What is the recommended Tesofensine dosage?

Tesofensine dosing varies by experience level. Beginners typically start at 0.25mg daily, moderate users at 0.5mg daily, and aggressive protocols use 1mg daily.

How do you reconstitute Tesofensine?

Tesofensine comes as a pre-filled device — no reconstitution needed.

What is the half-life of Tesofensine?

The half-life of Tesofensine is ~9 days (220 hours). This determines how frequently you need to dose for consistent blood levels.

Tesofensine

Weight LossOralPhase 3Grade C~9 days (220 hours) half-life

Weight ManagementAppetite RegulationFat LossMood Regulation24 weeks on / 4 weeks off

Benefits

Approximately 9-11% body weight loss at therapeutic doses in 24 weeks

Triple monoamine reuptake action targets appetite at the brain level

Oral once-daily capsule — no injections required

No significant blood pressure elevation at the 0.5 mg dose

Long half-life supports consistent appetite suppression

May help prevent weight regain when combined with other interventions

Different mechanism from GLP-1 agonists — potential add-on option

Half-Life

~9 days

Route

Oral

Frequency

Daily

Vial Sizes

0.25mg, 0.5mg, 1mg

BAC Water

Pre-filled

Safety Grade

Grade C

Open Tesofensine Dosage Calculator

Calculate exact syringe units for your vial and dose

About Tesofensine

Tesofensine is a triple monoamine reuptake inhibitor originally developed for Alzheimer's and Parkinson's disease, where it was found to produce significant unintended weight loss in trial participants. It works by blocking the reuptake of three key neurotransmitters — serotonin, norepinephrine, and dopamine — in the brain, increasing their availability at the synapse. This triple action distinguishes it from older weight loss drugs like sibutramine, which primarily targeted only two of the three monoamines. In Phase 2 clinical trials, tesofensine at 0.5 mg daily produced an average body weight reduction of 9.2% over 24 weeks when paired with a calorie-restricted diet, roughly double the effect seen with previously approved anti-obesity medications at the time. The 1.0 mg dose reached 10.6% weight loss. These results caught attention because tesofensine achieved GLP-1-class weight loss through an entirely different pathway — central nervous system appetite regulation rather than gut hormone signaling. Tesofensine suppresses appetite by increasing dopaminergic and noradrenergic tone in hypothalamic feeding circuits. Recent research shows it silences a subset of GABAergic neurons in the lateral hypothalamus, directly reducing the neural drive to eat. It may also modestly increase resting energy expenditure, adding a thermogenic component to its weight loss effect. The compound is taken as a once-daily oral capsule, which offers a practical advantage over injectable GLP-1 agonists. Its long half-life of approximately 9 days means steady-state plasma levels are reached after several weeks, and effects persist well beyond a single missed dose. Saniona's partner Medix completed a Phase 3 program confirming the weight loss and safety profile seen in earlier trials, and a regulatory submission in Mexico was filed in 2025. Tesofensine is not currently approved by the FDA or EMA.

Who Should Consider Tesofensine

Adults with BMI ≥30 (clinical obesity)
Adults with BMI ≥27 with weight-related comorbidities
Individuals who prefer oral medication over injectable GLP-1 therapy
Patients who have not responded to single-mechanism weight loss drugs
Adults seeking appetite suppression through central nervous system pathways

How Tesofensine Works

Tesofensine inhibits the presynaptic reuptake of three monoamine neurotransmitters: norepinephrine (NE), serotonin (5-HT), and dopamine (DA). By blocking the norepinephrine transporter (NET), serotonin transporter (SERT), and dopamine transporter (DAT), it increases extracellular concentrations of all three in brain feeding circuits. In vitro IC50 values are 1.7 nM for NE, 6.5 nM for DA, and 11 nM for 5-HT, indicating the strongest affinity at the norepinephrine transporter. The increased monoamine signaling activates alpha-1 adrenoceptors and dopamine D1 receptors in the hypothalamus, producing satiety and reducing food intake. Recent studies show tesofensine silences a subset of GABAergic neurons in the lateral hypothalamus that normally promote feeding behavior, providing a direct neuronal basis for its appetite-suppressing effects. A modest increase in resting energy expenditure may also contribute to net weight loss. Tesofensine is metabolized by CYP3A4 to its active metabolite M1, which retains monoamine reuptake inhibition and has a half-life of approximately 16 days, extending the pharmacological activity well beyond each dose.

