Indinavir

Usage

• Indinavir is prescribed, in combination with other antiretroviral agents, for the treatment of HIV infection. It is a protease inhibitor that works by inhibiting the protease enzyme, which is essential for HIV replication. This action reduces the viral load in the blood and helps to improve the immune system. It is important to understand that Indinavir does not cure HIV infection or AIDS. It also does not prevent the transmission of HIV to others.
• Pharmacological Classification: Antiretroviral, Protease Inhibitor

Alternate Names

• International/Regional Variations: The generic name “indinavir” is commonly used internationally.
• Brand Names: Crixivan

How It Works

• Pharmacodynamics: Indinavir inhibits HIV protease, preventing the cleavage of viral precursor proteins necessary for the assembly of infectious viral particles. This leads to the production of immature, non-infectious virions.
• Pharmacokinetics:
  • Absorption: Oral absorption is variable. Food can reduce absorption, therefore it is generally recommended to take indinavir on an empty stomach or with a light, low-fat meal. Ritonavir boosting can improve bioavailability and allow for less frequent dosing.
  • Metabolism: Primarily metabolized by the liver via CYP3A4 enzyme. This makes it susceptible to numerous drug interactions.
  • Elimination: Excreted in both urine and feces. Dosage adjustments may be required for patients with renal or hepatic impairment.
• Mode of Action: Indinavir competitively binds to the active site of HIV protease, blocking its function. This inhibition prevents the maturation of new virus particles, reducing the viral load.
• Receptor Binding/Enzyme Inhibition: Inhibits HIV protease enzyme.
• Elimination Pathways: Hepatic metabolism (CYP3A4), renal and fecal excretion.

Dosage

Standard Dosage

Adults:

• Unboosted Indinavir: 800 mg orally every 8 hours.
• Indinavir with Ritonavir Boosting: 800 mg indinavir with 100 mg or 200 mg ritonavir every 12 hours.
• It’s important to take indinavir on an empty stomach, one hour before or two hours after meals, unless boosted with ritonavir.

Children:

• Dosing is based on body surface area (BSA). A common dose is 500 mg/m² every 8 hours. However, due to the higher risk of nephrolithiasis and the availability of other protease inhibitors, indinavir is generally not recommended for children. Consult pediatric HIV treatment guidelines for specific recommendations.

Special Cases:

• Elderly Patients: Dose adjustments may be necessary based on kidney and liver function.
• Patients with Renal Impairment: Data for dose adjustment is limited. Use with caution and monitor closely.
• Patients with Hepatic Dysfunction: Mild to moderate hepatic impairment: 600 mg every 8 hours. No data are available for severe hepatic impairment.
• Patients with Comorbid Conditions: Use with caution in patients with diabetes, hemophilia, or hepatitis.

Clinical Use Cases

Indinavir’s usage is limited to the treatment of HIV infection in combination with other antiretroviral agents. It’s not indicated for specific clinical scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.

Dosage Adjustments

Dose modifications are necessary based on hepatic impairment, concomitant medications (especially CYP3A4 inhibitors or inducers), and pregnancy.

Side Effects

Common Side Effects

• Nausea, vomiting, diarrhea, abdominal pain
• Headache, dizziness, fatigue
• Rash, dry skin

Rare but Serious Side Effects

• Nephrolithiasis (kidney stones)
• Hepatotoxicity (liver damage)
• Hyperbilirubinemia (jaundice)
• Pancreatitis
• Fat redistribution (lipodystrophy)
• Hyperglycemia (high blood sugar)

Long-Term Effects

• Metabolic changes (dyslipidemia, insulin resistance)
• Chronic kidney disease (with prolonged nephrolithiasis)
• Cardiovascular disease (associated with metabolic changes)

Adverse Drug Reactions (ADR)

• Severe skin reactions (Stevens-Johnson syndrome)
• Anaphylaxis
• QT prolongation (rare)

Contraindications

• Hypersensitivity to indinavir
• Co-administration with certain medications metabolized by CYP3A4, where elevated levels can cause serious adverse events (e.g., alfuzosin, amiodarone, pimozide, rifampin, St. John’s wort, triazolam, ergot derivatives, simvastatin, lovastatin, etc.).

Drug Interactions

Indinavir is extensively metabolized by CYP3A4 and can interact with numerous medications. Examples include:

• CYP3A4 Inhibitors: Ketoconazole, itraconazole, ritonavir (can increase indinavir levels)
• CYP3A4 Inducers: Rifampin, St. John’s wort (can decrease indinavir levels)
• Other: Certain antiarrhythmics, HMG-CoA reductase inhibitors, sedatives, and many others.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (use only if benefit outweighs risk). Unboosted indinavir is not recommended during pregnancy due to lower drug exposures. Consult current HIV treatment guidelines for recommendations on antiretroviral use during pregnancy.
• Breastfeeding: Indinavir is present in human milk. Breastfeeding is not recommended for HIV-infected mothers due to the risk of HIV transmission.

Drug Profile Summary

• Mechanism of Action: HIV protease inhibitor, prevents viral maturation.
• Side Effects: Nausea, vomiting, diarrhea, kidney stones, liver problems, metabolic changes.
• Contraindications: Hypersensitivity, concomitant use of certain CYP3A4 substrates.
• Drug Interactions: Numerous, particularly with CYP3A4 inhibitors and inducers.
• Pregnancy & Breastfeeding: Not recommended.
• Dosage: 800 mg every 8 hours (unboosted), 800 mg with ritonavir every 12 hours (boosted).
• Monitoring Parameters: HIV RNA viral load, CD4 cell count, renal and liver function tests, blood glucose, lipid profile.

Popular Combinations

Indinavir is rarely used now. Historically, it was used with nucleoside reverse transcriptase inhibitors (NRTIs) like zidovudine and lamivudine. Ritonavir is used to boost indinavir levels.

Precautions

• Monitor renal function, particularly for signs of nephrolithiasis.
• Monitor liver function.
• Screen for diabetes and manage blood glucose as needed.
• Monitor lipid profile.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Indinavir?

A: 800 mg orally every 8 hours (unboosted) or 800 mg with ritonavir boosting every 12 hours.

Q2: What are the most common side effects of Indinavir?

A: Nausea, vomiting, diarrhea, abdominal pain, headache, and rash.

Q3: What are the serious side effects of Indinavir?

A: Kidney stones, liver damage, hyperbilirubinemia, pancreatitis, and metabolic abnormalities.

Q4: Can Indinavir be used during pregnancy?

A: Unboosted Indinavir is generally not recommended. Discuss alternative regimens with an expert in HIV and pregnancy management.

Q5: Can Indinavir be used during breastfeeding?

A: No, breastfeeding is not recommended for HIV-infected mothers.

Q6: What are the major drug interactions with Indinavir?

A: Indinavir interacts with numerous drugs metabolized by CYP3A4, including certain antiarrhythmics, statins, and antifungals.

Q7: How does Indinavir work?

A: Indinavir is a protease inhibitor that blocks the activity of HIV protease, preventing the formation of mature, infectious viral particles.

Q8: Does Indinavir cure HIV infection?

A: No, Indinavir does not cure HIV infection or AIDS, but it helps control the virus.

Q9: Why is adequate hydration important when taking Indinavir?

A: Adequate hydration helps prevent the formation of kidney stones, a common side effect of Indinavir.