#161

Check the FDA guidelines for animal to human conversion factors (HED: Human Equivalent Dose).

#162

For rat divide by 6.2 so 64.5 mg for an 80kg human. That would put the 80mg dose of Telmisartan well into the anxiolytic zone for a human of ~175 pounds.

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#163

I was looking at the potential benefits of rilmenidine, assuming it will become available in the US at some point. My conclusion is that rilmenidine is not appropriate for those of us with low resting and sleeping heart rates even if that rate is due to lifelong distance running, as it is in my case. My mean sleeping heart rate over a measured run of three years (as measured by Apple watch but also manually and by an automated BP cuff occasionally) is 45 BPM but it can occasionally drop to 40 or even 39 briefly. I think this low rate rules out rilmenidine for me. For now, I’m staying with 40 mg. telmisartan which reduces my mid- to high normal BP to mid-to low normal levels. With less evidence, I also reason that whatever merit there is to the purported link between telmisartan and cancer is significantly reduced with the 40 mg. dose.

2 Likes
#164

is there a link for this? @DrFraser what do you think of this purported link?

#165

I say no to the link.

Here is what Vera-Health.ai says …

The question of whether telmisartan, an angiotensin II receptor blocker (ARB), increases the rate of cancer has been investigated in various studies. Initial concerns arose from a meta-analysis suggesting a potential increased risk of cancer with ARBs, particularly with telmisartan
2
. However, subsequent research has largely refuted this association.

A large-scale FDA meta-analysis in 2011 found no evidence of increased cancer risk with ARBs, including telmisartan. Similarly, the ONTARGET and TRANSCEND trials, which included telmisartan, did not show a significant increase in cancer incidence. A 2013 meta-analysis by Bangalore et al. also found no significant association between ARBs and cancer risk. Furthermore, a 2020 population-based cohort study in Taiwan found no increased cancer risk with telmisartan compared to other ARBs.

While some case reports have suggested potential links between telmisartan/hydrochlorothiazide combination therapy and certain skin cancers, these are isolated instances and not supported by large-scale studies. For example, there are reports of nevus-associated cutaneous melanoma and basal cell carcinoma potentially linked to this drug combination, possibly due to nitrosamine contamination
1
3
. However, these findings are not consistent across broader research.

The current consensus among major health organizations, including the FDA, EMA, and WHO, is that there is no substantial evidence supporting an increased cancer risk with telmisartan. It is important for clinicians to consider these findings in the context of overall evidence and individual patient risk factors. Regular monitoring and vigilance are advised, especially when telmisartan is used in combination with hydrochlorothiazide, to detect any unusual skin changes or lesions.

In summary, based on the available evidence, telmisartan does not appear to increase the rate of cancer. Ongoing research and surveillance continue to ensure the long-term safety of telmisartan and other ARBs.

References

  1. Telmisartan/hydrochlorothiazide-induced nevus-associated cutaneous melanoma: first report in the medical literature
    Expert Review of Clinical Pharmacology
    Tchernev et al.
    9 citations
    2021
    This is the first reported case of a patient who developed a nevus-associated cutaneous melanoma after combination therapy with generic sartan and hydrochlorothiazide and the diverse but mutually potentiating pro-carcinogenic effects of this class of agents are discussed.

Show more
2. The Use of Telmisartan and the Incidence of Cancer.
American Journal of Hypertension
Tascilar et al.
11 citations
2016
Compared with other ARBs, telmisartan use was not associated with an increased risk of cancer overall or by cancer site, and this study provides reassurance as to the short-term safety of telMisartan.

Meta Analysis
Open Access
Show more
3. High Risk BCC of the Nose After Telmisartan Hydrochlorothiazide: Potential Role of Nitrosamine Contamination as Key Triggering Factor for Skin Cancer Development
Journal of Clinical Research in Dermatology
S et al.
0 citations
2023
The dermatological examination showed an elevated large lesion with crusts and regular borders located in the right upper nasal region, in close proximity to the right eye, which was suspected clinically for basal cell carcinoma.

Open Access
Show more
4. Telmisartan generates ROS-dependent upregulation of death receptor 5 to sensitize TRAIL in lung cancer via inhibition of autophagy flux.
International Journal of Biochemistry and Cell Biology
Rasheduzzaman et al.
28 citations
2018

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#166

I don’t think there’s such a thing (or at least there’s no evidence). See: Angiotensin II receptor blocker (ARB) experiences? - #34 by adssx

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#167

Just to be clear, I said “purported link” whereas the responses to that comment are pursuant to a definite link. If you read all of the available and relevant research as I have tried to do, the refutations have been strong enough to support my decision to take 40 mg. per day but I do not think the evidentiary base is zero. I also think the historical contamination issue has clouded and perhaps even fueled the purposted link.

