INTERAKSI OBAT DALAM

KLINIK

Hilda Muliana
Unit Farmasi
 Interaksi Obat

• Peristiwa dimana aksi suatu obat diubah

atau dipengaruhi oleh obat lain yang
diberikan bersamaan
• Kemungkinan terjadi → bila dua obat atau
lebih diberikan secara bersamaan/hampir
bersamaan → polifarmasi
Angka kejadian Interaksi Obat
Stokley, Drug Interaction, 2008
– Penelitian di USA → 4,1 % kejadian interaksi
– American study yg lain → 2,9% dan Swedish study → 1,9%
– Australian study → 4,4% kejadian interaksi
– Emergency Departement USA → 47-50% potensial drug interaction
– French study → 16%
Majalah Farmasi Indonesia, 17 (4), 2006
– Penelitian RSUD Prof Dr Marsono Soekarjo Purwokerto, 32 px dr 46 px
(69%) → potensi interaksi obat
 Tipe Interaksi Obat

1. Interaksi Farmasetik
Interaksi fisiko kimia → tjd rx fisiko kimiawi
antara obat-obat shg mengubah aktivitas
farmakologik obat
Mis. Rx obat2 yg dicampur dlm cairan scr
bersamaan (infus, suntikan)
2. Interaksi Farmakokinetik
Terjadi perubahan kdr obat dlm drh krn
perubahan proses ADME
 Proses absorbsi : food, chelation, GI motility, pH
Obat Interaksi dg Efek yg tjd
Tetrasiklin Ca2+, Mg2+, Fe3+ ↓ absorbsi tetrasiklin
Tetrasiklin NaHCO3 ↓ absorbsi tetrasiklin
Digoksin Metoklopramide ↓ absorbsi digoksin
Ampicillin Makanan ↓ absorbsi ampisilin
Captopril Makanan ↓ absorbsi captopril

Proses distribusi : ikatan protein, transport protein

Obat Interaksi dg Efek yg tjd
Tolbutamide Fenilbutason, Salisilat Hipoglikemia
Warfarin Salisilat Perdarahan
 Proses metabolisme : enzyme induction,
enzyme inhibitor

• Enzym induction :obat dpt memacu metabolisme

obat lain → mpcepat eliminasi obat tsb → ↑
kecepatan eliminasi → ↓ kdr obat dlm darah → kdr
optimal tdk tercapai
• Enzym inhibitor : metabolisme obat dihambat oleh
obat lain → ↑ kdr obat dlm darah → melampaui
ambang toksik
Cytochrome P 450 : Protein of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are
monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids
and other lipids.
Cytocrom P 450 yang paling penting : CYP1A2, CYP2C9, CYP2C19,
CYP2D6, CYP2E1, CYP3A4
Isoenzym Substrate Inhibitors Inducers
CYP1A2 Clozapine Cimetidine Polyccyclic
Cyclobenzaprine Ciprofloxacin Aromatic
Fluvoxamine Clarithromycin Hydrocarbon
Mexiletine Enoxacin (Cigarette Smoke)
Propanolol Erythromycin
Theophylin Fluvoxamine
Ofloxacin
Ticlopidin
CYP2C9 Diclofenac, Flurbiprofen Amiodarone, Phenobarbital
Ibuprofen Fluconazole Rifampin
Losartan Fluoxetine,
Naproxen Isoniazide
Phenytoin Ticlopidine,
Piroxicam Zafirlukast
Tolbutamide
Warfarin
CYP2C19 Amitriptiline, Clomipramine Cimetidine, Carbamazepine
Ciclophosphamide Fluoxetine
Diazepam Ketokonazole
Imipramine, Lansoprazole Lansoprazole,
Omeprazole, Phenytoin Omeprazole
Ticlopidine
Isoenzym Substrate Inhibitors Inducers
CYP2D6 Amitriptiline, Clomipramine Amiodarone, Rifampin
Codein, Fluoxetine
Dextromethorphan, Haloperidol,
Metoprolol Indinavir
Propanolol, Risperidone Quinidine
Ritonavir
Sertraline
CYP2E1 Acetaminophen Disulfiram Ethanol
Ethanol Isoniazide
Halothane
Isoflurane
CYP3A4 Alprazolam Amiodarone, Carbamazepine
Calcium channel blocker Cimetidine Phenytoin
Carbamazepine, Cisapride Clarythromicin, Rifampin
Cyclosporine Erythromicin Ritonavir
Lovastatine, Midazolam Grapefruit juice,
Simvastatin Itraconazole
Ketokonazole
Proses eskresi : metabolit melalui organ ekskresi
terutama ginjal, dpt mpengaruhi obat-obat lain.

