Darunavir 800 mg Tablet, Film Coated, 30-count — NDC 68180-346-06 (Billing 68180-0346-06)
This is a package of 30 tablets of Darunavir 800 mg Tablet, Film Coated from Lupin Pharmaceuticals, Inc., marketed since Jun 2023 and currently FDA-listed; retail pharmacies pay about $2.38 per tablet (NADAC). It is this product's only package size.
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 070245
- GCN: 33723
- GPI-14 (Medi-Span): 12104520000350
- HICL (First Databank): 033842
- AHFS class code: 08:18.08.08
- RxCUI (RxNorm): 670026
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Protease Inhibitor class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
- It treats HIV-1 infection in adults and children 3 years and older. You take it with ritonavir and other HIV medicines. It works by blocking an enzyme the virus needs to mature.
- Ritonavir boosts darunavir to levels high enough to work, and food helps your body absorb it. Without them, the medicine may not control the virus well. Please don't skip either on...
- Why do I have to take it with ritonavir and food?
- The most common are diarrhea, nausea, rash, headache, belly pain, and vomiting. Rash is often mild and may go away as you keep taking it. Call your doctor if the rash is severe or...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Darunavir — tap one for details:
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $2.382 | $71.46 / 30 tablets |
| Medicaid paysCMS SDUD · 12 mo | $4.43 | $132.87 / 30 tablets |
| Medicare drug plans payPart D · Q2 2026 | $5.53 | $165.78 / 30 tablets |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 68180-0346-06 You're viewing this Main listing | 30 TABLET, FILM COATED in 1 BOTTLE | 2023-06-01 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Darunavir 800 mg 31722-0089-30 | Camber | 30 tablets | $2.382 | AB | Availability likely | — |
| Darunavir 800 mg 59651-0086-30 | Aurobindo | 30 tablets | $2.382 | AB | Availability likely | — |
| Darunavir 800 mg 60219-1145-03 | Amneal | 30 tablets | $2.382 | AB | Availability likely | — |
| Darunavir 800 mg 60687-0819-21 | American | 30 tablets | $2.382 | AB | Availability likely | — |
| Darunavir 800 mgthis 68180-0346-06 | Lupin | 30 tablets | $2.382 | AB | Availability likely | — |
| Darunavir 600 and 800 mg 69097-0244-02 | Cipla | 30 tablets | $2.382 | AB | Availability likely | — |
| Darunavir 800 mg 72205-0185-30 | Novadoz | 30 tablets | $2.382 | AB | Availability likely | — |
| darunavir 800 mg 76282-0738-30 | EXELAN | 30 tablets | $2.382 | AB | Availability likely | — |
| Prezista 800 mg 59676-0566-30 | Janssen | 30 tablets | $70.107 | AB | Availability likely | +2843% |
| Darunavir 800 mg 43598-0705-05 | Dr.Reddys | 500 tablets | — | AB | FDA listed | — |
| Darunavir 600 and 800 mg 63629-5686-01 | Bryant | 15 tablets | — | AB | FDA listed | — |
| Darunavir 800 mg 68071-3910-03 | NuCare | 3 tablets | — | AB | FDA listed | — |
| Darunavir 800 mg 70771-1746-03 | Zydus | 30 tablets | — | AB | FDA listed | — |
| Darunavir 800 mg 71335-2611-01 | Bryant | 15 tablets | — | AB | FDA listed | — |
| Darunavir 800 mg 72578-0148-05 | Viona | 500 tablets | — | AB | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Sep 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Sep 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII OP1R32D61U
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Crospovidone is a synthetic polymer made from polyvinylpyrrolidone. It acts as a disintegrant, helping tablets break apart quickly in the stomach so the medicine dissolves and absorbs into the body.
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10 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 1, 2026
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Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Darunavir tablets, co-administered with ritonavir (darunavir/ritonavir), in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV-1) infection in adult and pediatric patients 3 years of age and older [ see Use in Specific Populations (8.4) and Clinical Studies (14) ]. Darunavir is a human immunodeficiency virus (HIV-1) protease inhibitor indicated for the treatment of HIV-1 infection in adult and pediatric patients 3 years of age and older.
Darunavir tablets must be co-administered with ritonavir (darunavir/ritonavir) and with other antiretroviral agents. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Testing: In treatment-experienced patients, treatment history genotypic and/or phenotypic testing is recommended prior to initiation of therapy with darunavir/ritonavir to assess drug susceptibility of the HIV-1 virus. ( 2.1 , 12.4 ) Monitor serum liver chemistry tests before and during therapy with darunavir/ritonavir. ( 2.1 , 2.2 , 5.2 ) Treatment-naïve adult patients and treatment-experienced adult patients with no darunavir resistance associated substitutions: 800 mg (one 800 mg tablet) taken with ritonavir 100 mg once daily and with food.
( 2.3 ) Treatment-experienced adult patients with at least one darunavir resistance associated substitution: 600 mg (one 600 mg tablet) taken with ritonavir 100 mg twice daily and with food. ( 2.3 ) Pregnant patients: 600 mg (one 600 mg tablet) taken with ritonavir 100 mg twice daily and with food. ( 2.4 ) Pediatric patients (3 to less than 18 years of age and weighing at least 10 kg): dosage of darunavir and ritonavir is based on body weight and should not exceed the adult dose.
Darunavir tablets should be taken with ritonavir and with food. ( 2.5 ) Darunavir/ritonavir is not recommended for use in patients with severe hepatic impairment. ( 2.6 )
2.1Testing Prior to Initiation of darunavir/ritonavir In treatment-experienced patients, treatment history, genotypic and/or phenotypic testing is recommended to assess drug susceptibility of the HIV-1 virus [ see Microbiology (12.4) ]. Refer to Dosage and Administration (2.3) , ( 2.4 ) and ( 2.5 ) for dosing recommendations. Appropriate laboratory testing such as serum liver biochemistries should be conducted prior to initiating therapy with darunavir/ritonavir [ see Warnings and Precautions (5.2) ].
2.2Monitoring During Treatment with darunavir/ritonavir Patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-treatment elevations of transaminases should be monitored for elevation in serum liver biochemistries, especially during the first several months of darunavir/ritonavir treatment [ see Warnings and Precautions (5.2) ].
2.3Recommended Dosage in Adult Patients Darunavir must be co-administered with ritonavir to exert its therapeutic effect. Failure to correctly co-administer darunavir with ritonavir will result in plasma levels of darunavir that will be insufficient to achieve the desired antiviral effect and will alter some drug interactions. Patients who have difficulty swallowing darunavir tablets can use the 100 mg per mL darunavir oral suspension.
