Comprehensive Guide to Darunavir: Uses, Dosage, Side Effects, and More
What is Darunavir?
Overview of Darunavir
Generic Name: Darunavir
Brand Name: Prezista, generics
Drug Group: Protease inhibitor (antiretroviral)
Commonly Used For
- Treat HIV-1 infection.
- Prevent viral replication in HIV patients.
- Manage antiretroviral therapy regimens.
Key Characteristics
Form: Oral tablets (75 mg, 150 mg, 400 mg, 600 mg, 800 mg) (detailed in Dosage section).
Mechanism: Inhibits HIV-1 protease, halting viral maturation.
Approval: FDA-approved (2006 for Prezista) and EMA-approved for HIV treatment.
Indications and Uses of Darunavir
Darunavir is indicated for the management of HIV-1 infection, offering potent viral suppression when used in combination therapy:
HIV-1 Infection: Treats HIV-1 in treatment-naïve and treatment-experienced adults and children (3+ years), reducing viral load and improving CD4 counts, per WHO and CDC guidelines.
Post-Exposure Prophylaxis (PEP): Used off-label as part of PEP regimens following occupational or non-occupational exposure to HIV, preventing infection when initiated within 72 hours, under infectious disease supervision.
Pre-Exposure Prophylaxis (PrEP) Adjunct: Investigated off-label to boost PrEP efficacy in high-risk populations when combined with other antiretrovirals, with emerging data from HIV prevention studies.
HIV-Associated Kaposi’s Sarcoma: Employed off-label to manage Kaposi’s sarcoma in HIV patients, reducing tumor progression when antiretroviral therapy is optimized, supported by oncology research.
HIV-Related Neurocognitive Disorders: Used off-label to address mild neurocognitive impairment in HIV, improving cognitive function, with evidence from neurological trials.
Pediatric HIV Management: Treats HIV-1 in children (3–17 years) with specific weight-based dosing, enhancing adherence and viral suppression, per pediatric HIV guidelines.
Resistance Management: Manages multi-drug-resistant HIV strains in treatment-experienced patients, requiring genotypic testing and ritonavir boosting, under specialist care.
Prevention of Mother-to-Child Transmission (PMTCT): Used off-label in pregnant women with HIV to reduce transmission risk, administered with other antiretrovirals, per obstetric and infectious disease protocols.
Chronic Hepatitis C Co-Infection: Investigated off-label to optimize HIV/HCV co-infection treatment, improving liver function when combined with direct-acting antivirals, supported by hepatology studies.
Dosage of Darunavir
Dosage for Adults
Treatment-Naïve (with ritonavir):
- 800 mg once daily with 100 mg ritonavir, taken with food.
Treatment-Experienced (with ritonavir):
- 600 mg twice daily with 100 mg ritonavir per dose, taken with food.
With Cobicistat (treatment-naïve or experienced):
- 800 mg once daily with 150 mg cobicistat, taken with food.
Dosage for Children
3–17 years (with ritonavir, weight-based):
- 10–15 kg: 200 mg twice daily with 32 mg ritonavir.
- 15–20 kg: 250 mg twice daily with 40 mg ritonavir.
- 20–30 kg: 375 mg twice daily with 48–50 mg ritonavir.
- 30–40 kg: 450 mg twice daily with 64 mg ritonavir.
- 40 kg: Adult dosing (600–800 mg), under pediatric supervision.
Not recommended under 3 years.
Dosage for Pregnant Women
Pregnancy Category C: Use only if benefits outweigh risks; adjust to 600 mg twice daily with 100 mg ritonavir, with viral load monitoring. Consult an obstetrician.
Dosage Adjustments
Renal Impairment: No adjustment needed; monitor in severe cases (CrCl <30 mL/min).
Hepatic Impairment: Mild (Child-Pugh A): No adjustment; moderate (Child-Pugh B): 600 mg with 100 mg ritonavir once daily; severe (Child-Pugh C): Avoid.
Elderly: Start with 600 mg once daily; increase cautiously with monitoring.