Obat Interaksi dg Efek yg tjd

Penisilin Probenesid ↑ kadar penislilin
Metotreksat Salisilat ↑ efek toksik mtx
Digoksin Kinidin toksisitas digoksin
Salisilat Probenesid toksisitas salisilat
Indometasin Probenesid tolsisitas salisilat
Lithium Tiazida toksisitas lithium
Aminoglikosida Furosemid nefrotoksik
aminoglikosida
3. Interaksi farmakodinamik
→ Pengaruh pada tempat kerja
• Additive / synergistic : interaksi dimana efek
dua obat yg bekerja pd tempat yg sama saling
mpkuat
Obat Efek yg tjd
Antipsychotics + antimuscarinic ↑ antimuscarinic effect
Antihypertensi + drug that cause ↑ antihypertensi effect
hypotension (Sildenafil,
Phenothiazines)
Beta-agonist bronchodilators + Hypokalemia
potassium-depleting drug
Drug prolong the QT interval +other Additive prolongation of QT interval,
drug that prolong the QT interval increased risk torsades de pointes
Amiodarone +Disopyramide
Cisapride + Ketokonazole /
Erythromisin
 Obat Efek yg tjd
Methotrexate + co trimoxazole Bone marrow megaloblastic due
to folic acid antagonism
Nephrotoxic drug + nephrotoxic ↑ nephrotoxic
drug
(aminoglikosida, ciclosporin,
cisplatin, vancomycin)
Neuromuskular blockers + drug ↑ Neuromuskular blockers
with neuromuscular blocking
effect (aminoglikosida)
Potassium suplements + Hyperkalemia
potassium sparing drug (ACE
inhibitor, angiotensin II receptor
antagonist, potassium-sparing
diuretics)
 • Antagonistic/ opposing : interaksi dimana efek
dua obat pd tempat yg sama saling
berlawanan atau menetralkan

Obat Interaksi dg Efek yg tjd

ACE inhibitor / loop NSAID Antihypertensive effect
diuretic opposed
Anticoagulant Vitamin K Anticoagulant effect
opposed
Antidiabetic Glucocorticoid Blood glucose-lowering
effects opposed
Levodopa Antiosychotics (those Antiparkinsonian
with dopamine effects opposed
antagonist effects)
Levodopa Tacrine Antiparkinsonian
effects opposed
Antineoplatics Megestrol Antineoplastics effects
possibly opposed
Interaksi obat dengan makanan

Kemungkinan yang menyebabkan dapat

terjadinya interaksi obat dengan makanan :
–Perubahan motilitas lamb dan usus →
kcepatan pengosongan lamb dr saat
msknya makanan
–Perubahan pH, sekresi asam
–Dipengaruhi absorbsi obat oleh proses
adsorbsi dan pbentukan kompleks
 Obat Efek yg tjd bila bersama
makanan
Indometasin ↓ absorbsi indometasin
Eritromisin ↓ absorbsi eritromisin
Rifampisin ↓ absorbsi rifampisin
Ampisillin ↓ absorbsi ampisillin
Tetrasiklin ↓ absorbsi tetrasiklin
Antasida ↓ absorbsi antasida
Cefaleksin ↓ absorbsi cefaleksin
Captopril ↓ absorbsi captopril
 SIGNIFIKANSI INTERAKSI OBAT
Evaluasi kemgkan tjdnya interaksi obat →
signifikansi klinik
Signifikansi klinik → berhub tipe interaksi dan
besarnya efek yg tjd
Faktor utama interaksi obat :
1. Significance rating → tingkat keberartian
interaksi obat, yg ditentukan dg nomor 1-5
berdsrkan tingkat interaksi
2. Onset → wkt yg diperlukan utk menghasilkan
efek klinis dari suatu interaksi, menentukan
seberapa penting tindakan yg harus dilakukan
untuk mhindari akibat dr suatu interaksi
 Onset ada 2 :
1) rapid (cepat) → efek yg tjd dlm wkt 24 jam
setelah pberian obat yg berinteraksi tindakan
pengatasannya sgr diperlukan utk mhindari efek
dr interaksi tsb
2) delayed (lambat) → efek tdk akan terlihat sampai
berhari-hari atau bminggu-minggu setelah obat
yg berinteraksi diberikan, shg tindakan sgr tidak
diperlukan
Tabel Tingkatan dari signifikansi
rating

