Whether you are a leader of an organization, your patient’s regular prescriber, or you cover for your partners on vacation; an understanding the risks related to exceeding FDA dosing recommendations can help you manage that risk. In malpractice claims, and clinical environments, I often see FDA guidance ignored, with no explanation. We should consider the implications of this, and create “standard work” to manage it.
This post is a one of many topics covered in my recent report “5 Lethal Mistakes Medical Directors Can Eliminate in Their Group” You can download that report by clicking on the link.
• Any prescription medication has an FDA “package insert” that outlines important safety information including starting dosage and in some cases a max dose. The indication for the use of the medication is also relevant here, along with potential interactions. Locating the most recent product label is important (in the case it has been updated), especially if you are obtaining it through means such as an internet search engine.
• Not all medications will indicate a “max dose”, but even where there isn’t, there is often a “maximum recommended starting dose”.
• When a provider with proper professional licensing credentials makes a decision to write a prescription, otherwise inconsistent with dosing guidance in the package insert, the FDA has no direct authority over the provider to prohibit this. The package insert is not a “law” per se.
• However, the limits set by the FDA are often defined for the purpose of patient safety. Therefore, if a provider wishes to ignore FDA guidance, it is reasonable and prudent to inform the patient of the intent to treat in a manner inconsistent with approved use, and the rationale for such action. (i.e. “off label use”).
• Perhaps more important, if a provider’s dosing exceeds the FDA guidance, this may expose the patient to a higher level of risk, compared with standard dosing.
• Again, a patient with decisional capacity should be informed of your intention to deviate from standard limits, be presented with a rationale for the risk (i.e. potential benefit). In addition, the patient or their surrogate should be informed of the potential complications that could occur, and provided an opportunity to ask questions. Alternatives to the higher risk plan should be considered and communicated.
• This model of introducing informed consent, when it occurs in the context of a conversation, is often referred to as “Shared Decision Making” and when documented satisfies many statutory and professional definitions of informed consent. (Consider the acronym “PRBAC” Procedure, Risk, Benefit, Alternatives, Capacity).
• Patients receiving medications prone to abuse (i.e. controlled substances) may have an isolated impairment in their capacity to weigh risks related to the therapy. The choice bias that is introduced by the knowledge of dependence and withdrawal in the short term; can eclipse long range goals and the rational decision making required for a beneficial care plan. A patient lacking in the capacity to weigh risks related to a therapy without substantial bias, lacks decisional capacity to engage in shared decision making, and therefore it may be unreasonable to deviate from FDA guidance in such a patient. Many therapies are dangerous even within the FDA dosing, and are reasonable to withhold in a patient unable to demonstrate a healthy respect for those risks. Defining medication risk behaviors (e.g. exceeding your dosing instructions) and monitoring for adherence, is a straightforward means of determining if a patient is a qualified candidate for ongoing therapy.
• To enhance oversight and risk surveillance, providers in your organization who engage in prescribing that otherwise exceeds product labeling could be asked to disclose these decisions to the medical director. As a casual request from the medical director, this would be arbitrary and of little use. However, if the providers as a group felt the patients would be safer (as a group), if all providers kept in the FDA dose range, then the providers that seek autonomy to exceed that range can disclose that as an exception, explicit in the chart, and to the patient.
Example: In January 2013, The FDA reduced the max dose of Zolpidim (Ambien) IR from 10mg to 5 mg, due to problematic behaviors and adverse events such as motor vehicle accidents. A medical director could choose make any of the following choices:
1. Do nothing, and expect all providers to “keep up to date”.
2. Send out a memo, inform the providers.
3. Mine the EMR, and selectively educate providers (will patients receive information?).
4. Mine the EMR, and educate providers AND patients.
5. Ask the providers not to exceed dosing without a review/approval process.
ANALYSIS: While answer #5 may appear to entail additional work, let’s examine 1-4.
Doing nothing (#1), likely does just that…nothing. It also misses an opportunity to create a standard infrastructure for responding to important changes in guidance from third parties.
The second (#2) is perhaps the simplest “reaction”. However, this style of leadership leads to “memo fatigue” because there are varying levels of importance and relevance of any information. If the Medical Director is simply the mouthpiece of the FDA, and every other regulatory agency, internal initiatives will suffer due to staff “plugging their ears”. It also doesn’t address the circumstance in which a provider, either intentionally or inadvertently continues dosing at the higher level. There are two circumstances where the provider does so intentionally: The first is with shared decision making/informed consent, and the second is simply a calculated risk without detailed explanation. Inadvertent dosing that exceeds FDA guidance can occur if the doctor “forgot” or was unaware of the max dose. In the case where the guidance comes down in the form of an email to all providers, there is little opportunity (e.g. six months later) to engage with data or providers on what was expected to occur, in response to the memo.
The third (#3) is reasonable, but probably should involve the provider, and it takes time.
The fourth action (#4) is still missing an expectation of how you would like your providers to respond to the shift in the FDA guidance, and therefore your capacity to definitively influence the outcome, or monitor it, is non-existent.
The fifth option (#5) is as easy as this: Any time the provider wishes to deviate from dosing guidance on Zolpidem (5 mg females), or Vyvance (70 mg/day) or other standard dosing guidance; a letter is generated to the patient, by the doctor, cc Medical Director:
“Dear Patient: You and I both feel you might benefit from exceeding the standard dose of __(med)___, which may increase risks for __(specify bad outcome)_____and this is otherwise reasonable because __(why?)_____. However this decision is provisional and may be further modified after discussion with you, your family, but also I need to consult a colleague. I’d also ask that you return a copy of this letter signed by a family member ____(spouse, etc.)________.
Then cc the Medical Director.
There are lots of different work styles among physicians, and lots of leadership styles as well. The big question here is what is the most reasonable and prudent way to approach medications with high risk, or to influence your organization in changing practice patterns in the face of new risk information, or prescribers whose dosing is inconsistent with the comfort level of their partners.