For many OTC drugs, listed dose covers most people
DEAR DR. ROACH: In the majority of over-the-counter medication, the dosing references "adults 12 years and older" and then gives a maximum dose. I'm 6 feet, 1 inch tall and weigh 220 pounds. The average 12-year-old is 125-ish pounds. I don't get it. Are we overdosing the 12-year-olds or limiting effectiveness for the older (or much heavier) folks?
Please consider my question, and answer in a thoughtful way considering the blood concentration level of a 12-year-old taking two aspirin vs. me taking the same two aspirin, and why that's OK. Should I be taking a weight-correlated dose of three to four aspirins? -- M.T.
ANSWER: The answer will depend on the specific drug ingested, but the primary answer is the same overall for most over-the-counter drugs: These drugs are generally so safe that a 12-year-old won't get close to overdose, even at a dose that is effective for most large adults.
For aspirin in particular, the toxicity is related to the blood levels, and blood levels are directly related to size. Weight is not the only factor affecting toxicity. Age, sex, kidney and liver function, diet and some lifestyle habits all may play a role. You are about 75% larger than the hypothetical 12-year-old (some of whom are larger than you), so your expected level of aspirin in the blood will be correspondingly lower. The 125-pound person might get all the benefit they need with one 325 mg aspirin tablet, while you will need two. Mild toxicity usually occurs when people take three to five times the recommended dose of aspirin.
When a drug has a large range between the minimum effective dose and a toxic dose, it is generally safe and may be appropriate for over-the-counter use. Pharmacologists call this the toxic-therapeutic ratio or the therapeutic index. Aspirin has a therapeutic index of 4, meaning that you have to take four times the effective dose for it to be toxic. This makes aspirin (relatively) less safe for an over-the-counter drug, compared with newer antihistamines, for example, which have a therapeutic index around 35.
Emergency room visits and hospital admissions are still common for accidental ingestion of aspirin. I want to re-emphasize that every person is different, and one 125-pound person may have toxicity at a dose another 125-pound person will not. (Puberty, incidentally, causes dramatic changes in metabolism of some drugs. My colleagues in pediatrics essentially always dose drugs by body weight.)
Drugs with narrow therapeutic indices need to be carefully monitored. A doctor must monitor the drug effect and toxicity, and adjust dosing as appropriate. These are not appropriate for over-the-counter use, and are often monitored by drug levels. One example of this is warfarin (Coumadin), an anticoagulant. Chemotherapy, which have some of the narrowest therapeutic indices of all drugs, are dosed based on careful measurement of weight and height, and kidney and liver function, and still requires exceptionally close monitoring. Personalized dosing of a few drugs is possible now by estimating enzyme activity through genetic analysis.