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Echinocandin antifungals Drug Anidulafungin (Eraxis)

Indication/Dosage Candidemia, candidiasis of esophagus, intra-abdominal and peritonitis Off-label: txt of Aspergillus IV powder, IV only

MOA Noncompetitive inhibitor of synthesis of - (1,3)-D-glucagon of the cell wall; decreased glucan content leads to osmotic instability and cell lysis

CI Hypersensitivity

Kinetics Preg: C PB: 84% T1/2: 27hrs

ADEs Hypokalemia, diarrhea, DVT, abnormal LFTs, hepatic necrosis, seizure, histamine-mediated rxn

Misc - do not admin as IV bolus -rate of infusion should not exceed 1.1mg/min -reconstitute with sterile water, then further with D5W or NS

Caspofungin (Cancidas)

Txt of Aspergillus in refractory pts, candidemia, febrile neutropenia IV powder, IV only

Inhibits synthesis of (1,3)-D-glucan, an essential component of the cell wall of susceptible fungi. Highest activity in regions of active cell growth. Mammalian cells do not require (1,3)D-glucan, limiting potential toxicity.

hypersensitivity

Preg: C PB: 97% T1/2: 9-11hrs

Micafungin (Mycamine)

Esophageal candidiasis, Candida prophylaxis is pts undergoing HSCT Off-label: infxn due to Aspergillus IV powder, IV only

semisynthetic lipopeptide (echinocandin) synthesized by a chemical modification of fermentation product of Coleophoma empetri F11899, that inhibits the synthesis of 1,3 beta-D-glucan,a fundamental constituent of fungal cell walls .

Hypersensitivity

Preg: C Substrate: 3A4 (minor) Inhibits: 3A4 (weak) PB: >99% to albumin Metab: forms M-1 (catechol) and M-2 (methoxy) T1/2: 11-21hrs

Hypotension, rash, diarrhea, peripheral edema, tachycardia, increased LFTs, complication of infusion, fever, shivering, erythema multiforme, SJS, pancreatitis, hepatic necrosis, liver failure, anaphylaxis, sepsis, septic shock, Nephrotoxicity, renal impairment pleural effusion, respiratory distress, respiratory failure, WBC, Hg, Hct, phlebitis, SCr Febrile neutropenia, hemolytic anemia, intravascular hemolysis, neutropenia, thrombocytopenia, hepatitis, renal impairment, druginduced anaphylaxis, D/N/V, mucosal inflammation, constipation, hypomagnesemia

- don t mix with dextrose - admin slowly over 1 hr; do not admin as bolus (phlebitis) - reconstitute with NS or bacteriostatic water - good against fluconazole resistant species

- add NS or D5W to vial - infuse over 1 hr; do not bolus - flush existing IV line prior to infusion

Azole Antifungals MOA: triazole antifungals that inhbit 14-alpha-demethylase ezyme needed to convert lanosterol to fecosterol in the biosynthesis of ergosterol. Depletes fungi of ergosterol. This means they cant construct their membranes properly causing them to stop dividing and causing static activity Drug Indication/Dosage CI Kinetics ADEs Misc Fluconazole (Diflucan) Candidiasis Hypersensitivity Preg: C N/V, LFTs, HA, torsades de - shown resistance among C. albicans in Inhibits: 2C9, 2C19, 3A4 pointes, SJS, seizure, alopecia HIV pts Admin: IV, po PB: 11-12% (long term) - C. glabrata less susceptibility Bioavail: >90% - max rate of infusion is 200mg/hr Dosage: IV sol, pow for susp, tablet T1/2: 30hrs - high CNS penetration Itraconazole (Sporanox) BBW: Heart failure BBW: high potential for interactions Voriconazole (Vfend) Candidiasis Admin: IV, po Dosage: capsule, solution Candidiasis Admin: IV, po Dosage: tablet, IV pow for sol, po pow for sol Concomitant use of carbamazepine, 3A4 substrates, ergot alkaloids, LA barbiturates, St. John s wort, rifampin, hypersensitivity Concomitant use with 3A4 drugs, hypersensitivity, pregnant women treating onychomycosis, Preg: C Substrate: 3A4 Inhibits: 3A4, PGP PB: 99.8% Metab: 3A4 to hydroxyitraconazole Preg: D Substrate: 2C9, 2C19 Inhibits: 2C9, 3A4 PB: 58% Metab: 2C19, 2C9, 3A4 Bioavial: 96% Rash, abnormal lipids, N, HA, upper respiratory problems, CHF, SJS, hepatoxicity, anaphylaxis - Infuse over 1 hr - after admin flush line with 15-20ml NS over 30sec-15min - Avoid pregnancy use contraception 2 mo post treatment - low CNS penetration - High CNS penetration - good against fluconazole resistant species