Significance Severity Documentation

Rating
1 major suspected or >
2 moderate suspected or >
3 minor suspected or >
4 major/moderate posible
5 minor posible
any posible
 3.Severity, ada 3 macam :
1) major → efek interaksi yg tjd kmgkan besar dpt
mengancam jiwa/dpt menyebakan
kerugian/kerusakan permanen
2) moderate → efek dpt menyebabkan
kemunduran status klinik pderita, shg mbthkan
perawatan tambahan, rwt inap atau
perpanjangan wkt rwt inap
3) minor → efek interaksi yg tjd ringan, shg tdk
perlu diperhatikan bahwa hal tsb akibat dr
interaksi obat, shg tdk diperlukan penangana
tambahan
 4. Documentation → apakah dpt menyebabkan
respon klinik dan penilaian kualitas klinik akibat
interaksi yg sesuai dg pustaka

1)established → terbukti, efek obat yg diubah telah

dibuktikan dg penelitian terkontrol
2)probable → efek interaksi sering tjd namun tdk
terbukti secara klinik, kdg hanya merupakan sugesti
krn banyaknya laporan kasus interaksi yg tjd
3)suspected → interaksi dpt tjd dg data kejadian yg
cukup namun diperlukan penelitain lbh lanjut
4)possible → interaksi mgk tjd, data yg sgt terbatas.
Interaksi dpt mbuktikan perubahan kinetik namun
tidak dapat diduga besarnya interaksi
5)unlikely → interaksi yg tjd tdk secara nyata
mengubah efek klinik, artinya efek yg tjd diragukan
krn blm ada bukti yg cukup
 UPAYA MENGHINDARI
DAMPAK NEGATIF :

– Hindari pemakaian obat gabungan (polifarmasi),

kec bila kondisi peny yg diobati memerlukan gab
obat yg terbukti bermanfaat secara ilmiah (co.
pengobatan TB, infeksi berat/sepsis)
– Jika memang hrs mberikan obat gabungan (> 2)
bersamaan, yakinkan bahwa tdk ada interaksi yg
merugikan, baik secara kinetik maupun dinamik
– Evaluasi efek sesudah pberian obat-obat scr
bersamaan untuk menilai efek samping/toksisitas
dr salah satu/ semua obat
 Khusus Interaksi farmasetik :

• jgn memberikan campuran obat (infus,

suntikan) kecuali yakin betul tidak ada
interaksi antar masing-masing obat
• dianjurkan sedapat mgk menghindari
pberian obat bersama-sama lwt infus
• memperhatikan petunjuk pberian obat dari
pbuatnya (manufactured leaflet) → u/
melihat peringatan pd pcampuran dan cara
pberian (parenteral)
Khusus Interaksi farmasetik :
• siapkan larutan hanya kalau diperlukan, jgn
mencampur larutan dan menyimpan nya
lama, karena tiap obat memiliki stabilitas yg
berbeda-beda
• pastikan tdk ada perubahan warna,
kekeruhan, precipitasi dari larutan, baik
sblm ataupun setelah dicampur
• jika hrs memberi per infus 2 mcm obat,
berikan lwt 2 jalur infus, kec yakin tdk ada
interaksi. Bila perlu, jgn ragu-ragu
menanyakan kpd apoteker/farmasi
TERIMA KASIH
 TABEL KOMPATIBILITAS OBAT DG BERBAGAI
LARUTAN INFUS
No Nama obat Nacl NaCl D5 D10 D5 RL D5 NaCl D5 NaCl D5 NaCl RL
0.45% 0.9% 0.225% 0.45% 0.9%
1 Albumin C C C C C
2 Amfoterisin X C C X C X X

