ID - Fungal, Viral, and Opportunistic Infections Flashcards
Yeasts
-Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei) -> C. albicans typically most susceptible of spp. while C. glabrata and C. krusei tend to be more resistant to types of azole antifungals
-Cryptococcus neoformans
Molds
-Aspergilus spp.
-Zygomycetes (Mucor and Rhizopus spp.)
Dimorphic fungi (exist as mold in lower temperatures and yeast at higher temperatures)
-Histoplasma capsultam
-Blastomyces dermatitidis
-Coccidioides immitis
Amphotericin B (AmpB):
-Types/Brands
-MOA
-ROA
-Typical coverage
-Typical indications
Types:
-AmpB deoxycholate (conventional)
-AmpB lipid complex (Abelcet)
-Liposomal AmpB (Ambisome)
MOA: binds to ergosterol, alterating cell membrane and permeability, causing cell death
RO: injection
Typical Coverage: BROAD spectrum
-Yeasts: most Candidia spp. and Cryptococcus neoformans
-Molds: Aspergillus spp., Zygomycetes
-Dimorphic fungi: Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis
Typical Indications: invasive fungal infections
-Cryptococcal meningitidis w/ flucytosine
-Histoplasmosis
-Mucormycosis
Amphotericin B (AmpB):
-What is different from the conventional formulation versus lipid formulations?
-Administration considerations
Lipid formulations of AmpB have less toxicities and less infusion rxns compared to conventional formulations
Administration Considerations:
-Compatible in D5W ONLY
-Lipid formulations must be filtered
-AmpB conventional requires premedication to reduce infusion rxns (APAP or NSAID, Benadryl, and/or hydrocortisone 30-60 minutes prior to infusion)
-NS boluses reduce risk of nephrotoxicity (increases urination to push drug out)
-Meperidine can be given to reduce severe rigors
-Both conventional and lipid formulations are yellow/orange in color
Amphotericin B (AmpB):
-AVEs
-BBW
-Monitoring
-DDIs
AVEs: INFUSION RXN (fever, chills, HA, malaise, rigors), increased or decreased BP, N/V, HYPOKALEMIA, HYPOMAGNESEMIA, NEPHROTOXOCITY, anemia
-Ambisome (liposomal AmpB): severe back/chest pain w/ first dose
BBW: MEDICATION ERRORS in dosing have resulted in cardiopulmonary arrest and death
-Conventional AmpB: do NOT EXCEED 1.5mg/kg/day (VERIFY PRODUCT AND DOSAGE)
Monitoring: renal fxn, LFTs, electrolytes (especially K and Mg), CBC
DDIs:
-Additive risk of nephrotoxicity w/ other nephrotoxic drugs (cisplatin, polymyxins, aminoglycosides, cyclosporine, tacrolimus, loop diuretics, NSAIDs, radiocontrast dye, vancomycin)
-Increased risk of digoxin toxicity due to hypokalemia
Flucytosine:
-Brand
-MOA
-ROA
-Typical Coverage
-Typical Indications
-AVEs
-BBW
Brand: Ancobon
MOA: penetrates fungal cells and is converted to fluorouracil which interferes w/ RNA and protein synthesis
-Flucytosine called “5-FC” similar to fluorouracil called “5-FU”
ROA: PO
Typical coverage/indications: ALWAYS in combo w/ AmpB (due to development of resistance) for invasive cryptococcal (meningitis) or Candida infections
AVEs: dose-related MYLEOSUPPRESSION (anemia, neutropenia, thrombocytopenia), increased BUN/SCr, liver injury, increased bilirubin, many CNS effects, hypoglycemia, hypokalemia, aplastic anemia
BBW: caution in renal fxn (monitor hematologic, renal, and hepatic status)
Azole Antifungals:
-Drugs/Brands/ROAs
-MOA
-Typical Coverage
-Typical Indications
-Class AVEs
Drugs:
-Fluconazole (Diflucan): PO, injection
-Itraconazole (Sporanox, Tolsura): PO
-Ketoconazole (Nizoral = OTC shampoo): PO, topical
-Voriconazole (Vfend): PO, injection
-Posaconazole (Noxafil): PO, injection
-Isavuconazonium sulfate (Cresemba): PO, injection
MOA: decrease ergosterol synthesis and cell membrane formation
Typical Coverage:
-Fluconazole: C. albicans, C. parapsilosis, C. tropicalis (limited C. glabrata coverage, C. krusei considered R)
-Itraconazole: Blastomycoses, Histoplasma
-Voriconazole: DOC for Aspergillus
Typical Indications:
-Fluconazole: oral thrush/candidiasis
-Itraconazole: nail bed infections (onychomycosis)
-Fluconazole, voriconazole: PENETRATE CNS (can use in fungal meningitis)
Class AVEs
1. Increased LFTs
2. QT prolongation (EXCEPT isavuconazonium)
Azole Antifungals: Dosing Considerations
1. What is the IV to PO ratio?
- Which azoles have sulfobutyl ether beta-cyclodextrin (SBECD) vehicle? Why does it matter?
- What is fluconazole dosing for vaginal candidiasis?
- 1:1 for all azoles
- Voriconazole, posaconazole –> in CrCl <50mL/min, vehicle accumulates and can worsen renal toxicity (PO TX preferred)
- 150 mg PO once
Azole Antifungals: Dosing Considerations
1. Which azole requires renal dose adjustment?
- Which azole should be taken with food?
