Corticosteroid Drug Interactions

Corticosteroids (also known as glucocorticoids) can produce serious adverse effects if taken chronically (e.g., for more than a week or two) and if taken with certain other drugs.

Corticosteroids have been successfully used for many years in the treatment of a wide variety of diseases such as inflammatory joint diseases, autoimmune disorders, inflammatory gastrointestinal diseases, asthma, acute gout, kidney diseases, as well as with cancer chemotherapy or after organ transplants.

Which corticosteroids are susceptible to toxic drug interactions?

Some corticosteroids, such as budesonide (RHINOCORT AQUA), dexamethasone (DECADRON, HEXADROL, MYMETHASONE), fluticasone (FLOVENT, FLOVENT DISKUS, FLOVENT ROTADISK, FLONASE) and methylprednisolone (MEDROL), are metabolized primarily by the enzyme CYP3A4. Corticosteroid toxicity can result when one of these corticosteroids is given with one of the many drugs that inhibit CYP3A4.

Other commonly used corticosteroids like prednisone (DELTASONE) and prednisolone (PRELONE) appear to be much less affected by CYP3A4 inhibitors, so if you are taking one of these corticosteroids you are probably at low risk of this type of interaction.

Which drugs increase the risk of corticosteroid toxicity?

For corticosteroids that undergo metabolism by CYP3A4, drugs that inhibit CYP3A4 are likely to increase corticosteroid blood levels and toxicity. Drugs that inhibit CYP3A4 are listed in Table 1.

What are the symptoms of corticosteroid toxicity?

Corticosteroid toxicity can increase blood sugar, which can cause or worsen diabetes, and increase blood pressure, which can cause or worsen hypertension. Many other organ systems also can be affected, resulting in bone fractures, muscle weakness, menstrual irregularities, cataracts, glaucoma, mood swings, poor wound healing and infections. Patients can develop Cushing’s syndrome — the symptoms of which include easy bruising, a swollen face, acne, increased facial hair and a “hump” on the patient’s back.

Do interactions occur only with oral or injected corticosteroids?

No, corticosteroid toxicity due to drug interactions has been reported with inhaled corticosteroids, nasal corticosteroids and even corticosteroids injected into the spinal fluid. Theoretically, it also could occur with extensive application of corticosteroids to the skin or rectum.

Can drug interactions reduce the effect of corticosteroids?

Unlike the interactions of corticosteroids with CYP3A4 inhibitors, (where only some corticosteroids appear to interact), drugs that reduce corticosteroid effect through “enzyme induction” probably interact with all corticosteroids. Unlike the interactions of corticosteriods with CYP3A4 inhibitors, (where only some corticosteroids appear to interact), drugs that reduce the effect of corticosteroids through “enzyme induction” probably interact with all corticosteroids. Enzyme induction causes the body to increase its production of the enzymes that metabolize drugs. With this type of interaction, the corticosteroid effect is reduced because the body eliminates the corticosteroid too rapidly. Enzyme inducers (drugs that should not be used with any corticosteroids) are listed in Table 2.

When a corticosteroid is being used for its “systemic” effects, such as for autoimmune diseases or cancer, or after organ transplants, its interactions with other drugs can have especially serious consequences. Nonetheless, when a corticosteroid is being used for “local” effects, (i.e., in the lung, nose or spinal fluid), enzyme inducers probably would not reduce the corticosteroid’s effectiveness.

What You Can Do

Corticosteroids are used for many different disorders, and it is important to carefully measure corticosteroid doses to avoid both toxicity and lack of efficacy. Other drugs may increase or decrease corticosteroid effects, and it is important to be alert for these drug interactions.

Consumers may report serious adverse events with corticosteroids or other drug-interaction problems to the FDA’s MedWatch Adverse Event Reporting program online or by regular mail, fax or phone.

Online: www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
Regular Mail: Use postage-paid FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
Fax: (800) FDA-0178
Phone: (800) FDA-1088

Table 1. Drugs That Can Cause Corticosteroid Toxicity

Table 2. Drugs That Can Reduce Corticosteroid Effect