Genetic Implications: Genetic Implications


Trade Name(s)

  • Prezcobix

Ther. Class.

Pharm. Class.
protease inhibitors
enzyme inhibitors


Treatment of HIV–1 infection in combination with other agents in patients who have no darunavir resistance.


  •  Darunavir– Inhibits HIV-1 protease, selectively inhibiting the cleavage of HIV-encoded specific polyproteins in infected cells. This prevents the formation of mature virus particles.
  • Genetic implication  Cobicistat– Strongly inhibits CYP3A enzymes, enhancing systemic exposure to darunavir.

Therapeutic Effect(s):

Increased CD4 cell counts and decreased viral load with subsequent slowed progression of HIV infection and its sequelae.



Absorption: Food enhances oral absorption.

Distribution: Unknown.

Protein Binding: 95% bound to plasma proteins.

Metabolism and Excretion: Extensively metabolized by CYP3A enzyme system. 41% eliminated unchanged in feces, 8% in urine.

Half-life: 15 hr.


Absorption: Absorption follows oral administration.

Distribution: Unknown.

Protein Binding: 97–98%.

Metabolism and Excretion: Metabolized by CYP3A and to a small extent by CYP2D6; 86.2 eliminated in feces, 8.2% in urine.

Half-life: 3–4 hr.


darunavir unknown2.5–4 hr12 hr
cobicistat unknown3 hr24 hr


Contraindicated in:

  • Concurrent use of other drugs for which changes in blood levels are associated with serious toxicity or loss of effectiveness;
  • Concurrent alfuzosin, dronedarone, colchicine (in renal/hepatic impairment), elbasvir/grazoprevir, ergot derivatives, lovastatin, lurasidone, midazolam (PO), pimozide, ranolazine, rifampin, sildenafil (Revatio), simvastatin, triazolam, or St. John's wort;
  • Concurrent alfuzosin, dronedarone, colchicine (in renal/hepatic impairment), elbasvir/grazoprevir, ergot derivatives, lovastatin, lurasidone, midazolam (PO), pimozide, ranolazine, rifampin, sildenafil (Revatio), simvastatin, triazolam, or St. John's wort;
  • Lactation: HIV may be transmitted in human milk, breastfeeding is not recommended.

Use Cautiously in:

  • Hepatic impairment;
  • Sulfonamide allergy;
  • Geri:  Consider age-related impairment in hepatic function, concurrent chronic disease states and drug therapy;
  • OB:  Use only if maternal benefit outweighs fetal risk;
  • Pedi:  Safe and effective use in children <18 yr has not been established.

Adverse Reactions/Side Effects

CNS: headache

GI: HEPATOTOXICITY, abdominal pain, diarrhea, nausea, vomiting


Endo: hyperglycemia

Misc: redistribution of body fat

* CAPITALS indicate life-threatening.
Underline indicate most frequent.



