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Drug Interactions - Table of contents
Dr. Gé za Lakner
Preventable Drug-Related Morbidity (PDRM) Important principles for physicians to consider when prescribing any drug Postmarket ADE Reports by Top-10 Ranked Classes of Suspect Drugs (FDA, 1995) Barriers to Improved Monitoring and Reporting of ADEs Factors affecting serum drug concentration Competitive interaction for serum protein binding of clinical significance Environmental factors affecting the activity of the intestinal monooxigenase systems Drug - Food Interaction of Grapefruit Juice Monogenic oxydative polymorphism drugs (template drug: debrisoquin) Pharmacogenetic enzyme variations of clinical significance Interactions between defibrillators and drugs Factors to consider before prescribing non-sedating antihistamines (terfenadine and astemizole) PDF created with FinePrint pdfFactory trial version Preventable Drug-Related Morbidity (PDRM)
• About 3.2% of all hospital admissions in the United States and Europe may be caused to a significant degree by preventable drug-relatedmorbidity (PDRM) in ambulatory care.
• This is the median incidence from seven well-designed studies • Incidentally, PDRM represents, on average, about one-half of all medication-related hospital admissions.
Proximal causes of drug-related morbidity (DRM)
• Inappropriate prescribing
• Unexpected adverse drug reactions (ADRs) • Overdose or underdose, either in general or for a specific patient • Failure to recognize symptoms, delay in response, inadequate follow-up Main components of the strategy
• Increase general awareness of the problem of PDRM.
• Develop and disseminate a means for health care programs to identify and assess medication use problems in their own population: developPDRM outcome indicators that could be used to screen populationdatabases • Develop a means to improve systems found to be unsafe • develop new process indicators for medication use • adapt quality improvement (QI) concepts to use in clinic, hospital, • Improve standards for medication use - determine minimum standards PDF created with FinePrint pdfFactory trial version Important principles for physicians to consider
when prescribing any drug
• Document all treatments the patient is taking, including over-the- counter therapies (such as appetite suppressants, herbs, and the like).
• Understand the pharmacology of the drugs that you prescribe, including their route of excretion, the type of liver metabolism if it exists, the half-life of the drug, and its bioavailability. The careful use of drugs alsorequires an understanding of the toxic-therapeutic ratio for the drug.
• Minimize the number of prescriptions you write if you can, thus avoiding the probability of drug--drug interactions.
• Be especially vigilant in high risk situations, especially therapy of the elderly, therapy of patients in an intensive care unit, or therapy ofpatients requiring multiple drugs or with co-existing illnesses such asrenal or hepatic impairment.
• If there is an unexpected deterioration or change in the patient condition, consider drug--drug interactions, which usually present in asubtle manner.
Dr. Jean T. Barbey - 20th Annual Scientific Sessions of the North American Society of Pacing and ElectrophysiologyDay 2 - May 13, 1999 PDF created with FinePrint pdfFactory trial version Adverse Drug Reactions (ADR)
ADR = any unexpected, unintended, undesired, or excessive response to a
medicine:
• requires discontinuing the medicine (therapeutic or diagnostic),
• requires changing the medication therapy, • requires modifying the dose (except for minor dosage adjustments), • necessitates admission to the hospital, • prolongs stay in a healthcare facility, • results in temporary or permanent harm, disability, or deathAmerican Society of Health-System Pharmacists (ASHP) • side effect = expected adverse pharmacological effect occurring in the • overdose toxicity = expected toxicity occurring at higher doses than • allergy = changed organic reactivity against a drug molecule which turned into an antigen upon previous exposition • idiosyncrasy = unforeseen events unrelated to the pharmacologic effects of the drug and are not allergic by their nature (e.g.
