Fungal Drug Pharmacology - PDF

FUNGAL Overview of the Drug Class Prototype: amphotericin b (Abelcet) Category: Polyene An=fungal Agent Primary Func9on: Amphotericin B is ac=ve against a broad spectrum of pathogenic fungi and is the drug of choice for most systemic mycoses. Unique Features: Amphote...

FUNGAL Overview of the Drug Class Prototype: amphotericin b (Abelcet) Category: Polyene An=fungal Agent Primary Func9on: Amphotericin B is ac=ve against a broad spectrum of pathogenic fungi and is the drug of choice for most systemic mycoses. Unique Features: Amphotericin B binds to the ergosterol component (member of the sterol family) of the fungal membrane. For a cell to be suscep=ble, its membrane must contain sterols. Bacterial membranes lack sterols; therefore, this agent is ineffec=ve against bacteria. Mechanism of Ac=on Amphotericin B binds to components of the fungal cell membrane-increasing permeability. This results in intracellular leakage, which reduces the organism’s viability. Depending on agent concentra=on and fungal suscep=bility, the ac=on could be fungista=c or fungicidal. Title: Mechanism of an9fungal drugs Cell wall Cell membrane  DNA Proteins Echinocandins, triterpenoids Azoles, polyenes, allylamines 5-fluorocytosine Side Effect Descrip9on Infusion Reac=ons Fever, chills, rigors, nausea, and headache frequently occur during infusion due to the release of proinflammatory cytokines. Pretreatment with diphenhydramine plus acetaminophen can reduce mild reac=ons. Phlebi=s can also occur. Pretreatment with heparin, administra=on through a large central vein, and changing peripheral venous sites can minimize risk. Nephrotoxicity Amphotericin B can commonly cause this adverse effect. This risk is dose dependent. If the total dose exceeds 4g, renal impairment is likely. Hypokalemia Clients with renal impairment are at risk of this adverse effect with amphotericin use. Hematologic Amphotericin B use increases the risk of bone marrow suppression, resul=ng Effects in normocy=c, normochromic anemia. Intrathecal Intrathecal administra=on can cause nausea, vomi=ng, headache, and back, Injec=on leg, and abdominal pain. Rare reac=ons can include visual disturbances, Reac=ons hearing impairment, and paresthesia.  Sordarins Indica=ons and Therapeu=c Uses Systemic Fungal Infec9ons: Amphotericin B is a drug of choice for most systemic mycoses. Side Effects and Adverse Reac=ons Precau=ons and Contraindica=ons Precau9ons Amphotericin B dosage should be reduced in clients with renal impairment. Due to toxicity, this drug should be administered for the shortest =me possible. Treatment is usually 6 to 8 weeks but may last 3 to 4 months. Contraindica9ons Contraindicated in clients with severe renal impairment. Black Box Warning Because of its toxicity, amphotericin B should only be administered for a poten=ally life-threatening infec=on. Drug Interac=ons Concomitant use of amphotericin B with other [nephrotoxic agents] such as [aminoglycosides, cyclosporine, or NSAIDs] increases the risk for renal damage.  Amphotericin poten=ates the an=fungal ac=on of [flucytosine], requiring a reduc=on in amphotericin B dosage. Combining these two medica=ons can enhance an=fungal treatment and reduce the poten=al for toxicity. Dosing, Administra=on, & Client Teaching Dosing Dosing varies based on the condi=on, severity, and client response. Check drug dosing guidelines for individualized dosing. Amphotericin B dosing is individualized based on disease severity and client tolerability. Ini=al test dose should be administered to assess the client’s reac=on. Amphotericin B is available in four formula=ons- conven=onal and three lipid-based formula=ons. The lipid-based formula=ons are as effec=ve as the conven=onal but are more costly and cause less toxicity. All formula=ons are administered intravenously and given daily or every other day for several months. Administra9on IV administra=on. Client Teaching Educate clients on poten=al adverse effects and when to report them. Labs to Monitor Basic Metabolic Panel  Monitor BUN, crea=nine, and crea=nine clearance during drug ini=a=on and every 3-4 days. Monitor potassium and magnesium on ini=a=on and every 3-4 days. Complete Blood Count (CBC) Monitor CBC for anemia on ini=a=on and every 3-4 days. Overview of the Drug Class Prototype: itraconazole (Sporanox) Category: Azole An=fungal Agents Primary Func9on: Similar to amphotericin B, the azoles are broad-spectrum an=fungal drugs. Unique Features: Azoles such as Itraconazole provide an alterna=ve to amphotericin B for trea=ng systemic mycoses. Azoles have lower toxicity than amphotericin b and can be administered by mouth. Mechanism of Ac=on Itraconazole inhibits the synthesis of ergosterol (sterol), resul=ng in