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- | Form | DISCOUNT CODE !
Generic name: testosterone
Dosage form: gel
Medically reviewed by Drugs.com. Last updated on May 1, 2019.
WARNING: TESTOSTERONE SECONDARY EXPOSURE
- Virilization has been reported in children who have been exposed to testosterone gel (see Warnings and Precautions (5.2) and Adverse Reactions (6.2)).
- Children should avoid contact with unwashed or uncleaned application sites in men using testosterone gel (see Dosage and Administration (2.2) and Warnings and Precautions (5.2))..
- Health care providers should advise patients to scrupulously follow recommended instructions for use (see Dosage and Administration (2.2), Warnings and Precautions (5.2) and Counseling Information (17))..
Indications and use for AndroGel
- Primary hypogonadism (congenital or acquired): testicular insufficiency due to cryptorchidism, bilateral torsion, orchitis, endemic testicular syndrome, orchiectomy, Klinefelt syndrome, chemotherapy or toxic lesions due to lymphadenitis. alcohol or heavy metals. These men generally have low serum testosterone and gonadotropin levels (follicle stimulating hormone (FSH), luteinizing hormone (LH)) above normal.
- Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin deficiency or luteinizing hormone (LHRH) or pituitary-hypothalamic lesion of tumors, trauma or radiation. These men have low serum testosterone levels, but their gonadotropin levels are normal or low.
- The safety and efficacy of AndroGel 1% in men with "age-related hypogonadism" (also known as "late hypogonadism") have not been established.
- The safety and effectiveness of AndroGel 1% in men under 18 years have not been established. (see Use in specific populations (8.4)).
- Topical testosterone products may have different doses, strengths or application instructions that may result in different systemic exposure (1, 12.3).
AndroGel Dosage and Administration
The dosage and administration of AndroGel at 1% differ from AndroGel at 1.62%. For dosage and administration of AndroGel 1.62%, refer to its complete prescribing information. (2)
Before starting AndroGel 1%, confirm the diagnosis of hypogonadism by making sure that serum testosterone concentrations have been measured in the morning at least two different days and that these serum concentrations are below normal.
Dosage and dose adjustment
The recommended starting dose of AndroGel 1% is 50 mg testosterone (two 25 mg sachets or one 50 mg sachet), topically applied once daily to the shoulders and upper arms and / or to the area abdomen (preferably at the same time each day). day).
To ensure the correct dosage, serum testosterone levels should be measured at regular intervals. If the serum testosterone concentration is below the normal range, the daily dose of AndroGel 1% may be increased from 50 mg to 75 mg and from 75 mg to 100 mg in the adult male, according to the instructions of the doctor. If the serum testosterone concentration exceeds the normal range, the daily dose of AndroGel 1% may be decreased. If the serum testosterone concentration consistently exceeds the normal range at a daily dose of 50 mg, treatment with AndroGel at 1% should be discontinued. In addition, serum testosterone levels should be evaluated periodically.
AndroGel 1% should be applied on clean, dry, healthy and intact skin of right and left arms and shoulders and / or right and left abdomen. The scope of application should be limited to the area that will be covered by the patient's short-sleeved T-shirt. Do not apply AndroGel 1% to any other part of the body, including the genitals, chest, armpits, knees and back. AndroGel 1% should be evenly distributed between the arms / shoulders of right and left or both sides of the abdomen.
After applying the gel, let the application site dry before you get dressed. Hands should be thoroughly washed with water and soap after application. Avoid fire, flames or smoking until the gel is dry, since alcohol-based products, including AndroGel 1%, are flammable.
All content should be inserted in the palm of the hand and immediately applied on the application sites. Alternatively, patients can squeeze some of the gel from the sachet in the palm of the hand and apply it to the application sites. Repeat until all the content has been applied.
- Children and women should avoid contact with unwashed or uncleaned application sites of men using AndroGel 1%.
- Patients should wash their hands with soap and water immediately after the application of AndroGel 1%.
- Patients should cover the application site (s) with clothing (eg, t-shirt) after drying the gel.
- Before any situation in which skin-to-skin contact is expected, patients should wash the application site thoroughly with soap and water to remove any testosterone residue.
- In the event that unwashed or uncleaned skin on which AndroGel 1% has been applied comes into direct contact with another person 's skin, the general contact area with that person should be washed at the same time. soapy water as soon as possible.
