What medications interact with ramelteon, phentermine, ezetimibe, buspirone, propranolol, modafinil, lamotrigine, pravastatin, famotidine, topiramate (Topamax), lurasidone (Latuda), and solifenacin?

Drug Interactions with the Listed Medication Regimen

Critical Interactions Requiring Immediate Attention

Propranolol combined with topiramate (Topamax) and phentermine creates a potentially dangerous interaction that requires careful monitoring or alternative therapy. 1

Beta Blocker Interactions

• Propranolol with phentermine poses a moderate to severe interaction risk due to opposing cardiovascular effects—phentermine increases sympathetic activity while propranolol blocks beta-adrenergic receptors, potentially masking tachycardia and hypertension warning signs. 2

• Propranolol combined with topiramate may produce additive effects on heart rate reduction, particularly when used with other rate-controlling agents. 1

Modafinil Interactions

• Modafinil acts as a moderate CYP inducer and can reduce plasma concentrations of multiple medications in this regimen, potentially decreasing their efficacy. 1

• Modafinil may reduce levels of lamotrigine through enzyme induction, requiring dose adjustments to maintain therapeutic effect. 3

• Modafinil can interact with phentermine through sympathomimetic potentiation, increasing cardiovascular risks including hypertension and tachycardia. 2

Ramelteon Interactions

• Ramelteon requires extreme caution with modafinil as CYP enzyme inducers can decrease ramelteon exposure by approximately 80%, significantly reducing efficacy. 4

• Ramelteon should be monitored closely if used with buspirone, though no specific interaction data exists; theoretical concerns involve additive CNS effects. 4

Lamotrigine Interactions

• Lamotrigine has no significant interactions with topiramate, levetiracetam, or gabapentin based on clinical studies. 3

• Lamotrigine clearance is not affected by the other medications in this regimen except potentially by modafinil through enzyme induction. 5, 3

Phentermine and Topiramate Combination

• The phentermine-topiramate combination is FDA-approved and studied extensively, showing manageable safety profiles when used together. 6

• Common adverse effects of this combination include dry mouth (13-21%), paresthesia (14-21%), constipation (15-17%), and insomnia (6-10%) at therapeutic doses. 6

• Depression-related adverse events occur in 4-7% and anxiety-related events in 5-8% with this combination, requiring monitoring when combined with buspirone. 6

Statin Interactions

• Pravastatin has minimal interaction potential with this medication regimen as it is not significantly metabolized by CYP3A4 and has low potential for drug interactions. 1

• Ezetimibe does not interact significantly with any medications in this regimen as it undergoes glucuronidation rather than CYP metabolism. 1

• Propranolol does not significantly affect statin metabolism, and combination therapy is considered reasonable. 1

Lurasidone (Latuda) Considerations

• Lurasidone is a CYP3A4 substrate and may have reduced efficacy when combined with modafinil due to enzyme induction, though specific interaction data is limited. 7

• Lamotrigine may potentially increase clozapine concentrations, but data on lurasidone interactions with lamotrigine are lacking; theoretical concerns exist for other antipsychotics. 7

Medications with Minimal Interaction Risk

• Famotidine has no significant interactions with this medication regimen as it does not undergo significant CYP metabolism and is primarily renally eliminated. 4

• Solifenacin has minimal documented interactions with the listed medications, though theoretical concerns exist regarding anticholinergic effects when combined with other CNS-active drugs. 1

• Buspirone interactions are primarily theoretical with this regimen, though caution is warranted with CNS depressants and drugs affecting serotonin. 8

Specific Monitoring Recommendations

• Monitor cardiovascular parameters closely (blood pressure, heart rate) with the propranolol-phentermine-topiramate combination, checking at baseline and every 2-4 weeks initially. 1, 2

• Assess sleep quality and daytime alertness if ramelteon efficacy appears reduced with modafinil co-administration. 4

• Watch for signs of lamotrigine toxicity or loss of seizure control if modafinil is started or stopped, as dose adjustments may be needed. 5, 3

• Monitor for mood changes, depression, or anxiety with the phentermine-topiramate combination, particularly given concurrent buspirone and lurasidone use. 6