increased membrane permeability and leakage of cellular components. Title: Mechanism of an9fungal drugs Cell wall  Cell membrane DNA Proteins Echinocandins, triterpenoids Azoles, polyenes, allylamines 5-fluorocytosine Sordarins Indica=ons and Therapeu=c Uses Systemic Fungal Infec9ons: Itraconazole is ac=ve against a broad spectrum of fungal pathogens. It is considered first-line therapy for blastomycosis, histoplasmosis, paracoccidioidomycosis, and sporotrichosis and is an alterna=ve to amphotericin b for aspergillosis, candidiasis and coccidioidomycosis. Superficial Fungal Infec9ons: Itraconazole can also treat superficial mycoses. Side Effects and Adverse Reac=ons Side Effect Descrip9on GI Upset Nausea, vomi=ng, and diarrhea are common. Side Effect Descrip9on Cardiac Itraconazole has a nega=ve inotropic ac=on that can cause a transient Suppression decrease in ejec=on frac=on. Hepa=c Injury Itraconazole has been associated with rare incidents of hepa=c failure resul=ng in fatali=es. Precau=ons and Contraindica=ons Precau9ons Use cau=on in clients with hepa=c dysfunc=on. Use with cau=on in heart failure and only when the benefit outweighs the risk. Black Box Warning Itraconazole should not be used to treat superficial mycoses in clients with heart failure, a history of heart failure, or other indica=ons of ventricular dysfunc=on. Drug Interac=ons Since [proton pump inhibitors] have a prolonged dura=on of ac=on, clients using these agents may have insufficient stomach acid content for itraconazole absorp=on. Itraconazole is a [CYP3A4 Inhibitor] and can increase levels of many other drugs, including [cisapride, pimozide, dofe9lide, and quinidine] which can increase the risk of [fatal ventricular dysrhythmias]. Other drugs influenced  by CYP3A4 inhibi=on include [cyclosporine, digoxin, warfarin, and sulfonylureas]. Drugs that raise gastric pH, such as [antacids, H2 antagonists, and proton pump inhibitors] can reduce the absorp=on of oral Itraconazole. Administer these agents at least 1 hour before itraconazole or 2 hours aeer. Dosing, Administra=on, & Client Teaching Dosing Dosing varies based on the condi=on, severity, and client response. Check drug dosing guidelines for individualized dosing. Itraconazole is available for PO use in suspension (10mg/ml) and capsules (100 mg). Capsules should be taken with food or cola (cola enhances absorp=on). Recommended dose is 200 mg once daily and can be increased to 200 mg twice daily if needed. Administra9on Oral administra=on. Client Teaching Educate clients about symptoms of hepa=c insufficiency (persistent nausea, anorexia, fa=gue, vomi=ng, RUQ pain, jaundice, dark urine, pale stools) and seek medical aien=on immediately if those symptoms occur. Labs to Monitor Basic Metabolic Panel Monitor the blood glucose levels of clients taking sulfonylureas with itraconazole as hypoglycemia can occur. Coagula9on Studies Monitor PT/INR for clients taking warfarin with itraconazole, as excessive an=coagula=on can occur. Serum Drug Levels Monitor drug levels of cyclosporine and digoxin for clients also taking itraconazole. Overview of the Drug Class Prototype: caspofungin (Cancidas) Category: Echinocandin An=fungal Agent Primary Func9on: Caspofungin is a narrow-spectrum IV an=fungal agent limited to aspergillus and candida species. Unique Features: These drugs are the newest class of an=fungal agents. In contrast to amphotericin B and the Azoles, which disrupt the fungal cell membrane, the echinocandins disrupt the fungal cell wall. Caspofungin is beier tolerated than amphotericin b with similar efficacy. Mechanism of Ac=on Caspofungin inhibits the biosynthesis of beta-1,3-d-glucan, an essen=al fungal cell wall component. Image Title: Mechanism of an9fungal drugs Cell wall Cell membrane DNA Proteins Echinocandins, triterpenoids Azoles, polyenes, allylamines 5-fluorocytosine Sordarins Indica=ons and Therapeu=c Uses Systemic Fungal Infec9ons: Caspofungin is approved for IV therapy of invasive aspergillosis in clients unresponsive or intolerant to amphotericin b or itraconazole or systemic candida infec=ons, including candidemia and candida-related peritoni=s, pleural space infec=ons, and intraabdominal abscesses. Side Effects and Adverse Reac=ons  Side Effect Descrip9on Histamine-Mediated Effects include rash, facial flush, pruri=s, anaphylaxis, or a sense of Reac=ons warmth related to histamine release. Injec=on Site Reac=ons Phlebi=s at the injec=on site. Common Reac=ons Fever, headache, rash, nausea, or vomi=ng. Precau=ons and Contraindica=ons Precau9ons Caspofungin is classified as an FDA Pregnancy risk Category C agent as it is embryotoxic in rats and rabbits. Avoid use in pregnancy unless the poten=al benefits outweigh the risks. Reduce dosage in clients with moderate hepa=c impairment. Contraindica9ons Avoid in clients with severe hepa=c impairment. Drug Interac=ons Drugs that induce CYP450 enzymes (like [efavirenz, nelfinavir, rifampin, carbamazepine, dexamethasone, and phenytoin]) may decrease caspofungin levels. Simultaneous caspofungin use with [tacrolimus] can decrease its plasma levels.  