Drug Interactionupdate

Drug interaction

PAGE 10 . 2552

Drug interaction

Severity Level 1

Drug interaction

( Significance rating ) onset,severity,and documentation

Onset: 2

Rapid:

24

Delayed:

Severity: risk/benefit 3

Major:

life-threatening or permanent damage

Moderate:

Minor:

( little effect )

Documentation: drug interaction 5

Established:proven to occur in well-controlled studies

Probable:very likely, but not proven clinically

Suspected:may occur, some good data, needs more study

Possible:could occur, but data are very limited

Unlikely:doubtful; no good evidence of an altered clinical effect

( Significance rating ) 1 5 Significance ratingSeverityDocumentation

1MajorSuspected or >

2ModerateSuspected or >

3MinorSuspected or >

4Major/ModeratePossible

5MinorAnyPossibleUnlikely

Drug interaction Significance rating = 1 ( Major and well-documented interaction )OnsetmechanismEffectManagement

1Aminoglycoside

(Gentamicin,Kanamycin,Streptomycin, Amikacin, Netilmicin, Tobramycin)Loop diuretics

( Furosemide )Rapid 2 ADR

2AmiodaroneFentanylRapid bradycardia cardiac output sinus arrest hypotensionMonitor hemodynamic function inotropic chronotropic pressure support bradycardia Epinephrine dose Atropine

3Protease Inhibitors

- Atazanavir

- Indinavir

- Lopinavir /Ritonavir

- Nelfinavir

- RitanavirDelayedProtease Inhibitorsmetabolism amiodarone amiodarone Ritonavir Nelfinavir amiodarone

4Quinolone

- Levofloxacin

- Moxifloxacin

- Sparfloxacin

- GatifloxacinDelayed cardiac arrhythmia Tosades de pointes Amiodarone Sparfloxacin Gatifloxacin, Levofloxacin prolong QT interval

5Anticholinesterases

(Pyridostigmine, MestinonR , Neosigmine)Corticosteroids

(Hydrocortisone, Methylprenisolone, Prednisolone, Dexamethasone, Betamethasone, Cortisone , Prednisone)Delayed Anticholinesterases myasthenia gravis muscle strength myasthenia gravis - steroid -

6Anticoagulant

( Warfarin )

Androgens

(Danazol)Delayed Anticoagulant activity , bleeding monitor PT , INR Warfarin Androgens

7

AmiodaroneDelayedAmiodarone metabolism Warfarin Warfarin Warfarin 30%-50% monitor PT ,INR 2-4 Warfarin Amiodarone Warfarin

8Azole antifungal (Fluconazole,

Ketoconazole,

Itraconazole)DelayedAzole antifungal metabolism Warfarin

Warfarin bleeding monitor PT ,INR Warfarin

9Cephalosporins

(Cefazolin,

Cefoperazone,

Cefoxitin,

Ceftriaxone)DelayedCephalosporins Warfarin like activity antiplatelet

Anticoagulant

activity bleeding Warfarin vitamin K

10DextrothyroxineDelayedDextrothyroxine hypoprothrombin time Warfarin

Dextrothyroxine Warfarin

11Erythromycin,

ClarithromycinDelayed Total body clearance Warfarin Anticoagulant

activity bleeding Warfarin Warfarin monitor coagulation parameters

12GemfibrozilDelayed Warfarin bleeding

monitor coagulation parameters

13H2-antagonist

(Cimetidine)DelayedCimetidine hepatic metabolism Warfarin Anticoagulant

activity bleeding monitor coagulation parameters Warfarin H2-antagonist famotidine

14MetronidazoleDelayedMetronidazole hepatic metabolism Warfarin Anticoagulant

activity bleeding monitor coagulation parameters Warfarin

15Phenobarbital(Barbiturate, Pentobarbiturate)Delayed Hepatic microsomal enzyme metabolic Warfarin Anticoagulant activity Warfarin barbiturate Warfarin 2-3 benzodiazepine

