Overview of Antifungal Drugs
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Questions and Answers

What is the prototype drug of the polyene antifungal agent category?

Amphotericin B

Which component does amphotericin B bind to in the fungal membrane?

  • Cholesterol
  • Ceramide
  • Ergosterol (correct)
  • Phosphatidylcholine

    • Amphotericin B is effective against bacteria due to its mechanism of action.

    False

    What is a common side effect of amphotericin B during infusion?

    <p>Fever, chills, rigors, nausea, and headache</p> Signup and view all the answers

    The recommended dose for Itraconazole is ______ mg once daily.

    <p>200</p> Signup and view all the answers

    What type of infections is caspofungin primarily used to treat?

    <p>Invasive aspergillosis and systemic candidiasis</p> Signup and view all the answers

    What is the main mechanism of action of flucytosine?

    <p>Disrupting DNA and RNA synthesis</p> Signup and view all the answers

    Terbinafine is contraindicated for clients with preexisting hepatic disease.

    <p>True</p> Signup and view all the answers

    Which laboratory tests should be monitored during therapy with flucytosine?

    <p>Basic Metabolic Panel and Complete Blood Count</p> Signup and view all the answers

    What is the recommended dosage of oral terbinafine for nail infection?

    <p>250 mg/day for 6-12 weeks</p> Signup and view all the answers

    What is the prototype drug for polyene antifungal agents?

    <p>Nystatin</p> Signup and view all the answers

    What are the dosage forms of topical terbinafine?

    <p>All of the above</p> Signup and view all the answers

    Nystatin can be administered both orally and topically.

    <p>True</p> Signup and view all the answers

    What is the main side effect of Nystatin?

    <p>GI upset</p> Signup and view all the answers

    What is the indication for using Acyclovir?

    <p>Infections caused by the herpes virus family</p> Signup and view all the answers

    Oseltamivir is primarily used to treat __________ A and B infections.

    <p>influenza</p> Signup and view all the answers

    What are the possible side effects of Paxlovid?

    <p>All of the above</p> Signup and view all the answers

    Paxlovid can be administered intramuscularly.

    <p>False</p> Signup and view all the answers

    What is the primary function of Nirmatrelvir in Paxlovid?

    <p>Blocks the activity of SARS-CoV-2-3CL protease</p> Signup and view all the answers

    Match the following drugs with their primary indication:

    <p>Terbinafine = Nail infections Nystatin = Candidiasis Acyclovir = Herpes virus infections Oseltamivir = Influenza A and B</p> Signup and view all the answers

    Which of these medications are considered PDE5 inhibitors?

    <p>Sildenafil</p> Signup and view all the answers

    Which drugs can interact with Paxlovid as inducers of CYP3A?

    <p>All of the above</p> Signup and view all the answers

    What is the standard dosage of Paxlovid?

    <p>300 mg nirmatrelvir with 100 mg ritonavir twice daily for five days</p> Signup and view all the answers

    Zidovudine is the medication of choice for preventing transmission of HIV during ______.

    <p>labor and delivery</p> Signup and view all the answers

    Breastfeeding is generally contraindicated for clients with HIV.

    <p>True</p> Signup and view all the answers

    What is the primary concern with using inhalation route drugs like zanamivir?

    <p>Potential effects on lung function</p> Signup and view all the answers

    In which condition should Paxlovid not be started until after inducers are discontinued?

    <p>COVID-19</p> Signup and view all the answers

    Match the following drugs with their classification during pregnancy:

    <p>Sildenafil = Used for pulmonary hypertension Ranolazine = Used for angina Colchicine = Used for gout Zidovudine = Prevent transmission of HIV</p> Signup and view all the answers

    What should clients be instructed to monitor while on Paxlovid?

    <p>Adverse effects</p> Signup and view all the answers

    What is the standard oral dosage of terbinafine for nail infection?

    <p>250 mg/day for 6-12 weeks</p> Signup and view all the answers

    What formulations is topical terbinafine available in?

    <p>Gel, spray, powder, and cream</p> Signup and view all the answers

    Baseline LFTs (serum alanine and aspartate __________) are recommended with oral dosing.

    <p>aminotransferases</p> Signup and view all the answers

    What is nystatin primarily indicated for?

    <p>The treatment of candidiasis</p> Signup and view all the answers

    What side effect is associated with nystatin?

    <p>Nausea</p> Signup and view all the answers

    Which drug is used to treat HSV and VZV infections?

    <p>Acyclovir</p> Signup and view all the answers

    What is a common route of administration for acyclovir?

    <p>Topical, oral, or IV</p> Signup and view all the answers

    Is it safe to give oral fluconazole to pregnant women?

    <p>False</p> Signup and view all the answers

    What is the primary function of oseltamivir?

    <p>To treat influenza</p> Signup and view all the answers

    Paxlovid is an oral antiviral medication for treating __________.

    <p>COVID-19</p> Signup and view all the answers

    What effect does ritonavir have in Paxlovid?

    <p>Boosts nirmatrelvir levels</p> Signup and view all the answers

    Which medication is used for pulmonary arterial hypertension?

    <p>Sildenafil</p> Signup and view all the answers

    What is the standard dosage of Paxlovid?

    <p>300 mg nirmatrelvir with 100 mg ritonavir twice daily</p> Signup and view all the answers

    Paxlovid can be started immediately after the administration of CYP3A inducers.

    <p>False</p> Signup and view all the answers

    What should be monitored in patients taking Paxlovid?

    <p>Renal function and hepatic function.</p> Signup and view all the answers

    Zidovudine is the medication of choice for preventing transmission of HIV during ______.

    <p>labor and delivery</p> Signup and view all the answers

    Which of the following is considered safe for use during pregnancy according to the newly revised guidelines?

    <p>Zidovudine</p> Signup and view all the answers

    At what age can Paxlovid be authorized for use in adolescents?

    <p>12 years of age and older</p> Signup and view all the answers

    Herpes Simplex Virus medications do not have any pregnancy risk.

    <p>False</p> Signup and view all the answers

    Match the medications to their classifications regarding pregnancy risk:

    <p>Sildenafil = Used for pulmonary arterial hypertension Zidovudine = Medication of choice for preventing HIV transmission during labor Acyclovir = Pregnancy Risk Category B agent Oseltamivir = Generally considered safe during pregnancy</p> Signup and view all the answers

    What is the prototype drug in the polyene antifungal class?

    <p>Amphotericin B</p> Signup and view all the answers

    Which of the following statements is true about the mechanism of action of Amphotericin B?

    <p>It binds to ergosterol in the fungal membrane.</p> Signup and view all the answers

    Amphotericin B is effective against bacterial infections.

    <p>False</p> Signup and view all the answers

    What side effect commonly occurs during the infusion of Amphotericin B?

    <p>Fever, chills, rigors, nausea, and headache</p> Signup and view all the answers

    Which of the following is a precaution when administering Amphotericin B?

    <p>Reduce dosage in clients with renal impairment.</p> Signup and view all the answers

    What is the mechanism of action of Itraconazole?

    <p>Inhibits the synthesis of ergosterol</p> Signup and view all the answers

    Itraconazole is less toxic than Amphotericin B.

    <p>True</p> Signup and view all the answers

    What are the indications for using Itraconazole?

    <p>Blastomycosis, histoplasmosis, paracoccidioidomycosis, and sporotrichosis</p> Signup and view all the answers

    Which side effect is associated with prolonged use of Itraconazole?

    <p>Hepatic injury</p> Signup and view all the answers

    What is Caspofungin primarily used to treat?

    <p>Invasive aspergillosis and systemic candida infections</p> Signup and view all the answers

    Which of the following reflects a side effect of Caspofungin?

    <p>Rashes and facial flush</p> Signup and view all the answers

    What is the primary function of Flucytosine?

    <p>It is used for treating candidiasis and cryptococcosis.</p> Signup and view all the answers

    What is a severe complication associated with Flucytosine therapy?

    <p>Hematologic effects</p> Signup and view all the answers

    What is the mechanism of action of Terbinafine?

    <p>Inhibits squalene epoxidase</p> Signup and view all the answers

    Which of the following is a contraindication for Terbinafine?

    <p>Clients with pre-existing hepatic disease</p> Signup and view all the answers

    Which of the following is a PDE5 inhibitor used for pulmonary arterial hypertension?

    <p>Sildenafil</p> Signup and view all the answers

    What is the standard dosage of Paxlovid?