Treatment-Naïve Adult Patients The recommended oral dose of darunavir is 800 mg (one 800 mg tablet) taken with ritonavir 100 mg (one 100 mg tablet or capsule) once daily and with food. Treatment-Experienced Adult Patients The recommended oral dosage for treatment-experienced adult patients is summarized in Table 1 . Baseline genotypic testing is recommended for dose selection.
However, when genotypic testing is not feasible, darunavir 600 mg taken with ritonavir 100 mg twice daily is recommended. Table 1: Recommended Darunavir/Ritonavir Dosage in Treatment-Experienced Adult Patients Baseline Resistance Formulation and Recommended Dosing Darunavir tablets with ritonavir tablets or capsule With no darunavir resistance associated substitutions V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V One 800 mg darunavir tablet with one 100 mg ritonavir tablet/capsule, taken once daily with food With at least one darunavir resistance associated substitutions , or with no baseline resistance information One 600 mg darunavir tablet with one 100 mg ritonavir tablet/capsule, taken twice daily with food
2.4Recommended Dosage During Pregnancy The recommended dosage in pregnant patients is darunavir 600 mg taken with ritonavir 100 mg twice daily with food. Darunavir 800 mg taken with ritonavir 100 mg once daily should only be considered in certain pregnant patients who are already on a stable darunavir 800 mg with ritonavir 100 mg on… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Darunavir Tablets 600 mg: orange colored, oval shaped, film-coated tablets debossed with 'LU' on one side and 'A42' on the other side. 800 mg: dark red colored, oval shaped, film-coated tablets debossed with 'LU' on one side and 'A46' on the other side. Tablets: 600 mg, and 800 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Co-administration of darunavir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index). Examples of these drugs and other contraindicated drugs (which may lead to reduced efficacy of darunavir) are listed below [ see Drug Interactions (7.3) ]. Due to the need for co-administration of darunavir with ritonavir, please refer to ritonavir prescribing information for a description of ritonavir contraindications.
Alpha 1-adrenoreceptor antagonist: alfuzosin Anti-gout: colchicine, in patients with renal and/or hepatic impairment Antimycobacterial: rifampin Antipsychotics: lurasidone, pimozide Cardiac Disorders: dronedarone, ivabradine, ranolazine Ergot derivatives, e.g. dihydroergotamine, ergotamine, methylergonovine Herbal product: St. John's wort (Hypericum perforatum) Hepatitis C direct acting antiviral: elbasvir/grazoprevir Lipid modifying agents: lomitapide, lovastatin, simvastatin Opioid Antagonist: naloxegol PDE-5 inhibitor: sildenafil when used for treatment of pulmonary arterial hypertension Sedatives/hypnotics: orally administered midazolam, triazolam Co-administration of darunavir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index).
( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) has been reported with darunavir/ritonavir. Monitor liver function before and during therapy, especially in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-treatment elevations of transaminases. Post-marketing cases of liver injury, including some fatalities, have been reported.
( 5.2 ) Skin reactions ranging from mild to severe, including Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms and acute generalized exanthematous pustulosis, have been reported. Discontinue treatment if severe reaction develops. ( 5.3 ) Use with caution in patients with a known sulfonamide allergy.
( 5.4 ) Patients may develop new onset diabetes mellitus or hyperglycemia. Initiation or dose adjustments of insulin or oral hypoglycemic agents may be required. ( 5.6 ) Patients may develop redistribution/accumulation of body fat or immune reconstitution syndrome.
( 5.7 , 5.8 ) Patients with hemophilia may develop increased bleeding events. ( 5.9 ) Darunavir/ritonavir is not recommended in pediatric patients below 3 years of age in view of toxicity and mortality observed in juvenile rats dosed with darunavir up to days 23 to 26 of age. ( 5.10 )
5.1Importance of Co-administration with Ritonavir Darunavir must be co-administered with ritonavir and food to achieve the desired antiviral effect. Failure to administer darunavir with ritonavir and food may result in a loss of efficacy of darunavir. Please refer to ritonavir prescribing information for additional information on precautionary measures.
5.2Hepatotoxicity Drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) has been reported with darunavir/ritonavir. During the clinical development program (N=3063), hepatitis was reported in 0.5% of patients receiving combination therapy with darunavir/ritonavir. Patients with pre-existing liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities including severe hepatic adverse events.
Post-marketing cases of liver injury, including some fatalities, have been reported. These have generally occurred in patients with advanced HIV-1 disease taking multiple concomitant medications, having co-morbidities including hepatitis B or C co-infection, and/or developing immune reconstitution syndrome. A causal relationship with darunavir/ritonavir therapy has not been established.
Appropriate laboratory testing should be conducted prior to initiating therapy with darunavir/ritonavir and patients should be monitored during treatment. Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-treatment elevations of transaminases, especially during the first several months of darunavir/ritonavir treatment. Evidence of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly) in patients on darunavir/ritonavir should prompt consideration of interruption or discontinuation of treatment.
5.3Severe Skin Reactions During the clinical development program (n=3063), severe skin reactions, accompanied by fever and/or elevations of transaminases in some cases, have been reported in 0.4% of subjects. Stevens-Johnson Syndrome was rarely (less than 0.1%) reported during the clinical development program. During post-marketing experience toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis have been reported.
Discontinue darunavir/ritonavir immediately if signs or symptoms of severe skin reactions develop. These can include but are not limited to severe rash or rash accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, or… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of labeling: Hepatotoxicity [see Warnings and Precautions (5.2) ] Severe Skin Reactions [see Warnings and Precautions (5.3) ] Diabetes Mellitus/Hyperglycemia [see Warnings and Precautions (5.6) ] Fat Redistribution [see Warnings and Precautions (5.7) ] Immune Reconstitution Syndrome [see Warnings and Precautions (5.8) ] Hemophilia [see Warnings and Precautions (5.9) ] Due to the need for co-administration of darunavir with ritonavir, please refer to ritonavir prescribing information for ritonavir-associated adverse reactions.
The most common clinical adverse drug reactions to darunavir/ritonavir (incidence greater than or equal to 5%) of at least moderate intensity (greater than or equal to Grade 2) were diarrhea, nausea, rash, headache, abdominal pain and vomiting. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. T r e a tment Naïve-Adults: TMC114-C211 The safety assessment is based on all safety data from the Phase 3 trial TMC114-C211 comparing darunavir/ritonavir 800/100 mg once daily versus lopinavir/ritonavir 800/200 mg per day in 689 antiretroviral treatment-naïve HIV-1-infected adult subjects.
