Rosuvastatin [Crestor] and Abiraterone [Zytiga]

[pjoshea13]

New anecdotal case from Belgium of an interaction [1].

"We hereby present a case of severe rhabdomyolysis resulting in acute on chronic kidney injury following abiraterone initiation in a patient previously under rosuvastatin."

"Abiraterone selectively inhibits CYP17 as well as the hepatic transporter OATP1B1. OATP1B1 is an efflux transporter, whose function is to extract several drugs from the portal blood, allowing them to undergo hepatic metabolism. We hypothesize that abiraterone-induced inhibition of plasmatic uptake of rosuvastatin by OATP1B1 increased plasmatic concentration of rosuvastatin, leading to toxicity on muscle cells. We therefore suggest that the association between rosuvastatin and abiraterone should be avoided."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/323...

J Oncol Pharm Pract

. 2020 May 12;1078155220923001. doi: 10.1177/1078155220923001. Online ahead of print.

Rhabdomyolysis and Acute Kidney Injury Induced by the Association of Rosuvastatin and Abiraterone: A Case Report and Review of the Literature

Ismail Ould-Nana 1 , Marine Cillis 2 , Marco Gizzi 3 , Valentine Gillion 4 , Philippe Hantson 1 , Ludovic Gérard 1

Affiliations collapse

Affiliations

1 Department of Intensive Care, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

2 Department of Clinical Pharmacy, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

3 Department of Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

4 Department of Nephrology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

PMID: 32397905 DOI: 10.1177/1078155220923001

Abstract

Introduction: Abiraterone acetate is an inhibitor of androgens biosynthesis, approved as first-line treatment in castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer. Abiraterone has been rarely associated with severe rhabdomyolysis, but the mechanism of muscle toxicity is unknown.

Case report: We hereby present a case of severe rhabdomyolysis resulting in acute on chronic kidney injury following abiraterone initiation in a patient previously under rosuvastatin.

Management and outcome: Rhabdomyolysis was resolutive after rosuvastatin and abiraterone discontinuation, and kidney function recovered. There was no recurrence of muscle toxicity after re-initiation of abiraterone alone.

Discussion: Abiraterone selectively inhibits CYP17 as well as the hepatic transporter OATP1B1. OATP1B1 is an efflux transporter, whose function is to extract several drugs from the portal blood, allowing them to undergo hepatic metabolism. We hypothesize that abiraterone-induced inhibition of plasmatic uptake of rosuvastatin by OATP1B1 increased plasmatic concentration of rosuvastatin, leading to toxicity on muscle cells. We therefore suggest that the association between rosuvastatin and abiraterone should be avoided.

Keywords: Abiraterone; OATP1B1; acute kidney injury; rhabdomyolysis; rosuvastatin; uptake transporter.

[Max135]

thanks for the post Patrick...

I think the connect between the statin I am taking and the abi has left me with muscle issues. Will stop the statin and see if that takes my nightly muscle cramps away.... new information that helps is always useful.

thanks again....

Max

[PhilipSZacarias]

Well, about the common sense method of reducing the dosage of the rosuvastatin? And vitamin D and metformin may ameliorate the effects of statins with respect to rhabdomyolysis. Cheers, Phil

[cesanon in reply to PhilipSZacarias]

Philip

" vitamin D and metformin may ameliorate the effects of statins with respect to rhabdomyolysis" PhilipSZacarias

Can you explain further?

Thanks

[Hidden in reply to cesanon]

Good question. I found this about vitamin D: ncbi.nlm.nih.gov/pmc/articl...

And this about metformin: pharmacytimes.com/resource-...

[PhilipSZacarias in reply to cesanon]

Hello cesanon, prior to being diagnosed with PCa, I was taking 10 mg Crestor and developed muscle craps, which caused me to discontinue the statin. After being diagnosed with PCa and reviewing the literature on the possible efficacy of statins in slowing progression I started taking 10 mg rosuvastatin again. After several months my blood work was still not in the acceptable range for LDL and since I had not experienced muscle cramps, I raised the dosage to 20 mg - its been over a year and so far no muscle cramps. The difference between before and after is that I am taking 4000 IU vitamin D and 2000 mg metformin.

The following references appear to support the use of Vitamin D and metformin to alleviate muscle cramps:

“Vitamin D Status Modifies the Association between Statin Use and Musculoskeletal Pain: A Population Based Study” PMID: 25437894

“Impact of vitamin D status on statin-induced myopathy” PMID: 29067242

“Metformin's impact on statin-associated muscle symptoms: An analysis of ACCORD study data and research materials from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center” PMID: 29577553

Cheers, Phil

[Hidden in reply to PhilipSZacarias]

Reduce the dose? That would reduce the manufacturer's profits! Crazy talk.

[pjoshea13 in reply to Hidden]

At Publix. 5 mg cost $4.87 / month; 40 mg cost $7.99.

At CVS: $68.75 & $71.88 !!!

But whatever the formula, I suspect that the profit doesn't vary much by dose.

-Patrick

rxsaver.retailmenot.com/dru...

[mcp1941 in reply to pjoshea13]

My co-pay for Crestor at CVS was $3.70

Mike P

[Hidden in reply to pjoshea13]

Cheap if you use insurance or a saving program (I use kroger and goodrx gold). My doctor told me that some of his patients pay MSRP for drugs. Depending on dosage, MSRP for rosuvastatin is over a hundred bucks.

But I wasn't totally serious about profits. However, my immediate thought was: reduce the dose - don't go completely off a desired medication unless there are other reasons, or if dose reduction removes the efficacy entirely, or if reduction doesn't remove the side effects. And even then talk to your doctor or research substances that might alleviate the side effects.

If this study is straightforward and the serum level increases, it seems like this is an obvious opportunity to reduce the dose. We're frequently looking for ways to increase bio-absorption of substances (e.g. curcumin) yet if it is done by accident it is frequently treated as a negative. Why? I don't know.

Good info though. Appreciate it. I take simvastatin and also AA so I'll think about how this might apply to me.

About the AA, the manufacturer hasn't renewed my copay assistance so the cost for 1000mg a day of AA is $300 a month. So I quartered the dose and take it with food and probably get about the same serum level for $75 a month. I talked to my onc and she's fine with this approach.

Do you know if there is a way to measure AA in the blood?

[PhilipSZacarias in reply to Hidden]

Profits aside...If abiraterone raises the blood concentration of rosuvastatin and causes muscle cramps then reducing the dosage to a level that is still effective for reducing LDL but not eliciting muscle cramps is the way to go. Cheers, Phil

[Garp41]

I read about permanent autoimmune muscle disease with Statins, and went off Crestor.

Doug

[Hidden]

Statins are strongly associated with decreased PrC mortality risk.