AZMIRO
Generic: TESTOSTERONE CYPIONATE
Basic Information
Manufacturer
Azurity Pharmaceuticals, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAMUSCULAR
FDA Set ID
235b5625-570d-3fba-e063-6394a90aa2d1
Indications & Usage
1 INDICATIONS & USAGE AZMIRO is indicated for testosterone replacement therapy in males in 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; or orchiectomy, Klinefelter’s syndrome, or toxic damage from alcohol or heavy metals, chemotherapy, or toxic damage from alcohol or heavy metals.
These men usually have low serum testosterone concentrations and gonadotropins (follicle stimulating hormone (FSH), luteinizing hormone (LH)) above the normal range [ see Dosage and Administration ( 2.2 ) ].
• 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 [ see Dosage and Administration (2.2) ].
Limitations of Use • Safety and efficacy of AZMIRO in men with “age- related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.
• Safety and efficacy of AZMIRO in pediatric patients below the age of 12 years have not been established [ see Use in Specific Populations ( 8.4 ) ].
AZMIRO is an androgen indicated for testosterone replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone ( 1 ): Limitations of Use: • Safety and efficacy of AZMIRO in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established ( 1 ).
• Safety and effectiveness in pediatric patients below the age of 12 years have not been established ( 8.4 ).
These men usually have low serum testosterone concentrations and gonadotropins (follicle stimulating hormone (FSH), luteinizing hormone (LH)) above the normal range [ see Dosage and Administration ( 2.2 ) ].
• 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 [ see Dosage and Administration (2.2) ].
Limitations of Use • Safety and efficacy of AZMIRO in men with “age- related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.
• Safety and efficacy of AZMIRO in pediatric patients below the age of 12 years have not been established [ see Use in Specific Populations ( 8.4 ) ].
AZMIRO is an androgen indicated for testosterone replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone ( 1 ): Limitations of Use: • Safety and efficacy of AZMIRO in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established ( 1 ).
• Safety and effectiveness in pediatric patients below the age of 12 years have not been established ( 8.4 ).
Adverse Reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed elsewhere in the labeling: • Polycythemia [ see Warnings and Precautions ( 5.1 ) ] • Venous Thromboembolism [ see Warnings and Precautions ( 5.2 )] • Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer [ see Warnings and Precautions ( 5.3 ) ] • Blood Pressure Increases [ see Warnings and Precautions ( 5.4 ) ] • Hepatic Adverse Effects [ see Warnings and Precautions ( 5.8 ) ] • Edema [ see Warnings and Precautions ( 5.9 ) ] • Sleep Apnea [ see Warnings and Precautions ( 5.10 ) ] • Gynecomastia [ see Warnings and Precautions ( 5.11 ) ] • Lipid Changes [ see Warnings and Precautions ( 5.12 ) ] • Hypercalcemia [ see Warnings and Precautions ( 5.13 ) ] • Decreased Thyroxine-binding Globulin [ see Warnings and Precautions ( 5.14 ) ] • Increases in Prolactin [ see Warnings and Precautions ( 5.15 ) ] • Adverse Effects on Bone Maturation [ see Warnings and Precautions ( 5.16 ) ] Common adverse reactions (incidence ≥4%) are injection site erythema and injection site reaction ( 6.1 ).
Other adverse reactions include: polycythemia, gynecomastia, headache, and depression ( 6.2 ).
To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc.
at 1-800-461-7449 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 practice.
The safety of AZMIRO was evaluated, in Study 1, a randomized, single-dose, open-label study conducted in 27 adult males with hypogonadism.
Patients were 18 to 65 years of age with a body mass index of 18 to 35 kg/m 2 .
Patients received a single intramuscular dose AZMIRO 200 mg or comparator intramuscular testosterone replacement therapy product and were observed for adverse reactions and injection site reactions over 31 days.
The most common adverse reactions in patients who received AZMIRO were injection site erythema (26%) and injection site reaction (4%).
All cases of injection site erythema and injection site reaction were categorized as mild based on a pre-defined injection site assessment scale that defined injection site reactions as mild if they were slight or barely perceptible.
