There is a minimal risk to individuals who are highly latex allergic to use multi-dose, rubber stoppered vials to extract medications or allergen vaccines. The amount of latex released by rubber stoppers is very low and somewhat variable. Repeated puncture of the rubber stopper increases the amount of allergen. However, given the prevalence of latex allergy in the atopic population and the number of allergen vaccines administered, the individual risk is extremely low. As with all decisions in clinical medicine, the risk and benefit need to be weighed. There are no alternatives of which I am aware to prepare vials without the use of rubber stoppers.
I have attached a prior question and answer from the Ask the Expert Archives for your review. The answer and references address these issues and includes a response from Dr. Jay Slater, Director of Division of Bacterial, Parasitic and Allergenic Products of the FDA. I also have referred your question to Dr. Bob Esch, Greer Laboratories, to determine if he can provide information from the allergy vaccine manufacturer perspective.
I hope this information is of help to you and your patient.
All my best.
Dennis K. Ledford, MD, FAAAAI
I received a response from Dr. Bob Esch.
To my knowledge, most, if not all stoppers used for allergenic extracts and diluents for allergenic extracts are now “latex-free.” Also, studies were conducted many years ago showing undetectable Hev b proteins in vialed solutions after hundreds of needle penetrations through the stopper. It is my recollection that “positive” intradermal skin test reactions with negative control solutions could detected when syringes containing rubber (latex) plungers were used. Again, I believe that now, syringe plungers are also “latex-free.
Risk of anaphylaxis to latex from injection obtained from rubber-stoppered vials
Our institution is hoping to help improve serving our patients with latex allergies. We attempt to get as many latex free products as possible in the pharmacy, but there are some drug vials that contain natural rubber latex in the stoppers, and there are not latex-free alternatives. According to our research, procedures like removing the stopper still do not eliminate the risk of latex contamination, but please feel free to correct us if you have information saying otherwise (e.g. that the amount from this contact is not Clinically relevant). What would you consider best practices for these kinds of meds, especially for the meds with no latex-free alternatives and chemotherapy vials, where even removing the stopper is impractical for our staff?
A: Unfortunately, I cannot give a definitive answer to your question. The best that we can say is that reactions to latex due to the amount of latex that would be obtained from a rubber-stoppered vial are rare, but they have been reported. Based upon this, different professional societies have advised different strategies.
I have copied for you below quotes from some of these societies as well as our answer to a previously posed similar question. When one reviews the literature and the suggestions of professional societies, one can see that recommendations have varied. This is due to the paucity of data that we have on this topic. Because of this, experts, quite naturally, differ in their recommendations.
The quote from the CDC gives one the option of assessing risk/benefit ratio. The American Association of Nurse Anesthetists (AANA), on the other hand, state that in a patient at risk, medication should be taken from opened multidose vials (removing the stoppers). A response to a question posed to the American Latex Allergy Association that was answered by Dr. Robert G. Hamilton (Ph.D.) sites a “one stick rule” as applicable in this situation.
Thus, the best that we can give you in terms of selecting a “best practice” for your institution would be to let review the material copied below and determine your policies based upon a consideration of these opinions in aggregate.
In closing, I would make one statement regarding a specific question you asked. Removing the stopper may not eliminate the risk of latex contamination, but we do know that the allergen increases with multiple sticks. It is very unlikely that there would be any significant allergen in the vial if the stopper from a multidose vial was removed prior to any use (as recommended by the AANA copied below).
Thank you again for your inquiry and we hope this response is helpful to you.
Latex in Vaccine Packaging
“If a person reports a severe (anaphylactic) allergy to latex, vaccines supplied in vials or syringes that contain natural rubber should not be administered unless the benefit of vaccination outweighs the risk for a potential allergic reaction. In these cases, providers should be prepared to treat patients who are having an allergic reaction. For latex allergies other than anaphylactic allergies (e.g., a history of contact allergy to latex gloves), vaccines supplied in vials or syringes that contain dry natural rubber or rubber latex may be administered." (ACIP General Recommendations on Immunization. 2011).
American Association of Nurse Anesthetists
222 South Prospect Avenue
Park Ridge, IL 60068
"Draw medication directly from opened multidose vials (remove stoppers) if medications are not available in ampoules."
