Alteplase

Usage

Alteplase is prescribed for the treatment of acute myocardial infarction (AMI), acute ischemic stroke (AIS), acute massive pulmonary embolism (PE), and for restoring function to occluded central venous access devices (CVAD). It is classified as a thrombolytic agent. Alteplase’s mechanism of action involves converting plasminogen to plasmin, an enzyme that degrades fibrin, the primary component of thrombi (blood clots). This fibrinolytic activity leads to the dissolution of existing clots.

Alternate Names

Alteplase is also known as recombinant tissue plasminogen activator (rt-PA). Brand names for alteplase include Activase, Cathflo Activase, and Actilyse.

How It Works

Pharmacodynamics: Alteplase acts by binding to fibrin within a thrombus. This binding catalyzes the conversion of plasminogen to plasmin, a serine protease. Plasmin then degrades the fibrin matrix of the thrombus, leading to its dissolution. Alteplase has a greater fibrin specificity than other plasminogen activators, such as streptokinase, potentially reducing the risk of systemic fibrinogenolysis and bleeding complications.

Pharmacokinetics: Alteplase is administered intravenously. It is rapidly cleared from the circulation primarily through hepatic metabolism, with a short half-life of approximately 5 minutes. Elimination is predominantly hepatic, with a small amount of renal excretion.

Mode of Action: Alteplase’s mode of action is highly specific to fibrin. It binds preferentially to fibrin-bound plasminogen, promoting localized plasmin generation and thrombolysis while minimizing systemic activation of plasminogen and the subsequent breakdown of circulating fibrinogen.

Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Alteplase exerts its effects through enzymatic activation rather than receptor binding, enzyme inhibition, or neurotransmitter modulation. Its primary interaction is with fibrin and plasminogen within the clot.

Elimination Pathways: Alteplase is mainly cleared via hepatic metabolism, with a negligible contribution from renal excretion. There’s no significant involvement of CYP450 enzymes in its metabolism.

Dosage

Standard Dosage

Adults:

• Acute Ischemic Stroke: 0.9 mg/kg (maximum 90 mg) IV over 60 minutes, with 10% of the total dose given as an initial IV bolus over 1 minute. Administer within 3-4.5 hours (some guidelines allow up to 9 hours in specific cases with perfusion mismatch confirmed by imaging) of symptom onset.

• Acute Myocardial Infarction: Accelerated regimen (within 6 hours of symptom onset):

  • <65 kg: 15 mg IV bolus, then 0.75 mg/kg (max 50 mg) over 30 minutes, followed by 0.5 mg/kg (max 35 mg) over 60 minutes.
  • ≥65 kg: Accelerated infusion (90 mins) total dose not exceeding 100 mg: 15 mg bolus then, 0.75 mg/kg (up to 50mg) over 30 mins then, 0.5 mg/kg (up to 35 mg) over 60 minutes.
  • 3-hour infusion (6-12 hours after symptom onset): 100 mg total dose: 6-10 mg IV bolus over 1-2 min, then 50-54 mg over the rest of the first hour, then 20 mg/hr for the next 2 hours. For <65kg, adjust the dose proportionally (1.25 mg/kg over 3 hrs total).

• Acute Massive Pulmonary Embolism: 100 mg IV infusion over 2 hours. For patients <65 kg, the total dose should not exceed 1.5 mg/kg.

• Central Venous Access Device Occlusion:

  • <30 kg: Instill a volume of 1 mg/mL solution equal to 110% of the internal lumen volume of the device (maximum 2 mg).
  • ≥30 kg: Instill 2 mg into the occluded device. May repeat dose after 2 hours if needed (maximum total dose of 4 mg in one session).

Children:

• Ischemic Stroke (2-17 years): 0.9 mg/kg (maximum 90 mg) IV over 60 minutes, with 10% of the total dose as an initial IV bolus over 1 minute. Administer within 4.5 hours of symptom onset.
• CVAD Occlusion: Refer to adult dosing.
• Other Conditions: Consult pediatric guidelines.

Special Cases:

• Elderly Patients: Caution is advised due to increased risk of bleeding. Consider lower doses in patients >75 years.
• Patients with Renal Impairment: No dose adjustment is typically necessary.
• Patients with Hepatic Dysfunction: Caution is recommended.
• Patients with Comorbid Conditions: Individualized dosing may be required depending on the condition.