Dosage Forms and Strengths
- A unit dose packet containing 25 mg of testosterone supplied in 2.5 g of gel.
- A unit dose packet containing 50 mg of testosterone supplied in 5 g of gel.
- AndroGel 1% is contraindicated in men with carcinoma of the breast or a known or suspected carcinoma of the prostate (see Warnings and Precautions (5.1), Adverse Reactions (6.1), and Non-clinical toxicology (13.1).
- AndroGel 1% is contraindicated in pregnant women. AndroGel 1% can cause virilization of the female fetus when administered to a pregnant woman. Pregnant women should be aware of the testosterone transfer potential in men treated with AndroGel 1%. If a pregnant woman is exposed to AndroGel 1%, she should be informed of the potential danger to the fetus. (see Warnings and Precautions (5.2) and Use in specific populations (8.1).
Warnings and precautions
Aggravation of benign prostatic hyperplasia (BPH) and potential risk of prostate cancer
- Patients with BPH treated with androgens have an increased risk of worsening the signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms.
- Patients treated with androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer before starting and during treatment with androgens (see Contraindications (4), Adverse Reactions (6.1) and Non-clinical toxicology (13.1).
Potential for secondary exposure to testosterone
Cases of secondary exposure resulting in virilization of children have been reported during post-marketing surveillance. Signs and symptoms include enlargement of the penis or clitoris, development of pubic hair, increased erection and libido, aggressive behavior, and advanced bone aging. In most cases, these signs and symptoms have regressed with the elimination of testosterone gel exposure. However, in a few cases, the enlarged genitalia did not return to normal height appropriate for their age, and their bone age remained slightly above their chronological age. The risk of transfer has been increased in some cases by failing to adhere to the appropriate use precautions of the topical testosterone product. Children and women should avoid contact with unwashed or uncleaned application sites in men using AndroGel 1% (see Dosage and Administration (2.2), Use in Specific Populations (8.1) and Clinical Pharmacology (12.3).
Any inappropriate modification of the genital size or the appearance of pubic hair or libido in the child, a change in the distribution of hair, a significant increase in acne or any other sign virilization in the adult woman should be reported to a doctor and the possibility of secondary exposure testosterone gel should also be brought to the attention of a doctor. The testosterone gel should be rapidly stopped until the cause of virilization has been identified.
Increases in hematocrit, reflecting the increase in red blood cell mass, may require a decrease or discontinuation of testosterone. Check for hematocrit before starting treatment. The hematocrit should also be re-evaluated 3 to 6 months after the start of treatment and once a year. If the hematocrit becomes high, stop the treatment until the hematocrit decreases to an acceptable concentration. An increase in red blood cell mass may increase the risk of thromboembolic events.
Venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), have been reported post-marketing in patients using testosterone-based products such as AndroGel 1%. Evaluate patients who report symptoms of pain, edema, heat, and erythema in the lower extremities for DVT and those with acute shortness of breath for PE. In case of suspicion of venous thromboembolic event, discontinue treatment with AndroGel 1% and initiate appropriate assessment and management (see Adverse Reactions (6.2)).
No long-term safety trial has been conducted to evaluate the cardiovascular consequences of testosterone replacement therapy in men. To date, epidemiological studies and randomized controlled trials have not been able to determine the risk of major adverse cardiovascular events, such as nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death, with use of testosterone -use. Some studies, but not all, have reported an increased risk of MACE associated with the use of testosterone replacement therapy in men.
Testosterone Abuse and Monitoring of Serum Testosterone Levels
Testosterone has been abused, usually at doses higher than those recommended for approved indication and in combination with other anabolic androgenic steroids. The abuse of anabolic androgenic steroids can lead to serious cardiovascular and psychiatric adverse effects (see Drug Abuse and Addiction (9)).
In case of suspicion of testosterone abuse, check the serum testosterone levels to make sure that they are within the therapeutic range. However, testosterone levels may be in the normal or subnormal range in men consuming synthetic testosterone derivatives. Advise patients about the serious side effects associated with testosterone abuse and androgenic anabolic steroids. Conversely, consider the possibility of testosterone abuse and anabolic androgen steroid abuse in patients with suspected serious cardiovascular or psychiatric adverse events.
Use in women
Potential for adverse effects on spermatogenesis
With high doses of exogenous androgens, including AndroGel 1%, spermatogenesis may be inhibited by feedback inhibition of FSH, which could lead to adverse effects on sperm parameters, including sperm count.
