Abciximab

Abciximab is an Antiplatelet agent belonging to the pharmacological class of Glycoprotein IIb/IIIa Inhibitor.

Abciximab has been approved to relieve symptoms and also for the treatment and maintenance of Unstable angina undergoing percutaneous coronary intervention, ST-elevation myocardial infarction or non-ST elevation myocardial infarction undergoing percutaneous coronary intervention.

Following intravenous bolus administration, Abciximab's unbound plasma concentrations experience a rapid decline, marked by an initial half-life of under 10 minutes, followed by a second-phase half-life of around 30 minutes, attributed to its rapid binding to GPIIb/IIIa receptors on platelets. Platelet function typically returns to baseline within 48 hours , while Abciximab persists in circulation for up to 15 days or more, albeit now in a platelet-bound state. Administering an intravenous bolus of 0.25 mg/kg Abciximab, followed by a continuous infusion of 10 μg/min (or weight-adjusted infusion, up to 0.125 μg/kg/min or a maximum of 10 μg/min), maintains relatively consistent unbound plasma levels throughout the infusion. After infusion cessation, free plasma concentrations decline rapidly over about six hours, followed by a gradual decrease.

The common side effects of Abciximab include Vision changes, Headache, Nausea, Vomiting, Heartburn, Stomach upset, Abdominal pain, Injection site reactions (pain, bleeding, irritation), Back pain, swelling of the extremities, and Low blood pressure.

Abciximab is available in the form of Injectable Solutions.

Abciximab is approved in Germany, Japan, Malaysia, India, the U.K., and China.

Abciximab, belonging to the pharmacological class of Glycoprotein IIb/IIIa Inhibitor, acts as an Antiplatelet agent.

Abciximab attaches to the intact GPIIb/IIIa receptor on platelets, a crucial member of the integrin family of adhesion receptors that plays a pivotal role in platelet aggregation. This attachment is believed to occur through steric hindrance and changes in shape, preventing larger molecules from accessing the receptor. This mechanism doesn't involve direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa. In addition, by binding to the vitronectin receptor (also known as αvβ3 integrin), abciximab hinders the functions orchestrated by this integrin, including cell adhesion. Furthermore, abciximab obstructs the Mac-1 receptor on monocytes and neutrophils, thereby impeding monocyte adhesion.

Abciximab has been approved to relieve symptoms and also for the treatment and maintenance of Unstable angina undergoing percutaneous coronary intervention,ST-elevation myocardial infarction or non-ST elevation myocardial infarction undergoing percutaneous coronary intervention.

Abciximab is found to be available in the form of Injectable Solutions.

Abciximab can be used in the following treatment:

• Unstable angina undergoing percutaneous coronary intervention
• ST-elevation myocardial infarction or non-ST elevation myocardial infarction undergoing percutaneous coronary intervention

Abciximab can help to relieve symptoms and also for the treatment and maintenance of Unstable angina undergoing percutaneous coronary intervention, ST-elevation myocardial infarction or non-ST elevation myocardial infarction undergoing percutaneous coronary intervention.

Abciximab is approved for use in the following clinical indications:

• Unstable angina undergoing percutaneous coronary intervention
• ST-elevation myocardial infarction or non-ST elevation myocardial infarction undergoing percutaneous coronary intervention

For patients with unstable angina undergoing percutaneous coronary intervention:

Initial intravenous (IV) administration of a 0.25 mg/kg bolus at the time of the procedure, followed by a continuous infusion of 0.125 mcg/kg/minute (up to a maximum of 10 mcg/minute). This infusion can be maintained for a duration of up to 12 hours .

For individuals with either ST-elevation myocardial infarction or non-ST elevation myocardial infarction undergoing percutaneous coronary intervention (off-label use):

Begin with an IV bolus of 0.25 mg/kg administered during the PCI procedure. Subsequently, initiate an infusion at a rate of 0.125 mcg/kg/minute (with a maximum limit of 10 mcg/minute) and sustain it for a maximum of 12 hours.

