Presentation on theme: "MOST COMMONLY PRESCRIBED ANTIFUNGAL AND ANTIVIRAL MEDICATIONS"— Presentation transcript:
1 MOST COMMONLY PRESCRIBED ANTIFUNGAL AND ANTIVIRAL MEDICATIONS Talk about drugs more globally, not specific details. That’s what you will get out of your drug cardsAnneliese Bodding-LongUniversity of WashingtonDoctor of Pharmacy Candidate, 2012
2 OBJECTIVESIdentify the commonly prescribed antifungal and antiviral medications, their mechanism of action, and what they are commonly prescribed forExplain common counseling points for each classIdentify the specific counseling points, side effects, and toxicities of these medications
4 VIRAL UPPER RESPIRATORY INFECTIONS OR “THE COMMON COLD” Caused by more than 200 virusesRhinovirus, influenza, coronavirus, respiratory syncytial virus, etc.Virus replicates and “sheds”Symptoms and shedding usually last 3-7 daysMost contagious the day before fever begins through 24 hours after fever endsSymptomsNasal congestion, non-productive cough,fever, muscle aches, sore throatVirus replicates in upper respiratory epithelium, sloughs of superficial cells which leads to virus shedding
5 WHEN TO TREAT THE COMMON COLD? Empiric use of antibioticsMore 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 treatmentRapid tests for influenza- results in 1 hrCan’t use if symptoms > 3 days, or recent LAIVFalse negatives and low sensitivityExpensiveAntibiotic therapy does help those infections with a positive culture for the “big three” bacterial suspectsH. influenzae, M. catarrhalis, or S. pneumoniaeAntibiotics are important to prevent secondary infectionsPneumonia, otitis media, bronchitis, sinusitisLAIV nasal vs. IMMost viral infections have a resolution of symptoms in 3-7 days and fully clear within 1-2 weeks. Bacterial infections can clear as well but may require antibiotics if they do not appear to be clearing on their own, are associated with too many symptoms, or are in an individual with many comorbid conditions.colored nasal discharge is a normal self-limited phase of the uncomplicated common cold. Treating with antibiotics in clinical trials does reduce the risk of persistent purulent discharge but adverse effects of antibiotics outweighed benefit of treatment.Some of us are natural colonizers of the big three bugs that cause complications of the common cold: H. influenzae, M. catarrhalis, or S. pneumoniae. So is it a positive culture or was always there? There is still controversy regarding whether diagnostic tests and treatment for influenza are cost-effective in healthy individuals who will likely resolve anyways. Diagnostic tests are expensive and many patients present after the time period If we take a culture and send the patient home on antibiotics then it comes back viral what do we do? Tell them to stop antibiotics, unforeseen risks of developing resistance either way?Each situation must be weighed individually for risk vs. benefit. Generally all treatment should be symptomatic (fluids, APAP for fever, etc) unless a secondary bacterial infection is suspected.
6 WHEN TO PROPHYLAX/TREAT INFLUENZA WITH AN ANTIVIRAL? High risk populations:≥65 years oldPregnant womenChronic medical conditionsDiabetes, asthma, COPD, cardiovascular disease, etcAsplenic patientsInfluenza requiring hospitalizationPrevent outbreakNursing homes, long-term care facilities, correctional facilitiesInfluenza A gains resistance very quickly, don’t want to use in everyoneDefined by CDC as high risk populations, more at risk from complications of influenzaPregnancy category CNo spleen, can’t remove capsulated bacteria- risk for secondary bacterial infectionEmpirically-without laboratory confirmation
7 ANTIVIRALS FOR INFLUENZA Oseltamivir (Tamiflu®)Oral capsuleOral suspension
8 MECHANISM OF ACTIONOseltamivir: inhibits influenza virus neuraminidase which stops viral particle releaseLAYMEN’s terms: prevents the infected host cell from releasing new virusReduces replication of virus
9 OSELTAMIVIR INDICATIONS ProphylaxisTreatmentInfluenza A & BH1N1Avian (H5N1)Prophylaxis should begin hr after exposure for best effectContinue for 10 daysQD therapyProphylaxis is NOT replacement for vaccineInfluenza A & BH1N1Avian (H5N1)Treatment should begin ASAP, or hr after onset of symptomsContinue for 5 daysBID therapyOseltamivir resistance?ZanamivirProphylaxis can continue for longer than 10 days in immunocompromised individuals or in H1N1 if they have continued exposure. (Continue 10 days past last exposure)There are oseltamivir resistant influenza strains particularly with Influenza A strain. Pandemic H1N1 less resistant than seasonal H1N1 There is another neuraminidase inhibitor Zanamivir (nasal inhalation) that can be used and has shown less resistance. There is also a class of antivirals called adamantanes which includes amantadine and rimantadine but they are only effective against Influenza A.
