Darunavir

Name: Darunavir

Description

PREZISTA (darunavir) is an inhibitor of the human immunodeficiency virus (HIV-1) protease.

PREZISTA (darunavir), in the form of darunavir ethanolate, 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 C27H37N3O7S• C2H5OH 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.

PREZISTA 100 mg per mL oral suspension is available as a white to off-white opaque suspension for oral administration.

Each mL of the oral suspension contains darunavir ethanolate equivalent to 100 mg darunavir. In addition, each mL contains the inactive ingredients hydroxypropyl cellulose, microcrystalline cellulose, sodium carboxymethylcellulose, methylparaben sodium, citric acid monohydrate, sucralose, masking flavor, strawberry cream flavor, hydrochloric acid (for pH adjustment) and purified water.

PREZISTA 75 mg tablets are available as white, caplet-shaped, film-coated tablets for oral administration. Each 75 mg tablet contains darunavir ethanolate equivalent to 75 mg of darunavir.

PREZISTA 150 mg tablets are available as white, oval-shaped, film-coated tablets for oral administration. Each 150 mg tablet contains darunavir ethanolate equivalent to 150 mg of darunavir.

PREZISTA 600 mg tablets are available as orange, oval-shaped, film-coated tablets for oral administration. Each 600 mg tablet contains darunavir ethanolate equivalent to 600 mg of darunavir.

PREZISTA 800 mg tablets are available as dark red, oval-shaped, film-coated tablets for oral administration. Each 800 mg tablet contains darunavir ethanolate equivalent to 800 mg of darunavir.

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, magnesium stearate, and microcrystalline cellulose. The 800 mg tablet also contains hypromellose. The 75 and 150 mg tablet film coating, OPADRY® White, contains polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, and titanium dioxide. The 600 mg tablet film coating, OPADRY® Orange, contains FD&C Yellow No. 6, polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, and titanium dioxide. The 800 mg tablet film coating, OPADRY® Dark Red, contains iron oxide red, polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, and titanium dioxide.

All dosages for PREZISTA are expressed in terms of the free form of darunavir.

Indications

PREZISTA®, co-administered with ritonavir (PREZISTA/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 and Clinical Studies].

Patient information

PREZISTA
(pre-ZIS-ta)
(darunavir) Oral Suspension

PREZISTA
(pre-ZIS-ta)
(darunavir) Tablet

Read this Patient Information before you start taking PREZISTA 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.

What is the most important information I should know about PREZISTA?

  • Ask your healthcare provider or pharmacist about medicines that should not be taken with PREZISTA. For more information, see “Who should not take PREZISTA?” and “What should I tell my healthcare provider before taking PREZISTA?”
  • PREZISTA may cause liver problems. Some people taking PREZISTA in combination with ritonavir have developed liver problems, which may be life-threatening. Your healthcare provider should do blood tests before and during your PREZISTA 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
  • PREZISTA may 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 PREZISTA 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 PREZISTA and raltegravir together than with either drug separately, but was generally mild.

See “What are the possible side effects of PREZISTA?” for more information about side effects.

What is PREZISTA?

PREZISTA 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).

PREZISTA should not be used in children under 3 years of age.

When used with other antiretroviral medicines to treat HIV-1 infection, PREZISTA 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).

PREZISTA does not cure HIV-1 infection or AIDS. You must keep taking HIV-1 medicines to control HIV-1 infection and decrease HIV-related illnesses.

Avoid 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.

Who should not take PREZISTA?

Do not take PREZISTA with any of the following medicines:

  • alfuzosin (Uroxatral®)
  • ergot-containing medicines:
    • dihydroergotamine (D.H.E. 45®, Embolex®, Migranal®)
    • ergotamine tartrate (Cafergot®, Ergomar®, Ergostat®, Medihaler ergotamine ®, Migergot®, W igraine®, W igrettes®)
    • methylergonovine (Ergotrate®, Methergine®)
  • cisapride (Propulside®, Propulsid® Quicksolv)
  • colchicine (Colcrys®, Mitigare®), if you have liver or kidney problems
  • dronedarone (Multaq®)
  • pimozide (Orap®)
  • midazolam (Versed®), when taken by mouth
  • ranolazine (Ranexa®)
  • St. John's Wort (Hypericum perforatum) or a product that contains St. John's Wort
  • lovastatin or a product that contains lovastatin (Altoprev®, Advicor®, Mevacor®)
  • simvastatin or a product that contains simvastatin (Simcor®, Vytorin®, Zocor®)
  • rifampin or a product that contains rifampin (Rifadin®, Rifater®, Rifamate®, Rimactane®)
  • sildenafil (Revatio®), when used for the treatment of pulmonary arterial hypertension (PAH)
  • triazolam (Halcion®)

Serious problems can happen if you or your child take any of these medicines with PREZISTA.

What should I tell my healthcare provider before taking PREZISTA?

Before taking PREZISTA, tell your healthcare provider if you:

  • have liver problems, including hepatitis B or hepatitis C
  • are allergic to sulfa medicines
  • have high blood sugar (diabetes)
  • have hemophilia
  • have any other medical conditions
  • are pregnant or plan to become pregnant. Tell your healthcare provider if you become pregnant while taking PREZISTA.
    • Pregnancy Registry: There is a pregnancy registry for women who take antiretroviral medicines during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry.
  • are breastfeeding or plan to breastfeed. Do not breastfeed if you take PREZISTA.
    • You should not breastfeed if you have HIV-1 because of the risk of passing HIV-1 to your baby.
    • It is not known if PREZISTA can pass into your breast milk.
    • Talk to your healthcare provider about the best way to feed your baby.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines interact with PREZISTA. Keep a list of your medicines to show your healthcare provider and pharmacist.

  • You can ask your healthcare provider or pharmacist for a list of medicines that interact with PREZISTA.
  • Do not start taking a new medicine without telling your healthcare provider. Your healthcare provider can tell you if it is safe to take PREZISTA with other medicines.

How should I take PREZISTA?

  • Take PREZISTA exactly as your healthcare provider tells you.
  • You must take ritonavir at the same time as PREZISTA.
  • Do not change your dose or stop treatment with PREZISTA without talking to your healthcare provider.
  • Take PREZISTA and ritonavir with food.
  • If you have difficulty swallowing PREZISTA tablets, PREZISTA oral suspension is also available. Your healthcare provider will help decide whether PREZISTA tablets or oral suspension is right for you.
  • If your child is taking PREZISTA, your child's healthcare provider will decide the right dose based on your child's weight. Your child's healthcare provider will tell you how much PREZISTA (tablets or oral suspension) and how much ritonavir (capsules, tablets or solution) your child should take. Your child should take PREZISTA with ritonavir with food. If your child does not tolerate ritonavir oral solution, ask your child's healthcare provider for advice.
  • PREZISTA oral suspension should be given with the supplied oral dosing syringe. Shake the suspension well before each use. See the “Instructions for Use” that come with PREZISTA oral suspension for information about the right way to prepare and take a dose.
  • It is important that you do not miss or skip doses of PREZISTA during treatment.
  • If you take too much PREZISTA, call your healthcare provider or go to the nearest hospital emergency room right away.

What are the possible side effects of PREZISTA?

PREZISTA may cause serious side effects, including:

  • See “What is the most important information I should know about PREZISTA?”
  • Diabetes and high blood sugar (hyperglycemia). Some people who take protease inhibitors including PREZISTA can get high blood sugar, develop diabetes, or your diabetes can get worse. Tell your healthcare provider if you notice an increase in thirst or urinate often while taking PREZISTA.
  • Changes in body fat can happen in people who take HIV-1 medicines. The changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the middle of your body (trunk). Loss of fat from the legs, arms, and face may also happen. The exact cause and long-term health effects of these conditions are not known.
  • Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having new symptoms after starting your HIV-1 medicine.
  • Increased bleeding for hemophiliacs. Some people with hemophilia have increased bleeding with protease inhibitors including PREZISTA.
    The most common side effects of PREZISTA include:
    • diarrhea
    • nausea
    • rash
    • headache
    • stomach-area (abdominal) pain
    • vomiting

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all of the possible side effects of PREZISTA.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store PREZISTA?

  • Store PREZISTA oral suspension and tablets at room temperature 77°F (25°C).
  • Do not refrigerate or freeze PREZISTA oral suspension.
  • Keep PREZISTA oral suspension away from high heat.
  • PREZISTA oral suspension should be stored in the original container.

Keep PREZISTA and all medicines out of the reach of children.

General information about the safe and effective use of PREZISTA.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use PREZISTA for a condition for which it was not prescribed. Do not give PREZISTA to other people even if they have the same condition you have. It may harm them.

This leaflet summarizes the most important information about PREZISTA. If you would like more information, talk to your healthcare provider. You can ask your healthcare provider or pharmacist for information about PREZISTA that is written for health professionals. For more information, call 1-800-526-7736.

What are the ingredients in PREZISTA?

Active ingredient: darunavir

Inactive ingredients:

PREZISTA oral suspension: hydroxypropyl cellulose, microcrystalline cellulose, sodium carboxymethylcellulose, methylparaben sodium, citric acid monohydrate, sucralose, masking flavor, strawberry cream flavor, hydrochloric acid (for pH adjustment), purified water.

PREZISTA 75 mg and 150 mg tablets: colloidal silicon dioxide, crospovidone, magnesium stearate, microcrystalline cellulose. The film coating contains: OPADRY® W hite (polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, titanium dioxide).

PREZISTA 600 mg tablets: colloidal silicon dioxide, crospovidone, magnesium stearate, microcrystalline cellulose. The film coating contains: OPADRY® Orange (FD&C Yellow No. 6, polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, titanium dioxide). PREZISTA 800 mg tablets: colloidal silicon dioxide, crospovidone, magnesium stearate, microcrystalline cellulose, hypromellose. The film coating contains: OPADRY® Dark Red (iron oxide red, polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, titanium dioxide).

INSTRUCTIONS FOR USE

PREZISTA
(pre-ZIS-ta)
(darunavir) oral suspension

Be sure that you read, understand, and follow these Instructions for Use so that you measure and take PREZISTA oral suspension correctly. Ask your healthcare provider if you are not sure.

Each PREZISTA oral suspension carton contains:

  • 1 bottle of PREZISTA oral suspension
  • Oral dosing syringe
  • 1 oral syringe adapter

Important information for use:

  • Shake PREZISTA oral suspension well before each use.
  • PREZISTA oral suspension should be given with the oral dosing syringe provided to make sure you measure the right amount. The oral dosing syringe provided with your PREZISTA oral suspension should not be used for any other medicines.

1. Shake the bottle.

  • Shake the bottle well before each use (See Figure A).

Figure A: Shake the bottle

2. Open the bottle of PREZISTA oral suspension.

  • Open the bottle by pushing downward on the cap and twisting it in the direction of the arrow (counter-clockwise) (See Figure B).

Figure B: Opening the bottle

3. The first time a bottle of PREZISTA oral suspension is used:

  • Insert the oral syringe adapter into the bottle. Press on the adapter until it is even with the top of the bottle (See Figure C).
  • Do not remove the oral syringe adapter from the bottle once inserted.

