Cyclosporine and Hydroxychloroquine Drug Interactions

Why is their a concern about using cyclosporine with hydroxchlorquine?

I’ve selected this question below for this week’s question of the week. It allows us to discuss an important drug interaction between cyclosporine and hydroxychlroquine (Plaquenil).

QUESTION

Dear Dr. Donovan.

I'm a 25 yr old woman with diagnosed lichen planopilaris (LPP). It's proven difficult to treat. My doc just prescribed plaquenil and cyclosporine, but I noticed on your handout that it says these drugs interact. Why do you not prescribe them together?

Thank you for your time!

ANSWER

Thanks for your excellent question. The reason is this: hydroxychloroquine (Plaquenil) can potentially Increase cyclosporine levels in the blood leading to higher cyclosporine in the blood and increase the risk of cyclosporine side effects.

Cyclosporine and hydroxychloroquine are two drugs that may have benefit the treatment of lichen planopilaris. The use of the two medications together (at the same time) carries the risk of increased side effects and elevated serum creatinine. Use of the two medications together is generally discouraged but if they are used together it should be done only under supervision of doctors who understand the proper monitoring that is necessary. Frequent blood pressure monitoring and frequent measurement of serum creatinine and frequent evaluation of side effects will be required.

Let’s take a look at what is known in the past.

The first indication of a potential interaction between cyclosporine was with “chloroquine” - a close cousin of hydroxychloroquine. In 1993, Finielz and colleagues published a study in the journal Nephron of a 28 year old kidney transplant patient who was stable on cyclosporine, prednisone and azathioprine. His creatinine level was 200 umol/L. His blood cyclosporine level was 105 ng/mL and his blood pressure was normal 130/80.

He then decided to go on vacation and started treatment with chloroquine for prevention of malaria. His blood pressure just 6 days later increased to 160/100, his creatinine level rose to 234 and his blood cyclosporine level rose more than four times to 470 ng/mL. His levels reduce again when chloroquine was stopped and levels rose yet again when the drug was given back.

An increase in cyclosporine levels has also been noted in patients using hydroxychloroquine (Plaquenil). Some rheumatologists in years gone by have studied this combination. But that’s not to say it’s not without potential risk - there are.

A 1996 study examined the benefits of combining cyclosporine to patents with rheumatoid arthritis who were not improving with hydroxychloroquine or methotrexate. We’ll focus here on the results of combining cyclosporine and hydroxychloroquine because this is what your question pertains to.

The study included 12 patients using both hydroxychloroquine and cyclosporine. During the study, the mean daily dose of CsA ranged from 2.5 to 4.2 mg/kg and at 6 months it was 3.3 mg/kg. The mean serum creatinine levels increased by 0.1 +/- 0.2 mg/dl in the patients treated with the two drugs. In 5 of 12 patients (41.6 %) there was a concerning increase in creatinine of more than 130 %. Other side effects seen in the combination were gastrointestinal side effects (41.6%), hypertrichosis (25%), gingival hyperplasia (25%), liver test abnormalities (8.3 %), and neurological problems (16.6%). This is not by any means a complete lists of side effects of cyclosporine - those will need to be reviewed with your doctor.

Conclusion

Thanks again for the great question. Yes, there most certainly is a potential drug interaction between cyclosporine and hydroxychloroquine that is very important for patients and treating physicians to be aware. Cyclosporine is notorious for drug interactions so I recommend that anyone who uses cyclosporine get in a routine of shouting out loudly “I am on cyclosporine - does this drug interact?”

Any patient started on combined hydroxychloroquine and cyclosporine treatment will need to first check that this was not an error by the prescriber. Sometimes this is what the prescriber intended - as seen above in the 1996 study I mentioned. This is not, however, all that common anymore. If it was not an error, the patient will need very, very close monitoring. Blood pressure will need to be measured daily during the starting period. Serum creatinine levels and serum cyclosporine levels will need to be measured very frequently and side effects will need to be closely monitored.

References

1] Uptodate.com

2] https://www.drugs.com/interactions-check.php?drug_list=763-0,1298-0

3] Salaffi et al. Combination therapy of cyclosporine A with methotrexate or hydroxychloroquine in refractory rheumatoid arthritis. Scand J Rheumatol. 1996;25(1):16-23.