Pruritis and anticoagulants
Question:
12/27/2017
I have a 69 year-old female patient with complaint of isolated, intense, generalized pruritis with use of anticoagulant medications. This has occurred with both Eliquis and Xarelto in the past (~ 1 year ago) and most recently has recurred since starting Coumadin 1 month ago. The pruritis starts ~ 2 hours after every dose (usually in the evening) and then resolves by the next morning. It is very disruptive to sleep. There has NEVER been any associated rash of ANY kind, no angioedema, difficulty breathing or swallowing. Intercurrently, she was treated with daily aspirin with complete resolution of pruritis, however is now requiring a long term anticoagulant due to stroke last month. Her PCP has attempted to treat her pruritis with daily Zyrtec and Hydroxyzine Qhs, without any improvement. I am hesitant to trial Doxepin, as she is already on Amitryptiline for depression. My questions are: 1) given the lack of any other symptoms, including rash/hives, do you think this could be IgE mediated (given quick onset after every dose)? 2) Is there available skin testing, and if so, would it be beneficial? 3) With the given history, do you think that a desensitization to Coumadin (or another anticoagulant) would be potentially beneficial?
Answer:
Thank you for your question. I received input from 2 of our experts. Please see their responses below:
From Dr. Eric Macy:
"Given the absence of hives, an IgE-mediated reaction or direct mast cell activation, is extremely unlikely. Given the absence of hives, or objective evidence for direct mast cell activation, then desensitization will not be possible. Verify normal kidney, liver, and thyroid function as alternative causes of itching without any rashes. Verify there are not any other drugs also being used, such as opiates, that have itching as a known side effect. Keep skin moist using a thick cream such as Eucerin and apply cream to skin while wet if dry skin. If cetirizine up to 40 mg a day and diphenhydramine 50 mg prior to sleep, fails to control the itching when taking coumadin, then discontinue the amitriptyline and consider a trial of doxepin 25 to 50 mg prior to sleep."
From Dr. David Lang:
"This is a challenging case. Several years ago, I was asked to see a patient who had exhibited pruritus to anti-coagulant medications, including warfarin. Warfarin has been reported to be efficacious as a treatment for chronic urticaria (1,2), and IgE mediated reaction to warfarin would be very unusual. In view of this, I proposed that we perform a double-blind, placebo-controlled (DBPC) challenge. After explaining the rationale for this, the patient agreed. Long story short: we had 3 placebo capsules and a 4th that contained the prescribed dose of warfarin, with the code made up by someone in our Pharmacy. The patient experienced pruritus after challenge dose #2. After breaking the code, we found she had reacted after taking two placebo capsules. Afterwards, she had no further problems taking warfarin daily as prescribed. I can’t guarantee this will be the outcome for your patient; however, the only downside is time (hers and yours) and resources that you have to offer in your outpatient clinic.
In setting this up, I would stipulate a priori that if she has pruritus associated with taking warfarin during the challenge that you and she agree to repeat the DBPC challenge at least once to eliminate the possibility that pruritus occurred due to chance.
The additional complication in this case is the latency between exposure and adverse reaction of 2 hours. This will need to be addressed in your protocol.
If the relationship between warfarin and pruritus is confirmed by DBPC challenge(s), there is a protocol published for desensitization to warfarin (3). If I were you, this would be my next step, as her reaction does not entail anaphylaxis and I believe this would be favorable from the standpoint of balancing the potential for benefit with the potential for harm/burden. In this report (3), the following doses were administered:
Dose (mg)
0.25
0.50
0.75
1.00
1.50
2.00
You did not mention the dose of warfarin your patient is taking. The above protocol will need to be adjusted in the context of her daily dose.
Citations
1) Mahesh PA, Pudupakkam VK, Holla AD, Dande T. Effect of warfarin on chronic idiopathic urticaria. Indian J Dermatol Venereol Leprol. 2009;75(2):187-9.
2) Parslew R, Pryce D, Ashworth J, Friedmann PS. Warfarin treatment of chronic idiopathic urticaria and angio-oedema. Clin Exp Allergy. 2000;30(8):1161-5.
3) Jameson T, Siri D. Induction of tolerance to warfarin after anaphylaxis with a desensitization protocol. Cardiology 2010; 115: 174-175.
As you can see, there are a number of considerations for this patient. I hope you find this information helpful.
Regards,
Daniel Jackson, MD FAAAAI