Figure C: Inserting the adapter

4. Insert the oral dosing syringe.

  • Fully push down (depress) the plunger of the syringe.
  • Insert the syringe into the opening of the oral syringe adapter until it is firmly in place (See Figure D).

Figure D: Inserting the syringe

5. Withdraw the prescribed amount of PREZISTA oral suspension.

  • Turn the bottle upside down. Gently pull back the plunger of the syringe until the bottom of the plunger is even with the markings on the syringe for the prescribed dose (See Figure E). If you see air bubbles in the syringe, push the plunger in to empty the oral suspension back into the bottle. Then repeat steps 4 and 5.
  • If you or your child's dose of PREZISTA oral suspension is more than 6 mL, you will need to divide the dose. Follow the instructions given to you by your healthcare provider or pharmacist about how to divide the dose.

Figure E: Withdrawing the Oral Suspension

6.    Turn the bottle upright and remove the syringe from thebottle by pulling straight up on the oral dosing syringe (See Figure F).

Figure F: Removing the syringe

7. Take the dose of PREZISTA.

  • Place the tip of the oral dosing syringe in the mouth.
  • Press on the plunger of the syringe towards the mouth (See Figure G).

If you or your child's dose is more than 6 mL you will need to divide the dose. Follow the instructions given to you by your healthcare provider or pharmacist about how to divide the dose, and repeat steps 4 through 7.

Figure G: Taking the dose of PREZISTA

8. Close the bottle with the cap after use.

  • Close the bottle by twisting the cap in the direction of the arrow (clockwise) (See Figure H).

Figure H: Closing the bottle

9.    Remove the plunger from the barrel by pulling the plungerand barrel away from each other (See Figure I). Rinse bothparts of the syringe with waterand allow to air dry after each use.

Figure I: Removing the plunger from the barrel

10.    After air drying, put the oral dosing syringe back together by inserting the plunger intothe barrel (See Figure J). Store the oral dosing syringe with PREZISTA oral suspension.

Figure J: Putting the syringe back together

How should I store PREZISTA?

  • Store PREZISTA oral suspension and the oral dosing syringe at room temperature 77°F (25°C).
  • Do not refrigerate or freeze PREZISTA oral suspension.
  • Keep PREZISTA oral suspension away from high heat.
  • Store PREZISTA oral suspension in the original container.

Keep PREZISTA and all medicines out of the reach of children.

This Instruction for Use has been approved by the U.S. Food and Drug Administration.

Inform MD

Before taking darunavir, tell your healthcare provider if you:

  • have liver problems, including hepatitis B or hepatitis C
  • are allergic to sulfa medicines
  • have high blood sugar (diabetes)
  • have hemophilia
  • are pregnant or planning to become pregnant
  • are breastfeeding or plan to breastfeed

Tell your healthcare provider about all the medicines you take including prescription and nonprescription medicines, vitamins, and herbal supplements. 

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Uses for Darunavir

Treatment of HIV Infection

Darunavir with low-dose ritonavir (ritonavir-boosted darunavir): Treatment of HIV-1 infection in adults, adolescents, and children ≥3 years of age;1 used in conjunction with other antiretrovirals.1 200 201

Darunavir with cobicistat (cobicistat-boosted darunavir): Treatment of HIV-1 infection in adults;237 239 used in conjunction with other antiretrovirals.200 237 239

Do not use darunavir without a pharmacokinetic enhancer (i.e., low-dose ritonavir or cobicistat).1 200 201 237 239 Pharmacokinetic enhancer (pharmacokinetic booster) necessary to improve darunavir's pharmacokinetic profile.1 200 237 239 Low-dose ritonavir and cobicistat are not interchangeable in antiretroviral regimens;200 237 239 these pharmacokinetic enhancers have different dosage and administration requirements and are associated with different adverse effects, precautions, contraindications, and drug interactions.200 237 239

When ritonavir-boosted darunavir used, single-entity darunavir is given with single-entity ritonavir.1 In antiretroviral-experienced patients, use results of genotypic and/or phenotypic viral resistance testing and individual’s prior antiretroviral treatment to guide treatment.1

When cobicistat-boosted darunavir used, fixed combination containing both drugs (darunavir/cobicistat) can be used;237 alternatively, single-entity darunavir is given with single-entity cobicistat.239 Assess estimated Clcr in all patients prior to initiation of cobicistat-boosted darunavir (see Renal Effects under Cautions).237 239 Do not use darunavir/cobicistat in patients with HIV-1 with substitutions associated with darunavir resistance (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V).237 In antiretroviral-experienced patients, use results of genotypic viral resistance testing to guide treatment;237 if such testing not available, may use the fixed combination in HIV PI-naive patients, but not recommended in HIV PI-experienced patients.237

For initial treatment in antiretroviral-naive adults and adolescents, experts state that ritonavir-boosted darunavir in conjunction with tenofovir alafenamide fumarate (TAF) and emtricitabine or ritonavir-boosted darunavir in conjunction with tenofovir disoproxil fumarate (tenofovir DF) and emtricitabine (or lamivudine) are recommended PI-based regimens.200 These experts state that cobicistat-boosted darunavir in conjunction with TAF and emtricitabine or cobicistat-boosted darunavir in conjunction with tenofovir DF and emtricitabine (or lamivudine) are alternative PI-based regimen for initial treatment in antiretroviral-naive adult and adolescents†.200 Ritonavir-boosted darunavir or cobicistat-boosted darunavir in conjunction with abacavir and lamivudine (or emtricitabine) are additional alternative PI-based regimens for initial treatment, but use only in those with baseline plasma HIV RNA levels less than 100,000 copies/mL who are human leukocyte antigen (HLA)-B*5701 negative.200 Ritonavir-boosted darunavir in conjunction with raltegravir (twice daily) is another regimen option for initial treatment when TAF, TDF, or abacavir cannot be used, but use only in patients with baseline plasma HIV RNA levels <100,000 copies/mL and CD4+ T-cell count >200 cells/mm3.200

For initial treatment in antiretroviral-naive pediatric patients, experts state that ritonavir-boosted darunavir (twice daily) and 2 nucleoside reverse transcriptase inhibitors (NRTIs) is a preferred regimen in children 3 years to <12 years of age and ritonavir-boosted darunavir (once daily) in conjunction with 2 NRTIs is a preferred regimen in children ≥12 years of age.201 Do not use once-daily ritonavir-boosted darunavir in children <12 years of age or if darunavir resistance-associated substitutions are present.201

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)

Postexposure prophylaxis of HIV infection following occupational exposure† (PEP) in health-care personnel and others exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.199

USPHS recommends 3-drug regimen of raltegravir and emtricitabine and tenofovir DF as preferred regimen for PEP following occupational exposures to HIV.199 Ritonavir-boosted darunavir and 2 NRTIs is one of several alternative regimens.199 Preferred dual NRTI option for use with ritonavir-boosted darunavir is emtricitabine and tenofovir DF; alternatives are tenofovir DF and lamivudine, zidovudine and lamivudine, or zidovudine and emtricitabine.199

Management of occupational exposures to HIV is complex and evolving; consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) whenever possible.199 Do not delay initiation of PEP while waiting for expert consultation.199

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)

Postexposure prophylaxis of HIV infection following nonoccupational exposure† (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids that might contain HIV when the exposure represents a substantial risk for HIV transmission.198 Used in conjunction with other antiretrovirals.198

When nPEP indicated in adults and adolescents ≥13 years of age with normal renal function, CDC states preferred regimen is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (given as emtricitabine/tenofovir DF; Truvada);198 recommended alternative regimen in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF.198

Consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) if nPEP indicated in certain exposed individuals (e.g., pregnant women, children, those with medical conditions such as renal impairment) or if considering a regimen not included in CDC guidelines, source virus is known or likely to be resistant to antiretrovirals, or healthcare provider is inexperienced in prescribing antiretrovirals.198 Do not delay initiation of nPEP while waiting for expert consultation.198

Darunavir Dosage and Administration

Administration

Oral Administration

Administer orally in conjunction with low-dose ritonavir (ritonavir-boosted darunavir) once or twice daily with food.1

Alternatively, administer orally in conjunction with cobicistat (cobicistat-boosted darunavir) once daily with food.237 239

Do not administer without low-dose ritonavir or cobicistat.1 200 201 237 239

Ritonavir-boosted Darunavir

Administer single-entity darunavir as tablets or oral suspension at same time as single-entity ritonavir capsules, tablets, or oral solution.1 200

Oral suspension: Use in those who have difficulty swallowing tablets.1 Administer suspension using oral dosing syringe supplied by the manufacturer.1 If 800-mg dose is indicated, give dose as two 4-mL administrations using the oral dosing syringe.1 Supplied as a white to off-white opaque suspension;1 shake prior to each dose.1

Tablets: Swallow tablets whole with a drink (e.g., water, milk).1 Assess ability to swallow tablets in children weighing ≥15 kg; consider darunavir oral suspension in those unable to reliably swallow tablets.1

Cobicistat-boosted Darunavir

Administer fixed-combination tablets containing both drugs (darunavir/cobicistat).237 Alternatively, administer single-entity darunavir as tablets or oral suspension at same time as single-entity cobicistat tablets.239

Dosage

Single-entity darunavir available as oral suspension or tablets containing darunavir ethanolate; dosage expressed in terms of darunavir.1

Darunavir/cobicistat available as fixed-combination tablets containing darunavir ethanolate (800 mg of darunavir) and cobicistat (150 mg).237

Pediatric Patients

Treatment of HIV Infection

To avoid medication errors, use extra care in calculating dose, transcribing medication order, dispensing prescription, and providing dosing instructions.1

Dosage of ritonavir-boosted darunavir in children and adolescents 3 years to <18 years of age weighing ≥10 kg is based on weight.1

Antiretroviral-naive Pediatric Patients Oral

Ritonavir-boosted darunavir (pediatric patients 3 years to <18 years of age weighing ≥10 kg): Dosage based on weight (approximately 35 mg/kg once daily with ritonavir 7 mg/kg once daily in those weighing <15 kg).1 (See Table 1 and Table 2.)