myelotoxicity of chloramphenicol) PDF created with FinePrint pdfFactory trial version Adverse Drug Experience
ADE = ADR + medication errors
Postmarket ADE Reports by
Top-10 Ranked Classes of
Suspect Drugs (FDA, 1995)
PDF created with FinePrint pdfFactory trial version Barriers to Improved Monitoring and Reporting of ADEs
• Fear of personal and organizational liability • Lack of resources for surveillance and reporting • Ambiguity in interpreting whether the medication was the cause of the • Minimal feedback provided to reporters • Lack of distinction between significant ADEs and minor ones • Surveillance and reporting functions without a leader Essential Antidote Medications
• Sodium polystyrene sulfonate (Kayexelate) PDF created with FinePrint pdfFactory trial version Factors affecting serum drug concentration
• age• gender• body weight• genetic potentials• inductors• nutrition• environment • liver• kidney• cardiovascular• pregnancy• changes in serum proteins PDF created with FinePrint pdfFactory trial version Classification of drug interactions
• according to the lifecycle of the drug
• extracorporal
• intracorporal
• pharmacokinetic = ADME
• Absorption
• Distribution
• Metabolism
• Excretion
• according to the playing parties
Pharmaceutical interactions
• potential physical interactions between drugs when they are mixed prior • intravenous incompatibilities, such as precipitation in a line when two agents are administered together• drugs may bind to intravenous bags or tubing and PDF created with FinePrint pdfFactory trial version Pharmacokinetic Interactions #1/3
Alterations in Absorption
• drugs of risk:
• ability to chelate (cations such as aluminum) • ability to alter gastrointestinal mobility (metoclopramide or narcotics) • ability to alter gastric pH (ketoconazole) • management: separate the times of administration • tetracycline - chelated by dairy products • fluoroquinolones - chelated by divalent cations, antacids, iron, sucralfate, and didanosine;
these drugs must also be separated by at least 2 hours -
important caveat: fluoroquinolone must be given first !
• drug-excipient interactions: can be actively used to the advantage of the formulator to increase the bioavailability of the druge.g. complexation with cyclodextrins or solid dispersion technology Protein-Binding Effects
• basic mechanism: drugs compete for protein- or tissue-binding sites;
when the drug is freed from a binding site, it may then effect anenhanced pharmacologic action • occupy most of the available binding sites • small volume of distribution + long half-life • e.g. warfarin and cotrimoxazole, digoxin and quinidine.
PDF created with FinePrint pdfFactory trial version Interactions during the absorption phase
• barbitures - antacids• warfarin - antacids• salycylate - antacids• Na-bicarbonate - tetracyclin • Change in GI motility (gastric emptying and intestinal peristalsis) • purgatives• parasympatholytics• parasympatholytics - L-DOPA• antacids - L-DOPA• griseofulvin - barbiturates• antibiotics - food• fat contents of food • tetracyclin - metals• cholestyramin• obstipantia• desferroxamine - iron PDF created with FinePrint pdfFactory trial version Protein binding of drugs in human serum
Anticoagulants
CNS
Antibiotics
NSAID
phenoprofen
OAD
Cardiovascular
Kidney
Competitive interaction for serum protein binding
of clinical significance
Freed drug
“ Attacking” drug
Consequence
NalidixatePhenylbutazonTCA (metabolite of PDF created with FinePrint pdfFactory trial version Pharmacokinetic Interactions #2/3
Changes in Drug Metabolism
• Cytochrome P-450 (CYP) isoenzymes are important for oxidative
• Extrahepatic isoenzymes: small intestine, kidneys, lungs, and brain • More than 30 CYP isoenzymes have been identified • Most commonly involved in drug metabolism are 3A4, 2D6, and 1A2 • Good understanding of substrates, inhibitors, and inducers can help predict the risk for drug interactions in certain drug combinations Enzyme induction = synthesis of metabolizing enzymes is stimulated;result is reduced plasma concentrations of the substrate agent due to theincreased metabolism; onset and offset is usually gradual and depends,among other factors, on half-life:• Rifampin’s short half-life enables induction of CYP3A4 and CYP2C within 24 hours (note: rifampin is a self-inducer !) • Phenobarbital, on the other hand, with a half-life of 3 to 5 days, takes up to a week to induce CYP3A4, CYP1A2, and CYP2C • Other inducers are rifabutin, carbamazepine, primidone, phenytoin Interactions between CYP isoenzymes and herbal products
• Garlic and melatonin may act as inhibitors, • St. John’s wort may be an inducer (observed with: indinavir, theophylline, cyclosporine, oral contraceptives, digoxin, phencoumoron,and dextromethorphan) • Grapefruit juice is an inhibitor of e.g. the CYP3A4 pathway, thus the metabolism of dyhydropyridines, saquinavir, cyclosporine, andverapamil.