Cardiovascular Outcomes TRAVERSE was a randomized, double-blind, cardiovascular outcomes study to assess the cardiovascular (CV) safety of topical testosterone gel compared to placebo in 5198 hypogonadal men aged 45 to 80 years with a history of CV disease or with multiple CV risk factors.
The primary outcome was the incidence of the composite endpoint of major adverse cardiovascular events (MACE), consisting of CV death, non-fatal myocardial infarction (MI), and non-fatal stroke The mean duration of therapy was approximately 22 months.
The mean duration of follow-up was 33 months.
Approximately 61% of all patients discontinued topical testosterone gel or placebo therapy.
The mean patient age (±SD) was 63.3 (7.9) years, with 2452 patients aged 65 years or more (47%); 2847 (about 55%) patients had pre-existing cardiovascular disease, whereas 2357 patients (about 45%) had an elevated cardiovascular risk at baseline, and mean BMI was 35 kg/m 2 .
Approximately 80% of patients were White, 17% were Black, and 3% were of other races or ethnic groups.
Approximately 69%, 84%, and 93% had diabetes mellitus, hyperlipidemia, and hypertension, respectively.
The mean serum testosterone concentration at baseline in patients receiving topical testosterone gel was 220.4 ng/dL (n=2596).
The mean serum testosterone concentrations at 12 months, 24 months, 36 months, and 48 months in patients receiving topical testosterone gel were 440.5 ng/dL (n=1683), 420.9 ng/dl (n=1125), 428.7 ng/dL (n=731), and 365.2 ng/dL (n=220), respectively.
For patients treated with topical testosterone gel, the incidence of MACE was 7.0% (n=182 events) and for those receiving placebo, the incidence of MACE was 7.3% (n=190 events).
The study demonstrated non-inferiority of topical testosterone gel versus placebo because the upper bound of 95% CI was less than the pre-specified risk margin, of 1.5 for MACE (Hazard Ratio 0.96 [95% CI: 0.78, 1.17]).
Additional Adverse Reactions Reported in TRAVERSE Additional adverse reactions reported in TRAVERSE at an incidence rate >2% in either treatment group and greater in topical testosterone gel versus placebo included: nonfatal arrythmias warranting intervention (5.2% vs 3.3%), atrial fibrillation (3.5% vs 2.4%), acute kidney injury (2.3% vs 1.5%) and bone fracture (3.5% vs 2.5%).
For the adverse reaction of bone fracture, each event was adjudicated by clinical review.
6.2 Other Adverse Reactions The following adverse reactions associated with the use of testosterone were identified in clinical studies or postmarketing reports.
Because some of these reactions were 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.
Administration site reactions : Inflammation and pain at the site of intramuscular injection.
Allergic : Hypersensitivity, including skin manifestations and anaphylactoid reactions.
Cardiovascular disorders : myocardial infarction, stroke.
Endocrine and urogenital : Gynecomastia, premature closure of bony epiphyses with termination of growth, precocious puberty.
Fluid and electrolyte disturbances : Retention of sodium, chloride, water, potassium, calcium, and inorganic phosphates.
Gastrointestinal: Nausea, cholestatic jaundice, alterations in liver function tests, rarely hepatocellular neoplasms and peliosis hepatis.
Hematologic : Suppression of clotting factors II, V, VII, and X, bleeding in patients on concomitant anticoagulant therapy, and polycythemia.
Nervous system : Increased or decreased libido, headache, anxiety, depression, and generalized paresthesia.
Reproductive system : Excessive frequency and duration of penile erections, oligospermia, and priapism Vascular disorders : Venous thromboembolism.
Skin and appendages : Male pattern baldness, seborrhea, and acne.
Special senses : Rare cases of central serous chorioretinopathy (CSCR).
Other adverse reactions include: polycythemia, gynecomastia, headache, and depression ( 6.2 ).
To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc.
at 1-800-461-7449 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 practice.
The safety of AZMIRO was evaluated, in Study 1, a randomized, single-dose, open-label study conducted in 27 adult males with hypogonadism.
Patients were 18 to 65 years of age with a body mass index of 18 to 35 kg/m 2 .