    <p>300 mg nirmatrelvir with 100 mg ritonavir twice daily for five days</p> Signup and view all the answers

    Paxlovid can be started immediately even if there are drug inducers present.

    <p>False</p> Signup and view all the answers

    Which medication is recommended for preventing transmission of HIV during labor and delivery?

    <p>Zidovudine</p> Signup and view all the answers

    Paxlovid should be initiated within ____ days of symptom onset.

    <p>five</p> Signup and view all the answers

    Which of the following medications are considered strict contraindications for breastfeeding due to HIV?

    <p>Zidovudine</p> Signup and view all the answers

    What should clients do regarding adverse effects while on Paxlovid?

    <p>Monitor and report them</p> Signup and view all the answers

    Match the following medications with their respective risks during pregnancy:

    <p>Zidovudine = Medication of choice for preventing HIV transmission Oseltamivir = Generally considered safe Acyclovir = Previously classified as Pregnancy Risk Category B Ranolazine = Used for angina</p> Signup and view all the answers

    Which of the following herbal products can interact with Paxlovid?

    <p>St. John's Wort</p> Signup and view all the answers

    Zanamivir is considered to have a clear safety profile for pregnant patients.

    <p>False</p> Signup and view all the answers

    What is the recommended dose of oral terbinafine for nail infection?

    <p>250 mg/day for 6-12 weeks</p> Signup and view all the answers

    What are the formulations available for topical terbinafine?

    <p>Gel, spray, powder, and cream</p> Signup and view all the answers

    What should clients be educated on when taking terbinafine?

    <p>Signs of hepatic dysfunction</p> Signup and view all the answers

    What baseline tests are recommended when prescribing oral terbinafine?

    <p>Liver function tests (LFTs)</p> Signup and view all the answers

    What is the primary function of nystatin?

    <p>Treatment of candidiasis</p> Signup and view all the answers

    How does nystatin work?

    <p>By binding to ergosterol and forming pores in the fungal cell wall</p> Signup and view all the answers

    Which of the following medications are contraindicated during pregnancy?

    <p>Oral fluconazole</p> Signup and view all the answers

    What category of drug is acyclovir?

    <p>Antiviral agent</p> Signup and view all the answers

    What is a common side effect of acyclovir?

    <p>Nephrotoxicity</p> Signup and view all the answers

    What is the primary use of oseltamivir?

    <p>Prevent and treat influenza A and B infections</p> Signup and view all the answers

    What is a unique feature of ritonavir in the treatment of COVID-19?

    <p>It boosts nirmatrelvir levels</p> Signup and view all the answers

    Acyclovir can be administered orally, topically, and intravenously.

    <p>True</p> Signup and view all the answers

    What should clients do to reduce the risk of renal injury when taking acyclovir?

    <p>Ensure adequate hydration</p> Signup and view all the answers

    What is the prototype drug for Polyene Antifungal Agents?

    <p>Amphotericin B (Abelcet)</p> Signup and view all the answers

    Amphotericin B is effective against bacterial infections.

    <p>False</p> Signup and view all the answers

    What unique feature allows Amphotericin B to work against fungi?

    <p>It binds to ergosterol in the fungal membrane.</p> Signup and view all the answers

    What are potential side effects of Amphotericin B?

    <p>Nephrotoxicity</p> Signup and view all the answers

    What additional medication can reduce mild infusion reactions of Amphotericin B?

    <p>Diphenhydramine plus acetaminophen</p> Signup and view all the answers

    What is the drug of choice for most systemic mycoses?

    <p>Amphotericin B</p> Signup and view all the answers

    Which of the following conditions is Itraconazole primarily used to treat?

    <p>Blastomycosis</p> Signup and view all the answers

    Itraconazole should not be used to treat superficial mycoses in clients with heart failure.

    <p>True</p> Signup and view all the answers

    Which drug is a narrow-spectrum IV antifungal agent approved for invasive aspergillosis?

    <p>Caspofungin (Cancidas)</p> Signup and view all the answers

    What are common side effects of Caspofungin?

    <p>Fever</p> Signup and view all the answers

    What class of drugs does Flucytosine belong to?

    <p>Pyrimidine Analog Antifungal Agent</p> Signup and view all the answers

    Flucytosine is commonly combined with which antifungal for treatment?

    <p>Amphotericin B</p> Signup and view all the answers

    Terbinafine is not effective against dermatophytes.

    <p>False</p> Signup and view all the answers

    Study Notes

    Overview of the Drug Class

    • Amphotericin B (Abelcet): This drug (polyene antifungal) is effective against a wide range of fungi and is frequently used for systemic fungal diseases. It attaches to ergosterol in the fungal membrane, increasing permeability and leading to cell death.
    • Itraconazole (Sporanox): An azole antifungal that offers an alternative to amphotericin B for systemic fungal infections. Azoles are less toxic and can be taken orally. Itraconazole inhibits ergosterol synthesis, causing cell membrane damage.
    • Caspofungin (Cancidas): This echinocandin antifungal is narrow spectrum and effective against Candida and Aspergillus species only. It is less toxic and more tolerated than amphotericin B. Caspofungin disrupts the fungal cell wall by inhibiting beta-1,3-D-glucan, a vital cell wall component.
    • Flucytosine (Ancobon): A pyrimidine analog antifungal with a narrow spectrum, it's particularly effective against Candida and C. neoformans. Often used in combination with amphotericin B. Flucytosine is taken up by fungal cells and converted into the metabolite 5-fluorouracil, disrupting DNA and RNA synthesis.
    • Terbinafine (Lamisil): An allylamine antifungal that is very effective against dermatophytes, less so against Candida species. It inhibits squalene epoxidase, thus interfering with ergosterol synthesis, a crucial element in the fungal cell membrane.
    • Nystatin (Mycostatin): A polyene antifungal used specifically for treating candidiasis, available orally and topically. It attaches to ergosterol, creating pores in the fungal cell wall, leading to cell death.

    Amphotericin B Side Effects

    • Common side effects include infusion reactions (fever, chills, rigors, nausea, and headache) due to cytokine release.
    • Nephrotoxicity is dose-dependent.
    • Hypokalemia can occur particularly in clients with renal impairment.
    • Hematologic effects can include bone marrow suppression, leading to anemia.
    • Intrathecal injection can cause nausea, vomiting, headache, back pain, leg pain, abdominal pain, as well as rare reactions like visual disturbances, hearing impairment, and paresthesia.

    Amphotericin B Precautions and Contraindications

    • Dosage should be reduced in clients with renal impairment.
    • Use only for potentially life-threatening fungal infections due to its toxicity.
    • Contraindicated in clients with severe renal impairment.

    Itraconazole Side Effects and Precautions

    • Gastrointestinal upset (nausea, vomiting, diarrhea) is common.
    • Cardiac suppression: Itraconazole can transiently decrease ejection fraction.
    • Hepatic injury: Rare but potentially fatal cases of liver failure have been reported.

    Itraconazole Precautions and Contraindications

    • Use cautiously in clients with liver dysfunction and heart failure.
    • Contraindicated in clients with heart failure, a history of heart failure, or other signs of ventricular dysfunction.

    Caspofungin Side Effects

    • Common side effects include fever, headache, rash, nausea, or vomiting.
    • Histamine-mediated reactions are possible: rash, facial flush, pruritus, anaphylaxis, or a sense of warmth.
    • Injection site reactions like phlebitis can occur.

    Caspofungin Precautions and Contraindications

    • Use cautiously in pregnancy due to embryotoxic effects in animals.
    • Reduce dosage in clients with moderate hepatic impairment.
    • Avoid in clients with severe hepatic impairment.

    Flucytosine Side Effects and Precautions

    • Hematologic effects: Bone marrow suppression is the most severe complication, potentially leading to neutropenia, thrombocytopenia, and, rarely, fatal agranulocytosis.
    • Hepatotoxicity: Mild and reversible liver dysfunction is common, severe cases are rare.
    • Use cautiously in clients with renal impairment due to prolonged half-life.
    • Use cautiously in clients with hematologic disorders and bone marrow suppression.

    Terbinafine Side Effects and Precautions

    • Gastrointestinal upset: Diarrhea, dyspepsia, and abdominal pain are common.
    • Skin reactions can occur.
    • Taste disturbance is possible.
    • Hepatotoxicity: Rare cases of liver transplant and even death have been reported.
    • Contraindicated for clients with pre-existing hepatic disease.

    Nystatin Side Effects

    • Gastrointestinal upset: Nausea, vomiting, or diarrhea possible.
    • Local irritation can occur with topical nystatin.
    • Not recommended for systemic fungal infections.

