DARTISLA ODT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DARTISLA ODT (DARTISLA ODT).
DARTISLA ODT is a combination of oxycodone, a full mu-opioid receptor agonist, and naltrexone, a mu-opioid receptor antagonist. Naltrexone is sequestered in the core and is released upon tampering to reverse opioid effects, intended for abuse-deterrence.
| Metabolism | Oxycodone is extensively metabolized by CYP3A4 and CYP2D6. Naltrexone undergoes extensive first-pass metabolism to 6β-naltrexol, primarily by dihydrodiol dehydrogenase (DD). |
| Excretion | Approximately 60% of a dose is excreted renally as unchanged drug and metabolites, with the remainder eliminated via biliary/fecal routes. Renal clearance accounts for about 30% of total clearance. |
| Half-life | The terminal elimination half-life is approximately 20-30 hours. This long half-life supports once-daily dosing and requires steady-state achievement within 5-7 days. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 2-3 L/kg, indicating extensive tissue distribution and penetration into extravascular tissues. |
| Bioavailability | The absolute oral bioavailability of the ODT formulation is approximately 80-90% due to minimal first-pass metabolism. |
| Onset of Action | Following oral administration (ODT), onset of clinical effect is observed within 1-2 hours, with peak plasma concentrations occurring at 2-4 hours. |
| Duration of Action | Duration of action is approximately 24 hours due to extended-release formulation, allowing for once-daily dosing. Clinical effects persist throughout the dosing interval. |
10 mg orally once daily, as an orally disintegrating tablet.
| Dosage form | TABLET, ORALLY DISINTEGRATING |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), reduce dose to 5 mg once daily. |
| Liver impairment | For Child-Pugh Class A: 5 mg once daily. Child-Pugh Class B: 5 mg once daily. Child-Pugh Class C: not recommended. |
| Pediatric use | Not established; safety and efficacy in pediatric patients (<18 years) have not been studied. |
| Geriatric use | No specific dose adjustment required, but monitor for increased sensitivity and adverse effects due to age-related reductions in hepatic and renal function; start at lower end of dosing range if warranted. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DARTISLA ODT (DARTISLA ODT).
| Breastfeeding | Excreted into breast milk. M/P ratio not reported; however, dextroamphetamine concentrations in milk are approximately 2-3 times higher than maternal plasma. Relative infant dose is estimated at 5-10% of maternal weight-adjusted dose. Potential for irritability, poor feeding, and growth impairment in breastfed infants. Manufacturer recommends avoiding breastfeeding during therapy. |
| Teratogenic Risk | Dartisla ODT (dextroamphetamine) is classified as Pregnancy Category C. First trimester: Associated with increased risk of congenital malformations, particularly cardiac defects (e.g., ventricular septal defect) and oral clefts, based on observational studies. Second and third trimesters: May cause fetal growth restriction, premature birth, and neonatal withdrawal syndrome (irritability, feeding difficulties). Increased risk of preeclampsia and placental abruption. Use only if maternal benefit outweighs fetal risk. |
■ FDA Black Box Warning
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; RISKS FROM CONCOMITANT USE WITH ALCOHOL; and RISK OF NALTREXONE-PRECIPITATED WITHDRAWAL.
| Serious Effects |
["Hypersensitivity to oxycodone, naltrexone, or any component","Significant respiratory depression","Acute or severe bronchial asthma","Paralytic ileus","Concurrent use of opioid antagonists or partial agonists"]
| Precautions | ["Addiction, abuse, and misuse","Life-threatening respiratory depression","Accidental ingestion","Neonatal opioid withdrawal syndrome","CYP3A4 interaction","Concomitant use with benzodiazepines or other CNS depressants","Severe hypotension","Gastrointestinal obstruction","Seizures","Adrenal insufficiency","Naltrexone-precipitated withdrawal if tampered"] |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they can increase levels of amiodarone and dronedarone, raising risk of toxicity. Take with meals to reduce gastrointestinal irritation. Avoid high-fat meals that may affect absorption. Limit alcohol intake as it may worsen liver effects. |
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| Fetal Monitoring | Baseline and periodic maternal blood pressure, heart rate, and weight monitoring; assess for signs of hypertension, tachycardia, and preeclampsia. Serial fetal growth ultrasound every 4-6 weeks to detect intrauterine growth restriction. Non-stress testing or biophysical profile in third trimester if concerns arise. Monitor neonate for withdrawal symptoms (irritability, hyperexcitability, poor feeding) for 48-72 hours postpartum. |
| Fertility Effects | May impair female fertility due to hormonal disturbances (e.g., menstrual irregularities, anovulation) associated with amphetamine use. In males, case reports indicate erectile dysfunction and decreased libido; no definitive data on spermatogenesis. Effects are likely reversible upon discontinuation. Not specifically studied for Dartisla ODT. |
| Clinical Pearls | DARTISLA ODT is a combination of amiodarone and dronedarone, used for maintenance of sinus rhythm in patients with atrial fibrillation. Note that dronedarone is contraindicated in NYHA Class IV heart failure or decompensated HF. Monitor liver function, thyroid, and pulmonary status due to amiodarone component. Avoid use with strong CYP3A4 inhibitors. ODT formulation should not be chewed or crushed. |
| Patient Advice | Take this medication exactly as prescribed, usually twice daily with meals. · Place the tablet on your tongue and let it dissolve; do not swallow it whole. · Avoid grapefruit juice and grapefruit products while taking this medication. · Report any signs of liver toxicity (yellowing skin/eyes, dark urine) or lung problems (cough, shortness of breath) immediately. · Inform your doctor if you have a history of heart failure, liver disease, or thyroid disorders. · Do not stop taking this medication abruptly without consulting your doctor. · Keep a regular schedule for taking this medication. |