Abciximab is available in the following dosage forms and strengths:

• Injectable Solutions : 2mg/ml

Injectable Solutions.

• Dosage Adjustments in Pediatric Patients:

There is found to be no detailed information regarding the use of Abciximab in the pediatric population.

There are no specific dietary requirements for Abciximab. It is typically prescribed as a medication and is not affected by food intake.

Abciximab may be contraindicated under the following conditions:

• Active internal bleeding.
• Recent clinically significant gastrointestinal (GI) or genitourinary (GU) bleeding within the past six weeks.
• History of cerebrovascular accident (CVA) within the last two years, or CVA with a significant remaining neurological deficit.
• Known hypersensitivity to any component of this product or to murine proteins.

Bleeding Risk and Abciximab:

Abciximab carries the potential to heighten the risk of bleeding, especially when used in conjunction with anticoagulants like heparin, other anticoagulants, or thrombolytics. In the Phase 3 trials, bleeding incidents were categorized as major, minor, or insignificant based on the Thrombolysis in Myocardial Infarction study group's criteria. Major bleeding events were defined as intracranial hemorrhage or a hemoglobin decrease exceeding 5 g/dL. Minor bleeding events encompassed spontaneous gross hematuria, spontaneous hematemesis, observed blood loss leading to a hemoglobin decrease of over 3 g/dL, or a decrease in hemoglobin by at least 4 g/dL without an identifiable bleeding source. Insignificant bleeding events included hemoglobin decline below 3 g/dL or a hemoglobin decrease of 3-4 g/dL without observable bleeding. In cases involving transfusions, the volume of blood lost was estimated using an adapted method from Landefeld et al.

EPIC Trial Findings:

In the EPIC trial, which employed a non-weight-adjusted standard heparin dose regimen, the most common complication during Abciximab therapy was bleeding within the initial 36 hours. Incidences of major bleeding, minor bleeding, and blood product transfusions exhibited significant increases. Notably, around 70% of patients treated with Abciximab who experienced major bleeding encountered it at the arterial access site in the groin. Furthermore, Abciximab-treated patients demonstrated higher frequencies of major bleeding events originating from gastrointestinal, genitourinary, retroperitoneal, and other sites.

Impact on Bleeding Rates:

The CAPTURE trial reported reduced bleeding rates, and the EPILOG trial further curtailed these rates through modified dosing schedules and specific patient management techniques. In the EPILOG trial, where the heparin and Abciximab dosing, sheath removal, and arterial access site guidelines from the PRECAUTIONS section were employed, the occurrence of major bleeding in Abciximab-treated patients receiving low-dose, weight-adjusted heparin was comparable to that in patients receiving placebo.

Weight Subgroups and Bleeding:

Subgroup analyses within the EPIC and CAPTURE trials unveiled that non-Q&G major bleeding was more frequent among Abciximab patients weighing less than 75 kg. Conversely, in the EPILOG trial, which employed weight-adjusted heparin dosing, the non-CABG major bleeding rates for Abciximab-treated patients didn't significantly differ based on weight subgroup.

Impact on CABG Surgery and Bleeding:

Available data suggests that Abciximab treatment wasn't linked to an elevated risk of significant bleeding in patients undergoing CABG surgery. The prevalence ranged from 3-5% in EPIC and 1-2% in the CAPTURE and EPILOG trials across all treatment arms. In certain cases, patients with prolonged bleeding times received platelet transfusions prior to surgery to address bleeding time concerns.

In the event of severe, uncontrollable bleeding that cannot be managed through pressure, the administration of Abciximab and any accompanying heparin should be promptly halted.

Precautions Regarding Bleeding:

Findings from the EPILOG trial highlight strategies to mitigate bleeding, including the use of low-dose, weight-adjusted heparin regimens, adherence to stricter anticoagulation guidelines, early removal of femoral arterial sheaths, meticulous patient and access site management, and adjustment of the Abciximab infusion dose based on weight.