10 OSELTAMIVIR PATIENT INFORMATION Administration:Take with or without foodFood may decrease GI upsetSuspension:Shake wellStore in fridgeContraindicationsNo live vaccines w/in 2 weeks before or 48 hours afterWhat to expect:Improvement of symptomsMay shorten duration of flu symptoms by 1-3 daysMay decrease risk of transmission to othersReduction in secondary antibiotic useLasts 10 days at room temperature, 17 days in fridgeLive attenuated influenza vaccine; vaccine requires immune response and replicating virus to establish immunity, obviously this would lead to diminished efficacy of the vaccineHow do you know if it’s working, should see improvement, if get worse see PCP
11 HERPES INFECTIONS HSV1 HSV2 Herpes Zoster Herpes labialis or “cold sores”, fever blistersHSV2Genital herpesAcquired through sexual contact, lifelong recurrent infectionCan by asymptomatic, still transmissibleHerpes ZosterVaricella zoster virusCauses chicken pox in children, shingles, and postherpetic neuralgiaHSV1- what learned from OTCPostherpetic neuralgia is pain after shingles
12 ANTIVIRALS FOR HERPES INFECTIONS Acyclovir (Zovirax®)Oral capsule, tablet, and IVOral suspensionTopical cream, ointmentValacyclovir (Valtrex®)Oral tabletFamciclovir (Famvir®)When would you use topical for what indicationAcyclovir is only one available topically. Topical use should only be for Shingles or cold sores. CDC discourages topical acyclovir use for genital herpes except in immunocompromised individuals
13 MECHANISM OF ACTIONAcyclovir: acts as a purine nucleotide analog to interfere with herpes viral DNA polymeraseValacylovir: Prodrug converted to acyclovirFamciclovir: Prodrug converted to penciclovir (acts similarly to acyclovir)LAYMEN’s terms: interferes with viral DNA replication by terminating the DNA chainProdrug- administered in inactive form and is activated in the body by metabolism or some other metabolic process to the active drug
14 INDICATIONS Acyclovir Valacyclovir Famciclovir Herpes Labialis (topical)Genital HerpesInitial, Recurrent, Chronic SuppressionHerpes Zoster (shingles)Varicella-zoster (chicken-pox)ValacyclovirHerpes LabialisGenital HerpesInitial, Recurrent, Reduction of Transmission, Chronic SuppressionHerpes ZosterVaricella-zosterFamciclovirInitial, Recurrent, Chronic SuppressionNote that Famciclovir is not approved to be used in chickenpox in children
15 COMMON COUNSELING POINTS Take with or without foodTake with extra fluidsTell patients to drink enough to urinate every few hoursTopical application:Use gloves, wash handsCover lesion, rub on gentlyAdverse Effects with oral medication:Headache, fatigueN/V/D/constipationMore SE with Herpes Zoster treatment (increased dose)Shingles lesions or genital lesionsEliminated completely by kidneys, will prevent kidney problemsTOPICAL?
