indinavir
| Product dosage: 400 mg | |||
|---|---|---|---|
| Package (num) | Per cap | Price | Buy |
| 30 | $4.12 | $123.56 $123.56 (0%) | 🛒 Add to cart |
| 60 | $3.13
Best per cap | $247.11 $187.85 (24%) | 🛒 Add to cart |
Synonyms | |||
Indinavir sulfate is a protease inhibitor antiretroviral medication used primarily in the management of HIV-1 infection. As one of the earlier drugs in this class, it represented a significant advancement in antiretroviral therapy when combined with other agents. The drug works by selectively binding to the protease enzyme active site, inhibiting the cleavage of viral polyprotein precursors into functional proteins needed for HIV replication. This results in the production of immature, non-infectious viral particles.
## 1. Introduction: What is Indinavir? Its Role in Modern Medicine
Indinavir belongs to the protease inhibitor class of antiretroviral medications, specifically developed to target HIV-1 protease. What is indinavir used for? Primarily, it’s indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents. The introduction of protease inhibitors like indinavir in the mid-1990s marked a turning point in HIV management, transforming AIDS from a terminal diagnosis to a manageable chronic condition for many patients. The benefits of indinavir in combination regimens were demonstrated in clinical trials showing significant reductions in viral load and increases in CD4 cell counts. Its medical applications extend to both treatment-naïve and treatment-experienced patients, though its use has declined with the development of better-tolerated alternatives with improved dosing schedules.
## 2. Key Components and Bioavailability Indinavir
The composition of indinavir centers around the active pharmaceutical ingredient indinavir sulfate. The release form is typically as 200mg, 333mg, or 400mg capsules for oral administration. Bioavailability of indinavir presents significant clinical challenges - the drug demonstrates approximately 65% oral bioavailability in the fasting state, but this decreases substantially when taken with food. Specifically, high-fat, high-calorie meals reduce AUC by approximately 80%. This necessitates strict administration guidelines: indinavir must be taken either 1 hour before or 2 hours after meals. The drug’s solubility is pH-dependent, with significantly improved absorption in an acidic environment. This characteristic has led to the common clinical practice of co-administering with acidic beverages in some cases to enhance absorption, though this approach requires careful monitoring.
## 3. Mechanism of Action Indinavir: Scientific Substantiation
Understanding how indinavir works requires examining its interaction with HIV protease at the molecular level. The mechanism of action involves competitive inhibition of the HIV-1 protease enzyme, which normally cleaves the gag and gag-pol polyprotein precursors into functional proteins essential for viral maturation. Indinavir binds to the protease active site with high affinity, mimicking the transition state of the natural substrate. This binding prevents the processing of viral polyproteins, resulting in the production of immature, non-infectious viral particles. The effects on the body include rapid reduction in plasma HIV RNA levels, typically achieving 1.5-2.0 log10 reductions in viral load within 4-8 weeks when used in combination regimens. Scientific research has demonstrated that the drug achieves therapeutic concentrations in lymphoid tissue, cerebrospinal fluid, and semen, contributing to its efficacy in suppressing viral replication in sanctuary sites.
## 4. Indications for Use: What is Indinavir Effective For?
Indinavir for HIV-1 Infection
The primary indication remains treatment of HIV-1 infection in combination with other antiretroviral agents. Clinical trials demonstrated that indinavir-containing regimens could achieve viral suppression below detectable limits in a significant proportion of patients when adherence was maintained.
Indinavir for Post-Exposure Prophylaxis
While not FDA-approved for this indication, indinavir has been used in occupational and non-occupational post-exposure prophylaxis regimens, typically in combination with two nucleoside reverse transcriptase inhibitors.
Indinavir for Prevention of Mother-to-Child Transmission
In certain scenarios, indinavir has been utilized as part of combination regimens for preventing perinatal transmission when other options are contraindicated or unavailable, though its use is limited by the availability of better-tolerated alternatives.
## 5. Instructions for Use: Dosage and Course of Administration
The recommended dosage for treatment-naïve adults is 800mg every 8 hours. The course of administration must account for the drug’s pharmacokinetics and food interactions. How to take indinavir properly is crucial for therapeutic success:
| Indication | Dosage | Frequency | Administration |
|---|---|---|---|
| HIV Treatment | 800mg | Every 8 hours | 1 hour before or 2 hours after meals |
| Dose with Rifabutin | 1000mg | Every 8 hours | With increased hydration |
| Hepatic Impairment | 600mg | Every 8 hours | With careful monitoring |
Side effects management often requires additional interventions. The most common adverse effects include nephrolithiasis (4-12% of patients), gastrointestinal intolerance, and indirect hyperbilirubinemia. Maintaining adequate hydration (at least 1.5 liters daily) is essential to reduce the risk of kidney stones.
## 6. Contraindications and Drug Interactions Indinavir
Contraindications include severe hepatic impairment, known hypersensitivity to indinavir or its components, and coadministration with certain medications that are highly dependent on CYP3A4 for clearance and for which elevated plasma concentrations are associated with serious adverse events. Key interactions with other drugs require careful management:
- Cisapride, terfenadine, astemizole: Contraindicated due to risk of cardiac arrhythmias
- Rifampin: Contraindicated due to significant reduction in indinavir levels
- Rifabutin: Requires indinavir dose increase to 1000mg every 8 hours
- Ketoconazole: May require indinavir dose reduction to 600mg every 8 hours
- St. John’s wort: Contraindicated due to reduced indinavir concentrations
Is it safe during pregnancy? Pregnancy Category C - no adequate well-controlled studies, should be used only if potential benefit justifies potential risk to fetus.
