MOST COMMONLY PRESCRIBED ANTIFUNGAL AND ANTIVIRAL MEDICATIONS

1. MOST COMMONLY PRESCRIBED ANTIFUNGAL AND ANTIVIRAL MEDICATIONS Anneliese Bodding-Long University of Washington Doctor of Pharmacy Candidate, 2012 boddia@uw.edu

2. OBJECTIVES • Identify the commonly prescribed antifungal and antiviral medications, their mechanism of action, and what they are commonly prescribed for • Explain common counseling points for each class • Identify the specific counseling points, side effects, and toxicities of these medications

3. ANTIVIRALS Influenza: • Oseltamivir Herpes Simplex/ Herpes Zoster: • Acyclovir • Valacyclovir • Famciclovir

4. VIRAL UPPER RESPIRATORY INFECTIONS OR “THE COMMON COLD” • Caused by more than 200 viruses • Rhinovirus, influenza, coronavirus, respiratory syncytial virus, etc. • Virus replicates and “sheds” • Symptoms and shedding usually last 3-7 days • Most contagious the day before fever begins through 24 hours after fever ends • Symptoms • Nasal congestion, non-productive cough, fever, muscle aches, sore throat

5. WHEN TO TREAT THE COMMON COLD? • Empiric use of antibiotics • More harm than good? Unnecessary adverse effects? Increase bacterial resistance? • “My snot’s yellowish-green, not clear. Is it bacterial?” • Should we culture, and is it an infection or normal colonization? • Cultures may take a few days to return from lab, pt often already has begun antibiotic treatment • Rapid tests for influenza- results in 1 hr • Can’t use if symptoms > 3 days, or recent LAIV • False negatives and low sensitivity • Expensive • Antibiotic therapy does help those infections with a positive culture for the “big three” bacterial suspects • H. influenzae, M. catarrhalis, or S. pneumoniae • Antibiotics are important to prevent secondary infections • Pneumonia, otitis media, bronchitis, sinusitis

6. WHEN TO PROPHYLAX/TREAT INFLUENZA WITH AN ANTIVIRAL? • High risk populations: • ≥65 years old • Pregnant women • Chronic medical conditions • Diabetes, asthma, COPD, cardiovascular disease, etc • Asplenic patients • Influenza requiring hospitalization • Prevent outbreak • Nursing homes, long-term care facilities, correctional facilities

7. ANTIVIRALS FOR INFLUENZA • Oseltamivir (Tamiflu®) • Oral capsule • Oral suspension

8. MECHANISM OF ACTION • Oseltamivir: inhibits influenza virus neuraminidase which stops viral particle release LAYMEN’s terms: prevents the infected host cell from releasing new virus

9. OSELTAMIVIR INDICATIONS Prophylaxis Treatment • Influenza A & B • H1N1 • Avian (H5N1) • Prophylaxis should begin 24-48hr after exposure for best effect • Continue for 10 days • QD therapy • Prophylaxis is NOT replacement for vaccine • Influenza A & B • H1N1 • Avian (H5N1) • Treatment should begin ASAP, or 12-48 hr after onset of symptoms • Continue for 5 days • BID therapy • Oseltamivir resistance? • Zanamivir

10. OSELTAMIVIR PATIENT INFORMATION Administration: • Take with or without food • Food may decrease GI upset • Suspension: • Shake well • Store in fridge Contraindications • No live vaccines w/in 2 weeks before or 48 hours after What to expect: • Improvement of symptoms • May shorten duration of flu symptoms by 1-3 days • May decrease risk of transmission to others • Reduction in secondary antibiotic use

11. HERPES INFECTIONS • HSV1 • Herpes labialis or “cold sores”, fever blisters • HSV2 • Genital herpes • Acquired through sexual contact, lifelong recurrent infection • Can by asymptomatic, still transmissible • Herpes Zoster • Varicella zoster virus • Causes chicken pox in children, shingles, and postherpetic neuralgia

12. ANTIVIRALS FOR HERPES INFECTIONS • Acyclovir (Zovirax®) • Oral capsule, tablet, and IV • Oral suspension • Topical cream, ointment • Valacyclovir (Valtrex®) • Oral tablet • Famciclovir (Famvir®) • Oral tablet

13. MECHANISM OF ACTION • Acyclovir: acts as a purine nucleotide analog to interfere with herpes viral DNA polymerase • Valacylovir: Prodrug converted to acyclovir • Famciclovir: Prodrug converted to penciclovir (acts similarly to acyclovir) LAYMEN’s terms: interferes with viral DNA replication by terminating the DNA chain

14. INDICATIONS • Acyclovir • Herpes Labialis (topical) • Genital Herpes • Initial, Recurrent, Chronic Suppression • Herpes Zoster (shingles) • Varicella-zoster (chicken-pox) • Valacyclovir • Herpes Labialis • Genital Herpes • Initial, Recurrent, Reduction of Transmission, Chronic Suppression • Herpes Zoster • Varicella-zoster • Famciclovir • Herpes Labialis • Genital Herpes • Initial, Recurrent, Chronic Suppression • Herpes Zoster

15. COMMON COUNSELING POINTS • Take with or without food • Take with extra fluids • Tell patients to drink enough to urinate every few hours • Topical application: • Use gloves, wash hands • Cover lesion, rub on gently • Adverse Effects with oral medication: • Headache, fatigue • N/V/D/constipation • More SE with Herpes Zoster treatment (increased dose)

