Usage
- Aviptadil is prescribed for the treatment of acute respiratory distress syndrome (ARDS) in patients with severe COVID-19. It has also been studied for other respiratory conditions like asthma, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary hypertension, pulmonary fibrosis, and sarcoidosis. Additionally, it has been used in the treatment of erectile dysfunction in some countries.
- Pharmacologically, Aviptadil is classified as a synthetic vasoactive intestinal peptide (VIP) analog.
- Its mechanism of action involves binding to VIP receptors, particularly VPAC1 receptors on alveolar type II cells in the lungs. This binding leads to a reduction in inflammatory cytokines, inhibits viral replication, and has vasodilatory and bronchodilating effects. It may also prevent surfactant depletion.
Alternate Names
- Aviptadil is also known as vasoactive intestinal peptide (VIP), RLF-100, and Zyesami (trade name).
How It Works
- Pharmacodynamics: Aviptadil binds to VIP receptors, specifically VPAC1, leading to a reduction in the release of inflammatory cytokines, such as TNF-alpha. This anti-inflammatory effect helps to mitigate the cytokine storm associated with ARDS and COVID-19. It also has vasodilatory effects, primarily on the pulmonary vasculature, leading to decreased pulmonary vascular resistance and pulmonary arterial pressure, with increased cardiac output.
- Pharmacokinetics: Aviptadil is primarily administered intravenously or via inhalation. It has a short half-life of approximately 1-2 minutes and an apparent volume of distribution of 14 mL/kg. Aviptadil is predominantly eliminated by the kidneys, with about 35% eliminated in the first 4 hours and 90% within 24 hours.
- Mode of Action: Aviptadil binds to VPAC1 receptors on alveolar type II cells, which are the same cells targeted by the SARS-CoV-2 virus. This binding prevents viral replication and the inflammatory cascade that leads to lung injury. It also affects pulmonary vasculature.
- Receptor Binding: Aviptadil primarily binds to VPAC1 receptors.
- Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults (for ARDS in severe COVID-19):
- Intravenous infusion: Administered via infusion pump in escalating doses over 3 consecutive days.
- Day 1: 0.166 mcg/kg/hr (equivalent to 1 vial)
- Day 2: 0.332 mcg/kg/hr (equivalent to 2 vials)
- Day 3: 0.498 mcg/kg/hr (equivalent to 3 vials)
- Infusion Duration: Depends on body weight.
- <60 kg: 14-hour infusions
- 60-90 kg: 12-hour infusions
-
90 kg: 10-hour infusions
Children:
- Limited data are available for pediatric use. Consult a specialist if considering Aviptadil for children.
Special Cases:
- Elderly Patients: Close monitoring is recommended, and dosage adjustments may be necessary.
- Patients with Renal Impairment: Dosage modifications are likely required due to the renal elimination of Aviptadil. Consult a nephrologist for guidance.
- Patients with Hepatic Dysfunction: While hepatic metabolism is not the primary elimination pathway, monitor patients closely.
- Patients with Comorbid Conditions: Use with caution in patients with cardiovascular or cerebrovascular conditions.
Clinical Use Cases
- Specific dosage recommendations for various clinical situations (intubation, surgical procedures, mechanical ventilation, ICU use, emergency situations) are still under investigation. Follow local guidelines and consult with specialists.
Dosage Adjustments
- Adjust dosages based on patient response and tolerance. Consider renal function, hepatic function, and other comorbid conditions.
Side Effects
Common Side Effects
- Diarrhea
- Hypotension
- Flushing (facial or cutaneous)
- Infusion-related reactions (e.g., tachycardia)
Rare but Serious Side Effects
- Allergic reactions (e.g., rash, itching, swelling, difficulty breathing, anaphylaxis)
- Severe hypotension
- Electrolyte imbalances
Long-Term Effects
- Long-term effects are not fully understood due to limited data on chronic use.
