Usage
- Darunavir is prescribed for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults and pediatric patients 3 years of age and older, in combination with other antiretroviral agents. It is used in treatment-naive (patients never treated for HIV) and treatment-experienced individuals.
- Pharmacological classification: Antiretroviral, protease inhibitor.
Alternate Names
- Darunavir is the generic name.
- Brand name: Prezista. Prezcobix (in combination with Cobicistat).
How It Works
- Pharmacodynamics: Darunavir inhibits HIV-1 protease, an enzyme crucial for viral replication. This inhibition prevents the cleavage of viral polyproteins, resulting in the formation of immature, non-infectious viral particles.
- Pharmacokinetics: Darunavir is administered orally and must be co-administered with a pharmacokinetic enhancer, either ritonavir or cobicistat, to increase its bioavailability. Darunavir is primarily metabolized by the liver (CYP3A4 enzyme system) and excreted in feces. Ritonavir inhibits CYP3A4, significantly increasing darunavir plasma concentrations. Cobicistat also inhibits CYP3A, boosting darunavir levels similarly to ritonavir, but cobicistat does not have antiretroviral activity itself. Absorption is enhanced when taken with food. Renal clearance is limited.
Dosage
Standard Dosage
Adults:
- Treatment-naive or treatment-experienced (without darunavir resistance-associated mutations): 800 mg darunavir with ritonavir 100 mg or cobicistat 150 mg once daily with food.
- Treatment-experienced (with at least one darunavir resistance-associated mutation): 600 mg darunavir with ritonavir 100 mg twice daily with food.
Children (3 to 17 years and ≥10 kg):
- Dosing is based on body weight and should not exceed the adult dose. Consult pediatric dosing tables based on weight bands and resistance status (available in sources like [2], [5]). Darunavir must be given with ritonavir and food. Cobicistat dosing has not been established in children.
Special Cases:
- Elderly Patients: Use with caution due to potential age-related changes in organ function. Monitor closely.
- Patients with Renal Impairment: No dose adjustment is required.
- Patients with Hepatic Dysfunction: No dose adjustment is required for mild to moderate impairment. Darunavir is contraindicated in severe hepatic impairment. Monitor those with chronic hepatitis B or C closely.
- Patients with Comorbid Conditions: Close monitoring recommended for patients with diabetes, hemophilia, hyperlipidemia, or a history of pancreatitis.
Clinical Use Cases
Darunavir is not specifically indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is specifically for chronic HIV-1 infection management.
Dosage Adjustments:
Dose adjustments are primarily based on treatment history and darunavir resistance mutations. Renal impairment does not necessitate dose modification.
Side Effects
Common Side Effects:
Diarrhea, nausea, vomiting, abdominal pain, headache, rash.
Rare but Serious Side Effects:
Drug-induced hepatitis, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), pancreatitis, new-onset or worsening diabetes, immune reconstitution inflammatory syndrome, bleeding in hemophiliac patients, allergic reactions (angioedema).
Long-Term Effects:
Lipodystrophy (fat redistribution), hyperlipidemia, cardiovascular risk increase.
Adverse Drug Reactions (ADR):
Severe skin reactions, hepatotoxicity, hypersensitivity reactions.
Contraindications
- Hypersensitivity to darunavir.
- Severe hepatic impairment (Child-Pugh Class C).
- Co-administration with drugs highly dependent on CYP3A for clearance and having a narrow therapeutic index (e.g., alfuzosin, amiodarone, rifampin, St. John’s Wort). Consult a drug interaction checker for a comprehensive list.
Drug Interactions
Numerous drug interactions exist. Consult a comprehensive drug interaction resource (e.g., [12]) for a detailed list. Significant interactions include those with:
- CYP3A inducers (e.g., rifampin): Reduce darunavir levels.
- CYP3A inhibitors (e.g., ketoconazole): Increase darunavir levels.
- Hormonal contraceptives: Reduced efficacy of hormonal contraceptives.
- Several other medications (e.g., some anticonvulsants, antifungals, antipsychotics).
Pregnancy and Breastfeeding
- Pregnancy: Darunavir/ritonavir is used during pregnancy when the benefits outweigh the risks. 600 mg twice daily with ritonavir 100 mg is the recommended regimen. Darunavir/cobicistat is not recommended during pregnancy.
- Breastfeeding: Breastfeeding is not recommended for women with HIV due to the risk of postnatal transmission. If replacement feeding is not possible, discuss alternative antiretroviral therapies with the patient.
Drug Profile Summary
- Mechanism of Action: HIV-1 protease inhibitor.
- Side Effects: Diarrhea, nausea, rash; severe skin reactions, hepatotoxicity, pancreatitis.
- Contraindications: Severe hepatic impairment; concomitant use of strong CYP3A inducers and drugs with narrow therapeutic index.
- Drug Interactions: Numerous (consult a drug interaction checker).
- Pregnancy & Breastfeeding: Darunavir/ritonavir usable with caution during pregnancy; breastfeeding not recommended.
- Dosage: See detailed dosage guidelines above.
- Monitoring Parameters: Liver function tests, lipid profile, blood glucose, viral load, CD4 count.
Popular Combinations
Darunavir is always used in combination with other antiretroviral agents. Ritonavir or cobicistat are co-administered to boost darunavir levels. Combinations are tailored to each patient based on resistance testing.
Precautions
- Pre-screen for hepatic dysfunction, diabetes, and other relevant comorbidities.
- Monitor liver function, lipids, and blood glucose during therapy.
- Counsel patients about drug interactions, including with hormonal contraceptives.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Darunavir?
A: See the detailed dosage guidelines provided above.
Q2: Is darunavir ever used as monotherapy for HIV?
A: No, darunavir must always be used in combination with other antiretroviral agents.
Q3: Can darunavir cure HIV infection?
A: No, darunavir does not cure HIV. It helps manage the infection, slowing its progression.
Q4: What should be done if a patient misses a dose of darunavir/ritonavir?
A: If missed within 12 hours of the usual time, take the missed dose as soon as possible. If more than 12 hours have passed, skip the missed dose and return to the regular schedule.
Q5: What are the key drug interactions to be aware of with darunavir?
A: Darunavir has many drug interactions. Key ones include interactions with strong CYP3A4 inducers and inhibitors, and reduced efficacy of hormonal contraceptives. Consult a comprehensive drug interaction resource for a detailed list.
Q6: How is darunavir/ritonavir dosing adjusted in pregnancy?
A: The recommended dose during pregnancy is darunavir 600 mg with ritonavir 100 mg twice daily with food. Darunavir/cobicistat is not recommended.
Q7: What are the most common side effects reported with darunavir?
A: Diarrhea, nausea, vomiting, abdominal pain, headache, and rash are common side effects.
Q8: What monitoring parameters are important when a patient is on darunavir therapy?
A: Monitor liver function tests, lipid profile, blood glucose, viral load, and CD4 cell count regularly.
Q9: Can Darunavir be prescribed to a patient with severe hepatic impairment?
A: No. Darunavir is contraindicated in patients with severe hepatic impairment (Child-Pugh class C).
