, anaphylactic shock, asthma, dermatitis allergic, hypersensitivity, leukocytoclastic vasculitis

Infections and Infestations: injection site abscess, prostate infection

Investigations: alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, blood glucose increased, blood pressure increased, blood prolactin increased, blood Estandron Prolongado (Testosterone Propionate) decreased, blood Estandron Prolongado (Testosterone Propionate) increased, blood triglycerides increased, gamma-glutamyltransferase increased, hematocrit increased, intraocular pressure increased, liver function test abnormal, prostate examination abnormal, prostatic specific antigen increased, transaminases increased

Metabolism and Nutrition Disorders: diabetes mellitus, fluid retention, hyperlipidemia, hypertriglyceridemia

Musculoskeletal and Connective Tissue Disorders: musculoskeletal chest pain, musculoskeletal pain, myalgia, osteopenia, osteoporosis, systemic lupus erythematosus

Neoplasms Benign, Malignant and Unspecified (including cysts and polyps): prostate cancer, prostatic intraepithelial neoplasia

Nervous System Disorders: stroke, cerebrovascular insufficiency, reversible ischemic neurological deficiency, transient ischemic attack

Psychiatric Disorders: aggression, anxiety, depression, insomnia, irritability, Korsakoff’s psychosis non-alcoholic, male orgasmic disorder, nervousness, restlessness, sleep disorder

Renal and Urinary Disorders: calculus urinary, dysuria, hematuria, nephrolithiasis, pollakiuria, renal colic, renal pain, urinary tract disorder

Reproductive System and Breast Disorders: azoospermia, benign prostatic hyperplasia, breast induration, breast pain, erectile dysfunction, gynecomastia, libido decreased, libido increased, prostate induration, prostatitis, spermatocele, testicular pain

Respiratory, Thoracic and Mediastinal Disorders: asthma, chronic obstructive pulmonary disease, cough, dysphonia, dyspnea, hyperventilation, obstructive airway disorder, pharyngeal edema, pharyngolaryngeal pain, pulmonary microemboli, pulmonary embolism, respiratory distress, rhinitis, sleep apnea syndrome, snoring

Skin and Subcutaneous Tissue Disorders: acne, alopecia, angioedema, angioneurotic edema, dermatitis allergic, erythema, hyperhidrosis, pruritus, rash

Vascular Disorders: cerebral infarction, cerebrovascular accident, circulatory collapse, deep venous thrombosis, hot flush, hypertension, syncope, thromboembolism, thrombosis, venous insufficiency.

7 DRUG INTERACTIONS

• Androgens may decrease blood glucose, and therefore may decrease insulin requirements 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 in patients taking warfarin (7.2).
• Use of Estandron Prolongado (Testosterone Propionate) with corticosteroids may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease (7.3).

7.1 Insulin

Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of anti-diabetic medication.

7.2 Oral Anticoagulants

Changes in anticoagulant activity may be seen with androgens, therefore more frequent monitoring of international normalized ratio and prothrombin time are recommended in patients taking warfarin, especially at the initiation and termination of androgen therapy.

7.3 Corticosteroids

The concurrent use of Estandron Prolongado (Testosterone Propionate) with corticosteroids may result in increased fluid retention and requires careful monitoring, particularly in patients with cardiac, renal or hepatic disease.

8 USE IN SPECIFIC POPULATIONS

Geriatric Patients: There are insufficient long-term safety data to assess the potential risks of cardiovascular disease and prostate cancer.

8.1 Pregnancy

Pregnancy Category X: Aveed is contraindicated in pregnant women or in women who may become pregnant. Estandron Prolongado (Testosterone Propionate) is teratogenic and may cause fetal harm. Exposure of a fetus to androgens, such as Estandron Prolongado (Testosterone Propionate), may result in varying degrees of virilizations. If this drug is used in pregnancy or if the patient becomes pregnant while taking this drug, the patient should be made aware of the potential hazard to the fetus.