3 Which azole has different bioavailability where the tablet dose does NOT equal the suspension dose?
- Fluconazole
- Posaconazole, Itraconazole (except solution - take OES)
- Posaconazole
Fluconazole, Itraconazole, and Ketoconazole:
-Administration considerations
-AVEs
-Warnings
-BBW
Adminsitration Considerations:
-Ketoconazole: topical because of high side effect profile
-Itraconazole, tables/capsules: take with food
-Itraconazole, solution: take OES
AVEs: INCREASED LFTS, QT PROLONGATION, HA, N/V, abdominal pain, rash, pruritus, dizziness, hair loss (or possible hair growth)
-Ketoconazole: possible altered hair texture
Warnings: hepatotoxicity
-Fluconazole: exfoliative skin rxns, NOT recommended in pregnancy
BBW:
-Itraconazole: can worsen or cause HEART FAILURE (do NOT use to treat oncychomycosis in pts w/ ventricular dysfunction or hx of heart failure)
-Ketoconazole: HEPATOTOXICITY (has led to transplant/death), QT PROLONGATION; use oral tablets ONLY when othertherapy unavailable or NOT tolerated and the benefits outweigh the risks
Voriconazole:
-Brand
-Administration considerations
Brand: Vfend, Vfend IV
Administration:
-Vfend: take OES at least 1 hour before or after a meal (hold sthe same w/ tube feedings)
-Use caution when driving AT NIGHT due to vision changes
-Avoid DIRECT SUNLIGHT
-Suspension: shake for 10 seconds before each use (do NOT refrigerate)
-In CrCl <50mL/min, IV vehicle SBECD accumulates (oral preferred - can do an IV loading dose)
Voriconazole:
-AVEs
-Warnings
-CI
-Monitoring
AVEs: VISUAL CHANGES (blurred vision, photophobia, altered color perception, altered visual acuity), INCREASED LFTS AND SCr, CNS TOXICITIY (HALLUCINATIONS, HA, dizziness), photosensitivity, low or high potassium
Warnings:
-HEPATOTOXICITY, VISUAL DISTURBANCES (OTIC NEURITIS and papilledema), PHOTOTOXICITY, QT PROLONGATION (correct K, Ca, and Mg prior to use)
-Avoid in pregnancy
-Others: nephrotoxicity, infusion-related rxns, serious skin rxns, skeletal adverse effects (fluorosis, periostitis), pancreatitis
CI: coadministration w/ barbiturates (long-acting), carbamazepine, efavirenz (>400mg/day), ergot alkaloids, pimozide, quinidine, rifabutin, rifampin, ritonavir (>/=800mg/day), sirolimus, or St. John’s Wort
Monitoring: LFTs, renal fxn, electrolytes, visual fxn (when used >28 days), trough concentration (toxicity more liekly with troughs >5mcg/mL)
Posaconazole:
-Brand
-Administration considerations
-AVEs
-Warnings
-CI
-Monitoring
Brand: Noxafil
Administration Considerations:
-Take WITH FOOD if PO
-In eGFR <50mL/min: SBECD vehicle can accumulate and worsen renal fxn (PO preferred)
AVEs: N/V/D, fever, HA, increased LFTs, rash, hypokalemia, hypomagnesemia, cough
Warnings:
-QT PROLONGATION (correct K, Ca, and Mg prior to use)
-Medication errors: suspensions and tablets are NOT interchangeable (tablet is better absorbed)
-Neurotoxicity when used w/ vincristine, due to increased vincristine levels (seizures, peripheral neuropathy, SIADH, paralytic ileus)
CI: coadministration w/ sirolimus, ergot alkaloids, pimozide, quinidine, atrovastatin, lovastatin, and simvastatin
Monitoring: LFTs, renal fxn, electrolytes, CBC
Isavuconazonium sulfate:
-Brand
-Administration considerations
-AVEs
-Warnings
-CI
-Monitoring
Brand: Cresemba
Administration considerations:
-Prodrug of isavuconazole
-Requires FILTER (0.2-1.2 micron) due to possible particulates
-Capsules must be protected from moisture (original container has desiccant)
AVEs: N/V/D, HA, injection site rxns, peripheral edema, hypokalemia, increased LFTS
Warnings: hepatotoxicity, infusion-related rxns (hypotension, dyspnea, chills, dizziness, tingling/numbness), hypersenstivity rxns (anaphylaxis, SJS/TEN), teratogenic, DDIs, particulates (undissolved IV drug)
CI: use w/ strong CYP3A4 inhibitors or inducers, familial short QT syndrome (causes QT SHORTENING – > NOT PROLONGATION)
Monitoring: LFTs, electrolytes
Azole Antifungal: DDIs
ALL:
-All azoles are moderate/strong CYP3A4 inhibitors (can increase Eliquis, Xarelto levels)
-Cuation in combo w/ QT-prolonging drugs
Other sites of inhibition:
-Itraconazole, ketoconazole: inhibit P-gp
-Fluconazole, voriconazole: inhibit CYP2C9 (can increase warfarin levels)
Acid-reducing DDIs:
-PPIs and cimetidine decrease absorption of posaconazole
-Absorption of itraconazole (Sporanox brand capsules) and ketoconazole REQUIRES ACIDIC GUT (seperate antacids two hours before and after)
-If PPIs/HR2RAs must be used w/ ketoconazole, take with an acidic beverage (ex. non-diet cola) to provide acidic environment
Voriconazole:
-Concentrations can increase dangerously w/ drugs that inhibit CYP2C19, 2C9, or 3A4 or with small dose increases. Exhibits first order kinetics followed by zero-order kinetics.
-do NOT use w/ barbiturates (long-acting), carbamazepine, efavirenz (>/=400mg/day), ergot alkaloids, pimozide, quinidine, rifabutin, rifampin, ritonavir (>/=800mg/day), sirolimus, or St. John’s Wort
Echinocandins:
-Drugs/Brands
-MOA
-ROA
-Typical Coverage
Drugs: caspofungin (Cancidas), micafungin (Mycamine), anidulafungin (Eraxis), rezafungin (Rezzayo)
MOA: inhibit synthesis of beta (1,3)-D-glucan (an essential component of fungal cell wall)
ROA: IV
Typical Coverage:
-Effective against MOST Candida spp (including strains R to azole antifungals: C. glabrata, C. krusei)
-Aspergillus spp (activity, but should be use IN COMBO w/ other regimens)
-Rezafungin: reserve for pt w/ limited or no alternative options (limited clinical and safety data)
Echinocandins:
-Administration considerations
-AVEs
-Warnings
-Monitoring
Administration considerations:
-All except rezfungin are given once daily
-do NOT require adjustment in renal impairment
-Very few DDIs
-Micafungin: REQUIRES light protection during administration
AVEs: overall well tolerated –> increased LFTs, HA, hypo- or hyperkalemia, hypomagnesemia, fevere, N/V/D, anemia, increased SCr, rash
-Caspofungin: severe skin rxns
Warnings: HISTAMINE-MEDIATED SYMPTOMS (rash, pruitus, facial swelling, flushing, hypotension, anaphylaxis)
Monitoring: LFTs
Nsytatin:
-Brand
-ROA
-Administration Considerations
-Typical Indications
-AVEs
Brand: Nystop
ROA: PO, topical
Administration (suspension): swish in mouth and retain for as long as possible (several minutes before swallowing)
Typical Indications:
-Oral Candidiasis (suspension)
-Intestinal Infections (PO tablets)
AVEs: N/V/D, stomach pain –> low systemic risk due to minimal GI absorption
Griseofulvin:
-ROA
-Administration considerations
-Typical Indications
-AVEs
-CI
-Monitoring
-DDI
ROA: PO
Adminsitration Considerations: take with FATTY MEAL to increase absorption OR with FOOD/MILK to avoid GI upset
Typical Indications: fungal infections of skin, hair, or nails
AVEs: PHOTOSENSITIVITY, INCREASED LFTs, HA, rash, uticaria, dizziness, leukopenia, severe skin rxns
-Cross PCN allergy rxn possible
CI: PREGNANCY, severe liver disease, prophyra
Monitoring: LFTs, renal fxn, CBC
DDI: increases metabolizes hormonal contraceptives (estrogen and progestin) –> use non-hormonal contraceptives
Miscellaneous antifungals:
1. Terbinafine: Brand of topical OTC cream, AVEs, warnings, DDIs
- Which antifungal comes as troches that are used for orophayngeal candidiasis?
