Natesto

Androgens

Hazardous Drugs Classification
NIOSH 2016 List: Group 3
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
INJECTABLES: Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
ORAL TABLETS/CAPSULES/ORAL LIQUID: Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Eye/face and respiratory protection may be needed during preparation and administration.
TOPICAL/TRANSDERMAL: Use double chemotherapy gloves and protective gown. Eye/face and respiratory protection may be needed during preparation and administration.

Testosterone undecanoate oral capsules:
Administer with food or meals.
Specific testosterone undecanoate oral products are not substitutable with each other as dosages differ with various dosage forms and brands.

Many testosterone injections are for intramuscular use only. Do NOT administer intravenously or intravascularly.
One testosterone enanthate injection product (Xyosted) is administered via subcutaneous injection only. Do NOT administer intravenously. Avoid intramuscular or intravascular injection.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Testosterone cypionate in oil injection:
Testosterone cypionate injection is a clear, colorless to pale yellow solution in cottonseed oil. Warming and shaking the vial should redissolve any crystals that may have formed during storage at temperatures lower than recommended.
Inject deep into the gluteal muscle. Take care to avoid intravascular injection.
For subsequent injections, alternate injection site.
 
Testosterone enanthate in oil injection:
Testosterone enanthate injection is a clear, colorless to pale yellow solution in sesame oil.
Inject deep into the gluteal muscle. Take care to avoid intravascular injection.
Inject testosterone enanthate slowly. Use of a wet needle or wet syringe may cause the testosterone enanthate solution to become cloudy but will not alter potency.
For subsequent injections, alternate injection site.
 
Testosterone undecanoate injection (Aveed injection):
Testosterone undecanoate injection is a clear, yellowish, sterile oily solution in refined castor oil.
Withdraw 3 mL (750 mg) of the 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 before injection.
The site for injection 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.
Inject testosterone undecanoate slowly and deeply into the gluteus medius muscle as follows. Take care to avoid intravascular injection.
Following antiseptic skin preparation, enter the gluteus medius muscle and maintain the syringe at a 90-degree angle with the needle in its deeply imbedded position.
Grasp the barrel of the syringe firmly with 1 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.
Monitor patient for 30 minutes following each injection in order to provide appropriate medical treatment in the event of serious pulmonary oil microembolism (POME) reaction or anaphylaxis.
Discard any unused portion in the vial.
For subsequent injections, alternate injection site between the right and left buttocks.

Testosterone Enanthate Subcutaneous Injection (Xyosted)
Testosterone enanthate injection is a clear, colorless to pale yellow solution in sesame oil. The product is a single-use auto-injector for weekly administration.
For subcutaneous injection only.
Do not use if the medicine is cloudy or if visible particles are present. You may notice an air bubble, this is normal.
Do not remove the cap until ready to inject.
Wash hands with soap and water.
Wipe the abdomen injection site with an alcohol swab. Allow the site to dry on its own. Only use the left or right side of the abdomen for injection sites. Do not use the area within 2 inches around the navel. Do not use in areas where the skin is tender, bruised, red, scaly, or hard. Avoid areas with scars, tattoos, or stretch marks.
Administering injection using Autoinjector:
Twist the cap to remove it. You may notice a few drops of liquid, this is normal. The auto-injector should be used or discarded after the cap is removed. Do not re-cap for later use.
Do not touch the needle end of the auto-injector with your hand or fingers after the cap is removed, doing so can cause injection and injury to your hands.
Position the auto-injector and gently squeeze the abdomen injection site to create a raised area. Hold that area firmly until after the injection is complete. Place the needle end of the auto-injector on the abdomen injection site. Keep the auto-injector straight at a 90-degree angle to the abdomen injection site.
Firmly push the auto-injector down on the abdomen site and continue to hold it down after you hear the "click". While holding the auto-injector down, slowly count from 1 to 10 to allow all of the medicine to be delivered. Keep holding the auto-injector down for a total of 10 seconds even if the injection is complete and the viewing window turns orange sooner.
It is normal if there is slight bleeding from the site after injection. If this occurs, hold a cotton ball or gauze on the area for a few seconds. Do not rub the area.
After injecting, inspect the viewing window of the auto-injector. It should be orange confirming the dose was administered. If the viewing window is not orange, do not use another auto-injector and do not attempt another injection. Call the healthcare provider or call the Xyosted information number 1-844-996-7833 for assistance.
Rotate injection sites with each injection.
Disposal: After completing the injection, dispose of the auto-injector and cap in an FDA-cleared sharps disposal container immediately after use; do not dispose of the auto-injector in the household trash.[63592]

Subcutaneous Implants
Testosterone implant pellets (Testopel)
Testosterone pellets are for subcutaneous implantation. Pellets may extrude or migrate from the insertion site if superficially implanted or if aseptic technique is not used.

Apply topically for transdermal absorption as transdermal patches, skin gels, solutions, or ointments.
Wash hands before and after application of any of these dosage forms. Take care not to touch the eyes or other mucous membranes.

General Administration Information:
For all products, allow the site to dry a few minutes before putting on clothing.
In order to maintain serum testosterone levels in the normal range, washing, showering, and swimming should be avoided for 5 to 6 hours after applying AndroGel 1% and for 2 hours after applying Androgel 1.62%, Testim, or Fortesta.
Direct contact of the gel-medicated skin with the skin of another person can result in the transfer of residual testosterone and absorption by the other person. This is particularly important for women or children that may come into contact with the treated area. Even a few minutes of contact may result in transfer of the drug. It is recommended that the treated area be clothed at all times prior to washing off residual drug. If direct skin-to-skin contact with another person is anticipated, the application sites must be washed thoroughly with soap and water. If another person comes in direct skin-to-skin contact with unwashed or unclothed treated skin, that person should wash the general area of contact with soap and water as soon as possible.
Patients should be advised that topical gels are typically flammable; therefore, fire, flame, and smoking should be avoided during use.
 
Administration of Specific Products:
AndroGel 1% packet: Open packets needed for proper dosing. Squeeze the entire contents of the dose into the palm of the hand and then immediately apply to the skin site; alternatively, squeeze a portion of the gel from the packet into the palm of the hand and apply to the application sites, repeating until the entire contents of the packet have been applied. Apply once daily (preferably in the morning) to clean, dry skin on the shoulders, upper arm or the abdomen. Do not apply to the genitals.
 