Certain conditions warrant special attention:

• Bleeding diathesis
• Use of oral anticoagulants within seven days unless prothrombin time is at least 1.2 times the control value
• Thrombocytopenia (platelet count < 100,000 cells/μL)
• Recent major surgery or trauma within six weeks
• Presence of an intracranial neoplasm, arteriovenous malformation, or aneurysm
• Severe uncontrolled hypertension
• Suspected or confirmed history of vasculitis
• Prior use of intravenous dextran before or during percutaneous coronary intervention
• Administering Abciximab to patients who have undergone systemic thrombolytic therapy requires careful consideration due to potential synergistic effects on bleeding.

Administration and Bleeding Prevention:

• Exercise caution with all potential bleeding sites (catheter insertion, arterial and venous punctures, cutdown sites, needle punctures, and sites like gastrointestinal, genitourinary, and retroperitoneal).
• Minimize intramuscular injections, arterial and venous punctures, use of urinary catheters, and other procedures that may lead to bleeding.
• Favor non-compressible sites over compressible ones when establishing intravenous access (e.g., avoid subclavian or jugular veins).
• For arterial access, only puncture the anterior wall of the femoral artery to prevent bleeding. Avoid the through-and-through technique. Placement of femoral vein sheaths should be limited unless necessary.
• During femoral artery sheath placement, patients should be on complete bed rest with their head elevated and the affected limb immobilized straight. BacWgroin pain can be managed with appropriate medication.
• Discontinue heparin immediately after the procedure and remove the arterial sheath within six hours if APTT ≥ 50 seconds or ACT < 175 seconds.
• Apply pressure to the femoral artery for at least 30 minutes following sheath removal, followed by a pressure dressing.
• Maintain bed rest for six to eight hours following sheath removal or discontinuation of Abciximab, or four hours after heparin discontinuation, whichever is later.
• Regularly monitor the sheath insertion site and distal pulses of the affected leg(s).
• Certain conditions like percutaneous coronary intervention within 12 hours of acute myocardial infarction onset, prolonged interventions, and failed interventions can increase bleeding risk when combined with Abciximab.

Use with Thrombolytics, Anticoagulants, and Antiplatelet Agents:

• Abciximab has been used alongside heparin and aspirin in various trials.
• Caution is advised when using Abciximab with other drugs affecting hemostasis, including thrombolytics, oral anticoagulants, non-steroidal anti-inflammatory drugs, dipyridamole, and ticlopidine.
• Limited experience with low molecular weight dextran and Abciximab has shown potential major bleeding events .

Thrombocytopenia:

• Monitor platelet counts before treatment, two to four hours after the Abciximab bolus dose, and at 24 hours or prior to discharge (whichever comes first).
• If acute platelet decrease occurs (platelet count < 100,000 cells/μL and decrease of at least 25% from pre-treatment level), verify with additional platelet counts drawn in separate tubes containing EDTA, citrate, and heparin to rule out pseudothrombocytopenia.
• Discontinue Abciximab and manage true thrombocytopenia accordingly.

Restoration of Platelet Function:

• Discontinue Abciximab in cases of serious uncontrolled bleeding or the need for emergency surgery.
• Platelet function may be partially restored through platelet transfusions if needed.

Alcohol can sometimes interact with certain medications, affecting their effectiveness or causing adverse effects. Additionally, alcohol may exacerbate certain medical conditions that Abciximab is prescribed for, such as blood clotting disorders.

The excretion of this drug into human milk has not been determined. Given that numerous drugs are excreted in human milk, prudence is advised when administering Abciximab to breastfeeding women.

Pregnancy:

Pregnancy category C:

Abciximab has not undergone animal reproductive studies, and its impact on fertility in both male and female animals remains uncertain. The potential for Abciximab to cause harm to a developing fetus or influence reproductive capabilities in pregnant women is also unknown. Administering Abciximab to a pregnant woman should only be considered if the necessity is clearly established.