Concomitant use of caspofungin with [cyclosporine] increases the risk for hepa=c injury. Dosing, Administra=on, & Client Teaching Dosing Dosing varies based on the condi=on, severity, and client response. Check drug dosing guidelines for individualized dosing. Caspofungin is not absorbed from the GI tract and must be given intravenously. Available in powder for saline recons=tu=on in 50mg and 70 mg. Treatment should include a 70 mg loading dose followed by daily maintenance dosing of 50 mg. Treatment dura=on depends on the disease's severity and the client's response. Capsofungin should be infused slowly over 1 hour. Administra9on IV administra=on slowly over one hour. Client Teaching Advise clients who are pregnant or considering pregnancy of the risks and benefits of using this drug. Educate clients to monitor for side effects and report to providers. Labs to Monitor Liver Func9on Tests (LFTS) Liver func=on tests should be done at ini=a=on and during use to monitor for hepa=c dysfunc=on. Serum Drug Levels If this drug is used concomitantly with tacrolimus, plasma levels of tacrolimus should be monitored. Pyrimidines Pyrimidine analog agents like flucytosine are oral an=fungal agents used for specific suscep=ble Candida and C. neoformans strains. Overview of the Drug Class Prototype: flucytosine (Ancobon) Category: Pyrimidine Analog An=fungal Agent Primary Func9on: Flucytosine is a narrow-spectrum an=fungal agent. Flucytosine fungicidal ac=vity is highest against suscep=ble strains of Candida and C. neoformans. Most other fungi are resistant to flucytosine. Unique Features: Flucytosine is almost always used in combina=on with amphotericin b due to commonly developed resistance. Mechanism of Ac=on Flucytosine is taken up by fungal cells and converted to the powerful an=metabolite 5-fluorouracil (5-FU). These metabolites disrupt fungal DNA and RNA synthesis. Flucytosine is rela=vely harmless to humans because  mammalian cells lack cytosine deaminase (an enzyme that converts flucytosine to 5-FU). Image Title: Mechanism of an9fungal drugs Cell wall Cell membrane DNA Proteins Echinocandins, triterpenoids Azoles, polyenes, allylamines 5-fluorocytosine Sordarins Indica=ons and Therapeu=c Uses Systemic Fungal Infec9ons: Flucytosine is indicated for trea=ng candidiasis and cryptococcosis. In trea=ng severe infec=ons such as systemic candidiasis and cryptococcal meningi=s, flucytosine should be combined with amphotericin b. Side Effects and Adverse Reac=ons  Side Effect Descrip9on Hematologic Bone marrow suppression is the most severe complica=on of therapy. This Effects includes the risk of reversible neutropenia or thrombocytopenia and a rare risk of fatal agranulocytosis. Hepatotoxicity Mild and reversible hepa=c dysfunc=on is common with flucytosine use, but severe hepa=c injury is rare. Precau=ons and Contraindica=ons Precau9ons Use cau=on in clients with renal impairment due to this drug’s prolonged half-life. Dosage must be reduced in clients with renal insufficiency. Use cau=on in clients with hematologic disorders and bone marrow suppression. Black Box Warning Use extreme cau=on in clients with renal impairment due to its long half- life. Drug Interac=ons [Amphotericin b] can cause nephrotoxicity, and although it is frequently combined with flucytosine, flucytosine excre=on necessitates adequate [kidney func9on], without which flucytosine [toxicity] can occur.  Since flucytosine can inhibit CYP450 enzymes, concomitant use of [cisapride, pimozide, dofe9lide, or quinidine] can raise their plasma levels and increase the risk of fatal dysrhythmias. Dosing, Administra=on, & Client Teaching Dosing Dosing varies based on the condi=on, severity, and client response. Check drug dosing guidelines for individualized dosing. Oeen administered combined with amphotericin b. Flucytosine is available in 250 mg and 500 mg capsules for oral administra=on. Dosing for clients with normal renal func=on is 50 – 150 mg/kg/day administered in four divided doses at 6-hour intervals. Dosage must be reduced for clients with renal insufficiency. Administra9on Oral administra=on. Client Teaching Educate clients to monitor for hematologic or hepa=c adverse effects. Labs to Monitor Basic Metabolic Panel (BMP)  Monitor renal func=on during therapy, including BUN/Crea=ne and Crea=ne Clearance. Complete Blood Count (CBC) Monitor platelet and leukocyte counts weekly. Liver