The total mean exposure for subjects in the darunavir/ritonavir 800/100 mg once daily arm and in the lopinavir/ritonavir 800/200 mg per day arm was 162.5 and 153.5 weeks, respectively. The majority of the adverse drug reactions (ADRs) reported during treatment with darunavir/ritonavir 800/100 mg once daily were mild in severity. The most common clinical ADRs to darunavir/ritonavir 800/100 mg once daily (greater than or equal to 5%) of at least moderate intensity (greater than or equal to Grade 2) were diarrhea, headache, abdominal pain and rash.
2.3% of subjects in the darunavir/ritonavir arm discontinued treatment due to ADRs. ADRs to darunavir/ritonavir 800/100 mg once daily of at least moderate intensity (greater than or equal to Grade 2) in antiretroviral treatment-naïve HIV-1-infected adult subjects are presented in Table 6 and subsequent text below the table. Table 6: Selected Clinical Adverse Drug Reactions to Darunavir/Ritonavir 800/100 mg Once Daily Excluding laboratory abnormalities reported as ADRs. of at Least Moderate Intensity (≥Grade 2) Occurring in ≥2% of Antiretroviral Treatment-Naïve HIV-1-Infected Adult Subjects (Trial TMC114-C211) N=total number of subjects per treatment group; FTC=emtricitabine; TDF=tenofovir disoproxil fumarate System organ class, preferred term, % Darunavir/Ritonavir 800/100 mg once daily + TDF/FTC N=343 Lopinavir/Ritonavir 800/200 mg per day +TDF/FTC N=346 Gastrointestinal Disorders Abdominal pain 6% 6% Diarrhea 9% 16% Nausea 4% 4% Vomiting 2% 4% General Disorders and Administration Site Conditions Fatigue <1% 3% Metabolism and Nutrition Disorders Anorexia 2% <1% Nervous System Disorders Headache 7% 6% Skin and Subcutaneous Tissue Disorders Rash 6% 7% Le ss Common Adverse Reactions Treatment-emergent ADRs of at least moderate intensity (greater than or equal to Grade 2) occurring in less than 2% of antiretroviral treatment-naïve subjects receiving darunavir/ritonavir 800/100 mg once daily are listed below by body system: Gastrointestinal Disorders : acute pancreatitis, dyspepsia, flatulence General Disorders and Administration Site Conditions : asthenia Hepatobiliary Disorders : acute hepatitis (e.g., acute hepatitis, cytolytic hepatitis, hepatotoxicity) Immune System Disorders : (drug) hypersensitivity, immune reconstitution syndrome Metabolism and Nutrition Disorders : diabetes mellitus Musculoskeletal and Co… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Co-administration of darunavir/ritonavir with other drugs can alter the concentrations of other drugs and other drugs may alter the concentrations of darunavir. The potential drug-drug interactions must be considered prior to and during therapy. ( 4 , 5.5 , 7 , 12.3 )
7.1Potential for darunavir/ritonavir to Affect Other Drugs Darunavir co-administered with ritonavir is an inhibitor of CYP3A, CYP2D6, and P-gp. Co-administration of darunavir and ritonavir with drugs that are primarily metabolized by CYP3A and CYP2D6 or are transported by P-gp may result in increased plasma concentrations of such drugs, which could increase or prolong their therapeutic effect and adverse events. Darunavir co-administered with ritonavir with drugs that have active metabolite(s) formed by CYP3A may result in reduced plasma concentrations of these active metabolite(s), potentially leading to loss of their therapeutic effect (see Table 10 ).
7.2Potential for Other Drugs to Affect Darunavir Darunavir and ritonavir are metabolized by CYP3A. In vitro data indicate that darunavir may be a P-gp substrate. Drugs that induce CYP3A activity would be expected to increase the clearance of darunavir and ritonavir, resulting in lowered plasma concentrations of darunavir and ritonavir.
Co-administration of darunavir and ritonavir and other drugs that inhibit CYP3A, or P-gp may decrease the clearance of darunavir and ritonavir and may result in increased plasma concentrations of darunavir and ritonavir (see Table 10 ).
7.3Established and Other Potentially Significant Drug Interactions Table 10 provides dosing recommendations as a result of drug interactions with darunavir/ritonavir. These recommendations are based on either drug interaction studies or predicted interactions due to the expected magnitude of interaction and potential for serious adverse events or loss of efficacy. The table includes examples of potentially significant interactions but is not all inclusive [see Contraindications (4) and Clinical Pharmacology (12.3) ] , and therefore the label of each drug that is co-administered with darunavir/ritonavir should be consulted for information related to the route of metabolism, interaction pathways, potential risks, and specific actions to be taken with regard to co-administration.
Table 10: Established and Other Potentially Significant Drug Interactions: Alterations in Dose or Regimen May be Recommended Based on Drug Interaction Studies or Predicted Interaction (see Contraindications (4) for a list of examples of contraindicated drugs) [see Clinical Pharmacology (12.3) for Magnitude of Interaction, Tables 15 and 16 ] Concomitant Drug Class Drug Name Examples Effect on Concentration of Darunavir Or Concomitant Drug Clinical Comment HIV-1-Antiviral Agents: Nucleoside Reverse Transcriptase Inhibitors (NRTIs) didanosine ↔ darunavir ↔ didanosine Didanosine should be administered one hour before or two hours after darunavir/ritonavir (which are administered with food).
HIV-1-Antiviral Agents: HIV-Protease Inhibitors (PIs) indinavir (The reference regimen for indinavir was indinavir/ritonavir 800/100 mg twice daily.) lopinavir/ritonavir saquinavir Other HIV protease inhibitors, except atazanavir [see Drug Interactions(7.4) ] ↑ darunavir ↑ indinavir ↓ darunavir ↔ lopinavir ↓ darunavir ↔ saquinavir The appropriate dose of indinavir in combination with darunavir/ritonavir has not been established. Appropriate doses of the combination have not been established. Hence, it is not recommended to co-administer lopinavir/ritonavir and darunavir, with or without ritonavir.
Appropriate doses of the combination have not been established. Hence, it is not recommended to co-administer saquinavir and darunavir, with or without ritonavir. As co-administration with darunavir/ritonavir has not been studied, co-administration is not recommended.
