Pome?

[MikeDaly1970]

Hi lads,

Taking Nebido every 8 weeks the past 6 years an no problems.

But just now, took my 4ml in buttock, immediately felt laboured breath and acute continuous coughing, it is just about stopping now after 10 minutes.

Coming back to normal now, but should I be worried

Thanks for advice

 

[madman]

Hi lads,

Taking Nebido every 8 weeks the past 6 years an no problems.

But just now, took my 4ml in buttock, immediately felt laboured breath and acute continuous coughing, it is just about stopping now after 10 minutes.

Coming back to normal now, but should I be worried

Thanks for advice

Rare occurrence but would be scary having it happen for the first time.

If your symptoms resolve fairly quick then this is a good sign.

Glad you are feeling better.

Take home point here:

*POME presenting as cough/syncope symptoms during TU injection is uncommon, occurring with about 2% of TU injections. It is rapid in onset, usually evident during or immediately after TU injection, and lasting for up to 10 min but resolving fully without serious sequelae.

*The mechanism of POME appears to involve inadvertent entry of injected oil vehicle into the venous circulation with subsequent transfer to the pulmonary microvasculature





Complications of injectable testosterone undecanoate in routine clinical practice (2015)

Testosterone replacement therapy for male hypogonadism due to pathological disorders of the reproductive system aims to restore the lifetime health outcomes of eugonadal men. While all testosterone products can provide effective testosterone replacement therapy, the choice of formulation is primarily determined by patient convenience and physician familiarity, aiming to assure long-term compliance with lifelong treatment (2).Similarly, while reviews of testosterone treatment focus mostly on efficacy rather than safety (10), generically,testosterone replacement therapy has a good safety record (11) while each product has specific side-effects mostly related to their mode of administration. For injectable testosterone esters in an oil vehicle, the most relevant are injection site pain (12) or haematoma, pulmonary oil microembolism (POME) (13, 14) and secondary polycythaemia (15). Most studies of testosterone’s safety profile originate from clinical trials primarily designed to meet the requirements of regulatory authorities to enable a product to be marketed. It is common experience that post-marketing safety profile may differ from the clinical development program that achieves marketing approval with key differences arising for reasons including detection of rare and previously unrecognised events,confounding by between-centres differences in clinical practice, commercial motivations of sponsors and theartificial framework of clinical registration trials. We have therefore undertaken a prospective surveillance study of TU injections in the routine clinical practice in an experienced single academic centre outside a research setting with a focus on POME, haematoma and polycythaemia.




Subjects and injections

The participants involved in this study were patients of the Andrology Department aged between 20 and 75 years,who were receiving testosterone replacement therapy for a variety of pathological disorders of the hypothalamic, pituitary or testis (but not andropause) or were female to-male transgender patients. Injections were administered by experienced nurses delivering deep i.m. injections of 1000 mg of TU in 4 ml of castor oil vehicle using a 21-gauge needle. Injections were administered deeply into the right and left gluteal muscle (on an alternating basis) slowly over a period of 2 min. The patients were observed until they left the clinic, in most cases within a few minutes of receiving their injection. When patients experienced POME symptoms, they were observed until the symptoms resolved,usually within 10 min of the onset.




Subjects and methods

Study design

This study was a prospective survey of patients attending the Andrology Department of Concord Hospital to receive TU injections between July 2010 and March 2014 for androgen deficiency due to pathological disorders of the hypothalamo–pituitary–testicular axis. Blood was sampled for serum testosterone monitoring before testosterone injection. Testosterone injections were administered by the clinical staff of the Andrology Department according to the standard protocol by slowly administering deep i.m. injection into the upper outer quadrant of the buttock after aspiration to exclude venous injection. At the time of each injection, clinical staff recorded demographic details and observations for POME episodes between start of injection and leaving the clinic. POME was considered to be present when an unexpected, non-productive cough occurred during or immediately after (within minutes) TU injection. The coughing episode occurred with or without a sensation of flushing, faintness or anxiety and was not due to a chronic cough, acute asthma or an upper respiratory tract infection. Symptoms usually took a few (up to 10) minutes to resolve.