16. COMMON COUNSELING POINTS, CONT • If taking chronically, explain importance of adherence to prevent outbreaks • Cost of therapy? Covered by insurance? • Reduction of stressors (may increase risk of outbreak) • Pts concerned should know toxicity of long-term therapy is minimal • Explain that this is not a cure, give realistic expectations • If taking medication episodically for genital herpes, take within 24 hours of outbreak symptoms (tingling) to suppress or reduce duration and severity • Reduces pain, length of time to healing, viral shedding • Practice SAFE SEX • Chronic therapy does reduce transmission risk • Use condom, avoid sex during outbreak

17. SPECIFIC PATIENT INFORMATION • Valacyclovir and famciclovir have longer half-lives than acyclovir, take less frequently • Example: Acyclovir 5 times a day x 5 days Valacyclovir 2 times a day x 3 days • May increase patient adherence to chronic med • Acyclovir and valacyclovir • Drug-Drug Interaction with probenicid • May increase levels of these antivirals, increase side effects

18. ANTIFUNGALS

19. FUNGAL INFECTIONS Superficial Infections • Tinea (dermatophyte) infections • Named for site of infection • Tinea pedis, corporis, cruris, capitus, etc • Onychomycosis • Infection of finger/toenails by dermatophytes • Sebborrheic dermatitis • Vaginal candidiasis (yeast infection) • Most common species is C. albicans, though other spp are on the rise • Antibiotic treatment can lead to overgrowth • OTC treatment possible if uncomplicated

20. FUNGAL INFECTIONS, CONT. • Oropharyngeal (thrush) and Esophageal candidiasis • Infection can spread from oral mucosa into esophagus • Risk factors include antibiotics, inhaled steroids, dentures, smoking, immunocompromised patients Systemic and Opportunistic Infections • Can gain entry through GI, lungs, or IV • Systemic candidiasis • Can include peritonitis, pneumonia, and others

21. ANTIFUNGAL MEDICATIONS • Azoles • Imidazoles: ketoconazole • Triazoles: fluconazole, itraconazole, voriconazole • Terbinafine • Nystatin

22. MECHANISM OF ACTION • Triazoles: inhibition of CYP450 enzyme dependent ergosterol synthesis • Ketoconazole and Terbinafine: interfere with fungal ergosterol biosynthesis • Nystatin: binds to sterols in cell membrane and changes permeability • LAYMEN’s terms: prevents proper production of fungal cell membrane resulting in cell death

23. AZOLES • Ketoconazole (Nizoral®) • Oral tablet & topicals: cream, gel, shampoo, foam • Fluconazole (Diflucan®) • Oral tablet and IV • Itraconazole (Sporanox®) • Oral capsule • Voriconazole (VFEND®) • Oral tablet and IV

24. OTHER ANTIFUNGALS • Terbinafine (Lamisil®) • Oral tablets • Topicals: cream, gel, solution • Nystatin (Nystat-RX®) • Oral tablets • Oral suspension • Vaginal tablets • Topical powder

25. MOST COMMON INDICATIONS Tinea Infections (1-4 wks) • Ketoconazole • Terbinafine Onychomycosis (6wks-1yr) • Itraconazole • Terbinafine Vaginal Candidiasis (1d-2wks) • Fluconazole • Nystatin Oropharyngeal Candidiasis (7-14d) • Fluconazole • Itraconazole • Nystatin Esophageal Candidiasis (14-21d) • Fluconazole • Itraconazole • Voriconazole Systemic Infections • Fluconazole • Voriconazole • Nystatin

26. PATIENT INFORMATION FOR ALL ANTIFUNGALS • Administration • Superficial fungal infections may take a LONG time to effectively treat (weeks to months) • Exception-Fluconazole for vaginal yeast infection • Important to counsel on adherence and time to effect • Onychomycosis • Side Effects • Oral: Headache, dizziness, changes in taste • GI upset: N/V/D • Can take with food to prevent • Exception- take voriconazole 1-2 hrs before meal • Topical: Irritation, burning, and dryness • Reminder to wash hands after administration

27. SPECIFIC PATIENT INFO Contraindications • Azoles and Terbinafine can lead to liver toxicity so liver function should be closely monitored • [US Black Box Warning] • Azoles (especially triazoles) have drug interactions since MOA involves P450 enzymes • Inhibit CYP3A4, 2C9, 2C19 (warfarin, phenytoin, benzodiazepines…) • Terbinafine also exhibits drug interactions • inhibits CYP2D6 (antidepressants, codeine…) • Ketoconazole and Itraconazole : separate from antacids by 2 to 4 hours. • Why? • Voriconazole: may cause visual disturbances, photophobia • Itraconazole: take with food to increase absorption

28. QUESTIONS?

29. QUIZ NEXT WEEK: • Know COMMON counseling points about the classes of antifungals and antivirals • Know the drugs in each class and their mechanisms of action (Laymen’s terms ok) • Know some SPECIFIC counseling points, side effects, and toxicities for these medications *Hint* look at items in bold or all caps 

30. FEEDBACK! • Please take out a ½ sheet of paper and respond to these questions: 1) What was the most useful information you learned today? 2) What questions remain about the lecture material? 3) What constructive feedback to you have? THANK YOU!