ID1_20-26.pdf Antibiotic Drug Interactions PDF

RxPrep Course Book | RxPrep 02019, RxPrep 02020 Sulfonamide Drug Interactions SMX /TMP is a moderate - strong inhibitor of CYP2C8 and CYP2C9 and can cause significantly T INR . Caution should be used in combination with warfarin (see the Learning Drug Interactions chapter for more information) . Le...

RxPrep Course Book | RxPrep 02019, RxPrep 02020 Sulfonamide Drug Interactions SMX /TMP is a moderate - strong inhibitor of CYP2C8 and CYP2C9 and can cause significantly T INR . Caution should be used in combination with warfarin (see the Learning Drug Interactions chapter for more information) . Levels of SMX /TMP can be i by CYP2C8 and CYP2C9 inducers . The therapeutic effects of SMX / TMP can be diminished by the use of leucovorin or levoleucovorin. The risk for hyperkalemia will T if used in combination with ACE inhibitors, ARBs, aliskiren, aldosterone receptor antagonists ( ARAs ) , potassium- sparing diuretics, NSAIDs, cyclosporine, tacrolimus, drospirenone -containing oral contraceptives or canagliflozin . KEY FEATURES OF SULFAMETHOXAZOLE / TRIMETHOPRIM Common Uses CA - MRSAskin infections, UTI, Pneumocystis pneumonia (PCP) 5:1 Ratio of SMX / TMP ( Dose by TMP) Single strength ( SS) tablet contains 80 mg TMP Double strength (DS) tablet contains 160 mg TMP usual dose is 1 tablet BID Sulfa Allergy Most sulfa allergies occur with SMX/TMP (rash /hives are common) Rarely, severe skin reactions (e.g., SJS or TEN) can occur; if rash is accompanied by a fever or systemic symptoms, seek emergency care INR T when used with warfarin. Use alternative antibiotic when possible. ANTIBIOTICS FOR GRAM - POSITIVE INFECTIONS VANCOMYCIN Vancomycin is a glycopeptide that inhibits bacterial cell wall synthesis by binding to the D -alanyl - D - alanine cell wall precursor and blocking peptidoglycan polymerization . Vancomycin only covers Gram - positive bacteria, including Staphylococci ( MRSA ) , Streptococci , Enterococci ( not VRE) and C. difficile ( using the PO route only ) . DRUG DOSING SAFETY/ SIDE EFFECTS / MONITORING Vancomycin (Vancocin, Firvanq oral solution) Systemic infections (IV only) IV: 15 - 20 mg / kg Q8-12H Capsule, oral solution, injection Dose based on total body weight WARNINGS Ototoxicity and nephrotoxicity; caution with use of other nephrotoxic or ototoxic drugs or with prolonged high serum concentrations (dose adjustment required in renal impairment) First -line treatment for MRSA infections Consider alternative drug when MRSA MIC 2 mcg/mL CrCI 20- 49 mL/min; Q24H CrCI < 20 mL/min: give 1 dose, then dose per levels Peripheral IV infusions should not exceed 5 mg/mL C. difficile infections (PO only) PO: 125 - 500 mg Q I D x l O days (upper end used for severe, complicated disease) No dose adjustment in renal impairment PO is used only for C. difficile colitis and enterocolitis, not for systemic infections Infusion reaction/red man syndrome (maculopapular rash, hypotension, flushing and chills from too rapid of an infusion rate - do not infuse faster than 1 gram per hour) SIDE EFFECTS Abdominal pain, nausea (oral route), phlebitis (irritation to vein), myelosuppression (neutropenia /thrombocytopenia), drug fever, severe skin reactions (SJS/ TEN) MONITORING Renal function, trough serum concentration at steady state (generally 30 minutes before the 4th or 5 th dose), WBC Goal trough: 15 - 20 mcg/mL - pneumonia, endocarditis, osteomyelitis, meningitis, bacteremia Goal trough: 10-15 mcg/ mL - other infections See lab interactions , storage requirements and renal dosage information near the end of this chapter . Vancomycin Drug Interactions The risk of nephrotoxicity is T when used with other nephrotoxic drugs ( e.g. , aminoglycosides, amphotericin B , cisplatin, polymyxins , cyclosporine, tacrolimus, loop diuretics, NSAIDs and radiographic contrast dye ) . Vancomycin can T the risk of ototoxicity when used with other ototoxic drugs ( e .g. , aminoglycosides, cisplatin , loop diuretics) . 