Update on Aveed (Nebido- testosterone undecanoate- long acting testosterone)

[Nelson Vergel]

Update on Aveed (Nebido- testosterone undecanoate- long acting testosterone):

After a few problems with the FDA review process that have slowed down its approval by 3 years, this was the last announcement:

"Endo Pharmaceuticals Inc., a subsidiary of Endo Health Solutions Inc. (Nasdaq: ENDP) announced today that the U.S. Food and Drug Administration (FDA) has accepted for review the complete response submission made by Endo to the new drug application (NDA) for its long-acting testosterone undecanoate injection, Aveed, intended for men diagnosed with hypogonadism. In connection with the acceptance, the FDA assigned Endo's NDA a new Prescription Drug User Fee Act (PDUFA) action date of Feb. 28, 2014."

The following map shows the countries were it is approved (in orange)

 

[Carlos]

How much does it cost now?

 

[Nelson Vergel]

Not approved in the US. It is a long acting testosterone injection that can be effective for 8-12 weeks. It costs about $150 per shot in Mexico so expect higher prices in the US


Testosterone undecanoate injections are known as the brand name Nebido around the world. In the United States it will be called Aveed. Aveed is currently under review for approval by the FDA. This ester may stay longer in your system so that less frequent injections may be needed. The injection is usually given once every 10 to 14 weeks, though the frequency will depend on your individual testosterone levels. After your first injection you may be asked to come back for another injection at week six. For use in the United States, the company claims that only five injections a year are needed (compared to 48 injections per year for a 100 mg per week regimen). In other countries, a large injection dose of 1000 mg are allowed. The FDA did not allow the manufacturer to use this dose in studies done in this country due to fears of side effects.

In an open-label study which enrolled 130 hypogonadal men with blood total testosterone levels below 300 ng/dL at study entry, Aveed was dosed as an intramuscular injection (750 mg) at baseline, at week four, and then every 10 weeks throughout the remainder of the 21-month study. Approximately 70 percent of patients completed all injections and 94 percent of them had total testosterone from 300 to 1,000 nanograms/ml through the entire study.

After Nebido was approved in Europe a small number of European patients experienced respiratory symptoms immediately following an intramuscular injection of 1000 mg in a 4 cc injection volume, (versus the 750 mg, 3 cc injection volume used in the United States). The makers of Nebidobelieve, and the FDA concurs, that the reaction is likely the result of a small amount of the oily solution immediately entering the vascular system from the injection site. This known yet uncommon complication of oil-based depot injections may be related to inappropriate injection technique or site.

The problem is characterized by short-term reactions involving an urge to cough or a shortness of breath. In some rare cases the reaction had been classified as serious or the patient had experienced other symptoms such as dizziness, flushing or fainting. In U.S. clinical trials of Nebido 750 mg (3 cc injection volume), the proposed dose in the U.S., there was a single, mild, non-serious case of oil-based coughing.

The U.S. manufacturer, Endo Pharmaceuticals, is gathering data to address concerns about the respiratory symptoms. It is not known how much longer it will take the get this product approved in the United States as of June 2010. And even if it gets approved, it may not be widely available for people to buy through private health insurance if the company decides to price it as high as gels.

 

[Nelson Vergel]

Effects of 5-Year Treatment With Testosterone Undecanoate on Lower Urinary Tract Symptoms in Obese Men With Hypogonadism and Metabolic Syndrome

This study showed that 5 years of Nebido (TU- testosterone undecanoate) treatment did not change International Prostate Symptom Score (IPSS), maximum urinary flow (Qmax) rate in milliliters, post-void residual (PVR) volume, or prostate size in obese hypogonadal men with metabolic syndrome and moderate lower urinary track symptoms (LUTS) at baseline. Therefore, long-term TU replacement therapy is a safe and effective treatment for reverting hypogonadal features related to metabolic syndrome and does not impact negatively on LUTS and prostate volume.

http://www.goldjournal.net/article/S0090-4295(13)01046-7/abstract

 

[Dr.V.P.C.]

Here in Brazil we have Nebido at about 170 USD .