- Which azole antifungal is used only for vulvovaginal candidiasis?
- What is miconazole typically used for?
- Lamisil AT; HA, increased LFTs, hepatotoxicity; DDIs: strong CYP2D6 inhibitor
- Clotrimazole
- Oteseconazole
- Oropharyngeal candidiasis (tabletss applied to upper gum region)
List the preferred and alternative regimens: Candidia albicans, oropharygneal infection (thrush)
-Preferred (mild): topical antifungals (clotrimazole, miconazole)
-Preferred (moderate/severe) or HIV (+): fluconazole
-Alternative: nystatin
List the preferred and alternative regimens: Candidia albicans, esophageal infection
-Preferred: fluconazole
-Alternative: echinocandin
List the preferred and alternative regimens: C. krusei and glabrata, blood stream infection
-Preferred: echinocandin
-Alternative: AmpB, high-dose fluconazole (susceptible isolates only)
List the preferred and alternative regimens: Aspergillus, invasive
-Preferred: Voriconazole
-Alternative: AmpB, Isavuconazonium
List the preferred and alternative regimens: Cryptococcus neoformans, meningitis
-Preferred: AmpB + flucytosine
-Alternative: high-dose fluconazole + flucytosine
List the preferred and alternative regimens: Dermatophytes, nail bed infection
-Prefered: terbinafine or itraconazole (confirm infection first)
-Alternative: fluconazole
Viruses:
1. Why are they referred to as “obligate intracellular parasites?
- Can viral infections be treated?
- Treatments focus on what types of targets for viral infections?
- They depend on host cell metabolic processes for survival
- Many virsuses have NO treatment
-Can treat: influenza, COVID-19, cold sores, varicella zoster virus, cytomegalvorius - Directly inhibiting viruses (antiviral agents) or augmeting/modifying host defenses to viral infections (immunomodulating agents)
Influenza:
1. Influenza ___ and __ are the strains that commonly infect humans.
- Who is most vulnerable to hospitalization and death?
- Diagnosis
- Vaccination is recommended annually for all those that are age ____ and older.
- Which drug class used to be used to teat/prevent influenza A, but now is no longer recommended from widespread resistance?
- A and B
- Pregnant pts, immunocompromised, childen <5 yo, adults >/= 65 yo, comorbid conditions (ex. CVD, DM, asthma)
- Diagnostic tests: molecular assays, antigen detection tests
-Rapid influenza diagnostic test often done as a nasopharyngeal swab - 6 months and older
- Adamantanes (amantadine, rimantadine)
Zanamivir:
-Brand
-MOA
-ROA
-Administration considerations
-AVEs
-Warnings
Brand: Relenza Diskhaler
MOA: neuraminidase inhibitor - inhibits enzyme that enables relase of new viral particles from infected cells in influenza
ROA: DPI inhaler
Administration Considerations:
-Active against influenza A and B, reducing duration of symptoms by about one day and reducing complications
-Should be STARTED WITHIN 48 hours of illness onset or exposure (if hospitalized, can start >48 hrs)
AVEs: HA, throat pain, cough
Warnings: neuropsychiatric events, BRONCHOSPASM (do NOT use in asthma/COPD or any breathing issues)
-Powder in drug is specifically more irritating
-Stop drug if wheezing or breathing problems develop
Oseltamivir:
-Brand
-MOA
-ROA
-AVEs
-Warnings
Brand: Tamiflu
MOA: neuraminidase inhibitor - inhibits enzyme that enables relase of new viral particles from infected cells in influenza
ROA: PO
AVEs: HEADACHE, NAUSEA/VOMITING, diarrhea, abdominal pain
Warnings: NEUROPSYCHIATRIC EVENTS (confusion, delirum, hallucinations, unusual behavior or self-injury) especially in young pts, serious skin rxns, anaphylaxis
-Discovered during swine flu when antivirals used on massive levels, and pts reported weird behaviors in their children
Oseltamivir:
-Administration Considerations
-Treatment and prophylaxis dosing
Administration Considerations:
-Active against influenza A and B, reducing duration of symptoms by about one day and reducing complications
-Should be STARTED WITHIN 48 hours of illness onset or exposure (if hospitalized, can start >48 hrs)
-Preferred in pregnancy over other neuramindase inhibitors
-Store reconstitution suspension at room temp x10D or in fridge x17D
Treatment dosing, age >12 yo: 75mg BID x5D
Prophylaxis dosing, age >12 yo: 75mg QD x10D
Premivir:
-Brand
-MOA
-ROA
Brand: Rapivab
MOA: neuaminidase inhibitor (same considerations as oseltamivir)
ROA: injection
Baloxavir marboxil:
-Brand
-MOA
-TX
-ROA/Dosing frequency
-Administration considerations
-AVEs
-Warnings
-DDIs
Brand: Xofluza
MOA: endonculease inhibitor, halting influenza replication
TX: treatment and post-exposure prophylaxis of influenza
ROA: PO as a single dose-regimen
Administration considerations:
-Start within 48 hours of symptom onset or exposure
-Store in original blister packaging
-Suspension: once reconstituted, administer wtihin 10 days storing at room temp; dose may require more than one bottle
AVEs: diarrhea
Warnings: hypersensitivity (including skin rxns: erythema multiforme, uticaria), monitor for secondary bacterial infections
DDIs: diary products, antacids, or toher supplkements containing polyvalent cations –> avoid
COVID-19: General Diagnosis/TX
Diagnosis: polymerase chain reaction (PCR) using a nasopharyngeal swab specimen and/or rapid antigen test
Testing positive:
-Isolate for at least 5 days after and continue to wear mask for 11 days
-Consult the CDC, NIH, and IDSA for most current recommendations
-Symptomatic care: hydration, analgesics/antipyretics, antitussives
-Prefered outpatient TX: nirmatrelvir/ritonavir (Paxlovid) –> BBW for DDIs from ritonavir (alternative: IV remdesivir, PO molnpiravir)
-Hospital TX: can include systemic steroids, antivirals (particularly remdesivir), and/or immunomodulator TX (baricitinib, tocilizumab)
Herpes Simplex Labialis (Cold Sores):
1. Usually from HSV__ in children, but can be caused by HSV__ in adults from oral/genital sex.
- Prevention of transmission
- Triggers of cold sores
- When is the optimal time to use topical or oral medication to reduce blister duration? What are the different drug options?