3< 22 | INFECTI0U 5 DI 5 EASES h BACKGROUND & ANTIBACTERIALS BY DRUG CLASS LIPOGLYCOPEPTIDES Lipoglycopeptides ( with the generic name suffix "- vancin") inhibit bacterial cell wall synthesis by l ) binding to the D-alanyl D -alanine portion of the cell wall , blocking polymerization and cross- linking of peptidoglycan, and 2) disrupting bacterial membrane potential and changing cell permeability ( due to the presence of a lipophilic side chain ). They have concentration dependent antibacterial activity and have similar coverage to vancomycin (with the exception that they only come in IV form and cannot be used to treat C. difficile infections). DRUG DOSING SAFETY/ SIDE EFFECTS /MONITORING Telavancin (Vibativ ) IV: 10 mg/kg daily Injection CrCI < 50 mL/min: dose BOXED WARNINGS Fetal risk - obtain pregnancy test prior to starting therapy; nephrotoxicity; T mortality with pre-existing moderate- to- severe renal impairment (CrCI 50 mL/min) when compared to vancomycin in pneumonia trials adjustment required Approved for complicated skin and soft - tissue infections (SSTI) and hospital-acquired and ventilator - associated pneumonia Infuse over 60 minutes to prevent infusion reaction CONTRAINDICATIONS Concurrent use of IV unfractionated heparin (UFH) WARNINGS Can falsely T coagulation tests (e.g., aPTT/ PT/ INR), but does not T bleeding risk; red man syndrome with rapid IV administration ( give over > 60 minutes); QT prolongation SIDE EFFECTS Metallic taste, N / V, T SCr foamy urine . MONITORING Renal function, pregnancy status Oritavancin (Orbactiv ) Injection Approved for SSTI Single- dose IV regimen: 1,200 mg Infuse over 3 hours CrCI < 30 mL/min: has not been studied, use with caution CONTRAINDICATIONS Oritavancin: use of IV UFH for 120 hours (5 days) after oritavancin administration due to interference (false elevations) with aPTT laboratory results WARNINGS Can cause falsely T PT/ INR for up to 12 hours and aPTT for up to 120 hours after a dose Oritavancin: use a different antibiotic if osteomyelitis is confirmed or suspected Dalbavancin (Dalvance) Injection Approved for SSTI Single - dose IV regimen: 1,500 mg Dalbavancin: infusion reactions (red man syndrome) with rapid IV administration; T ALT > 3 x the upper limit of normal Two- dose IV regimen: 1,000 mg x 1 then 500 mg one week later SIDE EFFECTS Infusion reaction (red man syndrome), N/V/ D, headache, rash . Infuse over 30 minutes CrCI < 30 mL/min (not on dialysis): dose adjustment required MONITORING Signs of osteomyelitis (oritavancin), LFTs, renal function NOTES Extremely long half -life allows a single- dose regimen for both See lab interactions , storage requirements and renal dosage information near the end of this chapter. Telavancin/Oritavancin Drug Interactions Avoid telavancin in patients with congenital long QT syndrome, known QT prolongation or uncompensated heart failure. Use caution with other medications known to prolong the QT interval ( see the Arrhythmias chapter ). Oritavancin is a weak inhibitor of CYP2C9 and CYP2C19, and a weak inducer of CYP3A4 and CYP2D6. Use caution when coadministered with drugs metabolized by these enzymes (including warfarin ). *2 . RxPrep Course Book | RxPrep © 2019 RxPrep © 2020 DAPTOMYCIN Daptomycin is a cyclic lipopeptide. It binds to cell membrane components, causing rapid depolarization; this inhibits all intracellular replication processes, including protein synthesis , and causes cell death. Daptomycin has concentration dependent antibacterial activity against most Gram - positive bacteria , including Staphylococci (MRSA ) and