The safety and effectiveness of medicines and other health products is dependent upon their proper use, particularly the proper route of administration. There are reasons why products are labeled as “for topical use only” or “do not swallow” – two recent warnings from the US FDA illustrate these issues.
Allergic Reactions with Use/Misuse of Denture Cleansers
The FDA recently announced reports of one death and 72 other adverse reactions in individuals who ingested denture cleansers meant to be used in a container with one’s dentures removed. A crucial oxidizing agent, salts of persulfate, can cause allergic reactions in susceptible individuals when swallowed, when swished in the mouth or, more alarmingly, even when residual cleanser solution remains on the dentures when reinserted.
[All sorts of biologists will recognize persulfate (ammonium salt) as the oxidizing agent used to catalyze the crosslinking of acrylamide monomers to make gels for the resolution of proteins and nucleic acids – that is, if you don’t have the luxury of purchasing per-poured gels]
An allergic reaction to persulfates may not occur after the first use or even until after many years of use. Symptoms of an allergic reaction may not appear for several minutes or even hours after actual use. Symptoms may include irritation, tissue damage, rash, hives, gum tenderness, breathing problems, and low blood pressure.
As a result of these cases, FDA is recommending that denture cleanser manufacturers clarify product instructions and offer a consumer education campaign (FDA’s PDF here). Moreover, FDA is recommending that manufacturers begin to investigate the potential for replacing persulfate with other oxidizing/bleaching agents that do not cause these hypersensitivity reactions:
To reduce misuse of denture cleansers, FDA is also recommending that manufacturers improve the directions on the label. Labeling revisions are needed to make it clear that these products are meant to clean dentures in a container, not while still in the mouth. Some patients have gargled or swallowed denture cleansers, resulting in abdominal pain, vomiting, seizures, breathing problems, and low blood pressure. Dentures should be thoroughly rinsed with water before they are placed in the mouth.
Inhale, Do Not Swallow Spiriva or Foradil Capsules
This FDA public health advisory may come as a surprise to many who don’t use bronchial inhalers. Spiriva® brand of tiotropium bromide and Foradil® brand of formeterol fumarate are inhalation powders used to treat asthma and chronic obstructive pulmonary disease (COPD) as “maintenance” medications, as opposed to fast-acting inhaled drugs like albuterol that are used during acute asthma attacks.
Supplied as capsules, they are meant to be used in inhalation devices HandiHaler® (Spiriva) and Aerolizer® (Foradil) – each of these drugs and devices require that the patient insert a capsule into an inhaler device, then press a button or buttons that pierces the capsule and allows the micronized drug powder to be inhaled.
For pharmacology background: tiotropium is of the anticholinergic drug class, meaning that it has a potent inhibitory effect against acetylcholine nerve-induced contraction of airways; formeterol is a β2 adrenergic receptor antagonist, or blocker, meaning that it mimics the effect of your own norepinephrine- or epinephrine-induced dilation of airways but in a much more sustained manner.
Back to these inhalable capsules: I look at these instructions and dosage forms and I’m even a bit confused at first – the capsules come in a blister pack that most of us associate with popping open and then swallowing the capsule. It’s a pretty new idea to use a capsule-piercing inhaler because most asthmatics are accustomed to using an inhaled spray where the little aerosol canister is attached to the inhalation device.
I look at the older gentleman in the masthead of this instructional page with the little kid playing doctor and he seems to be saying, “You have got to be kidding me. Where the hell is my old medicine?” A doc I know (not a pulmonologist) took one look at the instructions and said that she doubted if more than 10% of her patients would be able to use the product correctly.
There seems to be little danger directly in swallowing either of these capsules since the drugs are designed to be active when inhaled into the lung then broken down quickly when in the bloodstream and metabolized by the liver (although some minor side effects have been reported). The real danger is that patients with live-threatening bronchial diseases can essentially go unmedicated if the product is used improperly.
I understand the purpose of these inhaled powders: the particles containing the drug are much smaller than even the finest mist that could be produced by a spray inhaler, allowing the medicine to penetrate much more deeply into the lungs to smaller and smaller bronchioles.
In fact, this method first came on the scene in the form of a patented dosage form called a Diskus®. This micronized particle inhaler is self-contained: the medicine is encased inside the device on what looks like a tape with individual blisters. Each time the Diskus is opened and clicked, the mechanism opens one blister and you simply inhale. Much easier to use than fumbling with capsules and putting them into a device that you then activate and to inhale the powder.
Of course, the simpler Diskus device is patented by a company different from the one that makes Spiriva or Foradil. I claim no inside information whatsoever but I suspect that no financial agreement could be reached that would allow these two drugs to be sold in the Diskus dosage form. As a result, we’ve got patients with life-threatening illnesses, many of older age, fumbling around with blister-pack capsules not understanding they are to be inserted into a poker-piercer-inhaler thingie and not just swallowed straightaway.
I use a drug that comes in a Diskus format and it’s very easy and very effective. However, the pharmacy benefits management (PBM) company used by my health insurer recently informed me that they were raising the co-payment on my Diskus to a “higher-tier” and encouraged me to have my doc prescribe two other inhaled medication forms that are still less expensive even when combined.
Ease-of-use and minimization of the number of drugs needed (by formulating two or more drugs together into one product) is well-known to increase patient compliance, the percentage of doses taken as directed. Increasing patient compliance is the single most-cost effective approach in pharmacy to result in the most optimal management of disease. A ridiculous and cumbersome dosage form is not consistent with improving patient compliance, nor is asking a patient to use two separate drugs when a reasonable combination agent exists and has been used successfully by the patient.
Yes, yes, I know that cost issues influence these decisions and choices. And, yes, pharmacists can play a crucial role in educating patients on how to use these new inhalers, when they have the time to step away from the sweatshop.
Shouldn’t it be easier?