AndroGel 1% Pump: Each actuation of the metered dose pump dispenses 1.25 g of gel when fully depressed once (i.e., 4 pumps = 5 g; 6 pumps = 7.5 g; 8 pumps = 10 g) The pump must be primed before the first use by fully depressing the pump mechanism 3 times, and discarding any gel that is released during the priming. The entire dosage needed may be pumped into the palm of the hand and then immediately apply to the skin site or each individual actuation may be delivered into the palm of the hand and applied to the application sites, repeating until the entire dose has been applied. Alternatively, the gel can be directly applied to the application site which can prevent loss of product that may occur during transfer from the palm of the hand onto the application site. Apply once daily (preferably in the morning) to clean, dry skin on the shoulders, upper arm or the abdomen. Do not apply to the genitals.
 
Androgel 1.62% packet: Open packets needed for proper dosing. Squeeze the entire contents of the dose into the palm of the hand and then immediately apply to the skin site or squeeze a portion of the gel from the packet into the palm of the hand and apply to the application sites, repeating until the entire contents of the packet have been applied. Alternatively, the gel can be directly applied to the application site which can prevent loss of product that may occur during transfer from the palm of the hand onto the application site. Apply dose once daily in the morning to clean, dry skin of the shoulders and upper arms. Limit the application site to the area that will be covered by a short sleeve T-shirt. Do not apply to other parts of the body including the abdomen, genitals, chest, armpits or knees.
 
AndroGel 1.62% Pump: Each actuation of the metered dose pump dispenses 20.25 mg when fully depressed once (i.e., 1 pump = 20.25 mg; 2 pumps = 40.5 mg; 3 pumps = 60.75 mg; 4 pumps = 81 mg). The pump must be primed before the first use by fully depressing the pump mechanism 3 times, and discarding any gel that is released during the priming. Once primed, apply dose once daily in the morning to clean, dry skin of the shoulders and upper arms. Limit the application site to the area that will be covered by a short sleeve T-shirt. Do not apply to other parts of the body including the abdomen, genitals, chest, armpits or knees. Each individual actuation may be pumped into the palm of the hand and then applied to the skin site or pumped directly onto the application site. Regardless of method, apply the gel from one pump actuation to one shoulder and upper arm area, then apply each additional actuation to the alternate shoulder and upper arm area, repeating the application site as needed for dosage increases.
 
Testim packet: Open packets needed for proper dosing. Squeeze the entire contents of the dose into the palm of the hand and then immediately apply to the skin site; alternatively, squeeze a portion of the gel from the packet into the palm of the hand and apply to the application sites, repeating until the entire contents of the packet have been applied. Apply once daily (preferably in the morning) to clean, dry skin on the shoulders and/or upper arm. Do not apply to the genitals or abdomen. The gel may have an alcoholic or musk odor.
 
Fortesta gel: Apply gel to clean, dry, intact skin of the front and inner thighs. Do not apply to the genitals or other parts of the body. Using one finger, gently rub gel evenly onto the front and inner area of each thigh as directed. Avoid the area adjacent to the scrotum, and limit the application site to the area that will be covered by shorts or pants. Allow the gel to dry completely and cover with clothing. The pump must be primed before the first use by fully depressing the pump mechanism 8 times and discarding any gel that is released during the priming. Once primed, each actuation of the metered dose pump delivers 10 mg of testosterone. Apply the gel from one actuation (1 pump = 10 mg testosterone) to one thigh, then apply each additional actuation to the alternate thigh, repeating the application site as needed for dosage increases.

Androderm Transdermal System:
Apply patch to a dry, clean area of skin on the upper arms, thighs, back or abdomen immediately after opening the pouch and removing the protective release liner. If the liner is difficult to pull off or if you see adhesive sticking to the liner, DO NOT use the patch, throw it away and get a new one.
Press the system firmly in place, making sure there is good contact with the skin, especially around the edges.
Do not apply to the scrotum or bony areas of the body. Do not apply to an area that is oily, damaged, or irritated. Also, avoid applying on a part of the body that may be subject to prolonged pressure during sleep or sitting (e.g., the deltoid region of the upper arm, the greater trochanter of the femur, and the ischial tuberosity).
Washing, showering, and swimming should be avoided for a minimum of 3 hours after application.
Rotate sites daily and do not reuse a site for 7 days.
Removal of the Androderm patch before undergoing magnetic resonance imaging (MRI) is recommended because the patch contains aluminum.
Mild skin irritation may be ameliorated by treatment of the affected skin with over-the-counter topical hydrocortisone cream applied after system removal. Additionally, applying a small amount of 0.1% triamcinolone acetonide cream to the skin under the central drug reservoir of the Androderm transdermal system has been shown to reduce the incidence and severity of skin irritation. The administration of 0.1% triamcinolone acetonide cream does not significantly alter transdermal absorption of testosterone from the system. Ointment formulations should not be used for pretreatment as they may significantly reduce testosterone absorption.

Axiron topical solution:
Using the provided applicator, apply the solution to clean, dry, intact skin of the axilla, preferably at the same time each morning. Do not apply to any other part of the body including the scrotum, penis, abdomen, shoulders, or upper arms. Allow the solution to dry completely before dressing. If an antiperspirant or deodorant is used for personal hygiene, apply these products at least 2 minutes before applying the topical solution. The pump must be primed before the first use by fully depressing the pump mechanism 3 times, and discarding any solution that is released during the priming. To dispense the solution, position the nozzle over the applicator cup and carefully depress the pump once fully; the cup should be filled with no more than 1 pump actuation (30 mg testosterone). With the applicator upright, place it up into the axilla and wipe steadily down and up into the axilla. Do not use fingers or hand to rub the solution. If multiple applications are necessary for the required dose, alternate application between the left and right axilla. When repeat application to the same axilla is necessary, allow the solution to dry completely before the next application. After use, rinse the applicator under running water and pat dry with tissue. Wash hands with soap and water.
Following application, allow the site to dry a few minutes before putting on clothing.
Direct contact of the medicated skin with the skin of another person can result in the transfer of residual testosterone and absorption by the other person. To reduce accidental transfer, the patient should cover the application site(s) with clothing (e.g., a T-shirt) after the solution has dried. The application site should be washed with soap and water prior to any skin-to-skin contact regardless of the length of time since application. In the case of direct contact, the other person should wash the area of contact with soap and water as soon as possible.
Patients should be advised that the topical solution is flammable; therefore, fire, flame, and smoking should be avoided during use.
Advise patients to avoid swimming or washing the application site until 2 hours following application of solution.

Extemporaneous compounding of a Testosterone Cream:
NOTE: The extemporaneous compounded testosterone cream is not approved by the FDA for topical administration.
Several commercial compounding kits are available. Follow the directions of the manufacturer which are supplied with each kit for preparation instructions.