Func9on Tests (LFTs) Monitor LFTs weekly to monitor for hepatotoxicity. Serum Drug Levels Monitor flucytosine levels in clients concomitantly using amphotericin b. Overview of the Drug Class Prototype: terbinafine (Lamisil) Category: Allylamine An=fungal Agent Primary Func9on: Terbinafine is a highly ac=ve an=fungal agent against dermatophytes with less ac=vity against Candida species. Unique Features: Other agents representa=ve of this class includes naeifine. Mechanism of Ac=on  Terbinafine inhibits squalene epoxidase with resultant inhibi=on of ergosterol synthesis. Ergosterol synthesis is a key component of the fungal cell membrane. Image Title: Mechanism of an9fungal drugs Cell wall Cell membrane DNA Proteins Echinocandins, triterpenoids Azoles, polyenes, allylamines 5-fluorocytosine Sordarins Indica=ons and Therapeu=c Uses Systemic Fungal Infec9ons: Oral Terbinafine is indicated for systemic fungal infec=ons like =nea and onychomycosis. Superficial Fungal Infec9ons: Topical Terbinafine is indicated for superficial fungal infec=ons like =nea infec=ons, including corporis, cruris, and pedis. Side Effects and Adverse Reac=ons  Side Effect Descrip9on GI Upset Diarrhea, dyspepsia, and abdominal pain are common. Skin Reac=ons This dermatologic side effect can occur. Taste Altera=ons in this sense can occur. Disturbance Hepatotoxicity This adverse effect is an adverse effect of terbinafine with reports of liver transplanta=on and fatality. Precau=ons and Contraindica=ons Contraindica9ons: Contraindicated for clients with preexis=ng hepa=c disease. Drug Interac=ons Terbinafine is antagonized by [rifampin] when taken orally. Terbinafine plasma levels may be increased by [cime9dine] or [CYP2C9 and CYP3A4] inhibitors such as [fluconazole, ketoconazole, amiodarone]. Terbinafine may poten=ate the effects of [caffeine] or drugs metabolized by CYP2D6, such as [tricyclic an9depressants, SSRIs, and beta-blockers]. Dosing, Administra=on, & Client Teaching Dosing Dosing varies based on the condi=on, severity, and client response.  Check drug dosing guidelines for individualized dosing. Oral terbinafine is available in 250 mg tablets. Oral terbinafine for nail infec=on is 250 mg/day for 6-12 weeks. Oral terbinafine for =nea is 250 mg/day for 2-6 weeks. Topical terbinafine 1% is available in gel, spray, powder, and cream formula=ons with applica=on once or twice daily for 1-4 weeks. Administra9on Oral or topical administra=on. Client Teaching Clients should be educated on signs of hepa=c dysfunc=on and counseled to discon=nue therapy immediately and seek medical evalua=on. Labs to Monitor Liver Func9on Tests (LFTs) Baseline LFTs (serum alanine and aspartate aminotransferases) are recommended with oral dosing. Overview of the Drug Class Prototype: nysta9n (Mycosta9n) Category: Polyene An=fungal Agent Primary Func9on: Nysta=n is only indicated for the treatment of Candidiasis.  Unique Features: Nysta=n can be administered orally and topically. Mechanism of Ac=on Nysta=n forms pores in the fungal cell wall by binding to ergosterol. Indica=ons and Therapeu=c Uses Candidiasis: Nysta=n is considered first-line therapy for intes=nal candidiasis. Nysta=n is also u=lized for the treatment of candidal infec=ons of the skin, mouth (thrush), esophagus, and vaginal. Side Effects and Adverse Reac=ons Side Effect Descrip9on GI Upset Nausea, vomi=ng, or diarrhea. Local Irrita=on Topical nysta=n can cause this adverse effect. Precau=ons and Contraindica=ons Precau9ons: Nysta=n is not recommended for the treatment of systemic mycoses. Drug Interac=ons Nysta=n does not typically interact with other drugs. Dosing, Administra=on, & Client Teaching Dosing Dosing varies based on the condi=on, severity, and client response.  Check drug dosing guidelines for individualized dosing. Nysta=n can be administered orally and topically. Oral Nysta=n is supplied as a suspension, as well as tablets and lozenges, with doses ranging from 400,000 to 1 million units, 3-4 =mes daily. Vaginal tablets for treatment of vaginal candidiasis – dosage 100,000 units once daily for two weeks. Nysta=n cream, ointment, or powder formula=ons are available to treat candidiasis of the skin. Cream and ointments are recommended twice daily, while powder is applied three =mes daily. Administra9on Oral or topical administra=on. Client Teaching Educate clients to monitor for improvement of symptoms and adverse effects. Labs to Monitor Rou=ne laboratory monitoring is not indicated for nysta=n. Pregnant and Breasoeeding Clients In 2015, the FDA revised pregnancy labeling guidelines to move away from the A, B, C, D, X labels to the Pregnancy and Lacta=on Labeling Rule (PLLR), which requires labels to a summary of the risk of using the drug during pregnancy