The Kefauver-Harris amendment to the Federal Food, Drug, and Cosmetic Act requires that drug labeling take into consideration special problems such as those that may lead to death or serious injury and a warning be placed in a "prominently displayed box". This box has come to be known as a black-box warning because it is generally enclosed in a black border at the top of the package insert. This type of warning addresses the avoidance of the drug in certain high-risk patients or patient populations, dosing and/or drug interaction issues, the use of the drug in a particular clinical setting, or the need for special training prior to prescribing or administering the drug. It is the most serious warning associated with a particular drug.
Approximately 450 different drugs or drug entities carry black-box warnings. Most black-box warnings are informational only and address the avoidance or careful use of particular drugs in certain clinical situations (i.e. pregnancy) or in certain patient populations (i.e. patients with renal, cardiovascular, gastrointestinal, neurological, hepatic, bone marrow, or addictive disorders). However, a subset of drugs with black-box warnings also include well-defined "prerequisites" before they can be ordered, dispensed, and administered.
For example, the black-box warning associated with droperidol states that "the drug should be reserved for use in the treatment of patients who fail to show an acceptable response to other adequate treatments...and that patients about to receive droperidol should first undergo a 12-lead electrocardiogram... and those patients with prolonged Q-T intervals should not receive the drug...". The black-box warning for transdermal fentanyl, among other things, states that the drug shall only be used for persistent moderate to severe chronic pain in opioid-tolerant patients. In California, three institutions received immediate jeopardy (IJ) citations for promoting the use of droperidol as a first-line treatment of post-operative nausea and vomiting without requiring a 12-lead ECG prior to use. Similarly, three institutions in California received IJ citations for dispensing and administering transdermal fentanyl patches to patients for whom the drug was contraindicated based on its black-box warning. Other drugs with black-box "prerequisites" being used in the inpatient setting have thus far escaped scrutiny by regulators, although that too may be changing as drug utilization in the inpatient setting is being watched more closely by the Department of Public Health (DPH).
Because these "prerequisites" may be construed as imposing a "duty" on the part of the prescriber or institution, any breach of that duty leading to harm is, by definition, negligence, and exposes both parties to liability for negative outcomes. An interesting question is, does this duty extend to the pharmacy who dispenses the drug? We know that from a legal standpoint, inpatient pharmacies are expected to control and distribute drugs and biologicals "...in accordance with applicable standards of practice, consistent with Federal and State law...". This may include, but not be limited to, guidelines, protocols, policies, procedures, and systems which must be followed before the pharmacy can dispense the drugs. We also know that accreditation organizations such as JCAHO incorporate State and Federal laws into their accreditation standards and in general, their accreditation standards are nearly always stricter than the interpretive criteria used by the regulatory agencies. Therefore, since the inpatient pharmacy has to be involved at some point when black-box warning drugs are utilized, a reasonable person would conclude that these prerequisites, and thus a "duty", extend to them as well.
A more interesting question is, does this duty also extend to outpatient pharmacies? The answer so far is no, but that could change at any time. California pharmacy law does require both community pharmacies and pharmacies that provide services to long-term care (LTC) facilities "...to review a patient's drug therapy and medication record before each prescription drug is delivered...the review shall include screening for severe potential drug therapy problems...". Does this mean that a community or LTC pharmacy must, when presented with a prescription for a drug like transdermal fentanyl, question the patient or the patient's agent as to whether or not the patient is opioid-naive? So far, there is no case law regarding this matter and to date, no regulatory attacks have been made against community or LTC pharmacies who dispense black-box drugs contrary to prerequisites or contraindications. Will this change in the future? Attorneys are always on the lookout for new "duties" for healthcare professionals so my advice is, stay tuned.
For example, the black-box warning associated with droperidol states that "the drug should be reserved for use in the treatment of patients who fail to show an acceptable response to other adequate treatments...and that patients about to receive droperidol should first undergo a 12-lead electrocardiogram... and those patients with prolonged Q-T intervals should not receive the drug...". The black-box warning for transdermal fentanyl, among other things, states that the drug shall only be used for persistent moderate to severe chronic pain in opioid-tolerant patients. In California, three institutions received immediate jeopardy (IJ) citations for promoting the use of droperidol as a first-line treatment of post-operative nausea and vomiting without requiring a 12-lead ECG prior to use. Similarly, three institutions in California received IJ citations for dispensing and administering transdermal fentanyl patches to patients for whom the drug was contraindicated based on its black-box warning. Other drugs with black-box "prerequisites" being used in the inpatient setting have thus far escaped scrutiny by regulators, although that too may be changing as drug utilization in the inpatient setting is being watched more closely by the Department of Public Health (DPH).
Because these "prerequisites" may be construed as imposing a "duty" on the part of the prescriber or institution, any breach of that duty leading to harm is, by definition, negligence, and exposes both parties to liability for negative outcomes. An interesting question is, does this duty extend to the pharmacy who dispenses the drug? We know that from a legal standpoint, inpatient pharmacies are expected to control and distribute drugs and biologicals "...in accordance with applicable standards of practice, consistent with Federal and State law...". This may include, but not be limited to, guidelines, protocols, policies, procedures, and systems which must be followed before the pharmacy can dispense the drugs. We also know that accreditation organizations such as JCAHO incorporate State and Federal laws into their accreditation standards and in general, their accreditation standards are nearly always stricter than the interpretive criteria used by the regulatory agencies. Therefore, since the inpatient pharmacy has to be involved at some point when black-box warning drugs are utilized, a reasonable person would conclude that these prerequisites, and thus a "duty", extend to them as well.
A more interesting question is, does this duty also extend to outpatient pharmacies? The answer so far is no, but that could change at any time. California pharmacy law does require both community pharmacies and pharmacies that provide services to long-term care (LTC) facilities "...to review a patient's drug therapy and medication record before each prescription drug is delivered...the review shall include screening for severe potential drug therapy problems...". Does this mean that a community or LTC pharmacy must, when presented with a prescription for a drug like transdermal fentanyl, question the patient or the patient's agent as to whether or not the patient is opioid-naive? So far, there is no case law regarding this matter and to date, no regulatory attacks have been made against community or LTC pharmacies who dispense black-box drugs contrary to prerequisites or contraindications. Will this change in the future? Attorneys are always on the lookout for new "duties" for healthcare professionals so my advice is, stay tuned.