Hepatic side effects
Prolonged use of high doses of orally active androgen-17-alpha-alkyl (eg, methyltestosterone) has been associated with serious hepatic adverse events (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). . Peliosis hepatis can be a deadly or fatal complication. Long-term therapy with intramuscular testosterone enanthate has produced multiple hepatic adenomas. AndroGel 1% is not known to cause these side effects.
Androgens, including AndroGel 1%, can promote the 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 (6.2)).
The treatment of testosterone by hypogonadal men may potentiate sleep apnea in some patients, particularly those with risk factors such as obesity or chronic lung disease. (see Adverse Reactions (6.2)).
L & # 39; hypercalcemia
Androgens, including AndroGel 1%, should be used with caution in cancer patients at risk for hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium levels is recommended in these patients.
Globulin bound to decreased thyroxine
Androgens, including AndroGel 1%, may decrease thyroxine-binding globulin concentrations, resulting in decreased serum total T4 concentrations and increased T3 and T4 uptake by the resin. The concentrations of free thyroid hormones remain however unchanged and there is no clinical evidence of thyroid dysfunction.
Clinical Trial Experience
Since clinical trials are conducted under widely varying conditions, the adverse event rates observed in clinical trials of one drug can not be directly compared to the rates observed in clinical trials of another drug and may not be consistent with observed rates in practice.
|Junk event||Dosage of AndroGel 1%|
|50 mg||75 mg||100 mg|
|N = 77||N = 40||N = 78|
|Reaction of the application site||5%||3%||4%|
|Abnormal laboratory test *||6%||5%||3%|
|Prostate trouble **||3%||3%||5%|
|Testicular Trouble ***||3%||0%||0%|
|*Abnormal laboratory test occurred in nine patients with at least one of the following events: hemoglobin or high hematocrit, hyperlipidemia, elevated triglycerides, hypokalemia, decreased HDL, elevated blood glucose, elevated creatinine, elevated total bilirubin.|
|**Prostate disorders included five patients with prostate hypertrophy, one with BPH and one with high PSA scores.|
|***Testicular disorders have been reported in two patients: one with left varicocele and one with mild tenderness of the left testis.|
Six patients (4%) participating in this trial experienced side effects leading to discontinuation of AndroGel 1%. These events included: cerebral hemorrhage, seizures (none of which are considered to be related to the administration of AndroGel 1%), depression, sadness, memory loss, elevation of antigen specific prostate and hypertension. No 1% AndroGel patient was discontinued due to skin reactions.
In a separate and uncontrolled pharmacokinetic study of 10 patients, two adverse events were associated with AndroGel 1%; it was asthenia and depression in one patient and an increase in libido and hyperkinesia in the other.
In a 3-year flexible dose extension study, the incidence of all adverse events considered at least possibly related to AndroGel 1% treatment and reported by at least 1% of patients is shown in Table 2.
|Junk event||Percentage of subjects|
|(N = 162)|
|Abnormal laboratory test +||9.3|
|Reaction of the application site||5.6|
|Urinary symptoms *||3.7|
|Testicular Trouble **||1.9|
|+Abnormal laboratory test occurred in 15 patients with at least one of the following events: high AST, high ALT, high testosterone, high hemoglobin or hematocrit, high cholesterol, high cholesterol / LDL, high triglyceride levels, high HDL, creatinine high serum.|
|*Urinary symptoms included nocturia, urinary hesitancy, urinary incontinence, urinary retention, urinary urgency and low urinary flow.|
|**Testicular disorders included three patients. There were two with a non-palpable testicle and one with a slight sensitivity of the right testicles.|
In this study, discontinuation of treatment for adverse events included: two patients with application site reactions, one with renal failure and five with prostate disorders (increased serum PSA in 4 patients and increased PSA with enlargement of the prostate in a fifth patient).
During the initial 6-month study, the mean change in PSA values had a statistically significant increase of 0.26 ng / mL. Serum PSA was then measured every 6 months in 162 hypogonadal men treated with AndroGel 1% in the 3-year extension study. No statistically significant additional increases in mean PSA between 6 and 36 months were observed. However, an increase in serum PSA was observed in approximately 18% of patients. The overall mean change in serum PSA values from baseline for the whole group from month 6 to month 36 was 0.11 ng / mL.