HIV-1-Antiviral Agents: CCR5 co-receptor antagonists maraviroc ↑ maraviroc When used in combination with darunav… [Excerpted — this section continues on DailyMed.]
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: Total darunavir exposures were generally lower during pregnancy compared to postpartum period. The reduction in darunavir exposures during pregnancy were greater for once daily dosing compared to the twice daily dosing regimen. ( 8.1 , 12.3 ) Lactation: Women infected with HIV should be instructed not to breastfeed due to the potential for HIV transmission.
( 8.2 ) Pediatrics: Not recommended for patients less than 3 years of age. ( 8.4 )
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to darunavir during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) 1-800-258-4263. Risk Summary Prospective pregnancy data from the APR are not sufficient to adequately assess the risk of birth defects or miscarriage.
Available limited data from the APR show no statistically significant difference in the overall risk of major birth defects for darunavir compared with the background rate for major birth defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) [ see Data ]. The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15 to 20%.
The background risk of major birth defects and miscarriage for the indicated population is unknown. Studies in animals did not show evidence of developmental toxicity. Exposures (based on AUC) in rats were 3-fold higher, whereas in mice and rabbits, exposures were lower (less than 1-fold) than human exposures at the recommended daily dose [ see Data ].
Clinical Considerations The recommended dosage in pregnant patients is darunavir 600 mg taken with ritonavir 100 mg twice daily with food. Darunavir 800 mg taken with ritonavir 100 mg once daily should only be considered in certain pregnant patients who are already on a stable darunavir 800 mg with ritonavir 100 mg once daily regimen prior to pregnancy, are virologically suppressed (HIV-1 RNA less than 50 copies per mL), and in whom a change to twice daily darunavir 600 mg with ritonavir 100 mg may compromise tolerability or compliance [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ].
Data Human Data Darunavir/ritonavir (600/100 mg twice daily or 800/100 mg once daily) in combination with a background regimen was evaluated in a clinical trial of 36 pregnant women during the second and third trimesters, and postpartum. Eighteen subjects were enrolled in each BID and QD treatment arms. Twenty-nine subjects completed the trial through the postpartum period (6 to 12 weeks after delivery) and 7 subjects discontinued before trial completion, 5 subjects in the BID arm and 2 subjects in the QD arm.
The pharmacokinetic data demonstrate that exposure to darunavir and ritonavir as part of an antiretroviral regimen was lower during pregnancy compared with postpartum (6 to 12 weeks). Exposure reductions during pregnancy were greater for the once daily regimen as compared to the twice daily regimen [ see Clinical Pharmacology (12.3) ]. Virologic response was preserved.
In the BID arm, the proportion of subjects with HIV-1 RNA <50 copies/mL were 39% (7/18) at baseline, 61% (11/18) through the third trimester visit, and 61% (11/18) through the 6 to 12 week postpartum visit. Virologic outcomes during the third trimester visit showed HIV-1 RNA ≥50 copies/mL for 11% (2/18) of subjects and were missing for 5 subjects (1 subject discontinued prematurely due to virologic failure). In the QD arm, the proportion of subjects with HIV-1 RNA <50 copies/mL were 61% (11/18) at baseline, 83% (15/18) through the third trimester visit, and 78% (14/18) through the 6 to 12 week postpartum visit.
Virologic outcomes during the third trimester visit showed HIV-1 RNA ≥50 copies/mL for none of the subjects and were missin… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to darunavir during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) 1-800-258-4263. Risk Summary Prospective pregnancy data from the APR are not sufficient to adequately assess the risk of birth defects or miscarriage.
Available limited data from the APR show no statistically significant difference in the overall risk of major birth defects for darunavir compared with the background rate for major birth defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) [ see Data ]. The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15 to 20%.
The background risk of major birth defects and miscarriage for the indicated population is unknown. Studies in animals did not show evidence of developmental toxicity. Exposures (based on AUC) in rats were 3-fold higher, whereas in mice and rabbits, exposures were lower (less than 1-fold) than human exposures at the recommended daily dose [ see Data ].
Clinical Considerations The recommended dosage in pregnant patients is darunavir 600 mg taken with ritonavir 100 mg twice daily with food. Darunavir 800 mg taken with ritonavir 100 mg once daily should only be considered in certain pregnant patients who are already on a stable darunavir 800 mg with ritonavir 100 mg once daily regimen prior to pregnancy, are virologically suppressed (HIV-1 RNA less than 50 copies per mL), and in whom a change to twice daily darunavir 600 mg with ritonavir 100 mg may compromise tolerability or compliance [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ].
Data Human Data Darunavir/ritonavir (600/100 mg twice daily or 800/100 mg once daily) in combination with a background regimen was evaluated in a clinical trial of 36 pregnant women during the second and third trimesters, and postpartum. Eighteen subjects were enrolled in each BID and QD treatment arms. Twenty-nine subjects completed the trial through the postpartum period (6 to 12 weeks after delivery) and 7 subjects discontinued before trial completion, 5 subjects in the BID arm and 2 subjects in the QD arm.
The pharmacokinetic data demonstrate that exposure to darunavir and ritonavir as part of an antiretroviral regimen was lower during pregnancy compared with postpartum (6 to 12 weeks). Exposure reductions during pregnancy were greater for the once daily regimen as compared to the twice daily regimen [ see Clinical Pharmacology (12.3) ]. Virologic response was preserved.
In the BID arm, the proportion of subjects with HIV-1 RNA <50 copies/mL were 39% (7/18) at baseline, 61% (11/18) through the third trimester visit, and 61% (11/18) through the 6 to 12 week postpartum visit. Virologic outcomes during the third trimester visit showed HIV-1 RNA ≥50 copies/mL for 11% (2/18) of subjects and were missing for 5 subjects (1 subject discontinued prematurely due to virologic failure). In the QD arm, the proportion of subjects with HIV-1 RNA <50 copies/mL were 61% (11/18) at baseline, 83% (15/18) through the third trimester visit, and 78% (14/18) through the 6 to 12 week postpartum visit.
Virologic outcomes during the third trimester visit showed HIV-1 RNA ≥50 copies/mL for none of the subjects and were missing for 3 subjects (1 subject discontinued prematurely due to virologic failure). Darunavir/ritonavir was well tolerated during pregnancy and postpartum. There were no new clinically relevant safety findings compared with the known safety profile of darunavir/ritonavir in HIV-1 infected adults Among the 31 infants with HIV test results available data, born to the 31 HIV-infected pregnant women who completed trial through delivery or postpartum period, all 31 infants had test result… [Excerpted — this section continues on DailyMed.]