and lacta=on, data suppor=ng the summary, and counseling  informa=on. These labels must be updated when new informa=on is available. Although the PLLR is recommended, original labeling categories are s=ll oeen referenced in prac=ce and across seqngs and, therefore, provided below. Many azole an=fungal agents were previously classified as Pregnancy Risk Category C or D agents. Caspofungin is embryotoxic in rats and rabbits and was previously classified as a Pregnancy Risk Category C agent. Vulvovaginal Candidiasis occurs frequently during pregnancy. Only topical (intravaginal) azole therapies applied for seven days are recommended during pregnancy. Oral Fluconazole might be associated with spontaneous abor=on and congenital anomalies and, therefore, should not be used (CDC, 2021). Data regarding most an=fungals and breasoeeding is lacking. Most an=fungals are considered safe in low doses, except for Ketoconazole. Due to this agent’s high poten=al for hepatoxicity, Ketoconazole should be avoided in breasoeeding clients. Consider altered pharmacokine=cs related to pregnancy. Adolescents Many an=fungal agents are safely u=lized to treat systemic and superficial mycoses at reduced recommended doses. Itraconazole requires a lower dose in pediatric clients, with 5mg/kg twice daily as a star=ng dose.  Consider the ability of the family to manage a medica=on regimen. Older Adults The risk for achlorhydria (absent or reduced gastric hydrochloric produc=on) is greater in older adults. This condi=on could make the absorp=on of some an=fungal agents unpredictable. Plasma levels of commonly prescribed medica=ons in older adults (such as warfarin, phenytoin, and oral hypoglycemic agents) are increased by azoles. Medica=on reconcilia=on and safety with poly-pharmacy prac=ce should be priori=zed. Consider the ability of the client and support system to safely self- administer medica=ons without skipping or doubling doses. Consider altered pharmacokine=cs based on age-related changes. Consider polypharmacy and drug interac=ons Drugs Used to Manage Viral Infec=ons Title: HIV Replica9on Process Step 1 Binding to cell membrane Entry Inhibitors:  HIV binds to the receptors and co-receptors of CD4 cells, u=lizing its gp120 protein to facilitate this aiachment. Entry inhibitors block HIV's ini=al aiachment and fusion with the host cell. CCR5 antagonists such as maraviroc (Selzentry) bind to the CCR5 co- receptor on CD4 cells, blocking CCR5-tropic HIV strains from binding and, therefore, entry into the cell. Step 2 Fusion Fusion Inhibitors: Fusion inhibitors can prevent the virus from merging with the cell membrane. These medica=ons are reserved for trea=ng HIV-1 that has become resistant to other ART medica=ons. Fusion inhibitors like enfuvir=de (Fuzeon) work by aiaching to the gp41 subunit of the virus, preven=ng the HIV envelope from merging with the CD4 cell membrane. Step 3 Reverse Transcriptase Reverse Transcriptase Inhibitors: Once inside the host cell, HIV employs reverse transcriptase to convert its RNA into DNA using reverse transcriptase. Reverse transcriptase inhibitors interrupt the conversion of viral RNA to DNA, effec=vely preven=ng the viral gene=c material from being prepared for integra=on. Nucleoside/Nucleo=de Reverse Transcriptase Inhibitors (NRTIs) mimic the natural building blocks of DNA, leading to the premature termina=on of the  viral DNA strand. Examples include abacavir (Ziagen) and tenofovir (Viread). Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) like efavirenz (Sus=va) directly inhibit the reverse transcriptase enzyme, preven=ng HIV DNA synthesis. Step 4 Integra9on Integrase Strand Inhibitors: Once formed, viral DNA travels to the host cell nucleus and integrates into the host's DNA with the help of integrase, a process blocked by integrase strand transfer inhibitors. Integrase Strand Transfer Inhibitors (INSTIs), such as raltegravir (Isentress) and elvitegravir (Vitekta), thwart the integra=on of viral DNA into the host genome by inhibi=ng the HIV integrase enzyme, a key step for the virus to replicate. Step 5 Transcrip9on Step 6 and 7 Transla9on and viral assembly Step 8 Budding Protease Inhibitors: Aeer host DNA integra=on, the virus is transcribed, translated, assembled, and budded from the host cell. The new virus then must mature to become infec=ous, a process mediated by the HIV protease enzyme.  