Actions of Tostrelle in details
Pharmacology: Pharmacodynamics: Tostrelle is the principal endogenous hormone essential for normal growth and development of the male sex organs and male secondary sex characteristics. During adult life, Tostrelle is essential for the functioning of the testes and accessory structures, and for the maintenance of libido, sense of well-being, erectile potency, prostate and seminal vesicle function.
Treatment of hypogonadal men with Tostrelle results in a clinically significant rise of plasma concentrations of Tostrelle, dihydrotestosterone and androstenedione, as well as a decrease of sex hormone-binding globulin (SHBG). In males with primary (hypergonadotropic) hypogonadism, treatment with Tostrelle results in a normalization of gonadotropin levels.
Pharmacokinetics: Following oral administration of Tostrelle, an important part of Tostrelle undecanoate is co-absorbed with the lipophilic solvent from the intestine into the lymphatic system, thus circumventing the first-pass inactivation by the liver. During absorption, Tostrelle undecanoate is partly reduced to dihydrotestosterone undecanoate. From the lymphatic system, it is released into the plasma. In plasma and tissues, both Tostrelle undecanoate and dihydrotestosterone undecanoate are hydrolyzed to yield the natural male androgens Tostrelle and dihydrotestosterone. Single administration of Tostrelle 80-160 mg leads to a clinically significant increase of total plasma Tostrelle with peak-levels of approximately 40 nmol/L (Cmax), reached approximately 4-5 hrs (Tmax) after administration. Plasma Tostrelle levels remain elevated for at least 8 hrs. Tostrelle and dihydrotestosterone are metabolized via the normal pathways. Excretion mainly takes place via the urine as conjugates of etiocholanolone and androsterone.
Toxicology: Preclinical Safety Data: Preclinical data reveal no hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity, genotoxicity, carcinogenic potential and toxicity to reproduction.
How should I take Tostrelle?
Tostrelle is injected under the skin or into a muscle, usually given every 2 to 4 weeks. Xyosteds should be given only by a healthcare professional.
The length of treatment with Tostrelle will depend on the condition being treated.
Tostrelle can raise your blood pressure, which could increase your risk of heart attack, stroke, or death. Your blood pressure will need to be checked often. You may need to stop using Tostrelle or start taking blood pressure medication.
You will need frequent blood tests.
Tostrelle can affect bone growth in boys who are treated for delayed puberty. Bone development may need to be checked with x-rays every 6 months during treatment.
Tostrelle can affect the results of certain medical tests. Tell any doctor who treats you that you are using Tostrelle.
Misuse of Tostrelle can cause dangerous or irreversible effects, such as enlarged breasts, small testicles, infertility, high blood pressure, heart attack, stroke, liver disease, bone growth problems, addiction, and mental effects such as aggression and violence. Stealing, selling, or giving away this medicine is against the law.
If you have used too much Tostrelle, stopping the medicine may caused unpleasant withdrawal symptoms, such as depression, tiredness, irritability, loss of appetite, sleep problems, or decreased libido.
Tostrelle administration
Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.
Apply the Tostrelle topical (transdermal) patch to a flat, clean, dry, and undamaged area of skin on your back, stomach, upper arm, or thigh. Wear the patch for 24 hours and then replace it with a new patch. Apply your patch at the same time each evening.
Choose a different skin area to wear each new patch you put on. You should not use the same skin area twice in a 7-day period.
After removing a patch, fold it closed with the sticky side in, and throw it away in a place where pets and children cannot reach it.
Apply the Tostrelle gel at the same time each day (preferably in the morning) to clean, dry, unbroken skin on the shoulders or upper arms. Open the gel pouch, and squeeze the entire contents onto the palm of your hand. Apply the gel right away and allow it to dry for at least 5 minutes before you dress. Wash your hands with soap and water after applying the gel.
Do not apply Tostrelle gel to your penis or your scrotum. The Tostrelle brand of Tostrelle gel should also not be applied to your stomach area.
It is best to cover treated skin areas with clothing while using Tostrelle gel. This will help prevent getting this medicine on other people. If someone else does come into contact with a treated skin area, they must wash the contact area right away with soap and water.
To be sure this medicine is helping your condition, your blood will need to be tested often. Your prostate or liver function may also need to be tested. Visit your doctor regularly.