16Phenylbutazone

-Oxyphenbutazone

- PhenybutazoleDelayedPhenylbutazone metabolism warfarin plasma protein warfarin anticoagulant Bleeding Warfarin Phenylbutazone NSAID

17Quinine derivatives (Quinidine, Quinine)DelayedQuinine derivatives clotting factors Anticoagulant


18Salicylates

(aspirin,

methysalicylate;

topical)DelayedAspirin platelet aggregation gastric mucosa irritation Anticoagulant

Activity & hemorrhage aspirinmonitor coagulation parameters Warfarin

19Tetracyclines

- Doxycyline

- Minocycline

- Oxytetracycline

- TetracyclineDelayedBacteria Vitamin K warfarin monitor INR does Bleeding

20Thioamines

( Methimazole ,

PTU:Propylthiouracil)Delayed metabolism of clotting factor Anticoagulant

Activitymonitor coagulation parameters Warfarin

21Thyroid hormones (Levothyroxine, Thyroid)DelayedThyroid hormones Vitamin K dependent clotting factors Anticoagulant


22Sulfomamide (Sulfamethoxazole/

Trimethoprim, Sulfasalazine, Sulfamethoxazole)Delayed hepatic metabolism of S- warfarin Anticoagulant


23Vitamin EDelayed Vitamin E Vitamin K dependent clotting factors Warfarin bleeding monitor coagulation parameters Warfarin

24(-blocker

(atenolol , metroprolol, propanolol )VerapamilRapidVerapamil oxidative metabolism (-blocker 2 Monitor cardiac function,

25Phenothiazines

- Chlorpromazine

- ThioridazineDelayedChlorpromazine

First-pass metabolism propranolol Beta-Blocker metabolism Thioridazine cardiac arrhythmia Thioridazine Propranolol

26CarbamazepineMacrolide antibiotics

(erythromycin , clarithromycin)RapidMacrolide carbamazepine hepatic metabolism carbamazepine carbamazepine (ataxia,nystagmus,diplopia,

headache,vomiting,apnea,

seizure,coma ) carbamazepine

27ClozapineRitonavirDelayedRitonavir metabolism ClozapineClozapine totic Ritonavir Clozapine

28Corticosteroids

(prednisolone hydrocortisone, methylprenisolone)Rifampicin

DelayedRifampicin

Induce hepatic enzyme Corticosteroid Corticosteroid

Corticosteroids

29

AmiodaroneDelayed digoxin Digoxin digoxin Digoxin toxicity Digoxin

30Loop diuretics & thiazide diuretics

( Furosemide ,HCTZ)DelayedDiuretics potassium magnesium electrolyte Digitalis induced arrhythmiaMonitor potassium magnesium Sodium potassium sparing diuretics

31Macrolide antibiotics (Erythromycin , clarithromycin )Delayed 10 % Digoxin metabolized Digoxin reduce product (DRPs) Macrolide GI flora active form Digoxin

serum Digoxin levels, toxic of Digoxin Erythromycin Digoxin Digoxin toxicity Digoxin

32CyclosporinePhenytoinDelayed absorption Metabolism CyclosporinCyclosporin Cyclosporin Rifampin Cyclosporin SCr Rifampin

33RifampinDelayedRifampin metabolism Cyclosporine Cyclosporine 2 1-3 Cyclosporine Cyclosporine SCr

34Digoxin

AmiodaroneDelayed Digoxin Digoxin Digoxin Amiodarone

35-Loop diuretic (Furosemide)

-Thiazide Diuretic

(HCTZ, indapamide)DelayedK Mg Diuretic electrolyte arrhythmia K, Mg K Na potassium-sparing diuretic

36Propafenone

( Rytmonorm()Delayed Vd, CrCL Digoxin serum Digoxin levels, toxic Digoxin Digoxin Digoxin Propafenone