There are no specific food warnings related to the use of Abciximab has been found.

The adverse reactions related to Abciximab can be categorized as follows:

Common:

• Bleeding or easy bruising
• Nausea
• Vomiting
• Back pain
• Abdominal pain
• Headache

Less Common:

• Allergic reactions (rash, itching, swelling, severe dizziness, difficulty breathing)
• Changes in vision
• Heartburn
• Stomach upset
• Low blood pressure
• Slow heart rate
• Chest pain
• Swelling of the extremities
• Mood changes

Rare:

• Severe allergic reactions (e.g., anaphylaxis)
• Blood clotting problems
• Heart attack or worsening of heart conditions
• Stroke
• Kidney problems

The clinically relevant drug interactions of Abciximab is briefly summarized here:

Formal studies examining potential drug interactions with Abciximab have not been undertaken. Abciximab has been administered to individuals with ischemic heart disease concurrently taking a wide spectrum of medications used for angina, myocardial infarction, and hypertension. This range of medications includes heparin, warfarin, beta-adrenergic receptor blockers, calcium channel antagonists, angiotensin-converting enzyme inhibitors, intravenous and oral nitrates, and acetylsalicylic acid. Medications like heparin, other anticoagulants, thrombolytics, and antiplatelet agents can elevate the risk of bleeding. Given Abciximab's inhibition of platelet aggregation, it's important to exercise caution when using it alongside other drugs that affect blood clotting.

Individuals with elevated HACA titers might experience allergic or hypersensitivity reactions when exposed to other diagnostic or therapeutic monoclonal antibodies.

Considering the observed synergistic bleeding effects, prudent use of Abciximab therapy is recommended in patients who have undergone systemic thrombolytic therapy. In the GUSTO V trial, which randomized acute myocardial infarction patients, combining Abciximab and half-dose Reteplase was compared to full-dose Reteplase alone. The trial revealed a higher incidence of moderate to severe nonintracranial bleeding in patients receiving both Abciximab and half-dose Reteplase compared to Reteplase alone (4.6% vs. 2.3%, respectively). This difference was more pronounced in patients over 75 years old. Additionally, in this age group, a tendency towards an increased incidence of intracranial hemorrhage was noted in those taking Abciximab and half-dose Reteplase in contrast to those receiving only Reteplase.

In cases where immediate intervention is essential for unresponsive symptoms, it's advisable to first attempt percutaneous transluminal coronary angioplasty (PTCA) using Abciximab to rectify the situation. If PTCA and other suitable procedures prove ineffective and the angiographic findings suggest thrombosis as the cause, consideration may be given to administering supplemental thrombolytic therapy through the intracoronary route. Ahead of surgical procedures, the Ivy method should be employed to ascertain the bleeding time, which should ideally be 12 minutes or less.

The following are the side effects involving Abciximab:

• Vision changes
• Headache
• Nausea
• Vomiting
• Heartburn
• Stomach upset
• Abdominal pain
• Injection site reactions (pain, bleeding, irritation)
• Back pain
• Swelling of the extremities
• Low blood pressure
• Slow heart rate
• Chest pain
• Mood changes

The use of Abciximab should be prudent in the following group of special populations:

Pregnancy:

Pregnancy category C:

Abciximab has not undergone animal reproductive studies, and its impact on fertility in both male and female animals remains uncertain. The potential for Abciximab to cause harm to a developing fetus or influence reproductive capabilities in pregnant women is also unknown. Administering Abciximab to a pregnant woman should only be considered if the necessity is clearly established.

Lactation:

The excretion of this drug into human milk has not been determined. Given that numerous drugs are excreted in human milk, prudence is advised when administering Abciximab to breastfeeding women.

Pediatric:

The safety and efficacy of Abciximab in individuals under the age of 18 have not been confirmed.