  • ↑ blood levels and risk of toxicity from alfuzosin, dronedarone, elbasvir/grazoprevir,  ergot derivatives  (dihydroergotamine, ergotamine,  methylergonovine ), lovastatin, lurasidone, midazolam (oral), pimozide, ranolazine, sildenafil (Revatio), simvastatin, and  triazolam ; concurrent use contraindicated.
  •  Rifampin  ↑ metabolism and may ↓ antiretroviral effectiveness, concurrent use is contraindicated.
  • ↑ levels and risk of myopathy from atorvastatin, fluvastatin, pitavastatin, pravastatin, or  rosuvastatin ; use lowest dose of these agents; do not exceed atorvastatin or rosuvastatin dose of 20 mg/day.
  • Concurrent use with  indinavir  in a regimen containing atazanavir ↑ risk of hyperbilirubinemia and is contraindicated.
  • Concurrent use of more than one antiretroviral that requires another agent to ↑ blood levels, such as  two protease inhibitors  or a  protease inhibitor in conjunction with elvitegravir  may ↓ antiretroviral effectiveness; concurrent use is not recommended.
  • Concurrent use of darunavir with efavirenz, nevirapine, or  etravirine  may ↓ antiretroviral effectiveness and ↑ risk of resistance; concurrent use is not recommended.
  • Concurrent use of  darunavir  at a dose of 600 mg twice daily may ↓ antiretroviral effectiveness and ↑ risk of resistance; concurrent use at that dose is not recommended.
  • Concurrent use of other protease inhibitors, including fosamprenavir, saquinavir,  tipranavir  may ↓ antiretroviral effectiveness and ↑ risk of resistance; concurrent use is not recommended.
  • Should not be used concurrently with other  cobicistat-containing fixed-dose combinations  or  ritonavir-containing regimens or fixed-dose combinations due to cumulative effects on CYP3A.
  • ↑ levels of  maraviroc (when used concurrently ↓ maraviroc dose to 150 mg twice daily).
  • ↑ level/risk of toxicity/adverse reactions with  antiarrhythmics  including amiodarone, digoxin, disopyrramide, flecainide, mexiletine, propafenone, and  quindine ; careful monitoring and titration is recommended.
  •  Clarithromycin  and  erythromycin  may ↑ levels of darunavir and cobicistat; consider alternative anti-infectives.
  • ↑ blood levels/risk of toxicity with dasatinib, nilotinib, vinblastine, and  vincristine ; careful monitoring for toxicity and dose adjustments recommended.
  • May ↑ bleeding risk with  rivaroxaban ; avoid concurrent use.
  • May ↑ bleeding risk with  dabigatran in patients with renal impairment; avoid concurrent use.
  • Effect on warfarin is not known; monitor INR.
  •  Carbamazepine  and  oxcarbazepine  ↓ levels of cobicistat; consider alternative anticonvulsants or antiretroviral.
  • May ↑ levels of  clonazepam  and  carbamazepine ; careful anticonvulsant monitoring recommended.
  • May ↑ levels/effects of  tricyclic antidepressants  and  trazodone ; careful dosing of antidepressants recommended (effect on  SSRIs  in unknown).
  • Concurrent use with itraconazole, ketoconazole, and  voriconazole  may result in ↑ levels of itraconazole and ketoconazole (effect on voriconazole is unknown) and ↑ levels of cobicistat and darunavir; voriconazole use not recommended.
  • ↑ levels/risk of adverse reactions with  colchicine ; concurrent use in patients with renal/hepatic impairment contraindicated, for others ↓ dose ( for gout flare– 0.6 mg followed by 0.3 mg one hr later, may repeat no sooner than 3 days,  for prophylaxis of flare– if dose was originally 0.6 mg twice daily, decrease to 0.3 mg once daily, if original regimen was 0.6 mg once daily, ↓ to 0.3 mg every other day,  treatment of familial Mediterranean fever– daily dose should not exceed 0.6 mg or 0.3 mg twice daily).
  • ↑ levels/effects/risk of adverse reaction including neutropenia and uveitis with  rifabutin ; lower rifabutin dose to 150 mg every other day.
  • ↑ levels/effects of metoprolol, carvedilol, timolol, or any other  beta-blockers metabolized by CYP2D6 ; clinical monitoring recommended.
  • ↑ levels/effects of amlodipine, diltiazem, felodipine, nifedipine, verapamil, or any other  calcium channel blocker metabolized by CYP3A ; careful monitoring recommended.
  •  Dexamethasone  may ↓ levels/effects; consider use of alternative corticosteroid, such as beclomethasone or prednisolone.
  • May ↑ levels of systemic, inhaled, nasal, or ophthalmic  corticosteroids  (betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, prednisone, or  triamcinolone ; consider alternative corticosteroid such as beclomethasone or prednisolone.
  • Concurrent use with  bosentan  may result in ↑ levels/toxicity of bosentan and ↓ levels darunavir and cobicistat; dose alteration is required ( initiating bosentan in patients already receiving cobicistat with darunavir for 10 days or more– bosentan 62.5 mg daily or every other day, depending on tolerance initiating cobicistat with darunavir in patient already receiving bosentan – discontinue bosentan for 10 days, resume bosentan at 62.5 mg daily or every other day, depending on tolerance).
  •  H2 -receptor antagonists  including  famotidine  may decrease levels/effectiveness and ↑ risk of resistance; administer simultaneously or at least 10 hr after H2 –receptor antagonist (dose of H2 –receptor antagonist should not exceed famotidine 40 mg [or equivalent] twice daily in treatment-naïve patients or famotidine 20 mg [or equivalent] twice daily in treatment-experienced patients.
  • ↑ levels/risk of toxicity from  immunosuppressants metabolized by CYP3A  including cyclosporine, everolimus, sirolimus, and  tacrolimus ; therapeutic monitoring recommended.
  • ↑ levels of  salmeterol  and may ↑risk of serious adverse cardiovascular events; concurrent use is not recommended.
  • May ↑ levels/risk of respiratory depression with opioids including buprenorphine, buprenorphine/naloxone, fentanyl, and  tramadol ; carefully monitor  opioid  effects when cobicistat with darunavir is initiated, dose adjustment of opioid may be necessary.
  • May ↑ levels/effects of  neuroleptics that are metabolized by CYP3A or CYP2D6  including perphenazine, risperidone, and  thioridazine ; ↓ dose of neuroleptic may be necessary.
  • May ↑ levels and risk of adverse cardiovascular, ophthalmic and genitourinary effects of  PDE-5 inhibitors  including avanafil, sildenafil, tadalafil, and  vardenafil  avanafil  use is not recommended,  sildenafil – use for pulmonary hypertension is contraindicated, when used for erectile dysfunction single dose should not exceed 25 mg/48 hr,  tadalafil – for pulmonary hypertension-initiating tadalafil in patients receiving cobicistat with atazanavir and darunavir for at least 7 days– 20 mg once daily initially, may be titrated to 40 mg once daily, initiating cobicistat with darunavir in patients receiving tadalafil– discontinue tadalafil 24 hr prior to initiating cobicistat with darunavir, after 7 days reinstitute tadalafil at 20 mg once daily, may be increased to 40 mg once daily, for erectile dysfunction single dose should not exceed 10 mg/72 hr vardenafil– for erectile dysfunction single dose should not exceed 2.5 mg/72 hr.
  •  Proton-pump inhibitors  including  omeprazole  ↓ levels/effectiveness and ↑risk of resistance; in treatment–naïve patients, administer cobicistat with darunavir at least 12 hr after proton-pump inhibitors, dose of proton-pump inhibitor should not exceed omeprazole 20 mg daily or equivalent, in treatment-experienced patients concurrent use with proton-pump inhibitors is not recommended.
  • ↑ levels/ effects and risk of excess sedation/respiratory depression from some  sedative/hypnotics metabolized by CYP3A  including buspirone, diazepam, and  parenteral midazolam ; concurrent use with  oral midazolam  is contraindicated, concurrent with  other sedative/hypnotics metabolized by CYP3A  should be undertaken with caution, dose reduction may be necessary.
  • Effects are unknown with  artemether/lumefantrine ; monitor for ↓ antimalarial activity or QT prolongation.
  •  Rifapentine ↓ darunavir levels; concurrent use is not recommended.
  •  Didanosine  should be administered 1 hr before or 2 hr after darunavir/cobicistat.
  • May ↑ levels of  quetiapine ; if taking quetiapine when initiating therapy, consider alternative antiretroviral therapy or ↓ quetiapine dose to 1/6 of the original dose and monitor for adverse effects.
  • ↑ risk of hyperkalemia from  drosperinone/ethinyl estradiol  when used in a regimen containing atazanavir and cobicistat; concurrent use contraindicated.
  • May ↑  ticagrelor  levels; concurrent use not recommended.

