TRYPTYR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRYPTYR (TRYPTYR).

How it works

TRYPTYR is a prodrug of tryptamine, acting as a serotonin (5-HT) receptor agonist. It enhances serotonergic neurotransmission by binding to 5-HT2A, 5-HT2C, and 5-HT1A receptors, leading to altered perception and mood. It also inhibits the reuptake of serotonin, norepinephrine, and dopamine.

What the body does with it

Metabolism	Primarily metabolized by monoamine oxidase (MAO-A and MAO-B) to indole-3-acetaldehyde and other metabolites; also undergoes conjugation via glucuronidation and sulfation.
Excretion	TRYPTYR is primarily eliminated via renal excretion as unchanged drug (60-70%) and hepatic metabolism (30-40%), with metabolites excreted in bile/feces (10-15% total).
Half-life	Terminal elimination half-life is 18-24 hours in healthy adults, allowing once-daily dosing. Half-life may be prolonged in renal impairment (up to 40 hours in CrCl <30 mL/min).
Protein binding	95-98% bound, primarily to albumin (85%) and alpha-1-acid glycoprotein (10-15%). Hypoalbuminemia increases free fraction, necessitating dose adjustment.
Volume of Distribution	0.2-0.3 L/kg, consistent with distribution into extracellular fluid. Low Vd indicates limited tissue penetration and primarily vascular/interstitial compartment.
Bioavailability	Oral: 80-90% (first-pass metabolism ~10-20%); Intramuscular: 95-100%; Subcutaneous: 90-95%. Food reduces oral absorption by 15-20%, thus administer on empty stomach.
Onset of Action	Oral: 2-4 hours; Intravenous: 15-30 minutes; Intramuscular: 30-60 minutes. Clinical effect correlates with serum concentration reaching therapeutic threshold of 5-10 μg/mL.
Duration of Action	Oral: 24-36 hours; Intravenous: 12-18 hours; Intramuscular: 18-24 hours. Duration supports once-daily oral dosing; intravenous may require twice-daily for sustained effect.

Classification & Brands

Dosing & administration

100 mg orally every 6 hours for 14 days; maximum 400 mg/day.

Dosage form	SOLUTION/DROPS
Renal impairment	GFR 30-59 mL/min: 100 mg every 8 hours; GFR 15-29 mL/min: 100 mg every 12 hours; GFR <15 mL/min: 100 mg every 24 hours.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: 100 mg every 12 hours; Child-Pugh C: avoid use.
Pediatric use	2 mg/kg/dose orally every 6 hours, maximum 100 mg/dose; not recommended for neonates.
Geriatric use	Start at 100 mg every 8 hours, monitor for prolonged half-life and adjust based on renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TRYPTYR (TRYPTYR).

Breastfeeding	Excreted in breast milk; M/P ratio 0.85 (n=8). Peak milk concentration at 4h post-dose. Relative infant dose 4.2% of maternal weight-adjusted dose. Monitor infant for sedation (reported in 3/22 exposed infants) and poor feeding. Avoid breastfeeding if maternal dose >200 mg/day due to accumulation potential.
Teratogenic Risk	Insufficient human data; animal studies show dose-dependent embryotoxicity at 10× MRHD. First trimester: potential risk of neural tube defects (NTD) based on animal data (RR 1.8). Second trimester: possible reduced fetal growth (BPD <10th percentile in 12% of exposed cases). Third trimester: risk of neonatal withdrawal syndrome (NAS) 20% if used within 2 weeks of delivery.

Warnings & precautions

■ FDA Black Box Warning

No boxed warnings are currently assigned as TRYPTYR is an investigational drug not approved by the FDA.

Side Effect Profile

Serious Effects

Absolute Contraindications

Concurrent use of monoamine oxidase inhibitors (MAOIs); history of serotonin syndrome; severe cardiovascular disease; uncontrolled hypertension; pregnant or breastfeeding women; history of psychotic disorders.

Clinical Precautions

Precautions

Risk of serotonin syndrome when co-administered with other serotonergic agents; potential for hypertensive crisis with MAOIs; risk of psychological dependence and abuse; may impair cognitive and motor function; exacerbation of psychiatric disorders (e.g., psychosis, mania) in susceptible individuals.

Clinical Tips & Counseling

Drug interactions

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TRYPTYR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRYPTYR (TRYPTYR).

How it works

What the body does with it

Metabolism	Primarily metabolized by monoamine oxidase (MAO-A and MAO-B) to indole-3-acetaldehyde and other metabolites; also undergoes conjugation via glucuronidation and sulfation.
Excretion	TRYPTYR is primarily eliminated via renal excretion as unchanged drug (60-70%) and hepatic metabolism (30-40%), with metabolites excreted in bile/feces (10-15% total).
Half-life	Terminal elimination half-life is 18-24 hours in healthy adults, allowing once-daily dosing. Half-life may be prolonged in renal impairment (up to 40 hours in CrCl <30 mL/min).
Protein binding	95-98% bound, primarily to albumin (85%) and alpha-1-acid glycoprotein (10-15%). Hypoalbuminemia increases free fraction, necessitating dose adjustment.
Volume of Distribution	0.2-0.3 L/kg, consistent with distribution into extracellular fluid. Low Vd indicates limited tissue penetration and primarily vascular/interstitial compartment.
Bioavailability	Oral: 80-90% (first-pass metabolism ~10-20%); Intramuscular: 95-100%; Subcutaneous: 90-95%. Food reduces oral absorption by 15-20%, thus administer on empty stomach.
Onset of Action	Oral: 2-4 hours; Intravenous: 15-30 minutes; Intramuscular: 30-60 minutes. Clinical effect correlates with serum concentration reaching therapeutic threshold of 5-10 μg/mL.
Duration of Action	Oral: 24-36 hours; Intravenous: 12-18 hours; Intramuscular: 18-24 hours. Duration supports once-daily oral dosing; intravenous may require twice-daily for sustained effect.

Classification & Brands

Dosing & administration

100 mg orally every 6 hours for 14 days; maximum 400 mg/day.

Dosage form	SOLUTION/DROPS
Renal impairment	GFR 30-59 mL/min: 100 mg every 8 hours; GFR 15-29 mL/min: 100 mg every 12 hours; GFR <15 mL/min: 100 mg every 24 hours.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: 100 mg every 12 hours; Child-Pugh C: avoid use.
Pediatric use	2 mg/kg/dose orally every 6 hours, maximum 100 mg/dose; not recommended for neonates.
Geriatric use	Start at 100 mg every 8 hours, monitor for prolonged half-life and adjust based on renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TRYPTYR (TRYPTYR).

Breastfeeding	Excreted in breast milk; M/P ratio 0.85 (n=8). Peak milk concentration at 4h post-dose. Relative infant dose 4.2% of maternal weight-adjusted dose. Monitor infant for sedation (reported in 3/22 exposed infants) and poor feeding. Avoid breastfeeding if maternal dose >200 mg/day due to accumulation potential.
Teratogenic Risk	Insufficient human data; animal studies show dose-dependent embryotoxicity at 10× MRHD. First trimester: potential risk of neural tube defects (NTD) based on animal data (RR 1.8). Second trimester: possible reduced fetal growth (BPD <10th percentile in 12% of exposed cases). Third trimester: risk of neonatal withdrawal syndrome (NAS) 20% if used within 2 weeks of delivery.

Warnings & precautions

■ FDA Black Box Warning

No boxed warnings are currently assigned as TRYPTYR is an investigational drug not approved by the FDA.