- HSV1; HSV2
- Highly contagious - avoid kissing and sharing drinks when lesions ar oozing
- Stress/fatigue, stress to skin (acid peels, sun exposure), dental work
- Cold sore eruption is preceded by peridrome (symptoms that occur before lesions appear) of tingling, itching, or soreness which is the optimal time to use medication
Topical TX:
-Docosanol (Abreva): OTC –> apply 5x daily at first sign of outbreak, continue until healed
-Acyclovir (Zovirax): Rx –> apply 5x daily x4D (can also be used on genital sores)
-Others: acyclovir buccal tablet, penciclovir cream
Systemic TX: acyclovir, valacyclovir, famciclovir
Genital Herpes:
1. Caused by _______ virus
- General s/sx
- When must TX be initiated?
- General TX
- When is chronic suppressive therapy recommended for pts?
- HSV2
- Chronic life-long condition that may start as asymptomatic or with flu-like symptoms before development of pustular or ulcerative leasions on genitalia —> lesions usually begin as papules or vesicles that spread rapidly associated w/ itching, dysuria, and vaginal/urethral discharge
- Must initiate during prodrome period or within one day of lesion onset
4.
-Acyclovir: inexpensive, but dosed up to TID
-Valacyclovir: prodrug of acyclovir that reaches higher concentrations and less frequent dosing
-If R to acyclovir, will be R to valacylovir, likely R to famciclovir —> treat w/ foscarnet
- Pts w/ frequent recurrences (>6/year)
Invasive HSV Infections: TX
Viral encephalitis: IV acyclovir 10mg/kg/dose Q8H x14-21D
Esophagitis, pneumonitis: IV acyclovir 5mg/kg/dose Q8H
**Calculate dose by IBW
Acyclovir, Valacyclovir, and Famciclovir:
-Brands
-ROAs
-Adminsitration considerations
Drugs: acyclovir (Zovirax), valacyclovir (Valtrex), famciclovir
ROA: PO, topical (acyclovir), IV (acyclovir)
Administration considrations:
-Acyclovir dosing based on IBW including IN OBESE PTS
-Dose decrease or extended interval in renal impairment
-Valacylovir is prodrug of acyclovir (acyclovir NOT as absorbed as well PO)
-Famciclovir is prodrug of penciclovir
-NOT an actual TX of herpes infections (cold sores, chickenpox, shingles, or genital herpes) –> practice safe sex
-Start TX within 24 hours of onset of symptoms
Acyclovir, Valacyclovir, and Famciclovir:
-AVEs
-Warnings
-Resistance considerations
AVEs; malaise, HA, N/V/D, rash, pruriuts, increased LFTs, neutropenia, transient burning/stinging w/ topical formulations, anaphylaxis (famciclovir), increased BUN/SCr w/ crystal neuropathy (IV acyclovir)
Warnings:
-Caution in RENAL IMPAIRMENT, elderly, or those receive nephrotoxic drugs (infuse acyaclovir over at least one hour and maintain hydration to reduce renal tubular damage
-Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) has been reported in immuncompromised pts
Resistance:
-If R to acyclovir, R to valacyclovir or vice versa
-If R to acyclovir or valacyclovir, likely R to famciclovir
Varicella Zoster Virus.
1. Alternative name of VZV is __________ which is often an infection during childhood. The virus can lie dormant in the nerve for decatdes w/o causing any symptoms, and its recurrence is called __________.
- Prevention / General TX
- Chickenpox; Herpes Zoster (shingles)
2.
Prevention: shingles vaccine for Herpes Zoster in adults 50 yo or older and adults 19 yo or older who are immunosuppressed
-Pts previously vaccinated w/ Zostavasx should be re-vaccinated w/ Shingrix
-Pts w/ previous episode of shingles should be vaccined to decrease likelihood of recurrence/severity
-Helps to prevent POSTHERPETIC NEURAGLIA (PNA)
TX: initate at earliest sign of shingles (antiviral therapy most effective within 72 hours of rash development - the sooner, the better)
-Pain: topical medications such as Lidoderm patch/gel, neuropathic pain medication (gabapentin, pregabalin, duloxetine, TCAs), NSAIDs, or opioids
-Antiviral therapy: acyclovir x7D, valacylovir x7D, or famciclovir x7D
Cytomegalovirus (CMV):
1. What virus in the herpes family causes this?
- Complications/who is most at risk
- General TX
- Secondary prophylaxis
- HHV-5
- Immunocompromised pts at most risk with most common complications of retinitis, colitis, or esophagitis
3.
-DOC: ganciclovir or valgnaciclovir
-Refractory: foscarnet, cidofovir
-Post-transplant CMV disease refractory to all other TX: maribavir
- “Maintenance Therapy”
-CMV prophylaxis in kidney transplant if donor is CMV-(+) and recepient is (-): letermovir
-Solid organ trasplant at high risk (donor positive, recipient negative): ganciclovir, valganciclovir
Ganciclovir and valganciclovir:
-Brands
-ROA
-Administration considerations
-AVEs
-BBW
-Monitoring
Drugs: ganciclovir (Zirgan = opthalamic gel), valganciclovir (Valcyte)
ROA:
-Ganciclovir: injection, opthalamic gel
-Valganciclovir: PO
Adminisration considerations:
-Valganciclovir is prodrug of ganciclovir w/ better F
-Ganciclovir injection: reconstitute w/ sterile water NOT bacteriostatic water
-Valganciclovir solution: refrigerate when reconstituted, discard after 49 days
-Hazardous agent: special handling required
-Females should use contraception during TX and for 30D after (males: 90D after)
AVEs: fever, N/V/D, anorexia, increased SCr, seizures (rare), retinal detachment (in CMV retinitis)
BBW: MYLEOSUPPRESSION, carcinogenic, fetal toxicity, impaired fertility
Monitoring: CBC w/ differential, SCr, retinal exam
Cidofovir:
-ROA
-Administration considerations
-TX
-AVEs
-CI
-BBW
ROA: injection
Administration considerations:
-Pt should receive hydration before each dose and probenaecid before andf ater each dose to decrease nephrotoxicity
-Hazardous agent: special handling required
TX: CMV retinitis in HIV pts only
AVEs: myleosupression (less than ganciclovir), metabolic acidosis
CI:
-SCr > 1.5mg/dL, CrCl </= 55 mL/min, urine protein >/=100 mg/dL (>/=2+ proteinuria)
-Sulfa allergy
-Use w/ or within &D of other nephrotoxic drugs
-Direct intraocular injection
BBW: nephrotoxicity, neutropenia, carcinogenic, teratogenic
Foscarnet:
-Brand
-ROA
-Administration considerations
-AVEs
-BBW
Brand: Foscavir
ROA: injection
Administration considerations: do NOT exceed max infusion rate (increases toxicity)
AVEs: electrolyte abnormalities (low: K, Ca, Mg, Phos), increased BUN/SCr, Qt prolongation
BBW: RENAL IMPAIRMENT (prehydration recommended); seizures due to electrolylte imbalances (has led to status epilepticus or death)
Letermovir:
-Brand
-ROA
-Administration considerations
-AVEs
-CI
Brand: Prevymis
ROA: injection, PO
Administration considerations: IV vehicle (hydroxypropyl betadex) can accumuate if CrCl <50mL/min
AVEs: atrial fibrilaltion, tachycardia, peripheral edema, thromboyctopenia, N/V/D, fatigue, HA, cough
CI: concomitant use w/ pimozide, ergot alkaloids OR pitavastain and simvastatin if taking cyclosporine
Epstein-Barr Virus (EBV):
1. Otherwise known as ___________
2. Transmission
3. S/Sx
4. TX
- Mononucleosis –> “Mono”
- Bodily fluids, primarily saliva (kissing, sharing food/drinks/objects in contact w/ mouth)
- fatigue, fever, sore throat, swollen lymph nodes that usually resolve within 2-4 weeks
- NO TX exists
-Amoxicilin or ampicillin TX in child w/ EBV can cause non-pruritic rash that appears similar to allergic rxn (should NOT be included as an allergy)
Name immunocompromised states.