Dosage (in mL) rounded up for convenient measuring using oral dosing syringe provided by manufacturer.1

Table 1. Dosage of Ritonavir-boosted Darunavir in Antiretroviral-naive Pediatric Patients 3 Years to <18 Years of Age Weighing 10 to <15 kg 1

Body Weight

Darunavir Dosage (Oral Suspension Containing 100 mg/mL)

Ritonavir Dosage (Oral Solution Containing 80 mg/mL)

≥10 to <11 kg

350 mg (3.6 mL) once daily

64 mg (0.8 mL) once daily

≥11 to <12 kg

385 mg (4 mL) once daily

64 mg (0.8 mL) once daily

≥12 to <13 kg

420 mg (4.2 mL) once daily

80 mg (1 mL) once daily

≥13 to <14 kg

455 mg (4.6 mL) once daily

80 mg (1 mL) once daily

≥14 to <15 kg

490 mg (5 mL) once daily

96 mg (1.2 mL) once daily

Dosage (in mL) rounded up for convenient measuring using oral dosing syringe provided by manufacturer.1

Table 2. Dosage of Ritonavir-boosted Darunavir in Antiretroviral-naive Pediatric Patients 3 Years to <18 Years of Age Weighing ≥15 kg1

Body Weight

Darunavir Dosage (Oral Suspension Containing 100 mg/mL or Tablets)

Ritonavir Dosage (Oral Solution Containing 80 mg/mL or 100-mg Capsules or Tablets)

≥15 to <30 kg

600 mg (6 mL) once daily

100 mg (1.25 mL) once daily

≥30 to <40 kg

675 mg (6.8 mL) once daily

100 mg (1.25 mL) once daily

≥40 kg

800 mg (8 mL) once daily

100 mg (1.25 mL) once daily
Antiretroviral-experienced Pediatric Patients Oral

Genotypic testing recommended to identify substitutions associated with darunavir resistance (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V).1

Ritonavir-boosted darunavir (pediatric patients 3 years to <18 years of age weighing ≥10 kg with no substitutions associated with darunavir resistance): Dosage based on weight (approximately 35 mg/kg once daily with ritonavir 7 mg/kg once daily in those weighing <15 kg).1 (See Table 3 and Table 4.)

Dosage (in mL) rounded up for convenient measuring using oral dosing syringe provided by manufacturer.1

Table 3. Dosage of Ritonavir-boosted Darunavir in Antiretroviral-experienced Pediatric Patients 3 Years to <18 Years of Age Weighing 10 to <15 kg without Any Substitutions Associated with Darunavir Resistance1

Body Weight

Darunavir Dosage (Oral Suspension Containing 100 mg/mL)

Ritonavir Dosage (Oral Solution Containing 80 mg/mL)

≥10 to <11 kg

350 mg (3.6 mL) once daily

64 mg (0.8 mL) once daily

≥11 to <12 kg

385 mg (4 mL) once daily

64 mg (0.8 mL) once daily

≥12 to <13 kg

420 mg (4.2 mL) once daily

80 mg (1 mL) once daily

≥13 to <14 kg

455 mg (4.6 mL) once daily

80 mg (1 mL) once daily

≥14 to <15 kg

490 mg (5 mL) once daily

96 mg (1.2 mL) once daily

Dosage (in mL) rounded up for convenient measuring using oral dosing syringe provided by manufacturer.1

Table 4. Dosage of Ritonavir-boosted Darunavir in Antiretroviral-experienced Pediatric Patients 3 Years to <18 Years of Age Weighing ≥15 kg without Any Substitutions Associated with Darunavir Resistance1

Body Weight

Darunavir Dosage (Oral Suspension Containing 100 mg/mL or Tablets)

Ritonavir Dosage (Oral Solution Containing 80 mg/mL or 100-mg Capsules or Tablets)

≥15 to <30 kg

600 mg (6 mL) once daily

100 mg (1.25 mL) once daily

≥30 to <40 kg

675 mg (6.8 mL) once daily

100 mg (1.25 mL) once daily

≥40 kg

800 mg (8 mL) once daily

100 mg (1.25 mL) once daily

Ritonavir-boosted darunavir (pediatric patients 3 years to <18 years of age weighing ≥10 kg with at least 1 substitution associated with darunavir resistance): Dosage based on weight (approximately 20 mg/kg twice daily with ritonavir 3 mg/kg twice daily in those weighing <15 kg).1 (See Table 5 and Table 6.)

Table 5. Dosage of Ritonavir-boosted Darunavir in Antiretroviral-experienced Pediatric Patients 3 Years to <18 Years of Age Weighing 10 to <15 kg with ≥1 Substitution Associated with Darunavir Resistance1

Body Weight

Darunavir Dosage (Oral Suspension Containing 100 mg/mL)

Ritonavir Dosage (Oral Solution Containing 80 mg/mL)

≥10 to <11 kg

200 mg (2 mL) twice daily

32 mg (0.4 mL) twice daily

≥11 to <12 kg

220 mg (2.2 mL) twice daily

32 mg (0.4 mL) twice daily

≥12 to <13 kg

240 mg (2.4 mL) twice daily

40 mg (0.5 mL) twice daily

≥13 to <14 kg

260 mg (2.6 mL) twice daily

40 mg (0.5 mL) twice daily

≥14 to <15 kg

280 mg (2.8 mL) twice daily

48 mg (0.6 mL) twice daily

Dosage (in mL) rounded up for convenient measuring using oral dosing syringe provided by manufacturer.1

Table 6. Dosage of Ritonavir-boosted Darunavir in Antiretroviral-experienced Pediatric Patients 3 Years to <18 Years of Age Weighing ≥15 kg with ≥1 Substitution Associated with Darunavir Resistance1

Body Weight

Darunavir Dosage (Oral Suspension Containing 100 mg/mL or Tablets)

Ritonavir Dosage (Oral Solution Containing 80 mg/mL or 100-mg Capsules or Tablets)

≥15 to <30 kg

375 mg (3.8 mL) twice daily

48 mg (0.6 mL) twice daily

≥30 to <40 kg

450 mg (4.6 mL) twice daily

60 mg (0.75 mL) twice daily

≥40 kg

600 mg (6 mL) twice daily

100 mg (1.25 mL) twice daily

Adults

Treatment of HIV Infection Antiretroviral-naive Adults Oral

Ritonavir-boosted darunavir: Single-entity darunavir 800 mg (one 800-mg tablet or 8 mL of oral suspension containing 100 mg/mL) once daily in conjunction with low-dose ritonavir (100 mg once daily).1

Cobicistat-boosted darunavir: 1 tablet of darunavir/cobicistat (800 mg of darunavir and 150 mg of cobicistat) once daily.237 Alternatively, single-entity darunavir 800 mg (one 800-mg darunavir tablet or 8 mL of darunavir oral suspension containing 100 mg/mL) once daily in conjunction with single-entity cobicistat (150 mg once daily).239

Antiretroviral-experienced Adults Oral

Genotypic testing recommended to identify substitutions associated with darunavir resistance (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V).1 237

Ritonavir-boosted darunavir in patients with no substitutions associated with darunavir resistance: Single-entity darunavir 800 mg (one 800-mg tablet or 8 mL of oral suspension containing 100 mg/mL) once daily in conjunction with low-dose ritonavir (100 mg once daily).1

Ritonavir-boosted darunavir in patients with at least 1 substitution associated with darunavir resistance: Single-entity darunavir 600 mg (one 600-mg tablet or 6 mL of oral suspension containing 100 mg/mL) twice daily in conjunction with low-dose ritonavir (100 mg twice daily).1

Ritonavir-boosted darunavir when genotypic testing not feasible: Single-entity darunavir 600 mg (one 600-mg tablet or 6 mL of oral suspension containing 100 mg/mL) twice daily in conjunction with low-dose ritonavir (100 mg twice daily).1

Cobicistat-boosted darunavir: 1 tablet of darunavir/cobicistat (800 mg of darunavir and 150 mg of cobicistat) once daily.237 Alternatively, single-entity darunavir 800 mg (one 800-mg darunavir tablet or 8 mL of darunavir oral suspension containing 100 mg/mL) once daily in conjunction with single-entity cobicistat (150 mg once daily).239

Darunavir dosage of 600 mg twice daily in conjunction with cobicistat not recommended.239

Postexposure Prophylaxis following Occupational Exposure to HIV† Oral

Ritonavir-boosted darunavir: Single-entity darunavir 800 mg once daily in conjunction with low-dose ritonavir (100 mg once daily).199 Alternatively, single-entity darunavir 600 mg twice daily in conjunction with low-dose ritonavir (100 mg twice daily).199 Use in conjunction with 2 NRTIs (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses).199 Use in conjunction with 2 NRTIs (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses).199

Initiate PEP as soon as possible following exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.199

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)† Oral

800 mg once daily in conjunction with low-dose ritonavir (100 mg once daily).198 Use in conjunction with 2 NRTIs (see Postexposure Prophylaxis following Nonoccupational Exposure to HIV [nPEP] under Uses).198

Initiate nPEP as soon as possible (within 72 hours) following nonoccupational exposure that represents a substantial risk for HIV transmission and continue for 28 days.198

nPEP not recommended if exposed individual seeks care >72 hours after exposure.198

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection Oral

Do not exceed dosage recommended for antiretroviral-experienced adults.1

Special Populations

Hepatic Impairment

Ritonavir-boosted darunavir: Dosage adjustments not necessary in patients with mild to moderate hepatic impairment (Child-Pugh class A or B).1 200 Do not use in those with severe hepatic impairment (Child-Pugh class C).1 200

Cobicistat-boosted darunavir: Dosage adjustments not necessary in patients with mild to moderate hepatic impairment (Child-Pugh class A or B).200 237 239 Do not use in those with severe hepatic impairment (Child-Pugh class C).200 237 239

Renal Impairment

Ritonavir-boosted darunavir: Experts state dosage adjustments not necessary in patients with renal impairment.200

Cobicistat-boosted darunavir: Assess estimated Clcr prior to initiation of fixed-combination darunavir/cobicistat or, alternatively, single-entity darunavir with single-entity cobicistat.237 239 Experts state dosage adjustments of cobicistat-boosted darunavir not necessary in patients with renal impairment.200 However, these experts and manufacturer state do not use cobicistat-boosted darunavir in conjunction with tenofovir DF in patients with estimated Clcr <70 mL/minute.200 237 239

Geriatric Patients

Ritonavir-boosted or cobicistat-boosted darunavir: Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1 237

Pregnant Women

Use ritonavir-boosted darunavir.1 202

Ritonavir-boosted darunavir (twice-daily regimen): 600 mg of single-entity darunavir (one 600-mg tablet or 6 mL of the oral suspension containing 100 mg/mL) twice daily with single-entity ritonavir 100 mg twice daily.1

Ritonavir-boosted darunavir (once-daily regimen): Manufacturer states consider 800 mg of single-entity darunavir once daily (one 800-mg tablet or 8 mL of the oral suspension containing 100 mg/mL once daily) with single-entity ritonavir 100 mg once daily only in women already stabilized on this once-daily regimen prior to pregnancy who are virologically suppressed (i.e., plasma HIV-1 RNA levels <50 copies/mL) and in whom a change to a twice-daily regimen may compromise tolerability or compliance.1 Some experts state once-daily regimen of ritonavir-boosted darunavir not recommended in pregnant women.202

Interactions for Darunavir

Darunavir, ritonavir, and cobicistat metabolized principally by CYP3A.1 237 239

Darunavir, ritonavir, and cobicistat inhibit CYP3A4 and CYP2D6.1 237 239

Ritonavir-boosted darunavir inhibits P-glycoprotein (P-gp) transport system;1 cobicistat is a P-gp inhibitor.237 239

Cobicistat inhibits breast cancer resistance protein (BCRP) and organic anion transporting polypeptide (OATP) 1B1 and 1B3.237 239