16 COMMON COUNSELING POINTS, CONT If taking chronically, explain importance of adherence to prevent outbreaksCost of therapy? Covered by insurance?Reduction of stressors (may increase risk of outbreak)Pts concerned should know toxicity of long-term therapy is minimalExplain that this is not a cure, give realistic expectationsIf taking medication episodically for genital herpes, take within 24 hours of outbreak symptoms (tingling) to suppress or reduce duration and severityReduces pain, length of time to healing, viral sheddingPractice SAFE SEXChronic therapy does reduce transmission riskUse condom, avoid sex during outbreakQuality of life higher in patients undergoing suppressive therapy versus episodic therapy (who just treat based on outbreaks). Recommended to use chronic therapy if have 6+ outbreaks per year. Some patients may be very asymptomatic and may not require antivirals. Stress, get more sleep.Though most studies only followed for 1 year. Reoccurrences decrease over time. Patients should be re-evaluated to determine if they can go off chronic therapy
17 SPECIFIC PATIENT INFORMATION Valacyclovir and famciclovir have longer half- lives than acyclovir, take less frequentlyExample: Acyclovir 5 times a day x 5 daysValacyclovir 2 times a day x 3 daysMay increase patient adherence to chronic medAcyclovir and valacyclovirDrug-Drug Interaction with probenicidMay increase levels of these antivirals, increase side effectsPut in dosing schedule, don’t use acyclovir as much. This example shows recurrenceAcyclovir needs to be taken much more frequently depending on the infection, anywhere from four to 5 times a day for shingles and chickenpox, 2-5 times a day for suppressive therapy in genital herpes depending on the strength. Valacyclovir and famciclovir are max bid in genital herpes.Probenecid: used in gout and some STD treatments. This population likely has higher risk of STD’s so just be aware
19 FUNGAL INFECTIONS Superficial Infections Tinea (dermatophyte) infectionsNamed for site of infectionTinea pedis, corporis, cruris, capitus, etcOnychomycosisInfection of finger/toenails by dermatophytesSebborrheic dermatitisVaginal candidiasis (yeast infection)Most common species is C. albicans, though other spp are on the riseAntibiotic treatment can lead to overgrowthOTC treatment possible if uncomplicatedSuperficial involves the skin, hair and nails. Does anyone remember another name for onychomycosis? (tinea unguium) All tinea infections can be treated topically except….. Capitus and onychomycosisSubcutaneous is confined to the dermis or adjacent structures, very rare unless in tropical or exotic locationsSebborrheic dermatitis: inflammatory condition, overproduction of cells and sebum, overgrowth of normal skin fungus (yeast). Dandruff is a symptom of sebborrheic dermatitis but not all dandruff is caused by fungal overgrowth. Dandruff is always confined to scalp, whereas s.d. can be around nose and eyebrows as well.Do you remember some OTC treatments: clotrimazole cream and tablet, miconazole. When would someone have complicated yeast infection? Diabetes (high blood sugar, yeast may flourished), immunocompromised, pregnancy, recurrent infx.Oral and topical treatment are therapeutically equivalent, oral preferred due to convenience
20 FUNGAL INFECTIONS, CONT. Oropharyngeal (thrush) and Esophageal candidiasisInfection can spread from oral mucosa into esophagusRisk factors include antibiotics, inhaled steroids, dentures, smoking, immunocompromised patientsSystemic and Opportunistic InfectionsCan gain entry through GI, lungs, or IVSystemic candidiasisCan include peritonitis, pneumonia, and othersIndividuals can be carriers of Candida, and these risk factors give the yeast an opportunity to flourishSystemic is an infection involving the whole body, blood and internal organs. Opportunistic is an infection only occurring in immunocompromised individuals such as HIV infected individualsPeritonitis is inflammation of the peritoneum, which is the tissue that covers the abdominal organs. There are quite a few other systemic infections that are caused by other strains of fungi, such as invasive aspergillosis but I won’t be discussion anything other than candidia which is a yeast.
22 MECHANISM OF ACTIONTriazoles: inhibition of CYP450 enzyme dependent ergosterol synthesisKetoconazole and Terbinafine: interfere with fungal ergosterol biosynthesisNystatin: binds to sterols in cell membrane and changes permeabilityLAYMEN’s terms: prevents proper production of fungal cell membrane resulting in cell deathErgosterol is main sterol component of fungal cell membranes, inhibiting production of this allows increased permeability and leakageDisruptions in the biosynthesis of ergosterol cause significant damage to the cell membrane by increasing its permeability, resulting in cell lysis and death. Despite this mechanism of action, the triazoles are generally considered fungistatic against Candida species.