Visual disturbances, hallucinations, SJS/TEN, pancreatitis, colored vision, hepatoxicit, Creatinine increased

Drug Colistimethate Sodium (ColyMycin M)

Indications/ Dosage CF, disease due to G(-) bacteria resistant to other AB Inj powder, IV, inhalation, IM

MOA polypeptide antibiotic, penetrates and disrupts the bacterial cell membrane of susceptible strains of aerobic gram-negative bacteria; Hydrolyzed to colistin, which acts as a cationic detergent which damages the bacterial cytoplasmic membrane causing leaking of intracellular substances and cell death Forms pores in fungal membranes that allow ion flux, resulting in fungal cell death

CI Hypersensitivity

Kinetics Preg: C Metab: hydrolyzed to colistin T1/2: 2-3hrs IV Peak: 10 min

ADEs Neurotoxicity, nephrotoxicity, acute respiratory failure, respiratory arrest, respiratory tract paralysis Warnings: CNS toxicity, Renal toxicity, respiratory arrest, superinfection Fever, chills, rigor, shaking, N/V, cardiac arrest, massive inflammatory release if admin fast, Nephrotoxicity, hypotension, hypokalemia, hypomagnesemia, pain at inj site

Misc - IV preferred due to pain caused by IM

Amphotericin B liposomoal (AmBisome), Amp B conventional (Fungizone) BBW: use for txt of progressive infections, not noninvasive infx BBW: verify product name & dosage if dose >1.5mg/kg *BBW for Fungizone Polymyxin B BBW: Nephrotoxicity BBW: neurotoxicity BBW: safety in preg unknown BBW: IM/IT only for hospitalized pts Quinupristin/Dalfopristin (Synercid)

Hypersensitivity

Preg: B T1/2: 6.3-10.7hrs

Admin: IV Dosage

- give test dose over 1030min - meperidine rigors - give over couple hours

P. aeruginosa infection Off-label: sepsis Admin: IM, IT, IV, opth Dosage: inj pow for sol Infection of skin AND/OR subcutaneous tissue Off-lable: MRSA, vanc resistant Enterocccus Admin: IV Dosage: IV pow for sol

Binds to phospholipids, alters permeability, and damages the bacterial cytoplasmic membrane permitting leakage of intracellular constituents

Hypersensitivity, concurrent use of neuromuscular blockers

Preg: B PB: 79-92% T1/2: 6 hrs

Inj site pain, neurotoxicity, irritability, weakness, ataxia, numbness, blurred vision, neuromuscular blockade, paralysis, respiratory depression, nephrotoxicity

inhibits bacterial protein synthesis by binding to different sites on the 50S bacterial ribosomal subunit thereby inhibiting protein synthesis

Hypersensitivity

Preg: B

Inj site edema, inj site inflammation, inj site pain, inj site rxn, hyperbilirubinemia, MI, syncope, acidosis, GI hemorrhage, pancreatitis, hepatitis, anaphylaxis, myasthenia, cerebral hemorrhage, encephalopathy

- Infuse over 1 hr -flush line with D5W before and after

Metronidazole (Flagyl) BBW: possibly carcinogenic Admin: po,IV Dosage: capsule, tablet, , ER tab, cream, jelly/gel, lotion

active against most obligate anaerobic bacteria and protozoa by undergoing intracellular chemical reduction via mechanisms unique to anaerobic metabolism. Reduced metronidazole, which is cytotoxic but short-lived, interacts with DNA to cause a loss of helical structure, strand breakage, and resultant inhibition of nucleic acid

Hypersensitivity, EtOH use during and 3 days after use, concomitant use with or within last 2 st weeks of disulfiram , 1 trimester pregnancy

Preg: B Inhibits: 3A4 T1/2: 6-8hrs Peak: 1-2hrs

N, Jarisch Herxheimer rxn, HA, candida infection of genital region, vaginal discharge, SJS/TEN, leukpenia, asceptic meningitis, encephalopathy, peripheral neuropathy, seizure, otoxicity, hemolytic uremic syndrome

- do not use equipment containing Al - can cause reddish-brown urine

synthesis and cell death.