PDF created with FinePrint pdfFactory trial version Frequent parties in drug interactions
• antiarrhytmics• anticoagulants• antacides• anticonvulsives• antidiabetics• cytostatics• H2-receptor antagonists• psyhotropics (lithium, MAO-inhibitors)• heart glycosids• theophyllin Role of metabolites
• original compound is inactive:
• pro-drug (cyclophosphamid, phenacetin, phenylbutazon, D-vitamin)• quick metabolism (chloralhydrate, clofibrate) • original compound and its metabolic are
pharmacologically equivalent:
allopurinol, diazepam, imipramin, lidocain, morphin, nalidixate, probenecid, procainamid, propranolol, rifampycin, warfarin • the action of the metabolite differs from the original compound:
codein - morphin, prenylamin - amphetamin • the metabolite is responsible for toxicity:
INH, paracetamol, acetanilide, furosemid, chloramphenicol PDF created with FinePrint pdfFactory trial version CYP-450 system - Substrates
Inhibitors of CYP enzymes
Inducers of CYP Enzymes
PDF created with FinePrint pdfFactory trial version Environmental factors affecting the activity of
the intestinal monooxigenase systems
PDF created with FinePrint pdfFactory trial version Drug - Nutrient Interactions
Nutritient
Interaction
amounts) induces hypokalemiaand sodium retention large amounts of dietarysodium can reduce efficacy alkalinization of the urinemay impair elimination [*] Avoid cheddar, camembert, roquefort cheese.
Processed cheese, cottage cheese, mozzarella and gouda may be eaten in moderation.
PDF created with FinePrint pdfFactory trial version Drug - Food Interaction of Grapefruit Juice
Flavonoids contained in grapefruit juice:
• Naringin - a major flavonoid found in grapefruit juice having itself has no apparent effect on human cytochrome P-450 enzymes - is apparently hydrolyzedin the intestine to naringenin: which is a potent inhibitor of several enzymefamilies, including CYP3A4, CYP1A2, and 11-beta-hydroxysteroiddehydrogenase • Bergapten, a newly identified furocoumarin was detected in grape-fruit juice and Seville orange (!) juice, and it was found to be a mechanism-based inhibitorof CYP3A4.
Pharmacodynamic Effects
Greater decrease in mean arterial pressure andprolongation of P--R interval during grapefruit juiceadministration.
Concurrent grapefruit juice administration wasassociated with more frequent adverse effects, anincreased heart rate, and decreased diastolic bloodpressure compared with water or orange juice.
Psychometric performance tests were significantlyaltered during grapefruit juice administration.
Concurrent grapefruit juice administration wasassociated with an increased heart rate and minoreffects on systolic and diastolic blood pressures.
Heart rate increased slightly (10%) with concurrentgrapefruit juice administration.
No significant change in QTc interval between waterand grapefruit juice periods.
Increased QTc interval during grapefruit juiceadministration.
Increased drowsiness was observed during concurrentgrapefruit juice administration.