Guidelines for the Management of Latex Allergies and Safe Latex Use in Health Care Facilities
Gordon Sussman, M.D. and Milton Gold, M.D. American College of Allergy Asthma and Immunology
The exact latex-avoidance measures necessary to prevent IgE-dependent allergic- sensitization reactions are not clearly established. There have been rare case reports of systemic reactions from IV tubing after needle punctures of the rubber ports presumably due to latex allergy (Schwartz and Zurowski, 1993). However, another study found latex-allergenic proteins in a multi-dose vial only after 40 punctures of the rubber stopper (Yunginger et al., 1993). Natural rubber latex must be differentiated from butyl rubber, which is used in rubber stoppers, and from synthetic rubber in latex paints, neither of which poses hazards to patients sensitized to latex (Yunginger, 1995).
Yunginger J.W., R.T. Jones, J.M. Kelso, M.A. Warner, L.W. Hunt and C.E. Reed. "Latex allergen contents of medical and consumer rubber products." (Abstract) J Allergy Clin Immunol 91(1993): 241.
Yunginger, J.W. "Natural rubber latex." Immunology and Allergy Clinics of North America 15(1995): 583-95.
American Latex Allergy Association
Robert G. Hamilton,PhD Johns Hopkins University Medical School, Baltimore, Maryland
In a recent study that was just published (Primeau et al, Natural rubber pharmaceutical vial closures release latex allergens that produce skin reactions. The Journal of Allergy Clinical Immunology, 107:958-962, 2001), we found latex allergen in saline that was stored in contact with natural rubber stoppers and the puncturing event increased the level of allergen as detected by intradermal skin testing of latex allergic subjects. At our institution, we are continuing to use the one stick rule to minimize any increase in levels of latex allergen in medications with vials that may contain rubber stoppers. This is done for everyone. Moreover, we have concluded that the pharmacist cannot guarantee the type of material in any closure in any vial since this information is difficult to get from manufacturers. Thus, our nursing staff is increasing the extent of observation when any medication is given to a person deemed to be latex allergic by history and/or confirmatory blood or skin test. We hope that this study will
(1) encourage the FDA to force all pharmaceuticals to be labeled at “containing natural rubber latex” if rubber is in the packaging (such as the rubber stopper) and
(2) encourage the pharmaceutical manufacturers to use synthetic stoppers in any new medications.
- See more here.
Injections taken from rubber stoppered vials
Question posted 2/15/2012:
I have a patient that has a IgE level of 8.4 for latext allergy. No documented hx of anaphylactic reaction but is needing multiple vaccines that have latex involved. Should the vaccines be given? Is this level of IgE associated more with Type I or type IV? Thank you for your time.
Thank you for your follow-up letter with the additional information in response to my follow-up questions (below):
1. Question: Why was an IgE anti-latex test drawn?
Answer: This is a new recruit to military service and we test all of our new accessions because a severe latex allergy will disqualify them for military service.
2. Question: I will need the values for the particular tests that you utilized (in vitro tests for latex allergy come with a scale of values which indicate relative risks. The number 8.4 would not be of help unless we can obtain this scale that applies to the tests you ordered. Several companies perform this test and they each have their own scale).
Answer: We use Quest out of Chicago, ILL. They use <5 as non-allergic and > 5.1 as positive for allergy.
3. Question: I am not aware of latex being involved for any immunization except via the fact that they have latex caps on the vials. Are you worried about anything other than the cap on the vial?
No, it is just the latex caps on the vials. We do have some immunizations that come in pre-filled syringes that have latex on the plungers.
Based on the above, there is still one issue about which I have question. That is the value for serum-specific IgE to latex. These tests are usually not "positive versus negative" but are expressed in a range of values from negative, equivocal, low positive, moderate positive, et cetera, to very high positive. Quest usually uses two labs, both of which use the same scale which has several numerical divisions, thus grading the positivity. However, for the sake of argument, assuming that this test is significantly positive (actually a value of 8.7 on the normal scales that we use would be a high positive), I am going to attempt to answer your question as best we can.
Unfortunately, to the best of my knowledge, this answer will not be definitive, because there is some controversy as to the level of risk involved of having an anaphylactic reaction to latex particles leaked into a vial from multiple punctures through a hard rubber stopper. But the weight of evidence clearly supports the fact that such reactions are possible. The 2001 abstract below from The Journal of Allergy and Clinical Immunology demonstrates that latex allergen can be found in the contents of vials with rubber stoppers. In addition to this abstract I have also copied a couple of links to articles that discuss this issue as well as an abstract from the Annals of Pharmacotherapy for your perusal.
A review of this literature, taken as a whole, based on personal interpretation, is that such reactions can occur, but appear to be rare.