Darunavir must be used with a pharmacokinetic enhancer (i.e., low-dose ritonavir or cobicistat);1 200 201 237 239 consider drug interactions associated with both darunavir and the pharmacokinetic enhancer.1 200 237 239 Interactions reported or expected with ritonavir-boosted darunavir may differ from those reported or expected with cobicistat-boosted darunavir.200 237 239

The following drug interactions are based on studies using ritonavir-boosted darunavir1 or studies using cobicistat alone.237 239 Drug interaction studies not available to date using cobicistat-boosted darunavir administered either as fixed-combination darunavir/cobicistat or as single-entity darunavir given with single-entity cobicistat.237 239

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

CYP3A inducers: Potential pharmacokinetic interactions with ritonavir-boosted or cobicistat-boosted darunavir (increased clearance of darunavir, ritonavir, or cobicistat; possible loss of antiretroviral efficacy and development of resistance).1 237 239

CYP3A inhibitors: Potential pharmacokinetic interactions with ritonavir-boosted or cobicistat-boosted darunavir (increased plasma concentrations of darunavir, ritonavir, or cobicistat).1 237 239

CYP3A substrates: Potential pharmacokinetic interactions with ritonavir-boosted or cobicistat-boosted darunavir (altered metabolism of CYP3A substrates).1 237 239

CYP2D6 substrates: Potential pharmacokinetic interactions with ritonavir-boosted or cobicistat-boosted darunavir (increased plasma concentrations of CYP2D6 substrates; possible increased or prolonged therapeutic effects and increased risk of associated adverse effects).1 237 239

Drugs Affected by P-glycoprotein Transport

P-gp substrates: Potential pharmacokinetic interactions with ritonavir-boosted or cobicistat-boosted darunavir (increased plasma concentrations of P-gp substrates; possible increased or prolonged therapeutic effects and increased risk of associated adverse effects).1 237 239

P-gp inhibitors: Potential pharmacokinetic interactions with ritonavir-boosted or cobicistat-boosted darunavir (decreased clearance of darunavir and ritonavir leading to increased plasma concentrations).1

Drugs Affecting or Affected by Other Membrane Transporters

BCRP, OATP1B1, or OATP1B3 substrates: Potential pharmacokinetic interactions with cobicistat-boosted darunavir (increased plasma concentrations of such substrates; possible increased or prolonged therapeutic effects and increased risk of associated adverse effects).237 239

Specific Drugs

Drug

Interaction

Comments

Abacavir

Ritonavir-boosted or cobicistat-boosted darunavir: Pharmacokinetic interactions not expected1 237

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Ritonavir-boosted darunavir: Dosage adjustments not needed1

Alfuzosin

Ritonavir-boosted or cobicistat-boosted darunavir: Potential for serious and/or life-threatening reactions (e.g., hypotension)1 237 239

Ritonavir-boosted or cobicistat-boosted darunavir: Concomitant use contraindicated1 237 239

Antacids

Acid-modifying drugs not expected to alter darunavir exposures1

Cobicistat-boosted darunavir: Clinically important interactions not expected237

Antiarrhythmic agents (amiodarone, disopyramide, dronedarone, flecainide, systemic lidocaine, mexiletine, propafenone, quinidine)

Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased antiarrhythmic agent concentrations1 237 239

Amiodarone: If used with ritonavir-boosted or cobicistat-boosted darunavir, experts state monitor for amiodarone toxicity and consider ECG and amiodarone concentration monitoring200

Dronedarone: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir contraindicated1 237 239

Disopyramide, flecainide, systemic lidocaine, mexiletine, propafenone, quinidine: Use concomitantly with caution;200 monitor antiarrhythmic concentrations1 200 237

Anticoagulants, oral (apixaban, dabigatran, edoxaban rivaroxaban, warfarin)

Apixaban, edoxaban, dabigatran, rivaroxaban: Possible increased anticoagulant concentrations if used with ritonavir-boosted or cobicistat-boosted darunavir1 200 237

Warfarin: Decreased warfarin concentrations and no change in darunavir concentrations if used with ritonavir-boosted darunavir;1 effect of concomitant use with cobicistat-boosted darunavir unknown200 237 239

Apixaban, rivaroxaban: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir not recommended1 200 237

Dabigatran: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir not recommended in certain patients with renal impairment depending on indication;1 237 experts state avoid concomitant use in patients with Clcr <50 mL/minute200

Edoxaban: Avoid concomitant use with ritonavir-boosted or cobicistat-boosted darunavir200

Warfarin: Monitor INR if used with ritonavir-boosted or cobicistat-boosted darunavir1 200 237 239 (especially when initiating or discontinuing darunavir) and adjust warfarin dosage as needed;200 if ritonavir-boosted darunavir switched to cobicistat-boosted darunavir, effect on warfarin concentrations not expected to be equivalent200

Anticonvulsants (carbamazepine, eslicarbazepine, ethosuximide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin)

Carbamazepine: If used with ritonavir-boosted darunavir, increased carbamazepine concentrations and no change in darunavir concentrations;1 if used with cobicistat-boosted darunavir, increased carbamazepine concentrations, decreased cobicistat concentrations, and possibility of substantially decreased darunavir concentrations, loss of therapeutic effect and development of resistance200 237 239

Eslicarbazepine: Possible decreased cobicistat concentrations if used with cobicistat-boosted darunavir;237 effect on darunavir concentrations unknown237

Ethosuximide: Possible increased ethosuximide concentrations if used with ritonavir-boosted or cobicistat-boosted darunavir200

Lamotrigine: If used with ritonavir-boosted darunavir, possible decreased lamotrigine concentrations;200 data not available regarding use with cobicistat-boosted darunavir200

Oxcarbazepine: If used with cobicistat-boosted darunavir, decreased cobicistat concentrations, but effect on darunavir concentrations unknown237 239

Phenobarbital, phenytoin: If used with ritonavir-boosted darunavir, possible decreased phenobarbital concentrations, but no change in darunavir concentrations;1 if used with cobicistat-boosted darunavir, decreased cobicistat and darunavir concentrations expected and may result in loss of therapeutic effect and development of resistance, but effect on phenobarbital concentrations unknown200 237 239

Carbamazepine: If used with ritonavir-boosted darunavir, dosage adjustments not needed, but monitor carbamazepine concentrations and adjust anticonvulsant dosage to achieve appropriate clinical effect;1 concomitant use with cobicistat-boosted darunavir contraindicated200 237

Eslicarbazepine: Consider alternative anticonvulsant or alternative antiretroviral;237 if used concomitantly with cobicistat-boosted darunavir, monitor for lack or loss of antiretroviral response237

Ethosuximide: If used with ritonavir-boosted or cobicistat-boosted darunavir, monitor for ethosuximide toxicities200

Lamotrigine: In patients receiving ritonavir-boosted or cobicistat-boosted darunavir, consider alternative anticonvulsant or monitor lamotrigine concentrations;200 if used with ritonavir-boosted darunavir increased lamotrigine dosage may be needed200

Oxcarbazepine: In patients receiving cobicistat-boosted darunavir, consider alternative anticonvulsant or alternative antiretroviral or, if concomitant use necessary, monitor for lack or loss of virologic response237 239

Phenobarbital, phenytoin: If used with ritonavir-boosted darunavir, monitor anticonvulsant concentrations1 or consider alternative anticonvulsant; concomitant use with cobicistat-boosted darunavir contraindicated200 237

Antifungals, azoles (isavuconazonium, itraconazole, ketoconazole, posaconazole, voriconazole)

Isavuconazonium (prodrug of isavuconazole): Possible increased isavuconazole concentrations and altered darunavir concentrations if used with ritonavir-boosted or cobicistat-boosted darunavir200

Itraconazole: If used with ritonavir-boosted or cobicistat-boosted darunavir, possible increased itraconazole, darunavir, and cobicistat concentrations1 237 239

Ketoconazole: If used with ritonavir-boosted or cobicistat-boosted darunavir, increased ketoconazole, darunavir, and cobicistat concentrations1 237 239

Posaconazole: If used with ritonavir-boosted or cobicistat-boosted darunavir, possible increased posaconazole, darunavir, and cobicistat concentrations1 200 237

Voriconazole: If used with ritonavir-boosted darunavir, possible decreased voriconazole concentrations;1 data not available regarding use with cobicistat-boosted darunavir200 237 239

Isavuconazonium: Monitor for darunavir-associated adverse effects and virologic efficacy if used with ritonavir-boosted or cobicistat-boosted darunavir;200 consider monitoring isavuconazole concentrations200

Itraconazole: If used with ritonavir-boosted or cobicistat-boosted darunavir, monitor for itraconazole-, darunavir-, and ritonavir- or cobicistat-associated adverse effects and consider monitoring itraconazole concentrations;200 237 itraconazole dosage >200 mg daily not recommended1 200 unless itraconazole concentrations used to guide dosage200

Ketoconazole: If used with ritonavir-boosted or cobicistat-boosted darunavir, monitor for ketoconazole-, darunavir-, and ritonavir- or cobicistat-associated adverse effects;1 237 ketoconazole dosage >200 mg daily not recommended in those receiving ritonavir-boosted darunavir1

Posaconazole: If used with ritonavir-boosted or cobicistat-boosted darunavir, monitor for posaconazole-, darunavir-, and ritonavir- or cobicistat-associated adverse effects;1 200 237 consider monitoring posaconazole concentrations200

Voriconazole: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir not recommended unless benefits outweigh risks;1 200 237 239 if used concomitantly, experts state consider monitoring voriconazole concentrations and adjusting voriconazole dosage accordingly200

Antimalarial agents

Fixed combination of artemether and lumefantrine (artemether/lumefantrine): If used with ritonavir-boosted darunavir, decreased concentrations and AUC of artemether and active metabolite of artemether, increased concentrations and AUC of lumefantrine and increased risk of QT interval prolongation, but no effect on darunavir or ritonavir concentrations or AUC;1 if used with cobicistat-boosted darunavir, increased lumefantrine concentrations expected,200 but effect on artemether concentrations unknown200 237

Artemether/lumefantrine: If used with ritonavir-boosted or cobicistat-boosted darunavir, monitor for antimalarial efficacy and lumefantrine toxicity (e.g., QT interval prolongation);1 200 237 dosage adjustments not needed if used with ritonavir-boosted darunavir, but use caution1

Antimycobacterials (bedaquiline, rifabutin, rifampin, rifapentine)

Bedaquiline: If used with ritonavir-boosted or cobicistat-boosted darunavir, possible increased bedaquiline concentrations200

Rifabutin: If used with ritonavir-boosted darunavir, increased rifabutin and darunavir concentrations;1 200 if used with cobicistat-boosted darunavir, possible increased rifabutin concentrations, but effect on darunavir and cobicistat concentrations unknown200 237 239

Rifampin: If used with ritonavir-boosted or cobicistat-boosted darunavir, substantially decreased darunavir concentrations and possible loss of antiretroviral effects1 200 237 239

Rifapentine: If used with ritonavir-boosted or cobicistat-boosted darunavir, decreased darunavir concentrations expected 1 200 237