37QuinidineDelayedRenal,biliary clearance volume og distribution Digoxin Digoxin Digoxin Digoxin Digoxin 50% Quinidine Digoxin

38Tetracyclines (Doxycycline, Tetracycline, Minocycline) Delayed 10 % Digoxin metabolized Digoxin reduction product (DRPs) Tetracycline GI flora active Digoxin

serum Digoxin levels, toxic of Digoxin Tetracycline Digoxin Digoxin

39VerapamilDelayed serum Digoxin levels, toxic of Digoxin Digoxin Digoxin Digoxin

40Dopamine

phenyltoinRapid Dopamine catecholamines phenyltoin hypotension & cardiac arrest phenyltoin Dopamine IV drip phenyltoin

41Epinephrine(-blocker

( Propranolol )RapidNon-selective (-blocker

alpha- receptor Epinephrine vascular resistant baroreceptor bradycardia

blood pressure bradycardia Epinephrine (-blocker

3 Epinephrine vital sign selective (-blocker

42Ergot alkaloids

( dihydroergotamine, ergotamineMacrolide antibiotics (Erythromycin , clarithromycin )RapidMacrolide hepatic metabolism of ergotamine acute ergotism, N/ V, vasosplastic,

ischemia )

43NNRT Inhibitor

- EfavirenzDelayedNNRT Inhibitor

metabolism Ergot Ergot

44Protease Inhilaitor

- Indinavir

- Lopinavir/ Ritonavir

- Ritonavir

- SaquinavirDelayedProtease Inhibitor metabolism Ergot Ergot

45VoriconazoleDelayedVoriconazale metabolism Ergot Ergot

46FentanylProtease Inhibitor

- Indinavir

- Saquinavir-RitonavirDelayed Protease Inhibitor

metabolism Fentanyl Fentanyl respiratory function

47FlecainideRitonavirDelayedRitonavir metabolism FlecainideFlecainide RitonavirFlecainide

48FoscarmetCyclosporineDelayed hephrotoxicity renal failure monitor

49Haloperidol LithiumDelayed encephalopathic symptoms , brain damage, extrapyramidal symptoms, dyskinesias, fever , leucocytosis 3

50HMG-coA Reductase inhibitor ( Atorvastatin , simvastatin, pravastatin )CyclosporinDelayedCyclosporin metabolism HMG-Co A HMG-Co A

Myclysis, Rhabclomyolysis HMG-Co A

51Gemfibrozil Delayed myopathy rhabdomyolysis serum creatine kinase myopathy rhabdomyolysis ( unexplained muscle pain , tenderness or weakness )

52Macrolide antibiotics (erythromycin , clarithromycin, Azithromycin)DelayedMacrolide hepatic metabolism of HMG-coA Reductase inhibitor statins 40 % myopathy rhabdomyolysis myopathy rhabdomyolysis ( unexplained muscle pain , tenderness or weakness )

53Isoniazid

RifampicinDelayed Rifampicin metabolism isoniazid 2

54Macroclide Antibiotic (Erythromycin)Quinolones

- Gatiflcxacin

- Moxifloxacin

- SparfloxacinDelayed cardiac arrhythmias tcrsades de pointes Sparfloxacin Erythromycin Gatifloxacin ,

Moxifloxacin Erythromycin

55Methotrexate: MTXNSAIDs

(Diclofenac,IbuprofenNaproxen )

Delayed

renal clearance MTX MTX MTX NSAIDs Leucovorin MTX

56Penicillins

(Amoxicillin,

Piperacillin, Ampicillin, Cloxacillin, Dicloxacillin, Penicillin G,V)

DelayedPenicilln MTX renal clearance competition tubular secretion serum of MTX,( ) MTX MTX 2 /wk 2 Leucovorin

