Clinical pharmacology of tamoxifen ?

DorothyB · July 2019

I ran across this: https://www.ncbi.nlm.nih.gov/pubmed/7272932 and was wondering if anyone here was scientifically knowledgeable enough to translate it to understandable terms?

"Blood tamoxifen levels were determined for patients with metastatic breast cancer following initial and chronic dosing at twice daily 10 mg/m2 or a 20 mg/m2 single dose. Median time to response was six weeks. Blood tamoxifen levels at that time were ten-fold greater than those obtained after an initial single dose; however, steady-state values were not achieved until 16 weeks of chronic dosing."

Does this mean that it takes 16 weeks of daily dosing to get to the point where your blood levels are consistent at various times of the day??

"Tamoxifen half-life was 9-12 hours after the initial dose and seven days after chronic dosing."

This confuses me. A half-life is when the level in your blood is half what it was? or half of the amount in your blood from a daily dose? I can't figure out how a half-life could change by 14x (from 1/2 day to 7 days)

I actually found this link when I was looking to see what the half-life of tamoxifen is.

I will be starting this approx Aug 1 and want to start w/ a low dose and build up very slowly . . . but not sure how long to go before I increase the dose. Sounds like you need to take it a while before it is a steady level?

Thanks!

Jelson · July 2019

interesting, this article is from 1981. I don't think I read about half life of tamoxifen in the blood when researching for my own treatment. Most recent research discusses reducing the common daily dosage from 20 to 10 rather than building up to ? to reduce side-effects yet still be effective. Also, it is the metabolite of tamoxifen, endoxifen not tamoxifen itself which blocks the estrogen receptors in breast tissue. Circulating tamoxifen might indicate that it was not being metabolized. About 10 years ago there was a lot of discussion about genetic testing for how you personally metabolize tamoxifen which might indicate how much you actually will benefit. Talk to your Medical Oncologist!

Beesie · July 2019

"I will be starting this approx Aug 1 and want to start w/ a low dose and build up very slowly . . . but not sure how long to go before I increase the dose. Sounds like you need to take it a while before it is a steady level?"

Have you talked to your MO about this? Medical Oncologists study and train for 10 years to be able to understand this and advise on the most appropriate treatment regimen. I assume it's your MO who will be prescribing the Tamoxifen, which will therefore determine the dosage that you receive. Is there a reason why you need to figure this out for yourself?

Veeder14 · July 2019

Hi Dorothy,

I would also like clarification on the half life/dosage as well as specifics on how it works in the body. Not just the side effects it causes as I can feel those. When I asked my MO about specifics she just cites studies done but nothing more specific. I guess many patients don't want to know about the clinical pharmacology. I was referred to an endocrinologist to be evaluated for osteoporosis meds and asked how those type of meds would interact with the Tamoxifen and he didn't have answers for me. So, it would be nice to have a doctor knowledgeable in Tamoxifen to really answer my questions.

edj3 · July 2019

Veeder14, I'm none of those things but am about to start tamoxifen in September and have osteoporosis. I met w/ my (new!) endocrinologist this past Monday, and he's run a bunch of tests to rule out easy to fix causes for the osteoporosis. He laid out three options for me: Forteo or Tymlos (daily injections for two years, max); Prolia (injections every six months, duration TBD but probably a long time) or Fosamax. I also met with my medical oncologist yesterday and I asked his input, would any of the three be better or worse for me.

He visibly winced over Forteo or Tymlos, and said that Prolia would be best all around plus easier on me in terms of side effects.

So there's a data point of one for you.

DorothyB · July 2019

Jelson, interesting. I doubt my MO will do anything to see how I metabolize tamoxifen. He refused to do the other oncotype related test that would give me more detail about how much chemo might help me.

Beesie, yes MO will prescribe. Honestly, half-life itself probably doesn't matter except that I was trying to figure out how long I might expect to be at a particular dose before it was in full effect and I could try upping to the next level.