Geriatric Use:

The available clinical data is inadequate to establish whether patients aged 75 years or older exhibit distinct responses to Abciximab compared to younger patients.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Abciximab.

No instances of overdose with Abciximab have been reported in human clinical trials.

Pharmacodynamics:

When single bolus doses of Abciximab ranging from 0.15 mg/kg to 0.30 mg/kg were intravenously administered to human subjects, it led to swift and dose-dependent suppression of platelet function, as assessed by ex vivo platelet aggregation upon exposure to adenosine diphosphate (ADP), or by an extension of bleeding time. At the two highest doses (0.25 mg/kg and 0.30 mg/kg), approximately 80% of GPIIb/IIIa receptors were effectively blocked two hours after injection, nearly abolishing platelet aggregation in response to 20 pM ADP. The median bleeding time was notably extended to over 30 minutes with both doses, a substantial increase from the initial baseline of about five minutes.

Administering a single bolus dose of 0.25 mg/kg followed by a continuous infusion of 10 pg/min over periods spanning 12 to 96 hours in humans resulted in a sustained and significant blockade of GPIIb/IIIa receptors (at least 80% inhibition) and suppression of platelet function (ex vivo platelet aggregation triggered by 5 pM or 20 pM ADP being less than 20% of baseline), which persisted throughout the infusion period for the majority of patients. Similar outcomes were observed with a weight-adjusted infusion dose (0.125 μg/kg/min up to a maximum of 10 μg/min) in patients weighing up to 80 kg. In cases where patients were administered a 0.25 mg/kg bolus followed by a 5 μg/min infusion for 24 hours, initial receptor blockade and inhibition of platelet aggregation were comparable, but this response wasn't maintained during the entire infusion duration.

Residual low levels of GPIIb/IIIa receptor blockade persisted for over 10 days after the cessation of the infusion. Upon discontinuation of Abciximab infusion, platelet function gradually returned to its normal state. Within 12 hours after the infusion ended, bleeding time returned to less than 12 minutes for 15 out of 20 patients (75%), and within 24 hours for 18 out of 20 patients (90%). For ex vivo platelet aggregation triggered by 5 pM ADP, it rebounded to around 50% of baseline within 24 hours post-infusion termination for 11 of 32 patients (34%), and within 48 hours for 23 of 32 patients (72%). Similarly, for ex vivo platelet aggregation in response to 20 pM ADP, it reached around 50% of baseline within 24 hours for 20 of 32 patients (62%), and within 48 hours for 28 of 32 patients (88%).

Pharmacokinetics:

After the introduction through intravenous bolus delivery, the unbound Abciximab concentrations in the plasma experience a rapid reduction, demonstrating an initial half-life of less than 10 minutes, followed by a second-phase half-life spanning around 30 minutes. This phenomenon is likely associated with swift binding to the GPIIb/IIIa receptors on platelets. Generally, platelet functionality regains its normal state within a 48-hour period (1,2). However, Abciximab remains present in the bloodstream for a duration of 15 days or even longer, but now in a state bound to platelets. By administering a bolus dose of 0.25 mg/kg Abciximab intravenously, followed by a continuous infusion of 10 μg/min (or an infusion adjusted based on weight, ranging from 0.125 μg/kg/min up to a maximum of 10 μg/min), relatively steady unbound plasma concentrations are achieved throughout the duration of the infusion. As the infusion period concludes, there is a swift decrease in free plasma concentrations over approximately six hours, succeeded by a more gradual decline.

1. https://go.drugbank.com/drugs/DB00054
2. https://www.accessdata.fda.gov/drugsatfda_docs/label/1997/abcicen110597-lab.pdf
3. https://reference.medscape.com/drug/reopro-abciximab-342146
4. https://www.rxlist.com/reopro-drug.htm
5. https://pdf.hres.ca/dpd_pm/00042357.PDF
6. https://www.drugs.com/monograph/abciximab.html