57

Probenecid

Rapid

Probenecid Methotrexate

Methotrexate Methotrexate Methotrexate Leucovorin Methotrexate Methotrexate

58

Salicylates (Aspirin, Bismuth Subsalicylate) Rapid

Salicylates renal clearance Plasma MTX

toxic effect of Methtrexate Methotrexate Leucovorin Methotrexate

59

Sulfonamides

(Sulfamethoxazole, Sulfisoxazole,Trimethoprim +SMZ, Sulfasalazine, Trimethoprim)

Delayed

-synergistic anti-folate effects,

-sulfonamides MTX protein

- renal clearance MTX risk of Methotrexate toxicity (myelotoxicity,

pancytopenia,

megaloblastic anemia)

60

Metformin

Iodinated contrast material parenteral (iv urogram,

IV angiography)Rapid

Iodinated contrast material-induced renal failure metformin induced lactic acidosis 2 Metformin 48 . contrast media

61

Muscle relaxants (Atracurium,

Pancuronium, Tubocurarine)

Aminoglycosides(Gentamicin,

Netilmicin,

Streptomycin, Neomycin, Amikacin, Kanamicin)

Rapid

-

non depolarizing muscle relaxation respiratiory depression

neuromuscular Ca salt Anticholinesterase antidote

62

Penicillins

(Amoxicillin,

Piperacillin, Ampicillin, Cloxacillin, Dicloxacillin, Penicillin G,V)

Tetracyclines, (Oxytetracycline, Doxycycline, Monocycline, Tetracycline, Delayed Tetracycline Penicillins Penicillins

63Phenothizines

(Thioridazine)AmicdaroneDelayedprolong QT interval cardiac arrhythmiatorsade de pointes

64FluoxetineDelayedFluoxetine metabolism ThioridazineThioridazine cardiac arrhythmia torsade de pointes

65FluvoxamineDelayedFluoxetine metabolism Thioridazine cardiac arrhythmia torsades de pointes

66PimozideDelayedProlong QT interval cardiac arrhythmig torsade de pointes

67PimozideAzole Anifungal Agent

- Itraconazole

- KetoconazoleDelayedAzole Anifungal Agentmetabolism Pimozide

cardiac arrhythmia 2

68Macrolide Antibiotics

- Azithromycin

- Clarithromycin

- ErythromycinDelayedMacrolidemetabolism Pimozide

Pimozide

Cardiotoxicity Macrolide Pimozide

69Protease inhibitor

- indinavir

- Ritonavir

- atazanavirDelayedProtease inhibitormetabolism Pimozide

cardiac arrhythmia

70SertralineDelayed cardiac arrhythmia torsades de pointes

71VoriconazoleDelayedVoriconazolemetabolism Pimozide

cardiac arrhythmia torsade de pointes

72Potassium Preparations (KCI)Potasium-sparing Diuretic (Spironolactone,

Amiloride,

Triamterene)DelayedPotassium-sparing diuretics Potassium ion hyperkalemia hypokalemia serum Potassium

73

Potassium-sparing diuretics(Amiloride;

Moduretic )

ACE Inhibitors (enalapril, captopril, ramipril)

Delayed

serum level of potassium

hyperkalemaia arrhythmias

potassium renal dysfunction,

diabetes and the elderly

74PropafenoneRitonavirDelayedRitonavirmetabolism Propafenone Propafenone Ritonavir Propafenone

75PropoxypheneRitonavirDelayedRitonavirmetabolism Propoxyphene Propoxyphene Ritonavir Propoxyphene

76Quinidine

Amiodarone

Rapid Quinidine cardiac dysarhymias Qunidine Qunidine

77Protease inhibitor

- Nelfinavir

- RitonavirDelayedRitonavir metabolism Quinidine Quinidine Ritonavir NeL Quinidine

78VariconazoleDelayedVariconazolemetabolism Quinidinecardiac arrhythmig torsade de pointes2

79RisperidoneParoxetineRapidParoxetinemetabolism Risperidone Risperidone side effect serotonin syndrome muscle tone myoclonus Clinic Risperidone Parcxetine