PDF created with FinePrint pdfFactory trial version Monogenic oxydative polymorphism drugs
(template drug: debrisoquin)
Metabolic
Clinical consequence
pathways
Beta-blockers
alprenolol
Cardiovascular
encainid
Psychotropics
amiflamin
Other
metoxiphenamin
PDF created with FinePrint pdfFactory trial version Pharmacogenetic enzyme variations of clinical significance
Drug of risk
Heredity
Incidence
PDF created with FinePrint pdfFactory trial version Pharmacokinetic Interactions #3/3
Alterations in Elimination
• Mechanism
• Reduced renal excretion of one drug by another; Example: penicillin-probenecid interaction - probenicid blocksactive secretion of penicillin in the renal tubule Example: alkalinization of urine increases methotrexate elimination Pharmacodynamic Interactions
• are indicative of the pharmacologic actions of the interacting agents by additive or synergistic toxicity or, conversely, additive or synergisticactivity; examples:• Drugs used together that depress the central nervous system (CNS) usually interact, causing synergistic depression of the CNS • St. John’s wort: monoamine oxidase inhibition? + serotonin reuptake • Kava kava - risk for increased central nervous system depression when combined with other central nervous system depressants, suchas ethanol, conventional sedative hypnotics, and antidepressants • Methotrexate (used in patients with severe psoriasis, psoriatic arthritis or bullous diseases) and trimethoprim inhibit human dihydrofolatereductase - may cause severe myelosuppression PDF created with FinePrint pdfFactory trial version Drug interaction and renal function
Drug causing the
Mechanism
Clinical
interaction
consequence
PDF created with FinePrint pdfFactory trial version Interactions between defibrillators and drugs
• Implanted (“ cardioverter”) defibrillators combined with antiarrhytmic drugs:
• beneficial effect: slower ventricular tachycardia may allow increased
ease in pace terminability by implanted defibrillators • deleterious effect: ability of drugs to slow ventricular tachycardia to
below the rate cutoff for the device, thus leading to non-detection • V-W class Ia, Ib antiarrhythmics: either increase or cause no change • V-W class Ic : flecainide increase DFTs, propafenone appears to be • V-W class III: acute IV amiodarone has no effects on DFTs, although some studies have shown that it decreases DFTs; chronic amiodaronegenerally tends to increase DFTs; other class III agents, for examplesotalol, decrease defibrillation thresholds.
• Calcium channel blockers increase defibrillation thresholds.
• In modern defibrillator technology, there is sufficient safety margin between the defibrillation threshold measured at implant and themaximum output of the device, that drugs that increase DFT do notusually lead to inability to defibrillate.
Dr. John DiMarco - 20th Annual Scientific Sessions of the North American Society of Pacing and ElectrophysiologyDay 2 - May 13, 1999 PDF created with FinePrint pdfFactory trial version Factors to consider before prescribing
non-sedating antihistamines (terfenadine and astemizole)
• Concurrent use of other medications that prolong the QT interval • Antiarrhythmic Drugs
• Haloperidol (a structural analogue of terfenadine) • Concurrent use of ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, quinine, saquinavir, ritonavir, orindinavir.
• Electrolyte disturbances that predispose to torsades de pointes (ie, hypomagnesemia, hypokalemia, or hypocalcemia).
• Recurrent ventricular tachycardia.
• Substance abuse (since these patients may be more likely to take • Liver disease or chronic alcohol abuse (since these patients may have significant underlying liver disease).
Joette M. Meyer, Keith A. Rodvold : Drug Interactions Between Nonsedating Antihistamines and Anti-InfectiveAgents; in Infect. Med. 13(7):609-613,634 1996 PDF created with FinePrint pdfFactory trial version Drug interactions of ACEIs
Interaction
Clinical
significance
PDF created with FinePrint pdfFactory trial version Pharmacy and Therapeutics Committee
Functions
• Reviews all adverse drug reaction (ADR) reports and initiates/approves appropriate modifications to policies, procedures, • Reviews all requests for new formulary medications • Thoroughly evaluates all medications, based on efficacy and toxicity, and if the potential for adverse effects is high, the medication may be "Reserved" to specific practitioners, indications, or location of use within the institution, or may require specializedmonitoring, labeling, or use of standardized order sheets to minimize the risk of adverse drug events (ADEs) Adult IV Medication
• Provide information on high-risk medications regarding dose; indication; qualifications of healthcare professional required to Guidelines
administer medication -- ie, RN, LPN, critical care nurse; location of administration -- ie, critical care, general medical floor;monitoring parameters; and potential adverse effects that can be prevented from becoming actual ADEs.
