What are the safety concerns with teriflunomide (Aubagio) in a patient with multiple sclerosis (MS) who smokes?

Veozah Safety in Smokers with Multiple Sclerosis

I believe there is a misunderstanding in your question—Veozah (fezolinetant) is a medication for vasomotor symptoms of menopause, not a treatment for multiple sclerosis. The expanded question references teriflunomide (Aubagio), which is an MS disease-modifying therapy. I will address the safety of teriflunomide in MS patients who smoke.

Critical Safety Concerns with Teriflunomide in Smokers with MS

Smoking significantly increases cardiovascular and stroke risk in MS patients, and while teriflunomide itself does not have specific contraindications for smokers, the combination creates a compounded vascular risk profile that requires aggressive smoking cessation intervention. 1

Cardiovascular Risk Amplification

• Smoking doubles the risk of ischemic stroke in all populations, and MS patients already face elevated vascular risks 1
• Teriflunomide can increase blood pressure (mean systolic BP increase of +2.7 mmHg with 14 mg dose), and hypertension occurred in 4.3% of patients on the 14 mg dose versus 1.8% on placebo 2
• The combination of smoking-induced endothelial dysfunction and teriflunomide-associated blood pressure elevation creates synergistic cardiovascular risk 1

Mandatory Smoking Cessation Protocol

All MS patients who smoke must receive intensive smoking cessation counseling at every healthcare visit, with pharmacotherapy strongly recommended 1:

• First-line cessation pharmacotherapy options include:

  • Combination nicotine replacement therapy (21 mg patch + short-acting NRT for cravings) 1
  • Varenicline (0.5 mg daily days 1-3, then 0.5 mg twice daily days 4-7, then 1 mg twice daily weeks 2-12) 1
  • Bupropion ± NRT (150 mg daily days 1-3, then 150 mg twice daily thereafter) 1

• Varenicline is contraindicated in patients with brain metastases due to seizure risk, but this is not a concern in MS patients without metastatic disease 1

• Bupropion is contraindicated in patients with seizure risks, including those with stroke or brain metastases 1

Teriflunomide-Specific Safety Monitoring in Smokers

Enhanced monitoring is essential given the additive risks:

• Blood pressure must be checked before starting teriflunomide and periodically throughout treatment, with aggressive management of any elevation 2
• Liver function monitoring (ALT/AST) is required at baseline and monthly for the first 6 months, as hepatotoxicity risk may be compounded by smoking-related metabolic effects 2
• Complete blood count monitoring should occur at baseline and every 2-4 months to detect cytopenias, as smoking can affect hematologic parameters 3

Respiratory Considerations

• Teriflunomide carries a risk of interstitial lung disease, which may present acutely with cough, dyspnea, or fever 2
• Smoking-related chronic lung disease may complicate the detection and management of teriflunomide-associated respiratory adverse events 2
• Baseline pulmonary function testing should be considered in smokers before initiating teriflunomide, with additional respiratory work-up if results are abnormal 1

Clinical Decision Algorithm

For MS patients who smoke and require disease-modifying therapy:

1. Initiate intensive smoking cessation intervention immediately with behavioral counseling plus pharmacotherapy 1
2. Assess baseline cardiovascular risk factors including blood pressure, lipid panel, and diabetes screening 1
3. If teriflunomide is selected as the DMT:
   • Ensure blood pressure is controlled (<140/90 mmHg) before initiation 1
   • Complete baseline laboratory monitoring (CBC, CMP, LFTs, hepatitis B/TB screening) 3, 2
   • Consider baseline pulmonary function testing in active smokers 1
4. Implement enhanced monitoring schedule:
   • Monthly LFTs for first 6 months, then periodically 2
   • Blood pressure checks at every visit 2
   • CBC every 2-4 months 3

Common Pitfalls to Avoid

• Do not delay smoking cessation counseling until after MS treatment is established—address both simultaneously 1
• Do not assume teriflunomide-associated blood pressure elevation is clinically insignificant in smokers, as the combined effect substantially increases stroke risk 1, 2
• Do not overlook the need for accelerated elimination procedures if serious adverse events occur, as teriflunomide can remain in the system for up to 2 years without intervention 2
• Avoid environmental tobacco smoke exposure, which also increases cardiovascular disease risk 1

Alternative Considerations

If cardiovascular risk is prohibitively high or smoking cessation fails, consider alternative MS therapies with different risk profiles, though all MS patients who smoke require cessation intervention regardless of DMT choice 1