Twenty-nine patients (18%) fulfilled the criterion of serum PSA increase, as defined in the protocol, defined as> 2 times baseline or any serum PSA> 6 ng / mL. Most of them (25/29) met this criterion by at least doubling their PSA relative to the baseline. In most cases where PSA has at least doubled (22/25), the peak value of serum PSA was always less than 2 ng / mL. The first appearance of a predefined increase in serum PSA after baseline was observed at or before the 12th month in most patients meeting this criterion (23 of 29, 79%).
Four patients met this criterion with serum PSA> 6 ng / mL. In these cases, the maximum serum PSA values were 6.2 ng / mL, 6.6 ng / mL, 6.7 ng / mL, and 10.7 ng / mL. In two of these patients, prostate cancer was detected at the biopsy. The first patient's PSA levels were 4.7 ng / mL and 6.2 ng / mL at baseline and at month 6 / final, respectively. The second patient's PSA levels were 4.2 ng / mL, 5.2 ng / mL, 5.8 ng / mL and 6.6 ng / mL, respectively.
The following adverse reactions have been identified during the subsequent use of AndroGel 1% after approval. Since reactions are reported voluntarily by a population of uncertain size, it is not always possible to estimate their frequency reliably nor to establish a cause-and-effect relationship with it. exposure to the drug (Table 3).
|Blood and lymphatic system disorders:||High Hgb, Hct (polycythemia)|
|Cardiovascular disorders:||Myocardial infarction, stroke|
|General disorders and reactions at the site of administration:||Asthenia, edema, discomfort|
|Genitourinary disorders:||Altered urination|
|Hepatobiliary disorders:||Abnormal liver function tests (transaminases, increased GGTP, bilirubin, for example)|
|surveys:||High PSA, electrolyte changes (nitrogen, calcium, potassium, phosphorus, sodium), changes in serum lipids (hyperlipidemia, elevated triglyceride levels, decreased HDL cholesterol), decreased glucose tolerance, fluctuating testosterone levels, weight increase|
|Benign, malignant and unspecified tumors (cysts and polyps):||Prostate cancer|
|The nervous system:||Headache, dizziness, sleep apnea, insomnia|
|Psychiatric disorders:||Depression, emotional lability, decreased libido, nervousness, hostility, amnesia, anxiety|
|Disorders of the reproductive system and breast:||Gynecomastia, mastodynia, prostatic hypertrophy, testicular atrophy, oligospermia, priapism (frequent or prolonged erections)|
|Skin and subcutaneous disorders:||Acne, alopecia, application site reaction (pruritus, dry skin, erythema, rash, discolored hair, paresthesia), sweating|
|Vascular disorders:||Hypertension, vasodilation (flushing), venous thromboembolism|
Cases of secondary exposure to testosterone resulting in virilization of children have been reported during post-marketing surveillance. Clitoral enlargement (with surgical intervention) or penis, pubic hair development, increased erection and libido, aggressive behavior, and advanced bone aging are the most common signs and symptoms of these reported cases. In most cases for which a result has been reported, it has been reported that these signs and symptoms had regressed with the elimination of testosterone gel exposure. However, in a few cases, genital enlargement did not fully return to an age-appropriate normal size, and bone age remained slightly above chronological age. In some cases, direct contact with the application sites on the skin of men using testosterone gel has been reported. In at least one reported case, the rapporteur has considered the possibility of a secondary exposure of items such as testosterone gel users' shirts and / or other tissues, such as towels and towels. sheets. (see Warnings and Precautions (5.2)).
Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens can reduce blood glucose and hence insulin requirements.
Changes in anticoagulant activity can be observed with androgens. Therefore, more frequent monitoring of the International Normalized Ratio (INR) and prothrombin time is recommended in patients taking anticoagulants, particularly at the beginning and end of androgen therapy.
Concomitant use of testosterone with corticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention and requires close monitoring, particularly in patients with cardiac, renal or hepatic disease.
USE IN SPECIFIC POPULATIONS
AndroGel 1% is contraindicated in pregnant women. Testosterone is teratogenic and can be harmful to the fetus when it is administered to a pregnant woman, based on data from animal studies and its mechanism of action (see Contraindications (4) and clinical pharmacology (12.1). The exposure of a female fetus to androgens can result in different degrees of virilization. In animal development studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural alterations of reproductive tissues in female and male offspring. These studies did not meet current standards for toxicity studies for non-clinical development.