Enterococci ( both species of VRE , E. faecium and E . faecalis ) . DRUG DOSING SAFETY/ SIDE EFFECTS /MONITORING Daptomycin (Cubicin, Cubicin RF ) SSTI: 4 mg/kg IV daily WARNINGS Eosinophilic pneumonia - generally develops 2- 4 weeks after treatment initiation Injection Approved for complicated skin and soft - tissue infections (SSTI) and S. aureus ( MRSA) bloodstream infections, including right - sided endocarditis Bacteremia /right sided endocarditis: 6 mg/kg IV daily CrCI < 30 mL/min: dose adjustment required Myopathy and rhabdomyolysis - discontinue in patients with s /sx and CPK > 1,000 units/L (5 x ULN), or in asymptomatic patients with a CPK > 2,000 units/ L ( lOx ULN); consider temporarily withholding other drugs that can cause muscle damage (e.g., statins) during treatment . Can falsely T PT/INR but does not T bleeding risk Peripheral neuropathy SIDE EFFECTS * CPK, abdominal pain, pruritus, chest pain, edema, hypertension, acute kidney injury MONITORING CPK level weekly (more frequently if on a statin or with renal impairment): muscle pain/ weakness, s/ sx of neuropathy, dyspnea Do not use to treat pneumonia: drug is inactivated in the lungs by surfactant NOTES Cubicin: compatible with NS and LR (no dextrose) Cubicin RF: compatible with NS (no dextrose) but must use only sterile or bacteriostatic water for injection to reconstitute the lyophilized powder (before diluting further with NS) See lab interactions , storage requirements and renal dosage information near the end of this chapter: Daptomycin Drug Interactions Daptomycin can have additive risk of muscle toxicity when used in conjunction with statins. OXAZOLIDINONES Linezolid and tedizolid bind to the SOS subunit of the bacterial ribosome , inhibiting translation and protein synthesis. They have coverage similar to vancomycin, but also cover VRE ( E . faecium and E. faecalis ) . DOSING SAFETY/ SIDE EFFECTS / MONITORING Linezolid ( Zyvox ) PO/IV: 600 mg Q12H Tablet, suspension, No dose adjustment in renal impairment CONTRAINDICATIONS Do not use with or within 2 weeks of MAO inhibitors DRUG injection IV:PO ratio is 1:1 WARNINGS Duration-related myelosuppression (thrombocytopenia, anemia, leukopenia), peripheral and optic neuropathy when used > 28 days, serotonin syndrome, hypoglycemia caution with insulin or other hypoglycemic drugs, seizures, lactic acidosis; T BP - use caution and monitor BP in patients with uncontrolled hypertension and untreated hyperthyroidism SIDE EFFECTS Iplatelets,IHgb, 1WBC, HA, nausea, diarrhea.T LFTs MONITORING HR, BP BG (DM), weekly CBC, visual function . NOTES Do not shake linezolid suspension Tedizolid (Sivextro) PO/ IV: 200 mg daily for 6 days Tablet, injection Infuse over 1 hour, stable in NS Approved for SSTI No dose adjustment in renal impairment IV:PO ratio is 1:1 WARNINGS Consider alternative treatment in patients with neutropenia SIDE EFFECTS Nausea, diarrhea, paresthesias, hypertension, visual impairment, blurred vision (less Gl side effects and myelosuppresion compared to linezolid) See lab interactions, storage requirements and renal dosage information near the end of this chapter. : 36 22 I INFECTIOUS DISEASES It BACKGROUND & ANTIBACTERIALS BY DRUG CLASS Linezolid /Tedizolid Drug Interactions Linezolid and tedizolid are reversible monoamine oxidase inhibitors. Avoid tyramine -containing foods and serotonergic drugs ( see the Learning Drug Interactions chapter ). Linezolid can exacerbate hypoglycemic episodes; use caution in patients receiving insulin or oral hypoglycemic drugs (e.g., sulfonylureas ). QUINUPRISTIN/ DALFOPRISTIN This drug is a streptogramin; it binds to the 50S ribosomal subunit inhibiting protein synthesis. Quinupristin /dalfopristin covers most Gram - positive bacteria, including Staphylococci ( MRSA ) and Enterococcus