Tesofensine: Dosage & Administration

Tesofensine is a triple monoamine reuptake inhibitor originally developed for Parkinson's disease and Alzheimer's by NeuroSearch (Denmark), then repurposed for obesity after weight-loss signals emerged in neurological trials. The pivotal weight-loss trial was Astrup et al., Phase 2, published in The Lancet 2008.^[1] Phase 3 trials have run primarily in Mexico (Tesomet, Saniona / Medix).^[2]

The 0.5 mg dose is the most-commonly-cited research dose because it captures the bulk of weight-loss efficacy (~83% of the 1.0 mg result) at substantially lower cardiovascular cost. Phase 3 trials have explored 0.5 mg as a single agent and 0.5 mg combined with metoprolol (the Tesomet protocol) to offset the cardiovascular signal.^[2]

Tesofensine increases dopamine, norepinephrine, and serotonin signaling. The combined activation produces measurable insomnia at all doses, worst at 1.0 mg. Morning dosing (with breakfast or shortly after) is essential — evening dosing produces severe sleep disruption.

• Take once daily in the morning, typically with breakfast.
• Avoid afternoon dosing — even 12:00 dosing can interfere with sleep onset.
• Take consistently at the same time for steady-state plasma levels.
• With or without food: not strongly affected; food can reduce mild GI effects.

No formal titration is required (capsule, not injection), but starting at the lowest dose is prudent:

• Week 1–2: 0.25 mg once daily. Tolerance check.
• Week 3–4+: if tolerated, increase to 0.5 mg once daily. This is the standard maintenance dose.
• If still no significant weight loss at week 8–12 on 0.5 mg: some protocols increase to 1.0 mg, but with mandatory weekly BP and heart rate monitoring. 1.0 mg is not appropriate for patients with any cardiovascular risk factors.

Monitor resting heart rate and blood pressure weekly during the first month, then monthly. A sustained heart rate increase > 10 bpm or systolic BP increase > 10 mmHg from baseline warrants dose reduction or discontinuation.

Published trials used 24-week treatment periods. Phase 3 Tesomet trials have extended to 48 weeks. Long-term safety beyond 48 weeks is not characterized.

• No formal cycling protocol exists — tesofensine works through monoamine reuptake inhibition that does not appear to develop tolerance in the way that some weight-loss drugs do.
• Weight regain after discontinuation is expected, as with all pharmacological weight-loss agents.
• Periodic discontinuation (e.g., 4 weeks off every 6 months) is sometimes practiced to confirm the cardiovascular signal remains acceptable on re-challenge.

Tesofensine elevates serotonin, dopamine, and norepinephrine. Important interaction categories:

• MAOIs (phenelzine, tranylcypromine, selegiline, isocarboxazid): absolute contraindication. Combined use risks fatal hypertensive crisis or serotonin syndrome. Stop MAOI at least 14 days before starting tesofensine.
• SSRIs / SNRIs (fluoxetine, sertraline, venlafaxine, etc.): serotonin syndrome risk. Combination requires careful psychiatric supervision. Generally avoid.
• Other monoamine drugs (bupropion, atomoxetine, stimulants): additive sympathomimetic effects; avoid combining or use very low doses.
• Sympathomimetics (pseudoephedrine, phenylephrine, ephedrine): additive hypertension / heart rate effects.
• Dopamine agonists (levodopa, cabergoline, ropinirole, pramipexole): theoretical additive dopaminergic activity.
• Triptans (sumatriptan, etc.): serotonin syndrome risk.
• Lithium: serotonin syndrome risk.
• Caffeine: additive cardiovascular effects; minimize caffeine intake while on tesofensine.

• Capsules: store at room temperature (15–30°C / 59–86°F).
• Protect from moisture, light, and heat.
• Keep in original packaging with desiccant if provided.
• Do not store in bathroom (humidity).