Treating Hot Flashes Induced by Tamoxifen
Treating Hot Flashes Induced by Tamoxifen
Can venlafaxine be used to treat hot flashes that occur as a side effect of tamoxifen?
Tamoxifen is an anti-estrogen medication used for the treatment and prevention of breast cancer. Hot flashes (or 'hot flushes') are the most common adverse effect associated with tamoxifen use. This side effect often negatively affects a patient's quality of life, and it may result in nonadherence to the prescribed regimen.
Venlafaxine (Effexor, Wyeth-Ayerst Laboratories), a serotonin and norepinephrine reuptake inhibitor indicated for major depressive disorder, has been studied for treatment of hot flashes in women with a history of breast cancer. Loprinzi and colleagues performed a randomized, placebo-controlled, double-blind trial evaluating venlafaxine extended-release for treatment of hot flashes in breast cancer survivors and women concerned with breast cancer risk associated with hormone use. Most of these patients (69%) were taking tamoxifen.
The 4 groups studied were given either placebo daily (N = 50), venlafaxine 37.5 mg daily (N = 49), venlafaxine titrated to 75 mg daily (N = 43), or venlafaxine titrated to 150 mg daily (N = 49). After the 4-week study duration, median hot flash scores by patient report decreased 27%, 37%, 61%, and 61% for those groups, respectively; the 75-mg dose was found to be most effective. Adverse effects (ie, dry mouth, decreased appetite, nausea, constipation) were significantly greater in the 75-mg and 150-mg groups compared with placebo. Venlafaxine efficacy was similar for both tamoxifen users and non-users.
An open-label, longitudinal, 8-week continuation of the above trial was described by Barton and colleagues. Patients had the opportunity to start, continue, or titrate their previous venlafaxine dose up to 150 mg, to achieve a desirable efficacy level along with a tolerable toxicity level. Of the 102 patients who continued the study, 66% were taking tamoxifen. All groups reported a 60% to 68% mean decrease in hot flash scores from baseline. Other positive effects found in the venlafaxine groups included improved mood, less trouble sleeping, and less fatigue.
For treatment of hot flashes associated with tamoxifen, patients may be started on extended-release venlafaxine 37.5 mg daily. If adequate response is not achieved within 1 week, the dose may be titrated to 75 mg daily. Increasing the dose to 150 mg daily would likely increase side effects while not influencing efficacy.
The clinician should evaluate the potential for drug interactions when recommending an agent for tamoxifen-associated hot flashes. Importantly, tamoxifen activity may be reduced by certain medications (eg, selective serotonin reuptake inhibitors [SSRIs]), which are potent inhibitors of cytochrome P450 2D6. Venlafaxine is a weak inhibitor of 2D6 and only slightly reduces an active metabolite of tamoxifen, compared with other SSRIs.
While limited trial data suggest that venlafaxine may be an effective agent for hot flashes, more studies are needed to evaluate the role of venlafaxine for tamoxifen-associated hot flashes.
Question
Can venlafaxine be used to treat hot flashes that occur as a side effect of tamoxifen?
Response from the Expert
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Response from Joanna M. Pangilinan, PharmD Pharmacist, Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, Michigan |
Tamoxifen is an anti-estrogen medication used for the treatment and prevention of breast cancer. Hot flashes (or 'hot flushes') are the most common adverse effect associated with tamoxifen use. This side effect often negatively affects a patient's quality of life, and it may result in nonadherence to the prescribed regimen.
Venlafaxine (Effexor, Wyeth-Ayerst Laboratories), a serotonin and norepinephrine reuptake inhibitor indicated for major depressive disorder, has been studied for treatment of hot flashes in women with a history of breast cancer. Loprinzi and colleagues performed a randomized, placebo-controlled, double-blind trial evaluating venlafaxine extended-release for treatment of hot flashes in breast cancer survivors and women concerned with breast cancer risk associated with hormone use. Most of these patients (69%) were taking tamoxifen.
The 4 groups studied were given either placebo daily (N = 50), venlafaxine 37.5 mg daily (N = 49), venlafaxine titrated to 75 mg daily (N = 43), or venlafaxine titrated to 150 mg daily (N = 49). After the 4-week study duration, median hot flash scores by patient report decreased 27%, 37%, 61%, and 61% for those groups, respectively; the 75-mg dose was found to be most effective. Adverse effects (ie, dry mouth, decreased appetite, nausea, constipation) were significantly greater in the 75-mg and 150-mg groups compared with placebo. Venlafaxine efficacy was similar for both tamoxifen users and non-users.
An open-label, longitudinal, 8-week continuation of the above trial was described by Barton and colleagues. Patients had the opportunity to start, continue, or titrate their previous venlafaxine dose up to 150 mg, to achieve a desirable efficacy level along with a tolerable toxicity level. Of the 102 patients who continued the study, 66% were taking tamoxifen. All groups reported a 60% to 68% mean decrease in hot flash scores from baseline. Other positive effects found in the venlafaxine groups included improved mood, less trouble sleeping, and less fatigue.
For treatment of hot flashes associated with tamoxifen, patients may be started on extended-release venlafaxine 37.5 mg daily. If adequate response is not achieved within 1 week, the dose may be titrated to 75 mg daily. Increasing the dose to 150 mg daily would likely increase side effects while not influencing efficacy.
The clinician should evaluate the potential for drug interactions when recommending an agent for tamoxifen-associated hot flashes. Importantly, tamoxifen activity may be reduced by certain medications (eg, selective serotonin reuptake inhibitors [SSRIs]), which are potent inhibitors of cytochrome P450 2D6. Venlafaxine is a weak inhibitor of 2D6 and only slightly reduces an active metabolite of tamoxifen, compared with other SSRIs.
While limited trial data suggest that venlafaxine may be an effective agent for hot flashes, more studies are needed to evaluate the role of venlafaxine for tamoxifen-associated hot flashes.
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