Intranasal Administration
Natesto Nasal Gel:
Wash hands before and after application.
For intranasal use only; do not administer to other parts of the body.
For first time use of the Natesto nasal gel, prime the pump by depressing the pump 10 times over the sink and discarding any dispensed product. Wipe the tip of the dispenser clean with a dry tissue.
Before administration, instruct patient to blow their nose and remove dispenser cap.
Place the right index finger on the pump of the actuator and while in front of a mirror, slowly advance the tip of the actuator into the left nostril upwards until the finger on the pump reaches the base of the nose. Tilt the actuator so that the opening on the tip of the actuator is in contact with the lateral wall of the nostril to ensure that the gel is applied to the nasal wall.
Slowly depress the pump until it stops; depress pump completely to administer a full actuation. Each actuation of the metered dose pump dispenses 5.5 mg of testosterone.
Remove the actuator from the nose while wiping the tip along the inside of the lateral nostril wall to fully transfer the gel.
Using the left index finger, repeat steps for administration of the next actuation, this time to the lateral wall of the right nostril.
Wipe the tip of the actuator with a dry tissue, replace dispenser cap.
Two actuations total (1 actuation in each nostril) will deliver 11 mg of testosterone.
Press on the nostrils at a point just below the bridge of the nose and lightly massage.
Do not blow the nose or sniff for 1 hour after administration of the intranasal gel.
If any gel gets on the hands, it is recommended to wash hands with warm water and soap.
Replace the nasal gel dispenser when the top of the piston inside the dispenser reaches the arrow at the top of the inside label. The inside label may be found by unwrapping the outer flap from around the container.

erythrocytosis / Delayed / 1.3-14.0
prostatic hypertrophy / Delayed / 1.0-5.0
pulmonary oil microembolism / Rapid / 0-0.3
feminization / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
breast cancer / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
stroke / Early / Incidence not known
pulmonary embolism / Delayed / Incidence not known
thromboembolism / Delayed / Incidence not known
suicidal ideation / Delayed / Incidence not known
apnea / Delayed / Incidence not known
skin necrosis / Early / Incidence not known
hearing loss / Delayed / Incidence not known
teratogenesis / Delayed / Incidence not known
virilization / Delayed / Incidence not known
epiphyseal closure / Delayed / Incidence not known

hypertension / Early / 1.0-12.7
contact dermatitis / Delayed / 1.6-4.0
dysuria / Early / 0-3.0
prostatitis / Delayed / 0-3.0
hematuria / Delayed / 0-3.0
depression / Delayed / 1.0-3.0
confusion / Early / 0-3.0
polycythemia / Delayed / 0-2.0
hot flashes / Early / 1.0-1.0
edema / Delayed / 0-1.0
memory impairment / Delayed / 0-1.0
amnesia / Delayed / 0-1.0
hostility / Early / 0-1.0
elevated hepatic enzymes / Delayed / 0-1.0
hypoglycemia / Early / 0-1.0
hyperglycemia / Delayed / 0-1.0
wheezing / Rapid / 0-1.0
erythema / Early / 0-1.0
bullous rash / Early / 0-1.0
peripheral edema / Delayed / 2.0
priapism / Early / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known
testicular atrophy / Delayed / Incidence not known
infertility / Delayed / Incidence not known
fluid retention / Delayed / Incidence not known
hypercholesterolemia / Delayed / Incidence not known
hypertriglyceridemia / Delayed / Incidence not known
hyperlipidemia / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
peliosis hepatis / Delayed / Incidence not known
constipation / Delayed / Incidence not known
skin ulcer / Delayed / Incidence not known
furunculosis / Delayed / Incidence not known
osteoporosis / Delayed / Incidence not known
osteopenia / Delayed / Incidence not known
hypercalcemia / Delayed / Incidence not known
physiological dependence / Delayed / Incidence not known
psychological dependence / Delayed / Incidence not known

pruritus / Rapid / 1.9-37.0
pharyngitis / Delayed / 3.8-8.7
acne vulgaris / Delayed / 1.0-8.0
skin irritation / Early / 0-8.0
rhinorrhea / Early / 3.8-7.8
epistaxis / Delayed / 3.8-6.5
vesicular rash / Delayed / 0-6.0
headache / Early / 1.0-6.0
nasal irritation / Early / 3.8-5.9
parosmia / Delayed / 5.8-5.8
nasal dryness / Early / 4.2-4.2
nausea / Early / 0-4.0
vomiting / Early / 0-4.0
nasal congestion / Early / 3.9-3.9
sinusitis / Delayed / 3.8-3.8
mastalgia / Delayed / 0-3.0
gynecomastia / Delayed / 1.0-3.0
libido decrease / Delayed / 0-3.0
infection / Delayed / 0-3.0
polyuria / Early / 0-3.0
fatigue / Early / 0-3.0
emotional lability / Early / 1.0-3.0
gastroesophageal reflux / Delayed / 0-3.0
diarrhea / Early / 0-3.0
insomnia / Early / 0-2.3
irritability / Delayed / 0-2.0
abdominal pain / Early / 0-2.0
rash / Early / 0-2.0
abnormal dreams / Early / 0-1.3
hyperhidrosis / Delayed / 0-1.3
appetite stimulation / Delayed / 0-1.0
maculopapular rash / Early / 0-1.0
alopecia / Delayed / 0-1.0
hair discoloration / Delayed / 0-1.0
paresthesias / Delayed / 0-1.0
urticaria / Rapid / 0-1.0
folliculitis / Delayed / 0-1.0
lacrimation / Early / 0-1.0
libido increase / Delayed / 10.0
eructation / Early / 2.0
dyspepsia / Early / 2.0
spermatogenesis inhibition / Delayed / Incidence not known
oligospermia / Delayed / Incidence not known
azoospermia / Delayed / Incidence not known
nocturia / Early / Incidence not known
weight gain / Delayed / Incidence not known
anxiety / Delayed / Incidence not known
xerosis / Delayed / Incidence not known
seborrhea / Delayed / Incidence not known
injection site reaction / Rapid / Incidence not known
malaise / Early / Incidence not known
musculoskeletal pain / Early / Incidence not known
back pain / Delayed / Incidence not known
pelvic pain / Delayed / Incidence not known
arthralgia / Delayed / Incidence not known
chills / Rapid / Incidence not known
myalgia / Early / Incidence not known
asthenia / Delayed / Incidence not known
tinnitus / Delayed / Incidence not known
amenorrhea / Delayed / Incidence not known
oligomenorrhea / Delayed / Incidence not known
hirsutism / Delayed / Incidence not known