🧒 Pediatric Use ▾
8.4Pediatric Use Darunavir/ritonavir is not recommended in pediatric patients below 3 years of age because of toxicity and mortality observed in juvenile rats dosed with darunavir (from 20 mg/kg to 1000 mg/kg) up to days 23 to 26 of age [see Warnings and Precautions (5.10) , Use in Specific Populations (8.1) and Clinical Pharmacology (12.3) ] . The safety, pharmacokinetic profile, and virologic and immunologic responses of darunavir/ritonavir administered twice daily were evaluated in treatment-experienced HIV-1 infected pediatric subjects 3 to less than 18 years of age and weighting at least 10 kg.
These subjects were evaluated in clinical trials TMC114-C212 (80 subjects, 6 to less than 18 years of age) and TMC114-228 (21 subjects, 3 to less than 6 years of age) [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) and Clinical Studies (14.4) ] . Frequency, type, and severity of adverse drug reactions in pediatric subjects were comparable to those observed in adults [see Adverse Reactions (6.1) ] . Refer to Dosage and Administration (2.5) for twice-daily dosing recommendations for pediatric subjects 3 to less than 18 years of age and weighing at least 10 kg.
In clinical trial TMC114-C230, the safety, pharmacokinetic profile and virologic and immunologic responses of darunavir/ritonavir administered once daily were evaluated in treatment-naïve HIV-1 infected pediatric subjects 12 to less than 18 years of age (12 subjects) [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) and Clinical Studies (14.4) ]. Frequency, type, and severity of adverse drug reactions in pediatric subjects were comparable to those observed in adults [see Adverse Reactions (6.1) ]. Once daily dosing recommendations for pediatric patients 3 to less than 12 years of age were derived using population pharmacokinetic modeling and simulation.
Although a darunavir/ritonavir once daily dosing pediatric trial was not conducted in children less than 12 years of age, there is sufficient clinical safety data to support the predicted darunavir exposures for the dosing recommendations in this age group [see Clinical Pharmacology (12.3) ]. Please see Dosage and Administration (2.5) for once-daily dosing recommendations for pediatric subjects 3 to less than 18 years of age and weighing at least 10 kg. Juvenile Animal Data In a juvenile toxicity study where rats were directly dosed with darunavir (up to 1000 mg/kg), deaths occurred from post-natal day 5 at plasma exposure levels ranging from 0.1 to 1.0 of the human exposure levels.
In a 4-week rat toxicology study, when dosing was initiated on post-natal day 23 (the human equivalent of 2 to 3 years of age), no deaths were observed with a plasma exposure (in combination with ritonavir) 2 times the human plasma exposure levels.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of darunavir did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. In general, caution should be exercised in the administration and monitoring of darunavir in elderly patients, reflecting the greater frequency of decreased hepatic function, and of concomitant disease or other drug therapy [see Clinical Pharmacology (12.3) ].
🆘 Overdosage ▾
10 OVERDOSAGE Human experience of acute overdose with darunavir/ritonavir is limited. No specific antidote is available for overdose with darunavir. Treatment of overdose with darunavir consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. Since darunavir is highly protein bound, dialysis is unlikely to be beneficial in significant removal of the active substance.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Darunavir is an HIV-1 antiviral drug [see Microbiology (12.4) ] .
12.2Pharmacodynamics Cardiac Electrophysiology In a thorough QT/QTc study in 40 healthy subjects, darunavir/ritonavir doses of 1.33 times the maximum recommended dose did not affect the QT/QTc interval.
12.3Pharmacokinetics Pha rm a cokinetics in Adults General : Darunavir is primarily metabolized by CYP3A. Ritonavir inhibits CYP3A, thereby increasing the plasma concentrations of darunavir. When a single dose of darunavir 600 mg was given orally in combination with 100 mg ritonavir twice daily, there was an approximate 14-fold increase in the systemic exposure of darunavir.
Therefore, darunavir should only be used in combination with 100 mg of ritonavir to achieve sufficient exposures of darunavir. The pharmacokinetics of darunavir, co-administered with low dose ritonavir (100 mg), has been evaluated in healthy adult volunteers and in HIV-1-infected subjects. Table 11 displays the population pharmacokinetic estimates of darunavir after oral administration of darunavir/ritonavir 600/100 mg twice daily (based on sparse sampling in 285 patients in trial TMC114-C214, 278 patients in trial TMC114-C229 and 119 patients [integrated data] from trials TMC114-C202 and TMC114-C213) and darunavir/ritonavir 800/100 mg once daily (based on sparse sampling in 335 patients in trial TMC114-C211 and 280 patients in trial TMC114-C229) to HIV-1-infected patients.
Table 11: Population Pharmacokinetic Estimates of Darunavir at Darunavir/Ritonavir 800/100 mg Once Daily (Trial TMC114-C211, 48-Week Analysis and Trial TMC114-C229, 48-Week Analysis) and Darunavir/Ritonavir 600/100 mg Twice Daily (Trial TMC114-C214, 48-Week Analysis, Trial TMC114-C229, 48-Week Analysis and Integrated Data from Trials TMC114-C213 and TMC114-C202, Primary 24-Week Analysis) N=number of subjects with data Parameter Darunavir/Ritonavir 800/100 mg once daily Darunavir/Ritonavir 600/100 mg twice daily TMC114-C211 N=335 TMC114-C229 N=280 TMC114-C214 N=285 TMC114-C229 N=278 TMC114-C213 + TMC114-C202 (integrated data) N=119 AUC 24h (ng.h/mL) AUC 24h is calculated as AUC 12h *2.
Mean ± Standard Deviation 93026 ± 27050 93334 ± 28626 116796 ± 33594 114302 ± 32681 124698 ± 32286 Median (Range) 87854 (45000 to 219240) 87788 (45456 to 236920) 111632 (64874 to 355360) 109401 (48934 to 323820) 123336 (67714 to 212980) C 0h (ng/mL) Mean ± Standard Deviation 2282 ± 1168 2160 ± 1201 3490 ± 1401 3386 ± 1372 3578 ± 1151 Median (Range) 2041 (368 to 7242) 1896 (184 to 7881) 3307 (1517 to 13198) 3197 (250 to 11865) 3539 (1255 to 7368) Absorption and Bioavailability Darunavir, co-administered with 100 mg ritonavir twice daily, was absorbed following oral administration with a T max of approximately 2.5 to 4 hours.