One thing that I would suggest you do is have this young man seen by an allergist, because in vitro testing for latex allergy is certainly imperfect, and it would be wise to have him evaluated by someone who is familiar with latex allergy and can, if he/she chooses, try and confirm the positive reaction via skin testing. Although skin testing is also imperfect, it might help clarify the issue.
Finally, in addition, because of the uncertainty over reactions to latex obtained from rubber stoppers, especially their frequency, I am going to forward your inquiry to Dr. Jay Slater, who is an internationally known expert in latex allergy, and ask him to give us his comments. When I hear from Dr. Slater, I will send his response to you.
Thank you again for your inquiry and we hope this response is helpful to you.
Background: The release of allergenic proteins from natural rubber vial closures (stoppers) into aqueous pharmaceuticals may induce allergic reactions in individuals with latex allergy (LA) receiving medications from such vials.
Objective: The goal of this study was to determine whether solutions stored in vials containing natural rubber closures release allergenic proteins detectable by skin testing of subjects with LA.
Methods: Five pharmaceutical vial closures (2 natural rubber and 3 synthetic) were coded, inserted onto vials containing phenol-saline-human serum albumin, and stored in an inverted position before use. Twelve volunteers with and 11 volunteers without LA underwent skin testing with solutions from each of the 5 vials, either those not punctured (0P) or those punctured 40 times with a 21-gauge needle 12 to 24 hours before testing (40P).
Results: All intradermal skin test responses in the group without LA were negative. Two and 5 of the 12 subjects with LA had positive intradermal skin reactions to 0P and 40P solutions, respectively, from vials containing rubber closures. Two subjects with LA had inexplicable, positive, nonreproducible intradermal skin test reactions to solutions from vials containing bromobutyl but not vials with isoprene synthetic closures. In vitro inhibition analysis detected 6 to 7 AU/g latex allergen in extracts of cut natural rubber containing closures but not in extracts of synthetic closures.
Conclusion: Natural rubber vial closures released allergenic latex proteins into the tested solutions in direct contact during storage in sufficient quantities to elicit positive intradermal skin reactions in some individuals with LA. These data support a recommendation to eliminate natural rubber from closures of pharmaceutical vials. (J Allergy Clin Immunol 2001;107:958-62).
Allergic Reaction to Latex from Stopper of a Medication Vial
Local anesthetic cartridges and latex allergy: a literature review
[PDF] from cda-adc.ca
AR Shojaei, DA Haas - Journal-Canadian Dental Association, 2002 - cda-adc.ca
Risk of latex allergy from medication vial closures Ann Pharmacother March 1, 1999 vol. 33 no. 3 373-374
A latex allergy, like all allergies, is a serious matter that requires special precautions on behalf of patients and healthcare workers. The FDA final rule on the labeling of natural rubber-containing medical devices will assist in the creation of a latex-safe environment for latex-sensitive individuals. Currently, this ruling does not apply to medication vial closures that contain latex. Until further action by the FDA, the only way to determine whether a medication vial closure contains latex is by directly contacting the pharmaceutical manufacturer. Moreover, in order to rule whether special labeling should be mandatory for latex-containing medication vials, additional evidence is needed to clarify whether exposure to trace amounts of latex from a medication vial stopper can cause allergic reactions in individuals who are sensitive to latex.
We received a response from Dr. Jay Slater. Thank you again for your inquiry and we hope this response is helpful to you.
Phil Lieberman, M.D.
Response from Dr. Jay Slater:
My summary of this case: an otherwise healthy military recruit is screened for latex allergy using the Quest lab's test for latex-specific IgE. The stated purpose of the screening test is that severe latex allergy will disqualify [him] for military service. The result is positive although not, apparently, elevated enough for disqualification. The question is whether the recruit should be immunized as required, even though several of the vaccines may contain leeched latex allergen.
The predictive value of the positive test, in this case, is uncertain. Quest uses the ImmunoCap assay. In a recent study, Unsel et al (Int Arch Allergy Immunol 2012; 158:281-287) found that 30% and 9% of asymptomatic atopic and non-atopic patients had positive ImmunoCap latex results. Skin testing for latex was negative in all these patients, as was nasal provocation in the subset that consented to the challenge. The study was done in Turkey, but is certainly consistent with US experience.
The amount of latex allergen in vaccines is extremely small, and denying vaccination to this recruit would be an unreasonable overinterpretation of the real risk. Unless there is other information (risk factors, unexplained urticaria in possible exposure situations), I believe that the patient should undergo a full immunization series.
Jay Slater, M.D.
Phil Lieberman, M.D.
I hope this information is useful.
With warm regards,
Dennis K. Ledford, MD,FAAAAI