    Vaginal Candidiasis

    • Nystatin vaginal tablets are used to treat vaginal candidiasis.
    • The recommended dosage is 100,000 units once daily for two weeks.
    • Nystatin is also available as a cream, ointment, or powder for skin candidiasis.
    • Cream and ointments are applied twice daily, while powder is applied three times daily.
    • Educate clients to monitor for symptom improvement and adverse effects.

    Pregnancy and Lactation Considerations 

    • The FDA has switched from A, B, C, D, and X pregnancy categories to the Pregnancy and Lactation Labeling Rule (PLLR).
    • PLLR requires labels about medication risks during pregnancy and lactation, data supporting the summary, and relevant counseling information.
    • Many azole antifungals were formerly classified as Pregnancy Risk Category C or D agents.
    • Caspofungin was categorized as a Pregnancy Risk Category C agent due to being embryotoxic in rats and rabbits.
    • Only topical (intravaginal) azole therapies applied for seven days are recommended during pregnancy.
    • Oral Fluconazole might be linked to spontaneous abortion and congenital anomalies, so its use during pregnancy should be avoided.
    • Most antifungal agents are considered safe in low doses during breastfeeding, with the exception of Ketoconazole.
    • Ketoconazole's high potential for hepatotoxicity means it should be avoided in breastfeeding clients.
    • Consider altered pharmacokinetics related to pregnancy.

    Older Adults

    • Older adults have a higher risk of achlorhydria (reduced gastric hydrochloric production).
    • Achlorhydria can make the absorption of some antifungal agents unpredictable.
    • Azoles can increase plasma levels of commonly prescribed medications in older adults, including warfarin, phenytoin, and oral hypoglycemic agents.
    • Prioritize medication reconciliation and safety practices with polypharmacy.
    • Consider the client's ability and support system to safely self-administer medications.
    • Factor in altered pharmacokinetics based on age-related changes.

    HIV Replication Process

    • Entry - HIV attaches to CD4 cells using its gp120 protein.
    • Fusion - HIV merges with the cell membrane.
    • Reverse Transcriptase - HIV converts RNA into DNA using reverse transcriptase.
      • NRTIs like abacavir and tenofovir mimic DNA building blocks, interrupting the viral DNA strand.
      • NNRTIs like efavirenz inhibit reverse transcriptase, preventing viral DNA synthesis.
    • Integration - HIV DNA integrates into the host's DNA using integrase.
      • INSTIs like raltegravir and elvitegravir inhibit integrase, thwarting viral DNA integration.
    • Transcription and Translation
    • Viral Assembly
    • Budding
    • Viral Release and Maturation
      • Protease Inhibitors like atazanavir and darunavir block the protease enzyme, leading to non-infectious virus particles.

    Herpes Simplex Virus and Varicella-Zoster Virus

    • Prototype drug: acyclovir (Zovirax)
    • Mechanism of action: Acyclovir inhibits viral DNA synthesis by activating into acyclo-guanosine monophosphate (GMP) via the thymidine kinase enzyme. GMP is then converted to acyclo-guanosine triphosphate (GTP) which inhibits viral DNA polymerase and gets incorporated into viral DNA, blocking further DNA chain growth.
    • Indications:
      • Herpes simplex: Treatment for primary and recurrent mucocutaneous herpes simplex infections, including oral and genital herpes, by reducing the duration and severity of outbreaks.
      • Varicella zoster: Effective for varicella (chickenpox) and herpes zoster (shingles), especially when initiated within 24 hours of rash onset.

    Influenza

    • Prototype drug: oseltamivir (Tamiflu)
    • Mechanism of action: Oseltamivir inhibits the neuraminidase enzyme on the surface of the influenza virus. This prevents the release of new viral particles from infected cells, halting the spread of infection.
    • Indications:
      • Seasonal influenza: Approved for prevention and treatment in individuals one year of age and older.
      • Pandemic influenza: Used to prevent and treat certain pandemic influenza strains like H1N1 (swine flu) and H5N1 (avian flu).
    • Advise clients to take oseltamivir with food to reduce GI side effects.
    • Emphasize starting treatment as soon as possible after flu symptoms appear.
    • Inform clients about potential side effects, including rare severe skin reactions and CNS symptoms.

    COVID-19

    • Prototype drugs: ritonavir and nirmatrelvir (Paxlovid)

    • Mechanism of action: Nirmatrelvir blocks the activity of the SARS-CoV-2-3CL protease, an enzyme required for viral multiplication. Ritonavir slows nirmatrelvir breakdown, increasing its effectiveness.

    • Indications: Treatment for mild-to-moderate COVID-19 in clients 12 years and older weighing at least 40 kg who are at high risk for progression to severe COVID-19.

    • Black Box Warning: Paxlovid has significant drug interactions due to the inclusion of ritonavir, a potent CYP3A inhibitor. 

    • Instruct clients to complete the full treatment course and isolate according to public health guidelines.

    • Educate clients about adverse effects and report them when appropriate.

    • Monitor renal and hepatic function.### Herpes Simplex Virus and Varicella-Zoster

    • Ganciclovir and valganciclovir can be used with considerations for dosing adjustments based on renal function and potential side effects.

    • Lower doses are recommended for those with renal impairment.

    Influenza

    • Initiate early treatment with oseltamivir to maximize benefits and reduce complications.
    • Cautious use of zanamivir in those with underlying airway diseases, with dosing adjustments for renal impairment.
    • Early treatment initiation is emphasized for oseltamivir.

    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 hospitalization or death.
    • Dose adjustments and monitoring are advised for those with renal or hepatic impairment.

    General Considerations

    • Consider whether medications are indicated for certain age groups.
    • Consider the ability of the family to manage a medication regimen.
    • Consider altered pharmacokinetics based on age.

    Older Adults and Antiretroviral Medications

    • Potential for age-related changes in drug metabolism and elimination necessitates careful monitoring for adverse effects.
    • Consider the ability of the client and support system to safely self-administer medications without skipping or doubling doses.
    • Consider altered pharmacokinetics based on age-related changes.
    • Consider polypharmacy and drug interactions.

    Amphotericin B

    • Amphotericin B is a polyene antifungal agent and is effective against many pathogenic fungi, making it the drug of choice for many systemic mycoses.
    • It works by binding to ergosterol, a component of the fungal cell membrane, increasing permeability and causing intracellular leakage, which reduces the organism's viability.
    • Common side effects include infusion reactions (fever, chills, rigors, nausea, headache), nephrotoxicity, hypokalemia, and hematologic effects.
    • Dosage should be reduced in clients with renal impairment and it should be administered for the shortest time possible, typically 6 to 8 weeks but may last 3 to 4 months.
    • Contraindicated in clients with severe renal impairment and should only be used for potentially life-threatening infections due to its toxicity.
    • Concomitant use with other nephrotoxic agents increases the risk for renal damage.
    • Amphotericin potentiates the antifungal action of flucytosine, requiring a reduction in amphotericin B dosage.
    • Available in four formulations: conventional and three lipid-based. Lipid-based formulations are as effective as the conventional but are more costly and cause less toxicity.
    • It is administered intravenously, given daily or every other day for several months.

    Itraconazole

    • Itraconazole is an azole antifungal agent and is an alternative to amphotericin B for treating systemic mycoses. It has lower toxicity than amphotericin B and can be administered orally.
    • It works by inhibiting the synthesis of ergosterol, leading to increased membrane permeability and leakage of cellular components.
    • Common side effects include GI upset, cardiac suppression, and hepatic injury.
    • Use cautiously in clients with hepatic dysfunction and heart failure, only when the benefit outweighs the risk.
    • Contraindicated in clients with heart failure, a history of heart failure, or other indications of ventricular dysfunction.
    • It is a CYP3A4 inhibitor and can increase levels of many other drugs, including cisapride, pimozide, dofetilide, and quinidine, which can increase the risk of fatal ventricular dysrhythmias.
    • Available for oral use in suspension (10 mg/ml) and capsules (100 mg). Capsules should be taken with food or cola.
    • Recommended dose is 200 mg once daily and can be increased to 200 mg twice daily if needed.