Adult Chemotherapy
• Contain information similar to the above for antineoplastic agents, as this class of medications can be associated with significant Guidelines
Standardized Order Sheets
• Antibiotic order sheets ; Antineoplastic order sheets ; Total parenteral nutritional order sheets ; • Standard order sheets based on pathway contents -- ie, MI standing orders based on MI pathway Standardized Pathways
• Developed by multidisciplinary teams to decrease the variability in care.
RPh Attends
• By doing so, the RPh proactively evaluates patient’s medication profile for potential ADEs.
Multidisciplinary Rounds
Creatinine Clearance
• RPh monitors all renally eliminated medications and makes recommendations for dosage modification to prevent dose-related Monitoring Program
Metformin (glucophage)
• Evaluates renal function to ensure use is in accordance with FDA dosing recommendations to prevent the adverse effect of lactic Monitoring Program
Interaction Monitoring
• Monitor drug-drug and food-drug interactions, a preventable type of ADR Pharmacy Bulletin
• A newsletter distributed to the medical staff that focuses on rationale for drug therapy.
An issue is annually devoted to review of ADRs.
Allergy Documentation
• Any patient who experiences an ADR due to a hypersensitivity/allergic reaction is evaluated by a pharmacist, and the allergy information is added to the hospital-wide computer system to prevent the patient from inadvertently receiving the medication at afuture date.
IV Labels
• A significant number of cases of vancomycin-induced red-man syndrome were detected via ADR surveillance, leading to the addition of the warning statement, "Run over 1 hour" to all vancomycin minibags.
FDA Reports
• Warfarin/tramadol interaction resulting in prolongation of the prothrombin time was detected and reported to the FDA.
This report and others resulted in this drug interaction being added to the package insert • Subpotent diazepam injection was noted through surveillance. As a result, the institution changed brands of diazepam injection, • Angioedema associated with sumatriptan was reported to the FDA, and reports were published[26] to inform other healthcare practitioners of this potentially life-threatening reaction.
PDF created with FinePrint pdfFactory trial version Therapeutic Drug Monitoring (TDM)
1. profilactic drugs
2. low profile drugs: low therapeutic / toxic concentration ratio
3. doubtful compliance (in silent periods od chronic diseases)
4. desired therapeutic answer not achieved or
5. significant interindividual variations in the effect or
6. overdose , signs of toxicity (paradox intoxication)
7. changes in the pharmacokinetic properties fo the drug due to
secondary diseases (changes in hepatic and renal drug clearance) 9. possibility of drug interaction
(changes in the bound-free fraction of the drug) 10. changes in the physiological state of the patient
11. drug treatment should be documented (clinical studies)
12. racem drugs containing a kirality centre if the biological activity /
PDF created with FinePrint pdfFactory trial version "Red Flag" List and Alternatives
1. Cytochrome P-450 inhibitors: impair drug metabolism of other drugs which share the same pathway increase concentrations
of the co-administered drug.
DRUG CLASS
LIKELIHOOD OF A DRUG INTERACTION
ALTERNATIVES
HIV Protease
Ritonavir (Norvir® ) strongest
Saquinavir (Invirase® /Fortovase® ) has less potential to cause drug
inhibitors
Amprenavir (Agenerase® ) intermed
Indinavir (Crixivan® ) intermed
Nelfinavir (Viracept® )intermed
Saquinavir (Fortovase® / Invirase® ) - weakest
Macrolides
Erythromycin and clarithromycin (Biaxin® ) are both inhibitors Azithromycin (Zithromax® ) is not metabolized by CYP450 and
of CYP450, however, the inhibition may be greater with
may be substituted if clinically warranted erythromycin
Antifungals
Fluconazole (Diflucan® ) is associated with less drug interactions
Ketoconazole (Nizoral® ) > Itraconazole (Sporanox® ) >
when dosages of 200 mg or less are used. As dose is increased, Fluconazole (Diflucan® )
there is a greater potential for drug interactions.