faecium (VRE, but not E. faecalis ) . It is approved for complicated skin and soft - tissue infections, but is not well - tolerated; use is typically limited to vancomycin resistant E. faecium infections. DRUG DOSING SAFETY/ SIDE EFFECTS / MONITORING Quinupristin/ Dalfopristin (Synercid) IV: 7.5 mg/kg Q8 -12H Injection No dose adjustment in renal impairment SIDE EFFECTS Arthralgias /myalgias (up to 47% of patients), infusion reactions, including edema and pain at infusion site (up to 44% of patients), phlebitis (up to 40% of patients), hyperbilirubinemia (up to 35% of patients), CPK elevations, Gl upset, T LFTs Infuse over 60 minutes NOTES Dilute in D5 W only Administer via central line, such as a peripherally inserted central catheter (PICC), to avoid phlebitis See lab interactions, storage requirements and renal dosage information near the end of this chapter . Quinupristin/ Dalfopristin Drug Interactions Quinupristin /dalfopristin is a weak CYP3A4 inhibitor; it can T levels of CCBs, cyclosporine, dofetilide and others. TIGECYCLINE Tigecycline is a glycylcycline. It binds to the 3OS ribosomal subunit inhibiting protein synthesis; structurally, it is related to the tetracyclines. Tigecycline has a broad -spectrum of activity against Gram - positive bacteria, including Staphylococci ( MRSA ) and Enterococci ( VRE ) , Gram - negative bacteria , anaerobes and atypical organisms. Among the Gram - negatives, it has no activity against the "3 P's": Pseudomonas, Proteus, Providencia species. Tigecycline is approved for complicated skin and soft -tissue infections, intra-abdominal infections and community-acquired pneumonia; use is limited ( see Boxed Warning) . DRUG DOSING SAFETY/ SIDE EFFECTS / MONITORING Tigecycline ( Tygacll ) IV: 100 mg x 1 dose, then 50 mg Q12H BOXED WARNING T risk of death, use only when alternative treatments are not suitable Injection Derivative of minocycline Severe hepatic impairment: dose adjustment required No adjustment in renal impairment WARNINGS Hepatotoxicity, pancreatitis, photosensitivity, teeth discoloration in children < 8 years old (avoid use) Lower cure rates in ventilator - associated pneumonia SIDE EFFECTS N / V/ D, headache, dizziness, T LFTs, rash/severe skin reactions (SJS) NOTES Do not use for bloodstream infections; it does not achieve adequate concentrations in the blood since it is lipophilic (drug distributes quickly out of the blood into tissues) Reconstituted solution should be yellow-orange; discard if not this color See lab interactions , storage requirements and renal dosage information near the end of this chapter. Tigecycline Drug Interactions Tigecycline can T the INR in patients taking warfarin. 164 . RxPrep Course Book | RxPrep © 2019 RxPrep © 2020 ADDITIONAL BROAD- SPECTRUM DRUGS POLYMYXINS The polymyxin class consists of two drugs, colistimethate (sometimes referred to as colistin ) and polymyxin B. Colistimethate is an inactive prodrug that is hydrolyzed to colistin. Colistin acts as a cationic detergent and damages the bacterial cytoplasmic membrane, causing leaking of intracellular substances and cell death. Polymyxins cover Gram -negative bacteria, such as Enterobacter spp., E. coli , Klebsiella pneumoniae and Pseudomonas aeruginosa ( they do not cover Proteus spp.). Due to the risk of toxicides, they are used primarily for MDR Gram - negative pathogens in combination with other antibiotics. DRUG DOSING SAFETY/ SIDE EFFECTS / MONITORING Colistimethate sodium IV/IM: 2.5 - 5 mg/kg/dayin 2 - 4 divided doses WARNING Dose- dependent nephrotoxicity (monitor renal function and electrolytes), neurotoxicity (dizziness, headache, tingling, oral paresthesia, vertigo) (Coly - Mycin M ) Injection (can be used for inhalation administration) Dose is expressed in terms of colistin base