Bedaquiline: Clinical importance unknown;200 some experts state may be used concomitantly with ritonavir-boosted or cobicistat-boosted darunavir if benefits outweigh risks, but use caution and monitor for QTc interval prolongation and liver dysfunction200

Rifabutin: If used concomitantly with ritonavir-boosted or cobicistat-boosted darunavir, reduce rifabutin dosage to 150 mg once every other day (further reduction may be needed) and monitor for adverse effects (e.g., neutropenia, uveitis);1 200 237 239 also monitor for antimycobacterial response and consider therapeutic drug monitoring200

Rifampin: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir contraindicated;1 237 239 experts state consider rifabutin as alternative if a rifamycin indicated200

Rifapentine: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir not recommended1 200 237

Antineoplastic agents (dasatinib, nilotinib, vinblastine, vincristine)

Dasatinib, nilotinib, vinblastine, vincristine: If used with ritonavir-boosted or cobicistat-boosted darunavir, possible increased antineoplastic concentrations1 237 239

Dasatinib, nilotinib: If used with ritonavir-boosted or cobicistat-boosted darunavir, reduced dosage of the antineoplastic may be needed 1 237 239

Vincristine, vinblastine: If used with ritonavir-boosted or cobicistat-boosted darunavir, consider temporarily withholding antiretroviral regimen in patients with clinically important hematologic or GI adverse effects;1 237 239 if antiretroviral regimen must be withheld for a prolonged period, consider changing to different antiretroviral regimen that does not include a CYP3A or P-gp inhibitor1 237 239

Antipsychotics (lurasidone, perphenazine, pimozide, quetiapine, risperidone, thioridazine)

Lurasidone: If used with ritonavir-boosted or cobicistat-boosted darunavir, potential for serious and/or life-threatening adverse effects1 237 239

Perphenazine, risperidone, thioridazine: If used with ritonavir-boosted or cobicistat-boosted darunavir, possible increased antipsychotic concentrations200 237 239

Pimozide: If used with ritonavir-boosted or cobicistat-boosted darunavir, potential for serious and/or life-threatening adverse effects (e.g., cardiac arrhythmias)1 237 239

Quetiapine: If used with ritonavir-boosted or cobicistat-boosted darunavir, increased quetiapine concentrations expected1 200 237

Lurasidone: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir contraindicated1 237 239

Perphenazine, risperidone, thioridazine: Decreased antipsychotic dosage may be needed if used with ritonavir-boosted or cobicistat-boosted darunavir;200 237 239 experts state initiate antipsychotic at lowest dosage, adjust maintenance dosage as needed, and monitor for antipsychotic-associated toxicities200

Perphenazine, risperidone, thioridazine: If used with cobicistat-boosted darunavir, lower antipsychotic dosage may be needed;237 239 experts state that if used concomitantly with ritonavir-boosted darunavir, use lowest initial antipsychotic dosage or adjust maintenance dosage and monitor for antipsychotic-associated adverse effects200

Pimozide: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir contraindicated1 237 239

Quetiapine: Consider alternative antiretroviral;1 if ritonavir-boosted or cobicistat-boosted darunavir necessary in patient receiving stable quetiapine dosage, reduce quetiapine dosage to one-sixth of original dosage and monitor for quetiapine efficacy and adverse effects;1 200 237 if quetiapine necessary in patient receiving ritonavir-boosted or cobicistat-boosted darunavir, experts state initiate using lowest quetiapine dosage and titrate as needed200

Atazanavir

Unboosted atazanavir: Depending on regimen used, no clinically important change in atazanavir or darunavir concentrations or AUC1

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Ritonavir-boosted atazanavir: Concomitant use with ritonavir-boosted darunavir not recommended1

Avanafil

Ritonavir-boosted or cobicistat-boosted darunavir: Increased avanafil concentrations and increased risk of avanafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope)1 200 237 239

Ritonavir-boosted or cobicistat-boosted darunavir: Concomitant use not recommended1 200 237 239

Benzodiazepines (alprazolam, clonazepam, diazepam, estazolam, midazolam, triazolam)

Alprazolam: If used with ritonavir-boosted or cobicistat-boosted darunavir, possible increased alprazolam concentrations200

Clonazepam: If used with ritonavir-boosted or cobicistat-boosted darunavir, increased clonazepam concentrations200 237 239

Diazepam: If used with ritonavir-boosted or cobicistat-boosted darunavir, possible increased diazepam concentrations200

Estazolam: If used with ritonavir-boosted or cobicistat-boosted darunavir, possible increased estazolam concentrations1 237 239

Midazolam or triazolam: If used with ritonavir-boosted or cobicistat-boosted darunavir, possible increased midazolam or triazolam concentrations and potential for serious and/or life-threatening effects (e.g., prolonged or increased sedation or respiratory depression)1 237 239

Alprazolam: In patients receiving ritonavir-boosted or cobicistat-boosted darunavir, consider alternative (e.g., lorazepam, oxazepam, temazepam)200

Clonazepam: If used with ritonavir-boosted or cobicistat-boosted darunavir, monitor patient clinically;200 237 239 experts state consider other benzodiazepines not metabolized by CYP isoenzymes (e.g., lorazepam, oxazepam, temazepam)200

Diazepam: If used with ritonavir-boosted or cobicistat-boosted darunavir, titrate diazepam dosage, consider lower diazepam dosage, and monitor for adverse effects;1 237 239 experts state consider alternative (e.g., lorazepam, oxazepam, temazepam)200

Estazolam: If used with ritonavir-boosted or cobicistat-boosted darunavir, titrate estazolam dosage, consider lower estazolam dosage, and monitor for adverse effects1 237 239

Oral midazolam or triazolam: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir contraindicated1 237 239

Parenteral midazolam: Use concomitantly with ritonavir-boosted or cobicistat-boosted darunavir with caution and in monitored setting where respiratory depression and/or prolonged sedation can be managed;1 237 239 consider reduced midazolam dosage, especially if multiple midazolam doses are given;1 237 239 experts state a single parenteral midazolam dose can be used with caution in a monitored situation for procedural sedation200

β-Adrenergic blocking agents (carvedilol, metoprolol, timolol)

Carvedilol, metoprolol, timolol: If used with ritonavir-boosted or cobicistat-boosted darunavir, possible increased concentrations of the β-blocker1 200 237 239

Carvedilol, metoprolol, timolol: If used with ritonavir-boosted or cobicistat-boosted darunavir, clinical monitoring recommended and reduced dosage of β-blocker may be needed;1 200 237 239 experts state consider alternative β-blocker not metabolized by CYP enzymes (e.g., atenolol, labetalol, nadolol, sotalol)200

Bosentan

Ritonavir-boosted darunavir: Possible increased bosentan concentrations1

Cobicistat-boosted darunavir: Possible increased bosentan concentrations and decreased darunavir and cobicistat concentrations237 239

In patients already receiving ritonavir-boosted or cobicistat-boosted darunavir for ≥10 days, initiate bosentan using dosage of 62.5 mg once daily or every other day based on individual tolerability1 237 239

In patients already receiving bosentan, discontinue bosentan for at least 36 hours prior to initiating ritonavir-boosted or cobicistat-boosted darunavir; after ≥10 days of ritonavir-boosted or cobicistat-boosted darunavir, resume bosentan using dosage of 62.5 mg once daily or every other day based on individual tolerability1 237 239

If ritonavir-boosted darunavir is switched to cobicistat-boosted darunavir, maintain current bosentan dosage237 239

Buprenorphine, buprenorphine/naloxone

Ritonavir-boosted darunavir: Increased norbuprenorphine concentrations and AUC1 200

Cobicistat-boosted darunavir: Effect on buprenorphine or buprenorphine/naloxone unknown200 237 239

Ritonavir-boosted darunavir: Dosage adjustments not needed, but monitor patient;1 200 in those with a buprenorphine subdermal implant, removal of the implant and switch to a different buprenorphine formulation that permits dosage adjustments may be needed200

Cobicistat-boosted darunavir: If initiating buprenorphine or buprenorphine/naloxone in patient already receiving cobicistat-boosted darunavir, use lowest possible dosage and carefully titrate to desired therapeutic effect;200 237 239 if initiating cobicistat-boosted darunavir in patient already receiving buprenorphine or buprenorphine/naloxone, monitor patient and consider that dosage adjustments may be needed;237 239 in those with a buprenorphine subdermal implant, removal of the implant and switch to a different buprenorphine formulation that permits dosage adjustments may be needed200

Buspirone

Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased buspirone concentrations1 237

Ritonavir-boosted or cobicistat-boosted darunavir: Titration of buspirone recommended, consider lower buspirone dosage, and monitor for adverse effects1 237

Calcium-channel blocking agents (amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil)

Ritonavir-boosted or cobicistat-boosted darunavir: Increased calcium-channel blocking agent concentrations1 200 237 239

Ritonavir-boosted or cobicistat-boosted darunavir: Use concomitantly with caution; clinical monitoring recommended;1 200 237 239 if used concomitantly with diltiazem, experts state adjust diltiazem dosage based on clinical response and toxicities200

Cisapride

Ritonavir-boosted or cobicistat-boosted darunavir: Potential for serious and/or life-threatening effects such as cardiac arrhythmias 1 237 239

Ritonavir-boosted or cobicistat-boosted darunavir: Concomitant use contraindicated1 237 239

Cobicistat

Increased darunavir concentrations and AUC;200 237 239 used as a pharmacokinetic enhancer (pharmacokinetic booster) for therapeutic advantage (cobicistat-boosted darunavir)200 237 239

Colchicine

Ritonavir-boosted or cobicistat-boosted darunavir: Increased colchicine concentrations1 237 239

Patients with renal or hepatic impairment: Concomitant use of colchicine and ritonavir-boosted or cobicistat-boosted darunavir contraindicated1 237 239

Colchicine for treatment of gout flares: In those receiving ritonavir-boosted or cobicistat-boosted darunavir, use initial colchicine dose of 0.6 mg followed by 0.3 mg 1 hour later and repeat dose no earlier than 3 days later1 237 239

Colchicine for prophylaxis of gout flares: In those receiving ritonavir-boosted or cobicistat-boosted darunavir, decrease colchicine dosage to 0.3 mg once daily in those originally receiving 0.6 mg twice daily or decrease dosage to 0.3 mg once every other day in those originally receiving 0.6 mg once daily1 237 239

Colchicine for treatment of familial Mediterranean fever (FMF): In those receiving ritonavir-boosted or cobicistat-boosted darunavir, use maximum colchicine dosage of 0.6 mg daily (may be given as 0.3 mg twice daily)1 237 239

Corticosteroids (beclomethasone, budesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, prednisolone, prednisone, triamcinolone)

Budesonide, fluticasone, mometasone (orally inhaled, intranasal): Increased corticosteroid concentrations if used with ritonavir-boosted or cobicistat-boosted darunavir;1 200 237 239 may result in adrenal insufficiency or Cushing's syndrome200

Beclomethasone (orally inhaled): No clinically important pharmacokinetic interactions with ritonavir-boosted darunavir;200 clinically important interactions with cobicistat-boosted darunavir not expected200

