Hirulog

Hirulog Uses, Dosage, Side Effects, Food Interaction and all others data.

Hirulog directly inhibits thrombin by specifically binding both to the catalytic site and to the anion-binding exosite of circulating and clot-bound thrombin. Thrombin is a serine proteinase that plays a central role in the thrombotic process, acting to cleave fibrinogen into fibrin monomers and to activate Factor XIII to Factor XIIIa, allowing fibrin to develop a covalently cross-linked framework which stabilizes the thrombus; thrombin also activates Factors V and VIII, promoting further thrombin generation, and activates platelets, stimulating aggregation and granule release. The binding of bivalirudin to thrombin is reversible as thrombin slowly cleaves the bivalirudin-Arg3-Pro4 bond, resulting in recovery of thrombin active site functions.In in vitro studies, bivalirudin inhibited both soluble (free) and clot-bound thrombin, was not neutralized by products of the platelet release reaction, and prolonged the activated partialthromboplastin time (aPTT), thrombin time (TT), and prothrombin time (PT) of normal human plasma in a concentration-dependent manner. The clinical relevance of these findings is unknown.

Hirulog mediates an inhibitory action on thrombin by directly and specifically binding to both the catalytic site and anion-binding exosite of circulating and clot-bound thrombin. The action of bivalirudin is reversible because thrombin will slowly cleave the thrombin-bivalirudin bond which recovers the active site of thrombin.

Trade Name Hirulog
Availability Prescription only
Generic Bivalirudin
Bivalirudin Other Names Bivalirudin, Bivalirudina, Bivalirudinum
Related Drugs amlodipine, aspirin, metoprolol, carvedilol, propranolol, clopidogrel, atenolol, Plavix, Integrilin, Angiomax
Type
Formula C98H138N24O33
Weight Average: 2180.2853
Monoisotopic: 2178.985813062
Protein binding

Other than thrombin and red blood cells, bivalirudin does not bind to plasma proteins.

Groups Approved, Investigational
Therapeutic Class Anti-platelet drugs
Manufacturer
Available Country
Last Updated: September 19, 2023 at 7:00 am
Hirulog
Hirulog

Uses

Hirulog is used for:

  • Anticoagulant in Patients Undergoing PTCA/PCI or PCI with HITS/HITTS
  • Unstable Angina/Non-ST-Elevation MI (Off-label)
  • STEMI Undergoing Primary PCI (Off-label)
  • Heparin-induced Thrombocytopenia

Renal Impairment: The clearance of Hirulog was reduced approximately 20% in patients with moderate and severe renal impairment and was reduced approximately 80% in dialysis-dependent patients.The infusion dose of Hirulog may need to be reduced, and anticoagulant status monitored in patients with renal impairment
  • ClCr 30 to 50 mL/min: Administer infusion at rate of 1.75 mg/kg/h.
  • ClCr less than 30 mL/min: Reduce infusion rate to 1 mg/kg/h.
Hemodialysis: Reduce infusion rate to 0.25 mg/kg/h. No reduction in bolus dose needed.

Pediatric Use: The safety and effectiveness of Hirulog in pediatric patients have not been established.

Geriatric Use: Elderly patients experienced more bleeding events than younger patients. Patients treated with Hirulog experienced fewer bleeding events in each age stratum, compared to heparin.

Hirulog is also used to associated treatment for these conditions: Acute Coronary Syndrome (ACS), Thrombotic events

How Hirulog works

Inhibits the action of thrombin by binding both to its catalytic site and to its anion-binding exosite. Thrombin is a serine proteinase that plays a central role in the thrombotic process, acting to cleave fibrinogen into fibrin monomers and to activate Factor XIII to Factor XIIIa, allowing fibrin to develop a covalently cross-linked framework which stabilizes the thrombus; thrombin also activates Factors V and VIII, promoting further thrombin generation, and activates platelets, stimulating aggregation and granule release.

Dosage

Hirulog dosage

PCI/PTCA: IV Bolus dose of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for duration of PCI procedure. Five minutes after bolus dose, obtain ACT and administer additional bolus of 0.3 mg/kg if indicated.

HIT/HITTS: IV Bolus dose of 0.75 mg/kg, followed by a continuous infusion at a rate of 1.75 mg/kg/h for the duration of the procedure.

Continuation of Therapy: IV Infusion may be continued for up to 4 h post-procedure as indicated. After 4 h, an additional IV infusion of 0.2 mg/kg/h for up to 20 h may be given if needed.

Concomitant Therapy: Hirulog is intended for concurrent use with aspirin (300 to 325 mg/day).

