What medications can cause hot flashes?

Medications That Can Cause Hot Flashes

Primary Offender: Tamoxifen

Tamoxifen is the most clinically significant medication that causes hot flashes, occurring in 64-80% of treated women. 1

Tamoxifen-Induced Hot Flashes: Key Facts

• Hot flashes are the most frequent adverse reaction to tamoxifen in patients treated for metastatic breast cancer 1
• In adjuvant breast cancer trials, hot flashes occurred in 64% of tamoxifen-treated women versus 48% on placebo 1
• Severe hot flashes occurred in 45% of women on tamoxifen compared to 28% on placebo in the NSABP P-1 prevention trial 1
• Hot flashes were severe enough to cause 3.1% of women to withdraw from tamoxifen therapy (versus 1.5% on placebo) 1
• The incidence varies by study design: 19% in ECOG trials, 29% in Toronto studies, and up to 80% in NSABP trials 1

Comparison with Aromatase Inhibitors

• Anastrozole causes fewer hot flashes than tamoxifen: 36% with anastrozole versus 41% with tamoxifen in head-to-head adjuvant trials 1
• This represents one of the few advantages of aromatase inhibitors over tamoxifen regarding vasomotor symptoms 1

Other Endocrine Therapies

Ovarian Ablation

• Causes hot flashes in 46% of premenopausal women with metastatic breast cancer, compared to 33% with tamoxifen 1

Clinical Pitfalls and Management Considerations

The Tamoxifen-SSRI Interaction Paradox

When treating tamoxifen-induced hot flashes, avoid paroxetine and fluoxetine as they inhibit CYP2D6 and may reduce tamoxifen's conversion to its active metabolite endoxifen 2

Preferred alternatives for tamoxifen users include: 2, 3

• Venlafaxine (75 mg daily): 61% reduction in hot flash severity
• Gabapentin (900 mg daily): 46% reduction in hot flash severity
• Sertraline (50 mg daily): weak CYP2D6 effects, superior to placebo
• Citalopram or escitalopram: minimal CYP2D6 inhibition

First-Line Treatment Algorithm for Medication-Induced Hot Flashes

For women NOT on tamoxifen: 4

1. Fezolinetant (if available) - most targeted mechanism, no withdrawal syndrome
2. Venlafaxine 75 mg or paroxetine 12.5-25 mg daily
3. Gabapentin 900 mg daily (especially if nighttime symptoms predominate)

For women ON tamoxifen: 2, 3

1. Fezolinetant (no CYP2D6 interaction)
2. Venlafaxine 75 mg daily (minimal CYP2D6 effects)
3. Sertraline 50 mg daily or escitalopram 10-20 mg daily
4. Gabapentin 900 mg daily

Important Caveats

• SSRIs/SNRIs require gradual tapering to prevent discontinuation syndrome, particularly with venlafaxine, paroxetine, and desvenlafaxine 2
• 10-20% of patients discontinue SSRIs/SNRIs due to adverse effects (nausea, dry mouth, constipation, sexual dysfunction) 2, 5
• Individual response is highly variable: some women experience vigorous improvement while others worsen on the same SSRI 6
• Clonidine reduces hot flashes by up to 46% but has a 40% discontinuation rate due to dry mouth and drowsiness 2
• Response typically occurs within days to 1 week, allowing rapid assessment of efficacy 2