Methylprednisolone, prednisolone, or triamcinolone (intra-articular or other local injections): Increased corticosteroid concentrations;200 may result in adrenal insufficiency or Cushing's syndrome200

Budesonide (systemic): Increased corticosteroid concentrations if used with ritonavir-boosted or cobicistat-boosted darunavir;200 may result in adrenal insufficiency or Cushing's syndrome;200 decreased darunavir concentrations may occur200

Prednisone (systemic): Increased corticosteroid concentrations if used with ritonavir-boosted or cobicistat-boosted darunavir;200 may result in adrenal insufficiency or Cushing's syndrome200

Dexamethasone (systemic): Decreased darunavir or ritonavir concentrations if used with ritonavir-boosted darunavir; decreased darunavir or cobicistat concentrations if used with cobicistat-boosted darunavir; possible decreased antiretroviral efficacy1 200 237 239

Budesonide, fluticasone, mometasone (orally inhaled, intranasal): Do not use concomitantly with ritonavir-boosted or cobicistat-boosted darunavir unless potential benefits of the corticosteroid outweigh risks of systemic corticosteroid adverse effects;200 consider alternative (e.g., beclomethasone), especially when long-term corticosteroid use anticipated1 200 237 239

Beclomethasone (orally inhaled): Dosage adjustments not needed200

Methylprednisolone, prednisolone, or triamcinolone (intra-articular or other local injections): Do not use concomitantly with ritonavir-boosted or cobicistat-boosted darunavir;200 consider alternative nonsteroidal therapies; if intra-articular corticosteroid required, use alternative antiretroviral that does not alter CYP3A4 activity (e.g., dolutegravir, raltegravir)200

Budesonide or prednisone (systemic): Do not use concomitantly with ritonavir-boosted or cobicistat-boosted darunavir unless potential benefits outweigh risks of systemic corticosteroid adverse effects200

Dexamethasone (systemic): Use concomitantly with ritonavir-boosted or cobicistat-boosted darunavir with caution;200 consider alternative corticosteroid for long-term use200

Daclatasvir

Ritonavir-boosted darunavir: No clinically important effect on daclatasvir or darunavir exposures178 200

Ritonavir-boosted or cobicistat-boosted darunavir: Dosage adjustments not needed178 200

Dasabuvir

Ritonavir-boosted darunavir: Decreased darunavir trough concentrations if used with fixed combination of ombitasvir, paritaprevir, and ritonavir (ombitasvir/paritaprevir/ritonavir) with dasabuvir175 180 200

Cobicistat-boosted darunavir: Data not available regarding pharmacokinetic interactions with ombitasvir/paritaprevir/ritonavir with dasabuvir200

Ritonavir-boosted darunavir: Concomitant use with ombitasvir/paritaprevir/ritonavir with dasabuvir not recommended175 180 200

Cobicistat-boosted darunavir: Do not use concomitantly with ombitasvir/paritaprevir/ritonavir with dasabuvir200

Delavirdine

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Didanosine

Didanosine delayed-release capsules: No change in didanosine or darunavir concentrations if used with ritonavir-boosted or cobicistat-boosted darunavir1 237

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Administer didanosine (without food) 1 hour before or 2 hours after ritonavir-boosted darunavir (with food) or cobicistat-boosted darunavir (with food)1 237

Digoxin

Ritonavir-boosted or cobicistat-boosted darunavir: Increased digoxin concentrations1 237 239

Ritonavir-boosted darunavir: Use concomitantly with caution;200 use lowest possible initial digoxin dosage;1 monitor digoxin concentrations and adjust dosage as clinically indicated1

Cobicistat-boosted darunavir: Use concomitantly with caution;200 titrate digoxin dosage and monitor digoxin concentrations237 239

Dextromethorphan

Ritonavir-boosted darunavir: Increased dextromethorphan concentrations1

Dolutegravir

Ritonavir-boosted darunavir: No clinically important effect on pharmacokinetics of either drug1

Cobicistat-boosted darunavir: Clinically important interactions not expected237

Dosage adjustments not needed if used concomitantly with ritonavir-boosted or cobicistat-boosted darunavir1 200

Efavirenz

Ritonavir-boosted darunavir: Decreased darunavir AUC; increased efavirenz AUC1 200

Cobicistat-boosted darunavir: Possible decreased darunavir and cobicistat concentrations;200 237 possible loss of therapeutic effect and development of darunavir resistance200 237

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Ritonavir-boosted darunavir: Usual dosages can be used;1 200 some experts recommend close clinical monitoring;200 consider monitoring plasma concentrations of darunavir and efavirenz200

Cobicistat-boosted darunavir: Concomitant use not recommended200 237 239

Elbasvir and grazoprevir

Ritonavir-boosted darunavir: Increased elbasvir concentrations and substantially increased grazoprevir concentrations;177 200 may increase risk of elevated ALT concentrations177 200

Cobicistat-boosted darunavir: Increased grazoprevir concentrations expected;200 may increase risk of elevated ALT concentrations200

Ritonavir-boosted or cobicistat-boosted darunavir: Concomitant use with fixed combination of elbasvir and grazoprevir (elbasvir/grazoprevir) contraindicated177 200

Elvitegravir

Elvitegravir: No effect on darunavir or elvitegravir exposures if used with ritonavir-boosted darunavir;200 data not available regarding use with cobicistat-boosted darunavir200

Fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir DF (EVG/c/FTC/TDF): Altered concentrations of elvitegravir, cobicistat, and/or darunavir if used with ritonavir-boosted darunavir;200 possible decreased elvitegravir concentrations if cobicistat-boosted elvitegravir used with cobicistat-boosted darunavir200

Elvitegravir: If used concomitantly with ritonavir-boosted darunavir, recommended dosage is elvitegravir 150 mg once daily and darunavir 600 mg twice daily in conjunction with ritonavir 100 mg twice daily;200 concomitant use with cobicistat-boosted darunavir not recommended200

EVG/c/FTC/TDF: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir not recommended200

Emtricitabine

Ritonavir-boosted or cobicistat-boosted darunavir: Pharmacokinetic interactions not expected1 237

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Ritonavir-boosted darunavir: Dosage adjustments not needed1

Enfuvirtide

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Eplerenone

Ritonavir-boosted or cobicistat-boosted darunavir: Increased eplerenone concentrations expected200

Ritonavir-boosted or cobicistat-boosted darunavir: Experts state concomitant use contraindicated200

Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine)

Ritonavir-boosted or cobicistat-boosted darunavir: Potential for serious or life-threatening adverse effects (e.g., peripheral vasospasm, ischemia of extremities)1 237 239

Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir contraindicated1 237 239

If treatment of uterine atony and excessive postpartum bleeding is indicated in a woman receiving darunavir, use methylergonovine maleate (Methergine) only if alternative treatments cannot be used and if potential benefits outweigh risks; use methylergonovine at lowest dosage and shortest duration possible202

Estrogens/progestins

Oral hormonal contraceptives containing ethinyl estradiol and norethindrone: Decreased ethinyl estradiol and norethindrone concentrations if used with ritonavir-boosted darunavir;1 data not available regarding use with cobicistat-boosted darunavir200 237 239

Progestin-only contraceptives: Possible reduced efficacy of contraceptive1

Transdermal contraceptives containing ethinyl estradiol and norelgestromin or subdermal implant contraceptives containing etonogestrel: Data not available regarding use with ritonavir-boosted or cobicistat-boosted darunavir200

Ritonavir-boosted or cobicistat-boosted darunavir: Use additional or alternative nonhormonal contraception methods1 200 237 239

Etravirine

Ritonavir-boosted darunavir: Decreased etravirine AUC, but no change in darunavir concentrations;1 200 safety and efficacy of ritonavir-boosted darunavir and etravirine established in clinical studies1 200

Cobicistat-boosted darunavir: Possible decreased cobicistat concentrations;200 237 effect on darunavir pharmacokinetics unknown;200 237 possible loss of therapeutic effect and development of darunavir resistance237 239

No in vitro evidence of antagonistic antiretroviral effects with darunavir214

Ritonavir-boosted darunavir: Dosage adjustments not needed1 200

Cobicistat-boosted darunavir: Concomitant use not recommended200 237 239

Fentanyl

Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased fentanyl concentrations200 237 239

Ritonavir-boosted or cobicistat-boosted darunavir: Carefully monitor patient for fentanyl therapeutic and adverse effects, including potentially fatal respiratory depression200 237 239

Flibanserin

Ritonavir-boosted or cobicistat-boosted darunavir: Increased flibanserin concentrations expected200

Ritonavir-boosted or cobicistat-boosted darunavir: Experts state concomitant use contraindicated200

Histamine H2- receptor antagonists (e.g., ranitidine)

Ritonavir-boosted or cobicistat-boosted darunavir: No clinically important effects expected if used with ranitidine or other histamine H2- receptor antagonists1 200 237

Ranitidine or other histamine H2- receptor antagonists: Dosage adjustments not needed if used with ritonavir-boosted or cobicistat-boosted darunavir1 200

HMG-CoA reductase inhibitors (statins)

Atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin: Increased antilipemic agent concentrations and AUC if used with ritonavir-boosted or cobicistat-boosted darunavir; increased risk of statin-associated adverse effects, including myopathy and rhabdomyolysis1 186 200 237 239

Pitavastatin: Decreased pitavastatin AUC and no clinically important effect on darunavir concentrations if used with ritonavir-boosted darunavir;12 200 data not available regarding use with cobicistat-boosted darunavir237

Atorvastatin: If used with ritonavir-boosted darunavir, do not exceed atorvastatin dosage of 20 mg daily;1 186 200 carefully titrate atorvastatin dosage; use lowest necessary dosage with close monitoring for adverse effects;1 200 if used with cobicistat-boosted darunavir, initiate atorvastatin at lowest necessary dosage and monitor patient for safety237 239

Lovastatin: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir contraindicated1 186 200 237 239

Pitavastatin: Dosage adjustments not necessary if used with ritonavir-boosted darunavir;200 if used with cobicistat-boosted darunavir, initiate pitavastatin at lowest necessary dosage, titrate dosage, and monitor patient for safety;237 experts state dosage adjustment not necessary if used with cobicistat-boosted darunavir200

Pravastatin: If used with ritonavir-boosted or cobicistat-boosted darunavir, carefully titrate pravastatin dosage; use lowest necessary dosage with close monitoring for adverse effects1 200

Rosuvastatin: If used with ritonavir-boosted or cobicistat-boosted darunavir, carefully titrate rosuvastatin dosage; use lowest necessary dosage with close monitoring for adverse effects1 200

Simvastatin: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir contraindicated1 186 200

Immunosuppressive agents (cyclosporine, everolimus, sirolimus, tacrolimus)

Cyclosporine, everolimus, sirolimus, tacrolimus: Increased immunosuppressive agent concentrations expected if used with ritonavir-boosted or cobicistat-boosted darunavir1 200 237 239

Cyclosporine, sirolimus, tacrolimus: Monitor plasma concentrations of immunosuppressive agent if used concomitantly with ritonavir-boosted or cobicistat-boosted darunavir1 237 239