80Selective 5-HT1 receptor agonists

- sumatriptanErgot derivative

- Ergotamine

- DihydroergotamineRapidVasospasticVasospastic Selective 5-HT1 24 Ergot 5-HT1 agonist 2

81Serotonin Reuptake

InhibitorRapid Serotonin CNS Serotonin muscle tone shiverting, myoclonus monitor serotonin antiserotonin agent

82Serotonin Reuptake Inhibitors (Fluoxetine, Sertraline; Zoloft

Imipramine)Amiloride (Moduretic )Delayed myocardial sodium channel blockade Proarrhythmia reversal antiarrhythmic effect of Quinidine 2 monitor ECG

83SimvastatinProtease Inhibitor

- Atazanavir

- Indinavir

- Lopinavir/ Ritonavir

- Nelfinavir

- Ritonavir

- SaguinavirDelayedProtease Inhibitor

first-pass metabolismSimvastatin Simvastatin Side effect Simvastatin Nelfinavir Ritonavir

84Sympathomimetics DopaminePhenytoinRapid Dopamin myocardial effect Phenytoin Hypotension Cardiac arrest Phenytoin dcpamine infusion BP P Hypotension

85Thiopurines (Azathioprine,

Mercaptopurine )Verapamil

RapidVerapamil clearance Quinidine half-life Quinidine hypotension,

bradycardia,

ventricular tachycardia AV block

86TheophyllinesMAO Inhibitors (Selegiline)RapidMAO inhibitor serotonin CNS toxicity or Serotonin Syndrome (hypertension,

hyperthermia,

myoclonus (),mental status changes) 2 MAO inh.(Selegiline 14 SSRI (Fluoxetine, Sertraline)

87AllopurinolDelayedAllopurinol enzyme xanthine oxidase Mercaptopurine 6-Thiouric acid Thiopurines

Thiopurines

88HalothaneRapid

catecholamine-induced arrhythmias Halothane Theophylline Halothane Theophylline Enflurane

89VinblastineErythromycinDelayed Erythromycin metabolism Vinblastinetoxic side effect vinblastine

90VincristineAzole antifungal agent (Itraconazole)DelayedItraconazole vinca- alkaloid metabolism (CYP3A4) vinca-alkaloid toxicity (neutropenia) 2 vinca-alkaloid toxicity

91VoriconazaleBarbiturate

- PhencbarbitalDelayedBarbiturate metabolism Vinblastine Vinblastine 2

92CarbamazepineDelayedCarbamazepine metabolism Voriconazale Voriconazale 2

93RifampinDelayedRifampin metabolism Voriconazale Voriconazale 2

Drug1Drug 2Recommendation

WarfarinAmiodarone monitor

Danazol, Oxymetholone

Fluconazole, Itraconazole, Ketoconazole, Voriconazole

Phenobarbital

Fenofibrate, Gemfibrozil

Azithromycin, Clarithromycin, Erythromycin, Metronidazole

Quinolones Quinine ,Sulfasalazine, Cotrimoxazole, Doxycycline, Tetracycline

Aspirin, Methylsalicylate

NSAIDs , Celecoxib

Methimazole, Propylthiouracil

Levothyroxine

Vitamin E

Reference1. Tatro S. Drug Interaction Facts 2007. St. Louis: A Wolters Kluwer Company, 20072. Drug interaction. DRUGDEX( System. MICROMEDEX(Healthcare Series Vol. 127.Inc.,Englewood, Colorado. expires 3/2006.3. Lacy CF, Aramstrong LL, Goldman MP & Lance LL. Drug Information Handbook. 14 th ed. Ohio: Lexi-Comp; 2006-2007.

4. Reynolds J.E.F. Martindale The Extra Pharmacopoei, 29 th ed. London: The Pharmaceutical Press; 1993.

5. MIMS annual 19 th ed; 2007 6. Drug Interaction . cited 2009 Febuary 20 . Available from :https://www.thomsonhc.com/hcs/librarian/PFDefaultActionId/pf.LoginAction

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