8.3 Nursing Mothers

Although it is not known how much Estandron Prolongado transfers into human milk, Estandron Prolongado (Testosterone Propionate) is contraindicated in nursing women because of the potential for serious adverse reactions in nursing infants.

8.4 Pediatric Use

Safety and effectiveness of Estandron Prolongado (Testosterone Propionate) in pediatric patients less than 18 years old have not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses.

8.5 Geriatric Use

There have not been sufficient numbers of geriatric patients in controlled clinical studies with Estandron Prolongado to determine whether efficacy or safety in those over 65 years of age differs from younger subjects. Of the153 patients enrolled in the pivotal clinical study utilizing Estandron Prolongado (Testosterone Propionate), 26 (17.0%) were over 65 years of age. Additionally, there are insufficient long-term safety data in geriatric patients to assess the potentially increased risk of cardiovascular disease and prostate cancer.

Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH .

8.6 Renal Impairment

No studies were conducted in patients with renal impairment.

8.7 Hepatic Impairment

No studies were conducted in patients with hepatic impairment.

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

Estandron Prolongado contains Estandron Prolongado (Testosterone Propionate), a Schedule III controlled substance in the Controlled Substances Act.

9.2 Abuse

Drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. Abuse and misuse of Estandron Prolongado (Testosterone Propionate) are seen in male and female adults and adolescents. Testosterone, often in combination with other anabolic androgenic steroids (AAS), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse of men taking higher doses of legally obtained Estandron Prolongado (Testosterone Propionate) than prescribed and continuing Estandron Prolongado (Testosterone Propionate) despite adverse events or against medical advice.

Abuse-Related Adverse Reactions

Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids, and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression.

The following adverse reactions have also been reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility.

The following additional adverse reactions have been reported in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities.

The following adverse reactions have been reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty.

Because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

9.3 Dependence

Behaviors Associated with Addiction

Continued abuse of Estandron Prolongado (Testosterone Propionate) and other anabolic steroids, leading to addiction is characterized by the following behaviors:

• Taking greater dosages than prescribed
• Continued drug use despite medical and social problems due to drug use
• Spending significant time to obtain the drug when supplies of the drug are interrupted
• Giving a higher priority to drug use than other obligations
• Having difficulty in discontinuing the drug despite desires and attempts to do so
• Experiencing withdrawal symptoms upon abrupt discontinuation of use

Physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. Individuals taking supratherapeutic doses of Estandron Prolongado (Testosterone Propionate) may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism.

Drug dependence in individuals using approved doses of Estandron Prolongado (Testosterone Propionate) for approved indications has not been documented.

.

10 OVERDOSAGE

There have been no reports of overdosage in the Estandron Prolongado (Testosterone Propionate) clinical trials. There is one report of acute overdosage with use of an approved injectable Estandron Prolongado (Testosterone Propionate) product: this subject had serum Estandron Prolongado (Testosterone Propionate) levels of up to 11,400 ng/dL with a cerebrovascular accident.

Treatment of overdosage would consist of discontinuation of Estandron Prolongado (Testosterone Propionate) together with appropriate symptomatic and supportive care.

11 DESCRIPTION

Estandron Prolongado (Testosterone Propionate) (testosterone undecanoate) injection contains Estandron Prolongado (Testosterone Propionate) undecanoate (17β-undecanoyloxy-4-androsten-3-one) which is an ester of the androgen, Estandron Prolongado (Testosterone Propionate). Estandron Prolongado (Testosterone Propionate) is formed by cleavage of the ester side chain of Estandron Prolongado (Testosterone Propionate) undecanoate.