In developmental studies conducted in rats, rabbits, pigs, sheep and rhesus monkeys, pregnant animals received an intramuscular injection of testosterone during the period of organogenesis. Testosterone treatment at doses comparable to those used in testosterone replacement therapy resulted in structural disorders in female and male children. Structural alterations observed in women included increased ano-genital distance, phallus development, an empty scrotum, absence of external vagina, intrauterine growth retardation, reduced ovarian reserve and increased ovarian follicular recruitment. Structural alterations observed in male children included increased testicular weight, greater luminal diameter of the seminal tubes, and increased lumen frequency of the obstructed tubes. Une augmentation du poids de l'hypophyse a été observée chez les deux sexes.
L'exposition in utero à la testostérone a également entraîné des changements hormonaux et comportementaux chez la progéniture. Une hypertension a été observée chez des rates gravides et leur progéniture exposée à des doses environ deux fois supérieures à celles du traitement de substitution par la fortestostérone.
Femmes et hommes ayant un potentiel de reproduction
Pendant le traitement avec de fortes doses d'androgènes exogènes, y compris AndroGel à 1%, la spermatogenèse peut être inhibée par rétro-inhibition de l'axe hypothalamo-hypophyso-testiculaire. (voir Avertissements et précautions (5,8)). Une fertilité réduite est observée chez certains hommes prenant un traitement substitutif à la testostérone. Une atrophie testiculaire, une hyperfertilité et une infertilité ont également été rapportées chez des hommes qui abusent de stéroïdes anabolisants androgènes. (voir Abus de drogues et dépendance (9.2)). Quel que soit le type d'utilisation, l'impact sur la fertilité peut être irréversible.
L'innocuité et l'efficacité d'AndroGel 1% chez les patients pédiatriques âgés de moins de 18 ans n'ont pas été établies. Une utilisation inappropriée peut entraîner une accélération de l'âge osseux et la fermeture prématurée des épiphyses.
Le nombre de patients gériatriques participant à des études cliniques contrôlées utilisant AndroGel 1% n'a pas été suffisant pour déterminer si l'efficacité chez les personnes de plus de 65 ans diffère de celle des sujets plus jeunes. De plus, les données de sécurité à long terme sur les patients gériatriques sont insuffisantes pour évaluer les risques potentiels de maladie cardiovasculaire et de cancer de la prostate.
Toxicomanie et dépendance
L'abus de drogues est l'utilisation intentionnelle non thérapeutique d'une drogue, même une fois, pour ses effets psychologiques et physiologiques gratifiants. L’abus et l’abus de testostérone sont observés chez les hommes et les femmes adultes et les adolescents. La testostérone, souvent associée à d'autres stéroïdes anabolisants androgènes (AAS), et non obtenue sur ordonnance d'une pharmacie, peut être utilisée de manière abusive par les athlètes et les bodybuilders. Des cas d'abus chez les hommes prenant des doses de testostérone obtenues légalement plus élevées que celles prescrites et la testostérone continuée en dépit d'événements indésirables ou contre l'avis d'un médecin
Des effets indésirables graves ont été rapportés chez des individus qui abusent de stéroïdes anabolisants androgènes et qui incluent un arrêt cardiaque, un infarctus du myocarde, une cardiomyopathie hypertrophique, une insuffisance cardiaque congestive, un accident vasculaire cérébral, de l'hépatotoxicité et de graves manifestations psychiatriques, y compris dépression grave, maniacie hallucinations, hostilité et agression.
Les effets indésirables suivants ont également été rapportés chez les hommes: accidents ischémiques transitoires, convulsions, hypomanie, irritabilité, dyslipidémies, atrophie testiculaire, hypofertilité et infertilité.
Les effets indésirables supplémentaires suivants ont été rapportés chez les femmes: hirsutisme, virilisation, approfondissement de la voix, hypertrophie du clitoris, atrophie du sein, calvitie masculine et irrégularités menstruelles.
Étant donné que ces réactions sont signalées volontairement par une population de taille incertaine et peuvent inclure l'abus d'autres agents, il n'est pas toujours possible d'estimer de manière fiable leur fréquence ou d'établir un lien de causalité avec l'exposition au médicament.