    Caspofungin

    • Caspofungin is an echinocandin antifungal agent and is a narrow-spectrum IV antifungal agent limited to Aspergillus and Candida species.
    • It is the newest class of antifungal agents and works by disrupting the fungal cell wall, unlike amphotericin B and azoles, which disrupt the fungal cell membrane.
    • It is better tolerated than amphotericin B with similar efficacy and works by inhibiting the biosynthesis of beta-1,3-d-glucan, an essential fungal cell wall component.
    • Common side effects include histamine-mediated reactions, injection site reactions, and fever, headache, rash, nausea, or vomiting.
    • It is classified as an FDA Pregnancy risk Category C agent as it is embryotoxic in rats and rabbits. Avoid use in pregnancy unless the potential benefits outweigh the risks.
    • Dosage should be reduced in clients with moderate hepatic impairment.
    • Contraindicated in clients with severe hepatic impairment.
    • Drugs that induce CYP450 enzymes (like efavirenz, nelfinavir, rifampin, carbamazepine, dexamethasone, and phenytoin) may decrease caspofungin levels.
    • Simultaneous use with tacrolimus can decrease its plasma levels.
    • Concomitant use with cyclosporine increases the risk for hepatic injury.
    • It is not absorbed from the GI tract, must be given intravenously, and available in powder for saline reconstitution in 50 mg and 70 mg.
    • Treatment should include a 70 mg loading dose followed by daily maintenance dosing of 50 mg.

    Flucytosine

    • Flucytosine is a pyrimidine analog antifungal agent and is a narrow-spectrum antifungal agent with fungicidal activity highest against susceptible strains of Candida and C. neoformans.
    • It is almost always used in combination with amphotericin B due to commonly developed resistance.
    • It is taken up by fungal cells and converted to the powerful antimetabolite 5-fluorouracil (5-FU). These metabolites disrupt fungal DNA and RNA synthesis.
    • Mammalian cells lack cytosine deaminase, an enzyme that converts flucytosine to 5-FU, making it relatively harmless to humans.
    • Common side effects include hematologic effects (bone marrow suppression, neutropenia, thrombocytopenia, agranulocytosis), hepatotoxicity, and mild and reversible hepatic dysfunction.
    • Use cautiously in clients with renal impairment due to its prolonged half-life.
    • Dosage must be reduced in clients with renal insufficiency and use cautiously in clients with hematologic disorders and bone marrow suppression.
    • It is frequently combined with Amphotericin B, but its excretion necessitates adequate kidney function, without which flucytosine toxicity can occur.
    • Flucytosine can inhibit CYP450 enzymes, which can raise plasma levels of cisapride, pimozide, dofetilide, or quinidine and increase the risk of fatal dysrhythmias.
    • Available in 250 mg and 500 mg capsules for oral administration.
    • Dosing for clients with normal renal function is 50 – 150 mg/kg/day administered in four divided doses at 6-hour intervals.

    Terbinafine

    • Terbinafine is an allylamine antifungal agent and is highly active against dermatophytes with less activity against Candida species.
    • It works by inhibiting squalene epoxidase, resulting in inhibition of ergosterol synthesis, a key component of the fungal cell membrane.
    • Common side effects include GI upset, skin reactions, taste alterations, and hepatotoxicity.
    • Contraindicated in clients with pre-existing hepatic disease.
    • It is antagonized by rifampin when taken orally.
    • Terbinafine plasma levels may be increased by cimetidine or CYP2C9 and CYP3A4 inhibitors such as fluconazole, ketoconazole, or amiodarone.
    • Terbinafine may potentiate the effects of caffeine or drugs metabolized by CYP2D6, such as tricyclic antidepressants, SSRIs, and beta-blockers.
    • Available in 250 mg tablets.
    • For nail infection, the dosage is 250 mg/day for 6-12 weeks.
    • For tinea, the dosage is 250 mg/day for 2-6 weeks.
    • Topical Terbinafine 1% is available in gel, spray, powder, and cream formulations with application once or twice daily for 1-4 weeks.

    Nystatin

    • Nystatin is a polyene antifungal agent, indicated only for the treatment of candidiasis.
    • It can be administered orally and topically.
    • It forms pores in the fungal cell wall by binding to ergosterol.
    • It is considered first-line therapy for intestinal candidiasis and is used for other candidal infections like skin, mouth (thrush), esophagus, and vaginal.
    • Common side effects include GI upset and local irritation.
    • It is not recommended for the treatment of systemic mycoses.
    • Often administered as a suspension, tablets, and lozenges, with doses ranging from 400,000 to 1 million units, 3-4 times daily.

    Nystatin

    • Nystatin is an antifungal medication.
    • Nystatin is available in vaginal tablet, cream, ointment, and powder formulations.
    • Nystatin vaginal tablets are used to treat vaginal candidiasis.
    • Dosage for vaginal tablets is 100,000 units once daily for two weeks.
    • Nystatin cream and ointment are used to treat skin candidiasis.
    • Nystatin cream and ointment are recommended twice daily.
    • Nystatin powder is used to treat skin candidiasis.
    • Nystatin powder is recommended three times daily.
    • Nystatin can be administered orally or topically.
    • Routine laboratory monitoring is not indicated for nystatin.

    Antifungal Medications During Pregnancy

    • The FDA revised pregnancy labeling guidelines in 2015 and no longer uses the categories A, B, C, D, and X. Instead, labels now include a summary of the risk, supporting data, and counseling information.
    • 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 abortion and congenital anomalies and, therefore, should not be used.
    • Most antifungal agents were previously classified as Pregnancy Risk Category C or D agents.
    • Caspofungin is embryotoxic in rats and rabbits and it was previously classified as a Pregnancy Risk Category C agent.

    Antifungal Medications During Breastfeeding

    • Data regarding most antifungals and breastfeeding is lacking.
    • Most antifungals are considered safe in low doses, except for ketoconazole.
    • Ketoconazole should be avoided in breastfeeding clients due to its high potential for hepatotoxicity.

    Antifungal Medications in Adolescents

    • Many antifungal agents are safely utilized to treat systemic and superficial mycoses at reduced recommended doses.
    • Itraconazole requires a lower dose in pediatric clients, with 5 mg/kg twice daily as a starting dose.

    Antifungal Medications in Older Adults

    • The risk for achlorhydria (absent or reduced gastric hydrochloric acid production) is greater in older adults.
    • Achlorhydria can make the absorption of some antifungal agents unpredictable.
    • Plasma levels of commonly prescribed medications in older adults (such as warfarin, phenytoin, and oral hypoglycemic agents) are increased by azoles.

    HIV Replication Process & Antiretroviral Medications

    • The HIV replication process involves several steps, including binding to the cell membrane, fusion, reverse transcriptase, integration, transcription, translation and viral assembly, budding, and viral release and maturation.
    • Entry inhibitors: Block HIV's initial attachment and fusion with the host cell.
      • CCR5 antagonists (e.g., maraviroc) bind to the CCR5 co-receptor on CD4 cells, blocking CCR5-tropic HIV strains from binding and entering the cell.
    • Fusion inhibitors: Prevent the virus from merging with the cell membrane.
      • Fusion inhibitors (e.g., enfuvirtide) work by attaching to the gp41 subunit of the virus, preventing the HIV envelope from merging with the CD4 cell membrane.
    • Reverse transcriptase inhibitors: Interrupt the conversion of viral RNA to DNA.
      • Nucleoside/Nucleoside Reverse Transcriptase Inhibitors (NRTIs) (e.g., abacavir, tenofovir) mimic the building blocks of DNA, leading to premature termination of the viral DNA strand.
      • Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) (e.g., efavirenz) directly inhibit the reverse transcriptase enzyme, preventing HIV DNA synthesis.
    • Integrase strand transfer inhibitors (INSTIs): Block the integration of viral DNA into the host DNA.
      • INSTIs (e.g., raltegravir, elvitegravir) inhibit the HIV integrase enzyme, a key step for the virus to replicate.
    • Protease inhibitors: Block the protease enzyme, resulting in the release of non-infectious virus particles and hindering the virus's capacity to propagate and infect new cells.
      • Protease inhibitors (e.g., atazanavir, darunavir) are often combined with other drugs like ritonavir to enhance their efficacy.

    Antiretroviral Medications During Pregnancy

    • Some antiretroviral drugs are considered safer during pregnancy (e.g., previously classified as Pregnancy Risk Category B agents).
    • Zidovudine is the medication of choice for preventing transmission of HIV during labor and delivery, even though it was previously classified as Pregnancy Risk Category C agent.
    • Breastfeeding is generally contraindicated for clients with HIV due to the risk of viral transmission through breast milk.