MACROLIDES: MOA: Bacteriostatic. Bind to 50S ribosomal subunit, resulting in inhibition of protein synthesis. Nucleic acid synthesis is not affected. Spectrum: G+ aerobes (S. aureus, S. pneumonia), G- aerobes (H. influenza, M. catarrhalis, Legionella), anaerobes (peptostreptococcus, peptococcus, Bacteriodes [aka Prevotella]), M. pneumonia, Chlamydia pneumonia (TWAR), Agent Contraindications Dosage/Admin Kinetics Adverse effects Pt. Counseling Azithromycin (Zithromax, Zmax) Preg cat B Hypersensitivity Drug Interactions: Antiarrhythmic agents, fluoroquinolones (prolong QT), benzodiazepines (may increase CNS sedation), HMG CoA reductase inhibitors (rhabdomyalysis), Warfarin (anticoag effects enhanced) Available as 250, 500, 600mg tablets; powder for suspension, and lyophilized powder for injection (Zmax). Non-hospitalized: 5-day regimen 500mg po x 1 day then 250mg po x 4 days Or Azithromycin ER 2g x 1 day Hospitalized: 500mg IV as single daily dose x 2 days, followed by 500mg po x 7-10 days Available as 250mg, 500mg, 500mg ER tablets and granules for suspension. Non-hospitalized: 250 - 500mg po bid x 7 to 14 days Or ER 1000mg/day x7 days 1-2 g/day (only for previously healthy patients with no recent AB treatment). Not recommended at all per Sanford guide Half-life: 68 h Some hepatic metabolism to inactive. Excreted unchanged in bile QT prolongation Allergic reaction, pain at injection site, abdominal pain, N/V/D, vaginitis May take tablets without regard to meals. Take suspension on empty stomach.

Clarithromycin (Biaxin, Biaxin XL)

Same as above plus cimetidine, PPIs, Preg cat C

Erythromycin (Ery-tab)

Same as above Preg cat B

Bioavailability ~ 50% t - 3 to 9 hours Metabolized in liver to active metabolite. (CYP3A substrate) Renal clearance t - 1.6 h Metabolized in liver to inactive. (CYP3A substrate) Excreted in urine and bile

QT prolongation Headache, rash, abdominal pain, abnormal taste, N/V/D, flatulence,

May take without regard to meals. Grapefruit juice may inhibit metabolism! Take on empty stomach

Hepatic function impairment; Aggravation of myasthenia gravis symptoms

RESPIRATORY FLUOROQUINOLONES MOA: Bacteriocidal. Synthetic, broad-spectrum antibacterial agents that inhibit DNA gyrase and topoisomerase IV. Spectrum: G- (like everything Bacteroides, Chlamydia, Fusobacterium, H. influenza, Klebsiella, Mycoplasm, Pseudomonas), G+ (S. aureus, S. pneumonia), Atypical (Legionella, Mycoplasma, Chlamydia), Anaerobe (Bacteriodes, Peptostreptococcus, clostrid) Agent Contraindications Dosage/Admin Kinetics Adverse effects Pt. Counseling Moxifloxacin (Avelox, Vigamox) Gatifloxacin (Zymar) Boxed Warning: tendon rupture Drug Interactions: Antacids, cimetidine NOT AVAILABLE ANYMORE! Oral tablets, I.V.: 400 mg every 24 hours for 7-14 days Metabolized by glucuronide and sulfate conjugation (no CYP) QT Prolongation, Dizziness, decreased serum glucose, N, diarrhea, dermatologic hypersensitivity QT prolongation Do not take with antacids. May cause severe nausea or taste perversion. Use sunscreen

Levofloxacin (Levaquin)

Gemifloxacin (Factive) Ciprofloxacin (Cipro)

Boxed Warning: tendon rupture Drug Interactions: Antacids, cimetidine. Warfarin (increased INR levels) Clearance reduced in renal patients Same as above