activity CrCI < 80 mL/min: dose adjustment required Solutions for inhalation must be mixed immediately prior to administration Polymyxin B sulfate Injection NOTES Colistimethate sodium is a prodrug that is converted to colistin (the active form); assess dose carefully, as it can be represented in units of colistimethate sodium, mg of colistimethate sodium, or mg of colistin base activity Avoid use with other nephrotoxic medications Neurotoxicity can result in respiratory paralysis from neuromuscular blockade IV: 15,000- 25,000 units/kg/ day divided every 12 hours BOXED WARNINGS Nephrotoxicity (dose- dependent) CrCI < 80 mL/min: dose adjustment required Neurotoxicity (dizziness, tingling, numbness, paresthesia, vertigo) Safety in pregnancy is not established Should only be administered to hospitalized patients Avoid concurrent or sequential use of other neurotoxic or nephrotoxic drugs Neurotoxicity can result in respiratory paralysis from neuromuscular blockade MONITORING Renal function NOTES 1 mg = 10,000 units polymyxin B See lab interactions , storage requirements and renal dosage information near the end of this chapter. Polymyxin Drug Interactions Other nephrotoxic drugs can enhance the nephrotoxic effects ( refer to the Aminoglycoside section ). CHLORAMPHENICOL Chloramphenicol reversibly binds to the 50S subunit of the bacterial ribosome inhibiting protein synthesis. It covers Gram positives, Gram - negatives, anaerobes and atypical organisms. DRUG DOSING SAFETY/ SIDE EFFECTS / MONITORING Chloramphenicol IV: 50-100 mg/kg/day in divided doses Q 6H (max 4 grams/ day) BOXED WARNING Serious and fatal blood dyscrasias (aplastic anemia, pancytopenia - may be irreversible) Injection Rarely used due to adverse effects No adjustment in renal impairment, but use with caution WARNINGS Gray syndrome with high serum levels - circulatory collapse, cyanosis, acidosis, abdominal distention, myocardial depression, coma and death MONITORING CBC at baseline and every 2 days during therapy, LFTs, renal function, serum drug concentrations See lab interactions, storage requirements and renal dosage information near the end of this chapter. w 22 | INFECTIOUS DISEASES l BACKGROUND & ANTIBACTERIALS BV DRUG CLASS MISCELLANEOUS ANTIBIOTICS CLINDAMYCIN Clindamycin is a lincosamide which reversibly binds to the 50S subunit of the bacterial ribosome inhibiting protein synthesis. It covers most anaerobes and Gram- positive bacteria (including some community-associated MRSA) . It does not cover Enterococcus or Gram - negative pathogens. DRUG DOSING SAFETY/ SIDE EFFECTS / MONITORING Clindamycin (Cleocin ) PO: 150-450 mg Q6H Injection, capsule, suspension IV: 600-900 mg Q8H BOXED WARNING Colitis (C. difficile ) . . Topical: foam gel lotion, No dose adjustment in renal impairment kit, solution, swab (Cleocin -T, Clindagel , Clindacin ETZ , Clindacin Pac , Clindacin - P, Evoclin ) WARNING Severe or fatal skin reactions ( SJS /TEN /DRESS) SIDE EFFECTS N /V/ D, rash, urticaria, T LFTs (rare) NOTES An induction test (D- test) should be performed on S aureus that is susceptible to clindamycin but resistant to erythromycin; a flattened zone between the disks (positive D-test) indicates inducible clindamycin resistance and clindamycin should not be used Vaginal: cream, suppository (Clindesse, Cleocin) . Common uses: purulent and non-purulent skin infections, beta- lactam alternative for dental abscesses See lab interactions , storage requirements and renal dosoge information near tbe end of this chapter. METRONIDAZOLE AND RELATED DRUGS These antibiotics cause a loss of helical DNA structure and strand breakage resulting in inhibition of protein synthesis. Metronidazole has activity against anaerobes and protozoal infections. It is effective for bacterial