Argatroban
ACOVA
What it isSynthetic direct thrombin inhibitor given by IV infusion; standard anticoagulant for heparin-induced thrombocytopenia.
Why this oneIt has no cross-reactivity with HIT antibodies and, being hepatically cleared, works in the renal failure that often accompanies HIT.
What limits itNo antidote. Raises INR independently of warfarin, complicating transition: overlap is required, with an adjusted INR target.
Principal riskHemorrhage; dose reduction in hepatic impairment
Classes and tags
Clinical profile
FDA label
Read the full label on DailyMed ↗
NO BOXED WARNINGS
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Heparin-induced thrombocytopenia (HIT) — prophylaxis/treatment of thrombosis | Adults (no hepatic impairment) | IV 2 mcg/kg/min continuous infusion (discontinue heparin, obtain baseline aPTT first) | aPTT 1.5–3× baseline (not >100 sec); check 2 h after start and after any dose change | IV 10 mcg/kg/min |
| PCI in patients with or at risk for HIT | Adults (no hepatic impairment) | IV bolus 350 mcg/kg over 3–5 min + infusion 25 mcg/kg/min | ACT 300–450 sec (check 5–10 min after bolus/rate change); 15–30 mcg/kg/min per ACT | IV 40 mcg/kg/min with additional 150 mcg/kg boluses (procedural complications) |
Titration HIT: recheck aPTT 2 h after initiation/any change before adjusting; PCI: recheck ACT 5–10 min after each bolus or rate change
Renal Undefined
Hepatic HIT with moderate–severe impairment (Child-Pugh): start IV 0.5 mcg/kg/min, titrate carefully (clearance ↓4-fold; reversal may take >4 h). Avoid in PCI with clinically significant hepatic disease or AST/ALT ≥3× ULN
Instructions
- 250 mg/2.5 mL (100 mg/mL) concentrate: dilute 100-fold to 1 mg/mL in NS, D5W, or LR (e.g. 250 mg per 250 mL); do not mix with other drugs before dilution; invert bag 1 min; diluted solution stable 24 h at room temp in indoor light (96 h protected from light, room temp or refrigerated)
- 50 mg/50 mL (1 mg/mL) vial: ready for IV infusion — do NOT dilute; discard if cloudy/precipitate
- Continued anticoagulation after PCI: 2 mcg/kg/min adjusted to aPTT
- Warfarin conversion: no warfarin loading dose; overlap therapies; at argatroban ≤2 mcg/kg/min stop argatroban when INR >4 on combined therapy, recheck INR 4–6 h after stopping; at >2 mcg/kg/min first reduce to 2 mcg/kg/min and recheck INR in 4–6 h
Available strengths
- inj 1, 100 mg/mL
Contraindications
- Major bleeding
Cautions
- Hemorrhage can occur at any site — unexplained fall in hematocrit or BP may indicate bleeding; intracranial and retroperitoneal hemorrhage reported
- Increased bleeding risk: severe hypertension, recent lumbar puncture/spinal anesthesia/major surgery (brain, spinal cord, eye), bleeding disorders, GI lesions; concomitant antiplatelets/thrombolytics/anticoagulants
- Hepatic impairment: reduced clearance, prolonged anticoagulant effect after stopping
- aPTT is the monitoring test for HIT dosing; PT/INR prolonged beyond warfarin alone during coadministration
Adverse reactions
- HIT (>5%): dyspnea, hypotension, fever, diarrhea, sepsis, cardiac arrest
- PCI (>5%): chest pain, hypotension, back pain, nausea, vomiting, headache
- Bleeding: GI and GU/hematuria most common; major bleeding 5.3% in HIT trials
Pregnancy Limited data suggest no association with adverse fetal outcomes; anticoagulant use risks bleeding in mother and fetus — monitor
Lactation No data on presence in human milk (present in rat milk); weigh benefit vs risk
Cost
| Strength | #/mo | generic $/unit | CostPlus | |
|---|---|---|---|---|
| 1 mg/mL | inj | per unit | not offered | |
| 100 mg/mL | inj | per unit | not offered |
Open Argatroban in the interactive console ↗
Self-check
- Why can argatroban be used in renal failure accompanying HIT?
Hepatic clearance. - How does argatroban affect INR independently of warfarin?
Raises it.