- Prendre des doses supérieures à celles prescrites
- Consommation de drogues en dépit des problèmes médicaux et sociaux liés à la consommation de drogues
- Consacrer beaucoup de temps à obtenir le médicament lorsque son approvisionnement est interrompu
- Donner une priorité plus grande à la consommation de drogue qu'aux autres obligations
- Avoir des difficultés à interrompre le traitement malgré les désirs et les tentatives pour le faire
- Souffrant de symptômes de sevrage lors d'un arrêt brutal d'utilisation
La dépendance physique se caractérise par des symptômes de sevrage après l'arrêt brutal du médicament ou une réduction significative de la dose d'un médicament. Les personnes prenant des doses suprathérapeutiques de testostérone peuvent présenter des symptômes de sevrage pouvant durer des semaines ou des mois: humeur dépressive, dépression majeure, fatigue, soif de désir, agitation, irritabilité, anorexie, insomnie, diminution de la libido et hypogonadisme hypogonadotrope.
Un cas de surdosage aigu associé à l'utilisation d'un produit injectable approuvé à base de testostérone: des concentrations sériques de testostérone allant jusqu'à 11 400 ng / dL dans le sang, à la suite d'un accident vasculaire cérébral.
Le traitement du surdosage consisterait en l'arrêt d'AndroGel 1%, en lavant le site d'application avec de l'eau et du savon, ainsi qu'en des soins symptomatiques et de soutien appropriés.
L’ingrédient pharmacologique actif d’AndroGel 1% est la testostérone, un androgène. La testostérone USP est une poudre cristalline blanche à pratiquement blanche décrite chimiquement comme étant la 17-beta hydroxyandrost-4-en-3-one. La formule structurelle est:
Les ingrédients pharmacologiquement inactifs contenus dans AndroGel 1% sont le carbomère 980, l’éthanol à 67,0%, le myristate d’isopropyle, de l’eau purifiée et de l’hydroxyde de sodium. Ces ingrédients ne sont pas pharmacologiquement actifs.
AndroGel – Pharmacologie clinique
Mechanism of action
Les androgènes endogènes, notamment la testostérone et la dihydrotestostérone (DHT), sont responsables de la croissance et du développement normaux des organes sexuels masculins et du maintien des caractéristiques sexuelles secondaires. 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 chord thickening, 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’s syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).
AndroGel 1% delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate normal concentrations (298 – 1043 ng/dL) seen in healthy men. AndroGel 1% provides continuous transdermal delivery of testosterone for 24 hours following a single application to intact, clean, dry skin of the shoulders, upper arms and/or abdomen.
AndroGel 1% is a hydroalcoholic formulation that dries quickly when applied to the skin surface. The skin serves as a reservoir for the sustained release of testosterone into the systemic circulation. Approximately 10% of the testosterone dose applied on the skin surface from AndroGel is absorbed into systemic circulation. In a study with AndroGel 1% 100 mg , all patients showed an increase in serum testosterone within 30 minutes, and eight of nine patients had a serum testosterone concentration within normal range by 4 hours after the initial application. Absorption of testosterone into the blood continues for the entire 24-hour dosing interval. Serum concentrations approximate the steady-state concentration by the end of the first 24 hours and are at steady state by the second or third day of dosing.
With single daily applications of AndroGel 1%, follow-up measurements 30, 90 and 180 days after starting treatment have confirmed that serum testosterone concentrations are generally maintained within the eugonadal range. Figure 1 summarizes the 24-hour pharmacokinetic profiles of testosterone for hypogonadal men (less than 300 ng/dL) maintained on AndroGel 1% 50 mg or 100 mg for 30 days. The average (± SD) daily testosterone concentration produced by AndroGel 1% 100 mg on Day 30 was 792 (± 294) ng/dL and by AndroGel 1% 50 mg 566 (± 262) ng/dL.
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.
DHT concentrations increased in parallel with testosterone concentrations during AndroGel 1% treatment. The mean steady-state DHT/T ratio during 180 days of AndroGel treatment ranged from 0.23 to 0.29 (50 mg of AndroGel 1%/day) and from 0.27 to 0.33 (100 mg of AndroGel 1%/day).
There is considerable variation in the half-life of testosterone concentration 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.
When AndroGel 1% treatment is discontinued after achieving steady state, serum testosterone concentrations remain in the normal range for 24 to 48 hours but return to their pretreatment concentrations by the fifth day after the last application.