Administration of testosterone undecanoate injection has been associated with cases of serious pulmonary oil microembolism (POME) reactions as well anaphylactoid reactions. Reported cases of POME reactions occurred during or immediately after intramuscular injection of testosterone undecanoate. Symptoms included: cough, urge to cough, dyspnea, hyperhidrosis, throat tightening, chest pain, dizziness, and syncope. Most cases lasted a few minutes and resolved with supportive measures; however, some lasted up to several hours, and some required emergency care and/or hospitalization. When administering testosterone undecanoate, clinicians should take care to inject deeply into the gluteal muscle, avoiding intravascular injection. In addition to POME reactions, episodes of anaphylaxis, including life-threatening reactions, have also been reported following the intramuscular injection of testosterone undecanoate. Patients with suspected hypersensitivity reactions should not be retreated with testosterone undecanoate. After every administration, monitor patient for 30 minutes and provide appropriate medical treatment in the event of serious POME or anaphylactoid reactions. Due to the risk of serious POME and anaphylaxis reactions, testosterone undecanoate injection (Aveed) is only available through a restricted program called the Aveed REMS Program. Clinicians wanting to prescribe Aveed injection must be certified with the REMS Program for purposes of ordering or dispensing the product. Healthcare settings must also be certified with the REMS Program and must have the resources to provide emergency medical treatment in cases of serious POME and anaphylaxis. Further information is available at www.AveedREMS.com or call 1-855-755-0494 in the U.S.

The FDA has alerted clinicians and the public of a possible increased cardiovascular risk associated with approved and unapproved uses of testosterone products.[58958] Testosterone is only approved for use in men with low testosterone concentrations due to medical conditions, and not exclusively due to aging. FDA labeled indications for testosterone replacement therapy include hypogonadism due to disorders of the testicles, pituitary gland, or brain. Before initiating testosterone, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least 2 separate days and that these serum testosterone concentrations are below the normal range. Clinicians should inform patients of the risk associated with therapy and counsel them on seeking immediate medical attention if they experience signs and symptoms of a cardiovascular event.[30060] [33698] [42603] [42676] [42931] [42932] [42691] [42677] [44211] [56803] [57334] [63592] [64030] Use testosterone with caution in men with coronary artery disease. Long-term clinical safety trials with testosterone products have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. Data from epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events, such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of these events in association with the use of testosterone replacement therapy in men.[30060] [33698] [42603] [42676] [42931] [42691] [42677] [42932] [44211] [56803] [57334] [63592] [64030] An observational study in the U.S. Veteran Affairs health system reported than 3 years after coronary angiography, 25.7% of patients receiving testosterone therapy suffered a severe and/or fatal cardiovascular event (MI, stroke, death) compared to 19.9% of patients not receiving therapy.[56670] A second observational study investigated the incidence of acute non-fatal MI following an initial testosterone prescription in both younger (55 years and younger) and older (65 years of age and older) adult males (n = 55,593). The incidence rate of MI occurring within 90 days following the initial testosterone prescription was compared to the incidence rate of MI occurring in the year leading up to the first prescription. Among older males, a 2-fold increase in the risk of MI was observed within the 90-day window; among younger males with a pre-existing history of heart disease, a 2- to 3-fold increased risk of MI was observed. In contrast, no increased risk was observed in younger males without a history of heart disease.[56671] Edema (due to sodium and fluid retention) with or without congestive heart failure may be a serious complication of testosterone therapy of any type in patients with preexisting cardiac disease. In addition to discontinuation of the drug, diuretic therapy may be required. Increased blood pressure has also been reported with testosterone therapy; patients receiving testosterone therapy who have a history of hypertension should be closely monitored.[30060] [33698] [42603] [42676] [42931] [42691] [42677] [42932] [44211] [56803] [57334] [64030] The testosterone enanthate subcutaneous injection and testosterone undecanoate oral capsules carry a boxed warning, as they may cause hypertension that can increase the risk of major adverse cardiovascular events (MACE), including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular (CV) death. Because of this risk, use testosterone enanthate subcutaneous injection and testosterone undecanoate oral capsules only for the treatment of men with hypogonadal conditions associated with structural or genetic etiologies. Before initiating testosterone enanthate subcutaneous injection or testosterone undecanoate oral capsules, consider the patient's baseline cardiovascular risk and ensure blood pressure is adequately controlled. Check blood pressure (BP) approximately 3 weeks and 6 weeks after initiating testosterone undecanoate oral capsules or testosterone enanthate injection, respectively, and periodically after that. Treat new-onset hypertension or exacerbations of pre-existing hypertension. Re-evaluate whether the benefits of treatment outweigh the risks in patients who develop cardiovascular risk factors or cardiovascular disease during treatment.[63592] [64030] In clinical trials, testosterone enanthate subcutaneous injection increased systolic BP in the first 12 weeks of treatment by an average of 4 mmHg based on ambulatory blood pressure monitoring (ABPM) and by an average of 4 mmHg from baseline following 1 year of treatment on BP cuff measurements. In the 1-year trial, 10% of patients treated with this injection were started on antihypertensive medications or required changes to their antihypertensive medication regimen.[63592] In a clinical trial, testosterone undecanoate oral capsules increased systolic BP during 4 months of treatment by an average of 4.9 mmHg based on ABPM and by an average of 2.8 mmHg from baseline based on BP cuff measurements. Average BPs had not plateaued at the end of the trial. Seven percent of patients receiving testosterone undecanoate oral capsules were started on antihypertensive medications or required intensification of their antihypertensive medication regimen during the 4-month trial.[64030] These BP increases can increase the risk of MACE, with greater risk in patients with established cardiovascular disease or risk factors for CV disease. In some patients, the increase in BP may be too small to detect, but can still increase the risk for MACE.[63592] [64030] Additional risks associated with testosterone therapy of any type are venous thromboembolism, including deep vein thrombosis (DVT) and pulmonary embolism (PE). 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 and initiate appropriate workup and management.[30060] [33698] [42603] [42676] [42931] [42691] [42677] [42932] [44211] [56803] [57334] [63592] [64030]