  • For IV administration only. Not for intradermal, subcutaneous, IM, or intra-arterial administration.
  • Reconstitute powder for injection with 5 mL sterile water for injection. Gently swirl until powder is dissolved.
  • For initial bolus infusion, further dilute each reconstituted via in 50 mL of 5% dextrose in water or sodium chloride 0.9% for injection to yield a final concentration of 5 mg/mL.
  • For low rate infusion, further dilute each reconstituted vial in 500 mL of 5% dextrose in water or sodium chloride 0.9% for injection to yield a final concentration of 0.5 mg/mL.
  • Do not mix with the following drugs in the same IV line: alteplase, amiodarone, amphotericin B, chlorpromazine, diazepam, dobutamine, prochlorperazine, reteplase, streptokinase, vancomycin.
  • Reconstituted bivalirudin should be a clear to slightly opalescent, colorless to slightly yellow solution. Do not administer if reconstituted or diluted solution is discolored, cloudy, or contains particulate matter.
  • Maintain meticulous catheter technique, with frequent aspiration and flushing, paying special attention to minimizing conditions of stasis within the catheter or vessels.
  • Discard any unused reconstituted or diluted solution.

Side Effects

  • Bleeding, Body as a Whole: fever,infection, sepsis;
  • Cardiovascular: hypotension, syncope, vascular anomaly,ventricular fibrillation;
  • Nervous: cerebral ischemia, confusion, facialparalysis;
  • Respiratory: lung edema;
  • Urogenital: kidney failure, oliguria.

Toxicity

Based on a study by Gleason et al., the no-observed-adverse-effect level (NOAEL) for bivalirudin, administered to rats via intravenous infusion over a 24-hour period, was 2000 mg/kg/24 h.

Precaution

Bleeding Events: Although most bleeding associated with the use of Hirulog in PCI/PTCA occurs at the site of arterial puncture, hemorrhage can occur at any site. An unexplained fall in blood pressure or hematocrit should lead to serious consideration of a hemorrhagic event and cessation of Hirulog administration. Hirulog should be used with caution in patients with disease states associated with an increased risk of bleeding.

Coronary Artery Brachy therapy: An increased risk of thrombus formation, including fatal outcomes, has been associated with the use of Hirulog in gamma brachytherapy. If a decision is made to use Hirulog during brachytherapy procedures, maintain meticulous catheter technique, with frequent aspiration and flushing, paying special attention to minimizing conditions of stasis within the catheter or vessels.

Interaction

Co-administration of Hirulog with heparin, warfarin, thrombolytics, or GPIs was associated with increased risks of major bleeding events.

Food Interaction

  • Avoid echinacea.
  • Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.

Volume of Distribution

0.2L/kg

Elimination Route

Following intravenous administration, bivalirudin exhibits linear pharmacokinetics. The mean steady state concentration is 12.3 +/- 1.7mcg/mL after administration of an intravenous bolus of 1mg/kg followd by a 2.5mg/kg/hr intravenous infusion given over 4 hours.

Half Life

  • Normal renal function: 25 min (in normal conditions)
  • Creatinine clearance 10-29mL/min: 57min
  • Dialysis-dependant patients: 3.5h

Clearance

  • 3.4 mL/min/kg [Normal renal function]
  • 3.4 mL/min/kg [mild renal function]
  • 2.7 mL/min/kg [moderate renal function]
  • 2.8 mL/min/kg [severe renal function]
  • 1 mL/min/kg [Dialysis-dependent patients]

Elimination Route

Hirulog is cleared from plasma by a combination of renal mechanisms (20%) and proteolytic cleavage.

Pregnancy & Breastfeeding use

Pregnancy Category B. No adequate and well-controlled studies in pregnant women. As animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Hirulog is intended for use with aspirin . Because of possible adverse effects on the neonate and the potential for increased maternal bleeding, particularly during the third trimester, Hirulog and aspirin should be used together during pregnancy only if clearly needed.

Nursing Mothers: It is not known whether bivalirudin is excreted in human milk. As many drugs are excreted in human milk, caution should be exercised when Hirulog is administered to a nursing woman.

Contraindication

Hirulog is contraindicated in patients with: Active major
bleeding & Hypersensitivity (e.g., anaphylaxis) to Hirulog or its components

Acute Overdose

Cases of overdose of up to 10 times the recommended bolus or continuous infusion dose of Hirulog have been reported in clinical trials and in postmarketing reports. A number of the reported overdoses were due to failure to adjust the infusion dose of bivalirudin in persons with renal dysfunction including persons on hemodialysis . Bleeding, as well as deaths due to hemorrhage, have been observed in some reports of overdose. In cases of suspected overdosage, discontinue Hirulog immediately and monitor the patient closely for signs of bleeding. There is no known antidote to Hirulog. Hirulog is hemodialyzable

Storage Condition

Store at temperature not exceeding 30º C in a dry place. Do not freeze. Keep out of reach of children

Innovators Monograph

You find simplified version here Hirulog

Hirulog contains Bivalirudin see full prescribing information from innovator Hirulog Monograph, Hirulog MSDS, Hirulog FDA label

*** Taking medicines without doctor's advice can cause long-term problems.
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