Indinavir

Indinavir sulfate is a highly selective protease inhibitor indicated for the treatment of human immunodeficiency virus (HIV-1) infection. As a cornerstone of antiretroviral therapy, it functions by binding competitively to the active site of the HIV-1 protease enzyme, thereby preventing the cleavage of viral polyprotein precursors into functional proteins. This inhibition results in the production of immature, non-infectious viral particles, effectively reducing viral load and slowing disease progression. It is typically administered in combination with other antiretroviral agents as part of a structured treatment regimen to maximize efficacy and minimize the development of resistance.

Features

• Active pharmaceutical ingredient: Indinavir sulfate
• Pharmacologic class: HIV-1 protease inhibitor
• Available in 200 mg and 400 mg capsule formulations
• High oral bioavailability when administered under fasting conditions or with a light, low-fat meal
• Metabolized primarily via the hepatic CYP3A4 isoenzyme pathway
• Demonstrated efficacy in reducing viral RNA levels and increasing CD4+ cell counts in clinical trials

Benefits

• Significantly reduces HIV-1 viral load, supporting immune reconstitution
• Delays progression to AIDS-defining illnesses and mortality in treatment-naïve and experienced patients
• Enhances the durability of antiretroviral response when used in combination therapy
• Provides a well-characterized pharmacokinetic profile for predictable dosing
• Contributes to long-term virological suppression with adherence to prescribed regimen
• Offers flexibility in combination with various other antiretroviral classes

Common use

Indinavir is indicated for the treatment of HIV-1 infection in adults and pediatric patients older than 4 years, in combination with other antiretroviral agents. It is utilized across various clinical scenarios, including initial therapy for treatment-naïve individuals and as part of salvage regimens for those with prior treatment experience. Its use is guided by resistance testing where available, and it remains a consideration in resource-limited settings or specific resistance patterns. Clinical decision-making should incorporate viral load, CD4+ count, patient comorbidities, and potential drug interactions.

Dosage and direction

The recommended adult dosage is 800 mg orally every 8 hours. Administration should occur on an empty stomach (1 hour before or 2 hours after a meal) or with a light, low-fat snack to optimize absorption. For pediatric patients (4 years and older), the dosage is based on body surface area or weight, typically 500 mg/m² every 8 hours. Dosage adjustment is necessary in patients with mild to moderate hepatic impairment (reduce to 600 mg every 8 hours). Adherence to the strict 8-hour dosing interval is critical to maintain therapeutic drug levels and prevent resistance development.

Precautions

• Hydration: Maintain adequate hydration (at least 1.5 L daily) to reduce risk of nephrolithiasis
• Hepatic function: Monitor transaminases; dose reduction advised in hepatic impairment
• Hyperglycemia: May exacerbate or new-onset diabetes mellitus; monitor glucose levels
• Lipid abnormalities: May increase triglycerides and cholesterol; consider lipid-lowering agents if necessary
• Hemophilia: Reports of increased bleeding episodes; monitor closely
• Fat redistribution: May occur as part of lipodystrophy syndrome
• Immune reconstitution syndrome: May occur shortly after initiation of therapy

Contraindications

• Hypersensitivity to indinavir or any component of the formulation
• Coadministration with drugs highly dependent on CYP3A4 for clearance and with elevated plasma concentrations associated with serious and/or life-threatening events (e.g., alfuzosin, amiodarone, ergot derivatives, lovastatin, simvastatin, sildenafil for pulmonary hypertension, triazolam, oral midazolam)
• Severe hepatic impairment (Child-Pugh Class C)
• Concurrent use with rifampin, which significantly reduces indinavir plasma concentrations

Possible side effect

• Nephrolithiasis/urolithiasis (∼12% incidence)
• Nausea (∼12%), abdominal pain (∼9%), vomiting (∼8%)
• Hyperbilirubinemia (∼14%), asymptomatic elevation of indirect bilirubin
• Headache (∼6%), dizziness (∼5%), fatigue (∼4%)
• Rash (∼4%), dry skin (∼3%)
• Diarrhea (∼4%), dyspepsia (∼3%)
• Insomnia (∼3%), taste perversion (∼2%)
• Back pain (∼3%), myalgia (∼2%)

Drug interaction

• CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): Increase indinavir AUC; reduce indinavir dose to 600 mg every 8 hours with ketoconazole
• CYP3A4 inducers (e.g., efavirenz, nevirapine): Decrease indinavir concentrations; consider dosage adjustment
• Didanosine: Administer at least 1 hour apart on an empty stomach
• Atorvastatin: Possible increased statin levels; use lowest possible dose
• Rifabutin: Increases rifabutin levels; reduce rifabutin dose by 50%
• Sildenafil (for erectile dysfunction): Increases sildenafil AUC; maximum sildenafil dose 25 mg in 48 hours
• St. John’s wort: Avoid concomitant use (reduces indinavir concentrations)

Missed dose

If a dose is missed within 2 hours of the scheduled time, take it as soon as possible and resume the regular dosing schedule. If more than 2 hours have passed, skip the missed dose and take the next dose at the regularly scheduled time. Do not double the dose to make up for a missed one. Consistent adherence is crucial to maintain effective drug concentrations and prevent viral resistance.

Overdose

Limited experience with overdose. Single doses up to 2.4 g have been administered without ill effects. There is no specific antidote. Management should include supportive measures, including maintenance of hydration to minimize crystalluria and nephrolithiasis risk. Hemodialysis is unlikely to be beneficial due to high protein binding and extensive metabolism. Contact a poison control center for latest guidance.

Storage

Store at controlled room temperature 20°–25°C (68°–77°F); excursions permitted to 15°–30°C (59°–86°F). Keep container tightly closed and protect from moisture. Dispense in original container with desiccant. Do not use if capsules are discolored or show signs of deterioration. Keep out of reach of children and pets.

Disclaimer

This information is provided for educational purposes only and does not constitute medical advice. Treatment decisions must be made by a qualified healthcare professional based on individual patient characteristics. Always follow the prescribing information provided with the medication and consult appropriate clinical guidelines. The prescriber should be aware of the most current product labeling and emerging safety data.

Reviews

“Indinavir remains a valuable component of antiretroviral regimens, particularly in cases where newer agents are not accessible or appropriate. Its well-established efficacy profile is balanced by the need for meticulous adherence and monitoring for renal and metabolic effects.” – Infectious Disease Specialist, 15 years experience

“In our clinical practice, we reserve indinavir for specific scenarios where resistance patterns or drug access dictate its use. The three-times-daily dosing requires significant patient commitment, but the antiviral potency is undeniable when used correctly.” – HIV Clinical Pharmacist

“While newer agents offer improved convenience, indinavir’s role in the history of HIV treatment is significant. It requires careful management of drug interactions and side effects, but can be effective in motivated patients with appropriate support.” – Clinical Virologist