Accidental exposure to topical testosterone gels, solutions, or ointments has occurred in pediatric patients after contact between the child and the application site in treated individuals. Strict adherence to the recommended handling of clothing and application site care can limit the risk of accidental exposure; patients should be encouraged to practice these recommendations to avoid exposing other persons to the drug. The FDA recommends taking precautions to minimize the potential for accidental exposure of topical testosterone products by washing hands with soap and warm water after each application, covering application site with clothing, and removing medication with soap and water when contact with another person is anticipated. In the case of direct skin-to-skin contact with the site of testosterone application, the non-treated person should wash the area with soap and water as soon as possible. The adverse events reported from accidental exposure in pediatric patients include genitalia enlargement, development of pubic hair, advanced bone age, increased libido, and aggressive behavior. Symptoms resolved in most patients when exposure to the product stopped. However, in a few patients, the genitalia enlargement and advanced bone age did not fully return to expected measurements. Accidental exposure to a female of any age may result in virilization. In clinical studies, within 2 to 12 hours of application by male subjects, 15-minute sessions of vigorous skin-to-skin contact with a female partner resulted in serum female testosterone levels more than 2 times the female baseline values. When clothing covered the treated site on the male, the transfer of testosterone to the female was avoided.[42603] Most marketed testosterone products are indicated for use in men only; most products are not recommended for females due to lack of controlled evaluations and/or the potential for virilizing effects.[30060] [33698] [42603] [42676] [42691] [42931] [42932] [56803] [63592] [64030] Some dosage forms supply testosterone in excess of what should be prescribed to females under certain endocrine situations. Female patients receiving testosterone therapy should be closely monitored for signs of virilization (deepening of the voice, hirsutism, acne, clitoromegaly, and menstrual irregularities). At high doses, virilization is common and is not prevented by concomitant use of estrogens. Some virilization may be judged to be acceptable during palliative treatment for breast carcinoma; however, if mild virilism is evident, discontinuation of drug therapy is necessary to prevent long-term virilization.[42676] Testosterone is used off-label in transgender males (female to male) to support virilization.

Andro-L.A., Androderm, AndroGel, Aveed, AXIRON, Delatestryl, Depo-Testosterone, FORTESTA, JATENZO, KYZATREX, Natesto, Testim, Testopel, TLANDO, Virilon, Vogelxo, XYOSTED

Rx, schedule III

Primary androgen in humans synthesized by testes, ovaries, and adrenal cortex; available in a variety of dosage forms
Primarily used in males with primary hypogonadism or with hypogonadism due to medical conditions; may be used for a limited duration for constitutional delay of puberty; used off-label in men with sexual dysfunction due to low testosterone associated with aging
Not recommended for low testosterone status alone due to aging due to potential risk for cardiovascular events and stroke

Initially, 75 mg subcutaneously in the abdominal region once weekly. Measure total testosterone trough concentrations (measure 7 days after the most recent dose) following 6 weeks of dosing, following 6 weeks after dose adjustment, and then periodically during treatment. A trough concentration between 350 ng/dL and 650 ng/dL generally provides testosterone exposures in the normal range during the entire dosing interval. DOSE ADJUSTMENTS: Decrease the dose by 25 mg is the total testosterone trough concentration is 650 ng/dL or greater. Increase the dose by 25 mg if the total testosterone trough concentration is less than 350 ng/dL. Maintain the same dose if the total testosterone trough concentration is 350 ng/dL to 649 ng/dL.[63592]

Initially, 750 mg IM. After 4 weeks, give a repeat dose of 750 mg IM, then 750 mg IM every 10 weeks thereafter.

50 to 400 mg intramuscularly once every 2 to 4 weeks.

For the initiation of pubertal growth: 40 to 50 mg/m2 IM monthly until the growth rate falls to prepubertal levels. For the terminal growth phase: 100 mg/m2 IM monthly until growth ceases. Maintenance of virilization may be achieved with a dose of 100 mg/m2 IM twice monthly.

AndroGel topical gels are not interchangeable. Dosage and administration for AndroGel 1% differs from AndroGel 1.62%.

Initially, 5 grams of 1% gel (containing 50 mg of testosterone and delivering 5 mg of testosterone systemically) applied once daily (preferably in the morning) to clean, dry, intact skin of the upper arms and/or abdomen. Measure serum testosterone level 14 days later to ensure proper dosage. If the serum testosterone level is below the normal range or if the desired clinical response is not achieved, may increase to 7.5 grams once daily (containing 75 mg of testosterone and delivering 7.5 mg/day of testosterone systemically), and then to 10 grams once daily (containing 100 mg of testosterone and delivering 10 mg/day of testosterone systemically) as clinically indicated. Max: 10 grams/day.

AndroGel topical gels are not interchangeable. Dosage and administration for AndroGel 1.62% differs from AndroGel 1%.

Initially, 40.5 mg of gel (2 pump actuations or a single 40.5 mg packet) applied once daily in the morning to clean, dry, intact skin of the shoulders and upper arms. Measure serum testosterone level at 14 and 28 days after starting or adjusting dose. DOSE ADJUSTMENT: If the serum testosterone level is less than 350 ng/dL, increase daily dose by 20.25 mg (1 pump actuation or a single 20.25 mg packet); if 350 to 750 ng/dL, no dose change; if greater than 750 ng/dL, reduce daily dose by 20.25 mg (1 pump actuation or a single 20.25 mg packet). Measure serum testosterone periodically thereafter. Max: 81 mg/day (4 pump actuations or 2 of the 40.5 mg packets).

Initially, 5 grams gel (one tube containing 50 mg of testosterone and delivering 5 mg of testosterone systemically) applied once daily (preferably in the morning) to clean, dry, intact skin of the shoulders and/or upper arms. Measure morning serum testosterone levels roughly 14 days later to ensure proper dosage. DOSAGE ADJUSTMENT: If the serum testosterone level is below the normal range or if the desired clinical response is not achieved, may increase to 10 grams (2 tubes, delivering a total of 10 mg/day testosterone systemically) applied once daily. Max: 10 grams/day.

Initially, 40 mg (4 pump actuations) applied once daily in the morning to clean, dry, intact skin of the front and inner thighs. Titrate based on serum testosterone concentration drawn 2 hours after application on approximately days 14 and 35 after treatment initiation or dose adjustments. DOSE ADJUSTMENT: If the serum testosterone concentration is 2,500 ng/dL or greater, decrease the daily dose by 20 mg (2 pump actuations); if 1,250 to less than 2,500 ng/dL, decrease the daily dose by 10 mg (1 pump actuation); if 500 to less than 1,250 ng/dL, continue current dose; and if level less than 500 ng/dL, increase the daily dose by 10 mg (1 pump actuation). Minimum dose: 10 mg/day. Max: 70 mg/day.

Initially, 60 mg (2 pump actuations) applied once daily (preferably in the morning) to clean, dry, intact skin of the axilla. Measure serum testosterone concentration at 14 days later and draw 2 to 8 hours after application to ensure proper dosage. Target testosterone concentration: 300 to 1,050 ng/dL. DOSE ADJUSTMENT: If the testosterone concentration is less than 300 ng/dL, may increase to 90 mg once daily (3 pump actuations) or from 90 mg/day to 120 mg (4 pump actuations) once daily. If the serum testosterone concentration is more than 1,050 ng/dL while the patient is applying 60 mg/day, then decrease to 30 mg/day. If the serum concentration is more than 1,050 ng/dL while the patient is applying 30 mg/day (lowest) dose, then discontinue.

