Question:
5/25/2022
I saw a 28-year-old female who had an allergic reaction to Depo Provera injection. She received Depo Provera injections from age 18 to 20 years without adverse reactions. She then received Depo Provera at age 28 years. Within 5 minutes, she developed itching in the hands and bottom of feet followed by hives on chest and back, throat clearing and swelling of the throat and difficulty breathing. She was given epinephrine in the clinic and again in the ambulance on the way to the ER where symptoms improved. There were no other identifiable changes on that day.
She given a dose from a multidose vial which contains: Medroxyprogesterone acetate 150 mg, Polyethylene glycol 3350 28.9 mg, Polysorbate 80 2.41 mg, Sodium chloride 8.68 mg, Methylparaben 1.37 mg, Propylparaben 0.150 mg and where necessary: sodium hydroxide or hydrochloric acid, or both.
She received the primary series of the Moderna COVID vaccine without adverse reaction which contains the polyethylene glycol. She has also tolerated miralax. The Glasko Dtap which she tolerated contained: Each 0.5-mL dose is formulated to contain 5 Lf of tetanus toxoid, 2.5 Lf of diphtheria toxoid, 8 mcg of inactivated PT, 8 mcg of FHA, and 2.5 mcg of PRN, aluminum hydroxide as adjuvant, sodium chloride, formaldehyde, and polysorbate 80. It is recommended for her to be on some form of contraception. Her gynecologist would like to know if she can take other forms of progesterone such as levonorgestrel in the Mirena IUD or etonorgestrel in Nexplanon. Please let me know if there is information on cross reactivity between different progesterone medications or any potential testing that can be of benefit that is validated.
Answer:
I thank Dr. Kimberly Blumenthal for providing the following comprehensive response to your inquiry.
The ingredients of Depo Provera include: Medroxyprogesterone acetate 150 mg, Polyethylene glycol 3350 28.9 mg, Polysorbate 80 2.41 mg, Sodium chloride 8.68 mg, Methylparaben 1.37 mg, Propylparaben 0.150 mg and where necessary: sodium hydroxide or hydrochloric acid, or both.
Starting with the active ingredient, progesterone acetate can cause allergic reactions and although it can be used for skin testing, given a high prevalence of false-positive reactions, we have largely moved away from skin testing to progesterone acetate (Ref 1,2). I therefore do not consider it useful to do skin testing with progesterone acetate in this patient.
Next, we should consider the excipients polyethylene glycol (PEG) and polysorbate 80. Given the history of tolerance to Miralax/PEG3350, it seems unlikely there is allergy to PEG. That said, she should still be evaluated for PEG allergy now unless these were tolerated after the anaphylactic event. The assessment should include PEG skin testing, using miralax skin prick test (1:100, 1:10, 1:1) and methylprednisolone acetate skin prick (40 mg/mL) and intradermally (0.4 mg/mL, 4mg/mL) (Ref 1, 3). I would also consider a miralax challenge, if skin testing is negative (Ref 4). I will also note that tolerance to Moderna SpikeVax vaccine (excipient PEG-2000 conjugated to a lipid--2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide) does not mean there is no PEG allergy. Given the history of tolerance to PS 80 in DTAP, she seems unlikely allergic to PS 80 but if this DTAP was not given after the anaphylactic event, I would suggest skin testing to PS 80 using triamcinolone acetonide (prick testing 40 mg/mL then intradermal testing if negative 0.4 mg/ML, 4 mg/mL, Ref 3). While none of these tests are validated, they might prove useful in identification of the cause of anaphylaxis in this patient and potentially help to prevent reactions with future medications. If no skin testing is done, then I would make sure that the patient understands that that the allergy could have been due to active or inactive ingredients and some health systems don’t have allergy alerts for inactive ingredients.
Finally, the gynecologist would like to know about other forms of progesterone such as levonorgestrel (Mirena) and etonorgestrel (Nexplanon). I would work with the gynecologist on a safe drug challenge to one of these for the patient. Given that etonogestrel and levonorgestrel are available orally, there should be a safe dose to do a two-step observed drug challenge to ensure tolerance prior to mirena/nexplanon insertion. It may be more comfortable for the patient to do this with etonogestrel, given that oral levonorgestrel is emergency contraception/Plan B.
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I hope this question helps you in the care of your patient.
Jacqueline Pongracic, MD, FAAAAI