Estandron Prolongado (Testosterone Propionate) undecanoate is a white to off-white crystalline substance. The empirical formula of Estandron Prolongado (Testosterone Propionate) undecanoate is C₃₀H₄₈O₃ and a molecular weight of 456.7. The structural formula is:

FIGURE 2: Estandron Prolongado (Testosterone Propionate) Undecanoate

C₃₀H₄₈O₃ MW: 456.7

Estandron Prolongado (Testosterone Propionate) is a clear, yellowish, sterile oily solution containing Estandron Prolongado (Testosterone Propionate) undecanoate, a Estandron Prolongado (Testosterone Propionate) ester, for intramuscular injection. Each single use vial contains 3 mL of 250 mg/mL Estandron Prolongado (Testosterone Propionate) undecanoate solution in a mixture of 1500 mg of benzyl benzoate and 885 mg of refined castor oil.

Figure2

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Endogenous androgens, including Estandron Prolongado 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 Estandron Prolongado (Testosterone Propionate), 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).

12.3 Pharmacokinetics

Absorption

Estandron Prolongado (Testosterone Propionate) 750 mg delivers physiologic amounts of Estandron Prolongado (Testosterone Propionate), producing circulation Estandron Prolongado (Testosterone Propionate) concentrations that approximate normal concentrations (300-1000 ng/dL) seen in healthy men.

Estandron Prolongado (Testosterone Propionate) esters in oil injected intramuscularly are absorbed from the lipid phase. Cleavage of the undecanoic acid side chain of Estandron Prolongado (Testosterone Propionate) by tissue esterases releases Estandron Prolongado (Testosterone Propionate).

Following intramuscular injection of 750 mg of Estandron Prolongado (Testosterone Propionate), serum Estandron Prolongado (Testosterone Propionate) concentrations reach a maximum after a median of

7 days (range 4 – 42 days) then slowly decline (Figure 3). Steady state serum Estandron Prolongado (Testosterone Propionate) concentration was achieved with the 3^rd injection of Estandron Prolongado (Testosterone Propionate) at 14 weeks.

Figure 3 shows the mean serum total Estandron Prolongado (Testosterone Propionate) concentration-time profile during the 3^rd injection interval (at steady state, 14-24 weeks) for hypogonadal men (less than 300 ng/dL) given 750 mg Estandron Prolongado (Testosterone Propionate) at initiation, at 4 weeks, and every 10 weeks thereafter. Intramuscular injection of 750 mg of Estandron Prolongado (Testosterone Propionate) generates mean steady state serum total Estandron Prolongado (Testosterone Propionate) concentrations in the normal range for 10 weeks.

FIGURE 3: Mean (SD) Serum Total Estandron Prolongado (Testosterone Propionate)

Concentrations (ng/dL) at 14-24 Weeks

Distribution

Circulating Estandron Prolongado (Testosterone Propionate) is chiefly bound in the serum to sex hormone-binding globulin (SHBG) and albumin.

Approximately 40% of Estandron Prolongado (Testosterone Propionate) in plasma is bound to SHBG, 2% remains unbound (free), and the rest is loosely bound to albumin and other proteins.

Metabolism

Estandron Prolongado (Testosterone Propionate) undecanoate is metabolized to Estandron Prolongado (Testosterone Propionate) via ester cleavage of the undecanoate group. The mean (SD) maximum concentration of Estandron Prolongado (Testosterone Propionate) undecanoate was 90.9 (68.8) ng/dL on Day 4 following injection of Estandron Prolongado (Testosterone Propionate). Estandron Prolongado (Testosterone Propionate) undecanoate was nearly undetectable 42 days following injection of Estandron Prolongado (Testosterone Propionate).

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

DHT concentrations increased in parallel with Estandron Prolongado (Testosterone Propionate) concentrations during Estandron Prolongado (Testosterone Propionate) treatment. Average DHT concentrations during a dosing interval ranged from 244 to 451 ng/dL. The mean DHT:T ratios ranged from 0.05 to 0.07.

