Alternative form of Nubeqa

[kreg001]

I’m now nm or mm CRPCA. A rueful sort of progress. I started Nubeqa (w Lupron) early January. I’ll have a PSA draw next week.

1. Should I expect my PSA to show a decline after five weeks of Nubeqa?

2. I have an ileostomy (no large colon) and poo in a bag at end of small intestine. If my PSA isn’t declining it is possible the Nubeqa isn’t being completely absorbed (although I haven’t seen residual pill in my output but I don’t filter it either (ugh)). Crushing Nubeqa is prohibited when asked by others on the internet. Has anyone experienced difficulties with Nubeqa, e.g. difficulty swallowing, that required crushing or pre dissolving their Nubeqa?

As always, thank you. Every morning is a great morning.

[Tall_Allen]

This is from the package insert:

12.3 Pharmacokinetics

Following administration of 600 mg twice daily, darolutamide mean (%CV) steady-state peak plasma concentration (Cmax)is 4.79 mg/L (30.9%) and area under the plasma concentration-time curve from time 0 to 12 hours (AUC12h) is 52.82h•µg/mL (33.9%). Steady-state is reached 2–5 days after repeated dosing with food, with an approximate 2-fold accumulation.

The exposure (Cmax and AUC12) of the darolutamide and the active metabolite keto-darolutamide increase in a nearly dose-proportional manner in the dose range of 100 to 700 mg (0.17 to 1.17 times the approved recommended dosage). No further increase in darolutamide exposure was observed at 900 mg twice daily (1.5 times the approved recommended dosage).

Absorption

Darolutamide Cmax is reached approximately 4 hours after administration of a single 600 mg oral dose.

The absolute bioavailability is approximately 30% following oral administration of a NUBEQA tablet containing 300 mg darolutamide under fasted conditions.

Food Effect

Bioavailability of darolutamide increased by 2.0 to 2.5-fold when administered with food. A similar increase of exposure was observed for the active metabolite keto-darolutamide.

Distribution

The apparent volume of distribution of darolutamide after intravenous administration is 119 L. Protein binding is 92% for darolutamide and 99.8% for the active metabolite, keto-darolutamide. Serum albumin is the main binding protein for darolutamide and keto-darolutamide.

Elimination

The effective half-life of darolutamide and keto-darolutamide is approximately 20 hours in patients. The clearance (%CV) of darolutamide following intravenous administration is 116 mL/min (39.7%).

Metabolism

Darolutamide is primarily metabolized by CYP3A4, as well as by UGT1A9 and UGT1A1. Keto-darolutamide total exposure in plasma is 1.7-fold higher compared to darolutamide.

Excretion

After a single radiolabeled dose as an oral solution, a total of 63.4% of darolutamide-related material is excreted in the urine (approximately 7% unchanged) and 32.4% (approximately 30% unchanged) in the feces. More than 95% of the dose was recovered within 7 days after administration.

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So, it appears to me (please check with your oncologist) that it must be taken uncrushed with food, and that it is mostly (63%) excreted by the kidneys. Possibly, you might have to increase the dose by a third to make up for the 32% that would normally get excreted after passage through the large colon. Your oncologist may want to call Bayer to ask them about this.

[kreg001 in reply to Tall_Allen]

Wow! I didn’t think to read the entire insert and I’m sure I would have struggled with pharmacokinetics. Thank you. Hopefully my PSA will have dropped. I’ll know next Friday. I haven’t experienced any side effects so an increase in prescribed dosage shouldn’t be a major issue if the drop isn’t precipitous. .

[j-o-h-n in reply to kreg001]

I've been taking Lupron forever and my M.O. switched me over from Casodex to Nubeqa in April 2023. No problem/issues swallowing two Nubeqa pills, twice a day. As far as my Psa is concerned, here the the results to date:

P.S.A. 2.14% as of 02/20/23

P.S.A. 1.24% as of 04/03/23 Nubeqa Started

P.S.A. 1.49% as of 06/27/23

P.S.A. 1.26% as of 08/15/23

P.S.A. 0.80% as of 11/08/23

P.S.A. 0.72% as of 12/18/23

P.S.A. 0.61% as of 02/12/24

P.S.A. 0.49% as of 06/04/24

P.S.A. 0.41% as of 06/21/24

P.S.A. 0.62% as of 08/13/24

P.S.A. 0.41% as of 09/25/24

P.S.A. 0.40% as of 01/21/25

Good Luck, Good Health and Good Humor.

j-o-h-n

[kreg001 in reply to j-o-h-n]

Thank you. Dropped slowly but dropped. Does your MO consider you castration resistant? I read your bio. You’ve had quite a journey so far.

[j-o-h-n in reply to kreg001]

Does MY M.O. consider ME castration resistant? (WTFK?)That's a good question that I'll ask him next time we meet at the nudist colonist convention.

Good Luck, Good Health and Good Humor.

j-o-h-n

[kreg001]

Feb. 13, 2025 PSA has fallen to 0.12 from 3.7 in late December. Nubeqa doing its job despite concerns that ileostomy might hinder absorption. Going to start planning for the next few years. I’m a happy camper!