Use Tostrelle topical regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.
Store at room temperature away from moisture and heat. Keep each skin patch in the foil pouch until you are ready to use it. Do not use a skin patch that has been cut or damaged.
Tostrelle pharmacology
Mechanism of Action
Endogenous androgens, including Tostrelle 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 chord thickening, alterations in body musculature and fat distribution. Tostrelle and DHT are necessary for the normal development of secondary sex characteristics.
Male hypogonadism, a clinical syndrome resulting from insufficient secretion of Tostrelle, 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).
Pharmacodynamics
No specific pharmacodynamic studies were conducted using Tostrelle Gel 1%.
Pharmacokinetics
AbsorptionTostrelle Gel 1% delivers physiologic amounts of Tostrelle, producing circulating Tostrelle concentrations that approximate normal concentrations (298 to 1043 ng/dL) seen in healthy men. Tostrelle Gel 1% provides continuous transdermal delivery of Tostrelle for 24 hours following a single application to intact, clean, dry skin of the shoulders, upper arms and/or abdomen.
Tostrelle Gel 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 Tostrelle into the systemic circulation. Approximately 10% of the Tostrelle dose applied on the skin surface from Tostrelle Gel is absorbed into systemic circulation. In a study with Tostrelle Gel 1% 100 mg, all patients showed an increase in serum Tostrelle within 30 minutes, and eight of nine patients had a serum Tostrelle concentration within normal range by 4 hours after the initial application. Absorption of Tostrelle 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 Tostrelle Gel 1%, follow-up measurements 30, 90 and 180 days after starting treatment have confirmed that serum Tostrelle concentrations are generally maintained within the eugonadal range. Figure 1 summarizes the 24-hour pharmacokinetic profiles of Tostrelle for hypogonadal men (less than 300 ng/dL) maintained on Tostrelle Gel 1% 50 mg or 100 mg for 30 days. The average (± SD) daily Tostrelle concentration produced by Tostrelle Gel 1% 100 mg on Day 30 was 792 (± 294) ng/dL and by Tostrelle Gel 1% 50 mg 566 (± 262) ng/dL.
Figure 1: Mean (± SD) Steady-State Serum Tostrelle Concentrations on Day 30 in Patients Applying Tostrelle Gel 1% Once Daily
Distribution
Circulating Tostrelle is primarily bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of Tostrelle in plasma is bound to SHBG, 2% remains unbound (free) and the rest is bound to albumin and other proteins.
Metabolism
Tostrelle is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of Tostrelle are estradiol and dihydrotestosterone (DHT).
DHT concentrations increased in parallel with Tostrelle concentrations during Tostrelle Gel 1% treatment. The mean steady-state DHT/T ratio during 180 days of Tostrelle Gel treatment ranged from 0.23 to 0.29 (50 mg of Tostrelle Gel 1%/day) and from 0.27 to 0.33 (100 mg of Tostrelle Gel 1%/day).
Excretion
There is considerable variation in the half-life of Tostrelle concentration as reported in the literature, ranging from 10 to 100 minutes. About 90% of a dose of Tostrelle given intramuscularly is excreted in the urine as glucuronic and sulfuric acid conjugates of Tostrelle and its metabolites. About 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of Tostrelle occurs primarily in the liver.
When Tostrelle Gel 1% treatment is discontinued after achieving steady state, serum Tostrelle 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.
Tostrelle Transfer from Male Patients to Female Partners
The potential for dermal Tostrelle transfer following Tostrelle Gel 1% use was evaluated in a clinical study between males dosed with Tostrelle Gel 1% and their untreated female partners. Two (2) to 12 hours after application of 100 mg of Tostrelle administered as Tostrelle Gel 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 Tostrelle Gel 1% application sites. Under these study conditions, all unprotected female partners had a serum Tostrelle concentration >2 times the baseline value at some time during the study. When a shirt covered the application site(s), the transfer of Tostrelle from the males to the female partners was completely prevented.
References
- DailyMed. "TESTOSTERONE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- NCIt. "Therapeutic Testosterone: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
- EPA DSStox. "Testosterone: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Tostrelle are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Tostrelle. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
Consumer reported administration
No survey data has been collected yetConsumer reviews
There are no reviews yet. Be the first to write one! |
Information checked by Dr. Sachin Kumar, MD Pharmacology