Subjects and injections

The participants involved in this study were patients of the Andrology Department aged between 20 and 75 years,who were receiving testosterone replacement therapy for a variety of pathological disorders of the hypothalamic, pituitary or testis (but not andropause) or were female to-male transgender patients. Injections were administered by experienced nurses delivering deep i.m. injections of 1000 mg of TU in 4 ml of castor oil vehicle using a 21-gauge needle. Injections were administered deeply into the right and left gluteal muscle (on an alternating basis) slowly over a period of 2 min. The patients were observed until they left the clinic, in most cases within a few minutes of receiving their injection. When patients experienced POME symptoms, they were observed until the symptoms resolved,usually within 10 min of the onset.




Cough/syncope episodes

There were a total of 56 POME episodes observed in 43 patients, associated with TU giving an overall incidence of 19/1000 injections (95% CI 14–24 per 1000 injections). One patient experienced a POME episode during his first i.m. TU injection and the remainder had received between one and 30 TU injections (median 17 previous asymptomatic injections, inter-quartile range (IQR) 17) before their observed POME episode in this study.

POME episodes were experienced by patients due to a wide variety of underlying clinical conditions comprising Klinefelter’s syndrome (8, 19%), idiopathic hypogonadotrophic hypogonadism including Kallmann’s syndrome(7, 16%), hypogonadism following castration (4, 9%),pituitary tumour/surgery (4, 9%), chemotherapy (6, 14%),other (testicular pathology, male contraception 5, 12%) or F2M transgender (9,21%). These patients were aged between 22 and 74 years (26% aged!35 years, 42% aged 36–50 years, 19% aged 51–65 years and 12% aged 66 years and over) and had BMIs ranging from 15.2 to 38.3 kg/m2 (median 25.7 kg/m2; IQR 4.95 kg/m2). There was no significant difference between men who had a POME episode in the time since last injection and in serum testosterone immediately before the index injection (Table 2).

Onset of symptoms was during injection for 40% and duration of coughing (documented for 51/56 episodes) ranged between 1 and 10 min (median duration 3 min; IQR 3 min). Severity of symptoms (documented 53/56) was recorded as very mild or mild (66%), moderate (15%) or severe (19%). All episodes were managed conservatively within the clinic and supplementary oxygen was never required.

There was no significant difference between the rates of POME episodes observed between three experienced nurse injectors who administered 98% (2973) of all injections (Table 3). The risk of recurrent episodes of cough/syncope (Table 4) was significantly greater than that expected by chance (PZ0.034, extended Fisher’s test) deviating from a Poisson distribution (mean and variance Z0.12).




Discussion

Injectable TU has been marketed for over 10 years and is now one of the most commonly prescribed products for testosterone replacement therapy (8, 9). While the safety profile under clinical trial conditions is well established (16, 17, 18, 19, 20, 21), its complications in routine clinica lpractice outside clinical trials have been less clearly established.

This study provides the most detailed characterisation of the clinical features of POME since its original description in men having deep gluteal i.m. injections of 0.8 ml testosterone enanthate in castor oil vehicle (13).This was subsequently confirmed in a Chinese study involving regular gluteal i.m. injections of 500 mg TU in 4 ml mellaleuca (mistranslated as ‘tea seed’) oil (14). In this study, POME has a rapid onset, usually during injection or shortly thereafter, lasting !10 min (median 3 min) and mostly mild in severity with no lasting sequelae. Its occurrence seems unrelated to age, underlying cause of hypogonadism or experienced nurses administering injections. The study design precluded evaluating the impact on POME incidence of less experienced nurses or doctors. It may also underestimate the occurrence of POME episodes that occurred after the patients left the clinic; however, based on our experience we believe this is rare if it ever occurs. The incidence in this study of 19/1000 injections is close to the rate originally described of 15 (95% CL 6–29) per 1000 injections (13) where both used castor oil vehicle, although with more different volumes (4 vs 0.8 ml) per injection. These estimates are however very different from the much lower incidence of POME reported to the FDA during the clinical development (1.5 cases/10 000 injections) and during post-marketing surveillance (0.7 cases/10 000 injections) in the US registration clinical trials of injectable TU (750 mg in 3 ml castor oil) (22). This major apparent discrepancy may be due to the manner of recording POME in the US clinical trials, which were marked by the incidence of POME being a significant hurdle to FDA registration. In addition to reducing the injection volume from 4 to 3 ml, the sponsor of the clinical trials employed two independent adjudicators ,both former FDA employees without clinical experience of testosterone injections, who created an ad hoc case definition of POME after the conclusion of the trials.

