ANGIOMAX RTU
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ANGIOMAX RTU (ANGIOMAX RTU).
Direct thrombin inhibitor that reversibly binds to the active site of thrombin, blocking its interaction with substrates (fibrinogen, factor V, VIII, XIII, and protein C).
| Metabolism | Primarily metabolized via proteolytic cleavage (hydrolysis) by plasma proteases; minimal hepatic metabolism. |
| Excretion | Bivalirudin is cleared by a combination of renal elimination (approximately 20% unchanged in urine) and proteolytic cleavage (hepatic metabolism and other proteases). Renal clearance accounts for about 20% of total clearance. Fecal excretion is negligible (<1%). |
| Half-life | The terminal elimination half-life of bivalirudin is approximately 25 minutes in patients with normal renal function. In patients with moderate to severe renal impairment, the half-life is prolonged (e.g., up to 1 hour in patients with creatinine clearance <30 mL/min, and up to 3-4 hours in dialysis-dependent patients). This is clinically relevant for dosing adjustments and monitoring of anticoagulation. |
| Protein binding | Bivalirudin is approximately 34% bound to plasma proteins, primarily to albumin. Binding is reversible and does not saturate at therapeutic concentrations. |
| Volume of Distribution | The volume of distribution (Vd) of bivalirudin is approximately 0.2 L/kg, indicating distribution primarily in the extracellular fluid space. This low Vd reflects limited tissue penetration, consistent with its hydrophilic nature and primarily intravascular distribution. |
| Bioavailability | Bivalirudin is only administered intravenously; thus, oral bioavailability is 0%. As an IV drug, bioavailability is 100% when given by this route. |
| Onset of Action | Intravenous bolus administration of bivalirudin produces an immediate anticoagulant effect, with peak anticoagulation achieved within 5 minutes. The activated clotting time (ACT) is prolonged promptly after the bolus dose. |
| Duration of Action | The anticoagulant effect of bivalirudin lasts for approximately 1 hour after discontinuation of the infusion in patients with normal renal function. In patients with renal impairment, the effect may persist longer. The infusion is typically continued for the duration of the procedure (e.g., PCI) and for up to 4 hours post-procedure if needed. |
| Molecular Weight | 692.97 |
1 mg/kg intravenous bolus, followed by 0.15 mg/kg/min continuous intravenous infusion for up to 4 hours during percutaneous coronary intervention (PCI). For patients with heparin-induced thrombocytopenia (HIT) undergoing PCI, bolus 0.75 mg/kg, then 1.75 mg/kg/hour infusion for 4 hours.
| Dosage form | SOLUTION |
| Renal impairment | For creatinine clearance (CrCl) <30 mL/min: bolus 1 mg/kg, then infusion rate 0.15 mg/kg/min (no dose reduction needed per FDA labeling, but caution advised). For dialysis-dependent patients: avoid use or reduce infusion to 0.1 mg/kg/min. |
| Liver impairment | No specific Child-Pugh based dose adjustments; use with caution in severe hepatic impairment as bivalirudin is partially metabolized by the liver. |
| Pediatric use | Not FDA-approved for pediatric use. Limited data: for PCI in children, consider 0.75 mg/kg bolus followed by 1.75 mg/kg/hour infusion based on adult HIT protocol; adjust for renal function. |
| Geriatric use | No specific dose adjustment required based on age alone, but renal function declines with age; monitor CrCl and adjust according to renal guidelines. |
| 1st trimester | Animal studies have shown fetal harm. No adequate human studies in first trimester. Use only if potential benefit justifies potential risk to fetus. |
| 2nd trimester | May cause fetal harm (oligohydramnios, fetal renal dysfunction) when used during second trimester. Use only if clearly needed. |
| 3rd trimester | Direct-acting renin inhibitor: contraindicated in pregnancy due to risk of fetal renal dysfunction, oligohydramnios, and neonatal morbidity/mortality. Avoid in third trimester. |
Clinical note
Comprehensive clinical and safety monograph for ANGIOMAX RTU (ANGIOMAX RTU).
| Placental transfer | Animal studies indicate placental transfer. Human data limited; molecule size suggests potential for crossing. |
| Breastfeeding | Unknown if excreted in human milk. Due to potential for serious adverse reactions in nursing infants, decide whether to discontinue nursing or discontinue drug, taking into account importance of drug to mother. |
■ FDA Black Box Warning
Do not administer intramuscularly; increased risk of bleeding; fatal bleeding events have occurred.
| Serious Effects |
PregnancyHistory of angioedema related to previous use of renin inhibitors
| Precautions | Bleeding risk: Major hemorrhages may occur; monitor coagulation parameters (ACT) during PCI., Hypersensitivity reactions: Anaphylaxis and allergic reactions reported., Renal impairment: Dose adjustment required in moderate to severe renal impairment (creatinine clearance <30 mL/min)., Pregnancy: Category B; use only if clearly needed., Geriatric use: Increased risk of bleeding in elderly patients. |
| Food/Dietary | No food interactions have been reported for bivalirudin. No specific dietary restrictions are necessary. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | ANGIOMAX (bivalirudin) is a direct thrombin inhibitor. Animal studies have not demonstrated teratogenic effects. In humans, there are no adequate and well-controlled studies in pregnant women. Based on its mechanism and limited data, the risk is likely low, but it should be used only if clearly needed. No specific trimester risks have been identified. |
| Fetal Monitoring | Monitor activated clotting time (ACT) or partial thromboplastin time (aPTT) to assess anticoagulation status. Monitor for signs of bleeding in both mother and fetus. Fetal heart rate monitoring should be considered if used during pregnancy. |
| Fertility Effects | No human data on fertility. Animal studies have not shown impaired fertility at clinically relevant doses. The effect on human fertility is unknown. |
| Clinical Pearls | Angiomax RTU (bivalirudin) is a direct thrombin inhibitor used primarily in percutaneous coronary intervention (PCI) and for patients with heparin-induced thrombocytopenia (HIT). It has a short half-life (~25 minutes) and is cleared renally, so dose adjustment is required in renal impairment (CrCl <30 mL/min). No routine monitoring of aPTT or ACT is needed as effects are predictable, but ACT can be measured if desired. Reversal is not required but may be achieved with recombinant factor VIIa or hemodialysis if necessary. |
| Patient Advice | This medication is used to prevent blood clots during heart procedures or in certain blood disorders. · It is given intravenously (IV) by a healthcare professional. · Common side effects include bleeding at the injection site, back pain, and headache. · Report any signs of bleeding such as unusual bruising, red or black stools, or coughing up blood. · Avoid activities that increase bleeding risk, such as contact sports or using sharp objects, until the effects of the medication have worn off. · Inform all healthcare providers that you are taking this medication before any surgery or dental work. |