    Antiretroviral Medications in Adolescents

    • As adolescents approach adult body size, dosing regimens may transition to adult dosing.
    • It is important to address the risk of transmission through sexual activity and promote safe sex practices.

    Acyclovir for Herpes Simplex Virus and Varicella Zoster Virus

    • Prototype: Acyclovir (Zovirax)
    • Category: Antiviral agent
    • Primary function: Treats infections caused by the herpesvirus family, including herpes simplex viruses (HSV), varicella-zoster virus (VZV), and cytomegalovirus (CMV).
    • Unique features: Specifically targets viral DNA synthesis, minimizing effects on human cells.
    • Mechanism of action: Inhibits viral DNA synthesis by undergoing activation to acyclo-guanosine monophosphate (GMP) via the thymidine kinase enzyme. GMP is then converted to acyclo-guanosine triphosphate (GTP) which inhibits viral DNA polymerase and gets incorporated into viral DNA, blocking further DNA chain growth.
    • Indication and therapeutic uses:
      • Herpes Simplex Virus: Treatment of choice for primary and recurrent mucocutaneous herpes simplex infections, including oral and genital herpes, by reducing the duration 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 effective, especially when treatment is initiated 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 infections, especially in cases where more potent drugs like ganciclovir are contraindicated.
    • Side Effects:
      • Infusion site reactions: IV therapy can cause phlebitis and inflammation at the IV insertion site.
      • Nephrotoxicity: Kidney injury can occur due to deposition of the drug into the renal tubules, which may be reversible by ensuring adequate hydration and ensuring IV formulations are infused slowly.
      • CNS side effects: Agitation, tremors, delirium, hallucinations, myoclonus, headache, and vertigo.
      • GI upset: Nausea, vomiting, and diarrhea are common side effects.
    • Precautions and Contraindications:
      • Precautions: Use caution in clients with renal impairment and adjust dosage accordingly.
      • Drug interactions: Due to acyclovir's potential for nephrotoxicity, use caution with simultaneous administration of other nephrotoxic drugs.
    • Dosing, Administration, and Client Teaching:
      • Dosing: Dosing varies based on the condition, severity, and client response. Check drug dosing guidelines for individualized dosing.
      • Administration: Topical, oral, or IV administration. Administer IV acyclovir slowly (over one hour).
      • Client teaching: Advise clients to ensure adequate hydration 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 practices around the infected areas to support healing and reduce the risk of spreading the infection. 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.
    • Laboratory Monitoring:
      • Basic Metabolic Panel (BMP): Monitor serum creatinine and blood urea nitrogen levels to assess for nephrotoxicity.

    Acyclovir During Pregnancy and Breastfeeding

    • Acyclovir, famciclovir, and valacyclovir were previously classified as Pregnancy Risk Category B agents, indicating no evidence of risk in humans. However, consideration is needed due to potential risks and limited studies on breastfeeding clients.

    Oseltamivir for Influenza

    • Prototype: Oseltamivir (Tamiflu)
    • Category: Neuraminidase inhibitor antiviral agent
    • Primary function: Prevent and treat influenza A and B infections.
    • Unique features: Effective against certain pandemic strains like H1N1 (swine flu) and H5N1 (avian flu).
    • Mechanism of action: Inhibits the neuraminidase enzyme on the surface of the influenza virus. This inhibition prevents the release of new viral particles from infected cells, effectively halting the spread of infection within the body.
    • Indications and therapeutic uses: Seasonal Influenza: Approved for the prevention and treatment of influenza A and B in individuals one year of age and older. It can help reduce the duration 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 Reactions:
      • Hypersensitivity: Anaphylaxis, Stevens-Johnson syndrome, or skin reactions.
      • CNS Effects: Delirium or abnormal behavior.
      • GI upset: Nausea and vomiting.
    • Precautions and Contraindications:
      • Precautions: Treatment should be initiated as soon as possible after symptoms begin. Monitor for CNS effects, especially in children and adolescents.
      • Drug interactions: Since oseltamivir can decrease the immune response to the live influenza vaccine, oseltamivir should be discontinued at least two days before vaccination.
    • Dosing, Administration, and Client Teaching:
      • Dosing: Dosing varies based on the condition, severity, and client response. Check drug dosing guidelines for individualized dosing. Available as oral tablets or powders that can be reconstituted for suspension. For influenza treatment for clients 13 years and older, dosing starts at 75 mg twice daily for five days, starting no later than two days after symptom onset. Dosages for children are weight-based. For influenza prevention, 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 prophylactic doses for up to 42 days.
      • Administration: Oral administration.
      • Client teaching: Advise clients to take oseltamivir with food to reduce the likelihood of GI side effects. Emphasize the importance of starting treatment as soon as possible after flu symptoms appear for maximum effectiveness. Inform clients about the potential side effects, including the rare risk of severe skin reactions and CNS symptoms, and instruct clients or caregivers to report such effects immediately. Clarify that oseltamivir is not a substitute for the flu vaccine and recommend annual vaccination as the primary method of influenza prevention.
    • Laboratory Monitoring:
      • Routine laboratory monitoring is not indicated for oseltamivir.

    Oseltamivir During Pregnancy and Breastfeeding

    • Oseltamivir is generally considered safe, but zanamivir’s, another influenza drug, safety profile is less clear due to its inhalation route and potential effects on lung function.

    Ritonavir and Nirmatrelvir (Paxlovid) for COVID-19

    • Prototype: Ritonavir and nirmatrelvir (Paxlovid)
    • Category: Paxlovid is an oral antiviral medication composed of nirmatrelvir and ritonavir tablets, co-packaged for treating COVID-19.
    • Primary function: Treat mild-to-moderate COVID-19 in patients 12 years of age and older weighing at least 40 kg who are at high risk for progression to severe COVID-19, including hospitalization or death.
    • Unique features: Ritonavir boosts nirmatrelvir levels by inhibiting its metabolism.
    • Mechanism of action: Paxlovid works by preventing the SARS-CoV-2 virus from replicating within the body. Nirmatrelvir blocks the activity of the SARS-CoV-2-3CL protease, a key enzyme the virus needs to multiply. Ritonavir slows the breakdown of nirmatrelvir, increasing its effectiveness.
    • Indications and therapeutic uses:
      • Mild-to-Moderate COVID-19: Paxlovid is indicated for treating 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 Reactions:
      • Altered taste: A frequent side effect of Paxlovid is a change in taste perception, commonly reported as a metallic or bitter taste.
      • GI upset: Gastrointestinal upset, including diarrhea, is observed in some clients taking Paxlovid.
      • Hypersensitivity: Paxlovid can trigger hypersensitivity responses, ranging from mild skin reactions to severe conditions such as anaphylaxis, necessitating immediate discontinuation of the medication and appropriate medical intervention.
      • Liver injury: Elevations in liver enzymes have been reported in clients taking Paxlovid.
    • Precautions and Contraindications:
      • Precautions: Use with caution in clients with renal or hepatic impairment.
      • Contraindications: Contraindicated in clients with a history of significant hypersensitivity to any of its components. Contraindicated in clients with severe renal or hepatic impairment.
    • Black Box Warning:
      • This medication has many significant drug interactions due to the inclusion of ritonavir, a potent CYP3A inhibitor. This can cause toxicity of other medications in a client’s drug regimen.
    • Drug Interactions:
      • Paxlovid can cause significant interactions with drugs metabolized by CYP3A due to its inhibition of that enzyme, potentially leading to toxicity and severe or life-threatening reactions. This includes many medications, including (but not limited to):
        • Antiarrhythmic medications like amiodarone, flecainide, dronedarone, propafenone, and quinidine.
        • Antipsychotics like lurasidone and pimozide.
        • HMG-CoA reductase inhibitors like lovastatin and simvastatin.
        • PDE5 inhibitors like sildenafil used for pulmonary arterial hypertension.
        • Sedatives like triazolam or midazolam.
        • Antianginals like ranolazine.
        • Medications for gout like colchicine.
      • Paxlovid can cause interactions with drugs that are inducers of CYP3A, causing reductions in Paxlovid plasma concentrations, reduced efficacy, and potentially drug resistance. This means that Paxlovid cannot be started until after these inducers are discontinued:
        • Anticonvulsants like carbamazepine, phenobarbital, primidone, and phenytoin.
        • TB drugs like rifampin and rifapentine.
        • Herbal products like St. John’s Wort.
        • Cancer treatment drugs like apalutamide.
    • Dosing, Administration, and Client Teaching:
      • Dosing: Dosing varies based on the condition, severity, and client response. Check drug dosing guidelines for individualized dosing. Paxlovid should be initiated as soon as possible after 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.
      • Administration: Oral administration. 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.
    • Laboratory Monitoring:
      • Basic Metabolic Panel (BMP): Monitor renal function to determine if adjustments in dosing are required.
      • Liver Function Tests (LFTs): Monitor hepatic function due to the potential for hepatotoxicity.