Concomitant Medications: Adjust if combined with CYP3A4 inducers/inhibitors, altering boosting dose.
Additional Considerations
- Take this active ingredient with food to enhance absorption.
- Use a pill organizer for consistent timing with boosting agents.
How to Use Darunavir
Administration:
- Swallow tablets whole with a meal or snack, using water; avoid crushing or chewing.
- Take with ritonavir or cobicistat as prescribed, maintaining the same schedule.
Timing: Use once or twice daily with meals, as directed, maintaining consistency.
Monitoring: Watch for rash, jaundice, or signs of liver issues (e.g., dark urine).
Additional Tips:
- Store at 20–25°C (68–77°F), protecting from moisture and heat.
- Keep out of reach of children due to toxicity risk.
- Report severe fatigue, abdominal pain, or signs of allergic reaction immediately.
Contraindications for Darunavir
Hypersensitivity: Patients with a known allergy to Darunavir or sulfa drugs.
Severe Hepatic Impairment: Contraindicated in Child-Pugh Class C due to toxicity risk.
Concurrent Use with Certain Drugs: Avoid with strong CYP3A4 inducers (e.g., rifampin) or contraindicated medications (e.g., ergot derivatives).
Warnings & Precautions for Darunavir
General Warnings
Hepatotoxicity: Risk of liver injury; monitor liver enzymes regularly.
Severe Skin Reactions: Risk of Stevens-Johnson syndrome; discontinue if rash worsens.
Hyperlipidemia: May increase cholesterol/triglycerides; check lipid profiles.
Immune Reconstitution Syndrome: Risk of inflammation in early therapy; monitor closely.
Drug Resistance: Risk with non-adherence; ensure compliance.
Additional Warnings
Diabetes Mellitus: May exacerbate hyperglycemia; monitor blood sugar.
Hemophilia: Increases bleeding risk; manage with factor replacement if needed.
Osteonecrosis: Rare with long-term use; assess joint pain.
Renal Impairment: Monitor in severe cases; adjust if necessary.
Hypersensitivity Reactions: Rare anaphylaxis; discontinue if swelling occurs.
Use in Specific Populations
Pregnancy: Category C; use only if essential with viral monitoring.
Breastfeeding: Avoid due to HIV transmission risk; monitor infant.
Elderly: Higher risk of toxicity; start with lower doses.
Children: Limited to 3+ years; supervise closely.
Renal/Hepatic Impairment: Adjust dose; avoid in severe cases.
Additional Precautions
- Inform your doctor about liver disease, diabetes, or medication history before starting this medication.
- Adhere strictly to dosing; missing doses increases resistance risk.
Overdose and Management of Darunavir
Overdose Symptoms
- Nausea, diarrhea, or abdominal pain.
- Severe cases: Liver failure, rash, or hyperkalemia.
- Headache, dizziness, or fatigue as early signs.
- Seizures with extremely high doses.
Immediate Actions
Contact the Medical Team: Seek immediate medical help.
Supportive Care: Administer activated charcoal if ingested recently, monitor vital signs, and provide IV fluids.
Specific Treatment: Manage liver function, electrolytes, and symptoms; no specific antidote.
Monitor: Check liver enzymes, kidney function, and heart rate for 24–48 hours.
Additional Notes
- Overdose risk is low; store securely.
- Report persistent symptoms (e.g., jaundice, confusion) promptly.
Side Effects of Darunavir
Common Side Effects
- Diarrhea (5–10%, transient)
- Nausea (3–8%, manageable with food)
- Headache (2–6%, relieved with rest)
- Rash (2–5%, monitor for severity)
- Fatigue (1–4%, decreases with tolerance)
These effects may subside with dose adjustment.
Serious Side Effects
Seek immediate medical attention for:
- Hepatic: Jaundice, hepatitis, or liver failure.
- Dermatologic: Stevens-Johnson syndrome or toxic epidermal necrolysis.
- Metabolic: Hyperlipidemia, hyperglycemia, or lactic acidosis.
