Is it safe to take Luvox (fluvoxamine) and Xanax (alprazolam) together?

Fluvoxamine and Alprazolam Combination: Safety Concerns and Management

The combination of fluvoxamine (Luvox) and alprazolam (Xanax) should be avoided when possible due to significant drug interactions that can lead to excessive sedation, impaired psychomotor performance, and potentially dangerous central nervous system depression. 1

Pharmacokinetic Interaction

• When fluvoxamine and alprazolam are co-administered, plasma concentrations and other pharmacokinetic parameters of alprazolam approximately double, with oral clearance reduced by about 50%, resulting in decreased psychomotor performance and memory 1
• Fluvoxamine inhibits hepatic oxidation through which alprazolam is metabolized, significantly reducing its clearance 1
• This interaction may be even more pronounced at higher fluvoxamine doses (300mg daily), as fluvoxamine exhibits non-linear pharmacokinetics over the dosage range of 100-300mg 1

Clinical Risks

• The FDA has issued a black box warning about combining opioid medications with benzodiazepines due to risks of slowed breathing and death, highlighting the dangers of combining CNS depressants 2
• The combination increases risk for:
  • Excessive sedation and impaired cognition 1
  • Decreased psychomotor performance 1
  • Increased risk of falls 3
  • Potentially dangerous respiratory depression 2

Management Recommendations

If the combination cannot be avoided:

• The initial alprazolam dosage should be at least halved and titrated to the lowest effective dose 1
• No dosage adjustment is required for fluvoxamine 1
• Monitor closely for signs of excessive sedation, confusion, or coordination problems 3
• Consider alternative anxiety treatments with less interaction potential 3
• Be aware that both medications have potential for tolerance and dependence, requiring regular reassessment 3

Alternative Approaches

• Consider non-pharmacological approaches for anxiety such as cognitive behavioral therapy 3
• For anxiety, non-benzodiazepine options might be safer to combine with fluvoxamine if necessary 3
• Benzodiazepines metabolized by glucuronidation (e.g., lorazepam, oxazepam, temazepam) are less likely to be affected by fluvoxamine and may be safer alternatives 1

Special Precautions

• Flumazenil, a benzodiazepine antagonist, has no role in the management of cardiac arrest due to benzodiazepine overdose but may be used to reverse excessive sedation known to be due to benzodiazepines in a patient without known contraindications 2
• Abrupt discontinuation of either medication may lead to withdrawal symptoms, so tapering is recommended if discontinuation is necessary 3
• The combination should be used with particular caution in elderly patients and those with respiratory conditions, as they are more susceptible to adverse effects 2

Monitoring

• Monitor for signs of excessive sedation, confusion, or impaired coordination 3
• If signs of respiratory depression develop, immediate medical attention is required 2
• Be alert for any signs of serotonin syndrome, which may include mental status changes, autonomic instability, neuromuscular aberrations, and/or gastrointestinal symptoms 1