James,
I worked for 20 years as an analytical chemist and was responsible for running experiments to determine the expiration dates of our medicines. We were always conservative when setting limits.
There are many factors that affect the stability of medications. The most easily controlled by the end user is temperature. As a general rule for biological compounds near human temperatures the rate of decomposition approximately doubles with each 18° F rise in temperature and is roughly halved with each 18° F fall in temperature. So if the shelf life of a medicine is six months at 90° F and about three months at 110° F. That same medicine is expected to decompose about the same amount during four years in a refrigerator as it would in one year at room temperature or 16 years in a freezer.
Once a package has been opened oxygen, water, or microorganisms may enter the medicine and dramatically shorten it’s shelf life. In general