The potential for dermal testosterone transfer following AndroGel 1% use was evaluated in a clinical study between males dosed with AndroGel 1% and their untreated female partners. Two (2) to 12 hours after application of 100 mg of testosterone administered as AndroGel 1% by the male subjects, the couples (N = 38 couples) engaged in daily, 15-minute sessions of vigorous skin-to-skin contact so that the female partners gained maximum exposure to the AndroGel 1% application sites. Under these study conditions, all unprotected female partners had a serum testosterone concentration >2 times the baseline value at some time during the study. When a shirt covered the application site(s), the transfer of testosterone from the males to the female partners was completely prevented.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats.
Clinical Trials in Adult Hypogonadal Males
AndroGel 1% was evaluated in a multi-center, randomized, parallel-group, active-controlled, 180-day trial in 227 hypogonadal men. The study was conducted in 2 phases. During the Initial Treatment Period (Days 1-90), 73 patients were randomized to AndroGel 1% 50 mg daily, 78 patients to AndroGel 1% 100 mg daily, and 76 patients to a non-scrotal testosterone transdermal system. The study was double-blind for dose of AndroGel 1% but open-label for active control. Patients who were originally randomized to AndroGel 1% and who had single-sample serum testosterone concentrations above or below the normal range on Day 60 were titrated to 75 mg daily on Day 91. During the Extended Treatment Period (Days 91-180), 51 patients continued on AndroGel 1% 50 mg daily, 52 patients continued on AndroGel 1% 100 mg daily, 41 patients continued on a non-scrotal testosterone transdermal system (5 mg daily), and 40 patients received AndroGel 1% 75 mg daily. Upon completion of the initial study, 163 enrolled and 162 patients received treatment in an open-label extension study of AndroGel 1% for an additional period of up to 3 years.
Mean peak, trough and average serum testosterone concentrations within the normal range (298-1043 ng/dL) were achieved on the first day of treatment with doses of 50 mg and 100 mg of AndroGel 1%. In patients continuing on AndroGel 1% 50 mg and 100 mg, these mean testosterone concentrations were maintained within the normal range for the 180-day duration of the original study. Figure 2 summarizes the 24-hour pharmacokinetic profiles of testosterone administered as AndroGel 1% for 30, 90 and 180 days. Testosterone concentrations were maintained as long as the patient continued to properly apply the prescribed AndroGel 1% treatment.
Table 4 summarizes the mean testosterone concentrations on Treatment Day 180 for patients receiving 50 mg, 75 mg, or 100 mg of AndroGel 1%. The 75 mg dose produced mean concentrations intermediate to those produced by 50 mg and 100 mg of AndroGel 1%.
|50 mg||75 mg||100 mg|
|N = 44||N = 37||N = 48|
|VSavg||555 ± 225||601 ± 309||713 ± 209|
|VSmax||830 ± 347||901 ± 471||1083 ± 434|
|VSmin||371 ± 165||406 ± 220||485 ± 156|
Of 129 hypogonadal men who were appropriately titrated with AndroGel 1% and who had sufficient data for analysis, 87% achieved an average serum testosterone concentration within the normal range on Treatment Day 180.
In patients treated with AndroGel 1%, there were no observed differences in the average daily serum testosterone concentrations at steady-state based on age, cause of hypogonadism, or body mass index.
DHT concentrations increased in parallel with testosterone concentrations at AndroGel 1% doses of 50 mg/day and 100 mg/day, but the DHT/T ratio stayed within the normal range, indicating enhanced availability of the major physiologically active androgen. Serum estradiol (E2) concentrations increased significantly within 30 days of starting treatment with AndroGel 1% 50 or 100 mg/day and remained elevated throughout the treatment period but remained within the normal range for eugonadal men. Serum levels of SHBG decreased very slightly (1 to 11%) during AndroGel 1% treatment. In men with hypergonadotropic hypogonadism, serum levels of LH and FSH fell in a dose- and time-dependent manner during treatment with AndroGel 1%.
Phototoxicity in Humans
The phototoxic potential of AndroGel 1% was evaluated in a double-blind, single-dose study in 27 subjects with photosensitive skin types. The Minimal Erythema Dose (MED) of ultraviolet radiation was determined for each subject. A single 24 (+1) hour application of duplicate patches containing test articles (placebo gel, testosterone gel, or saline) was made to naive skin sites on Day 1. On Day 2, each subject received five exposure times of ultraviolet radiation, each exposure being 25% greater than the previous one. Skin evaluations were made on Days 2 to 5. Exposure of test and control article application sites to ultraviolet light did not produce increased inflammation relative to non-irradiated sites, indicating no phototoxic effect.