Excretion

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

Effect of Body Weight and Body Mass Index (BMI)

Analysis of serum Estandron Prolongado (Testosterone Propionate) concentrations from 117 hypogonadal men in the 84-week clinical study of Estandron Prolongado (Testosterone Propionate) indicated that serum Estandron Prolongado (Testosterone Propionate) concentrations achieved were inversely correlated with the patient’s body weight. In 60 patients with pretreatment body weight of ≥100 kg, the mean (±SD) serum Estandron Prolongado (Testosterone Propionate) average concentration was 426 ± 104 ng/dL. A higher serum Estandron Prolongado (Testosterone Propionate) average concentration (568 ± 139 ng/dL) was observed in 57 patients weighing 65 to 100 kg. A similar trend was also observed for maximum serum Estandron Prolongado (Testosterone Propionate) concentrations.

In 70 patients with pretreatment body mass index of >30 kg/m², the mean (±SD) serum Estandron Prolongado (Testosterone Propionate) average concentration was

445 ± 116 ng/dL. Higher serum Estandron Prolongado (Testosterone Propionate) average concentrations (579 ± 101 ng/dL and 567± 155ng/dL) were observed in patients with BMIs <26 kg/m² and 26 to 30 kg/m²,respectively. A similar trend was also observed for maximum serum Estandron Prolongado (Testosterone Propionate) concentrations.

Figure3

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis and Mutagenesis and Impairment of Fertility

Carcinogenicity

Estandron Prolongado (Testosterone Propionate) 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 Estandron Prolongado (Testosterone Propionate) into some strains of female mice increases their susceptibility to hepatoma. Estandron Prolongado (Testosterone Propionate) is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats.

Mutagenicity

Mutagenic effects of Estandron Prolongado (Testosterone Propionate) undecanoate were not detected in a battery of in vitro tests including bacterial mutation assays (Ames test) and chromosomal aberration tests in human lymphocytes. Estandron Prolongado (Testosterone Propionate) undecanoate was also negative in an in vivo bone marrow micronucleus assay in mice. Estandron Prolongado (Testosterone Propionate) was negative in the in vitro Ames and in the in vivo mouse micronucleus assays.

Impairment of Fertility

The administration of exogenous Estandron Prolongado (Testosterone Propionate) has been reported to suppress spermatogenesis in the rat, dog and non-human primates, which was reversible on cessation of the treatment.

14 CLINICAL STUDIES

14.1 Estandron Prolongado Replacement Therapy

Estandron Prolongado (Testosterone Propionate) was evaluated for efficacy in an 84-week, single-arm, open-label, multicenter study of 130 hypogonadal men. Eligible patients weighed at least 65 kg, were 18 years of age and older (mean age 54.2 years), and had a morning serum total Estandron Prolongado (Testosterone Propionate) concentrations <300 ng/dL (mean screening Estandron Prolongado (Testosterone Propionate) concentration 215 ng/dL). Patients were Caucasian (74.6%), Black (12.3%), Hispanic (10.8%) and of Other ethnicities (2.3%). The mean body mass index was 32 kg/m².

All patients received injections of Estandron Prolongado (Testosterone Propionate) 750 mg at baseline, at 4 weeks, and then every 10 weeks thereafter.

The primary endpoint was the percentage of patients with average serum total Estandron Prolongado (Testosterone Propionate) concentration (C_avg) within the normal range (300-1000 ng/dL) after the third injection, at steady state.

The secondary endpoint was the percentage of patients with maximum total Estandron Prolongado (Testosterone Propionate) concentration (C_max) above three pre-determined limits: greater than 1500 ng/dL, between 1800 and 2499 ng/dL, and greater than 2500 ng/dL.

A total of 117 out of 130 hypogonadal men completed study procedures through Week 24 and were included in the evaluation of Estandron Prolongado (Testosterone Propionate) pharmacokinetics after the third Estandron Prolongado (Testosterone Propionate) injection. Ninety-four percent (94%) of patients maintained a C_avg within the normal range (300 to 1000 ng/dL). The percentages of patients with C_avg below the normal range (less than 300 ng/dL) and above the normal range (greater than 1000 ng/dL) were 5.1% and 0.9%, respectively.

Table 2 summarizes the mean (SD) serum total Estandron Prolongado (Testosterone Propionate) pharmacokinetic parameters at steady state for these 117 patients.