The absolute oral bioavailability of a single 600 mg dose of darunavir alone and after co-administration with 100 mg ritonavir twice daily was 37% and 82%, respectively. In vivo data suggest that darunavir/ritonavir is an inhibitor of the P-glycoprotein (P-gp) transporters. E ffects of Food on Oral Absorption When darunavir tablets were administered with food, the C max and AUC of darunavir, co-administered with ritonavir, is approximately 40% higher relative to the fasting state.
Within the range of meals studied, darunavir exposure is similar. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 gms fat) to 928 Kcal (56 gms fat). Distribution: Darunavir is approximately 95% bound to plasma proteins.
Darunavir binds primarily to plasma alpha 1-acid glycoprotein (AAG). M e tabolism: In vitro experiments with human liver microsomes (HLMs) indicate that darunavir primarily undergoes oxidative metabolism. Darunavir is extensively metabolized by CYP enzymes, primarily by CYP3A.
A mass balance study in healthy volunteers showed that after a single dose administration of 400 mg 14 C-darunavir, co-administered with 100 mg ritonavir, the majority of t… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Darunavir is an HIV-1 antiviral drug [see Microbiology (12.4) ] .
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Darunavir Tablets, 600 mg are supplied as orange colored, oval shaped, film-coated tablets debossed with 'LU' on one side and 'A42' on the other side. Darunavir Tablets, 800 mg are supplied as dark red colored, oval shaped, film-coated tablets debossed with 'LU' on one side and 'A46' on the other side. Darunavir Tablets are packaged in bottles in the following configuration: 600 mg tablets - bottles of 60 (NDC 68180-345-07) 800 mg tablets - bottles of 30 (NDC 68180-346-06) Storage Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature].
Keep darunavir tablets out of reach of children.
📋 Description ▾
11 DESCRIPTION Darunavir is an inhibitor of the human immunodeficiency virus (HIV-1) protease. Darunavir tablets contain the active ingredient darunavir, (present as darunavir ethanolate) which has the following chemical name: [(1S,2R)-3-[[(4-aminophenyl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1 (phenylmethyl)propyl]-carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester monoethanolate. Its molecular formula is C 27 H 37 N 3 O 7 S • C 2 H 5 OH and its molecular weight is 593.73.
Darunavir ethanolate has the following structural formula: Darunavir ethanolate is a white to off-white powder with a solubility of approximately 0.15 mg per mL in water at 20°C. Darunavir tablets 600 mg are available as orange colored, oval shaped, film-coated tablets debossed with 'LU' on one side and 'A42' on the other side. Each 600 mg tablet contains darunavir 600 mg (present as darunavir ethanolate).
Darunavir tablets 800 mg are available as dark red colored, oval shaped, film-coated tablets debossed with 'LU' on one side and 'A46' on the other side. Each 800 mg tablet contains darunavir 800 mg (present as darunavir ethanolate). During storage, partial conversion from ethanolate to hydrate may occur; however, this does not affect product quality or performance.
Each tablet also contains the inactive ingredients colloidal silicon dioxide, crospovidone, hypromellose [800 mg] magnesium stearate and microcrystalline cellulose. Each tablet film-coating contains FD & C yellow #6/ Sunset Yellow FCF Aluminium Lake [600 mg], iron oxide red [800 mg], polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, and titanium dioxide. All strengths for darunavir are expressed in terms of the free form of darunavir.
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💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instruction for Use). Instructions for Use Advise patients to take darunavir and ritonavir with food every day on a regular dosing schedule, as missed doses can result in development of resistance. Darunavir tablets must always be used with ritonavir in combination with other antiretroviral drugs.
Advise patients not to alter the dose of either darunavir or ritonavir, discontinue ritonavir, or discontinue therapy with darunavir tablets without consulting their physician [see Dosage and Administration (2) ] . Hepatotoxicity Inform patients that drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) has been reported with darunavir co-administered with 100 mg of ritonavir. Advise patients about the signs and symptoms of liver problems [see Warnings and Precautions (5.2) ] .
Se v e r e Skin Reactions Inform patients that skin reactions ranging from mild to severe, including Stevens-Johnson Syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, have been reported with darunavir co-administered with 100 mg of ritonavir. Advise patients to discontinue darunavir/ritonavir immediately if signs or symptoms of severe skin reactions develop. These can include but are not limited to severe rash or rash accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia [see Warnings and Precautions (5.3) ] .
Drug Interactions Darunavir/ritonavir may interact with many drugs; therefore, advise patients to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products, including St. John's wort [see Contraindications (4) , Warnings and Precautions ( 5.4 , 5.5 ) and Drug Interactions (7) ] . Contraception Instruct patients receiving combined hormonal contraception or the progestin only pill to use an effective alternative (non-hormonal) contraceptive method or add a barrier method during therapy with darunavir/ritonavir because hormonal levels may decrease [see Drug Interactions (7.3) and Use in Specific Populations (8.3) ] .
Fat Redistribution Inform patients that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy, including darunavir/ritonavir, and that the cause and long-term health effects of these conditions are not known at this time [see Warnings and Precautions (5.7) ] . Immune Reconstitution Syndrome Advise patients to inform their healthcare provider immediately of any symptoms of infection, as in some patients with advanced HIV infection (AIDS), signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started [see Warnings and Precautions (5.8) ].
Pregnancy Registry Inform patients that there is an antiretroviral pregnancy registry to monitor fetal outcomes of pregnant women exposed to darunavir [ see Use in Specific Populations (8.1) ] . La ctation Instruct women with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in breast milk [see Use in Specific Populations (8.2) ] . All brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc.
The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products. LUPIN and the are registered trademarks of Lupin Pharmaceuticals, Inc. Manufactured for: Lupin Pharmaceuticals, Inc.
Naples, FL 34108 United States. Manufactured by: Lupin Limited Nagpur 441 108 INDIA. Revised: October 2024 Image
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Pha rm a cokinetics in Adults General : Darunavir is primarily metabolized by CYP3A. Ritonavir inhibits CYP3A, thereby increasing the plasma concentrations of darunavir. When a single dose of darunavir 600 mg was given orally in combination with 100 mg ritonavir twice daily, there was an approximate 14-fold increase in the systemic exposure of darunavir.