1 patch of the 4 mg/day system (not two 2 mg/day systems) applied nightly to an area of dry, clean skin on the upper arms, thighs, back or abdomen and worn for 24 hours. Approximately 2 weeks following initiation or any dose change, measure the early morning serum testosterone concentration following system application the previous evening. DOSE ADJUSTMENT: If the serum concentration is outside the target range of 400 to 930 ng/dL, increase the daily dose to 6 mg (i.e., one 4 mg/day and one 2 mg/day system) or decrease the daily dose to 2 mg (i.e., one 2 mg/day system), maintaining nightly application.

Administer 11 mg gel (2 pump actuations; 1 actuation per nostril) nasally 3 times daily for a total of 33 mg/day [administer once in the morning, once in the afternoon, and once in the evening (6 to 8 hours apart, preferably at the same times each day]. Measure serum total testosterone concentrations periodically, starting 1 month after initiating treatment. When total testosterone concentrations consistently exceed 1,050 ng/dL, discontinue testosterone therapy. If total testosterone concentration is consistently less than 300 ng/dL, consider alternate therapy.

237 mg PO twice daily with food (in the morning and the evening), initially. Individualize the dosage based on the patient's serum testosterone concentration. Minimum recommended dose: 158 mg PO twice daily. Max: 396 mg PO twice daily. Measure serum testosterone concentrations (measure 6 hours after the morning dose in plain tubes, clotted at room temperature for 30 minutes prior to centrifugation) 7 days after starting treatment or following dose adjustment and periodically after that.

225 mg (taken as two 112.5 mg capsules) PO twice daily with food, in the morning and the evening. Measure serum testosterone concentrations (measure 8 to 9 hours after the morning dose) 3 to 4 weeks after starting treatment and periodically after that.

200 mg PO twice daily with food, initially. Individualize the dosage based on the patient's serum testosterone concentration. Minimum recommended dose: 100 mg PO once daily in the morning. Max: 400 mg PO twice daily. For total daily doses greater than 100 mg, administer the same dose in the morning and evening. Measure serum testosterone concentrations (3 to 5 hours after the morning dose) 7 days after starting treatment or following dose adjustment and periodically after that.

Generally, 150 to 450 mg (2 to 6 pellets) is inserted subcutaneously by a health care professional every 3 to 6 months. The dosage is based on individual requirements and the gradual reduction of the amount administered parenterally. Therapeutic effects of the pellets typically lasts for 3 to 4 months, but sometimes as long as 6 months.

50 to 200 mg intramuscularly once every 2 to 4 weeks for a limited period. Or, 40 to 50 mg/m2/dose intramuscularly monthly for 6 months. Patients are not routinely treated since these patients represent a normal variant in pubertal timing and usually have favorable outcomes for final height and reproductive capacity. Adolescent males are selected to receive a short course of testosterone therapy if psychological problems are exacerbated by the delay.

Generally, 150 to 450 mg (2 to 6 pellets) is inserted subcutaneously by a health care professional every 3 to 6 months. For delayed puberty, the lower end of the dosing range is typically sufficient. Treatment is usually only required for 4 to 6 months. Patients are not routinely treated since these patients represent a normal variant in pubertal timing and usually have favorable outcomes for final height and reproductive capacity. Adolescent males are selected to receive a short course of testosterone therapy if psychological problems are exacerbated by the delay.

200 to 400 mg intramuscularly once every 2 to 4 weeks.

Safety and efficacy have not been established; not FDA- approved. Guidelines recommend usual dosing. Initially, 750 mg IM. After 4 weeks, give a repeat dose of 750 mg IM, then 750 mg IM every 10 weeks thereafter. Re-evaluate symptoms within 12 months and periodically after that; discontinue if there is no improvement.

Safety and efficacy have not been established; not FDA- approved. Guidelines recommend usual dosing. 50 to 400 mg IM once every 2 to 4 weeks. Re-evaluate symptoms within 12 months and periodically after that; discontinue if there is no improvement.

Not FDA-approved; commercial dose forms for women not available in the U.S. Apply 5 mg topically once daily, at approximately the same time each day, to either the upper outer thigh or buttock. Clinical trials have shown that there is a 4 to 8 week time lag between starting testosterone treatment and an improvement in sexual motivation. If no improvement in symptoms within 3 months and if the testosterone concentration is within the premenopausal reference range, a dose increase up to 10 mg topically once daily can be used with follow up clinical and biochemical monitoring. This dose should only rarely be exceeded. If there is no improvement in symptoms after 6 months of continuous therapy, treatment should be discontinued and alternative options be considered. Guidelines support testosterone for HSDD as several studies have showed efficacy with 2 mg to 10 mg once daily applied topically as a patch, gel, cream, or spray, given as monotherapy or as combination with estrogen products.

