DOJOLVI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DOJOLVI (DOJOLVI).
DOJOLVI (defibrotide) is a mixture of single-stranded and double-stranded oligonucleotides derived from porcine intestinal mucosa. Its mechanism is not fully characterized but is thought to protect endothelial cells from activation and injury, and to promote a pro-fibrinolytic and anti-thrombotic microenvironment by enhancing tissue plasminogen activator (tPA) activity and decreasing plasminogen activator inhibitor-1 (PAI-1) activity.
| Metabolism | Defibrotide is metabolized primarily by alkaline phosphatases and nucleotidases in the liver and kidney to mono- and oligonucleotides, which are further degraded to nucleosides and bases. No significant involvement of CYP450 enzymes. |
| Excretion | Primarily excreted unchanged in feces (approximately 90%) via biliary elimination; renal excretion accounts for less than 5% of the dose. |
| Half-life | Terminal elimination half-life is approximately 2.4 hours in patients with intact gastrointestinal function; this short half-life allows for rapid clearance but may require frequent dosing. |
| Protein binding | Approximately 97–99% bound to plasma proteins, primarily albumin and to a lesser extent lipoproteins. |
| Volume of Distribution | Apparent volume of distribution (Vd) is approximately 0.6 L/kg, indicating distribution primarily within the extracellular fluid and plasma volume. |
| Bioavailability | Oral bioavailability is not applicable as DOJOLVI is administered via nasogastric or gastrostomy tube; absorption is essentially complete with enteral administration due to minimal first-pass metabolism. |
| Onset of Action | When administered via nasogastric or gastrostomy tube, clinical effect (reduction in blood triglycerides) begins within 1–2 hours after administration. |
| Duration of Action | Duration of triglyceride-lowering effect is approximately 6–8 hours, consistent with the half-life; repeated dosing every 6 hours is recommended to maintain effect. |
For patients with homozygous familial hypercholesterolemia (HoFH), the recommended dose of DOJOLVI (lomitapide) is 5 mg orally once daily initially, titrated based on tolerability: 5 mg for at least 2 weeks, then increase to 10 mg, then to 20 mg, then to 40 mg, then to 60 mg (maximum recommended dose). Dose increases should occur at intervals of at least 4 weeks.
| Dosage form | LIQUID |
| Renal impairment | No specific dosage adjustment is recommended for patients with mild to moderate renal impairment. For severe renal impairment (eGFR <30 mL/min/1.73 m²), use with caution and consider a lower starting dose (e.g., 5 mg) due to increased exposure. |
| Liver impairment | DOJOLVI is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh class B or C). For mild hepatic impairment (Child-Pugh class A), the recommended starting dose is 5 mg once daily and titrate slowly, with a maximum dose of 40 mg daily. |
| Pediatric use | The safety and effectiveness of DOJOLVI in pediatric patients have not been established. Use is not recommended in patients under 18 years of age. |
| Geriatric use | Clinical studies did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. No specific dose adjustments are recommended, but use with caution due to potential for increased sensitivity and comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DOJOLVI (DOJOLVI).
| Breastfeeding | No data on presence in human milk; M/P ratio unknown. Given the high lipid content and lack of safety data, discontinue breastfeeding or postpone therapy based on importance to mother. |
| Teratogenic Risk | No human data available; in animal studies, no teratogenicity observed at clinically relevant doses. However, due to the high fat content of the drug formulation, use during pregnancy is not recommended unless clearly necessary, as elevated triglycerides can exacerbate gestational risks. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Concurrent use with systemic thrombolytic therapy"]
| Precautions | ["Hemorrhage: Increased risk of bleeding; monitor coagulation parameters and signs of bleeding, and discontinue if significant bleeding occurs.","Hypersensitivity reactions: May occur; discontinue if severe.","Fetal harm: Based on animal data, may cause fetal harm; advise pregnant women of potential risk."] |
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| Monitor maternal triglyceride and lipid panel monthly; if used in pregnancy, monitor fetal growth and amniotic fluid index via ultrasound per standard obstetrical care. |
| Fertility Effects | No data on human fertility; animal studies showed no adverse effects on fertility at clinically relevant doses. |