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April 14, 2016

哪些藥物交互作用需要注意,但電腦系統的警訊卻常被忽略 ?


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摘自 Pharmacist's Letter, 2004, June Issue
By Alycia Lin
根據四種常用的藥物交互作用參考工具 ( MICROMEDEX- DRUG-REAX, Evaluation of Drug Interactions, Drug Interaction Facts, Drug Interactions: Analysis and Management) , 406 種藥物交互作用中,有9種被這四種參考工具認為是主要且嚴重的交互作用。但現在的電腦系統常因為沒能特別指出這些主要,可能致命的交互作用,當警訊出現 時,常被醫療人員以"跳過"的方式繼續執行開藥給藥的動作。
這些嚴重的交互作用如 MAOI 併用 pseudoephedrine(很多感冒藥的成分)或併用抗憂鬱藥 (如SSRI, TCAs), 以及雖不致命但需要注意的交互作用,如 NSAIDs + 降血壓藥,beta-blockers + sulfonylureas 降血糖藥 。
一定要注意安全濃度範圍較小的藥, 如: warfarin, digoxin, levothyroxine, lithium, carbamazepine, phenytoin, theophylline..., 即使增加一點濃度都可能造成破壞性的結果。
請注意常見的會引起其他藥物濃度改變的藥物, 如 ketoconazole, erythromycin 這些肝功能酵素抑制劑,和rifampin...等肝功能酵素催化劑 。
還要注意不同醫師開的藥物,例如甲醫師開ACE inhibitor, 乙醫師開 K-Sparing Diuretic (如 spironolactone) 就可能造成病人鉀離子濃度的過高。
以下是這些重要的藥物交互作用表格:
 