Protease inhibitors block the protease enzyme, resul=ng in the release of non-infec=ous virus par=cles and hindering the virus's capacity to propagate and infect new cells. Examples include atazanavir (Reyataz) and darunavir (Prezista), which are oeen combined with other drugs like ritonavir to enhance their efficacy. Step 9 Viral release and matura9on Management of Herpes Simplex Virus and Varicella-Zoster Virus Overview of the Drug Class Prototype: acyclovir (Zovirax) Category: An=viral Agent Primary Func9on: Acyclovir is used to treat infec=ons caused by the herpesvirus family, including herpes simplex viruses (HSV), varicella-zoster virus (VZV), and, to a lesser extent, cytomegalovirus (CMV). Unique Features: Acyclovir specifically targets viral DNA synthesis, minimizing effects on human cells. Mechanism of Ac=on  Acyclovir inhibits viral DNA synthesis by undergoing ac=va=on to acyclo−guanosine monophosphate (GMP) via the thymidine kinase enzyme. GMP is then converted to acyclo−guanosine triphosphate (GTP) which then inhibits viral DNA polymerase and gets incorporated into viral DNA, blocking further DNA chain growth. Indica=ons and Therapeu=c Uses Herpes Simplex Virus: Acyclovir is the treatment of choice for primary and recurrent mucocutaneous herpes simplex infec=ons, including oral and genital herpes, by reducing the dura=on and severity of outbreaks. Varicella Zoster Virus: For varicella (chickenpox) in children, adolescents, and adults, and herpes zoster (shingles) in older adults, high doses of oral acyclovir are effec=ve, especially when treatment is ini=ated within 24 hours of rash onset to reduce pain and accelerate healing. Cytomegalovirus: Although most strains of CMV are resistant to acyclovir, it may have limited use in certain CMV infec=ons, especially in cases where more potent drugs like ganciclovir are contraindicated. Side Effect Descrip9on Infusion Site IV therapy can cause phlebi=s and inflamma=on at the IV inser=on site. Reac=ons Nephrotoxicity Kidney injury can occur due to deposi=on of the drug into the renal tubules, which may be reversible by ensuring adequate hydra=on and ensuring IV formula=ons are infused slowly. CNS Side Effects Agita=on, tremors, delirium, hallucina=ons, myoclonus, headache, and ver=go. GI Upset Nausea, vomi=ng, and diarrhea are common side effects. Side Effects and Adverse Reac=ons Precau=ons and Contraindica=ons Precau9ons Use cau=on in clients with renal impairment and adjust dosage accordingly. Drug Interac=ons Due to acyclovir’s poten=al for [renal injury], use cau=on with simultaneous administra=on of other [nephrotoxic drugs]. Dosing, Administra=on, & Client Teaching Dosing Dosing varies based on the condi=on, severity, and client response. Check drug dosing guidelines for individualized dosing.  Administered topically, orally, and intravenously, with dosing guidelines varying based on the condi=on being treated and the client's renal func=on. Ensure adequate hydra=on during administra=on to prevent kidney injury. Reduce dosage for clients with impaired kidney func=on. Administra9on Topical, oral, or IV administra=on. Administer IV acyclovir slowly (over one hour). Client Teaching Advise clients to ensure adequate hydra=on and monitor for symptoms of renal injury. Teach clients to apply topical forms with a finger cot or glove to prevent spreading the virus to other parts of the body or to other people. Teach clients to maintain good hygiene prac=ces around the infected areas to support healing and reduce the risk of spreading the infec=on. Inform clients that acyclovir does not cure herpes viruses. Educate clients with genital herpes about the importance of avoiding sexual contact during outbreaks and to always use condoms to reduce the risk of transmission. Labs to Monitor Basic Metabolic Panel (BMP)  Monitor serum crea=nine and blood urea nitrogen levels to assess for nephrotoxicity. Management of Influenza Overview of the Drug Class Prototype: oseltamivir (Tamiflu) Category: Neuraminidase Inhibitor An=viral Agent Primary Func9on: Oseltamivir is primarily used to prevent and treat influenza A and B infec=ons. Unique Features: Oseltamivir is also effec=ve against certain pandemic strains like H1N1 (swine flu) and H5N1 (avian flu). Mechanism of Ac=on Oseltamivir inhibits the neuraminidase enzyme on the surface of the influenza virus. This inhibi=on prevents the release of new viral par=cles from infected cells, effec=vely hal=ng the spread of infec=on within the body. Indica=ons and Therapeu=c Uses Seasonal Influenza: Oseltamivir is approved for the preven=on and treatment of influenza A and B in individuals one year of age and older. It can help reduce the dura=on and severity of flu symptoms. Pandemic Influenza: Oseltamivir is also used to prevent and treat certain pandemic influenza strains like H1N1 (swine flu) and H5N1 (avian flu). Side Effects and Adverse Reac=ons Side Effect Descrip9on Hypersensi=vity Anaphylaxis, Stevens-Johnson syndrome, or skin reac=ons. CNS Effects Delirium or abnormal behavior. GI Upset Nausea and vomi=ng. Precau=ons and Contraindica=ons Precau9ons Treatment should be ini=ated as soon as possible aeer symptoms begin. Monitor for CNS effects, especially in children and adolescents. Drug Interac=ons Since oseltamivir can decrease the [immune response] to the [live influenza vaccine], oseltamivir should be discon=nued at least [two days] before vaccina=on. Dosing, Administra=on, & Client Teaching Dosing Dosing varies based on the condi=on, severity, and client response. Check drug dosing guidelines for individualized dosing. Available as oral tablets or powders that can be recons=tuted for suspension.  