    Paxlovid During Pregnancy

    • Data on the use of Paxlovid during pregnancy is insufficient.

    General Considerations in Pregnancy

    • Consider altered pharmacokinetics related to pregnancy.

    Herpes Simplex Virus and Varicella-Zoster

    • Ganciclovir and valganciclovir are treatment options.
    • Dose adjustments for renal function are necessary.
    • Potential side effects must be considered

    Influenza

    • Oseltamivir should be initiated early for maximum benefit.
    • Oseltamivir reduces complications.
    • Cautious use of zanamivir in those with underlying airway diseases.
    • Dosing adjustments for renal impairment are advised.

    COVID-19

    • Paxlovid is authorized for adolescents 12 years and older.
    • Paxlovid is authorized for those weighing at least 40 kg.
    • Paxlovid is authorized for individuals with mild-to-moderate COVID-19.
    • Paxlovid is authorized for individuals at high risk for severe COVID-19.
    • Individuals should have a high risk for progression to severe COVID-19.
    • Individuals included in the authorization require hospitalization or death.
    • Dosage adjustments and monitoring are advised for those with renal or hepatic impairment.

    General Considerations

    • Consider medication indications for specific age groups.
    • Assess the family's ability to manage medication regimens.
    • Consider altered pharmacokinetics based on age.

    Older Adults

    • Potential for age-related changes in drug metabolism and elimination necessitate careful monitoring for adverse effects.

    Antiretroviral Medications

    • Consider the ability of the client and support system to safely self-administer medications.
    • Ensure safe administration of medications, avoiding skipping or doubling doses.
    • Consider altered pharmacokinetics based on age-related changes.
    • Consider polypharmacy and drug interactions.

    Amphotericin B

    • Prototype Polyene antifungal agent
    • Broad spectrum, effective against most systemic mycoses and preferred agent for many
    • Binds to ergosterol in fungal cell membrane, disrupting permeability and causing intracellular leakage, thus reducing viability
    • Can be fungistatic or fungicidal, depending on agent concentration and fungal susceptibility
    • Common side effects include infusion reactions, nephrotoxicity, hypokalemia, and hematologic effects
    • Intrathecal injection can cause nausea, vomiting, headache, back, leg, and abdominal pain
    • Renal impairment increases risk of nephrotoxicity
    • Shortest possible duration of treatment recommended due to toxicity
    • Usually administered for 6-8 weeks, but can last 3-4 months
    • Contraindicated in clients with severe renal impairment
    • Should only be used for potentially life-threatening infections due to toxicity
    • Can increase risk of renal damage when combined with other nephrotoxic agents (aminoglycosides, cyclosporine, NSAIDs)
    • Can potentiate the antifungal action of flucytosine, allowing for dosage reduction of amphotericin B
    • Available in four formulations: conventional and three lipid-based formulations
    • Lipid-based formulations are more costly but cause less toxicity
    • Administered intravenously daily or every other day for several months
    • Monitor BUN, creatinine, and creatinine clearance during drug initiation and every 3-4 days
    • Monitor potassium and magnesium on initiation and every 3-4 days
    • Monitor CBC for anemia on initiation and every 3-4 days

    Itraconazole

    • Prototype Azole antifungal agent
    • Broad-spectrum antifungal, alternative to amphotericin B for treatment of systemic mycoses
    • Lower toxicity than amphotericin B, can be administered orally
    • Inhibits synthesis of ergosterol, increasing membrane permeability and causing leakage of cell components
    • Effective against a broad spectrum of fungal pathogens
    • First-line therapy for blastomycosis, histoplasmosis, paracoccidioidomycosis, and sporotrichosis
    • Alternative to amphotericin B for aspergillosis, candidiasis, and coccidioidomycosis
    • Can also be used for superficial mycoses
    • Common side effects include GI upset, cardiac suppression, and hepatic injury
    • Use with caution in clients with hepatic dysfunction
    • Use with caution in heart failure, only if the benefit outweighs the risk
    • Should not be used for superficial mycoses in clients with heart failure, a history of heart failure, or other signs of ventricular dysfunction
    • Proton pump inhibitors can reduce itraconazole absorption due to prolonged duration of action and insufficient stomach acid
    • Inhibits CYP3A4 and can increase levels of other drugs, including cisapride, pimozide, dofetilide, and quinidine. This heightened risk may lead to fatal ventricular dysrhythmias.
    • Other drugs affected by CYP3A4 inhibition include cyclosporine, digoxin, warfarin, and sulfonylureas.
    • Drugs that raise gastric pH (antacids, H2 antagonists, proton pump inhibitors) can reduce oral itraconazole absorption, administer these medications at least 1 hour before itraconazole or 2 hours after
    • Available for oral use as a suspension (10 mg/mL) and capsules (100 mg)
    • Capsules should be taken with food or cola (cola enhances absorption)
    • Recommended dose is 200 mg once daily, can be increased to 200 mg twice daily if needed
    • Educate clients about symptoms of hepatic insufficiency (persistent nausea, anorexia, fatigue, vomiting, RUQ pain, jaundice, dark urine, pale stools) and to seek immediate medical attention if they occur
    • Monitor blood glucose levels of clients taking sulfonylureas as hypoglycemia can occur
    • Monitor PT/INR for clients taking warfarin as excessive anticoagulation can occur
    • Monitor drug levels of cyclosporine and digoxin for clients also taking Itraconazole

    Caspofungin

    • Prototype Echinocandin antifungal agent
    • Narrow-spectrum IV antifungal, limited to aspergillus and candida species
    • Newest class of antifungal agents
    • Disrupts fungal cell wall, unlike amphotericin B and azoles which disrupt the fungal cell membrane
    • Better tolerated than amphotericin B with similar efficacy
    • Inhibits the biosynthesis of beta-1,3-d-glucan, an essential fungal cell wall component
    • Approved for IV therapy of invasive aspergillosis in clients unresponsive or intolerant to amphotericin B or Itraconazole
    • Used for systemic candida infections including candidemia and candida-related peritonitis, pleural space infections, and intra-abdominal abscesses
    • Side effects can include histamine-mediated reactions, injection site reactions, and common reactions such as fever, headache, rash, nausea, or vomiting
    • Classified as an FDA Pregnancy risk Category C agent as it is embryotoxic in rats and rabbits. Avoid use during pregnancy unless benefits outweigh the risks.
    • Reduce dosage in clients with moderate hepatic impairment
    • Avoid in clients with severe hepatic impairment
    • Drugs that induce CYP450 enzymes (efavirenz, nelfinavir, rifampin, carbamazepine, dexamethasone, and phenytoin) may decrease caspofungin levels
    • Simultaneous use with tacrolimus can decrease its plasma levels
    • Concomitant use with cyclosporine increases the risk for hepatic injury
    • Not absorbed from the GI tract, must be given intravenously
    • Available in powder form for saline reconstitution in 50 mg and 70 mg
    • Treatment includes a 70 mg loading dose followed by daily maintenance dosing of 50 mg
    • Treatment duration depends on disease severity and client response
    • Infuse slowly over 1 hour
    • Advise pregnant or potentially pregnant clients of risks and benefits of using this drug
    • Educate clients to monitor for side effects and report to providers
    • Monitor liver function tests at initiation and during use to monitor for hepatic dysfunction
    • Monitor plasma levels of tacrolimus if this drug is used concomitantly

