Tesofensine side effects and risks

Reported side effects

• Dry mouth: Originally reported at 0.5 mg: 42.0% versus 11.5% placebo. Safety events were later found under reported., moderate (source)
• Nausea: Originally reported at 0.5 mg: 20.0% versus 9.6% placebo., moderate (source)
• Insomnia: Originally reported at 0.5 mg: 12.0% versus 1.9% placebo., moderate (source)
• Hard stools: Originally reported at 0.5 mg: 14.0% versus 3.8% placebo., moderate (source)
• Constipation: Originally reported at 1 mg: 16.3%; 0.5 mg: 2.0%; placebo: 7.7%. Frequency varies with dose., moderate (source)
• Diarrhea: Originally reported at 0.5 mg: 8.0% versus 5.8% placebo., moderate (source)
• Headache: Originally reported at 0.5 mg: 34.0% versus 40.4% placebo., moderate (source)
• Dizziness: Originally reported at 0.5 mg: 10.0% versus 3.8% placebo., moderate (source)
• Vomiting: Originally reported at 0.5 mg: 6.0% versus 1.9% placebo., moderate (source)
• Raised heart rate or palpitations: 0.5 mg increased mean heart rate by 7.4 beats/min versus placebo. Palpitations were reported., serious (source)
• High blood pressure: 1 mg increased blood pressure in TIPO 1; individual risk cannot be estimated reliably., serious (source)
• Anxiety, mania, depression or unusual behavior: Serious psychiatric events occurred in small Tesomet studies. A population rate is unknown., serious (source)

Stop and get help if

• Chest pain, fainting or a racing/irregular heartbeat: Stop exposure and get urgent medical care.
• Fever with confusion, sweating, shaking or muscle twitching: Seek emergency care for possible serotonin toxicity.
• Hallucinations, mania, severe agitation or suicidal thoughts: Stop exposure and seek urgent assessment; immediate danger needs emergency care.
• Swollen tongue or throat, or trouble breathing: Seek emergency care for a possible severe allergic reaction.
• Confusion, severe headache or seizures while taking desmopressin: Seek urgent care; low blood sodium is possible.
• Persistent low glucose, confusion or inability to swallow safely: Use the prescribed hypoglycemia plan and seek urgent care.

Who should avoid it

• pregnant: Pregnancy was excluded from obesity trials; fetal safety has not been established.
• breastfeeding: Breastfeeding was excluded; milk transfer and infant safety are unknown.
• tryingToConceive: Trials required contraception. No evidence-based preconception washout is established.
• under18: General obesity dosing is not established under 18. A small PWS trial does not validate general pediatric use.
• eatingDisorderHistory: Appetite suppression can worsen restrictive eating; obesity trials excluded eating disorders.
• heartCondition: Heart rate can rise. Trials excluded major heart disease, arrhythmias and recent heart attack or stroke.
• uncontrolledBloodPressure: Tesofensine can raise blood pressure; uncontrolled hypertension was excluded from trials.
• psychiatricCondition: Anxiety, mania, paranoia and mood changes occurred. Bipolar illness or psychosis requires particular review.
• depressionOrSuicidalThoughts: Trials screened mood and suicidality; serious depression was reported in a short Tesomet study.
• kidneyDisease: Kidney function affected modeled exposure; significant impairment was excluded. No validated dose adjustment exists.
• liverDisease: Significant liver disease was excluded; metabolism involves CYP3A4. No validated adjustment is available.
• seizureDisorder: Epilepsy was excluded from TIPO-1; seizure risk has not been defined.
• diabetes: Reduced intake may change glucose medicine needs. Diabetes trials used additional glucose monitoring.
• other: Known allergy to tesofensine or its tablet ingredients should stop use.
• other: Uncontrolled thyroid disease was excluded; it may compound heart-rate and weight effects.
• other: Uncontrolled glaucoma and significant eye disease were excluded from the obesity trial.
• surgeryPlanned: Tell the anesthesia team about exposure; the drug clears over weeks. No validated stop interval was found.
• testedAthlete: Tesofensine is named in WADA 2026 S6.B and prohibited in competition.
• other: Metoprolol protocols only: the label blocks severe bradycardia. TM005 also excluded resting heart rate <50 beats/min.
• other: Metoprolol protocols only: the label contraindicates metoprolol with second- or third-degree heart block.
• other: Metoprolol protocols only: sick sinus syndrome is a label contraindication unless a permanent pacemaker is in place.
• other: Metoprolol protocols only: the label contraindicates metoprolol during cardiogenic shock.
• other: Metoprolol protocols only: the label blocks use in decompensated heart failure. TM005 also excluded this condition.
• other: Metoprolol protocols only: allergy to metoprolol or any component of its tablet is a label contraindication and a TM005 exclusion.

Interactions

• MAO inhibitors: Avoid combining monoamine reuptake blockade with MAO inhibition: predicted serotonin toxicity or dangerous blood-pressure changes. MAOIs were excluded.
• Serotonergic medicines and supplements: Predicted serotonin-toxicity risk; SSRIs/SNRIs were prohibited in Tesomet trials. Direct interaction rates are unknown.
• Stimulants and other appetite suppressants: Overlapping stimulant effects may worsen heart rate, pressure, anxiety and sleep. Other appetite suppressants were excluded from trials.
• Strong CYP3A4 inhibitors: Itraconazole increased exposure; effects with other strong CYP3A4 inhibitors are predicted, not directly measured.
• Insulin and sulfonylureas: Reduced food intake and weight loss can lower glucose medicine needs. Hypoglycemia risk is inferred; combination data are limited.
• Metoprolol and other beta blockers: Metoprolol was studied with tesofensine. It can slow the heart or lower pressure; it does not remove psychiatric risk.
• Desmopressin: The trial protocol flags possible additive water retention and low sodium. The interaction is theoretical.
• GLP-1 drugs and experimental appetite drugs: Formal stack trials are lacking. Reduced intake, nausea and heart-rate effects may overlap; community results cannot establish safety.

Product quality risks

• A 2026 study measured 483 mcg in one capsule labeled 500 mcg. One product cannot establish market-wide quality.
• No independent market-wide tesofensine purity, contamination or counterfeit survey was located.
• FDA documented manufacturing-quality failures at an API distributor and identified tesofensine as ineligible for 503A compounding.
• Oral product purity does not establish sterility or safety for injection.