For influenza treatment for clients 13 years and older, dosing starts at 75 mg twice daily for five days, star=ng no later than two days aeer symptom onset. Dosages for children are weight-based. For influenza preven=on, the dosage is half the treatment dosage, administered once daily. Candidates for prophylaxis include those exposed to the flu or nursing home residents. Nursing home residents should take prophylac=c doses for up to 42 days. Administra9on Oral administra=on. Client Teaching Advise clients to take oseltamivir with food to reduce the likelihood of GI side effects. Emphasize the importance of star=ng treatment as soon as possible aeer flu symptoms appear for maximum effec=veness. Inform clients about the poten=al side effects, including the rare risk of severe skin reac=ons and CNS symptoms, and instruct clients or caregivers to report such effects immediately. Clarify that oseltamivir is not a subs=tute for the flu vaccine and recommend annual vaccina=on as the primary method of influenza preven=on. Labs to Monitor Rou=ne laboratory monitoring is not indicated for oseltamivir.  Management of COVID-19 Overview of the Drug Class Prototype: ritonavir and nirmatrelvir (Paxlovid) Category: Paxlovid is an oral an=viral medica=on composed of nirmatrelvir and ritonavir tablets, co-packaged for trea=ng COVID-19. Primary Func9on: This medica=on is used for trea=ng mild-to-moderate COVID-19 in pa=ents 12 years of age and older weighing at least 40 kg who are at high risk for progression to severe COVID-19, including hospitaliza=on or death. Unique Features: Ritonavir boosts nirmatrelvir levels by inhibi=ng its metabolism. Mechanism of Ac=on Paxlovid, two tablets (nirmatrelvir and ritonavir) co-packaged for trea=ng COVID-19, works by preven=ng the SARS-CoV-2 virus from replica=ng within the body. Nirmatrelvir blocks the ac=vity of the SARS-CoV-2-3CL protease, a key enzyme the virus needs to mul=ply. Ritonavir slows the breakdown of nirmatrelvir, increasing its effec=veness. Indica=ons and Therapeu=c Uses Mild-to-Moderate COVID-19: Paxlovid is indicated for trea=ng mild-to- moderate COVID-19 in clients 12 years and older weighing at least 40 kg at high risk for developing severe disease. Side Effects and Adverse Reac=ons  Side Effect Descrip9on Altered Taste A frequent side effect of Paxlovid is a change in taste percep=on, commonly reported as a metallic or biier taste. GI Upset Gastrointes=nal upset, including diarrhea, is observed in some clients taking Paxlovid. Hypersensi=vity Paxlovid can trigger hypersensi=vity responses, ranging from mild skin reac=on severe condi=ons such as anaphylaxis, necessita=ng immediate discon=nua=on the medica=on and appropriate medical interven=on. Liver Injury Eleva=ons in liver enzymes have been reported in clients taking Paxlovid. Precau=ons and Contraindica=ons Precau9ons Use with cau=on in clients with renal or hepa=c impairment. Contraindica9ons Contraindicated in clients with a history of significant hypersensi=vity to any of its components. Contraindicated in clients with severe renal or hepa=c impairment. Black Box Warning This medica=on has many significant drug interac=ons due to the inclusion of ritonavir, a potent CYP3A inhibitor. This can cause toxicity of other medica=ons in a client’s drug regimen. Drug Interac=ons Paxlovid can cause significant interac=ons with drugs metabolized by CYP3A due to its inhibi=on of that enzyme, poten=ally leading to [toxicity and severe or life-threatening reac9ons]. This includes many medica=ons, including (but not limited to): o An=arrhythmic medica=ons like [amiodarone, flecainide, dronedarone, propafenone, and quinidine]. o An=psycho=cs like [lurasidone and pimozide]. o HMG-CoA reductase inhibitors like [lovasta9n and simvasta9n]. o PDE5 inhibitors like [sildenafil] used for pulmonary arterial hypertension. o Seda=ves like [triazolam or midazolam]. o An=anginals like [ranolazine]. o Medica=ons for gout like [colchicine]. Paxlovid can cause interac=ons with drugs that are inducers of CYP3A, causing [reduc9ons in Paxlovid plasma concentra9ons, reduced efficacy, and poten9ally drug resistance]. This means that Paxlovid cannot be started un=l aeer these inducers are discon=nued: o An=convulsants like [carbamazepine, phenobarbital, primidone, and phenytoin]. o TB drugs like [rifampin and rifapen9ne].  