- Cardiovascular: Prolonged QT interval or heart block.
- Allergic: Rash, angioedema, or anaphylaxis.
Additional Notes
- Regular monitoring for liver function, lipids, and immune status is advised.
- Report any unusual symptoms (e.g., yellow skin, severe weakness) immediately to a healthcare provider.
Drug Interactions with Darunavir
This active ingredient may interact with:
- CYP3A4 Inhibitors/Inducers: Alters levels (e.g., ketoconazole, rifampin); adjust dose.
- Statins: Increases myopathy risk (e.g., simvastatin); use alternatives.
- Antiarrhythmics: Enhances toxicity (e.g., amiodarone); monitor ECG.
- Oral Contraceptives: Reduces efficacy; use backup methods.
- Anticonvulsants: Alters metabolism (e.g., carbamazepine); adjust dose.
Action: Provide your healthcare provider with a complete list of medications.
Patient Education or Lifestyle
Medication Adherence: Take this antiretroviral as prescribed to manage HIV, following the exact schedule.
Monitoring: Report rash, jaundice, or fatigue immediately.
Lifestyle: Avoid alcohol; maintain a balanced diet.
Diet: Take with food to enhance absorption; avoid high-fat meals.
Emergency Awareness: Know signs of liver failure or allergic reaction; seek care if present.
Follow-Up: Schedule regular check-ups every 3–6 months to monitor viral load and liver health.
Pharmacokinetics of Darunavir
Absorption: Well-absorbed orally (peak at 2.5–4 hours); enhanced with food.
Distribution: Volume of distribution ~88 L; 95% protein-bound.
Metabolism: Hepatic via CYP3A4 to inactive metabolites.
Excretion: Primarily fecal (80%) as unchanged drug; half-life 15 hours.
Half-Life: 15 hours, with ritonavir boosting extending effect.
Pharmacodynamics of Darunavir
This drug exerts its effects by:
Inhibiting HIV-1 protease, preventing viral particle maturation.
Reducing viral load and improving immune function in HIV.
Demonstrating high genetic barrier to resistance with boosting.
Exhibiting dose-dependent liver and lipid effects.
Storage of Darunavir
- Temperature: Store at 20–25°C (68–77°F); protect from moisture.
- Protection: Keep in original container, away from light.
- Safety: Store in a locked container out of reach of children due to toxicity risk.
- Disposal: Dispose of unused tablets per local regulations or consult a pharmacist.
Frequently Asked Questions (FAQs)
Q: What does Darunavir treat?
A: This medication treats HIV-1 infection.
Q: Can this active ingredient cause rash?
A: Yes, rash may occur; report if severe.
Q: Is Darunavir safe for children?
A: Yes, for 3+ years with a doctor’s guidance.
Q: How is this drug taken?
A: Orally as tablets with food, as directed.
Q: How long is Darunavir treatment?
A: Lifelong for HIV management.
Q: Can I use Darunavir if pregnant?
A: Yes, with caution; consult a doctor.
Regulatory Information for Darunavir
This medication is approved by:
U.S. Food and Drug Administration (FDA): Approved in 2006 (Prezista) for HIV treatment.
European Medicines Agency (EMA): Approved for HIV-1 management.
Other Agencies: Approved globally for HIV; consult local guidelines.
References
- U.S. Food and Drug Administration (FDA). (2023). Prezista (Darunavir) Prescribing Information.
- Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
- European Medicines Agency (EMA). (2023). Darunavir Summary of Product Characteristics.
- EMA’s comprehensive information on the medication’s indications and precautions in Europe.
- National Institutes of Health (NIH). (2023). Darunavir: MedlinePlus Drug Information.
- NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
- World Health Organization (WHO). (2023). WHO Guidelines on HIV Treatment: Darunavir.
- WHO’s recommendations for Darunavir in HIV therapy.
- Journal of Acquired Immune Deficiency Syndromes. (2022). Darunavir in HIV Resistance.
- Peer-reviewed article on Darunavir efficacy (note: access may require a subscription).
