People with allergies to ferns (family Polypodiaceae) should avoid polypodium.

Isolated reports of itching or stomach upset are published. Studies of a different fern species, Polypodium vulgare, report sedation, changes in heart function in animals, low blood pressure, and rapid heart rate. Avoid driving and use of heavy machinery when taking Polypodium leucotomos extract due to theoretical sedative effects. People with heart disease or those being treated for heart disorders or high blood pressure should use caution.

The use of polypodium during pregnancy or breastfeeding is not recommended, because there is little information about its safety.

For psoriasis, a dose of 120 milligrams of anapsos (Polypodium leucotomos extract), taken daily by mouth, has been used for short periods of time in limited research. For UV radiation 7.5 milligrams per kilogram has been studied. For dementia, preliminary research reports using 360 milligrams daily for four weeks. Safety and effectiveness are not clear.

No clear topical (on the skin) dosing regimen has been reported or established.

Little information is available about the use of polypodium in children, and safety is not clear.

Polypodium may increase the amount of drowsiness caused by some drugs. Examples include benzodiazepines such as lorazepam (Ativan®) or diazepam (Valium®), barbiturates such as phenobarbital, narcotics such as codeine, some antidepressants, and alcohol. Caution is advised while driving or operating machinery.

Most testing has been done with a related fern species, Polypodium vulgare. Animal studies show that this related plant can affect the function of the heart and lower blood pressure. In theory, the use of Polypodium leucotomos extract with medications that affect heart function or lower blood pressure may cause the effects of these drugs to increase. Use caution if combining polypodium with heart medications such as beta-blockers, calcium channel blockers, or digoxin.

In theory, polypodium may increase the amount of drowsiness caused by some herbs or supplements.

In studies of a related fern species, Polypodium vulgare, animals treated with the herb developed low blood pressure and changes in heart function. In theory, the use of Polypodium leucotomos extract with herbs or supplements that lower blood pressure may cause the blood pressure to fall too low.

For the same reason, be cautious if using Polypodium leucotomos extract with herbs or supplements that have possible cardiac glycoside ingredients, which can affect the function of the heart. Notably, bufalin/chan suis is a Chinese herbal formula that has been reported as toxic or fatal when taken with cardiac glycosides.