Dispensing / Prescribing Against Labeled Warnings
-See Detail-Document #220332 for a list of drugs with a Black Box Warning-
Background
There is confusion regarding whether it's legal to prescribe or dispense drugs against a black box warning or contraindication in the product labeling. This document reviews the differences between contraindications and black box warnings and addresses the legality of dispensing or prescribing contraindicated or black box warning meds. It also reviews ways to possibly limit liability when using these medicines against package labeling.
Contraindication vs Black Box Warning
All medicines have benefits and risks. Contraindications in drug labeling denote that the risk of use outweighs the benefit in particular situations.1 Contraindications in drug package labeling are usually considered "absolute" contraindications. "Relative" contraindications are listed in the warnings section of the labeling. Examples of contraindications listed in prescription package labeling include using metformin in patients with renal insufficiency or ACE inhibitors in patients who've experienced angioedema while on an ACE inhibitor.
Black box warnings are different than contraindications. These are designed to highlight information regarding serious adverse reactions or safety hazards that may lead to death or serious injury.1-3 Over 300 medications now have black box warnings.2 The Food and Drug Administration (FDA) provides boxed warnings in several situations: when a drug presents a unique risk compared to other drugs in the class, when a potential adverse reaction is severe, or when such reactions can be prevented or reduced through restricted use or by following defined cautions.1
Although some boxed warnings include contraindications, many times they are just precautions for use. Some warnings may describe significant drug interactions, the need for enhanced monitoring, or the need for special training to prescribe.1 For metformin, the black box warning emphasizes the risk of lactic acidosis. In addition to the renal insufficiency contraindication, it adds patients over age 80 and heart failure patients requiring meds as populations of concern. The boxed warning for ACE inhibitors reviews the risk of use during pregnancy. These precautionary warnings are listed under the warnings section of the package labeling.
Black box warnings are usually based on clinical data derived after a drug is marketed, but may be based on serious animal data as well. Additionally, warnings that appear in black boxes may be associations; causation does not have to be demonstrated.2,4 An example of association without demonstrated proof is the black box warning communicating the link between topical calcineurin inhibitors (e.g., Elidel, Protopic) and cancer.
Legality
The Food and Drug Administration (FDA) clearly states it doesn't regulate the practice of medicine or pharmacy.1 Therefore, information contained in package labeling provided by the FDA doesn't confer legality. However, prescribing or dispensing against package labeling may increase liability in the case of an adverse event. If a pharmacist or prescriber is sued for malpractice in this situation, it'll probably be for negligence, as a deviation from the standard of care. Therefore, the practitioner will be judged against how a qualified peer with the same information and experience would act in a similar situation.3
Prescribing medications against package labeling does occur. In one study 10% of patients were prescribed at least one drug with a boxed warning. However, only 0.7% of patients received a drug in violation of the warning.4 The most common drugs prescribed against a boxed warning were azathioprine, carbamazepine, valproate, lithium, metformin, propoxyphene, and potassium-sparing diuretics.
For contraindicated medications, one study found that patients were given meds with potential drug-drug or drug-disease contraindications at an incidence of 1.9 per 1000 patient years. Awareness of the problem was only documented 33% of the time.5
Pharmacist Liability
For many years, pharmacists were found negligent only if an error occurred during the dispensing process. Pharmacists were not held liable for failing to warn patients since this could have been considered second-guessing the prescriber.6 This view is changing and many states now hold pharmacists accountable for "duty to warn." Around 8% of all malpractice claims against pharmacists now involve the pharmacist's duty to warn.7
If you are filling a prescription against package labeling, call the prescriber and make sure they are aware of the contraindication or warning. Have alternatives ready to suggest. If the prescriber insists on giving the medicine to the patient, document that you've spoken to the prescriber.
In addition to speaking with the prescriber, educate the patient about the risks of the medication. Give the patient specific information regarding the potential problems associated with taking the medicine against package labeling. Be careful not to undermine the prescriber-patient relationship or to indicate that you disagree with the prescriber. Document your patient interaction as well as your prescriber communication. Consider using the "Consult Confirmation" form to fax to providers that's contained in this Detail-Document.
Prescriber Liability
Prescribing a drug against a contraindication or warning is considered an "off-label" use, similar to using a drug for a nonapproved indication. However, since the risk of patient harm may be higher in this situation, legal experts recommend being more vigilant. If you need to prescribe a drug that is contraindicated in your patient or has a black box warning, you should document in the chart why you feel the benefits outweigh the risks. By doing this, you acknowledge awareness of the risks associated with the drug and are giving specific reasons as to why you are prescribing it.
Although some experts promote the use of informed consent documents that patients sign, these are not required. However, your approach to communicating with the patient should be similar to getting informed consent for a procedure. Plan on discussing benefits and risks and reviewing alternative therapies with the patient. Tell patients of the specific contraindication or black box warning and why these are issues. Be specific in your documentation with regards to what you discussed with the patient. Often times, just saying "discussed benefits and risks" is not enough.8 Consider discussing the "Sample Informed Consent" form we've created with your attorney to see if a similar approach is appropriate for you.
Conclusion
It's not against the law to prescribe or dispense a medication against package labeling, but doing so can increase legal liability. There are extra steps that can be taken to reduce liability in case of a bad outcome. Communicating risks with patients and documenting this education will help verify that the patient was given appropriate information.
Project Leader in preparation of this Detail-Document: Melissa Blair, Pharm.D., FCCP, FASHP, BCPS, CDE - Assistant Editor
References
- Murphy S, Roberts R. Black box 101: how the food and drug administration evaluated, communicates, and manages drug benefit/risk. J Allergy Clin Immunol 2006;117:34-9.
- Products with "black box" warnings. Pharmacist's Letter/Prescriber's Letter 2006;22(3):220332.
- Aaronson DW. The black box warning and allergy drugs. J Allergy Clin Immunol 2006;117:40-4.
- Lasser KE, Seger DL, Yu T, et al. Adherence to black box warnings for prescription medications in outpatients. Arch Intern Med 2006;166:338-44.
- Chen Y, Avery AJ, Neil KE, et al. Incidence and possible causes of prescribing potentially hazardous/contraindicated drug combinations in general practice. Drug Saf 2005;28:67-80.
- Vivian JC. Precedent: the failure to warn. US Pharmacist 2005;7:52-6.
- Anon. Pharmacist's Mutual Claims Study 2007. http://www.phmic.com/web.nsf/pages/DrugReview.html (Accessed September 12, 2007).
- Office of the General Counsel. Informed consent. American Medical Association. http://www.ama-assn.org/ama/pub/category/print/4608.html. (Accessed September 11, 2007).
Cite this Detail-Document as follows: Dispensing / prescribing against labeled warnings. Pharmacist's Letter/Prescriber's Letter 2007;23(10):231001.
October 2007