SYNDROS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SYNDROS (SYNDROS).
Dronabinol is a cannabinoid receptor type 1 (CB1) agonist, activating CB1 receptors in the central nervous system to inhibit emetic signals and stimulate appetite. It also has partial agonist activity at cannabinoid receptor type 2 (CB2).
| Metabolism | Primarily hepatic via cytochrome P450 (CYP) 3A4 and 2C9 isoenzymes; undergoes extensive first-pass metabolism to active and inactive metabolites. |
| Excretion | Approximately 65% of a dose is excreted in feces (primarily as hydroxylated and carboxylated metabolites) and 35% in urine (as metabolites, with <5% unchanged drug). |
| Half-life | Terminal elimination half-life is 28–61 hours (mean ~32 hours) in adults; prolonged with high-fat meal. Clinical context: Steady state achieved in 5–6 days. |
| Protein binding | 97–99% bound, primarily to albumin and lipoproteins. |
| Volume of Distribution | Vd: 10–80 L/kg (mean ~30 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability: ~10–20% (variable due to extensive first-pass metabolism); increased 2- to 4-fold with a high-fat meal. |
| Onset of Action | Orally: onset of appetite stimulation within 30–60 minutes; antiemetic effect begins within 1 hour. |
| Duration of Action | Duration of appetite stimulation: 4–6 hours; antiemetic effect persists up to 6 hours. Clinical notes: Effects may persist longer with repetitive dosing due to accumulation. |
5 mg/m² orally 1-3 hours before chemotherapy, initially; may increase by 2.5 mg/m² increments as tolerated, maximum 15 mg/m² per dose.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; insufficient data for severe impairment (eGFR <30 mL/min); use with caution. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use due to potential for encephalopathy. |
| Pediatric use | Safety and efficacy not established in pediatric patients; not recommended under 18 years. |
| Geriatric use | No specific dose adjustment; monitor for increased sensitivity to adverse effects (e.g., dysphoria, hypotension). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SYNDROS (SYNDROS).
| Breastfeeding | Dronabinol is excreted into human milk. The M/P ratio is not specifically determined for dronabinol; however, THC (active component) has an M/P ratio of approximately 0.04 based on limited data. Because of the potential for adverse effects on the nursing infant, such as developmental delay and sedation, breastfeeding is not recommended during SYNDROS therapy. An alternative method of infant feeding should be considered. |
| Teratogenic Risk | Dronabinol (SYNDROS) is classified as FDA Pregnancy Category C. Animal studies have shown embryotoxicity and fetotoxicity at doses similar to human therapeutic doses. There are no adequate and well-controlled studies in pregnant women. First trimester exposure may be associated with a small increased risk of neural tube defects. Second and third trimester exposure may affect fetal brain development, including potential long-term neurobehavioral effects. Dronabinol crosses the placenta. Use only if potential benefit justifies potential risk to the fetus. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to dronabinol or any cannabinoid or sesame oil (capsule contains sesame oil)","Concurrent use with disulfiram or metronidazole due to alcohol content in oral solution (however, Syndros is a dronabinol solution; contraindication applies to alcohol-containing formulations – note: Syndros contains alcohol; label contraindicates concurrent use with disulfiram or metronidazole)"]
| Precautions | ["Risk of psychiatric adverse reactions, including dysphoria, hallucinations, paranoia, and worsening of pre-existing mental illness","Central nervous system depressant effects and impairment of cognitive function, motor skills, and judgment; caution when driving or operating machinery","Potential for abuse, tolerance, and dependence (Schedule III controlled substance)","May increase heart rate and blood pressure; use with caution in patients with cardiovascular disease","Seizures: May lower seizure threshold in patients with epilepsy","Pancreatitis: Cases reported; monitor for symptoms"] |
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| Fetal Monitoring | Monitor maternal vital signs (heart rate, blood pressure) and mental status for signs of excessive sedation, euphoria, or dysphoria. Assess for potential abuse or dependence. Fetal monitoring includes serial ultrasound assessments for growth restriction if used in second/third trimester. Evaluate fetal movement patterns if prolonged use. Monitor neonatal outcomes for signs of withdrawal or neurobehavioral effects. |
| Fertility Effects | Dronabinol may impair fertility. In animal studies, THC reduced sperm count, motility, and viability in males; in females, it disrupted estrous cycles and ovulation. In humans, THC can suppress gonadotropin release, leading to reversible reductions in testosterone, sperm parameters, and menstrual irregularities. These effects are generally reversible upon discontinuation. |