Available as 250, 500, 750mg tabs, 25mg/mL solution, Injection solution 5mg/mL or 25mg/mL Dosage: PO/ IV 500mg/d x 7- 14d or 750mg/d x 5 days Tablets 320mg Take 320mg po qday x 5-7 days IV, po. IV sol, oral pow for sol

Limited metabolism. Excreted in urine mostly as unchanged drug. t : 6-8h Limited hepatic metabolism (CYP not involved); excreted in urine (36%) and feces (61%); t = 7h Preg: C

Hypersensitivity, concomitant tizanidine admin

QT prolongation, HA, insomnia, dizziness, N/V/D, taste disturbance, constipation, dyspepsia, pharyngitis, hypoglycemia HA, dizziness, rash, N/V/D, phototoxicity, QT prolongation N/D, dizziness, burning sensation in eye, restlessness, SJS/TEN, peripheral neuropathy, seizure, tendon rupture, aplastic anemia, agranulocytosis, photosensivitiy,

Do not take with antacids. May cause severe nausea or taste perversion. Use sunscreen and avoid direct sunlight Do not take with antacids. Use sunscreen and avoid direct sunlight - Don t take with milk, yogurt - Take 2hrs before or 6 hrs after Mg/Al containing antacids or products containing Ca, Fe, Zn - Avoid caffeine

AMINOPENICILLINS MOA: Bacteriocidal. Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs), which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. May be combined with beta-lactamase inhibitor (clavulanic acid) Spectrum: G+ (Strep. pneumonia, not good for Staph), Very little Gram neg., Anaerobes (Peptococcus, Peptostreptococcus, Clostridium) Agent Contraindications Dosage/Admin Kinetics Adverse effects Pt. Counseling Amoxicillin (Amoxil, Trimox, Moxatag) Penicillin allergy, infectious mononucleosis (rash will develop), caution in renal patients Drug interactions: oral contraceptives Penicillin allergy, clavulanate hypersensitivity, hepatic or renal impairment, infectious mononucleosis (rash) Penicillin allergy, mononucleosis, renal patients Penicillin allergy, Cystic fibrosis (causes rash and fever) Available as capsules, tablets, chewable tablets, and powder for suspension. Dosage: 875mg q 12 h Or 500mg q 8 h for 10 days? Available as tablets, extended release tablets, chewable tablets, and powder for suspension. Dosage for CAP: ER tablet:two 1000mg tablets q12h x 7-10 days Available as injection powder for reconstitution Dosage: IV 3g q6h IV 4.5g q 6 h x 7-14 days Partially hepatic metabolism; Rapid, complete absorption; t = 1h Clavulanate hepatic metabolism, renal excretion t = 1h Excreted in urine (90% as unchanged drug) Anxiety, confusion, dizziness, rash, black hairy tongue, NVD, tooth discoloration May take with food

Amoxicillin with Clavulanate (Augmentin, Aug. ER, Aug. ES-600; Amoclan) Ampicillin-sulbactam (Unasyn) Piperacillin-tazobactam (Zosyn)

Diarrhea, rash, vaginitis, nausea, vomiting, and others from above

May take with food

Fever, penicillin encephalopathy, seizure, N/V/D, black hairy tongue, sore mouth Confusion, convulsions, fever, anaphylaxis, myoclonus, hypokalemia, prolonged PT

CEPHALOSPORINS MOA: Usually bactericidal. Inhibit mucopeptide synthesis in the bacterial cell wall, making it defective and osmotically unstable Spectrum: Depends on class Agent Generation / Spectrum Contraindications Dosage/Admin Cefpodoxime proxetil (Vantin) Cefprozil (Cefzil) Cefuroxime (Ceftin, Zinacef) 3 gen G+ (staph, strep), G- (H. influenza, M. catarrhalis, Pseudomonas) nd 2 gen G+ (staph, strep), G- (H. influ., M. cat) 2nd gen G+ (staph, strep), G- (H. influ., M. cat),
rd