Clinically Important Drug Interactions Encountered in Ambulatory and Community Pharmacy Practices
Lead author: Beth A. Lesher, Pharm.D., BCPS
Interacting Drug Combinationa Findingsb Recommendations/Commentsb
Object Drug Precipitant Drug
Anticoagulants
Anisindione (Miradon)
Dicumarol
Warfarin (Coumadin)
Thyroid hormones:
Levothyroxine (Levothroid, Synthroid, etc)
Liothyronine (Cytomel)
Liotrix (Thyrolar)
Thyroid
Dextrothyroxine (Choloxin)
Increased risk of bleeding due to increased metabolism of vitamin K-dependent clotting factors
  • Monitor INR when starting or stopping thyroid hormones
  • Anticoagulant dose may need to be adjusted to maintain desired INR
  • Patients stabilized on thyroid hormones and considered euthyroid will respond normally to anticoagulant therapy
Benzodiazepines
Alprazolam
(Xanax)
Clonazepam (Klonopin)b
Diazepam
(Valium)b
Midazolam (Versed)b
Triazolam (Halcion)
Azole antifungal agents:
Fluconazole (Diflucan)
Itraconazole (Sporanox)
Ketoconazole (Nizoral)
Increased benzodiazepine serum concentrations due to inhibition of cytochrome p450 3A enzymes
  • Avoid combination if possible
  • If combination is required, reduce benzodiazepine dose
  • Consider using a benzodiazepine metabolized by glucuronidation such as temazepam (Restoril) or lorazepam (Ativan)
  • Monitor for sedation when starting, stopping, or changing the azole antifungal dose
Carbamazepine (Tegretol) Propoxyphene (Darvon and others) Increased carbamazepine serum levels and risk of toxicity due to decreased carbamazepine hepatic metabolism
  • Avoid combination if possible
  • If combination is required, carbamazepine serum concentrations must be closely monitored
  • Carbamazepine dosage reductions are typically needed
Cyclosporine (Neoral, etc) Rifamycins:
Rifampin (Rifadin, Rimactane)
Rifabutin (Mycobutin)
Rifapentine (Priftin)
Decreased cyclosporine serum levels and increased risk of organ rejection due to increased cyclosporine clearance and decreased cyclosporine systemic bioavailability
  • Avoid combination if possible
  • If combination is required, cyclosporine levels must be closely monitored
  • Cyclosporine dosage increases between 2.5 to 5 times baseline are typically needed. In some cases this is prophylacticly done when combination therapy is started.
  • Effect may persist for 1 to 3 weeks after rifamycins are discontinued
Dextromethorphan MAO inhibitors:
Isocarboxazid (Marplan)
Phenelzine (Nardil)
Selegiline (Eldepryl and others)
Tranylcypromine (Parnate)
Increased risk of serotonin syndrome (e.g., hypertension, hyperpyrexia, abnormal movements, coma, and death) due to altered catecholamine uptake and metabolism
  • Combination therapy is contraindicated
  • MOA inhibitor therapy must be discontinued 14 days prior to the initiation of dextromethorphan therapy
Digoxin Clarithromycin (Biaxin)
Erythromycinb
Increased digoxin levels due to inhibition of p-glycoprotein
  • Avoid combination if possible
  • If combination therapy is required, reduce the digoxin dose temporarily
  • Monitor digoxin serum levels and for signs of digoxin toxicity
  • Effect of other macrolides on p-glycoprotein is unknown
Ergot alkaloids
Dihydroergotamine (D.H.E. 45)
Ergotamine (Cafergot and others)
Methylsergide
Macrolide antibiotics:
Clarithromycin (Biaxin)
Erythromycin
Troleandomycin
Increased risk of acute ergotism characterized by nausea, vomiting, and vasospastic ischemia due to inhibition of cytochrome p450 3A4 enzymes
  • Combination therapy is contraindicated
  • Other macrolides (azithromycin, dirithromycin) might be less likely to interact
Estrogen-progestin products (oral contraceptives) Rifampin Increased risk of breakthrough bleeding and contraception failure due to induction of cytochrome p450 enzymes
  • Advise patient to use another method of contraception
Ganciclovir (Cytovene) Zidovudine (Retrovir) Increased risk of hematologic toxicities such as anemia and neutropenia due to an unknown mechanism
  • Avoid combination therapy if possible
  • If combination therapy is required, monitor complete blood cell counts frequently
MAO inhibitors
Isocarboxazid (Marplan)
Phenelzine (Nardil)
Selegiline (Eldepryl and others)
Tranylcypromine (Parnate)
Anorexiants:
Amphetamine
Benzphetamine
Dexfenfluramine
Dextroamphetamine (Dexedrine)
Diethylpropion (Tenuate)
Fenfluramine
Maxindol (Mazanor, Sanorex)
Methamphetamine (Desoxyn)
Phendimetrazine (Obizine, Prelu-2, Adipost, and others)
Phentermine (Ionamine, Phentride, Feramine, and others)
Phenylpropanolamine
Sibutramine (Meridia)
Increased risk of hypertensive crisis or serotonin syndrome due to increased norepinephrine availability
  • Combination therapy is contraindicated
  • MAO inhibitor therapy should be discontinued 14 days prior to starting anorexiant therapy
  • Anorexiant therapy should be discontinued 14 days prior to starting MAO inhibitor therapy
MAO inhibitors
Isocarboxazid
Phenelzine (Nardil)
Selegiline (Eldepryl and others)
Tranylcypromine (Parnate)
Sympathomimetics:
Dopamine
Ephedrine
Isometheptene mucate
Mephentermine
Metaraminol
Phenylephrine
Pseudoephedrine
Increased risk of hypertensive crisis due to increased norephinephrine availability
  • Avoid combination therapy
  • If combination therapy is required, monitor blood pressure and for frequent headaches or palpitations
  • If hypertensive crisis occurs, discontinue MAO inhibitor therapy and administer phentolamine 5 mg slow intravenous push to lower blood pressure
Meperidine (Demerol) MAO inhibitors:
Isocarboxazid (Marplan)
Phenelzine (Nardil)
Selegiline (Eldepryl and others)
Tranylcypromine (Parnate)
Increased risk of cardiovascular instability, hyperpyrexia, agitation, seizures, diaphoresis, and coma due to an unknown mechanism
  • Combination therapy is contraindicated
  • MAO inhibitor therapy should be discontinued for 14 days prior to starting meperidine therapy
Methotrexate (Rheumatrex, Trexall) Trimethoprim (Proloprim, Trimpex)
Trimethoprim-sulfamethoxazole (Bactrim, Septra)
Increased risk of methotrexate toxicity due to synergistic effects on folate metabolism
  • Avoid combination therapy
  • If combination therapy is required, monitor for signs of hematologic toxicities including complete blood cell counts