3 Amikasin C C C C C C C C C
4 Aminophilin C C C C C C C C C
5 Amiodaron C* C*

6 Ampisilin C P X X X X C*
7 As Ascorbat C C C C C C C C C
8 Asetazolamid C C C C C C C
9 Aciklovir C C
10 Aztreonam C C
11 Bleomycin C C*

12 Dexamehason C C C

13 Diazepam C* C* C*

14 Diphenhydramine C C C C C C C C C

15 Digoksin C C C C C C
No Nama obat Nacl NaCl D5 D10 D5 RL D5 NaCl D5 NaCl D5 NaCl RL
0.45% 0.9% 0.225% 0.45% 0.9%
16 Doxorubicin C C C

17 Dopamin C C C C C C C

18 Droperidol C C C

19 Epinephrin C C C C C C C C

20 Fenitoin C* X C*

21 Fenobarbital C C C C C C C C C
22 Flukonazole C C

23 Fluorouracil C C C C C

24 Fosfomisin C C
25 Furosemide C C C C C C

26 Gansiklovir C C
27 Gentamycin C C C C C

28 Heparin C C* C C* C C C* C*

29 Kalium KLorida C C C C C C C C C
30 Kalsium C C C C C C C C
Glukonas
31 Kanamycin C C C C C

32 Karboplatin C C C C

33 Klindamycin C C C C C C C
34 Kloramphenikol C C C C C C C C C
35 Klorpromazin C C C C C C C C C
No Nama obat Nacl NaCl D5 D10 D5 RL D5 NaCl D5 NaCl D5 NaCl RL
0.45% 0.9% 0.225% 0.45% 0.9%
36 Kotrimoksasol C C* C* C C C

37 Kuinidin sulfat C

38 Lidikain HCl C C C C C C C

39 Magnesium C C C C
sulfat
40 Metotreksat C C C C

41 Metildopa C C C C

42 Metilprednisolo C C* C C C*
n
43 Metoklopramid C C C C
e
44 Metronidazole C C C

45 Nidazolam C C C

46 Morfin sulfat C C C C C C C C C
47 Natrium C C C C X C C C C*
bikarbonat
48 Nitrogliserin C C* C* C C C C

49 Oksitosin C C C C C C C C C
50 Propanolol C C C C C C
No Nama obat Nacl NaCl D5 D10 D5 RL D5 NaCl D5 NaCl D5 NaCl RL
0.45% 0.9% 0.225% 0.45% 0.9%
51 Ranitidin C C C C* C C

52 Sefazolin C C C C C C C

53 Sefepim C C C C C

54 Sefoperazone C C

55 Sefotaksim C C C C C C C

56 Seftazidim C C C C
57 Seftriakson C C C C C C*
58 Siklofosfamide C C C C C C

59 Siklosporin C C
60 Simetidin C C C C C C C C
61 Sicplatin C C C* C C C
62 Tetrasiklin C C C C C C C C
63 Vankomisin C C C C C C

64 Verapamil C C C C C C C

65 Vinkristin C C C

Ket . D5 : dextrose 5%, D10 : dextrose 10%, RL : ringer laktat, C : compatible, X : uncompatible
No Nama obat Nacl NaCl D5 D10 D5 RL D5 NaCl D5 NaCl D5 NaCl RL
0.45% 0.9% 0.225% 0.45% 0.9%
51 Ranitidin C C C C* C C

52 Sefazolin C C C C C C C

53 Sefepim C C C C C

54 Sefoperazone C C

55 Sefotaksim C C C C C C C

56 Seftazidim C C C C
57 Seftriakson C C C C C C*
58 Siklofosfamide C C C C C C

59 Siklosporin C C
60 Simetidin C C C C C C C C
61 Sicplatin C C C* C C C
62 Tetrasiklin C C C C C C C C
63 Vankomisin C C C C C C

64 Verapamil C C C C C C C

65 Vinkristin C C C

Ket . D5 : dextrose 5%, D10 : dextrose 10%, RL : ringer laktat, C : compatible, X : uncompatible
 TABEL INTERAKSI OBAT
(Medfacts Pocket Guide of Drug Interactions, 2004; Stockley Drug
Interaction, 2008; Drug Interaction Facts, 2004)
Data yg diambil  rating scale that potensial interaction has a moderate to major severity