- Disease that destroy components of immune response, primarily HIV with CD4 T lymphocyte count <200 cells/mm3 (definining criteria for AIDs)
- Use of systemic steroids for 14 days or longer at a prednisone equivalent of >/= 20mg/day or >/=2mg/kg/day
- Asplenia (lack of functioning spleen) due to sickle cell disease or splenectomy
- Use of immunosuppressants for autoimmune conditions or post-transplant
- Use of cancer chemotherapy that destroy WBCs, particularly if severe neutropenia (ANC <500 cells/mm3)
Primary prophylaxis in HIV: Pneumocystitis jirovecii pneumonia (PJP or PCP)
-Criteria to start prophylaxis
-Primary regimen
-Alternatives
-Criteria for D/C
Criteria to start: CD4 count <200 cells/mm3 or AIDS-defining illness or oropharyngeal candidiasis
Preferred regimen: Bactrim DS QD (or SS)
Alternatives:
-Bactrim DS 3x weekly
-Sulfa allergy: dapsone OR atovaquone
-Dapsolone alone OR with pyrimethamine + leucovorin (rescue therapy for pyrimethamine-induced myleosuppression)
-Atovoquone alone OR with pyrimethamine + leucovorin
-G6PD deficiency: inhaled pentamidine
Criteria to D/C: CD4 count >200 for >3 months and remains on anti-retroviral therapy (ART)
Primary prophylaxis in HIV: Toxoplasma gondii encephalitis
-Criteria to start prophylaxis
-Primary regimen
-Alternatives
-Criteria for D/C
Criteria to start prophylaxis: toxoplasma IgG (+) AND CD4 count <100 cells/mm3
Primary regimen: Bactrim DS QD
Alternatives:
-Bactrim 3x weekly or SS QD
-Sulfa allergy: atovaquone OR atovaquone + pyrimethamine + leucovorin OR daspone + pyrimethamine + leucovorin
Criteria to D/C: CD4 count >200 cells/mm3 for >3 months and remains on anti-retroviral thearpy (ART)
Primary prophylaxis in HIV: Mycobacterium avium complex (MAC)
-Criteria to start prophylaxis
-Primary regimen
-Alternatives
-Criteria for D/C
Criteria to start prophylaxis: if NOT taking ART, CD4 count <50 cells/mm3, and NO active MAC infection
-NOT recommneded if ART started immediately
-RULE OUT dissemintated MAC disease: needs several drugs for TX
Primary regimen: azithromycin 1200mg weekly or 600mg twice weekly
Alternatives: clarithromycin 500mg BID
Criteria to D/C: taking fully suppressive ART
Opportunistic Infection (OI) TX: Candidasis (“Thrush”)
-Preferred regimen
-Alternative regimen
-Secondary prophylaxis
Prefered regimen: fluconazole
-In HIV: prefered to have systemic disease even in mild
Alternative regimen:
-Oropharyngeal: itraconazole, posaconazole, topicals (clotrimazole troche, nystatin)
-Esophageal: voriconazole, isavuconazonium, echinocandin
Secondary prophylaxis: NOT usually recommended
Opportunistic Infection (OI) TX: Cryptoccocal meningitis
-Preferred regimen
-Alternative regimen
-Secondary prophylaxis
Preferred regimen: amphotericin B (liposomal preferred) + flucytosine
Alternative:
-High dose fluconazole + flucytosine
-High dose fluconazole + amphotericin B
Secondary prophylaxis: low dose fluconazole
Opportunistic Infection (OI) TX: Cytomegalovirus (CMV)
-Preferred regimen
-Alternative regimen
-Secondary prophylaxis
Preferred regimen: valganciclovir PO or ganciclovir IV
Alternative regimen: if toxicities to ganciclovir or resistant strains, foscarnet or cidofovir
Secondary prophylaxis: none
-For HIV: continue ART and maintain CD4 count >100 cells/mm3
Opportunistic Infection (OI) TX: Mycobacterium avium complex (MAC)
-Preferred regimen
-Alternative regimen
-Secondary prophylaxis
Preferred regimen: clarithyomycin or azithromycin AND ethambutol
Alternative regimen: add 3rd or 4th agent (rifabutin, amikacin, streptomycin, moxifloxacin, or levofloxacin)
Secondary prophylaxis: same as primary prophylaxis
Opportunistic Infection (OI) TX: Pneumocystitis jirovecii pneumonia (PJP or PCP)
-Preferred regimen
-Alternative regimen
-Secondary prophylaxis
Preferred regimen: Bactrim (high dose - see ID) +/- prednisone OR methylprednisolone for 21 days
Alternative regimen: pentamidine IV OR clindamycin + primaquine
Secondary prophylaxis: same as primary prophylaxis
Opportunistic Infection (OI) TX: Toxoplasmosis gondii encephaliitis
-Preferred regimen
-Alternative regimen
-Secondary prophylaxis
Preferred regimen: pyrimethamine + leucovorin + sulfadiazine
-Leucovorin helping prevent myleosuppression with pyrimethamine
Alternative regimen:
-Bactrim
-Clindamycin + pyrimethamine + leucovorin
Secondary prophylaxis: same as TX, but reduced doses
Human immunodeficiency virus (HIV):
1. HIV is a ssRNA retrovirus that uses machinery to host _________ to replicate which then viral copies busrt through the cell membrane to destroy the cell.
- When HIV continues to replicate, the viral load ______(increases/decreases).
- When can the immune system no longer ward off opportunistic infections (OIs) and specific malignancies related to acquired-immunodeficiency (AIDs)?
- How is HIV transmitted?
- What is vertical transmission?