Adverse Drug Reactions (ADR)
- Severe allergic reactions
- Significant hypotension requiring intervention
- Severe diarrhea
Contraindications
- Hypersensitivity to Aviptadil or any of its components
- Severe cardiovascular or cerebrovascular conditions (use with caution)
- Pregnancy and breastfeeding (consult a specialist)
- End-stage liver disease
- Active C. difficile infection
Drug Interactions
- Limited data are available on drug-drug interactions.
- Caution is advised when using Aviptadil with antihypertensive medications as it can potentiate hypotensive effects.
- Monitor patients closely when co-administering with corticosteroids or immunosuppressants.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not established. Aviptadil is contraindicated during pregnancy due to potential fetal risks observed in animal studies.
- Breastfeeding: Aviptadil is contraindicated during breastfeeding due to unknown risks to infants.
Drug Profile Summary
- Mechanism of Action: Synthetic VIP analog; binds to VPAC1 receptors, reducing inflammation, improving oxygenation, and potentially preventing viral replication.
- Side Effects: Diarrhea, hypotension, flushing, infusion-related reactions, allergic reactions (rare).
- Contraindications: Hypersensitivity, severe cardiovascular/cerebrovascular conditions, pregnancy, breastfeeding, end-stage liver disease, active C. difficile infection.
- Drug Interactions: Limited data; caution with antihypertensives, corticosteroids, and immunosuppressants.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: IV infusion, escalating doses over 3 days; adjust based on weight and patient response.
- Monitoring Parameters: Blood pressure, heart rate, respiratory status, electrolyte levels.
Popular Combinations
- Limited data are available on beneficial drug combinations. The combination of Aviptadil with phentolamine is approved for erectile dysfunction in some countries. Further research is needed to establish effective combinations for other indications.
Precautions
- Pre-screening for allergies and relevant medical conditions (cardiovascular, cerebrovascular, hepatic, renal).
- Monitor vital signs (blood pressure, heart rate, respiratory rate) closely.
- Monitor for electrolyte imbalances.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Aviptadil in ARDS associated with severe COVID-19?
A: Adults: IV infusion at escalating doses (0.166, 0.332, and 0.498 mcg/kg/hr) over 3 consecutive days. Dosage adjustments may be needed depending on weight and patient tolerance. Pediatric dosing is not well established.
Q2: What is the mechanism of action of Aviptadil?
A: Aviptadil primarily binds to VPAC1 receptors on alveolar type II cells, reducing inflammation and potentially inhibiting viral replication.
Q3: What are the common side effects of Aviptadil?
A: Diarrhea, hypotension, flushing, and infusion-related reactions (e.g., tachycardia).
Q4: Is Aviptadil safe to use during pregnancy or breastfeeding?
A: No, Aviptadil is contraindicated in both pregnancy and breastfeeding.
Q5: Are there any significant drug interactions with Aviptadil?
A: Limited data are available; caution is advised with antihypertensives, corticosteroids, and immunosuppressants. Close monitoring of patients is essential.
Q6: What are the contraindications for Aviptadil use?
A: Hypersensitivity, severe cardiovascular or cerebrovascular conditions, pregnancy, breastfeeding, end-stage liver disease, and active C. difficile infection.
Q7: How is Aviptadil eliminated from the body?
A: Primarily via renal excretion. Dosage adjustments may be needed in patients with renal impairment.
Q8: What monitoring parameters are important for patients receiving Aviptadil?
A: Blood pressure, heart rate, respiratory status, and electrolyte levels.
Q9: What is the role of Aviptadil in treating erectile dysfunction?
A: In some countries, Aviptadil, in combination with phentolamine, is approved for the treatment of erectile dysfunction. This involves intracavernosal injection. The dose used for ED is considerably lower than the dose for ARDS.
Q10: Are there any other uses of Aviptadil being investigated?
A: Aviptadil has been studied in clinical trials for various respiratory conditions, including asthma, COPD, cystic fibrosis, pulmonary hypertension, pulmonary fibrosis, and sarcoidosis.