## 7. Clinical Studies and Evidence Base Indinavir
The effectiveness of indinavir was established in several landmark clinical studies. Merck Study 028 demonstrated that indinavir monotherapy produced mean HIV RNA reductions of 1.5-2.0 log10 copies/mL. The ACTG 320 trial showed that indinavir plus zidovudine and lamivudine reduced the risk of AIDS-defining illness or death by 50% compared to two-drug therapy alone. Physician reviews from the late 1990s consistently noted the dramatic improvements in patient outcomes with indinavir-containing regimens, though also highlighted the challenges of adherence to the strict dosing schedule and side effect management. More recent scientific evidence has positioned indinavir as a historical benchmark against which newer protease inhibitors are compared, with current guidelines generally favoring agents with better tolerability and more convenient dosing.
## 8. Comparing Indinavir with Similar Products and Choosing a Quality Product
When comparing indinavir with similar protease inhibitors, several factors distinguish it from newer agents. Which indinavir is better isn’t the right question - rather, how does it compare to alternatives like ritonavir-boosted darunavir or atazanavir? The key differences include:
- Dosing frequency: Indinavir requires TID dosing vs QD for many modern PIs
- Food restrictions: Indinavir has significant food interactions vs many newer agents that can be taken with food
- Toxicity profile: Higher rates of nephrolithiasis and hyperbilirubinemia than some alternatives
- Genetic barrier: Lower genetic barrier to resistance than boosted PIs
How to choose between antiretrovirals depends on individual patient factors, resistance patterns, comorbidities, and potential drug interactions. For quality assessment, ensure proper storage conditions (room temperature, protected from moisture) and verify manufacturer credentials.
## 9. Frequently Asked Questions (FAQ) about Indinavir
What is the recommended course of indinavir to achieve results?
Treatment should be continuous as part of a combination regimen, with viral load monitoring at 4-8 weeks to assess response. Most patients achieving viral suppression should continue indefinitely, with regimen reevaluation if toxicity or virologic failure occurs.
Can indinavir be combined with antidepressant medications?
Yes, but with caution. SSRIs like fluoxetine may increase indinavir levels, while indinavir may increase tricyclic antidepressant concentrations. Close monitoring and potential dose adjustments are recommended.
How does indinavir affect cholesterol levels?
Protease inhibitors as a class may cause lipid abnormalities. Indinavir is associated with increases in triglycerides and cholesterol in some patients, requiring monitoring and possible lipid-lowering therapy.
What monitoring is required during indinavir therapy?
Regular monitoring includes HIV RNA, CD4 count, liver function tests, bilirubin, serum creatinine, urinalysis, and clinical assessment for nephrolithiasis symptoms.
## 10. Conclusion: Validity of Indinavir Use in Clinical Practice
The risk-benefit profile of indinavir must be considered in the context of available alternatives. While historically important and still effective, its use has diminished due to dosing challenges and side effect profile. The main benefit remains its proven efficacy in combination regimens, particularly when resistance patterns or other factors limit options. Current expert recommendation generally reserves indinavir for scenarios where newer agents are contraindicated or unavailable, or when historical treatment response supports its continued use.
I remember when we first started using indinavir back in ‘97 - the excitement in the HIV clinic was palpable, but man, we were flying blind on some of this. Had this one patient, Carlos, 42-year-old guy who’d been through every nucleoside available and was down to 80 CD4 cells. Started him on the new triple therapy with indinavir, and within three months his viral load went from 250,000 to undetectable. Never seen anything like it - it felt like we’d pulled him back from the brink.
But the practical challenges… we had huge arguments in our team about how to manage the food restrictions. Our head pharmacist insisted on absolute adherence to the 1-hour-before/2-hours-after rule, while some of the younger attendings thought we were being too rigid. Then the kidney stones started showing up - I must’ve sent at least a dozen patients to the ER that first year. We learned the hard way that you can’t just write the prescription, you have to drill the hydration thing into people repeatedly.
The bilirubin elevations threw us initially too - first time I saw a patient with yellow eyes but normal LFTs otherwise, I was convinced we were missing something. Took us a while to recognize the pattern and stop panicking about every asymptomatic hyperbilirubinemia. What surprised me was how many patients actually preferred the strict timing - gave them a sense of control over their treatment, something concrete to focus on.
We lost Carlos last year to hepatocellular carcinoma - unrelated to his HIV, ironically. But he made it 25 years after that initial diagnosis, saw his kids graduate college, met his grandkids. When I run into patients from those early indinavir days now, there’s this shared understanding of what we went through together - the side effect management, the strict scheduling, the constant problem-solving. They’ll sometimes joke about carrying their pill containers and water bottles everywhere. The newer drugs are definitely easier, but there’s something about having fought through those early treatment challenges that created a different kind of therapeutic relationship.