- CD4 T-helper cells
- Increase
- CD4 <200 cells/mm3
- Bodily fluids (blood, semen, vaginal/rectal secretions, or breast milk), mucus membranes, or open wounds
-Most commonly from unprotected vaginal or rectal sex or sharing injection drug equipment
- When a mother passes HIV to her child
HIV: Replication Stages and potential drug targets
- Binding and attachment: HIV attaches to CD4 cell and a co-receptor (CCR5 and/or CXCR4)
-CCR5 antagonist: maraviroc
-Attachment inhibitor: fostemasvir
-Post-attachment inhibitor: ibalizumab-uiky - Fusion: HIV viral envelop fuses w/ cell membrane and can enter cell to release inner capsid containing HIV RNA and viral enzymes
-Fusion inhibitor: enfuviritide - Reverse Transcription: HIV RNA converted to DNA
-NRTIs and NNRTIs - Nuclear Import: HIV capsid transported into cell nucleus
-Capsid inhibitor: lenacapavir - Integration: Integrase inserts HIV DNA into host DNA
-INSTIs - Transcription and Translation: host cell machinery used to transcribe and translate HIV DNA into RNA nad proteins
-NO drug targets - Assembly: new HIV RNA, proteins, and enzymes (including protease) assesmble at cell surface
-Capsid inhibitor: lenacapavir - Budding and Maturation: immature virus pinches off cell and protease breaks up the long viral protein chains to infect other cells
-PIs, capsid inhibitor: lenacapavir
HIV: Screening
-How to screen for HIV
-OTC screening
Initial Screen: HIV-1 and HIV-2 antibodies and p24 antigens
-p24 antigen: structural protein that makes up most of the viral capsid
If intial screen positive: confirm with second HIV-1 and HIV-2 antibody differentiation immunoassay (can determine if its HIV-1 or HIV-2)
-If nonreactive or indeterminate: HIV-1 nucleic acid test (quantifies viral load)
-If reactive: HIV positive
OTC: OraQuick (swab from upper and lower gums) —> if positive, confirm w/ laboratory test
-Testing sooner than 3 months after exposure can lead to false negative from antibody development lag
Who should screen for HIV?
Everyone: once per lifetime in those 13-64 yo unless at high risk
Annual Screening:
1. Hx of STIs, hepatitis, or TB
2. Sexual hx: partner w/ HIV, multiple partners, partner w/ unknown sexual hx, men who have sex with men especially between 13-24 yo
3. Sharing drug injection equipment
Highest risk of transmission: anal transmision > needle sharing > vaginal transmission
Acute HIV infection:
-S/Sx
-Progression to aids
-HIV wasting syndrome and TX
S/Sx: non-specific flu-like symptomas (ex. fever, myalgia, swollen lymph nodes, rash) which last a few days to weeks
Progression to AIDs:
-CD4 Count <200 cells/mm3
-AIDS-defining condition (OIs, malignancy - Kaposi’s sarcoma, and HIV wasting syndrome)
HIV wasting syndrome: unwanted weight loss of more than 10% of person’s body weight
-TX to stimulate appetite: dronabinol (Marinol, Syndros), megestrol (progestin)
HIV:
-Initial evaluation (labs)
-Goals of TX
-Considerations when starting TX
Initial evaluation:
-CD4 count: major indicator of immune function and determines if pts need OI prophylaxis
-HIV viral load: indicator of response to ART (antiretroviral therapy)
-Resistance testing to ART
-Others: CMP, CBC, urinalysis, HepB/C, pregnancy test, HLA-B*5701 (if abacavir added), tropism assay (if maraviroc added)
Goals:
-U=U (Undetectable = Untransmittable): <200 copies/mL of HIV –> 100% untransmittable for sexual transmission
-Infection prevention: raise CD4 count, vaccines, prophylaxis for opportunistic infections (OIs) if needed
Considerations when starting: immune reconstitution inflammatory syndrome typically when medications are started and higher risk in low CD4 counts <100
-Body’s immune system begins to recover, but inflammation ramps up
-Continue TX with supportive care
HIV regimens: TX-naive pts
Preferred regimen of 2 NRTIs + 1 INSTI (Dovato is exception); most have an INSTI with high barrier to resistance; fixed dosing (avoid in CrCl <30mL/min)
-One pill, QD regimens: Biktarvy (bictegravir / emtricitabine / TAF), Triumeq (dolutegravir / abacavir / lamivudine), and Dovato (dolutegravir / lamivudine)
-Two pills, QD regimens: Tivicay (dolutegravir) + Truvada (emtricitabine / TDF) OR Tivicay + Descovy (emtricitabine / TAF)
HIV regimens: Alternative regimens
2 NRTIs + 1 “base” (PI, NNRTI, or INSTI)
-NRTI backbone: TDF or TAF or abacavir + emtricitabine or lamvudine*
-PI based: darunavir or atazanavir boosted w/ cobicistat or ritonavir
-NNRTI based: efavirenz, rilpivirine, doravirine
-INSTI based: elvitegravir (only in combos), raltegravir
*Emtricitabine and lamivudine should NOT ber used together since both are cytosine analogs that will have no additional benefit (potentially antagonistic effects since similar structure and would complete with each other)
*Alternative regimens: more DDIs/AVEs, lower resistance barrier (except PIs), less virologic efficacy
HIV regimens: ART in pregnancy
May continue regimen in most cases
-New starts: 3 components (dolutegravir or booster darunavir + dual NRTI backbone)
-Perinatal transmission prophylaxis: maternal administration of IV zidovudine prior to delivery or neonatal administration of ART
Pre-exposure prophylaxis (PrEP):
1. When is PrEP indicated?
2. What must be screened for prior to PrEP?
3. What are PrEP options?
4. What should the follow up be?
- Engaged in high-risk activities (multiple sexual partners, men who have sex with men, IV drug use)
- Prior to therapy:
-Confirm HIV-negative since regimen is NOT appropriate for TX and resistance can develop
-Ask about recent symptoms: helps consider lag time in detectable antibody
-Screen for: hepatitis B and STIs - Options:
-PO options: Truvada (if CrCl 60mL/min or greater) or Descovy (if CrCL 30mL/min or greater)
-IM: cabotegravir: administered by healthcare provider for 2 doses then Q2 months - Follow Ups:
-Truvada, Descovy: Q3 months
-Cabotegravir: 1 month after 1st injection then Q2 months
-Continue to test for HIV and confirm (-) result
Post-exposure prophylaxis (PEP):
1. When is PEP indicated?
2. What are the types of PEP?
3. What are PEP options?
4. What is the follow up?
- Indicated when:
-Emergency exposure from bodily fluids w/ known or suspected HIV
-Able to start treatment within 72 hours of exposure - Types:
-Nonoccupational (nPEP): for use after sex w/o condom, injection drug use, etc.