Therefore, darunavir should only be used in combination with 100 mg of ritonavir to achieve sufficient exposures of darunavir. The pharmacokinetics of darunavir, co-administered with low dose ritonavir (100 mg), has been evaluated in healthy adult volunteers and in HIV-1-infected subjects. Table 11 displays the population pharmacokinetic estimates of darunavir after oral administration of darunavir/ritonavir 600/100 mg twice daily (based on sparse sampling in 285 patients in trial TMC114-C214, 278 patients in trial TMC114-C229 and 119 patients [integrated data] from trials TMC114-C202 and TMC114-C213) and darunavir/ritonavir 800/100 mg once daily (based on sparse sampling in 335 patients in trial TMC114-C211 and 280 patients in trial TMC114-C229) to HIV-1-infected patients.
Table 11: Population Pharmacokinetic Estimates of Darunavir at Darunavir/Ritonavir 800/100 mg Once Daily (Trial TMC114-C211, 48-Week Analysis and Trial TMC114-C229, 48-Week Analysis) and Darunavir/Ritonavir 600/100 mg Twice Daily (Trial TMC114-C214, 48-Week Analysis, Trial TMC114-C229, 48-Week Analysis and Integrated Data from Trials TMC114-C213 and TMC114-C202, Primary 24-Week Analysis) N=number of subjects with data Parameter Darunavir/Ritonavir 800/100 mg once daily Darunavir/Ritonavir 600/100 mg twice daily TMC114-C211 N=335 TMC114-C229 N=280 TMC114-C214 N=285 TMC114-C229 N=278 TMC114-C213 + TMC114-C202 (integrated data) N=119 AUC 24h (ng.h/mL) AUC 24h is calculated as AUC 12h *2.
Mean ± Standard Deviation 93026 ± 27050 93334 ± 28626 116796 ± 33594 114302 ± 32681 124698 ± 32286 Median (Range) 87854 (45000 to 219240) 87788 (45456 to 236920) 111632 (64874 to 355360) 109401 (48934 to 323820) 123336 (67714 to 212980) C 0h (ng/mL) Mean ± Standard Deviation 2282 ± 1168 2160 ± 1201 3490 ± 1401 3386 ± 1372 3578 ± 1151 Median (Range) 2041 (368 to 7242) 1896 (184 to 7881) 3307 (1517 to 13198) 3197 (250 to 11865) 3539 (1255 to 7368) Absorption and Bioavailability Darunavir, co-administered with 100 mg ritonavir twice daily, was absorbed following oral administration with a T max of approximately 2.5 to 4 hours.
The absolute oral bioavailability of a single 600 mg dose of darunavir alone and after co-administration with 100 mg ritonavir twice daily was 37% and 82%, respectively. In vivo data suggest that darunavir/ritonavir is an inhibitor of the P-glycoprotein (P-gp) transporters. E ffects of Food on Oral Absorption When darunavir tablets were administered with food, the C max and AUC of darunavir, co-administered with ritonavir, is approximately 40% higher relative to the fasting state.
Within the range of meals studied, darunavir exposure is similar. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 gms fat) to 928 Kcal (56 gms fat). Distribution: Darunavir is approximately 95% bound to plasma proteins.
Darunavir binds primarily to plasma alpha 1-acid glycoprotein (AAG). M e tabolism: In vitro experiments with human liver microsomes (HLMs) indicate that darunavir primarily undergoes oxidative metabolism. Darunavir is extensively metabolized by CYP enzymes, primarily by CYP3A.
A mass balance study in healthy volunteers showed that after a single dose administration of 400 mg 14 C-darunavir, co-administered with 100 mg ritonavir, the majority of the radioactivity in the plasma was due to darunavir. At least 3 oxidative metabolites of darunavir have been identified in humans; all showed activity that was at least 90% less than the activity of darunavir against wild-type HIV-1. E limination: A mass balance study in healthy volunteers showed that after single dose… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics Cardiac Electrophysiology In a thorough QT/QTc study in 40 healthy subjects, darunavir/ritonavir doses of 1.33 times the maximum recommended dose did not affect the QT/QTc interval.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Description of Adult Clinical Trials The evidence of efficacy of darunavir/ritonavir is based on the analyses of 192-week data from a randomized, controlled open-label Phase 3 trial in treatment-naïve (TMC114-C211) HIV-1 infected adult subjects and 96-week data from a randomized, controlled, open-label Phase 3 trial in antiretroviral treatment-experienced (TMC114-C214) HIV-1-infected adult subjects. In addition, 96-week data are included from 2 randomized, controlled Phase 2b trials, TMC114 C213 and TMC114-C202, in antiretroviral treatment-experienced HIV-1-infected adult subjects.
14.2Treatment-Naïve Adult Subjects T M C114-C211 TMC114-C211 is a randomized, controlled, open-label Phase 3 trial comparing darunavir/ritonavir 800/100 mg once daily versus lopinavir/ritonavir 800/200 mg per day (given as a twice daily or as a once daily regimen) in antiretroviral treatment-naïve HIV-1 infected adult subjects. Both arms used a fixed background regimen consisting of tenofovir disoproxil fumarate 300 mg once daily (TDF) and emtricitabine 200 mg once daily (FTC). HIV-1-infected subjects who were eligible for this trial had plasma HIV-1 RNA greater than or equal to 5000 copies/mL.
Randomization was stratified by screening plasma viral load (HIV-1 RNA less than 100,000 copies/mL or greater than or equal to 100,000 copies/mL) and screening CD4+ cell count (less than 200 cells/mm 3 or greater than or equal to 200 cells/mm 3 ). Virologic response was defined as a confirmed plasma HIV-1 RNA viral load less than 50 copies/mL. Analyses included 689 subjects in trial TMC114-C211 who had completed 192 weeks of treatment or discontinued earlier.