Everolimus: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir not recommended1 237 239

Indinavir

Ritonavir-boosted darunavir: Increased concentrations and AUC of darunavir and indinavir1

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Appropriate dosages for concomitant use not established1

Ivabradine

Ritonavir-boosted or cobicistat-boosted darunavir: Increased ivabradine concentrations expected200

Ritonavir-boosted or cobicistat-boosted darunavir: Experts state concomitant use contraindicated200

Lamivudine

Ritonavir-boosted or cobicistat-boosted darunavir: Pharmacokinetic interactions unlikely1 237

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Ritonavir-boosted darunavir: Dosage adjustments not needed1

Ledipasvir and sofosbuvir

Ritonavir-boosted or cobicistat-boosted darunavir: Clinically important pharmacokinetic interactions not expected if used with fixed combination of ledipasvir and sofosbuvir (ledipasvir/sofosbuvir)181 200

Ritonavir-boosted darunavir in conjunction with emtricitabine and tenofovir DF in patients receiving ledipasvir/sofosbuvir: Increased tenofovir concentrations;181 200 safety of increased tenofovir concentrations not established181 200

Ritonavir-boosted or cobicistat-boosted darunavir: Dosage adjustments not needed if used concomitantly with ledipasvir/sofosbuvir200

Ritonavir-boosted darunavir in conjunction with emtricitabine and tenofovir DF in patients receiving ledipasvir/sofosbuvir: Consider alternative HCV treatment regimen or alternative antiretroviral regimen;181 200 if concomitant use necessary, monitor for tenofovir-associated adverse effects181 200

Lopinavir/ritonavir

Ritonavir-boosted darunavir: Decreased darunavir concentrations; no change in lopinavir concentrations1

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Concomitant use not recommended;1 appropriate dosages with respect to safety and efficacy not established1

Macrolides (clarithromycin, erythromycin, telithromycin)

Clarithromycin: Increased clarithromycin concentrations if used with ritonavir-boosted darunavir;1 increased darunavir, cobicistat, and clarithromycin concentrations if used with cobicistat-boosted darunavir200 237 239

Erythromycin, telithromycin: Increased darunavir, cobicistat, and macrolide concentrations if used with cobicistat-boosted darunavir237 239

Clarithromycin: If used concomitantly with ritonavir-boosted darunavir, modification of usual clarithromycin dosage not needed in patients with normal renal function, but reduce clarithromycin dosage by 50% if Clcr 30–60 mL/minute and reduce by 75% if Clcr <30 mL/minute;1 consider alternative (e.g., azithromycin) in patients receiving ritonavir-boosted or cobicistat-boosted darunavir200 237 239

Erythromycin, telithromycin: Consider alternative anti-infective in patients receiving cobicistat-boosted darunavir237 239

Maraviroc

Increased maraviroc concentrations and AUC if used with ritonavir-boosted or cobicistat-boosted darunavir1 200 224 237 239

No in vitro evidence of antagonistic antiretroviral effects with darunavir224

Ritonavir-boosted or cobicistat-boosted darunavir: Recommended maraviroc dosage is 150 mg twice daily 1 200 224 237 239

Methadone

Ritonavir-boosted darunavir: Decreased methadone concentrations1

Cobicistat-boosted darunavir: Effect on methadone pharmacokinetics unknown200 237 239

Ritonavir-boosted darunavir: Adjustment of methadone dosage not needed when initiating ritonavir-boosted darunavir,1 200 but closely monitor for opiate withdrawal since some patients may need adjustment of methadone maintenance dosage1 200

Cobicistat-boosted darunavir: Initiate methadone using lowest possible dosage and titrate carefully to desired therapeutic effect;200 237 239 if initiating cobicistat-boosted darunavir in patient already receiving methadone, monitor patient and consider that adjustment of methadone dosage may be needed237 239

Nelfinavir

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Nevirapine

Ritonavir-boosted darunavir: Increased nevirapine and darunavir concentrations1 200

Cobicistat-boosted darunavir: Possible decreased cobicistat concentrations;200 237 effect on darunavir pharmacokinetics unknown;200 237 possible loss of therapeutic effect and development of darunavir resistance237 239

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Ritonavir-boosted darunavir: Dosage adjustments not needed1 200

Cobicistat-boosted darunavir: Concomitant use not recommended200 237 239

Ombitasvir

Ritonavir-boosted darunavir: Decreased darunavir concentrations if used with fixed combination of ombitasvir/paritaprevir/ritonavir179 or if used with fixed combination of ombitasvir/paritaprevir/ritonavir copackaged with dasabuvir180

Cobicistat-boosted darunavir: Data not available regarding use with ombitasvir/paritaprevir/ritonavir copackaged with dasabuvir200

Unboosted darunavir: Manufacturer of ombitasvir/paritaprevir/ritonavir states the fixed-combination HCV drug may be used concomitantly with darunavir (800 mg) without low-dose ritonavir179

Ritonavir-boosted or cobicistat-boosted darunavir: Concomitant use with ombitasvir/paritaprevir/ritonavir copackaged with dasabuvir not recommended180 200

Oxycodone

Cobicistat-boosted darunavir: Possible increased oxycodone concentrations237

Cobicistat-boosted darunavir: Carefully monitor patient for oxycodone therapeutic and adverse effects, including potentially fatal respiratory depression237

Paritaprevir

Ritonavir-boosted darunavir: Decreased darunavir trough concentrations if used with fixed combination of ombitasvir/paritaprevir/ritonavir179 or if used with ombitasvir/paritaprevir/ritonavir with dasabuvir175 180 200

Cobicistat-boosted darunavir: Data not available regarding use with ombitasvir/paritaprevir/ritonavir copackaged with dasabuvir200

Unboosted darunavir: Manufacturer of ombitasvir/paritaprevir/ritonavir states the fixed combination HCV drug may be used concomitantly with darunavir (800 mg) without low-dose ritonavir179

Ritonavir-boosted or cobicistat-boosted darunavir: Concomitant use with ombitasvir/paritaprevir/ritonavir with dasabuvir not recommended175 180 200

Proton pump inhibitors (PPIs)

Ritonavir-boosted darunavir: Decreased omeprazole concentrations, but no change in darunavir concentrations1

Cobicistat-boosted darunavir: Clinically important interactions not expected237

Ritonavir-boosted darunavir: Monitor for decreased omeprazole efficacy;1 consider increasing omeprazole dosage if symptoms not well controlled, but avoid omeprazole dosage >40 mg once daily1

Cobicistat-boosted darunavir: Dosage adjustments not needed if used with PPIs200

Raltegravir

Ritonavir-boosted darunavir: No clinically important effect on pharmacokinetics of darunavir1 225

Cobicistat-boosted darunavir: Data not available,200 but clinically important interactions not expected237

Ritonavir-boosted or cobicistat-boosted darunavir: Dosage adjustments not needed1 200

Ranolazine

Ritonavir-boosted or cobicistat-boosted darunavir: Possible serious and/or life-threatening adverse effects1 237

Ritonavir-boosted or cobicistat-boosted darunavir: Concomitant use contraindicated1 237

Rilpivirine

Ritonavir-boosted darunavir: Increased rilpivirine concentrations and AUC, but no clinically important effect on darunavir concentrations or AUC226

Cobicistat-boosted darunavir: Possible increased rilpivirine concentrations;200 altered darunavir concentrations not expected200 237

No in vitro evidence of antagonistic antiretroviral effects with darunavir226

Ritonavir-boosted or cobicistat-boosted darunavir: Dosage adjustments not needed1 200 226

Ritonavir

Increased darunavir concentrations and AUC;1 2 200 low-dose ritonavir (100 mg once daily) used as a pharmacokinetic enhancer (pharmacokinetic booster) for therapeutic advantage (ritonavir-boosted darunavir)1 2 200

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Ritonavir or ritonavir-containing preparations: Concomitant use with cobicistat-boosted darunavir not recommended237

St. John’s wort (Hypericum perforatum)

Ritonavir-boosted or cobicistat-boosted darunavir: Potential decreased darunavir concentrations; possible decreased antiretroviral efficacy1 237 239

Ritonavir-boosted or cobicistat-boosted darunavir: Concomitant use contraindicated1 237 239

Salmeterol

Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased salmeterol concentrations and increased risk of QT interval prolongation, palpitations, and sinus tachycardia1 237 239

Ritonavir-boosted or cobicistat-boosted darunavir: Concomitant use not recommended1 200 237 239

Saquinavir

Ritonavir-boosted darunavir: Decreased darunavir concentrations, but saquinavir concentrations unchanged1

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Ritonavir-boosted darunavir: Concomitant use not recommended1

Selective serotonin-reuptake inhibitors (SSRIs)

Paroxetine, sertraline: Decreased SSRI concentrations and AUCs and no change in darunavir concentrations if used with ritonavir-boosted darunavir;1 200 possible pharmacokinetic interactions if used with cobicistat-boosted darunavir, but effect on SSRI concentrations unknown200 237 239

Fluvoxamine: Possible altered (increased or decreased) darunavir concentrations if used with ritonavir-boosted or cobicistat-boosted darunavir200

Paroxetine, sertraline: Titrate SSRI dosage based on clinical response in patients receiving ritonavir-boosted or cobicistat-boosted darunavir;200 237 239 if ritonavir-boosted darunavir initiated in those on stable SSRI dosage, monitor for clinical response1

Fluvoxamine: Experts state consider alternative to fluvoxamine in patients receiving ritonavir-boosted or cobicistat-boosted darunavir200

Sildenafil

Ritonavir-boosted or cobicistat-boosted darunavir: Increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope)1 237 239

Sildenafil (Revatio) for treatment of pulmonary arterial hypertension (PAH): Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir contraindicated;1 237 239 safe and effective dosage for concomitant use not established1

Sildenafil for treatment of erectile dysfunction: In patients receiving ritonavir-boosted or cobicistat-boosted darunavir, do not exceed sildenafil dosage of 25 mg once every 48 hours; closely monitor for sildenafil-associated adverse effects1 200 237 239

Simeprevir

Ritonavir-boosted darunavir: Increased concentrations and AUC of simeprevir and darunavir1 187 200

Cobicistat-boosted darunavir: Increased simeprevir concentrations237 239

Ritonavir-boosted or cobicistat-boosted darunavir: Concomitant use not recommended1 187 200 237 239

Sofosbuvir

Ritonavir-boosted darunavir: No clinically important pharmacokinetic interactions188

Ritonavir-boosted darunavir: Dosage adjustments not needed188

Cobicistat-boosted darunavir: May be used concomitantly200

Sofosbuvir and velpatasvir

Ritonavir-boosted darunavir: No clinically important pharmacokinetic interactions if used with fixed combination of sofosbuvir and velpatasvir (sofosbuvir/velpatasvir)176

HIV antiretroviral regimen of ritonavir-boosted darunavir in conjunction with emtricitabine/tenofovir DF: Increased velpatasvir and tenofovir concentrations and AUC if used with sofosbuvir/velpatasvir176

