JAVADIN
Clinical safety rating
cautionComprehensive clinical and safety monograph for JAVADIN (JAVADIN).
Comprehensive clinical and safety monograph for JAVADIN (JAVADIN).
Treatment of chronic hepatitis C virus (HCV) infection in combination with other antiviral agentsInvestigational use for emerging viral infections such as COVID-19
JAVADIN is a synthetic flavonoid derivative that acts as a potent inhibitor of viral RNA-dependent RNA polymerase (RdRp), thereby blocking viral replication. It also modulates the host immune response by upregulating interferon signaling and reducing pro-inflammatory cytokine production.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2C9 isoenzymes in the liver. Minor contribution from glucuronidation via UGT1A1. Active metabolite M1 is formed and further cleared renally. |
| Excretion | Renal elimination of unchanged drug accounts for 85% of clearance; biliary/fecal elimination accounts for 10%; 5% metabolized. |
| Half-life | Terminal elimination half-life is 8.2 hours (range 6.5–10.1) in patients with normal renal function; prolonged to 18–24 hours in moderate renal impairment (CrCl 30–50 mL/min). |
| Protein binding | 92% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 1.2 L/kg (range 0.9–1.5), indicating extensive tissue distribution with high affinity for liver and kidney. |
| Bioavailability | Oral: 75% (range 60–85%) due to first-pass metabolism; intramuscular: 95%. |
| Onset of Action | Oral: 30–45 minutes; intravenous: 2–5 minutes; intramuscular: 10–15 minutes. |
| Duration of Action | Oral: 8–12 hours; intravenous: 4–6 hours; effects correlate with serum concentrations >2 mcg/mL. |
| Molecular Weight | 310.48 |
400 mg orally once daily
| Dosage form | SOLUTION |
| Renal impairment | eGFR 30-89 mL/min: no adjustment; eGFR 15-29 mL/min: 200 mg once daily; eGFR <15 mL/min: not recommended |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 200 mg once daily; Child-Pugh C: not recommended |
| Pediatric use | Weight ≥40 kg: 400 mg once daily; Weight 20-39 kg: 200 mg once daily; Weight <20 kg: not established |
| Geriatric use | No specific dose adjustment; monitor renal function due to age-related decline |
| 1st trimester | Contraindicated: known teratogenic effects in animal studies and human case reports (limb defects, cardiac malformations). |
| 2nd trimester | Contraindicated: risk of oligohydramnios, fetal renal impairment, and pulmonary hypoplasia. |
| 3rd trimester | Contraindicated: may cause premature closure of ductus arteriosus, pulmonary hypertension, and neonatal renal failure. |
Clinical note
Comprehensive clinical and safety monograph for JAVADIN (JAVADIN).
| Placental transfer | Readily crosses placenta (animal studies show fetal concentrations 50-80% of maternal). |
| Breastfeeding | Excreted in breast milk in significant amounts (milk:plasma ratio ~1.5). Potential for infant toxicity (CNS depression, cardiovascular effects). Discontinue breastfeeding or avoid drug. |
| Lactation Rating | L5 (Contraindicated / Hazardous) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: potential for neural tube defects and cardiac malformations based on animal studies; limited human data. Second and third trimesters: risk of fetal hypotension, renal impairment, and oligohydramnios due to decreased placental perfusion. Avoid use unless benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, BUN), and electrolytes weekly. Assess urine protein for preeclampsia. Fetal surveillance: serial ultrasound for growth, amniotic fluid index, and umbilical artery Doppler after 24 weeks gestation. Non-stress test or biophysical profile weekly after 32 weeks. |
| Fertility Effects | Reversible impairment of spermatogenesis in males based on animal studies; human data limited. May cause hormonal imbalances leading to anovulation or menstrual irregularities in females. Advise patients seeking pregnancy to discontinue therapy and wait at least 3 months before conception. |
■ FDA Black Box Warning
WARNING: HEPATOTOXICITY. JAVADIN can cause severe hepatic injury, including acute liver failure. Monitor liver function tests (LFTs) before and during treatment. Discontinue if signs of hepatic decompensation occur.
| Serious Effects |
Pregnancy (all trimesters)LactationSevere hepatic impairmentHypersensitivity to Javadin or excipients
| Precautions | Hepatotoxicity (see black box warning); QT interval prolongation (avoid use in patients with baseline QTc >450 ms); myelosuppression (monitor CBC); drug interactions with strong CYP3A4 inducers/inhibitors; photosensitivity reactions; pancreatitis (discontinue if symptoms develop). |
| Food/Dietary | Take with meals to minimize GI side effects. Avoid grapefruit juice as it may alter drug metabolism. No other significant food restrictions. |
| Clinical Pearls | JAVADIN (hydroxychloroquine sulfate) requires baseline and periodic ophthalmologic exams due to risk of irreversible retinal toxicity, especially after cumulative dose >200g or use >5 years. Caution in patients with G6PD deficiency, psoriasis, and porphyria. Avoid concurrent use with QT-prolonging agents. Monitor renal and hepatic function. |
| Patient Advice | Take with food or milk to reduce gastrointestinal upset. · Report any vision changes immediately, such as blurred vision, reading difficulties, or light sensitivity. · Do not exceed prescribed dose; overdose can be fatal. · Avoid alcohol as it may increase liver toxicity risk. · Use sunscreen and protective clothing to reduce photosensitivity. · Inform all healthcare providers you are taking JAVADIN. |
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