1 Like
#168

Could you please post some evidence? I haven’t found anything (besides the Turkish commentary of a random dude).

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#169

I think it has been posted many times in the earlier evidence and some was source for the, what, 2010 metanalysis. I’m going for the logic of inquiry @adssx. Subsequent research findings running in the opposite direction have not eliminated the possibility of a causal thread or more, perhaps operative under specific conditions and not others. We have see a shift in the preponderance of evidence line not complete refutations. And doesn’t some of the more recent evidence employ the “short term” qualifier because the scope of their inquiry did not permit a stronger claim? Metanalysis, in particular, is limited in this way.

1 Like
#170

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70106-6/abstract

This one? It was barely significant back then in 2010 (“Patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7·2% vs 6·0%, risk ratio [RR] 1·08, 95% CI 1·01–1·15; p=0·016)”) and more recent papers looking at larger populations refuted the claim. You’ll always find a paper claiming that x is good or bad for y. Then it’s about the weight of the evidence.

Here are the latest papers that looked at the topic and that all cite the 2010 study:

Long-term exposure to antihypertensive drugs and the risk of cancer occurrence: evidence from a large population-based study 2024: “Long-term evaluation of exposure to antihypertensive drugs did not show consistent associations between thiazides, angiotensin-receptor blockers, or angiotensin-converting-enzyme inhibitors and the risk of cancer occurrence. A weak association was observed between cancer and the duration of exposure to calcium channel blockers and beta-blockers.” (340k people, 10y follow up)

Current Status and Future Perspective of On co-Hypertension 2024
“There has been significant debate regarding the association between RAS inhibitors and cancer development. While the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and morbidity) trial showed that candesartan treatment reduced cardiovascular mortality, cancer-related mortality was higher in the candesartan group.39 A subsequent meta-analysis of the cancer risk of ARBs indicated that ARBs increase the risk of lung cancer and that the cancer risk with ARBs is higher in patients with greater cumulative exposure.40,41 In contrast, a network meta-analysis of 70 RCTs showed that all antihypertensive drugs, including ARBs, were not associated with an increased cancer risk or cancer-related death.42 The largest cohort study conducted in the United Kingdom revealed that angiotensin-converting enzyme inhibitors (ACEi) were associated with a 14% increased risk of lung cancer compared with ARBs, even after adjusting for confounding factors such as age, gender, smoking, and history of lung disease.43 In another meta-analysis utilizing data from 260,447 individual subjects across 33 RCTs, there was no association between the use of any class of antihypertensive drugs and cancer risk, except for the CCBs, which showed an HR of 1.06 (95% CI: 1.01–1.11).24 However, the median observation period in this study was 4.2 years, and the longer-term effects are unknown.”

Association between 19 medication use and risk of common cancers: A cross-sectional and Mendelian randomisation study 2024: Chinese paper, I don’t know if the journal is good, they find a reduced risk for prostate cancer and ACEI/ARB.

Retrospective analysis of neoplasms in patients using angiotensin receptor blockers 2024: “In recent years, regulatory agencies have raised concerns about the presence of potentially carcinogenic substances in certain formulations of ARBs. Specifically, nitrosamines and azido compounds have been identified in some ARB products. Nitrosamines are known to have carcinogenic properties and are related with an increased risk of neoplasm. Because of these results, progressive recalls of affected ARB products have been initiated to ensure patient safety.” I think only valsartan was recalled in 2018 ( Update on review of recalled valsartan medicines: preliminary assessment of possible risk to patients | European Medicines Agency (EMA) ) and I understand from this paper that if there was a cancer risk it wasn’t due to the underlying drug but to previous formulations. Am I correct?

5 Likes
#171

Telmisartan 40mg increases my resting heart rate (normally around 55 bpm during the day, now up to 65). I moved the dose to the morning because it also worsens my insomnia. For some reason, it seems to activate my sympathetic nervous system, even though literature generally suggests the opposite effect. Now that I’ve moved it to the morning, my resting heart rate is better immediately upon waking but gradually increases after taking Telmisartan.

By the way, dapagliflozin works oppositely for me; it lowers my resting heart rate and calms my nervous system. I take dapagliflozin in the afternoon: Sympatholytic Mechanisms for the Beneficial Cardiovascular Effects of SGLT2 Inhibitors: A Research Hypothesis for Dapagliflozin’s Effects in the Adrenal Gland.