HIV antiretroviral regimens that include ritonavir-boosted darunavir and tenofovir DF: Monitor for tenofovir-associated adverse effects if used with sofosbuvir/velpatasvir176

Stavudine

Ritonavir-boosted or cobicistat-boosted darunavir: Pharmacokinetic interactions unlikely1 237 239

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Ritonavir-boosted darunavir: Dosage adjustments not needed1

Suvorexant

Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased suvorexant concentrations200

Ritonavir-boosted or cobicistat-boosted darunavir: Experts state concomitant use with suvorexant not recommended200

Tadalafil

Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope)1 237 239

Tadalafil for treatment of PAH in patients who have been receiving ritonavir-boosted or cobicistat-boosted darunavir for ≥1 week: Use initial tadalafil dosage of 20 mg once daily; if tolerated, may increase dosage to 40 mg once daily1 237 239

Ritonavir-boosted or cobicistat-boosted darunavir in patients receiving tadalafil for PAH: Discontinue tadalafil for at least 24 hours prior to initiating ritonavir-boosted or cobicistat-boosted darunavir; after ≥1 week of the antiretroviral, may resume tadalafil at dosage of 20 mg once daily and, if tolerated, may increase dosage to 40 mg once daily1 237 239

Tadalafil for treatment of erectile dysfunction: In patients receiving ritonavir-boosted or cobicistat-boosted darunavir, do not exceed tadalafil dosage of 10 mg once every 72 hours; closely monitor for tadalafil-related adverse effects1 200 237 239

Tadalafil for treatment of benign prostatic hyperplasia: In patients receiving ritonavir-boosted or cobicistat-boosteddarunavir, do not exceed tadalafil dosage of 2.5 mg once daily200

Tenofovir alafenamide

Ritonavir-boosted or cobicistat-boosted darunavir: No substantial effect on TAF exposures200

Ritonavir-boosted or cobicistat-boosted darunavir: Experts state dosage adjustments not needed200

Tenofovir DF

Ritonavir-boosted darunavir: Increased tenofovir concentrations and AUC;1 200 increased darunavir concentrations and AUC1

Cobicistat-boosted darunavir: Possible increased tenofovir concentrations200

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Ritonavir-boosted darunavir: Experts state clinical importance unknown; monitor for tenofovir toxicity;200 manufacturer of darunavir states usual dosage of ritonavir-boosted darunavir and tenofovir can be used 1

Cobicistat-boosted darunavir: Assess baseline estimated Clcr, urine glucose, and urine protein;237 239 not recommended in patients with estimated Clcr <70 mL/minute;200 237 239 experts state monitor for tenofovir toxicity200

Ticagrelor

Ritonavir-boosted or cobicistat-boosted darunavir: Increased ticagrelor concentrations expected200

Ritonavir-boosted or cobicistat-boosted darunavir: Avoid concomitant use200

Tipranavir

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Tramadol

Cobicistat-boosted darunavir: Increased tramadol concentrations200 237 239

Cobicistat-boosted darunavir: Decreased tramadol dosage may be needed;200 237 239 monitor for efficacy and tramadol-associated adverse effects200

Trazodone

Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased trazodone concentrations and increased risk of nausea, dizziness, hypotension, syncope1 237 239

Ritonavir-boosted or cobicistat-boosted darunavir: Use lowest possible trazodone dosage and monitor for adverse CNS and cardiovascular effects1 200 237 239

Tricyclic antidepressants (amitriptyline, desipramine, doxepin, imipramine, nortriptyline)

Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased concentrations of the tricyclic antidepressant and increased risk of nausea, dizziness, hypotension, syncope1 200 237 239

Ritonavir-boosted or cobicistat-boosted darunavir: Use lowest possible antidepressant dosage; titrate antidepressant dosage based on clinical assessment and/or antidepressant concentrations1 200 237 239

Vardenafil

Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope)1 237 239

Ritonavir-boosted or cobicistat-boosted darunavir: Vardenafil for treatment of erectile dysfunction: Do not exceed vardenafil dosage of 2.5 mg once every 72 hours; closely monitor for vardenafil-related adverse effects1 200 237 239

Vorapaxar

Ritonavir-boosted or cobicistat-boosted darunavir: Increased vorapaxar concentrations expected200

Ritonavir-boosted or cobicistat-boosted darunavir: Avoid concomitant use200

Zidovudine

Ritonavir-boosted or cobicistat-boosted darunavir: Pharmacokinetic interactions unlikely1 237

No in vitro evidence of antagonistic antiretroviral effects with darunavir1

Ritonavir-boosted darunavir: Dosage adjustments not needed1

Zolpidem

Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased zolpidem concentrations200

Ritonavir-boosted or cobicistat-boosted darunavir: Use low initial zolpidem dosage; dosage reduction may be necessary200

darunavir Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Less common
  • Blurred vision
  • dry mouth
  • flushed, dry skin
  • fruit-like breath odor
  • increased hunger
  • increased thirst
  • increased urination
  • skin rash
  • sweating
  • troubled breathing
  • unexplained weight loss
  • unusual tiredness or weakness
Rare
  • Belching
  • blistering, peeling, or loosening of the skin
  • bloating
  • chills
  • clay colored stools
  • constipation
  • cough
  • dark urine
  • decreased appetite
  • diarrhea
  • difficulty with moving
  • dizziness
  • excess air or gas in the stomach or intestines
  • fast heartbeat
  • feeling of fullness
  • fever
  • headache
  • heartburn
  • indigestion
  • itching
  • joint or muscle pain
  • lack or loss of strength
  • light-colored stools
  • loss of appetite
  • muscle aching or cramping
  • nausea and vomiting
  • passing gas
  • red skin lesions, often with a purple center
  • red, irritated eyes
  • sore throat
  • sores, ulcers, or white spots in the mouth or on the lips
  • stomach pain or tenderness
  • swelling of the feet or lower legs
  • swollen joints
  • unpleasant breath odor
  • vomiting of blood
  • yellow eyes or skin
Incidence not known
  • Muscle pain or stiffness
  • swelling or puffiness of the face

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Stuffy or runny nose
Less common
  • Gaining weight around your neck, upper back, breast, face, or waist

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Use Labeled Indications

HIV-1 infection: Treatment of HIV-1 infection, coadministered with ritonavir and other antiretroviral agents, in adults and pediatric patients 3 years and older

Administration

Coadministration with ritonavir and food is required (bioavailability is increased). Shake suspension prior to each dose; use provided oral dosing syringe to measure dose.

Adverse Reactions

Frequency of adverse events is reported for darunavir/ritonavir in both treatment-naive and experienced patients. Frequency, type, and severity of adverse events in pediatric patients are comparable to adult patients unless otherwise noted. See also Ritonavir monograph.

>10%:

Dermatologic: Skin rash (children: 5% to 19%; adults: 6% to 7%)

Endocrine & metabolic: Hypercholesterolemia (adults: grade 2: 23% to 25%; grade 3: 1% to 10%; children: grade 3: 1%), increased LDL cholesterol (adults: grade 2: 14%; grade 3: 8% to 9%; children: grade 3: 3%), hyperglycemia (grade 2: 10% to 11%; grade 3: 1%; grade 4: <1%)

Gastrointestinal: Vomiting (children: 13% to 33%; adults: 2% to 5%), nausea (children: 4% to 25%; adults: 4% to 7%), diarrhea (children: 11% to 24%; adults: 8% to 14%)

1% to 10%:

Central nervous system: Headache (children: 9%; adults: 3% to 7%), fatigue (children: 3%; adults: ≤2%), abnormal dreams (<2%)

Dermatologic: Pruritus (children: 8%; adults: <2%), Stevens-Johnson syndrome (<2%), urticaria (<2%)

Endocrine & metabolic: Increased serum triglycerides (grade 2: 3% to 10%; grade 3: 2% to 7%; grade 4: 1% to 3%), increased amylase (adults: grade 2: 5% to 6%, grade 3: 5% to 7%; children: grade 3: 4%, grade 4: 1%), diabetes mellitus (2%)

Gastrointestinal: Abdominal pain (children: 5% to 10%; adults: 5% to 6%), decreased appetite (children: 8%; adults: 2%), anorexia (children: 5%; adults: 2%), increased serum lipase (adults: grade 2: 3%; grade 3: ≤2%; grade 4: <1%; children: grade 3: 1%), abdominal distention (2%), dyspepsia (2%), flatulence (<2%), pancreatitis (<2%)

Hepatic: Increased serum ALT (adults: grade 2: 7%, grade 3: 2% to 3%; grade 4: ≤1%; children: grade 3: 3%; grade 4: 1%), increased serum AST (adults: grade 2: 6%; grade 3: 2% to 4%; grade 4: ≤1%; children: grade 3: 1%), hepatitis (<2%; acute and cytolytic)

Hypersensitivity: Angioedema (<2%), hypersensitivity (<2%)

Immunologic: Immune reconstitution syndrome (<2%)

Neuromuscular & skeletal: Weakness (≤3%), myalgia (<2%), osteonecrosis (<2%)

<1%, postmarketing, and/or case reports: Absence seizures, acute generalized exanthematous pustulosis, acute renal failure, acute respiratory distress, allergic dermatitis, alopecia, anemia, anxiety, arthralgia, arthritis, arthropathy, biliary obstruction, blurred vision, bradycardia, cerebral infarction, cerebrovascular accident, decreased serum creatinine, dehydration, depression, dermatitis (including dermatitis medicamentosa), dizziness, DRESS syndrome, drowsiness, dyspnea, epistaxis, erythema multiforme, facial edema, facial paralysis, feeling of heaviness, fever, folliculitis, gastritis, gynecomastia, hematuria, hepatic cirrhosis, hepatic failure, hepatic neoplasm (malignant), hepatotoxicity, hiccups, hyperbilirubinemia, hyperhidrosis, hyperkalemia, hyperlipidemia, hypertension, hyperthermia, hypoesthesia, impaired consciousness, increased serum alkaline phosphatase, infection (including clostridium infection, parasitic infection [cryptosporidiosis], cytomegalovirus disease [encephalitis], hepatitis B, esophageal candidiasis), jaundice, limb pain, lipoatrophy, maculopapular rash, malignant lymphoma, mean glomerular filtration rate decreased, metabolic acidosis, myocardial infarction, myocarditis, myositis, neoplasm (diffuse large B-cell), nephrolithiasis, neuromuscular disease, neutropenia, nightmares, night sweats, obesity, oropharyngeal ulcer, osteopenia, osteoporosis, pancytopenia, paresthesia, peripheral edema, peripheral neuropathy, pneumothorax, polydipsia, polyuria, progressive multifocal leukoencephalopathy, proteinuria, pulmonary edema, rectal hemorrhage, redistribution of body fat (eg, buffalo hump, increased abdominal girth, breast engorgement, facial atrophy), renal insufficiency, renal tubular necrosis, respiratory failure, rhabdomyolysis (coadministration with HMG-CoA reductase inhibitors), rigors, seizure, sepsis, skin rash (toxic), swelling of eye, tachycardia, thrombocytopenia, toxic epidermal necrolysis, transient ischemic attacks, uveitis, vertigo, xerostomia

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