†Indicates off-label use

Generally, androgen use is contraindicated in patients with severe hepatic dysfunction. Specific guidelines for dosage adjustment in hepatic impairment are not available; use caution in patients with mild to moderate hepatic disease.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Abarelix: (Major) Concomitant use of androgens or estrogens with abarelix is relatively contraindicated, as both could counteract the therapeutic effect of abarelix.
Acarbose: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Alogliptin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Alogliptin; Metformin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Alogliptin; Pioglitazone: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Alpha-glucosidase Inhibitors: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Canagliflozin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Canagliflozin; Metformin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Corticosteroids: (Moderate) Monitor for fluid retention during concurrent corticosteroid and testosterone use. Concurrent use may result in increased fluid retention.
Cyclosporine: (Moderate) Androgens may increase concentrations of cyclosporine, potentially increasing the risk of nephrotoxicity. Until further data are available, close monitoring of cyclosporine serum concentrations is prudent during coadministration with androgens.
Dapagliflozin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Dapagliflozin; Metformin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Dapagliflozin; Saxagliptin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Darbepoetin Alfa: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to darbepoetin alfa, reducing the amount required to treat anemia.
Degarelix: (Major) Concomitant use of androgens with degarelix is relatively contraindicated, as androgens could counteract the therapeutic effect of degarelix.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Empagliflozin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Empagliflozin; Linagliptin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Empagliflozin; Linagliptin; Metformin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Empagliflozin; Metformin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Epoetin Alfa: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to epoetin alfa, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
Ertugliflozin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Ertugliflozin; Metformin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Ertugliflozin; Sitagliptin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Glipizide; Metformin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Glyburide; Metformin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Goserelin: (Major) Avoid concurrent use of androgens with gonadotropin releasing hormone (GnRH) agonists such as goserelin. Goserelin inhibits steroidogenesis; concomitant use with androgens may counteract this therapeutic effect.
Histrelin: (Major) Avoid concurrent use of androgens with gonadotropin releasing hormone (GnRH) agonists such as histrelin. Histrelin inhibits steroidogenesis; concomitant use with androgens may counteract this therapeutic effect.
Incretin Mimetics: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Insulins: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Leuprolide: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
Leuprolide; Norethindrone: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
Linagliptin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Linagliptin; Metformin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Lonapegsomatropin: (Moderate) Somatropin can induce (i.e., increase) the activity of cytochrome-mediated metabolism of antipyrine clearance in man. Thus, this predicts that somatropin may affect other drugs metabolized via this pathway, like testosterone.
Meglitinides: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Metformin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Metformin; Repaglinide: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Metformin; Rosiglitazone: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Metformin; Saxagliptin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Metformin; Sitagliptin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Methoxy polyethylene glycol-epoetin beta: (Moderate) Androgens are known to stimulate erythropoiesis. Despite the fact that endogenous generation of erythropoietin is depressed in patients with chronic renal failure, other tissues besides the kidney can synthesize erythropoietin, albeit in small amounts. Concurrent administration of androgens can increase the patient's response to MPG-epoetin beta, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
Miglitol: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Nafarelin: (Major) Gonadotropin releasing hormone (GnRH) agonists (i.e.,nafarelin) inhibit steroidogenesis, therefore the concomitant use of these agents with androgens may counteract this therapeutic effect. Avoid concurrent use of androgens with GnRH agonists.
Oxymetazoline: (Moderate) The drug interaction potential between intranasal testosterone (e.g., Natesto) and other intranasally administered drugs other than sympathomimetic decongestants is unknown. Therefore, concomitant use of intranasal testosterone with intranasal drugs other than sympathomimetic decongestants (e.g., oxymetazoline) is not recommended. Eighteen males with seasonal allergic rhinitis were treated with intranasal testosterone and randomized to receive oxymetazoline (30 minutes prior to intranasal testosterone) or no treatment. In general, serum total testosterone concentrations were decreased by 21-24% in males with symptomatic allergic rhinitis, due to the underlying condition. A mean decrease in AUC and Cmax (2.6% and 3.6%, respectively) for total testosterone was observed in males with symptomatic seasonal rhinitis when treated with oxymetazoline compared to untreated patients. Concomitant use of oxymetazoline does not impact the absorption of testosterone.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with testosterone. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Pioglitazone; Metformin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Pramlintide: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Pretomanid: (Major) Avoid coadministration of pretomanid with testosterone, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and testosterone. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Saw Palmetto, Serenoa repens: (Major) Drug interactions with Saw palmetto, Serenoa repens have not been specifically studied or reported. Saw palmetto extracts appear to have antiandrogenic effects. The antiandrogenic effects of Saw palmetto, Serenoa repens would be expected to antagonize the actions of androgens; it would seem illogical for patients taking androgens to use this herbal supplement.
Saxagliptin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
SGLT2 Inhibitors: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Sitagliptin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Somatropin, rh-GH: (Moderate) Somatropin can induce (i.e., increase) the activity of cytochrome-mediated metabolism of antipyrine clearance in man. Thus, this predicts that somatropin may affect other drugs metabolized via this pathway, like testosterone.
Sotagliflozin: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Soy Isoflavones: (Moderate) Theoretically, the soy isoflavones may counteract the activity of the androgens.
Sulfonylureas: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Thiazolidinediones: (Moderate) 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 decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Triptorelin: (Major) Gonadotropin releasing hormone (GnRH) agonists (i.e.,triptorelin) inhibit steroidogenesis, therefore the concomitant use of these agents with androgens may counteract this therapeutic effect. Avoid concurrent use of androgens with GnRH agonists.
Warfarin: (Moderate) Testosterone can increase the anticoagulant action of warfarin. Serious bleeding has been reported in some patients with this drug-drug interaction. Although the mechanism is unclear, testosterone may reduce procoagulant factors. Reduction of warfarin dosage may be necessary if testosterone therapy is coadministered. More frequent monitoring of INR and prothrombin time in patients taking such oral anticoagulants is recommneded, especially at the initiation and termination of androgen therapy. It is unclear if testosterone can augment the anticoagulant response to heparin therapy or if testosterone alters the effect of other non-coumarin oral anticoagulants in a similar manner.

Androderm Transdermal Film ER: 2mg, 4mg, 24h
AndroGel/FORTESTA/Testim/Testosterone/Vogelxo Transdermal Gel: 0.5g, 1%, 1.62%, 10mg
Andro-L.A./Aveed/Delatestryl/Depo-Testosterone/Testosterone Cypionate/Testosterone Enanthate/Virilon Intramuscular Inj Sol: 1mL, 100mg, 200mg, 250mg
AXIRON/Testosterone Topical Sol: 1.5mL, 30mg
JATENZO/KYZATREX/Testosterone Undecanoate/TLANDO Oral Cap: 100mg, 112.5mg, 150mg, 158mg, 198mg, 200mg, 237mg
Natesto Nasal Gel: 1actuation, 5.5mg
Testopel Subcutaneous Imp: 75mg
XYOSTED Subcutaneous Inj Sol: 0.5mL, 50mg, 75mg, 100mg

Dependent on indication for therapy, as well as route of administration and specific product chosen for use.

Dependent on indication for therapy, as well as route of administration and specific product chosen for use.

Dependent on indication for therapy, as well as route of administration and specific product chosen for use.

Dependent on indication for therapy, as well as route of administration and specific product chosen for use.

Safety and efficacy have not been established.

Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis, and scrotum; the development of male hair distribution, such as facial, pubic, chest, and axillary hair; laryngeal enlargement; vocal cord thickening; alterations in body musculature; and fat distribution. Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter syndrome or Leydig cell aplasia, whereas secondary hypogonadism (also known as hypogonadotropic hypogonadism) is the failure of the hypothalamus (or pituitary gland) to produce sufficient gonadotropins (FSH, LH).

