Some pharmacists and most patients don’t immediately recognize that some prescriptions medications are hazardous materials. That is not the same thing as dangerous (necessarily), because prescription medications are safe as long as they are used in the manner that they are prescribed. The hazardous label comes not from the Food and Drug Administration (FDA), but the Environmental Protection Agency (EPA).
From time to time the news media will cover a story about ground water (streams etc) having measurable concentrations of antibiotics or steroids. These amounts generally are very, very small, but the implications to the population in general and the environment are real.
Proper disposal of unused medications, therefore, is important. Many pharmacies (in Iowa for example) participate in a Take-Away program for non-controlled drug disposal. This program helps divert unused medications from the landfill and possible infiltration into our ground water supply by incinerating the medications at an EPA registered waste facility to render them harmless.
Of course, some medications are more worrisome than others. Very few medications make the EPA’s list of acutely toxic substances. One common exception, however, is warfarin (the generic of Coumadin, a blood thinning agent). Warfarin is also used in commercial rodent poisons, and even a small amount can impact the blood clotting physiology of humans and other animals.
The Resource Conservation and Recovery Act (RCRA) is the regulation that defines hazardous waste in the United States. Warfarin appears on both the P and U lists of hazardous waste (depending on the concentration of warfarin in the product). And while the tablets of warfarin (once dispensed to the patient) are exempt from any special disposal requirements (as they have been used for their intended purpose), the residual (the dust that may remain in the container after all tablets are gone) has not been used for its intended purpose, and is therefore subject to the RCRA and its requirements.
This interpretation of 54 FR 31335-31336 (July 28, 1998) by the EPA means that pharmacies must comply with the requirements of the RCRA (see 40 CFR 261.2) when disposing of the empty warfarin bottles. This is where things get a bit more complicated. If a pharmacy generates enough waste (greater than 1 kg / month), it is subject to a host of extra rules. Fortunately, it is the weight of the residual powder (measurable in milligrams), not the weight of the bottles, that is considered. This makes all but the largest pharmacies most likely categorized as conditionally exempt generators.
But being a conditionally exempt generator doesn’t mean these bottles can simply be thrown away. These bottles must still be disposed of in a manner consistent with RCRA guidelines. In order to discard the bottles into the traditional waste stream (for example, a landfill), the bottles must be RCRA empty (as defined by 40 CFR 261.3), requiring a triple rinse with a solvent documented to remove the hazardous materials. From a practical angle, this is not feasible, as the rinse material would then be a P-listed waste, and the simple act of rinsing would actually increase the amount of waste on hand.
There have been a couple of EPA guidances on this topic published in the past few years that are worth reading:
- October 2011 Letter (Boston Field Office)
- November 2011 Letter (Washington DC Office)
Concentration is the Key
The most important aspect of this problem is the dual nature of warfarin as it is classified by the RCRA. At concentrations of above 0.3%, warfarin is listed as acutely toxic and on the P-List. At lower concentrations, the same product becomes U-Listed. The “intended use” interpretation for the residue only appears to apply to P-Listed substances, and at lower concentrations, less stringent disposal rules would apply.
The second (November) guidance above does address some anecdotal evidence that the amount of warfarin residue might potentially be U-Listed. Limited testing referenced in the letter showed residue of warfarin in a single dose package was about 36 micrograms. This is in line with our estimates done with an analytical balance. The residual powder in a bottle of 1000 tablets averaged about 13 mg (equivalent to 650 micrograms warfarin).
The reporting of concentration as a percent, however, leads to difficulty in interpretation. For example, If an empty bottle of 1000 warfarin 10 mg tablets contains 13 mg of residue equivalent to 0.650 mg warfarin, the concentration of warfarin (reported as a percent of the initial warfarin contained in the bottle) is 0.0026%. In other words, the bottle is 99.9974% empty. But the concentration of the residual powder would be still 5% w/w warfarin, identical to the tablets themselves.
This relative nature of percent has created some confusion. Consider the State of Florida’s own guidance, which uses the first calculation example above to calculate warfarin in the empty bottle as under 0.3% (of the initial warfarin concentration). The guidance states that the FDEP has determined that the containers are therefore identified as U-Listed. The November guidance from the FDA, however, clearly specifies the second calculation (the warfarin concentration (w/w%) of the powder residual itself). This guidance essentially relegates every strength of warfarin tablet (and the residual dust they generate) as P-Listed.
What is also not clear is if RSRA rules allow the dilution of the P-listed agent to attain U-listed status. If an “empty” warfarin bottle contains 15 mg of residue (containing 0.7 mg warfarin), adding an additional 200 mg of lactose ( or other pharmaceutical powder diluent) and mixing until homogenous would render the %w/w concentration of warfarin less than the 0.3%, making the bottle subject to U-listing procedures. For reference, 200 mg of lactose a small pile size of a dime. Without official guidance from the EPA, using a strategy like this would incur significant risk.
Best Practice
The rules created by the RCRA cover the industrial generation of waste. Procedures referenced within the rules talk about a variety of instances, but examples often illustrate a much larger scale of waste than a pharmacy would generate. For example, discussions referencing containers like railroad tanker cars, a scale that only a pharmaceutical manufacturer might approach. Empty bottles that formerly contained pharmaceuticals really should be subject to more specific and appropriate rules. The EPA guidance from October 2011 noted that they were currently evaluating certain aspects of the management of hazardous pharmaceutical wastes in healthcare settings, but no new guidances are available since 2011.
In the end, because each bottle contains (less than one milligram of) warfarin, pharmacies should continue segregate and send away empty warfarin bottles for incineration at an EPA licensed facility. Companies like Sharps Compliance Inc and others can help a pharmacy manage these wastes. One possible way to kill two birds with one stone is to use a program like Sharps Compliance’s Take-Away containers. These container can be used to dispose of unused, non-scheduled, patient medications, including warfarin tablets. Patient medications could be aggregated into an empty warfarin bottle, and when the bottle is full, the entire bottle (with patient medications AND the P-listed warfarin residue) can be placed in the Take-Away box for incineration according the EPA guidelines.