How Supplied/Storage and Handling
|NDC Number||Package Size|
|0051-8425-30||30 packets (a unit dose packet containing 25 mg of testosterone provided in 2.5 g of gel)|
|0051-8450-30||30 packets (a unit dose packet containing 50 mg of testosterone provided in 5 g of gel)|
Patient Counseling Information
Use in Men with Known or Suspected Prostate or Breast Cancer
Potential for Secondary Exposure to Testosterone and Steps to Prevent Secondary Exposure
Secondary exposure to testosterone in children and women can occur with the use of testosterone gel in men (see Warnings and Precautions (5.2)). Cases of secondary exposure to testosterone have been reported in children.
- In children; unexpected sexual development including inappropriate enlargement of the penis or clitoris, premature development of pubic hair, increased erections, and aggressive behavior
- In women; changes in hair distribution, increase in acne, or other signs of testosterone effects
- The possibility of secondary exposure to testosterone gel should be brought to the attention of a healthcare provider
- AndroGel 1% should be promptly discontinued until the cause of virilization is identified
Strict adherence to the following precautions is advised to minimize the potential for secondary exposure to testosterone from testosterone gel in men (see Medication Guide):
- Children and women should avoid contact with unwashed or unclothed application site(s) of men using testosterone gel
- Patients using AndroGel 1% should apply the product as directed and strictly adhere to the following:
- Wash hands with soap and water after application
- Cover the application site(s) with clothing after the gel has dried
- Wash the application site(s) thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated
- In the event that unwashed or unclothed skin to which AndroGel 1% has been applied comes in contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible (see Dosage and Administration (2.2), Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)).
Potential Adverse Reactions with Androgens
- Changes in urinary habits such as increased urination at night, trouble starting your urine stream, passing urine many times during the day, having an urge that you have to go to the bathroom right away, having a urine accident, being unable to pass urine and 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.
Patients Should Be Advised of the Following Instructions for Use:
- Read the Medication Guide before starting AndroGel 1% therapy and to reread it each time the prescription is renewed
- AndroGel 1% should be applied and used appropriately to maximize the benefits and to minimize the risk of secondary exposure in children and women
- Keep AndroGel 1% out of the reach of children
- AndroGel 1% is an alcohol based product and is flammable; therefore avoid fire, flame or smoking until the gel has dried
- It is important to adhere to all recommended monitoring
- Report any changes in their state of health, such as changes in urinary habits, breathing, sleep, and mood
- AndroGel 1% is prescribed to meet the patient’s specific needs; therefore, the patient should never share AndroGel 1% with anyone.
- Wait 5 hours before swimming or washing following application of AndroGel 1%. This will ensure that the greatest amount of AndroGel 1% is absorbed into their system.
Read this Instructions for Use for AndroGel 1% before you start using it and each time you get a refill. Il peut y avoir de nouvelles informations. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment.
- Before applying AndroGel 1%, make sure that your shoulders, upper arms or stomach are clean, dry, and there is no broken skin.
- The application sites for AndroGel 1% are the shoulders, upper arms or stomach area (abdomen) that will be covered by a short sleeve t-shirt (see Figure A). Do not apply AndroGel 1% to any other parts of your body such as your penis, scrotum, chest, armpits (axillae), knees, or back.
- Tear open the packet completely at the dotted line. Squeeze from the bottom of the packet to the top.
- Squeeze all of the AndroGel 1% out of the packet into the palm of your hand.
- Apply AndroGel 1% to the application site. You may also apply AndroGel 1% from the packet directly to the application site.
- Let the application areas dry completely before putting on a t-shirt.
- AndroGel 1% is flammable until dry. Let AndroGel 1% dry before smoking or going near an open flame.
- Wash your hands with soap and water right away after applying AndroGel 1%.
- Avoid showering, swimming, or bathing for at least 5 hours after you apply AndroGel 1%.
- Store AndroGel 1% at room temperature between 68ºF to 77ºF (20ºC to 25ºC).
- Safely throw away used AndroGel 1% in the household trash. Be careful to prevent accidental exposure of children or pets.
- Keep AndroGel 1% away from fire.
|Labeler – AbbVie Inc. (078458370)|