    Flucytosine

    • Prototype Pyrimidine analog antifungal
    • Narrow-spectrum antifungal
    • Fungicidal activity highest against susceptible strains of Candida and C. neoformans, most other fungi are resistant
    • Almost always combined with amphotericin B due to commonly developing resistance
    • Taken up by fungal cells and converted to the potent anti-metabolite 5-fluorouracil (5-FU)
    • These metabolites disrupt fungal DNA and RNA synthesis
    • Relatively harmless to humans because mammalian cells lack cytosine deaminase, the enzyme that converts flucytosine to 5-FU
    • Indicated for treating candidiasis and cryptococcosis
    • In severe infections such as systemic candidiasis and cryptococcal meningitis, should be combined with amphotericin B
    • Most severe complication of therapy is bone marrow suppression, including reversible neutropenia or thrombocytopenia, rare risk of fatal agranulocytosis
    • Mild and reversible hepatic dysfunction is common, severe hepatic injury is rare
    • Use with caution in clients with renal impairment due to prolonged half-life, dosage must be reduced in renal insufficiency
    • Use with caution in clients with hematologic disorders and bone marrow suppression
    • Use with extreme caution in clients with renal impairment due to its long half-life
    • Amphotericin B can cause nephrotoxicity, but it is frequently combined with flucytosine, adequate kidney function is required to prevent flucytosine toxicity
    • Can inhibit CYP450 enzymes, so concomitant use of cisapride, pimozide, dofetilide, or quinidine can raise their plasma levels and increase the risk of fatal dysrhythmias
    • Available in 250 mg and 500 mg capsules for oral administration
    • Dosing for clients with normal renal function is 50-150 mg/kg/day administered in four divided doses at 6-hour intervals
    • Dosage must be reduced for clients with renal insufficiency
    • Educate clients to monitor for hematologic or hepatic adverse effects
    • Monitor renal function during therapy, including BUN/creatine and creatine clearance
    • Monitor platelet and leukocyte counts weekly
    • Monitor LFTs weekly to monitor for hepatotoxicity
    • Monitor flucytosine levels in clients concomitantly using amphotericin B

    Terbinafine

    • Prototype Allylamine antifungal agent
    • Highly active antifungal against dermatophytes, less activity against Candida species
    • Other representatives of the class include naftifine
    • Inhibits squalene epoxidase, resulting in inhibition of ergosterol synthesis, a key component of the fungal cell membrane
    • Indicated for systemic fungal infections such as tinea and onychomycosis
    • Topical terbinafine indicated for superficial fungal infections such as tinea corporis, cruris, and pedis
    • Common side effects include GI upset, skin reactions, taste alterations, and hepatotoxicity
    • Contraindicated for clients with pre-existing hepatic disease
    • Antagonized by rifampin when taken orally
    • Plasma levels may be increased by cimetidine or CYP2C9 and CYP3A4 inhibitors such as fluconazole, ketoconazole, or amiodarone
    • May potentiate the effects of caffeine or drugs metabolized by CYP2D6 such as tricyclic antidepressants, SSRIs, and beta-blockers
    • Available as 250 mg tablets
    • Dosage for nail infection is 250 mg/day for 6-12 weeks
    • Dosage for tinea is 250 mg/day for 2-6 weeks
    • Topical terbinafine 1% is available in gel, spray, powder, and cream formulations
    • Apply topically once or twice daily for 1-4 weeks
    • Educate clients about signs of hepatic dysfunction and counsel them to discontinue therapy immediately and seek medical evaluation
    • Baseline LFTs (serum alanine and aspartate aminotransferases) are recommended with oral dosing

    Nystatin

    • Prototype Polyene antifungal agent

    • Only indicated for treatment of candidiasis

    • Can be administered orally and topically

    • Forms pores in the fungal cell wall by binding to ergosterol

    • Considered first-line therapy for intestinal candidiasis

    • Also used for treating candidal infections of the skin, mouth (thrush), esophagus, and vagina

    • Side effects include GI upset and local irritation

    • Not recommended for treatment of systemic mycoses

    • Does not typically interact with other drugs

    • Available as suspension, tablets, and lozenges

    • Doses range from 400,000 to 1 million units, 3-4 times daily### Nystatin

    • Nystatin is an antifungal agent used for vaginal and cutaneous candidiasis.

    • It is available in various formulations including vaginal tablets, cream, ointment, and powder.

    • The dosage for vaginal tablets is 100,000 units once daily for two weeks for vaginal candidiasis.

    • Twice daily application is recommended for skin candidiasis when using the cream or ointment formulation.

    • For the powder, applications are administered three times a day.

    • Nystatin is available in oral and topical formulations.

    • Routine laboratory monitoring is not indicated for nystatin.

    Pregnancy and Breastfeeding Considerations

    • The FDA replaced the A, B, C, D, and X pregnancy category labels with the Pregnancy and Lactation Labeling Rule (PLLR).
    • The PLLR summarizes risks and provides supporting data for drug use during pregnancy and breastfeeding.
    • Many azole antifungals were previously categorized as Pregnancy Risk Category C or D agents.
    • Topical azole therapies applied for seven days are recommended for vulvovaginal candidiasis during pregnancy.
    • Oral fluconazole might be associated with spontaneous abortion and congenital anomalies and should be avoided during pregnancy.
    • Data regarding most antifungal agents and breastfeeding is lacking.
    • Most antifungal agents are considered safe in low doses, except for ketoconazole.
    • Ketoconazole should be avoided in breastfeeding clients due to its potential for hepatotoxicity.
    • Consider altered pharmacokinetics related to pregnancy.

    Adolescent Considerations

    • Many antifungal agents are safely used to treat systemic and superficial mycoses at reduced doses in adolescents.
    • Itraconazole dosage should be adjusted to 5mg/kg twice daily for pediatric clients.
    • Consider family ability to manage medication regimens.

    Older Adult Considerations

    • Older adults are at increased risk for achlorhydria (absent or reduced gastric hydrochloric acid production).
    • Achlorhydria could make the absorption of some antifungal agents unpredictable.
    • Plasma levels of commonly prescribed medications in older adults (warfarin, phenytoin, and oral hypoglycemic agents) are increased by azoles.
    • Prioritize medication reconciliation and safety with polypharmacy (use of multiple medications).
    • Consider ability of clients and support systems to safely administer medications without skipping or doubling doses.
    • Consider altered pharmacokinetics due to age-related changes.
    • Consider polypharmacy and drug interactions.

    HIV Replication Process and Drug Classes

    • HIV binds to receptors and co-receptors of CD4 cells through its gp120 protein.
    • Entry inhibitors block HIV attachment and fusion with the host cell.
    • CCR5 antagonists, like maraviroc (Selzentry), bind to the CCR5 co-receptor on CD4 cells, blocking CCR5-tropic HIV strains from entering the cell.
    • Fusion inhibitors prevent the virus from merging with the cell membrane.
    • Fusion inhibitors, like enfuvirtide (Fuzeon), attach to the gp41 subunit of the virus to prevent the HIV envelope from merging with the CD4 cell membrane.
    • Reverse transcriptase converts HIV RNA into DNA.
    • Reverse transcriptase inhibitors interrupt the conversion of viral RNA to DNA.
    • Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs), like abacavir (Ziagen) and tenofovir (Viread), mimic natural DNA building blocks and prematurely terminate the viral DNA strand.
    • Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs), like efavirenz (Sustiva), directly inhibit the reverse transcriptase enzyme.
    • Integrase Strand Inhibitors (INSTIs), such as raltegravir (Isentress) and elvitegravir (Vitekta), inhibit the integrase enzyme, preventing viral DNA from integrating into the host genome.
    • Protease inhibitors block the protease enzyme that is responsible for viral maturation and prevent the release of infectious virus particles.
    • Protease inhibitors, like atazanavir (Reyataz) and darunavir (Prezista), are often combined with other drugs, like ritonavir, to enhance their efficacy.

    Herpes Simplex Virus and Varicella-Zoster Virus Treatment

    • Acyclovir (Zovirax) is a antiviral agent used to treat infections caused by the herpesvirus family.
    • Acyclovir specifically targets viral DNA synthesis, minimizing effects on human cells.
    • Acyclovir inhibits viral DNA synthesis by undergoing activation to acyclo-guanosine monophosphate (GMP) via the thymidine kinase enzyme.
    • GMP is then converted to acyclo-guanosine triphosphate (GTP), which inhibits viral DNA polymerase and incorporates into viral DNA.
    • Acyclovir is the treatment of choice for primary and recurrent mucocutaneous herpes simplex infections, including oral and genital herpes.
    • High doses of oral acyclovir are effective for varicella (chickenpox) and herpes zoster (shingles), especially when initiated within 24 hours of rash onset.
    • Although acyclovir has limited use in cytomegalovirus (CMV) infections, it may be used when more potent drugs like ganciclovir are contraindicated.