Ketoconazole (Nizoral® ) and Itraconazole (Sporanox® ) are Topical antifungals such as clotrimazole (Mycelex® ) troches and
potent inhibitors of CYP450
nystatin may be useful for prophylaxis of thrush or minor
infections. For more severe fungal infections, amphotericin B
(Fungizone® , Abelcet® , AmBisome® , Amphotec® ) may be used
Non-nucleoside
Delavirdine (Rescriptor® ) is a potent inhibitor of CYP450
While it may be beneficial in some cases to use delavirdine to
potentially raising concentrations of other drugs increase concentrations of other drugs (e.g. protease inhibitors), transcriptase
Efavirenz (Sustiva® ) is a mixed inhibitor/inducer,
alternatives in this class would be nevirapine and efavirenz
inhibitors
(Sustiva® ) or perhaps nucleoside analogs (i.e., didanosine
[Videx® ], zidovudine [Retrovir® ]) if clinically appropriate
H2 Antagonists
Cimetidine (Tagamet® ) is a CYP450 inhibitor with a high
i.e. Ranitidine (Zantac® )
or Famotidine (Pepcid® )
Charles Flexner, MD and Steven Piscitelli, PharmD: Managing Drug-Drug Interactions in HIV Disease ; MedScape CME
PDF created with FinePrint pdfFactory trial version 2. Cytochrome P-450 Inducers:
INDUCING DRUG
STRENGTH
ALTERNATIVES
Rifamycins:
Potent inducers of CYP450 and may
For patients receiving protease inhibitors, rifampin should be
Rifabutin (Mycobutin® ) and
avoided. However, rifabutin (Mycobutin® ) may be used with
Rifampin (Rifadin® , Rimactane® )
indinavir (Crixivan® ), amprenavir (Agenerase® ) and nelfinavir
(Viracept® ) at one-half the normal dose (150 mg/day). For ritonavir
(Norvir® ), rifabutin (Mycobutin® ) can be used on an every-other-
day basis or 3 times weekly at one half the normal dose (150 mg q
M-W-F). In patients requiring MAC prophylaxis, azithromycin
(Zithromax® ) or clarithromycin (Biaxin® ) may be substituted for
rifabutin
HIV Protease inhibitors:
Moderate inducers of CYP450, potentially In this class Alternatives would be:
Nelfinavir (Viracept® ) and
amprenavir (Agenerase® )
Ritonavir (Norvir® )
indinavir (Crixivan® )
saquinavir (Fortovase® )
delavirdine (Rescriptor® )
or perhaps nucleoside analogs, i.e.