Drug-Natural Products:

 St. John's wort  may ↓ blood levels and antiretroviral effectiveness; concurrent use is contraindicated.


PO (Adults): One tablet (darunavir 800 mg/cobicistat 150 mg) once daily.


Tablets: darunavir 800 mg/cobicistat 150 mg


  • Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
  • Assess for allergy to sulfonamides.
  • Monitor patient for development of rash; usually maculopapular and self-limited during first 4 wk. May cause Stevens-Johnson syndrome or toxic epidermal necrolysis. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.

Lab Test Considerations:

Genetic implication Obtain HIV genotypic testing for antiretroviral treatment experienced patients prior to starting therapy.

  • Monitor viral load and CD4 counts regularly during therapy.
  • May cause ↑ serum AST, ALT, GGT, total bilirubin, alkaline phosphatase, pancreatic amylase, pancreatic lipase, triglycerides, total cholesterol, and uric acid concentrations. Monitor hepatic function prior to and periodically during therapy. Hepatotoxicity may require interruption or discontinuation of therapy.
  • Assess CCr before starting therapy.
  • If administered with tenofovir, assess urine glucose and urine protein at baseline and monitor CCr, urine glucose, and urine protein. Monitor serum phosphorus in patients with or at risk for renal impairment

Potential Diagnoses


  • PO Administer once daily with food.

Patient/Family Teaching

  • Explain purpose of cobicistat/darunavir ( Prezcobix ) to patient; must be taken with other antiretroviral medications. Instruct patient to take  Prezcobix  as directed with food. Take missed doses as soon as remembered if within 12 hr; if more than 12 hr, skip dose and take next dose as scheduled; do not double doses. Do not stop taking  Prezcobix  without consulting health care professional. Advise patient to read  Patient Information  prior to starting therapy and with each Rx refill in case of change.
  • Instruct patient that  Prezcobix  should not be shared with others.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's Wort.
  • Inform patient that  Prezcobix  does not cure AIDS or prevent associated or opportunistic infections. Darunavir does not reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom during sexual contact and to avoid sharing needles or donating blood to prevent spreading the AIDS virus to others. Advise patient that the long-term effects of  Prezcobix  are unknown at this time.
  • Inform patient that  Prezcobix  may cause hyperglycemia, hepatotoxicity, and severe skin reactions. Advise patient to notify health care professional promptly if signs of hyperglycemia (increased thirst or hunger; unexplained weight loss; increased urination; fatigue; or dry, itchy skin), immune reconstitution syndrome (signs and symptoms of inflammation from previous infections [Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP, or tuberculosis]), hepatotoxicity (unexplained fatigue, anorexia, nausea, jaundice, abdominal pain, or dark urine), or rash occur.
  • Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
  • Rep:  Instruct females using hormonal contraceptives to use an alternative nonhormonal method of contraception. Advise patient to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding. If pregnant patient is exposed to  Prezcobix , register patient in  Antiretroviral Pregnancy Registry  by calling 1-800-258-4263.
  • Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

Evaluation/Desired Outcomes

  • Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
  • Decrease in viral load and improvement in CD4 cell counts.
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