TABLE 2

Mean (SD) Serum Total Estandron Prolongado (Testosterone Propionate) Concentrations at Steady State

C_avg = average concentration; C_max = maximum concentration; C_min = minimum concentration

The percentage of patients with C_max >1500 ng/dL was 7.7%. No patient had a C_max >1800 ng/dL.

16 HOW SUPPLIED/STORAGE AND HANDLING

Estandron Prolongado (Testosterone Propionate), NDC 67979-511-43: 750 mg/3 mL (250 mg/mL) Estandron Prolongado (Testosterone Propionate) undecanoate sterile injectable solution is provided in an amber glass vial with silver-colored crimp seal and gray plastic cap. Each vial is individually packaged in a carton box.

Store at controlled room temperature 25 ºC (77 ºF); excursions permitted to 15 - 30 ºC (59 - 86 ºF) in its original carton until the date indicated.

Before use, each vial should be visually inspected. Only vials free from particles should be used.

Single Use Vial. Discard unused portion.

17 PATIENT COUNSELING INFORMATION

See FDA-Approved Medication Guide

Advise patients of the following:

17.1 Risks of Serious Pulmonary Oil Microembolism and Anaphylaxis

• Serious pulmonary oil microembolism (POME) reactions, involving cough, urge to cough, shortness of breath, sweating, throat tightening, chest pain, dizziness, and syncope, have been reported to occur during or immediately after the injection of intramuscular Estandron Prolongado (Testosterone Propionate) undecanoate. The majority of these events lasted a few minutes and resolved with supportive measures; however, some lasted up to several hours and some required emergency care and/or hospitalization.
• Episodes of anaphylaxis, including life-threatening reactions, have also been reported to occur following the injection of intramuscular Estandron Prolongado (Testosterone Propionate) undecanoate.
• Both serious POME reactions and anaphylaxis can occur after any injection of Estandron Prolongado (Testosterone Propionate) undecanoate during the course of therapy, including after the first dose.
• Advise the patient to read the Estandron Prolongado (Testosterone Propionate) REMS information sheet titled "What You Need to Know About Estandron Prolongado (Testosterone Propionate)^® Treatment: A Patient Guide.
• Instruct patients to remain at the healthcare setting for 30 minutes after each Estandron Prolongado (Testosterone Propionate) injection.

17.2 Men with Known or Suspected Carcinoma of the Prostate or Breast

Men with known or suspected prostate or breast cancer should not use Estandron Prolongado .

17.3 Potential Adverse Reactions to Androgens

Patients should be informed that treatment with androgens may lead to adverse reactions which include:

• Changes in urinary habits, such as increased urination at night, trouble starting the urine stream, passing urine many times during the day, having an urge to go the bathroom right away, having a urine accident, or being unable to pass urine or weak urine flow
• Breathing disturbances, including those associated with sleep or excessive daytime sleepiness
• Too frequent or persistent erections of the penis
• Nausea, vomiting, changes in skin color, or ankle swelling

17.4 Patients Should be Advised of the Following Instructions for Use

• Read the Medication Guide before starting Estandron Prolongado (Testosterone Propionate) therapy and reread the Guide before each injection.
• Adhere to all recommended monitoring.
• Report any changes in their state of health, such as changes in urinary habits, breathing, sleep, and mood.

Distributed by:

Endo Pharmaceuticals Solutions Inc.

Malvern, PA 19355

Estandron Prolongado (Testosterone Propionate) is a registered trademark of Endo Pharmaceuticals Inc.

© 2017 Endo Pharmaceuticals Solutions Inc. All rights reserved.

Revised: July 2017

Estandron Prolongado (Testosterone Propionate)^® (Uh-Veed)

(testosterone undecanoate)

injection

Read this Medication Guide before you receive Estandron Prolongado (Testosterone Propionate) and before each injection. There may be new information. This Medication Guide does not take the place of talking with your doctor about your medical condition or your treatment.