 

[Nelson Vergel]

FRI-132: Effects of Continuous Treatment up to 11 Years with Testosterone Undecanoate Injections (TU) in 115 Hypogonadal Men on Hormonal, Anthropometric and



Abstract:Introduction:
The longest-term follow-up on testosterone replacement therapy (TRT) in hypogonadal men in the literature is 6 years. In this registry study, we assessed effects of TRT beyond this period.
Methods:
Single-center, cumulative, prospective, registry study of 262 hypogonadal men receiving TU for up to 11 years. Cut-off for total testosterone (T): ≤ 12 nmol/L (~350 ng/dl). In 147 men, TRT had been temporarily discontinued due to reimbursement issues or diagnosis of prostate cancer. In 115 men reported here, TRT was never interrupted for up to 11 years. 115 men were treated for a minimum of 4 years, 114 for 5, 97 for 6, 70 for 7, 57 for 8, 48 for 9, and 23 for 10 years. 4 patients dropped out, 2 due to relocation, 2 were lost to follow-up for unknown reasons. Measures were taken at every other visit. Results at the end of 10 years follow-up are reported.
Results:
Mean age was 59.05 ± 9.36 years (min.: 19; max.: 80).
Total T increased from 7.84 ± 2.34 nmol/L to trough levels (measured prior to the following injection) between 17 and 20 nmol/L, free T from 150.31 ± 65.24 to 400-500 pmol/L, and SHBG decreased from 40.12 ± 20.73 to 33.11 ± 22.14 nmol/L (p<0.0001).
Mean waist circumference decreased from 106.47 ± 8.72 to 92.33 ± 5.32 cm. The decrease was statistically significant vs baseline (p<0.0001) and significant vs previous year for the first 7 years. Mean weight decreased from 97.3 ± 12.88 to 84.65 ± 7.04 kg. The decrease was statistically significant vs baseline (p<0.0001) and significant vs previous year for the first 8 years. Mean BMI decreased from 30.81 ± 4.33 to 27.06 ± 2.49 kg/m[SUP]2[/SUP] The decrease was statistically significant vs baseline (p<0.0001) and significant vs previous year for the first 8 years. Weight reduction was progressive and accumulated to 18.51 ± 6.46% after 10 years. The reduction of waist circumference was 11.98 ± 5.03%.
Total cholesterol (TC) decreased from 251.15 ± 46.77 to 172.02 ± 12.09 mg/dl (p<0.0001 vs baseline, statistical significance vs previous year for the first 7 years), LDL from 156.9 ± 25.43 to 98.09 ± 17.62 (p<0.0001 vs baseline, statistical significance vs previous year for the first 3 years), triglycerides (TG) from 235.72 ± 89.26 to 158.04 ± 20.99 (p<0.0001 vs baseline, statistical significance vs previous year for the first 4 years). HDL increased from 42.41 ± 12.61 to 56.52 ± 6.34 mg/dl (p<0.0001 vs baseline, statistical significance vs previous year for the first 3 years).
TC:HDL ratio improved from 6.59 ± 2.82 to 3.08 ± 0.33 (p<0.0001). Non-HDL cholesterol decreased from 208.74 ± 52.35 to 115.5 ± 11.31 mg/dl (p<0.0001, statistical significance vs previous year for the first 7 years). TG:HDL ratio improved from 6.24 ± 3.53 to 2.82 ± 0.38 (p<0.0001).
No major adverse cardiovascular event (MACE) occurred during the entire observation time.
Conclusions:
Long-term TRT improved anthropometric and lipid parameters in hypogonadal men in a meaningful and sustained fashion.
Disclosure: AAY: Investigator, Bayer Schering Pharma. GD: statistical analyses, Bayer Schering Pharma. FS: Employee, Bayer Schering Pharma. Nothing to Disclose: DJY, AMT
Sources of Research Support: Bayer Pharma AG partially funded data entry and statistical analyses.

 

[Nelson Vergel]

Using a standardized self-evaluation questionnaire for assessing psychosexual effects of TU treatment, it was found that scores for sexual thoughts/fantasies and sexual interest/desire doubled. Also the score for satisfaction of sex life increased. Improvements were seen for waking erections, total number of erections, and of ejaculations (Figure 2). The psychological parameters for depression, fatigue, and anxiety decreased within the first 3&#8211;6-weeks and remained stable. There were no statistically significant differences between TE and TU. No significant change was observed in the score for aggressiveness in either group, indicating that this parameter was not affected by the treatment provided. These results obtained in hypogonadal men are paralleled in some respects by the study of O'Connor et al (2004) showing that a single injection of 1000 mg TU to 28 eugonadal young men, elevating mean T levels above normal, was associated with significant increases in anger-hostility from baseline to week 2 after the injection. It was accompanied by an overall reduction in fatigue-inertia, and did not increase aggressive behavior or induce any changes in non-aggressive or sexual behavior.