didanosin e (Videx® )
zidovudine (Retrovir® ) could be used if clinically appropriate
Non-nucleoside reverse
Moderate inducers of CYP450, potentially Alternatives in this class would be delavirdine or perhaps nucleoside
transcriptase inhibitors:
Nevirapine (Viramune® ) and
didanosine (Videx® )
Efavirenz (Sustiva® )
zidovudine (Retrovir® )
if clinically appropriate
Anticonvulsants:
Major / moderate inducers of CYP450,
If clinically warranted, possible alternative anti-epileptics include:
Phenobarbital
valproic acid (Depakene® , Depakote® )
Phenytoin (Dilantin® )
gabapentin (Neurontin® )
Carbamazepine (Tegretol® )
lamotrigine (Lamictal® )
topiramate (Topamax® )
tigabine (Investigational Tabitril® )
Charles Flexner, MD and Steven Piscitelli, PharmD: Managing Drug-Drug Interactions in HIV Disease ; MedScape CME
PDF created with FinePrint pdfFactory trial version 3. Metabolized drugs with narrow therapeutic indexes:
CATEGORY
ALTERNATIVES / NOTES
Non-sedating
Terfenadine (Seldane® ) Astemizole (Hismanal® )
Newer non-sedating antihistamines such as fexofenadine (Allegra® )
antihistamines
*although removed from US market, patients may and loratadine (Claritin® ) can be safely used with P450 inhibitors, as
still have supplies
well as most over-the counter preparations Antiarrythmics
Flecainide (Tambocor® ) Encainide (Enkaid® )
Antiarrhythmic therapy should be closely monitored and used with Quinidine
caution in patients receiving inhibitors of cytochrome P-450 Long-acting opiate
Fentanyl (Sublimaze® , Duragesic® )
Alternative analgesics include hydromorphone, codeine, and
analgesics
NSAIDs, particularly in patients receiving ritonavir (Norvir® )
Promotility agents
Cisapride (Propulsid® )
Metoclopramide (Reglan® )
Long-acting
Midazolam (Versed® ) Triazolam (Halcion® )
benzodiazepines
Ergotamines and
dihydroergotamine
Illicit drugs
Ecstacy/XTC/MDMA
Coumarin anticoagulants
Warfarin (Coumadin® )
Oral contraceptives
Oral contraceptives should not be given concurrently with P450
inducers, as this can decrease their concentrations and lead to
unwanted pregnancy
4. Renally cleared drugs with narrow therapeutic indices:
DRUG / NOTES
ALTERNATIVES
Foscarnet (Foscavir® )
Adjust dose for renal function with these agents Ganciclovir (Cytovene® )
Cidofovir (Vistide) may be used if clinically appropriate, but this agent can
cause irreversible renal insufficiency
Aminoglycosides:
Other antibiotics covering gram – bacteria: Gentamycin
Aztreonam (Azactram® )
Tobramycin
Broad Spectrum penicillins and cephalosporins
Amikacin (Any drugs that are nephrotoxic may decrease aminoglycoside
clearance and increase likelihood of aminoglycoside toxicity)
Charles Flexner, MD and Steven Piscitelli, PharmD: Managing Drug-Drug Interactions in HIV Disease ; MedScape CME
PDF created with FinePrint pdfFactory trial version 5. Drugs with specific requirements for absorption:
REQUIREMENTS
ALTERNATIVES
Ketoconazole (Nizoral® )
Require an acidic gastric pH for optimal absorption - avoid in Fluconazole can be substituted if clinically appropriate.
Itraconazole (Sporanox® ) patients with achlorhydria or those receiving H2-antagonists, Topical antifungals such as clotrimazole (Mycelex® )
troches and nystatin may be useful for prophylaxis of thrush
or minor involvement. For more severe fungal infections,
amphotericin B (Fungizone® , Abelcet® , AmBisome® ,
Amphotec® ) may be used
Didanosine (Videx® )
Must be taken on an empty stomach and separated from Administer didanosine (Videx® ) once daily on empty
indinavir by one hour since the buffer component may impair stomach to lessen inconvenience associated with indinavir.
indinavir (Crixivan® ) absorption
Can use alternative nucleoside analogs if clinicallyappropriate Fluoroquinolones
Must be separated from di- and trivalent cations (calcium
Separate quinolone from cations by 2-4 hours - administer
products, antacids, iron preparations, DDI, etc) to avoid
quinolone first. Also, other antimicrobials with appropriate
chelation and decreased therapeutic effect coverage (i.e. cephalosporins) may be used if clinically
appropriate
Charles Flexner, MD and Steven Piscitelli, PharmD: Managing Drug-Drug Interactions in HIV Disease ; MedScape CME
PDF created with FinePrint pdfFactory trial version

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