What to Expect

Weeks 1-2

0.25 mg

Initiation phase. Mild appetite reduction may begin. Common early side effects include dry mouth and mild nausea. Plasma levels are building toward steady state due to the long half-life.

Weeks 3-4

0.25 mg

Appetite suppression becomes more noticeable as plasma levels approach steady state. Side effects typically begin to stabilize. Heart rate should be monitored.

Weeks 5-8

0.5 mg

Dose escalation to therapeutic level. Appetite suppression is pronounced. Early weight loss of 3-5% expected. Steady-state concentrations of both parent compound and active metabolite M1 are established.

Weeks 9-16

0.5 mg

Peak weight loss rate. Clinical trials showed approximately 9% mean weight loss at 0.5 mg by this period. Improved energy levels and reduced food cravings reported by many users.

Weeks 17-24

0.5 mg maintenance

Continued steady weight loss. Phase 2 data showed 9.2% mean body weight reduction at 24 weeks with 0.5 mg. Weight loss rate begins to plateau as a new metabolic equilibrium is reached.

Dosing Protocol

Level	Dose / Injection	Frequency
Beginner	0.25mg	Daily
Moderate	0.5mg	Daily
Aggressive	1mg	Daily

Note: Oral capsule — no reconstitution needed. Triple monoamine reuptake inhibitor (serotonin, norepinephrine, dopamine). Not FDA-approved. Phase 3 completed in Mexico. Take once daily in the morning. Active metabolite M1 has a ~16-day half-life, contributing to prolonged activity. Monitor heart rate during treatment.

How to Inject Tesofensine

Take one capsule orally once daily, preferably in the morning with or without food. No difference in pharmacokinetics between fed and fasted states. Start at 0.25 mg daily for 2-4 weeks, then increase to 0.5 mg if tolerated. The 0.5 mg dose is the expected therapeutic dose based on clinical trial data. Do not exceed 1.0 mg daily.

Cycling Protocol

On Period

24 weeks

Off Period

4 weeks

Clinical trials administered tesofensine continuously for 24 weeks. Long-term cycling data beyond 24 weeks is limited. Work with a prescribing physician to determine duration of use. The long half-life (~9 days) means pharmacological effects persist for several weeks after the last dose.

Pharmacokinetics

Half-Life

220h

Bioavailability

Oral: >90%

Tmax

6-8 hours

Data Confidence

moderate

Source: Population PK model, Lehr et al. Br J Clin Pharmacol 2007 (PMID: 17324246) — 234h mean; ~220h commonly cited

Pharmacokinetics — Active Dose Over Time

Loading the interactive decay curve.

Side Effects

Dry mouth, nausea, constipation, diarrhea, insomnia, and headache are the most frequently reported effects. Heart rate increases of 5-8 bpm are common at therapeutic doses. The 1.0 mg dose showed a higher incidence of adverse events than 0.5 mg. No significant blood pressure changes were observed at the 0.5 mg dose. Withdrawal rate due to adverse events was approximately 13% with tesofensine versus 6% with placebo in Phase 2 trials.

Contraindications

Uncontrolled hypertension or tachycardia
History of cardiovascular disease (stroke, heart attack, arrhythmia)
Concurrent use of MAO inhibitors or other monoamine reuptake inhibitors (SSRIs, SNRIs)
Pregnancy or breastfeeding
Severe hepatic impairment (CYP3A4-dependent metabolism)
History of seizure disorders
Known hypersensitivity to tesofensine or any excipients
Glaucoma (narrow-angle)

Drug Interactions

MAO inhibitors — contraindicated; risk of serotonin syndrome and hypertensive crisis
SSRIs and SNRIs — increased serotonin syndrome risk due to overlapping monoamine effects
CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) — may increase tesofensine plasma levels; dose adjustment may be needed
CYP3A4 inducers (rifampin, carbamazepine, phenytoin) — may reduce tesofensine efficacy
Sympathomimetics (pseudoephedrine, amphetamines) — additive cardiovascular effects; increased heart rate and blood pressure risk
Tramadol and other serotonergic analgesics — increased seizure and serotonin syndrome risk