The essential major criterion was paroxysmal cough with undue emphasis on the paroxysmal pattern. Using this case definition and written reports from centres, they discounted 97% (107 of 110 reports in 102 men) of putative POME reports with 23 regarded as ‘intermediate’ and 84 as not POME. No specific definition of‘intermediate’ cases was provided, but if the ‘intermediate' cases were included the rate of POME is comparable with our findings (13 vs 19/1000 injections). Systematic under reporting of adverse cardiovascular effects of testosterone has been reported in commercially sponsored clinical trials (23).

The mechanism of POME appears to involve inadvertent entry of injected oil vehicle into the venous circulation with subsequent transfer to the pulmonary microvasculature. The basis for this interpretation arises from experimental animal studies showing pulmonary embolism in dogs and rabbits following i.m. injection of vegetable oils (24). There is also corroborative clinical evidence of lymphogenic absorption in humans after oil vehicle depot injections (25) as well as following accidental introduction of oil-based radio contrast into the bloodstream during myelography, which produced cough and radiographic visualisation of contrast in the lungs (26, 27, 28). This non-thrombotic mechanism of POME should not be confused with the numerous prothrombotic genetic thrombophilias, such as Factor V Leiden (29). These features suggest that POME would be a random event, an interpretation supported by the lack of influence of age, underlying disease or between-injector differences among experienced nurses; however, the non random risk of recurrence suggests that additional factors such as anatomical differences between individuals or of expectation by non-blinded reporters may be involved. Interestingly, confirming the higher than expected rate of POME recurrence, in the reported US clinical trials, eight of 102 men (8%) experienced a second episode of POME and one of ten men (10%) with ‘intermediate’ POME.




In conclusion, TU injection is a generally safe and well-tolerated treatment. POME presenting as cough/syncope symptoms during TU injection is uncommon, occurring with about 2% of TU injections. It is rapid in onset, usually evident during or immediately after TU injection, and lasting for up to 10 min but resolving fully without serious sequelae. While it appears to be a random event, unrelated to age, underlying disease or which experienced nurse injector, based on inadvertent access of the oil vehicle to the venous system, its risk of recurrence exceeds chance. Haematoma after deep i.m.TU injection is rare even among men using anti platelet or anticoagulant medications at the time of injection and while mild polycythaemia is relatively common, it is rarely severe or requiring specific treatment other than optimising inter-injection interval

 

[MikeDaly1970]

Thanks for all the information bro, appreciate it.

Ya it was quite scary, so based on all you sent me, I don't need to go to ER right.

You see I was thinking if oil went into vein and went to lungs, where did it go then? Could it clot, I thought I should get a CT scan to rule out a clot. Suppose that's from a lay mans way of thinking.

 

[madman]

Thanks for all the information bro, appreciate it.

Ya it was quite scary, so based on all you sent me, I don't need to go to ER right.

You see I was thinking if oil went into vein and went to lungs, where did it go then? Could it clot, I thought I should get a CT scan to rule out a clot. Suppose that's from a lay mans way of thinking.

You will be fine.

Nebido and Aveed (testosterone undecanoate) both contain castor oil.


*POME is NOT a blood clot

*AVEED® contains castor oil and POME is believed to be caused by tiny droplets of castor oil that have traveled to the lungs




AVEED® (testosterone undecanoate)

Why a 30-Minute Wait?

Patients must remain at the doctor's office for 30 minutes following each injection with AVEED®, because AVEED® may cause serious side effects. These side effects may occur during or right after an injection.

AVEED® can cause a temporary but potentially serious condition called a pulmonary oil microembolism (POME). POME is NOT a blood clot. AVEED® contains castor oil and POME is believed to be caused by tiny droplets of castor oil that have traveled to the lungs. Castor oil is one of the ingredients that enables AVEED® to be injected every 10 weeks after the first month of therapy.

AVEED® may also cause a severe allergic reaction called anaphylaxis.

Because of these serious potential risks, it's important that you talk to your doctor about whether the benefits of receiving AVEED® outweigh these potential risks. Ask your doctor or nurse if you are unsure about the risks of AVEED®.

Among 3,556 patients in worldwide clinical trials*:

• 9 POME events occurred in 8 patients
• 2 events of anaphylaxis occurred

*Patients treated with intramuscular testosterone undecanoate.