Tamoxifen and Ropinirole drug interaction?

[Pianopooh]

Hello forum posters -- the following is from a question my friend and I were talking about last night:

"Have any of you heard about a new study that has found a drug-drug interaction between tamoxifen and ropinirole? We have an insurance company that claims there is an interaction and won't allow the two to be filled together."

I searched through pharmacy sources and only came up with how the drug works. CYP2D6 inhibitors: May increase the levels/effects of tamoxifen. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.

Does anyone have any idea of a d-d interaction? Any help will be appreciated, thank you!

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[RxWildcat]

What does the insurance co say the interaction is?

 

[PharmDstudent]

"Dosage adjustment may be required if Requip is used with estrogen or CYP450 1A2 inhibitors, such as ciprofloxacin." http://www.requip.com/hcp/treating_rls_with_requip/safety_and_tolerability.html

"Interactions between Requip (ropinirole) and Estradiol (estradiol):
estradiol and ropinirole (Moderate Drug-Drug)
MONITOR: Coadministration with estrogen-containing drugs may increase the plasma concentrations of ropinirole. Data from a population pharmacokinetic study revealed that estrogens, mainly ethinyl estradiol at 0.6 to 3 mg over a 4-month to 23-year period, reduced the oral clearance of ropinirole by up to 36% in 16 patients. The mechanism of interaction has not been described.

MANAGEMENT: Dosage adjustment for ropinirole should not be necessary in patients already on estrogen therapy because patients must be carefully titrated to tolerance or adequate effect. However, if estrogen therapy is initiated or discontinued during treatment with ropinirole, then patients should be monitored for altered ropinirole effects and the dosage adjusted as necessary."
(http://www.drugs.com/drug-interactions/requip_d04215_estradiol_d00537.html)

"How Does Tamoxifen Work?
To grow and reproduce, breast cancer cells require the female hormone estrogen. Tamoxifen is an "anti-estrogen" and works by competing with estrogen to bind to estrogen receptors in breast cancer cells. Tamoxifen is formally known as a selective estrogen receptor modulator (SERM). By blocking estrogen in the breast, tamoxifen helps slow the growth and reproduction of breast cancer cells."

Tamoxifen targets estrogen receptors...

"CYP 450 enzymes involved in the metabolism of Tamoxifen: 1A2, 2A6, 2B6, 2C9, 2D6, 2E1, 3A4"
(http://www.edhayes.com/CYP450-1.html)

Tamoxifen is metabolized by 1A2...

Final conclusion:
If Tamoxifen does not inhibit 1A2, it should not reduce the metabolism of Requip. However, there could be two things at play that could make the combination suspect of an interacition: Tamoxifen binds to estrogen receptors, so its estrogenic action alone could require a dosage adjustment of Requip. Or, if the 1A2 enzymes become saturated with Tamoxifen due to greater affinity for the receptor, then Requip may not be metabolized as quickly, which would require a dosage adjustment.

 

[AggiePharmer]

"Final conclusion:
If Tamoxifen does not inhibit 1A2, it should not reduce the metabolism of Requip. However, there could be two things at play that could make the combination suspect of an interacition: Tamoxifen binds to estrogen receptors, so its estrogenic action alone could require a dosage adjustment of Requip. Or, if the 1A2 enzymes become saturated with Tamoxifen due to greater affinity for the receptor, then Requip may not be metabolized as quickly, which would require a dosage adjustment.

Good post. I haven't come across any evidence that would suggest inhibition of 1A2 by TAM, but I'll ask some of my PK associates if they've seen anything that may suggest a downregulation along the lines of CYP1A2.

However, because Tamoxifen is also tissue specific (ER antagonist in breast, ER agonist in endometrium), it's possible that such estrogenicity may corroborate the decreased Ropinirole clearance rates you've cited above. I don't doubt the overlapping affinities for both drugs on 1A2, either.

Come to think of it, find me a drug that's not impacted by either CYP1A2, 2E1, or 2D6 nowadays...

 

[Pianopooh]

Thanks for all the responses! I have sent the message to my friend, and awaiting to what she has to say when she forwards it to her pharmacist. I will ask her what the insurance company specifically said to her.