Raloxifene (Evista) Interactions
- Ampicillin
- Black Cohosh, Cimicifuga racemosa
- Cholestyramine
- Desiccated Thyroid
- Levothyroxine
- Liotrix
- Soy Isoflavones
- Warfarin
Raloxifene (Evista) Interactions
With coadministration of ampicillin, peak raloxifene concentrations are reduced by 28% and absorption is reduced 14%. These effects are consistent with decreased-enterohepatic cycling associated with antibiotic reduction of enteric bacteria. However, these effects are not considered clinically important since the overall systemic exposure to raloxifene remains unaffected.
The systemic exposure of raloxifene is not affected by concurrent administration of calcium carbonate or aluminum and magnesium hydroxide-containing antacids.
Theoretically, the soy isoflavones may compete with drugs that selectively modulate estrogen receptors. Soy isoflavones should be used with caution in patients taking raloxifene.
Raloxifene may delay and reduce the oral absorption of levothyroxine (T4). In a case report, a patient with chronic but treated hypothyroidism was taking a stable dose of levothyroxine. The patient required increasing doses of levothyroxine when raloxifene was co-administered; the TSH level remained elevated and serum T4 remained decreased despite an increase in oral levothyroxine dosage. An absorption interaction was suspected and the patient rechallenged on two occasions; a decrease in serum T4 was observed whenever raloxifene and levothyroxine were administered concurrently. The patient’s levothyroxine dosage requirements returned to baseline and the TSH value normalized when levothyroxine and raloxifene were administered 12 hours apart rather than simultaneously. The mechanism for the observed interaction is unknown. In theory, raloxifene might cause malabsorption of any thyroid hormone containing T4 (e.g., desiccated thyroid, levothyroxine, liotrix) if administered at the same time. Patients prescribed raloxifene while taking these thyroid hormones should be advised to take the drugs at separate times (e.g., 12 hours apart) until more data are available.
A single dose of cholestyramine causes a 60% reduction in the absorption and enterohepatic cycling of raloxifene. The coadministration of cholestyramine and raloxifene is not recommended. Although not specifically studied, other anion exchange resins are expected to have a similar effect.
A 10% decrease in prothrombin time was observed in a single-dose study of raloxifene with warfarin. If raloxifene is given concurrently with warfarin or other coumarin derivatives, the INR should be carefully monitored when starting or stopping therapy with raloxifene. No clinically relevant effects of warfarin on plasma concentrations or therapeutic activity of raloxifene have been noted.
It is unknown if phytoestrogen compounds like black cohosh, Cimicifuga racemosa, potentiate or interfere with the therapeutic activity of selective-estrogen receptor modifier (SERM) therapies like tamoxifen, toremifene, or raloxifene. Since black cohosh may potentially suppress luteinizing hormone (LH) or have estrogen-receptor binding activity, interactions could theoretically occur. Clinically, black cohosh has been studied in combination with tamoxifen in breast cancer survivors; the data are not conclusive regarding clinical benefit in managing hot flashes in this population. The effects of black cohosh may be dependent on the underlying endogenous estrogen balance and age of the female patient (i.e., pre- versus post-menopausal), and the presence of other health conditions (e.g., pregnancy). Interactions remain primarily theoretical, as clinical documentation of harmful interactions is lacking. It is recommended that patients discuss the use of black cohosh with their practioner prior to combining therapy with SERMs.
[ Last revised: 7/27/2004 5:00:00 PM ]
References
. Wade C, Kronenberg F, Kelly A, et al. Hormone-modulating herbs: implications for women’s health. JAMWA 1999;54:181-3.
. Duker EM, Kopanski L, Jarry H, et al. Effects of extracts from Cimicifuga racemosa on gonadotropin release in menopausal women and ovariectomized rats. Planta Med 1991;57:420 - 4.
. Eagon PK, Tress NB, Ayer HA, et al. Medicinal botanicals with hormonal activity (abstract 1073). Proc Amer Assoc Cancer Res 1999:40.
. Lieberman S. A review of Cimicifuga racemosa (black cohosh) for the symptoms of menopause. Journal of Women’s Health 1998;7:525 - 9.
. Smolinske SC. Dietary supplement-drug interactions. JAMWA 1999;54:191 - 2.
. Siraj ES, Gupta MK, Reddy SK. Raloxifene causing malabsorption of levothyroxine. Arch Intern Med 2003;163:1367 - 70.
. Duffy C, Cyr M. Phytoestrogens: potential benefits and implications for breast cancer survivors. J Womens Health (Larchmt). 2003 Sep;12(7):617 - 31.
. Evista® (raloxifene) package insert. Indianapolis, IN: Eli Lilly and Company; 2003 Jun.
. Hernandez Munoz G, Pluchino S. Cimicifuga racemosa for the treatment of hot flushes in women surviving breast cancer. Maturitas 2003;44(Suppl 1):S59 - 65.
. Jacobson JS, Troxel AB, Evans J, et al. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol 2001;19:2739 - 45.
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