Patients received a single intramuscular dose AZMIRO 200 mg or comparator intramuscular testosterone replacement therapy product and were observed for adverse reactions and injection site reactions over 31 days.
The most common adverse reactions in patients who received AZMIRO were injection site erythema (26%) and injection site reaction (4%).
All cases of injection site erythema and injection site reaction were categorized as mild based on a pre-defined injection site assessment scale that defined injection site reactions as mild if they were slight or barely perceptible.
Cardiovascular Outcomes TRAVERSE was a randomized, double-blind, cardiovascular outcomes study to assess the cardiovascular (CV) safety of topical testosterone gel compared to placebo in 5198 hypogonadal men aged 45 to 80 years with a history of CV disease or with multiple CV risk factors.
The primary outcome was the incidence of the composite endpoint of major adverse cardiovascular events (MACE), consisting of CV death, non-fatal myocardial infarction (MI), and non-fatal stroke The mean duration of therapy was approximately 22 months.
The mean duration of follow-up was 33 months.
Approximately 61% of all patients discontinued topical testosterone gel or placebo therapy.
The mean patient age (±SD) was 63.3 (7.9) years, with 2452 patients aged 65 years or more (47%); 2847 (about 55%) patients had pre-existing cardiovascular disease, whereas 2357 patients (about 45%) had an elevated cardiovascular risk at baseline, and mean BMI was 35 kg/m 2 .
Approximately 80% of patients were White, 17% were Black, and 3% were of other races or ethnic groups.
Approximately 69%, 84%, and 93% had diabetes mellitus, hyperlipidemia, and hypertension, respectively.
The mean serum testosterone concentration at baseline in patients receiving topical testosterone gel was 220.4 ng/dL (n=2596).
The mean serum testosterone concentrations at 12 months, 24 months, 36 months, and 48 months in patients receiving topical testosterone gel were 440.5 ng/dL (n=1683), 420.9 ng/dl (n=1125), 428.7 ng/dL (n=731), and 365.2 ng/dL (n=220), respectively.
For patients treated with topical testosterone gel, the incidence of MACE was 7.0% (n=182 events) and for those receiving placebo, the incidence of MACE was 7.3% (n=190 events).
The study demonstrated non-inferiority of topical testosterone gel versus placebo because the upper bound of 95% CI was less than the pre-specified risk margin, of 1.5 for MACE (Hazard Ratio 0.96 [95% CI: 0.78, 1.17]).
Additional Adverse Reactions Reported in TRAVERSE Additional adverse reactions reported in TRAVERSE at an incidence rate >2% in either treatment group and greater in topical testosterone gel versus placebo included: nonfatal arrythmias warranting intervention (5.2% vs 3.3%), atrial fibrillation (3.5% vs 2.4%), acute kidney injury (2.3% vs 1.5%) and bone fracture (3.5% vs 2.5%).
For the adverse reaction of bone fracture, each event was adjudicated by clinical review.
6.2 Other Adverse Reactions The following adverse reactions associated with the use of testosterone were identified in clinical studies or postmarketing reports.
Because some of these reactions were 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.
Administration site reactions : Inflammation and pain at the site of intramuscular injection.
Allergic : Hypersensitivity, including skin manifestations and anaphylactoid reactions.
Cardiovascular disorders : myocardial infarction, stroke.
Endocrine and urogenital : Gynecomastia, premature closure of bony epiphyses with termination of growth, precocious puberty.
Fluid and electrolyte disturbances : Retention of sodium, chloride, water, potassium, calcium, and inorganic phosphates.
Gastrointestinal: Nausea, cholestatic jaundice, alterations in liver function tests, rarely hepatocellular neoplasms and peliosis hepatis.
Hematologic : Suppression of clotting factors II, V, VII, and X, bleeding in patients on concomitant anticoagulant therapy, and polycythemia.
Nervous system : Increased or decreased libido, headache, anxiety, depression, and generalized paresthesia.
Reproductive system : Excessive frequency and duration of penile erections, oligospermia, and priapism Vascular disorders : Venous thromboembolism.
Skin and appendages : Male pattern baldness, seborrhea, and acne.
Special senses : Rare cases of central serous chorioretinopathy (CSCR).