Kinetics De-esterified in GI tract to active metabolite cefpodoxime

Adverse effects Diarrhea, N/V, rash, HA, vaginitis

Pt. Counseling Take with or without food

Ceph allergy

Ceph allergy

Ceph allergy Pen allergy

Tablets: 100mg, 200mg Granules for susp: 50mg/5mL,100mg/5mL Dosage: 200mg q 12h x 14 days 250mg, 500mg tablet Powder for suspension Dosage for CAP not listed Available as oral tablet and suspension, and IV/IM injection and infusion

Same as above

Same as above Eosinophilia

anaerobes (Bacteriodes, Peptococcus, Peptostrepto-coccus) Cefotaxime (Claforan) 3 gen G+ (Staph, strep), G- (H. influ., Klebsiella, Pseudomonas), anaerobes (Bacteriodes, Fusiparum, Peptococcus, Peptostreptococ) 3rd gen G+ (Staph, strep), G- (H. influ., Klebsiella, Pseudomonas), anaerobes (Bacteriodes)
rd

Renal patients Drug interactions: H2RAs, antacids Same as above

Dosage for CAP: IM/IV: 750mg q 8 h IV: 1-2g q 6-8h x 4-7 days Arrhythmia after rapid IV injection; N/V/D, rash May cause elevated INR Same as above

Ceftriaxone (Rocephin)

Cefepime (Maxipime)

3 gen Same as above

rd

Use with caution in patients with seizure disorders

I.V.: 1 g once daily, usually in combination with a macrolide; consider 2 g/day for patients at risk for more severe infection and/or resistant organisms (ICU status, age >65 years, disseminated infection) IV: 1-2 g every 12 hours for 10 days

CARBAPENEMS MOA: Static/Cidal. Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins; which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested. Spectrum: Broad spectrum G+/G-. No MRSA or enterococcus. Ertapenem has no pseudomonas activity Agent Contraindications Dosage/Admin Kinetics Adverse effects Misc Doripenem (Doribax) Anaphylactic rxn to other beta-lactams or other drugs in class Hypersensitivity, renal patients, patients with CNS problems (seizure potential), IM dose is mixed with lidocaine, so inquire about lidocaine sensitivity Hypersensitivity, renal patients, patients with CNS problems (seizure potential), IM dose is mixed with lidocaine, so inquire about lidocaine sensitivity Hypersensitivity, renal patients, patients with CNS problems (seizure potential), IV over 1 hr Dosage: IV pow for susp IM, IV: 1 g/day; duration of total antibiotic treatment: 10-14 days (Note: Duration includes possible switch to appropriate oral therapy after at least 3 days of parenteral treatment, once clinical improvement demonstrated.) I.M.: Mild/moderate: 500-750 mg every 12 hours Pseudomonas infections: I.V.: 500 mg every 6 hours; Note: Higher doses may be required based on organism sensitivity For CAP: give in combo with ciprofloxacin, levofloxacin, or aminoglycoside Pseudomonas: I.V.: 1 g every 8 hours Preg: B rash, HA, yeast infections, phlebitis, N, SJS/TEN, C.diff, seizure Edema, chest pain, HTN, tachycardia, HA, altered mental status, fever, insomnia, N/V/D - Does not cover Pseudomonas - better for community acquired infections - IM product contains lidocaine

Ertapenem (Invanz)

No CYP-mediated metabolism

Imipenem and Cilastin (Primaxin)

High seizure risk

Meropenem (Merrem IV)

HA, anemia, N/V/D, hypoglycemia

Cilastatin prevents renal metabolism of imipenem by competitive inhibition of dehydropeptidase along the brush border of the renal tubules. - Not effective for MRSA - 50% cross allergic with pens - Only one approved for meningitis

MONOBACTAMS MOA: Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested. Monobactam structure makes cross-allergenicity with beta-lactams unlikely. High degree of resistance to hydrolysis by beta-lactamase. Spectrum: G- (H. influenza, Klebsiella, Pseudomonas)

Agent Aztreonam (Azactam, Cayston)

Contraindications Rare cross-allergy to cephs and pens. Use with caution in renal patients

Dosage/Admin Available as oral inhalation (Cayston), and IM/IV injection Dosage: I.V.: 2 g every 6-8 hours; maximum: 8 g/day Give in combo with levofloxacin or moxifloxacin, or gatifloxacin, with or without aminoglycoside

Kinetics

Adverse effects Rash, N/V/D, thrombophlebitis, pain at injection site

Pt. Counseling