ANDROGEL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ANDROGEL (ANDROGEL).
Androgen receptor agonist; testosterone replacement therapy to restore serum testosterone to physiologic levels.
| Metabolism | Hepatic via CYP3A4, CYP2C9, and 17β-hydroxysteroid dehydrogenase; metabolites include estradiol and dihydrotestosterone. |
| Excretion | Approximately 90% of a topical dose is excreted in urine as conjugated and unconjugated metabolites, with about 6% excreted in feces via bile; renal elimination is the primary route. |
| Half-life | The terminal elimination half-life of testosterone from AndroGel is approximately 10-12 hours when applied topically, but due to continuous absorption from the skin depot, serum levels are sustained over 24 hours, allowing once-daily dosing. |
| Protein binding | Approximately 98% of circulating testosterone is protein-bound: 40-50% bound to sex hormone-binding globulin (SHBG) and 50-60% loosely bound to albumin. |
| Volume of Distribution | The apparent volume of distribution of testosterone is about 1.0 L/kg, reflecting extensive distribution into tissues, particularly muscle, skin, and male reproductive organs. |
| Bioavailability | Bioavailability of testosterone from AndroGel is approximately 10-14% of the applied dose, due to limited skin permeation and first-pass metabolism (though minimal with transdermal route). For comparison, oral testosterone bioavailability is <1%, while intramuscular testosterone enanthate has 100% bioavailability. |
| Onset of Action | AndroGel applied topically to the shoulders, upper arms, or abdomen: serum testosterone levels rise within 30 minutes, but full therapeutic effect (e.g., normalization of hypogonadal symptoms) is typically achieved after 2-4 weeks of daily application. |
| Duration of Action | With once-daily application, serum testosterone levels remain within the normal range for 24 hours; clinical effects (e.g., libido, energy) persist as long as treatment is continued. Withdrawal leads to return to hypogonadal state within 1-2 weeks. |
| Action Class | Androgens |
| Brand Substitutes | Androfil Gel, Testoheal Gel, Androtas Gel, Cernos Gel, Androrise Gel |
50 mg (5 g gel) applied topically once daily, preferably in the morning. Dose may be adjusted between 25 mg (2.5 g gel) and 100 mg (10 g gel) based on serum testosterone levels.
| Dosage form | GEL |
| Renal impairment | No specific dose adjustment is provided for renal impairment. Use with caution in patients with severe renal impairment due to potential for fluid retention. |
| Liver impairment | Contraindicated in patients with Child-Pugh class C (severe hepatic impairment). Use with caution and monitor liver function in mild to moderate hepatic impairment; no specific dose reduction guidelines exist. |
| Pediatric use | Not indicated in pediatric patients under 18 years of age; safety and efficacy have not been established. |
| Geriatric use | Elderly patients may be more sensitive to androgens, and require careful monitoring for prostate enlargement, prostate cancer, and fluid retention. Start at the lowest dose (25 mg daily) and titrate based on serum testosterone levels and clinical response. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ANDROGEL (ANDROGEL).
| Breastfeeding | Testosterone is excreted into breast milk with an estimated M/P ratio of 0.1-0.3. It may cause virilization in nursing infants. Breastfeeding is not recommended during AndroGel therapy. |
| Teratogenic Risk | AndroGel (testosterone) is contraindicated in pregnancy. Testosterone is a teratogen with masculinization of female fetuses (clitoral enlargement, labial fusion, urogenital sinus abnormalities) when exposed during the first trimester. Second and third trimester exposure may cause pseudohermaphroditism in females. Risk is highest during the first 12 weeks of gestation. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Known hypersensitivity to testosterone or gel components","Prostate cancer","Breast cancer (males)","Women who are pregnant or may become pregnant (risk to fetus)"]
| Precautions | ["Risk of secondary exposure to testosterone (children) – avoid skin contact","Polycythemia (monitor hematocrit)","Prostate enlargement/cancer risk","Cardiovascular risk (especially in elderly)","Spermatogenesis suppression","Hepatic effects (monitor liver function)","Edema (in patients with preexisting conditions)"] |
| Food/Dietary | No specific food interactions. Grapefruit juice may increase testosterone levels due to CYP3A4 inhibition, but clinical significance is unclear. Avoid excessive alcohol intake as it may affect testosterone levels and liver function. |
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| Fetal Monitoring |
| Monitor for signs of virilization in both mother and fetus. Perform ultrasound to assess fetal genital development if exposure occurs. Measure maternal serum testosterone levels to ensure therapeutic levels and avoid excessive exposure. Monitor maternal liver function, lipid profile, and hemoglobin due to potential adverse effects. |
| Fertility Effects | AndroGel can suppress spermatogenesis by inhibiting gonadotropin release (FSH, LH), leading to decreased sperm count and motility, potentially causing male infertility. Effects are reversible upon discontinuation. In females, testosterone may impair ovulation. |
| Clinical Pearls | Apply to clean, dry, intact skin on shoulders, upper arms, or abdomen. Avoid application to genitals or chest due to higher absorption and risk of transfer. Wash hands after application. Allow gel to dry before dressing. Monitor serum testosterone, hematocrit, PSA, and lipid profile. Contraindicated in men with breast or prostate cancer. May cause erythrocytosis, sleep apnea, or worsening of BPH. Risk of testosterone transfer to women or children; cover application site or wash skin before contact. |
| Patient Advice | Apply AndroGel once daily at the same time each morning to clean, dry, intact skin on shoulders, upper arms, or abdomen. · Do not apply to genitals or chest. · Wash hands thoroughly with soap and water after application. · Allow gel to dry completely before dressing or coming into contact with others. · Avoid swimming, showering, or bathing for at least 5 hours after application. · If skin contact with another person is likely, cover the application site with clothing or wash the area before contact. · Keep AndroGel away from children and women of childbearing potential. · Report any signs of deep vein thrombosis (leg swelling, pain, warmth), heart attack (chest pain, shortness of breath), or stroke (sudden weakness, confusion, vision changes). · Regular blood tests are required to monitor testosterone levels, red blood cell count, prostate health, and cholesterol. · AndroGel may interact with blood thinners (e.g., warfarin) and corticosteroids; inform all healthcare providers. |