vaginosis, trichomoniasis, giardiasis, amebiasis, C. difficile and is used in combination regimens for intra -abdominal infections. Tinidazole is structurally related to metronidazole, but activity is limited to protozoa (giardiasis, amebiasis) , trichomoniasis and bacterial vaginosis organisms. Secnidazole, a newer drug in the class, is only indicated for bacterial vaginosis. DRUG DOSING SAFETY / SIDE EFFECTS / MONITORING Metronidazole ( Flagyl , Metro) PO/ IV: 500-750 mg Q8-12H or 250- 500 mg Q6- 8H BOXED WARNING Possibly carcinogenic based on animal data Tablet, capsule, injection No dose adjustment in renal impairment Topical: MetroCream, Metrogel, MetroLotion, Take immediate- release tablets with food to >1 Gl upset CONTRAINDICATIONS Pregnancy (1st trimester), use of alcohol or propylene glycol - containing products during treatment or within 3 days of treatment discontinuation (disulfiram reaction) Noritate, Rosadan IV:PO ratio is 1:1 Vaginal: MetroGel Vaginal, Nuvessa Vandazole . Metronidazole: use of disulfiram within the past 2 weeks Tinidazole: breastfeeding WARNINGS CNS effects: seizures, peripheral neuropathy Metronidazole: aseptic meningitis, encephalopathy, optic neuropathy Tinidazole (Tindamax ) 2 grams PO daily Tablet Take with food to minimize Gl effects Metallic taste HA. nausea, furry tongue, darkened urine, dizziness, rash /severe skin reactions (SJS/TEN) No adjustment in renal impairment NOTES See the ID II chapter for a discussion on use for STIs in pregnancy Secnidazole (Solosec ) PO: 2 gram single dose Granule packet Sprinkle contents of 1 packet onto applesauce, yogurt, or pudding and consume within 30 minutes; do not chew the granules WARNINGS Possibly carcinogenic (based on animal data with structurally similar drugs) Approved only for bacterial vaginosis 166 SIDE EFFECTS . SIDE EFFECTS Vulvovaginal candidiasis HA, N /D See lab interactions, storage requirements and renal dosage information near the end of this chapter. . RxPrep Course Book | RxPrep © 2019, RxPrep © 2020 Metronidazole and Tinidazole Drug Interactions Metronidazole is a weak inhibitor of CYP3A4 and CYP2C9. Tinidazole is a minor substrate of CYP3A4. Metronidazole and tinidazole should not be used with alcohol ( during and for 3 days after discontinuation of treatment ) due to a potential disulfiram -like reaction ( abdominal cramping , nausea / vomiting, headaches, and flushing ). Metronidazole, and potentially tinidazole, can T INR in patients taking warfarin. FIDAXOMICIN Fidaxomicin inhibits RNA polymerase, resulting in inhibition of protein synthesis and cell death. It is used for C. difficile infections. DRUG DOSING SAFETY/ SIDE EFFECTS / MONITORING Fidaxomicin (Dificid ) PO: 200 mg BID x 10 days Tablet No dose adjustment in renal impairment WARNINGS Not effective for systemic infections - absorption is minimal SIDE EFFECTS N / V, abdominal pain, Gl bleeding, anemia . See lab interactions, storage requirements and renal dosage information near the end of this chapter RIFAXIMIN Rifaximin inhibits bacterial RNA synthesis by binding to bacterial DNA- dependent RNA polymerase. It is structurally related to rifampin. It covers E. coli. DRUG DOSING SAFETY/ SIDE EFFECTS / MONITORING Rifaximin ( Xifaxan ) Travelers' diarrhea: Tablet PO: 200 mg TID x 3 days SIDE EFFECTS Peripheral edema, dizziness, headache, flatulence, nausea, abdominal pain, rash/pruritus Reduction of hepatic encephalopathy recurrence: PO: 550 mg BID NOTES Not effective for systemic infections (< 1% absorption) Irritable bowel syndrome w /diarrhea ( IBS- D): PO: 550 mg TID x 14 days Used as salvage treatment in patients with C. difficile infection No dose adjustment in renal impairment . See lab interactions , storage requirements and renal dosage information near the end of this chapter 36: