Anagrelide hydrochloride and Atazanavir Sulfate

• Generic Name: anagrelide
• Dosage Forms: n.a.
• Other Brand Names: Agrylin

Reduction of elevated platelet counts and associated risk of thromboembolic and hemorrhagic events in patients with thrombocythemia secondary to essential thrombocythemia (ET) and other myeloproliferative disorders. Has been designated an orphan drug by FDA for the treatment of ET.

Management of ET generally based on a risk-stratification approach. Treatment with a cytoreductive agent (e.g., anagrelide, hydroxyurea) usually reserved for patients at high risk (i.e., age >60 years, previous history of thrombosis, and/or platelet count ≥1,500,000/mm3) of developing thromboembolic and/or hemorrhagic complications. Some clinicians also recommend cytoreductive therapy in intermediate-risk ET patients (e.g., 40–60 years of age, platelet count >1,000,000/mm3, and cardiovascular risk factor [smoking, arterial hypertension, hypercholesterolemia, or diabetes mellitus] or familial thrombophilia).

Hydroxyurea (often combined with low-dose aspirin) generally considered drug of choice in high-risk patients with ET because of proven efficacy and infrequent acute toxicity. However, because of potential leukemogenic effects with hydroxyurea when used long term or sequentially with other cytotoxic drugs, anagrelide or interferon alfa suggested as alternative therapy in high-risk patients, particularly younger patients (<40–60 years of age), and in those who do not respond to or cannot tolerate hydroxyurea. Consider cautious use of low-dose aspirin concomitantly with anagrelide based on relative risks of thrombosis and arterial hemorrhage in individual patients. (See Specific Drugs or Foods under Interactions.)

• Generic Name: atazanavir
• Dosage Forms: n.a.
• Other Brand Names: Reyataz

Atazanavir with low-dose ritonavir (ritonavir-boosted atazanavir): Treatment of HIV-1 infection in adults, adolescents, and pediatric patients ≥3 months of age; used in conjunction with other antiretrovirals.

Atazanavir with cobicistat (cobicistat-boosted atazanavir): Treatment of HIV-1 infection in adults; used in conjunction with other antiretrovirals.

Unboosted atazanavir (i.e., without low-dose ritonavir or cobicistat): Treatment of HIV-1 infection in adults and adolescents ≥13 years of age; used in conjunction with other antiretrovirals.

Atazanavir usually used in conjunction with a pharmacokinetic enhancer (i.e., low-dose ritonavir or cobicistat). Pharmacokinetic enhancer (pharmacokinetic booster) used to improve atazanavir's pharmacokinetic profile. Low-dose ritonavir and cobicistat are not interchangeable in antiretroviral regimens; these pharmacokinetic enhancers have different dosage and administration requirements and are associated with different adverse effects, precautions, contraindications, and drug interactions.

When ritonavir-boosted atazanavir used, single-entity atazanavir is given with single-entity ritonavir.

When cobicistat-boosted atazanavir used, fixed combination containing both drugs (atazanavir/cobicistat) can be used; alternatively, single-entity atazanavir is given with single-entity cobicistat. Assess estimated Clcr in all patients prior to initiation of cobicistat-boosted atazanavir (see Renal Effects under Cautions).

For initial treatment in antiretroviral-naive adults and adolescents, experts state that ritonavir-boosted atazanavir in conjunction with tenofovir alafenamide fumarate (TAF) and emtricitabine or ritonavir-boosted atazanavir in conjunction with tenofovir disoproxil fumarate (tenofovir DF) and emtricitabine (or lamivudine) are alternative PI-based regimens. These experts state that cobicistat-boosted atazanavir in conjunction with TAF and emtricitabine or cobicistat-boosted atazanavir in conjunction with tenofovir DF and emtricitabine (or lamivudine) are alternative PI-based regimens for initial treatment in antiretroviral-naive adults and adolescents. Ritonavir-boosted or cobicistat-boosted atazanavir in conjunction with abacavir and lamivudine are other regimen options for initial treatment in antiretroviral-naive patients when recommended or alternative regimens cannot be used, but use only in those with baseline plasma HIV RNA levels <100,000 copies/mL who are human leukocyte antigen (HLA)-B*5701 negative.

For initial treatment in antiretroviral-naive pediatric patients, experts state that ritonavir-boosted atazanavir in conjunction with 2 nucleoside reverse transcriptase inhibitors (NRTIs) is a preferred regimen in those ≥3 years of age and an alternative regimen in those 3 months to <3 years of age weighing 5–25 kg.

Experts state that unboosted atazanavir is not recommended for initial treatment in antiretroviral-naive adults, adolescents, or children because it is less potent than boosted atazanavir.

Unboosted atazanavir should not be used in antiretroviral-experienced (previously treated) patients with prior virologic failure. If using ritonavir-boosted atazanavir or cobicistat-boosted atazanavir in antiretroviral-experienced patients, treatment should be guided by number of baseline primary PI resistance substitutions.

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.

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

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. Do not delay initiation of PEP while waiting for expert consultation.

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. Used in conjunction with other antiretrovirals.

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); recommended alternative regimen in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF.

CDC states that ritonavir-boosted atazanavir is an alternative antiretroviral that can be used in nPEP regimens.

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. Do not delay initiation of nPEP while waiting for expert consultation.