What is the most important information I should know about Estandron Prolongado (Testosterone Propionate)?

Estandron Prolongado (Testosterone Propionate) may cause serious side effects, including:

• A serious lung problem. Estandron Prolongado (Testosterone Propionate) can cause a serious lung problem called a pulmonary oil microembolism (POME) reaction. POME is caused by tiny droplets of oil that have traveled to the lungs. Symptoms of a POME reaction may include:

o cough or urge to cough

o difficulty breathing

o sweating

o tightening of your throat

o chest pain

o dizziness

o fainting

• Serious allergic reactions (anaphylaxis). Estandron Prolongado (Testosterone Propionate) can cause a serious allergic reaction right after receiving the injection. Some of these allergic reactions may be life threatening.

These reactions can happen after you receive your first dose of Estandron Prolongado (Testosterone Propionate) or may happen after receiving more than 1 dose.

You may need emergency treatment in a hospital, especially if these symptoms get worse over the 24 hours after

your AVEED injection.

These side effects may happen during or right after each injection. To be sure that you are not having one

of these reactions:

o You need to stay in the doctor’s office, clinic, or hospital for 30 minutes after having your Estandron Prolongado (Testosterone Propionate) injection so

that your doctor can watch you for symptoms of POME or a serious allergic reaction.

o You can only get Estandron Prolongado (Testosterone Propionate) at your doctor’s office, clinic, or hospital.

Estandron Prolongado (Testosterone Propionate) is only available through a restricted program called the Estandron Prolongado (Testosterone Propionate) Risk Evaluation and Mitigation Strategy (REMS) Program. For more information about the Estandron Prolongado (Testosterone Propionate) REMS Program go to www. AveedREMS.com or call 1-855-755-0494.

What is Estandron Prolongado (Testosterone Propionate)?

Estandron Prolongado (Testosterone Propionate) is a prescription medicine that contains Estandron Prolongado (Testosterone Propionate). Estandron Prolongado (Testosterone Propionate) is used to treat adult males who have low or no Estandron Prolongado (Testosterone Propionate) due to certain medical conditions.

Estandron Prolongado (Testosterone Propionate) is only for adult males who need Estandron Prolongado (Testosterone Propionate) replacement therapy and when the benefit of receiving Estandron Prolongado (Testosterone Propionate) is more than the risk of POME and anaphylaxis.

Your healthcare provider will test your blood before you start and while you are taking Estandron Prolongado (Testosterone Propionate).

It is not known if AVEEDis safe or effective to treat men who have low Estandron Prolongado (Testosterone Propionate) due to aging.

It is not known if Estandron Prolongado (Testosterone Propionate) is safe and effective for use in children younger than 18 years old. Improper use of Estandron Prolongado (Testosterone Propionate) may affect bone growth in children.

Estandron Prolongado (Testosterone Propionate) is a controlled substance (CIII) because it contains Estandron Prolongado (Testosterone Propionate) that can be a target for people who abuse prescription medicines.

Estandron Prolongado (Testosterone Propionate) is not meant for use in women.

Who should not receive Estandron Prolongado (Testosterone Propionate)?

Do not receive Estandron Prolongado (Testosterone Propionate) if you:

• have breast cancer
• have or might have prostate cancer
• are pregnant or may become pregnant or are breastfeeding. Estandron Prolongado (Testosterone Propionate) may harm your unborn or breastfeeding baby.
• are allergic to Estandron Prolongado (Testosterone Propionate) or to any of the ingredients in Estandron Prolongado (Testosterone Propionate). See the end of this leaflet for a complete list of ingredients in Estandron Prolongado (Testosterone Propionate).

Talk to your doctor before receiving this medicine if you have any of the above conditions.

What should I tell my doctor before receiving Estandron Prolongado (Testosterone Propionate)?

