Fosamprenavir Calcium and Lofexidine Hydrochloride

• Generic Name: fosamprenavir
• Dosage Forms: n.a.
• Other Brand Names: Lexiva, Telzir

Treatment of HIV-1 infection in adults, adolescents, and certain pediatric patients ≥4 weeks of age; used in conjunction with other antiretrovirals.

Used in conjunction with low-dose ritonavir (ritonavir-boosted fosamprenavir) or without low-dose ritonavir (unboosted fosamprenavir); usually used in PI-based regimens that include a PI and 2 nucleoside reverse transcriptase inhibitors (NRTIs).

For initial treatment in antiretroviral-naive adults or adolescents, experts state fosamprenavir (with or without low-dose ritonavir) not recommended. Regimens that include unboosted fosamprenavir may be associated with virologic failure and may result in selection of mutations that confer resistance to fosamprenavir and darunavir; clinical trial data for ritonavir-boosted fosamprenavir more limited compared with data available for other ritonavir-boosted PIs.

For initial treatment in antiretroviral-naive pediatric patients, experts state ritonavir-boosted fosamprenavir not recommended in any age group because other more advantageous ritonavir-boosted PIs are available. Fosamprenavir (without low-dose ritonavir) also not recommended for pediatric patients of any age because of concerns related to inconvenient dosing and possibility of selection of resistance mutations.

Consider the following factors when initiating ritonavir-boosted fosamprenavir: Data insufficient to determine whether a regimen that includes ritonavir-boosted fosamprenavir is as effective as a regimen that includes the fixed-combination of lopinavir and ritonavir (lopinavir/ritonavir) in adults who previously received PIs (PI-experienced). Once-daily ritonavir-boosted fosamprenavir not recommended in PI-experienced adults or in any pediatric patient.

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 disoproxil fumarate (tenofovir DF) as preferred regimen for PEP following occupational exposures to HIV. Fosamprenavir (with or without low-dose ritonavir) and 2 NRTIs can be considered an alternative regimen, but use for PEP only with expert consultation. 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 in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF.

CDC states that fosamprenavir is an alternative antiretroviral that can be used in nPEP regimens, but use in such regimens only with expert consultation.

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.

• Generic Name: lofexidine
• Dosage Forms: n.a.
• Other Brand Names: Lucemyra

Used for mitigation of opiate withdrawal symptoms to facilitate abrupt opiate discontinuance.

Not a treatment for opiate use disorder (OUD); use in patients with OUD only in conjunction with a comprehensive treatment program.

In patients with OUD, opiate withdrawal management (i.e., detoxification) generally involves short-term use of tapering dosages of buprenorphine (opiate partial agonist) or methadone (full opiate agonist) to reduce withdrawal symptoms. However, α2-adrenergic agonists (e.g., lofexidine, clonidine) also used for symptomatic relief of noradrenergic-mediated opiate withdrawal symptoms (e.g., lacrimation, sweating, shivering, rhinorrhea) in inpatient and outpatient settings and may allow for withdrawal over a shorter period of time.

α2-Adrenergic agonists appear to be less effective than buprenorphine or methadone for management of opiate withdrawal; some experts suggest α2-adrenergic agonists may be most useful in withdrawal management as adjuncts to opiate agonists or partial agonists, to facilitate transition to opiate antagonist (naltrexone) treatment for relapse prevention, or when opiate agonist or partial agonist therapy is contraindicated, unacceptable, or unavailable.

Concomitant supportive therapy for other withdrawal symptoms (e.g., abdominal cramping, diarrhea, nausea and vomiting, muscle spasms, anxiety or restlessness, insomnia) often used.

Several small comparative studies suggest lofexidine and clonidine have similar efficacy in managing opiate withdrawal symptoms but lofexidine may cause less hypotension. Must also consider greater cost of lofexidine compared with off-label clonidine use.

Because of potential for hypotension and bradycardia, some experts state that α2-adrenergic agonists are not drugs of choice for opiate withdrawal management in geriatric patients or patients with coronary insufficiency, ischemic heart disease, bradycardia, or cerebrovascular disease.

In patients receiving long-term opiate analgesia, withdrawal symptoms generally managed by slow tapering of the opiate analgesic dosage.