Testosterone is administered orally, nasally, intramuscularly, subcutaneously, and applied to the skin as a topical gel, solution, or transdermal systems for transdermal absorption, or by implantation of long-acting pellets. In serum, testosterone is bound to protein. It has a high affinity for sex hormone binding globulin (SHBG) and a low affinity for albumin. The albumin-bound portion freely dissociates. The affinity for SHBG changes throughout life. It is high during prepuberty, declines during adolescence and adult life, then rises again in old age. The active metabolite DHT has a greater affinity for SHBG than testosterone. Elimination half-life is 10-100 minutes and is dependent on the amount of free testosterone in the plasma. Testosterone is metabolized primarily in the liver to various 17-keto steroids. It is a substrate for hepatic cytochrome P450 (CYP) 3A4 isoenzyme. Estradiol and dihydrotestosterone (DHT) are the major active metabolites, and DHT undergoes further metabolism. Testosterone activity appears to depend on formation of DHT, which binds to cytosol receptor proteins. Further metabolism of DHT takes place in reproductive tissues. About 90% of an intramuscular testosterone dose is excreted in the urine as conjugates of glucuronic and sulfuric acids. About 6% is excreted in the feces, largely unconjugated. There is considerable variation in the half-life of testosterone as reported in the literature, ranging from 10 to 100 minutes.[30060] [34721]
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-glycoprotein (P-gp)
Testosterone is a substrate for CYP3A4. Testosterone is also a substrate and inhibitor of P-gp transport.[34721] [34722]

Testosterone undecanoate oral capsules deliver physiologic amounts of testosterone, producing testosterone concentrations that approximate normal concentrations seen in healthy men. Available branded products are not therapeutically substitutable with one another due to dosage and pharmacokinetic differences.[64030]
Testosterone undecanoate oral capsules, liquid filled (Jantenzo): In a clinical trial at a starting dose of 237 mg PO twice daily with meals, the dosage was adjusted, as needed, on days 14 and 56 between a minimum of 158 mg twice daily and a maximum of 396 twice daily based on the average plasma testosterone concentration obtained over 24 hours after the morning dose. The average daily NaF-EDTA plasma testosterone concentration was 403 (+/- 128) nanograms/dL at the end of treatment. The normal eugonadal range in the NaF-EDTA plasma was 252 to 907 ng/dL in this study. The titration scheme for use in clinical practice is based on serum total testosterone. In patients completing at least 105 days of testosterone undecanoate oral capsules administered twice daily had a mean 24-hour average concentration of 403 ng/dL and a mean maximum concentration of 1,008 ng/dL.[64030]
Testosterone undecanoate oral capsules (Tlando): Following oral administration of 225 mg of testosterone undecanoate capsules in 95 hypogonadal males, maximum serum testosterone concentrations were observed at a median (Tmax) of about 5 hours. The mean maximum (Cmax) serum testosterone concentrations observed were 979 ng/dL and 989 ng/dL following the morning and evening doses, respectively. The average serum testosterone concentrations over 24 hours observed following administration was 476 ng/dL. Following administration, the mean serum dihydrotestosterone (DHT) over 24 hours was 108 ng/dL, the mean serum testosterone undecanoate over 24 hours was 11,100 nanograms/dL and the mean serum dihydrotestosterone undecanoate over 24 hours was 4,700 ng/dL.
Testosterone undecanoate oral capsules (Kyzatrex): In a clinical trial at a starting dose of 200 mg PO twice daily with meals, the dosage was adjusted, as needed, on days 28 and 56 between a minimum of 100 mg/day (morning-only) to a maximum of 400 mg twice per day based on the plasma testosterone concentration obtained by a single blood draw collected 3 to 5 hours after the morning dose. The average daily NaF/EDTA plasma testosterone concentration was 393.3 (+/-113.6) ng/dL after 90 days of treatment. The normal eugonadal range in NaF/EDTA plasma was 222 to 800 ng/dL in this study.

Intramuscular parenteral testosterone formulations have been developed that reduce the rate of testosterone secretion, with esters being less polar and slowly absorbed from intramuscular sites. Esters have a duration of action of 2 to 4 weeks following IM administration. The esters are hydrolyzed to free testosterone, which is inactivated in the liver.

Subcutaneous Injection Route
-Xyosted: Following weekly subcutaneous injection for 12 weeks, serum testosterone concentrations reached a maximum after a median of 11.9 hours post-dose (5.8 to 168.7 hours) then slowly declined. Steady state testosterone concentration was achieved by week 6. At week 12, the mean Cmax was 215 ng/dL, with a mean Tmax of 11.9 hours. The mean AUC (0 to 168 hour) was 21,385 ng/hour/dL.
 
Subcutaneous Implant Route
-Testopel: The duration of action of testosterone subcutaneous implantable pellets (Testopel) is usually 3 to 4 months, but may last as long as 6 months.

-Topical solution or gel: Roughly 10% of an applied topical dosage of testosterone skin gel or ointment is systemically absorbed with once daily dosing; absorption of the gel and solution from the skin occurs continually over the 24 hour dosing interval, which indicates that the skin acts as a reservoir for sustained-release. Application of testosterone solution or gel delivers physiologic circulating testosterone that resembles normal concentration range seen in healthy men. Steady-state concentrations are achieved after approximately 14 days of solution application; when the solution is stopped, pre-treatment testosterone concentrations are achieved in approximately 7 to 10 days.
 
-Transdermal patches: Patches can be applied to any healthy skin site other than on the scrotum or bony areas. Daily application of two Androderm 2.5 mg skin patches in the late evening results in serum testosterone concentrations that approach those of healthy young men and follow normal circadian variation. The first day of dosing results in morning serum testosterone concentrations within the normal range. There is no testosterone accumulation with continued use. Following removal of the patch, hypogonadal status returns within 24 hours. Baseline serum testosterone concentrations may be reduced because endogenous secretion of testosterone may be suppressed by testosterone transdermal. The pharmacokinetic effects of showering after a single application of Androderm 4 mg/day were assessed in 16 hypogonadal males. Showering 3 hours after application increased the average concentration by 0.5% and decreased the Cmax by 0.4% respectively, as compared to not showering. The systemic exposure (AUC) was similar following applications with or without showering 3 hours after application.

Intranasal Route
Following intranasal administration, maximum testosterone concentration is achieved within approximately 40 minutes. The average daily testosterone concentration produced by intranasal testosterone administration (33 mg total daily dose) and assessed on Day 90 of treatment was 421 (+/- 116) ng/dL. A half-life ranging from 10 to 100 minutes is observed following intranasal application.

Testosterone topical solution, transdermal patches, and gels are contraindicated in lactating women who are breast-feeding. It is recommended that other testosterone formulations be avoided during breast-feeding.[33698] [42931] [42691] [42676] [42677] [42932] [44211] [56803] [57334] [63592] [42932] [42676] [64030] Testosterone distribution into breast milk has not been determined; it is unclear if exposure would exceed levels of the hormone normally found in human milk. Significant exposure to testosterone via breast-feeding may have adverse androgenic effects on the infant and the drug may also interfere with proper establishment of lactation in the mother.[46948] Alternative methods to breast-feeding are recommended in lactating women receiving testosterone therapy.