Nitrates
Nitroglycerin
Isosorbide dinitrate (Isordil)
Isosorbide mononitrate (Imdur, ISMO, Monoket)
Sildenafil (Viagra), Tadalafil (Cialis)b, Vardenafil (Levitra)b Increased hypotensive effects due to increased levels of cyclic guanosine monophosphate (cGMP)
  • Combination therapy is contraindicated
  • The length of time required between discontinuation of nitroglycerin therapy and safe administration of sildenafil, etc. is not known
Pimozide (Orap) Macrolide antibiotics:
Azithromycin (Zithromax)b
Clarithromycin (Biaxin)
Dirithromycin (Dynabac)
Erythromycin
Troleandomycin
Increased risk of cardiotoxicity manifested as QT prolongation, torsdes de pointes, and cardiac arrest due to inhibition of cytochrome p450 3A enzymes
  • Combination therapy is contraindicated with all macrolides (including azithromycin per pimozide product labeling)
Pimozide (Orap) Azole antifungal agents:
Fluconazole (Diflucan)
Itraconazole (Sporanox)
Ketoconazole (Nizoral)
Increased risk of cardiotoxicity manifested as QT prolongation, torsdes de pointes, and cardiac arrest due to additive cardiac effects or to inhibition of cytochrome p450 3A4 enzymes
  • Combination therapy is contraindicated
SSRIs
Citalopram (Celexa)
Escitalopram (Lexapro)b
Fluoxetine (Prozac, Sarafem)
Fluvoxamine (Luvox)
Nefazodone (Serzone)c
Paroxetine (Paxil)
Sertraline (Zoloft)
Venlafaxine (Effexor)c
MAO inhibitors:
Isocarboxazid (Marplan)
Phenelzine (Nardil)
Selegiline (Eldepryl and others)
Tranylcypromine (Parnate)
Increased risk of a serotonin syndrome (e.g., CNS irritability, shivering, myoclonus, altered consciousness) due to inhibition of serotonin reuptake
  • Combination therapy is contraindicated
  • MAO inhibitor therapy should be discontinued 14 days prior to starting SSRI therapy
  • SSRI therapy should be discontinued 7 days for nefazodone and venlafaxine; 14 days for citalopram, escitalopram, fluvoxamine, paroxetine, and sertraline; and 35 days for fluoxetine prior to starting MAO inhibitor therapy
Theophyllines Quinolones:
Ciprofloxacin (Cipro)
Enoxacin (Penetrex)
(no longer available)
Norfloxacin (Noroxin)b
Risk of increased theophylline plasma concentrations and toxicity due to inhibition of cytochrome p450 enzymes
  • Avoid combination therapy if possible
  • If combination therapy is required, monitor theophylline levels and for signs of theophylline toxicity
  • Theophylline dosage adjustments may be needed
Theophyllines Fluvoxamine (Luvox) Risk of increased theophylline plasma concentrations and toxicity due to inhibition of cytochrome p450 1A2 enzymes
  • Avoid combination if possible
  • If combination therapy is required reduce theophylline dose to one-third of baseline dose
  • Decrease theophylline dose by one-third when starting theophylline therapy in patients receiving fluvoxamine
  • Monitor theophylline levels and for signs of theophylline toxicity
Thiopurines
Azathioprine (Imuran)
Mercaptopurine (Purinethol)
Allopurinol (Zyloprim) Increased risk of thiopurine toxicity manifested as nausea, vomiting, leucopenia, and anemia due to inhibition of xanthine oxidase
  • Avoid combination if possible
  • If combination therapy is required, reduce azathioprine or mercaptopurine dose to one-forth to one-third of baseline
  • Monitor for hematologic toxicity
Warfarin (Coumadin) Sulfinpyrazone (Anturane) Increased risk of bleeding due to impaired metabolism of the (S)-warfarin enantiomer
  • Monitor INR closely when adding or discontinuing sulfinpyrazone therapy
  • Warfarin dosage adjustments may be needed
Warfarin (Coumadin) Nonsteroidal anti-inflammatory drugs:
Celecoxib (Celebrex)
Diclofenac (Cataflam, Voltaren)
Etodolac (Lodine)
Flurbiprofen (Ansaid)
Fenoprofen (Nalfon)
Ibuprofen (Motrin)
Indomethacin (Indocin)
Ketoprofen (Orudis)
Ketorolac (Toradol)
Meclofenamate
Mefenamic acid (Ponstel)
Nabumetone (Relafen)
Naproxen (Naprosyn)
Oxaprozin (Daypro)
Piroxicam (Feldene)
Rofecoxib (Vioxx)
Sulindac (Clinoril)
Tolmetin (Tolectin)
Valdecoxib (Bextra)b
Increased risk of bleeding due to gastric erosion (all) and inhibition of platelet aggregation (traditional NSAIDs)
  • Monitor INR closely
  • Monitor for signs of bleeding, especially from the gastrointestinal tract
Warfarin (Coumadin) Cimetidine (Tagamet) Increased risk of bleeding due to decreased warfarin metabolism
  • Avoid combination when possible
  • If combination therapy is required, monitor INR closely until stabilized at desired anticoagulation level
Warfarin (Coumadin) Fibric acid derivatives:
Clofibrate (Atromid)
(no longer available)
Fenofibrate (TriCor, Lofibra)
Gemfibrozil (Lopid)
Increased risk of bleeding due to an unknown mechanism
  • Monitor INR closely when adding or discontinuing fibric acid therapy
  • If clofibrate therapy is started, recommendations are to decrease the warfarin dose by one-half
  • Warfarin dosage adjustments may be needed
Warfarin (Coumadin) Barbiturates:
Amobarbital (Amytal)
Butabarbital (Busodium, Butisol)
Butalbital
Mephobarbital (Mebaral)
Phenobarbital (Luminal, Solfoton)
Secobarbital (Seconal)
Decreased anticoagulant effect due to increased warfarin metabolism
  • Monitor INR closely when adding or discontinuing barbiturates
  • Warfarin dosage adjustments may be needed
a This list was developed in conjunction with the Centers for Disease Control and Prevention in early 2002 for use by ambulatory and community pharmacists.4 This list should not be considered all-inclusive; other clinically significant drug interactions do exist. For example, interactions involving drugs marketed after early 2002 and clinically important drug-drug interactions encountered in other practice settings such as a hospital or homecare pharmacy are not included.
b Information not included in the paper by Malone and colleagues.
c Included with SSRIs because of similar pharmacologic profiles.4
Abbreviations: INR, international normalized ratio; MAO, monoamine oxidase; SSRIs, selective serotonin reuptake inhibitors
 
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http://web2.tmu.edu.tw/b8303016/2-1.htm
 













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