o Herbal products like [St. John’s Wort]. o Cancer treatment drugs like [apalutamide]. Dosing, Administra=on, & Client Teaching Dosing Dosing varies based on the condi=on, severity, and client response. Check drug dosing guidelines for individualized dosing. Paxlovid should be ini=ated as soon as possible aeer a COVID-19 diagnosis and within five days of symptom onset. The standard dosage is 300 mg nirmatrelvir with 100 mg ritonavir twice daily for five days. For clients with moderate renal impairment, the dose should be adjusted to 150 mg nirmatrelvir with 100 mg ritonavir twice daily for five days. Administra9on Oral administra=on. There are two different drugs in the package. Client Teaching Instruct clients to complete the full treatment course. Instruct clients to isolate according to current public health guidelines in their area. Educate clients to monitor for adverse effects and report them when appropriate. Labs to Monitor Basic Metabolic Panel (BMP) Monitor renal func=on to determine if adjustments in dosing are required based on renal func=on are specified. Liver Func9on Tests (LFTs) Monitor hepa=c func=on due to the poten=al for hepatotoxicity. Pregnant and Breasoeeding Clients An9retroviral Medica9ons In 2015, the FDA revised pregnancy labeling guidelines to move away from the A, B, C, D, and X labels to the Pregnancy and Lacta=on Labeling Rule (PLLR), which requires labels to a summary of the risk of using the drug during pregnancy and lacta=on, data suppor=ng the summary, and counseling informa=on. These labels must be updated when new informa=on is available. Although the PLLR is recommended, original labeling categories are s=ll oeen referenced in prac=ce and across seqngs and therefore provided below. Certain an=retroviral drugs, previously classified as Pregnancy Risk Category B agents, are considered safer during pregnancy. Others may pose higher risks and require more careful risk-benefit analysis. Zidovudine is the medica=on of choice for preven=ng transmission of HIV during labor and delivery, even though it was previously classified as Pregnancy Risk Category C agent.  Breasoeeding is generally contraindicated for clients with HIV due to the risk of viral transmission through breast milk. Herpes Simplex Virus and Varicella-Zoster Acyclovir, famciclovir, and valacyclovir were previously classified as Pregnancy Risk Category B agents, indica=ng no evidence of risk in humans. However, considera=on is needed due to poten=al risks and limited studies on breasoeeding clients. Influenza Oseltamivir is generally considered safe, but zanamivir's safety profile is less clear due to its inhala=on route and poten=al effects on lung func=on. COVID-19 Data on the use of Paxlovid during pregnancy is insufficient. General Consider altered pharmacokine=cs related to pregnancy. Adolescents An9retroviral Medica9ons As they approach adult body size, dosing regimens may transi=on to adult dosing. Consider lifestyle and preferences to help with adherence to medica=on schedules.  Address the risk of transmission through sexual ac=vity, along with safe sex prac=ces. Herpes Simplex Virus and Varicella-Zoster Ganciclovir and valganciclovir can be used with considera=ons for dosing adjustments based on renal func=on and poten=al side effects. Influenza Ini=ate early treatment with oseltamivir to maximize benefits and reduce complica=ons. COVID-19 Paxlovid is authorized for use in adolescents 12 years of age and older weighing at least 40 kg with mild-to-moderate COVID-19 who are at high risk for progression to severe COVID-19, including hospitaliza=on or death. General Consider whether medica=ons are indicated for certain age groups. Consider the ability of the family to manage a medica=on regimen. Consider altered pharmacokine=cs based on age. Older Adults An9retroviral Medica9ons Poten=al for age-related changes in drug metabolism and elimina=on necessitates careful monitoring for adverse effects. Herpes Simplex Virus and Varicella-Zoster  No specific contraindica=ons, but lower doses are recommended for those with renal impairment. Influenza Emphasis on early treatment ini=a=on for oseltamivir and cau=ous use of zanamivir in those with underlying airway diseases, with dosing adjustments for renal impairment. COVID-19 Dose adjustments and monitoring are advised for those with renal or hepa=c impairment. General Consider the ability of the client and support system to safely self- administer medica=ons without skipping or doubling doses. Consider altered pharmacokine=cs based on age-related changes. Consider polypharmacy and drug interac=ons.