Obat Interaksi dg Efek potensial Managemen

ADRENERGIC MODIFIERS
Clonidine Beta blockers Increased blood pressure Monitor blood pressure
(acebutolol,
betaxolol, carteolol,
esmolol, metoprolol,
nadolol, penbutolol,
pindolol,propanolol,
timolol)
Tricyclic antidepressant Loss of blood pressure Avoid combination
(amitriptiline, control. Increased
clomipramine) risk of hypertensive
crisis
Methyldopa Sympathomimetics Increased blood pressure Monitor blood pressure
(dobutamine,
dopamin, ephedrin,
epinephrin,
norepinephrin,
pseudoephedrin)
Prazocin Beta blockers Increased postural Monitor for symptoms of
(acebutolol, betaxolol, hypotension postural hypotension
carteolol, esmolol,
metoprolol, nadolol,
penbutolol, pindolol,
propanolol, timolol)

Verapamil Increased postural Monitor for symptoms of

hypotension postural hypotension

ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACEIs) : Benazepril, Captopril,

Enalapril, Fosinopril, Lisinopril, Perindopril, Quinapril, Trandolapril
ACEIs-class Indomethacin Decreased ACEIs Monitor blood pressure

Potassium-sparing Elevated serum Monitor serum potassium

diuretics (amiloride, potassium
spironolacton)

Captopril Food Decreased GI absorbtion Administer captoril 1 hour

of captopril before meals

ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs)

ARBs-class Lithium Increase concentration Monitor lithium

lithium concentration and for
signs/symptoms of
toxicity
BETA BLOCKERS : Cardio-selective (acebutolol, atenolol, betaxolol, bisoprolol, esmolol, metoprolol, nadolol)
Non Cardio-selective (carteolol, carvedilol, labetalol, penbutolol, pindolol, propanolol, sotalol, timolol)

Cardio-selective and Non
Cardio-selective Beta
Blockers-class
Barbiturat (amobarbital, Decreased bioavability of Increase beta blocker dose if
pentobarbital, phenobarbital) beta blocker necessary
Cimetidine Increased concentration of Monitor cardiovaskular status.
BB Decreased BB if necessary

NSAID (ibuprofen, Decreased effects of BB Monitor blood pessure.

indomethacin, naproxen, Increase BB dose in
piroxicam) necessary
Verapamil Increased effects of both Monitor cardiovaskular status.
drugs Decrease dose of one or both
drugs if necessary

Atenolol Ampicillin Decrease effects of atenolol Separate administration

times. Monitor blood
pressure. Increase atenolol
dose if necessary

CALCIUM-CHANNEL BLOCKERS (CCBs) : Amlodipin, Diltiazem, Felodipin, Nicardipin, Nifedipin,

Nimodipin, Verapamil
Diltiazem Carbamazepine Increased concentration of Monitor carbamazepin
carbamazepin concentration. Adjust dose as
needed when starting or
stopping diltiazem

Theophylline (aminophilin, Increased concentration of Monitor theophylin

theophilin) theophilyn concentration. Adjust
theophylin dose as needed
when starting or stopping
diltiazem
Nifedipin Barbiturat (amobarbital, Decreased effects of Monitor cardiovaskular
pentobarbital, nifedipin status. Increases
phenobarbital) nifedipin dose if
necessary
Cimetidin Increased effects of Adjust nifedipin dose as
nifedipin needed when starting,
stopping, or changing
dose of cimetidin. Use
alternatif histamin H2
antagonist (eg, ranitidin)

Rifampin Decreased effects of Monitor cardiovaskular

nifedipin status. Adjust nifedipin
dose as needed when
starting or stopping
rifampin

Verapamil Digoxin Increased concentration Monitor cardiovaskular

of digoksin status and digoxin
concentration. Decrease
digoxin dose in
necessary

MISCELLANEOUS ANTIHYPERTENSIVE AND CARDIOVASKULAR AGENTS

Digoksin Aminoglicoside Decreased concentration Monitor digoksin

(kanamycin, neomycin, of digoksin concentration. Increase
paromomycin) digoksin
Amiodarone Increased concentration of Monitor digoksin
digoksin concentration and for
signs/symtoms of digolsin
toxicity. Decrease digoksin
dose in necessary