-Occupational (oPEP): healthcare personel exposure typically from needlesticks - Options: take within 72 hours and for 28 days
-Truvada: if CrCl 60mL/min or greater PLUS
-Dolutegravir or raltegravir - Follow up: should receive baseline HIV antibody test then follow up at 4-6 weeks, 3 months, and 6 months post exposure
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs):
-Drugs/Brands
-MOA
-Administration Considerations
-Resistance Considerations
Drugs: abacavir (Ziagen), emtricitabine (Emtriva), lamivudine (Epivir), zidovudine (Retrovir), tenofovir disoproxil fumarate (TDF: Viread), tenofovovir alafenamide (TAF - only in combo products)
MOA: inhibits conversion of HIV RNA to HIV DNA
Administration Considerations:
-Vemlidy (TAF): single entity product for HepB, ONLY in combo w/ HIV
-Renal dose adjustements except in abacavir
-CrCl <50mL/min: do NOT start TDF
-CrCl <30mL/min: do NOT start TAF
-Zidovudine: administered IV during labor and delivery to prevent perinatal HIV transmission
-Lamivudine: has two different strengths, make sure to use higher strength in HIV
Resistance Considerations: LOW barrier to resistance
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs):
-AVEs
-Warnings
-BBW
-Unique considerations of drugs
AVEs: most common are diarrhea and nausea
Warnings: lactic acidosis, hepatomegaly with steatosis
BBW
-Severe HepB exacerbation if D/C of emtricitabine, lamivudine, or tenofovir-containing products
-Epivir-HBV: low dose of lamivudine that needed for TX of HIV
-Lamivudine: fatty liver
Unique Considerations:
-Abacavir: risk of hypersensitivity risk ESPECIALLY if HLA-B*5701 (REQUIRED to test prior) –> never rechallenge
-Emtricitabine: hyperpigmentation of palms of hands or soles of feet
-Zidovudine: hepatomegaly w/ steatosis; hematologic toxicity (anemia, neutropenia) –> will occur that high MCV is an indication of adherence
-TDF renal impairment and Fanconi syndrome (renal tubular injery, electrolyte abnormalities, and decreased BMD > TAF
-TAF: lipid abnormalities
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs):
-Drugs/Brands
-MOA
-Administration Considerations
-Resistance Considerations
Drugs: contain “vir” – efavirenz, rilpivirine (Edurant), doravirine (Pifeltro), etravirine (Intelence), nevirapine
MOA: prevents conversion of HIV RNA to HIV DNA
Administration Considerations:
-Rilpivirine PO: take with meals and water, do NOT initiate if viral load >100,000 copies/mL and.or CD4 count <200 cells/mm3 (higher failure rate)
-Efavirenz: food increases F and risk for CNS effects –> take OES to avoid and QHS to sleep through side effects
Resistance Consideration: lower barrier to resistance than INSTIs or PIs
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs):
-AVEs
-DDIs
-Unique Considerations
AVEs: hepatotoxicity, rash including severe reactions
DDIs:
-ALL: major CYP3A4 substrates
-Rilpivirine, doravirine: do NOT use w/ strong CYP3A4 inducers (treatment failure)
-Efavirenz, etravirine: moderate inducers of CYP3A4
-Rilpivirine: avoid PPIs, take H2RAs at least 12 hours before or 4 hours after, take antacids at least 2 hours before or 4 hours after
Unique Considerations:
-Efavirenz: increased cholestrol/TG, psychiatric sympoms (depression/SI), CNS effects (impaired concentration, abnormal dreams, confusion), that usually lasts generally resolves in 2-4 weeks
-Rilpivirine: depression, increased SCr (no effect on eGFR)
-Nevirapine: highest risk of severe rash
Integrase Strand Transfer Inhibitors (INSTIs):
-Drugs/Brands
-MOA
-Administratoin considerations
-Resistance considerations
Drugs: -“gravir”; bictegravir, elvitegravir, cabotegravir (Vocabria, Apretude), dolutegravir (Tivicay), raltegravir (Isentress, Isentress HD)
MOA: prevents HIV DNA from inserting into host cell DNA
Administration considerations:
-Once daily: Biktarvy, Stribild, Genvoya, Tivicay, Triumeq, Dovato, Isentress
-BID: Isentress
-Apretude (cabotegravir XR IM injection): only for PrEP
-Vocabria (cabotegravir PO): indicated for optional lead-in TX to assess tolerability of Cabenuva injection (cabotegravir/rilpivirine) or bridge therapy in pts that have missed >7D
-CrCl <70mL/min: do NOT start Stribild
-CrCl <50mL/min: D/C Stribild
-CrCl <30mL/min: do NOT start Biktarvy or Genvoya
Resistance Considerations: bictegravir and dolutegravir have higher barrier to resistance than NRTIs, NNRTIs, and other INSTIs
Integrase Strand Transfer Inhibitors (INSTIs):
-AVEs
-Warnings
-DDIs
-Unique Considerations
AVEs: weight gain, insomnia
Warnings: rare risk of depresion/SI in pre-existing psychiatric conditions
DDIs: PO agents - always need to seperate from polyvalent cations –> look at package insert to determine exact timing (2 hours before or 6 hours after)
Unique considerations:
-Bictegravir, dolutegravir: increased SCr via inhibitor of tubular section (no imapact on eGFR)
-Raltegravir, dolutegravir: increased CPK, myopathy, rhabdomyloysis, hypersensivity rxn
-Dolutegravir: hepatotoxicity especially in coinfection of HCV/HBV
-Cabotgravir: injection site rxns
-Elvitegravir: coformulated w/ cobicistat (strong CYP3A4 inhibitor)
Protease Inhibitors (PIs):
-Drugs/Brands
-MOA
-Administration Considerations
-Resistance Considerations
Drugs: -“navir”; atazanavir (Reyataz), darunavir (Prezista), fosamprenavir, tipranavir (Aptivus), lopinavir/ritonavir (Keletra)
MOA: prevents long viral protein chains from being broken down into smaller chains for budding and maturation
Administration Considerations:
-Recommended w/ booster (ritonavir or cobicostat) –> ritonavir is a PI, but only used at low doses for PK boosting
-No renal dose adjustments
-Darunavir, atazanavir: CF to minimize GI AVEs
-Atazanavir: needs acidic gut for absorption
Resistance Considerations: HIGH barrier to resistance
Protease Inhibitors (PIs):
-AVEs
-Warnings
-DDIs
-Unique Considerations
AVEs: D/N common
-Metabolic abnormalities: increased BP, LDL, TG, body fat, lipodystrophy
-Hepatic dysfunction: increased LFTs, hepatitis, and/or exacerbation of hepatic disease
-Hypersensitivity rxns: rash, angioedema, bronchospasm, anaphylaxis
Warnings: sulfa allergy (caution in darunavir, fosamprenavir, tipranavir)
DDIs:
-ALL: major CYP3A4 substrates and most strong CYP inhibitors
-Atazanavir: avoid PPis w/ unboosted; take boosted atazanavir at least 12 hours after PPI (do NOT exceed omeprazole 20mg or equivalent)
Unique Considerations:
-Lopinavir/ritonavir (Kaletra): PO solution contains 42% alcohol and can cause disulfiram rxns if taken w/ metronidazole
-Atazanavir: hyperbilirubinemia, but does NOT require D/C and reversible (doesn’t actually indicate liver harm)
Brand Names for Combinations:
1. Biktarvy = ___________ + ________ + _________
- Delstrigo = ________ + _________ + __________
- Symtuza = ________ + _______ + _______ + ______
- Epzicom = __________ + ________
**Any specific criteria to receive regimen?
- Biktarvy = bictegravir / emtricitabine / TAF
- Delstrigo = doravirine / lamivudine / TDF
- Symtuza = darunavir / cobicistat / emtricitabine / TAF
- Epzicom = abacavir / lamivudine
-Criteria: test for HLA-B*5701
Brand Names for Combinations:
1. Cimduo = ____________ + ___________
- Symfi or Symfi Lo = ________ + ________+ _______
- Dovato = ________ + ____________
- Triumeq = _________ + _______ + __________
**Any specific criteria to receive regimen?
- Cimduo = lamivudine / TDF
- Symfi = efavirenz / lamivudine / TDF
- Dovato = dolutegravir / lamivudine
- Triumeq = dolutegrabvir / abacavir / lamivudine
-Criteria: test for HLA-B*5701
Brand Names for Combinations:
1. Cabenuva = _________ + __________
- Complera = _________ + __________ + __________
- Odefsey = __________ + _________ + ___________
- Combivir = _________ + _________
**Any specific criteria to receive regimen?
- Cabenuva = cabotegravir / rilpivirine
-Criteria: meant to replace regimen w/ undetected viral load - Complera = rilpivirine / emtricitaibine / TDF
- Odefsey = rilpivirine / emtricitabine / TAF
- Combivir = lamivudine / zidovudine
Brand Names for Combinations:
1. Truvada = ________ + __________
- Juluca = __________ + _____________
- Stribild = _________ + ________ + ________ + ______
- Genvoya = ________ + _______ + ______ + ______
- Descovy = ________ + __________
**Any specific criteria to receive regimen?
- Truvada = emtricitabine / TDF
- Juluca = dolutegravir / rilpivirine
-Criteria: meant to replace regimen w/ undetected viral load - Stribild = elvitegravir / cobicistat / emtricitabine / TDF
- Genvoya = elvitegravir / cobicistat / emtricitabine / TAF
- Descovy = emtricitabine / TAF
Maraviroc:
-Brand
-MOA
-ROA
-Safety Concerns
-When to use
Brand: Selzentry
MOA: blocks HIV from binding and subsquently entering the CD4 cell in virus strains that use the CCR5 co-receptor
ROA: PO
Safety Concerns:
-BBW: Hepatotoxicity
-Hypersenstivity rxn (including SJS/TEN)
-Orthostatic hypotension int pts w/ renal impairment
-do NOT use in severe impairemnt <30mL/min and taking potent CYP3A4 inhibitors/inducers
When to use: MUST have toposim assay done before; CANNOT use in strains with CXCR4 or mixed co-receptors
Fostemasvir:
-Brand
-MOA
-ROA
-Safety issues
-When to use
Brand: Rukobia
MOA: converted to tamsavir (active form) that binds to gp120 subunit of HIV envelop proteins, inhibiting interaction between virus and CD4 host cell
ROA: PO
Safety Issues:
-do NOT use w/ strong CYP3A4 inducers
-Must maintain effective HBV TX in pts coinfected with HBV
-Can increase SCr (higher risk if underlying renal disease)
When to use: in combo with other ART in heavily-TX experience pts failing current therapy
Ibalizumab-uiyk:
-Brand
-MOA
-ROA
-Safety concerns
-When to use
Brand: Trogarzo
MOA: MAB that binds to a select domain of CD4 cell receptors, blocking entry of virus into cell
ROA: IV administered by healthcare professional
Safety Concerns:
-Infusion-related rxns: observe for 1 hour after first infusion
-Diarrhea, nausea, dizziness, rash
When to Use: in combo w/ other ART in heavily-TX experienced pts who are failing current therapy
Enfuviritide:
-Brand
-MOA
-ROA
-Safety concerns
-When to use
Brand: Fuzeon
MOA: prevents HIV from fusing to CD4 cell membrane, preventing virus entry into cell
ROA: SQ
Safety concerns:
-Risk of bacterial pneumonitis, hypersensitivity rxns
-Local injection site rxns (occurs in nearly ALL pts): pain, erythema, nodules, cysts, ecchymosis, N/D, fatigue
When to use: reserved as salvage therapy with extensive HIV resistance
Lenacapavir:
-Brand
-MOA
-ROA
-Safety concerns
-When to use
Brand: Sunlenca
MOA: inhibits multiple stages of HIV including capsid transport into nucleus, virus assembly, and capsid formation resulting in malformed capsid
ROA: PO, SQ
Safety concerns:
-CI with strong CYP3A4 inducers
-Local injection site rxns: erythema, induration, nodule, pain, swelling
When to use: in combo with other ARTs in heavily TX-expierneced pts who are failing current therapy
What is the criteria to using Dovato?
- Viral load <500,000 copies/mL
- NO HBV coinfection
- NO resistance to either component
PK boosters in HIV:
-Drugs
-Administration considerations
Drugs: cobicistat (Tybost), ritonavir (Norvir)
Administration:
-Administer at same time as requiring boosting
-NOT interchangeable, do NOT use together
-Ritonavir: 100-200mg PO QD or BID CF
-Cobicistat: 150mg PO QD CF
HIV: drugs generally to avoid with PIs and PK boosting:
-Alpha-1a blockers (ex. alfuzosin, silodosin, tamsulosin)
-Amiodarone, dronedarone
-Anticoagulants/antiplatelets
-Azole antifungals
-PIs for hepatitis C (ex. grazoprevir, glecaprevir)
-Lovastatin and simvastatin
-PDE5is for pulmonary HTN (ex. sildenafil, tadalafil)
-Strong CYP3A4 inducers
-Systemic, inhaled, and intranasal steroids (except beclomethasone)
For the following HIV medications, specify whether it should be taken CF or OES:
1. Stribild
- Genvoya
- Symfi, Symfi Lo
- CF - due to cobicistat
- CF - due to cobicistat
- OES - due to efavirenz (reduce CNS AVEs)
For the following HIV medications, specify whether it should be taken CF or OES:
1. Symtuza
- Evotaz
- Prezcobix
ALL: CF due to cobicistat
