SYNDROS
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 314.47 |
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 | Dronabinol is a synthetic cannabinoid; animal studies indicate fetal risk; use only if benefit outweighs risk. |
| 2nd trimester | Avoid use; potential for fetal cannabinoid exposure and adverse neurobehavioral effects. |
| 3rd trimester | Avoid use; maternal use may cause neonatal withdrawal and low birth weight. |
Clinical note
Comprehensive clinical and safety monograph for SYNDROS (SYNDROS).
| Placental transfer | Dronabinol crosses the placenta readily; detectable in fetal circulation. |
| Breastfeeding | Dronabinol is excreted in breast milk; due to potential for adverse effects on infant development and neurobehavior, breast-feeding is not recommended. |
| Lactation Rating | L5 - Contraindicated |
| 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. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to dronabinol or cannabinoidsHistory of schizophrenia or bipolar disorder
| 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 |
| Food/Dietary | Food with high fat content may increase dronabinol absorption; take consistently with or without food to avoid variability. Grapefruit and grapefruit juice may increase dronabinol levels; avoid concurrent use. |
| Clinical Pearls | Syndros (dronabinol oral solution) is a synthetic delta-9-tetrahydrocannabinol (THC) used for chemotherapy-induced nausea and vomiting (CINV) and anorexia with weight loss in AIDS patients. It has a high first-pass metabolism; avoid use in patients with hepatic impairment. Onset is faster than capsules; dosing must be individualized based on prior cannabis exposure. Monitor for CNS depression and avoid concurrent use with other CNS depressants. Syndros contains alcohol (5% v/v); use cautiously in patients with alcohol intolerance or liver disease. Contraindicated in patients with a history of hypersensitivity to THC or sesame oil (vehicle). |
| Patient Advice | Take Syndros 1 to 3 hours before chemotherapy for CINV, or twice daily before lunch and dinner for AIDS-related anorexia. · Avoid driving or operating machinery until you know how Syndros affects you, as it can cause dizziness, drowsiness, and altered judgment. · Do not drink alcohol or take other sedating medications while using Syndros, as this increases the risk of severe sedation. · Report any mood changes, depression, or suicidal thoughts to your healthcare provider immediately. · Store at room temperature (20-25°C) and protect from light; do not freeze. · If you are pregnant, planning to become pregnant, or breastfeeding, discuss use with your doctor; THC can pass into breast milk. · Use a calibrated measuring device for the oral solution (provided with the medication) to ensure accurate dosing. |
Loading safety data…