In issuing the advisory, officials warned over-the-counter medications accounted for 12 percent of general aviation crashes in the past decade, ABC News reported.
An estimated 450,000 pilots of small and private aircraft were told in a letter to be aware of the "ubiquitous presence of sedating antihistamines" in medications for allergies, colds and sleep aids.
The letter advised pilots to wait as long as five times after the period the medications are effective before flying and to pay attention to any side effects.
For a medication that lasts eight hours, that could require the pilot to stay on the ground for 40 hours after taking the drug, said Bruce Landsberg, president of the Aircraft Owners and Pilots Association Foundation.
Commercial pilots are required to undergo blood tests annually to check for any medications, but general aviation pilots are not.
A brochure published by Federal Aviation Administration advised pilots not to fly if they depend on a medication to fly safely. It also said pilots taking medication for a chronic medical condition should consult their physician or pharmacist for possible side effects.