Demographics and baseline characteristics were balanced between the darunavir/ritonavir arm and the lopinavir/ritonavir arm (see Table 19 ). Table 19 compares the demographic and baseline characteristics between subjects in the darunavir/ritonavir 800/100 mg once daily arm and subjects in the lopinavir/ritonavir 800/200 mg per day arm in trial TMC114-C211. Table 19: Demographic and Baseline Characteristics of Subjects in Trial TMC114-C211 FTC=emtricitabine; TDF=tenofovir disoproxil fumarate Darunavir/ritonavir 800/100 mg Once Daily + TDF/FTC N=343 Lopinavir/ritonavir 800/200 mg Per Day + TDF/FTC N=346 Demographic characteristics Median age (years) (range, years) 34 (18 to 70) 33 (19 to 68) Sex Male 70% 70% Female 30% 30% Race White 40% 45% Black 23% 21% Hispanic 23% 22% Asian 13% 11% Baseline characteristics Mean baseline plasma HIV-1 RNA (log 10 copies/mL) 4.86
4.84Median baseline CD4+ cell count (cells/mm 3 ) (range, cells/mm 3 ) 228 (4 to 750) 218 (2 to 714) Percentage of patients with baseline viral load ≥100,000 copies/mL 34% 35% Percentage of patients with baseline CD4+ cell count <200 cells/mm 3 41% 43% Week 192 outcomes for subjects on darunavir/ritonavir 800/100 mg once daily from trial TMC114-C211 are shown in Table 20 . Table 20: Virologic Outcome of Randomized Treatment of Trial TMC114-C211 at 192 Weeks N = total number of subjects with data; FTC = emtricitabine; TDF = tenofovir disoproxil fumarate Darunavir/ritonavir 800/100 mg Once Daily + TDF/FTC N=343 Lopinavir/ritonavir 800/200 mg Per Day + TDF/FTC N=346 Virologic success HIV-1 RNA <50 copies/mL 70% 95% CI: 1.9; 16.1 61% Virologic failure Includes patients who discontinued prior to Week 192 for lack or loss of efficacy and patients who are ≥50 copies in the 192-week window and patients who had a change in their background regimen that was not permitted by the protocol.
12% 15% No virologic data at Week 192 window Window 186 to 198 Weeks. Reasons Discontinued trial due to adverse event or death Includes patients who discontinued due to adverse event or death at any time point from Day 1 through the time window if this resulted in no virologic data on treatment during the specified window. 5% 13% Discontinued trial for other reasons Other includes: withdrew consent, loss to follow-up, etc., if the viral load at t… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis and Mutagenesis Darunavir was evaluated for carcinogenic potential by oral gavage administration to mice and rats up to 104 weeks. Daily doses of 150, 450 and 1000 mg/kg were administered to mice and doses of 50, 150 and 500 mg/kg was administered to rats. A dose-related increase in the incidence of hepatocellular adenomas and carcinomas were observed in males and females of both species as well as an increase in thyroid follicular cell adenomas in male rats.
The observed hepatocellular findings in rodents are considered to be of limited relevance to humans. Repeated administration of darunavir to rats caused hepatic microsomal enzyme induction and increased thyroid hormone elimination, which predispose rats, but not humans, to thyroid neoplasms. At the highest tested doses, the systemic exposures to darunavir (based on AUC) were between 0.4 and 0.7-fold (mice) and 0.7- and 1-fold (rats), relative to those observed in humans at the recommended therapeutic doses (600/100 mg twice daily or 800/100 mg once daily).
Darunavir was not mutagenic or genotoxic in a battery of in vitro and in vivo assays including bacterial reserve mutation (Ames), chromosomal aberration in human lymphocytes and in vivo micronucleus test in mice. Impairment of Fertility No effects on fertility or early embryonic development were observed with darunavir in rats.
📄 Patient Package Insert ▾
PATIENT INFORMATION DARUNAVIR (dar-UE-na-vir) TABLETS Rx only Read this Patient Information before you start taking darunavir and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
Also read the Patient Information leaflet for ritonavir. W h at is the most important information I should know about Darunavir? A s k your healthcare provider or pharmacist about medicines that should not be taken with darunavir.
For more information, see "Who should not take darunavir?" and "What should I tell my healthcare provider before taking darunavir?" Darunavir m a y cause liver problems. Some people taking darunavir in combination with ritonavir have developed liver problems, which may be life-threatening. Your healthcare provider should do blood tests before and during your darunavir and ritonavir combination treatment.
If you have chronic hepatitis B or C infection, your healthcare provider should check your blood tests more often because you have an increased chance of developing liver problems. Tell your healthcare provider if you have any of the below signs and symptoms of liver problems. dark (tea colored) urine yellowing of your skin or whites of your eyes pale colored stools (bowel movements) nausea vomiting pain or tenderness on your right side below your ribs loss of appetite tiredness D arunavir m a y cause severe or life-threatening skin reactions or rash.
Sometimes these skin reactions and skin rashes can become severe and require treatment in a hospital. Tell your healthcare provider right away if you develop a rash. Stop taking darunavir and ritonavir combination treatment and tell your healthcare provider right away if you have any skin changes with symptoms below: fever tiredness muscle or joint pain blisters or skin lesions mouth sores or ulcers red or inflamed eyes, like "pink eye" (conjunctivitis) Rash occurred more often in people taking darunavir and raltegravir together than with either drug separately but was generally mild.
See "What are the possible side effects of darunavir?" for more information about side effects. W h at is darunavir? Darunavir is a prescription HIV-1 (Human Immunodeficiency Virus-type 1) medicine used with ritonavir and other antiretroviral medicines to treat HIV-1 infection in adults and children 3 years of age and older.
HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome). Darunavir should not be used in children under 3 years of age. When used with other antiretroviral medicines to treat HIV-1 infection, darunavir may help: reduce the amount of HIV-1 in your blood.
This is called "viral load". increase the number of CD4+ (T) cells in your blood that help fight off other infections. Reducing the amount of HIV-1 and increasing the CD4+ (T) cells in your blood may improve your immune system. This may reduce your risk of death or getting infections that can happen when your immune system is weak (opportunistic infections).
Darunavir do e s not cure HIV-1 infection or AIDS. You must keep taking HIV-1 medicines to control HIV-1 infection and decrease HIV-related illnesses. A v o id doing things that can spread HIV-1 infection to others: Do not share or re-use needles or other injection equipment.
Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades. Do not have any kind of sex without protection. Always practice safe sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.
Ask your healthcare provider if you have any questions on how to prevent passing HIV to other people. W h o should not take darunavir? Do not take darunavir with any medicine that contains: alfuzosin colchicine, if you have liver or kidney problems dronedarone elbasvir and grazoprevir ergot-containing medicines: dihydroergotamine ergotamine tartrate methyle… [Excerpted — this section continues on DailyMed.]
📄 Package Label / Principal Display Panel ▾
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL Darunavir Tablets Rx Only 600 mg NDC 68180-345-07 Bottle Label - 60 Tablets Darunavir Tablets Rx Only 800 mg NDC 68180-346-06 Bottle Label - 30 Tablets 600 mg-60's Tablets 800 mg-30's Tablets