Letrozole (brand name Femara) is primarily used to treat hormone receptor-positive breast cancer in postmenopausal women and as an aid in fertility treatments. It is a non-steroidal aromatase inhibitor that blocks the aromatase enzyme, which converts androgens into estrogens. This action severely lowers the body’s estrogen levels, depriving estrogen-dependent cancer cells of the necessary growth stimulus. Due to this potent mechanism, certain substances, foods, and physical states must be avoided to maintain the drug’s effectiveness and prevent adverse health consequences.
Medications and Supplements to Halt
The most significant contraindication is the concurrent use of any medication containing estrogen, which directly counteracts Letrozole’s therapeutic goal. Hormone replacement therapy (HRT) or estrogen-containing birth control pills must be stopped. Introducing external estrogen negates the drug’s action of suppressing estrogen production, preventing the necessary estrogen deprivation that slows cancer cell growth.
Another substance requiring careful management is Tamoxifen, a selective estrogen receptor modulator (SERM). Combining Letrozole and Tamoxifen is generally avoided because studies show Tamoxifen can reduce the plasma concentration of Letrozole by 35% to 40%. This reduction potentially compromises the efficacy of the aromatase inhibitor, though sequential therapy is sometimes used.
Letrozole is extensively metabolized in the liver, primarily by cytochrome P450 (CYP) enzymes, particularly CYP3A4. Substances that either inhibit or induce these enzymes can dangerously alter the concentration of Letrozole in the bloodstream. Potent CYP3A4 inhibitors like ketoconazole could significantly increase Letrozole levels, raising the risk of side effects.
Conversely, CYP enzyme inducers, such as the herbal supplement St. John’s Wort, accelerate the metabolism of Letrozole. This leads to reduced drug levels and decreased therapeutic effectiveness. Patients should avoid or discuss the use of any supplements known to influence liver enzyme function with their healthcare provider.
Dietary Restrictions and Lifestyle Adjustments
A specific dietary item to avoid is grapefruit and its juice, as it contains compounds that interfere with drug metabolism. Grapefruit inhibits the CYP3A4 enzyme in the intestinal wall. This inhibition can potentially increase the drug’s concentration in the blood, increasing the risk of side effects.
Alcohol consumption should be minimized or avoided entirely while taking Letrozole because the drug is processed by the liver. Excessive alcohol intake places an additional strain on the liver, which is responsible for clearing the medication. Since Letrozole can cause side effects like fatigue and dizziness, alcohol can worsen these effects, impairing coordination and judgment.
Due to the possibility of side effects like dizziness, fatigue, and somnolence, patients should avoid activities that require high levels of mental alertness until they understand how the drug affects them. Operating heavy machinery or driving a vehicle should be approached with caution, especially during the initial phase of treatment. These neurological side effects necessitate a temporary lifestyle adjustment.
Absolute Contraindications and Immediate Concerns
The most absolute contraindication for Letrozole is pregnancy, as the drug is highly teratogenic and can cause serious birth defects. Letrozole’s mechanism of action—severely suppressing estrogen—is incompatible with a healthy pregnancy. Women of reproductive potential must use effective, non-hormonal contraception consistently throughout the treatment period and for a specified time after the last dose, typically three weeks.
Pre-existing severe organ impairment necessitates avoidance or a substantial dosage reduction. Letrozole is cleared through the liver, and patients with severe hepatic impairment may experience significantly increased drug exposure. This requires the dosage to be cut in half. Similarly, severe renal impairment warrants careful monitoring.
A serious long-term concern is the accelerated loss of bone mineral density (BMD) due to the profound suppression of estrogen, a hormone that helps maintain bone strength. Letrozole therapy increases the risk of developing osteoporosis and bone fractures. Routine dual-energy X-ray absorptiometry (DEXA) scans are often mandated to assess bone health at baseline and throughout treatment so that preventative treatments, such as bisphosphonates, can be initiated if bone density declines too sharply.