Clinical Use Cases

Dosing remains consistent with standard dosages regardless of the clinical setting (Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations).

Dosage Adjustments

Dose adjustments are primarily weight-based, particularly for AMI and stroke. For hepatic impairment, individualization of dosage may be needed based on the severity of dysfunction. Genetic polymorphisms affecting drug metabolism are not currently relevant to alteplase dosing.

Side Effects

Common Side Effects

Bleeding (including internal bleeding, bruising, and bleeding from puncture sites), nausea, vomiting, fever.

Rare but Serious Side Effects

Intracranial hemorrhage, stroke, angioedema, allergic reactions (anaphylaxis), cholesterol embolism.

Long-Term Effects

No specific long-term side effects from a single course of alteplase are typically reported.

Adverse Drug Reactions (ADR)

Significant ADRs requiring immediate intervention include major bleeding (especially intracranial), severe allergic reactions, and stroke.

Contraindications

• Absolute: Active internal bleeding, any history of intracranial hemorrhage, recent intracranial or spinal surgery/trauma, known bleeding diathesis, severe uncontrolled hypertension, aortic dissection.
• Relative: History of stroke, recent major surgery or trauma, uncontrolled hypertension, conditions increasing bleeding risk (e.g., peptic ulcer, hemorrhagic ophthalmic conditions).

Drug Interactions

Alteplase interacts with anticoagulants (e.g., heparin, warfarin, DOACs), antiplatelet agents (e.g., aspirin, clopidogrel), and NSAIDs, increasing the risk of bleeding. No significant CYP450 interactions are known. Concomitant use of these medications should be carefully evaluated.

Pregnancy and Breastfeeding

Alteplase is FDA Pregnancy Category C. It is embryocidal in rabbits. Use only if potential benefit outweighs fetal risk. It is unknown if alteplase is excreted in human milk. Caution is advised during breastfeeding.

Drug Profile Summary

• Mechanism of Action: Converts plasminogen to plasmin, leading to fibrinolysis and clot breakdown.
• Side Effects: Bleeding, nausea, vomiting, fever; rarely, intracranial hemorrhage, stroke, angioedema.
• Contraindications: Active bleeding, intracranial hemorrhage history, recent surgery/trauma, bleeding disorders.
• Drug Interactions: Anticoagulants, antiplatelet agents, NSAIDs.
• Pregnancy & Breastfeeding: Category C; use with caution.
• Dosage: Refer to detailed dosage guidelines.
• Monitoring Parameters: Neurological status, blood pressure, signs of bleeding, hemoglobin, hematocrit, platelets, fibrinogen.

Popular Combinations

Alteplase may be administered concurrently with heparin and aspirin for AMI. However, this combination increases bleeding risk.

Precautions

• General Precautions: Monitor for bleeding and allergic reactions. Monitor neurological status (in stroke patients) and vital signs. Assess for contraindications before administering.
• Specific Populations: Assess risk/benefit carefully in elderly, pregnant/breastfeeding women, and children.
• Lifestyle Considerations: No specific lifestyle considerations.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Alteplase?

A: Dosing depends on the indication. See detailed dosage section above.

Q2: What is the maximum dose of Alteplase for acute ischemic stroke?

A: 90 mg.

Q3: What are the major contraindications for Alteplase use?

A: Active internal bleeding, history of intracranial hemorrhage, recent intracranial or spinal surgery/trauma, severe uncontrolled hypertension, aortic dissection.

Q4: What are the most common side effects of Alteplase?

A: Bleeding, nausea, and vomiting.

Q5: Can Alteplase be used in pregnant women?

A: It’s a Pregnancy Category C drug. Use only if the benefit outweighs the potential fetal risk.

Q6: How is Alteplase administered for central venous access device occlusion?

A: It is instilled directly into the occluded catheter.

Q7: What are the key monitoring parameters during Alteplase therapy?

A: Neurological status, blood pressure, signs of bleeding, hemoglobin, hematocrit, platelets, fibrinogen levels.

Q8: How does Alteplase interact with other anticoagulants?

A: It increases the risk of bleeding when used with other anticoagulants or antiplatelet agents.

Q9: What is the role of Alteplase in acute myocardial infarction?

A: It reduces mortality and the incidence of heart failure by dissolving the clot causing the infarction.