Do you think my resting heart rate will normalize if I wait a few weeks or a couple of months? I’ve been on a 40mg dose for about four weeks now, and I was on a 20mg dose for a couple of months before that. My blood pressure has decreased and is now around 112/73.

Does anyone else have similar experiences?

EDIT: I’m wondering if it could be a compensatory mechanism, with the body resisting the drop in blood pressure and possibly resolving over time? Or should I reduce the dose back to 20mg?

1 Like
#172

Just throwing it out there, I wonder if this may not be the result of some kind of interaction between drugs. For example, we do know that dapagliflozin (which you take) does interact with telmisartan:

https://www.drugs.com/drug-interactions/dapagliflozin-with-telmisartan-3506-0-2152-0.html#:~:text=Interactions%20between%20your%20drugs&text=Dapagliflozin%20may%20cause%20salt%20and,in%20pulse%20or%20heart%20rate.

Quote:

" Dapagliflozin may cause salt and water loss, which may increase the risk of dehydration and low blood pressure when used with telmisartan or similar medications. You may experience headache, dizziness, lightheadedness, fainting, and/or changes in pulse or heart rate. Use caution when getting up from a sitting or lying position, and let your doctor know if you develop these symptoms. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Keep yourself hydrated by drinking plenty of fluids unless otherwise directed. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor."

Note, that it does mention RHR, but it might be an atypical reaction, unless there are widespread reports of such an effect in patients.

However the larger point is that when adding any drug, it is always important to consider DDI (drug-drug interactions), because a reaction to the newly introduced drug may not be down to the drug itself, but to some unanticipated or unknown DDI, especially if that reaction is atypical, as is the case for you with an atypical elevation of RHR upon introduction of higher dose telmisartan. Some DDI are dose dependant, and occur at higher but not lower doses.

You might want to experiment, if practical, with your drug and supplement stack to see if there isn’t some unusual DDI going on with telmi.

3 Likes
#173

Anything is possible, but I don’t have any other symptoms besides those mentioned. My blood pressure isn’t too low, or at least it hasn’t shown up as low in any measurements.

I think I’ll wait a couple more weeks, and if my resting heart rate doesn’t decrease or I get more symptoms, I’ll reduce the dose back to 20mg.

#174

As long as you’re experimenting with doses, you may consider 80mg teli. Sometimes there are non-linear reaction curves, perhaps U-shaped, where 20mg and 80 mg give you no RHR effect, but 40mg does. There is little difference between 80mg vs 40mg impact on BP reduction, so you may not be doing anything too crazy trying 80mg. If the 80mg gives you a bigger jump in RHR than 40mg, then you have your answer wrt. the linear effect of dose of teli on RHR.

2 Likes
#175

On the topic of experimenting with doses, is telmisartan ok to pill split? I have 80mg pills on order, but want to try 40mg first.

#176

Telmisartan 40 mg/day has not altered my resting or sleeping heart rates (now ~44 & 46 bpm). I have multi year dataset on those metrics and it is not possible to detect the point at which I introduced telmisartan less than a year ago. I really haven’t noticed any effects other than a kind of calm approach to events (for lack of a more accurate term) that is difficult to describe.

5 Likes
#177

I believe you can split the tablet, as Ratiopharm tablets have a score line ready.

#178

I’ve been cutting mine in half and it hasn’t been a problem. Cut away!

1 Like
#179

It’s quite likely any negative/cancer effect is a result of contamination of the base compound due to the manufacturing process. The base compound must be mixed with excipients in the process for either capsulation and pressing into tablets. That mixing process is critical with respect to added heat during mixing. This added heat can create nitrosamines, which are carcinogenic.

Mixing large qty’s of powder generates heat through friction.

This is an “old” issue and there have been recalls on various drugs due to this exact issue.

Subsequently, the Food and Drug administration (FDA) announced that they have started testing all the other drugs in the ARB class for nitrosamines, since the synthesis of other ARBs can have similarities to the synthesis of valsartan and nitrosamines can be a common impurity developing during synthesis of all ARBs [8]. Later on, N-nitrosodiethylamine (NDEA), another possibly carcinogenic nitrosamine, was identified in at least 3 different ARB containing drug products, namely valsartan, losartan and irbesartan, resulting in further recalls in 2018 and 2019 [9–11]. This was followed by the discovery of a third nitrosamine in several ARB drug products, again resulting in recalls [12]. Moreover, throughout 2021, multiple lots of three different ARBs were progressively recalled again, this time due to another potentially carcinogenic impurity, namely azido compounds

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#180

I had thought it was just the empagliflozin that was making me incredibly thirsty. It may in fact have been the telmisartan + empagliflozin that was doing this. This explains my incredibly enhanced thirst. Thanks @CronosTempi

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