Cholestyramine Decreased concentration of Separate administration

digoksin times. Monitor for decreased
digoksin effects. Increase
dogoksin dose in necessary

Cyclosporine Increased concentration of Monitor digoksin

digoksin concentration and for
signs/symtoms of digolsin
toxicity. Decrease digoksin
dose in necessary

Itraconazole Increased concentrations of Monitor digoksin

digoksin in premature infants concentration and for
signs/symtoms of digolsin
toxicity. Decrease digoksin
dose in necessary

Loop diuretics (furosemid) Increased risk of arrhythmia Monitor serum potassium and
magnesium concentration
Macrolide (clarithromicin,
erythromicin)
Metoclopramide
Spironolacton
Thiazide Diuretics (HCT)
Thioamines (propylthiouracil)
Thyroid hormon (
levothyroxine, thyroid)
Verapamil
Increased concentration of
digoksin
Decreased concentration of
digoksin
Decrease inotropic effects
Increased risk of arrhytmia
Increased concentration of
digoksin
Decreased concentration of
digoksin
Increased concentration of
digoksin
Monitor digoksin
concentration and for
signs/symtoms of digolsin
toxicity. Decrease digoksin
dose in necessary
Monitor for decreased
digoksin effects. Increase
digoksin dose in neccesary
Monitor for decreased
digoksin effects. Increase
digoksin dose if necessary
Monitor serum potassium and
magnesium concentration
Monitor digoksin
concentration and for
signs/symtoms of digolsin
toxicity. Decrease digoksin
dose in necessary
Increase digoksin dose if
necessary in hypothyroid
patients if they become
euthyroid
Monitor digoksin
concentration and for
signs/symtoms of digolsin
toxicity. Decrease digoksin
dose in necessary
Epinephrine Beta blockers (carteolol,
nadolol, penbutolol, pindolol,
propanolol, timolol)
ANTIBACTERIAL ANTIBIOTICS
AMINOGLICOSIDE : amikacin, gentamycin, kanamycin, neomycin, streptomicin, tobramycin
Aminoglikosida-class Cephalosporin (cefamandole,
cefazolin, cefonicid,
cefoperazone, cefotaxime,
cefotetan, cafalotin,
ceftazidim, ceftizoxime,
ceftriakson, cefuroksim,
cephradine)
Loop diuretics (furosemide)
NSAIDs (diklofenak,
ibuprofen, ketoprofen,
ketorolac, piroxicam,
mefemanic acid, naproxen)
Penicillin (ampicillin,
methicillin, nafcillin, oxacillin,
penicillin G, piperacillin,
ticarcilin)
Initial Hypertensive episode,
followed by reflex bradycardia
Increase risk of nephrotoxicity
Increased risk of auditory
toxicity
Increased concentration of
aminoglikosida in premature
infants
Inactivation of aminoglikosida
Avoid combination if possible.
Discontinue Beta blockers 3
dats prior to epinephrine use
in posibble. Otherwise
monitor vital signs and use IV
chlorpromazine, IV
hydralazin, IV aminophilin,
and/or IV atropine if
necessary
Monitor aminoglikosida
concentration and kdney
function
Avoid excessive dose of
either drug. Monitor
aminoglikosida concentration.
Use alternative antibiotic if
possible
Avoid combination if possible.
Otherwise, decrease
aminoglikoside dose before
starting NSAID. Monitor
aminoglikosida concentration
and renal function
Do not mix drugs in same
solution. Separate
administration times by at
least 2 hours
CEPHALOSPORIN : Cefamandole, Cefazolin, Cefoperazone, Cefotaxime, Ceftazidim, Ceftizoxime, Ceftriakson,
Cefuroksim, Cephalothin, Cephradine
Cephalosporin-class Aminoglikosida Increase risk of Monitor aminoglikosida
nephrotoxicity concentration and kdney
function

Ethanol Disulfuram-like reaction Avoid combination

PENICCILLIN : Amoxicillin, Ampicillin, Cloxacillin, Dicloxacillin, Penicillin G, Penicillin V, Piperacillin, Ticarcilin