A few reasons for looking into it. Emotionally - I like to understand and it gives me a little sense of control since so much is not in my control. Also, a little lack of faith in doctors. I totally trust my PCP - and she told me that tamoxifen made her suicidal. My RO (like many have experienced) told me that my nausea isn't related to radiation. Either she or her PA (both were in the room at the time) told me that since I did radiation first, I would get less chemo. Turns out that the recommended chemo does not include taxol . . . but that isn't because I did radiation. Instead it is the protocol for my particular cancer and many others with similar diagnosis are also getting the same protocol excluding taxol before radiation. The MO's "job" is to do all he can to prevent recurrence in all patients. This is why he recommends chemo, although he did say he could understand why I might refuse it. In addition, I know my body. I used to take benadryl to help me sleep and could take two w/ no issues in the morning. After not taking it for a while, I took ONE Advil PM and 10+ hours later when I drove down my street, I recognized that I shouldn't be driving. My body really reacts to pain meds and other meds as well. What doesn't phase most really knocks me out until I get used to it.

As much as I don't want to take tamoxifen, I do recognize the benefit, so want to do all I can to be sure that I can tolerate it. MO said if side effects are too bad, he won't lower dose, but instead will put me on one of the aromatose inhibitors - which will probably make my osteoporosis worse. I want to start off very gradually in the hopes that side effects will be tolerable. I haven't discussed too much with him yet. Appt is July 31st at which time I will tell him that I am refusing chemo and he will then be ready to prescribe tamoxifen.

Veeder, thanks

Edj - I am doing Boniva almost once a month. MO did not wince at that so suspect it is ok to help w/ osteoporosis during chemo and probably during tamoxifen. Will ask when he gives me prescription. I also started switching last month from a regular calcium supplement to a plant based calcium supplement.

Hopeful82014 · July 2019

FWIW - My survivorship care center (part of the cancer center) has an oncology pharmacist on staff. She occasionally speaks to support groups and is also available by phone or email to answer questions about our medications. She was very helpful and enlightening when I had questions about Aromasin's chemistry vs. Femara, as well as providing insight in to interactions, etc. For anyone dealing with these AIs and tam. it could be well worthwhile to check for a similar professional on staff.

Veeder14 · July 2019

Your welcome Dorothy. Hopeful2014, thank you for the suggestion about speaking with an oncology pharmacist.

runor · July 2019

Dorothy, from what I gathered in my reading of low dose tamoxifen trials (there aren't many and they aren't considered conclusive) it seemed the approach was to start the subjects off on a 20mg dose, to get the drug in their system and THEN dial it back. So that's what I did and continue to do. On Sunday I take 20 mg. Monday, Tuesday, 10 mg. Wednesday is another full 20mg, Thurs, Fri and Sat are 10 mg. That is what I have chosen to do. My oncologist did not tell me this was okay. He did not suggest it. I told him, this is what I'm doing and why. He said some tamoxifen is better than no tamoxifen. Am I playing with my life? That is a philosophical question as well as a medical one. I just know I wanted to stay on the drug and didn't want to be so miserable that I quit. On half a dose I have has the full smorgasbord of side effects. But some of them have gotten better over time and none of them have been so bad that I have considered quitting. The leg cramps come close though!

Goldfish4884 · July 2019

I have tried all 3 aromatase inhibitors over the last 20 months, could not tolerate any of them so I am starting Tamoxifin this week. I asked my oncologist about starting slow at 5 mg, he didn't seem to think it made a difference but said I could take the 20 mg every other day to start if I wanted to. He also wants to see me back in 3 months to see how I am doing. He said to give it a good try as some of the initial side effects might subside after a few months. Anyone else find this to be true. I will give it my best try but at 71 years old if the side effects are too much I plan on quitting all meds and just taking my chances. Any words of wisdom would be appreciated. I currently take Vitamin D, magnesium, calcium, and glucosamine.

Salamandra · July 2019

I'm much younger but I did find that I had some initial side effects that subsided. The joints stuff subsided pretty fast for me, within a week or two. The stomach side effects took literally months and copious Prilosec to subside, but they did eventually subside completely. I had other side effects that did not subside, but at least for me it was true that the initial impact of the drug was not indicative of the long term.

gb2115 · July 2019

I am the opposite, initially I had minimal side effects, but over a couple of years they are worse and building. So I don't think starting with a smaller dose would have helped me. No way to ever know how you might react to something.

Clinical pharmacology of tamoxifen ?

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