23 AZOLES Ketoconazole (Nizoral®) Fluconazole (Diflucan®) Oral tablet & topicals: cream, gel, shampoo, foamFluconazole (Diflucan®)Oral tablet and IVItraconazole (Sporanox®)Oral capsuleVoriconazole (VFEND®)Fun fact: fluconazole oral dose is equivalent to the IV dose, makes it easy to convert someone to PO
24 OTHER ANTIFUNGALS Terbinafine (Lamisil®) Nystatin (Nystat- RX®) Oral tabletsTopicals: cream, gel, solutionNystatin (Nystat- RX®)Oral tabletsOral suspensionVaginal tabletsTopical powderLamisil also OTC for treatment of athletes foot (tinea pedis) or jock itch and ring worm (tinea corporis, tinea cruris)There are multiple brand names for Nystatin. This is just one of them
25 MOST COMMON INDICATIONS Tinea Infections (1-4 wks)KetoconazoleTerbinafineOnychomycosis (6wks-1yr)ItraconazoleVaginal Candidiasis (1d- 2wks)FluconazoleNystatinOropharyngeal Candidiasis (7-14d)FluconazoleItraconazoleNystatinEsophageal Candidiasis(14-21d)VoriconazoleSystemic InfectionsBy no means ALL of the indications that they can be used for. Additionally, in each case the provider must have an understanding that the fungi they are treating will be susceptible to the drug, otherwise resistance will prevent treatment. Resistance will likely lead to reoccurrence and treatment failure.Ketoconazole is not often used systemically because the other azoles because have less drug interactions, higher safety profiles, and higher efficacy for invasive infectionsFormulations used differently:
26 PATIENT INFORMATION FOR ALL ANTIFUNGALS AdministrationSuperficial fungal infections may take a LONG time to effectively treat (weeks to months)Exception-Fluconazole for vaginal yeast infectionImportant to counsel on adherence and time to effectOnychomycosisSide EffectsOral: Headache, dizziness, changes in tasteGI upset: N/V/DCan take with food to preventException- take voriconazole 1-2 hrs before mealTopical: Irritation, burning, and drynessReminder to wash hands after administrationCounseling is crucial for fungal infections because patient adherence is directly linked to therapeutic outcome. If the patient has realistic goals initially, that there will be slow improvement over time, they are more likely to follow-through with therapy than give up after a week with no change. In onychomycosis which takes months to treat due to slow growing toenails, let the patient know that sometimes the nail will not return to normal appearance even when the fungus has been eradicated.Fluconazole for vaginal yeast infection is a one time dose, flu has half-life of 30 hours, vaginal concentrations are roughly equivalent to plasma. Symptoms begin to improve in 24 hoursItraconazole capsules should be taken with food to increase absorptionVoriconazole should be taken 1-2 hours before food to maximize absorption
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 enzymesInhibit CYP3A4, 2C9, 2C19 (warfarin, phenytoin, benzodiazepines…)Terbinafine also exhibits drug interactionsinhibits CYP2D6 (antidepressants, codeine…)Ketoconazole and Itraconazole : separate from antacids by 2 to 4 hours.Why?Voriconazole: may cause visual disturbances, photophobiaItraconazole: take with food to increase absorptionLiver functions is often tested before long-term therapy and every 6 weeks thereafter.Black Box warning is something the FDA attaches to a drug or drug class so that practitioners are aware of a specific side effect or interactionItraconazole is a good choice for onychomycosis if the patient is on CYP2D6 drugs because Terbinifine inhibits CYP2D6Oral ketoconazole/itraconazole absorption is pH dependent, so it is is decreased by antacids. Be aware if pt is on H2 antagonists and PPI they will likely have reduced absorption due to increased gastric pHWhat’s an example of a PPICYP issues:Ketoconazole: CYP3A4 substrate, inhibits 2C9 and 3A4Fluconazole: inhibits all threeItraconazole: CYP3A4 substrate, inhibits 2C and 3A4Voriconazole: CYP2C19 substrate, inhibits all three
29 QUIZ NEXT WEEK:Know COMMON counseling points about the classes of antifungals and antiviralsKnow 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!