DARUNAVIR
| DARUNAVIR (da-run'a-ver) Prezista Classifications: antiretroviral agent; hiv protease inhibitor; Therapeutic:antiretroviral; protease inhibitor Prototype: Saquinavir Pregnancy Category: B |
Availability
300 mg tablets
Action
Darunavir is an inhibitor of HIV-1 protease that selectively inhibits the cleavage of HIV polyproteins in infected cells, thereby preventing the maturation of virus particles.
Therapeutic Effect
Darunavir reduces the viral load (decreases the number of RNA copies) and increases the number of T helper CD4 cells.
Uses
Treatment of HIV infection, usually in combination with two nucleoside reverse transcriptase inhibitors, such as lamivudine and zidovudine.
Contraindications
Hypersensitivity to darunavir or protease inhibitors, ritonavir; pancreatitis; lactation. Safety and efficacy in children have not been established.
Cautious Use
Hepatic function impairment, hepatitis; severe renal impairment, chronic renal failure; hemophilia A or B; diabetes mellitus; diabetes ketoacidosis; hyperglycemia; elderly; pregnancy (category B).
Route & Dosage
| HIV Infection Adult: PO 600 mg b.i.d. with 100 mg ritonavir PO |
Administration
Oral- Give with food and coadminister with 100 mg ritonavir.
- Tablets must be swallowed whole.
- Store at 15°–30° C (59°–86° F). Protect from light and moisture.
Adverse Effects (≥2%)
CNS: Headache. GI: Abdominal pain, constipation, diarrhea, vomiting. Skin: Stevens-Johnson syndrome.Interactions
Drug: azole antifungals and indinavir increase the levels of darunavir. Coadministration of other inhibitors of CYP3A4 may also increase darunavir. anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin), corticosteroids (e.g., dexamethasone), efavirenz, rifamycins (e.g., rifampin, rifabutin), and saquinavir may decrease darunavir levels. Darunavir may increase the levels of azole antifungals, corticosteroids, efavirenz, indinavir, rifamycins, amiodarone, bepridil, lidocaine, quinidine, calcium channel blockers (e.g., nifedipine, nicardipine, felodipine), clarithromycin, immunosuppressants (e.g., cyclosporine, sirolimus, tacrolimus), phosphodiesterase type 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil), and trazodone, due in part to its ability to inhibit CYP3A4. Darunavir decreases the levels of the lopinavir/ritonavir combination, oral contraceptives (e.g., ethinyl estradiol, norethindrone), methadone, selective serotonin reuptake inhibitors [SSRIs (e.g., paroxetine, sertraline)], and warfarin. Coadministration of darunavir with benzodiazepines (e.g., midazolam, triazolam) increases the risk of prolonged or increased sedation or respiratory depression. Coadministration of darunavir with ergot alkaloids may increase ergot toxicity. Coadministration of darunavir with hmg coa reductase inhibitors increases the risk of myopathy. Combination use of darunavir with pimozide increases the risk of cardiac arrhythmias. Food: Food enhances the bioavailability of darunavir. Herbal: St. John's wort decreases the level of darunavir.Pharmacokinetics
Absorption: 82% absorbed (in combination with ritonavir). Peak: 2.5–4 h. Distribution: 95% protein bound. Metabolism: In the liver. Elimination: Primarily fecal (80%) with minor elimination in urine. Half-Life: 15 h.Nursing Implications
Assessment & Drug Effects
- Monitor for and report S&S of pancreatitis, as this may be an indication for discontinuation of darunavir.
- Monitor for S&S of skin rash. Notify physician immediately if a severe rash appears.
- Monitor diabetics for loss of glycemic control.
- Lab tests: Periodic CD4+ cell count, plasma HIV-RNA, lipid profile, LFTs; and plasma glucose.
- Increase monitoring of INR with concurrent warfarin therapy.
- Monitor for adverse effects or loss of efficacy of concurrent medications, as many drug interactions occur with darunavir.
Patient & Family Education
- Follow directions for taking the drug (see Administration). If a dose is missed by more than 6 h, wait until the next regularly scheduled dose. If a dose is missed by less than 6 h, take a dose and continue with the next regularly scheduled dose.
- Tell your health care professional about all medications you are taking, including non-prescription drugs, nutritional supplements, or herbal products.
- Ensure that you know which medicines should NOT be taken with darunavir, as serious consequences could occur.
- Report any of the following to a health care provider: blistering, redness, or peeling skin or mucus membranes; severe skin rash.
- Use or add a barrier contraceptive if using an estrogen-containing oral contraceptive in order to prevent pregnancy.
Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; 
Canadian drug name; 
Prototype drug