Before receiving Estandron Prolongado (Testosterone Propionate), tell your doctor if you:

• have breast cancer
• have or might have prostate cancer
• have urinary problems due to an enlarged prostate
• have heart problems
• have liver or kidney problems
• have problems breathing while you sleep (sleep apnea)
• have any other medical conditions

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Receiving Estandron Prolongado (Testosterone Propionate) with certain other medicines can affect each other. Especially tell your doctor if you take:

• insulin
• medicines that decrease blood clotting
• corticosteroids

Ask your doctor or pharmacist for a list of these medicines, if you are not sure.

Know the medicines you take. Keep a list of your medicines and show them to your doctor and pharmacist when you get a new medicine.

How will I receive Estandron Prolongado (Testosterone Propionate)?

See “What is the most important information I should know about Estandron Prolongado (Testosterone Propionate)?”

Your doctor will inject Estandron Prolongado (Testosterone Propionate) deep into the muscle of your buttock. You will get 1 injection when you start, 1 injection 4 weeks later and then 1 injection every 10 weeks.

Your doctor will test your blood before you receive and while you are receiving Estandron Prolongado (Testosterone Propionate).

What are the possible side effects of Estandron Prolongado (Testosterone Propionate)?

Estandron Prolongado (Testosterone Propionate) can cause serious side effects including:

• see “What is the most important information I should know about Estandron Prolongado (Testosterone Propionate)?”
• if you already have enlargement of your prostate gland, your signs and symptoms can get worse while receiving Estandron Prolongado (Testosterone Propionate). This can include:

o increased urination at night

o trouble starting your urine stream

o having to pass urine many times during the day

o having an urge that you have to go to the bathroom right away

o having a urine accident

o being unable to pass urine or weak urine flow

• changes in certain blood tests
• possible increased risk of prostate cancer. Your doctor should check you for prostate cancer or any other prostate problems before you receive and while you are receiving Estandron Prolongado (Testosterone Propionate).
• blood clots in the legs or lungs. Signs and symptoms of a blood clot in your leg can include leg pain, swelling or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain.
• possible increased risk of heart attack or stroke.
• in large doses Estandron Prolongado (Testosterone Propionate) may lower your sperm count.
• liver problems. Symptoms of liver problems may include:

o nausea or vomiting

o yellowing of your skin or whites of your eyes

o dark urine

o pain on the right side of your stomach area (abdominal pain)

• swelling of your ankles, feet, or body, with or without heart failure. This may cause serious problems for people who have heart, kidney, or liver disease.
• enlarged or painful breasts.
• have problems breathing while you sleep (sleep apnea).

Call your doctor right away if you have any of the serious side effects listed above.

The most common side effects of Estandron Prolongado (Testosterone Propionate) include:

• acne
• pain at the injection site
• increased prostate specific antigen (a test used to screen for prostate cancer)
• increased estradiol level
• low Estandron Prolongado (Testosterone Propionate) level
• feeling tired
• irritability
• increased red blood cell count
• difficulty sleeping
• mood swings

Other side effects include more erections than are normal for you or erections that last for a long time.

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

These are not all the possible side effects with Estandron Prolongado (Testosterone Propionate). For more information, ask your doctor or pharmacist.

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

General information about Estandron Prolongado (Testosterone Propionate)

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.

This Medication Guide summarizes the most important information about Estandron Prolongado (Testosterone Propionate). If you would like more information, talk with your doctor. You can ask your doctor or nurse for information about Estandron Prolongado (Testosterone Propionate) that is written for health professionals. For more information, go to www. AVEEDUSA.com or call 1-800-462-3636.

What are the ingredients in Estandron Prolongado (Testosterone Propionate)?

Active ingredient: Estandron Prolongado (Testosterone Propionate) undecanoate

Inactive ingredients: refined castor oil, benzyl benzoate

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Distributed by:

Endo Pharmaceuticals Solutions Inc.

Malvern, PA 19355

Estandron Prolongado (Testosterone Propionate) is a registered trademark of Endo Pharmaceuticals Inc.

© 2016 Endo Pharmaceuticals Solutions Inc. All rights reserved.

Approved: 10/2016

85534041

carton