    Acyclovir Side Effects and Adverse Reactions:

    • Infusion site reactions: IV therapy can cause phlebitis and inflammation at the IV insertion site.
    • Nephrotoxicity: Kidney injury can occur due to deposition of the drug into the renal tubules.
    • CNS Side Effects: Agitation, tremors, delirium, hallucinations, myoclonus, headache, and vertigo.
    • GI Upset: Nausea, vomiting, and diarrhea

    Acyclovir Precautions and Contraindications:

    • Use caution in clients with renal impairment and adjust the dosage accordingly.
    • Use caution with simultaneous administration of other nephrotoxic drugs due to Acyclovir's potential for renal injury.
    • Ensure adequate hydration during administration to prevent kidney injury.
    • Reduce dosage for clients with impaired kidney function.

    Acyclovir Administration and Client Teaching:

    • Topical, oral, or IV administration.
    • Administer IV acyclovir slowly (over one hour).
    • Advise clients to ensure adequate hydration and monitor for symptoms of renal injury.
    • Teach clients to apply topical forms with a finger cot or glove to prevent spreading the virus.
    • Teach clients to maintain good hygiene practices around infected areas.
    • 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.
    • Monitor serum creatinine and blood urea nitrogen levels to assess for nephrotoxicity (Basic Metabolic Panel).

    Influenza Management

    • Oseltamivir (Tamiflu) is a neuraminidase inhibitor antiviral agent used to prevent and treat influenza A and B infections.
    • Oseltamivir is also effective against pandemic strains like H1N1 (swine flu) and H5N1 (avian flu).
    • Oseltamivir inhibits the neuraminidase enzyme on the surface of the influenza virus, preventing the release of new viral particles.
    • Oseltamivir is approved for the prevention and treatment of influenza A and B in individuals one year of age and older.
    • It is also used to prevent and treat pandemic influenza strains like H1N1 (swine flu) and H5N1 (avian flu).

    Oseltamivir Side Effects and Adverse Reactions:

    • Hypersensitivity: Anaphylaxis, Stevens-Johnson syndrome, or skin reactions.
    • CNS Effects: Delirium or abnormal behavior.
    • GI Upset: Nausea and vomiting.

    Oseltamivir Precautions and Contraindications:

    • Treatment should be initiated as soon as possible after symptoms begin.
    • Monitor for CNS effects, especially in children and adolescents.
    • Oseltamivir should be discontinued at least two days before influenza vaccination as it can decrease the immune response.

    Oseltamivir Administration and Client Teaching:

    • Oseltamivir is available as oral tablets or powders that can be reconstituted for suspension.
    • For influenza treatment for clients 13 years and older, the dosage starts at 75mg twice daily for five days, starting no later than two days after symptom onset.
    • Dosages for children are weight-based.
    • For influenza prevention, 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 prophylactic doses for up to 42 days.
    • Advise clients to take oseltamivir with food to reduce GI side effects.
    • Emphasize the importance of starting treatment as soon as possible after flu symptoms appear.
    • Inform clients about the potential side effects, including the rare risk of severe skin reactions and CNS symptoms.
    • Clarify that oseltamivir is not a substitute for the flu vaccine and recommend annual vaccination as the primary method of influenza prevention.
    • Routine laboratory monitoring is not indicated for oseltamivir.

    COVID-19 Management

    • Paxlovid is an oral antiviral medication composed of nirmatrelvir and ritonavir tablets, co-packaged for treating COVID-19.
    • It is used to treat mild-to-moderate COVID-19 in patients 12 years of age and older weighing at least 40 kg who are at high risk for progression to severe COVID-19.
    • Ritonavir boosts nirmatrelvir levels by inhibiting its metabolism.
    • Nirmatrelvir blocks the activity of the SARS-CoV-2-3CL protease, a key enzyme the virus needs to multiply.
    • Paxlovid is indicated for treating mild-to-moderate COVID-19 in clients 12 years and older weighing at least 40 kg at high risk for developing severe disease.

    Paxlovid Side Effects and Adverse Reactions:

    • Altered Taste: Change in taste perception, commonly reported as metallic or bitter taste.
    • GI Upset: Gastrointestinal upset, including diarrhea.
    • Hypersensitivity: Hypersensitivity responses, ranging from mild skin reactions to severe conditions like anaphylaxis.
    • Liver Injury: Elevations in liver enzymes.

    Paxlovid Precautions and Contraindications:

    • Use caution in clients with renal or hepatic impairment.
    • Contraindicated in clients with a history of significant hypersensitivity to any of its components.
    • Contraindicated in clients with severe renal or hepatic impairment.

    Paxlovid Black Box Warning:

    • Significant drug interactions due to the inclusion of ritonavir, a potent CYP3A inhibitor.
    • Paxlovid can cause toxicity of other medications in a client's drug regimen.

    Paxlovid Drug Interactions:

    • Paxlovid can cause significant interactions with drugs metabolized by CYP3A, potentially leading to toxicity and severe or life-threatening reactions.
    • Interactions with drugs that induce CYP3A can lead to reduced Paxlovid plasma concentrations, reduced efficacy, and potentially drug resistance.

    Paxlovid Administration and Client Teaching:

    • Paxlovid should be initiated as soon as possible after a COVID-19 diagnosis and within five days of symptom onset.
    • The standard dosage is 300mg nirmatrelvir with 100mg ritonavir twice daily for five days.
    • For clients with moderate renal impairment, the dose should be adjusted to 150mg nirmatrelvir with 100mg ritonavir twice daily for five days.
    • 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.
    • Monitor renal function to determine if adjustments in dosing are required (Basic Metabolic Panel).
    • Monitor hepatic function due to the potential for hepatotoxicity (Liver Function Tests).

    Antiretroviral Medications & Pregnancy and Breastfeeding:

    • Certain antiretroviral drugs are considered safer during pregnancy. Others may pose higher risks and require careful risk-benefit analysis.
    • Zidovudine is the medication of choice for preventing transmission of HIV during labor and delivery.
    • Breastfeeding is generally contraindicated for clients with HIV due to the risk of viral transmission.

    Herpes Simplex Virus and Varicella-Zoster and Pregnancy and Breastfeeding:

    • Acyclovir, famciclovir, and valacyclovir were previously classified as Pregnancy Risk Category B agents.
    • Limited studies on breastfeeding clients require cautious consideration due to potential risks.

    Influenza and Pregnancy and Breastfeeding:

    • Oseltamivir is generally considered safe during pregnancy and breastfeeding.
    • Zanamivir's safety profile is less clear due to its inhalation route and potential effects on lung function.

    COVID-19 and Pregnancy and Breastfeeding:

    • Data on the use of Paxlovid during pregnancy is insufficient.
    • Consider altered pharmacokinetics related to pregnancy.

    Adolescent & Antiretroviral Medications:

    • Dosing regimens may transition to adult dosing for adolescents as they approach adult body size.

    • Consider lifestyle and preferences to help with adherence to medication schedules.

    • Address the risk of transmission through sexual activity, along with safe sex practices.### Herpes Simplex Virus and Varicella-Zoster

    • Ganciclovir and valganciclovir can be used for treatment, but require dosage adjustments based on renal function and potential side effects.

    Influenza

    • Early treatment with oseltamivir is recommended to maximize benefits and reduce complications.
    • Zanamivir should be used cautiously in individuals with underlying airway diseases.
    • Dosage adjustments for oseltamivir and zanamivir are required for patients with renal impairment.

    COVID-19

    • Paxlovid is authorized for use in adolescents aged 12 and older weighing at least 40 kg with mild to moderate COVID-19 and a high risk of progression to severe COVID-19.
    • Dosage adjustments and monitoring are advised for those with renal or hepatic impairment.

    General Considerations

    • Consider the appropriateness of medications for different age groups.
    • Evaluate the family's capacity to manage a medication regimen.
    • Account for potential age-related alterations in pharmacokinetics.

    Older Adults

    • Monitor for adverse effects due to potential age-related changes in drug metabolism and elimination.

    Antiretroviral Medications

    • Monitor for adverse effects due to potential age-related changes in drug metabolism and elimination.

    Herpes Simplex Virus and Varicella-Zoster (Older Adults)

    • Lower doses are recommended for individuals with renal impairment.

    Influenza (Older Adults)

    • Early treatment initiation with oseltamivir is crucial.
    • Zanamivir should be used cautiously in those with underlying airway diseases.
    • Dosage adjustments are needed for renal impairment.

    COVID-19 (Older Adults)

    • Dosage adjustments and monitoring are advised for those with renal or hepatic impairment.

    General Considerations (Older Adults)

    • Assess the client's and their support system's ability to safely self-administer medications and prevent missed or double doses.
    • Account for age-related changes in pharmacokinetics.
    • Consider the potential for polypharmacy and drug interactions.

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