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686335/

 

[Nelson Vergel]

[h=2]Effect and safety of testosterone undecanoate in the treatment of late-onset hypogonadism: A meta-analysis - Abstract[/b]
Asian Journal of Urology- May 18, 2015

OBJECTIVE: To evaluate the efficacy and safety of testosterone undecanoate (TU) in the treatment of late-onset hypogonadism (LOH) by meta-analysis.
METHODS: We searched Pubmed (until April 1, 2014), Embase (until March 28, 2014), Cochrane Library (until April 17, 2014), CBM (from January 1, 2001 to February 2, 2014), CNKI (from January 1, 2001 to February 2, 2014), Wanfang Database (from January 1, 2000 to February 2, 2014), and VIP Database (from January 1, 2000 to Febru ary 2, 2014) for randomized controlled trials of TU for the treatment of LOH. We evaluated the quality of the identified literature and performed meta-analysis on the included studies using the Rveman5. 2 software.
RESULTS: Totally, 14 studies were included after screening, which involved 1 686 cases. Compared with the placebo and blank control groups, TU treatment significantly increased the levels of serum total testosterone (SMD = 6.22, 95% CI 3.99 to 8.45, P < 0.05) and serum free testosterone (SMD = 4.35, 95% CI 1.86 to 6. 85, P < 0.05) but decreased the contents of luteinizing hormone (WMD = -2.23, 95% CI -4.03 to -0.42, P < 0.05), sex hormone binding globulin (WMD = 2.00, 95% CI 1.38 to 2.63, P < 0.05). TU also remarkably reduced the scores of Partial Androgen Deficiency of the Aging Males (WMD = -9.49, 95% CI -12.96 to -6.03, P < 0.05) and Aging Males Symptoms rating scale (WMD = -2.76, 95% CI -4.85 to -0.66, P < 0.05) but increased the hemoglobin level (SMD = 2.35, 95% CI 0.29 to 4.41, P < 0.05) and packed-cell volume (SMD = 4.35, 95% CI 1.36 to 7.33, P < 0.05). However, no significant changes were shown in aspertate aminotransferase, alanine transaminase, prostate-specific antigen, or prostate volume after TU treatment (P > 0.05).
CONCLUSION: TU could significantly increase the serum testosterone level and improve the clinical symptoms of LOH patients without inducing serious adverse reactions. However, due to the limited number and relatively low quality of the included studies, the above conclusion could be cautiously applied to clinical practice.

 

[Nelson Vergel]

This is the frequency recommended for Nebido (outside the US). Injections of 1000 mg each (4 ml)





The dose and frequency approved for Aveed (The name for Nebido in the US) is this one. 750 mg shots (3 ml)

 

[widget]

My concern with it would be that TRT often requires dosage adjustments when starting. It isn't as easy to manipulate the dosage when injecting every 10 weeks. I may be less cynical after seeing it used though

 

[CoastWatcher]

My concern with it would be that TRT often requires dosage adjustments when starting. It isn't as easy to manipulate the dosage when injecting every 10 weeks. I may be less cynical after seeing it used though

Yep, it could be like climbing into a car for a very long, uncomfortable ride.

 

[Kristian]

This is the frequency recommended for Nebido (outside the US). Injections of 1000 mg each (4 ml)

View attachment 1513



The dose and frequency approved for Aveed (The name for Nebido in the US) is this one. 750 mg shots (3 ml)

View attachment 1514

Even though this is the recommended dose, would it be possible/desireable to split this dose into weekly injections? For example 0,3 ml Aveed/Nebido pr. week?
Personally I have done both. And I must say I do prefer a weekly injection with a small needle in the shoulder. The 4 ML injection of Nebido is a big injection and must be done with deep intramuscular injection. It is more painful.
Comments/thoughts?

 

[Nelson Vergel]

Shorter interval between testosterone undecanoate doses may boost levels in hypogonadism

Testosterone undecanoate injected at 8-week intervals for men with hypogonadism may reduce fluctuations and increase mean testosterone levels compared with a 10-week dose regimen, according to data from a modeling study. “The currently approved 10-week dose regimen of testosterone undecanoate...

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