People who have allergies to plants in Agavaceae family should be cautious in using agave. Contact dermatitis after exposure to the sap of Agave americana has been reported in rare cases.

The stiff, erect leaves of some agave plants are tipped with sharp needles, which can cause injury upon contact. Multiple reports of skin rash from Agave americana exist.

Vascular damage from crystals in agave has been reported. There are reports of irritant contact dermatitis from Agave americana when used incorrectly as a hair-restorer.

Pulque consumption may be associated with liver disease (cirrhosis) and increased death rate.

Some constituents of Agave sisalana, have high hemolytic activity, and may be potentially toxic.

Calcium oxalate crystals, found in prickly pear and agave, may have caused microwear of human teeth.

Significant increases in homocysteine levels and a tendency to increase blood glucose concentration and to decrease insulin sensitivity were found in healthy, non-obese young men who consumed tequila daily.

Women from rural areas of the central plateau of Mexico drink a mild alcoholic beverage called pulque as to stimulate breast milk flow (as a galactogogue). The relatively small amount of ethanol taken in by infants through milk is unlikely to have harmful effects. However, pulque intake during breastfeeding may have adverse influences on postnatal growth in some Mexican populations.

Anordin and dinordin, prepared with steroids derived from the sisal plants Agave sisilana and Agave americana have been used for their antifertility effects. These agents, whose anti-fertility properties have been confirmed by scientists in Sweden and the United States, constitute a potential new family of contraceptives promising the advantage of having to be taken only once or twice a month instead of the 20 times per month necessary with the ordinary pill.

There is no proven safe or effective dose for agave in adults.

There is no proven safe or effective dose for agave in children.

Steroid hormone precursors are obtained from agave leaves. Caution is advised when taking agave with other steroidal agents.

Contraceptive and anti-fertility effects have been reported with the use of agave. In theory, caution is advised when taking agave with other contraceptive agents, such as birth control pills.

Agave may alter blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.

Steroid hormone precursors are obtained from agave leaves. Caution is advised when taking agave with other herbs with steroidal properties.

Agave may alter blood sugar levels. Caution is advised when using medications that may also alter blood sugar. Patients taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.