Penicillin-class Food Decreased or delayed GI Administer penicillin at
absorbtion of oral least 2 hours before or
penicillin after a meal

Aminoglikosida Inactivation of Do not mix drugs in

aminoglikosida same solution. Separate
administration times by
at least 2 hours

Ampicillin Allopurinol Increase rate of Decrease allopurinol

ampicillin associated skin dose or use alternative
rash drug if rash develops

Atenolol Decreased effects of Separate administration

atenolol times. Monitor blood
pressure. Increase
atenolol dose if
necessary
QUINOLONES : Ciprofloxacin, Gatifloxacin, Levofloxacin, Moxifloxacin, Ofloxacin, Sparfloxacin
Quinolone -class Iron salts (Fe fumarate, Fe
gluconate, Fe sulfat)
Antacids (Aluminum hidrixide,
aluminum-magnesium
hydroxide, calcium
carbonate)
Sucralfate
Ciprofloxacin, Norfloxacin Food (milk)
AZOLE ANTIFUNGALS : Fluconazole, Itraconazole, Ketokonazole, Mocinazole, Vorikonazole
Azole antifungals-class Grapefruit Juice
Ketokonazole, Itraconazole Hydantoins (Phenytoin)
Proton pump inhibitors
(Esomeprazole,
Lansoprazole, Omeprazole,
Pantoprazole, Rabeprazole)
Itraconazole Food/cola
Decreased GI absorbtion of Avoid combination
quinolone
Decreased GI absorbtion of Separate administration times
quinolone by at least 2 hours
Decreased GI absorbtionof Administer sucralfat at least 6
quinolone hours after quinolone
Decreased GI absorbtion Avoid combination
ciprofloxacin/norfloxacin
Decreased GI absorbtion of Avoid combination
azole antifungal
Decreased effects of Avoid combination
itraconazole/ketokonazole.
Increased effects of
hydantoin
Decreased GI absorbtion of Avoid combination if possible
itraconazole/ketokonazole
Increased GI absorbtion of Administer drug immediately
itraconazole after meals
ANTIMYCOBACTERIAL AGENTS

Isoniazid Rifampin Increased risk Monitor liver function

hepatotoxic tests. Discontinue one or
both drugs if necessary

Rifamycin-class Isoniazide Increased risk Monitor liver function

(Rifabutin, Rifampin, hepatotoxic tests. Discontinue one or
Rifapentine) both drugs if necessary

ANTICOAGULANTS/THROMBOLYTIC AGENTS

Heparin Salisilat (aspirin) Increased risk of bleeding Monitor for

Warfarin Acetaminophen
Amiodarone
Azole antifungals
(fluconazole, itraconazole,
ketokonazole, miconazole)
sign/symptoms of
bleeding
Increased effects of Limit acetaminophen use.
warfarin Monitor INR more
frequently with chronic or
high dose of
acetaminophen
Increased effects of Monitor INR. Decrease
warfarin warfarin dose empirically
and adjust warfarin dose
as needed
Increased effects of Monitor INR. Adjust
warfarin warfarin dose as needed
when starting or stopping
azole antifungal
Cephalosporins Increased effects of warfarin Monitor INR. Adjust warfarin
dose as needed when starting
or stopping cephalosporin

Cimetidine Increased effects of warfarin Avoid combination if possible.

Otherwise, monitor INR and
decrease warfarin dose if
necessary. Use alternative
histamin H2 antagonist (eg
ranitidin)

Macrolide antibiotics Increased effects of warfarin Monitor INR. Decrease

warfarin dose if necessary

Metronidazole Increased effects of warfarin Monitor INR. Decrease

warfarin dose if necessary

NSAID Increased effects of warfarin Monitor INR and for

Increased risk of bleeding signs/symptoms of bleeding.
Treat symptomatically

Penicillin Increased effects of warfarin Monitor INR. Decrease

with large doses of IV warfarin dose if necessary
penicillin. Nafcillin and
Dicloxacillin can cause
warfarin resistance

Salicylates (aspirin) Increased effects of warfarin Avoid large doses of aspirin.

with large doses of salisylate. Monitor INR and for
Increased risk of bleeding with signs/symptoms of bleeding.
any aspirin dose Treat symtomatically