DRUG INTERACTIONS

No. Drug-Drug Interactions Severity Documentation Summary

1 Concurrent use of
CLOPIDOGREL and
NICARDIPINE may result in
decreased antiplatelet effect and
increased risk of thrombotic
Clopidogrel Hydrogen Sulfate
Fair events. (enzim berebut
+ Nicardipine HCl Major
pemetabolisme, clopidogrel tidak
aktif sehingga membutuhkan
enzim pengaktivasi) namun
penggunaan nicardipin pada pasien
ini tidak lama (sementara)

Warning:
Concurrent use of CLOPIDOGREL and NICARDIPINE may result in decreased antiplatelet effect and
increased risk of thrombotic events.

Clinical Management:

Coadministration of clopidogrel and niCARdipine, a calcium channel blocker, may decrease the effect of
clopidogrel on platelet inhibition, and increase the risk of atherothrombotic events (Siller-Matula et al, 2008;
Lee et al, 2011). The addition of cilostazol may reduce these potentially harmful interactions (Lee et al,
2011). Use caution if clopidogrel and niCARdipine are used concurrently and monitor patients for loss of
clopidogrel efficacy.

Onset:
Not Specified

Severity:
Major

Documentation:
Fair

Probable Mechanism:
inhibition of CYP3A-mediated clopidogrel activation by niCARdipine

Summary:

Although the effects from coadministration of clopidogrel and niCARdipine (a calcium channel blocker
(CCB)) have not been studied in a large number of patients, in 2 prospective studies, other CCBs
significantly decreased the effect of clopidogrel on platelet activity by CYP3A inhibition of the activation of
clopidogrel to its active metabolite, and increased subsequent thrombotic events (Siller-Matula et al, 2008;
Lee et al, 2011). The addition of cilostazol may reduce these potentially harmful interactions (Lee et al,
2011). Caution is advised if clopidogrel and CCBs, such as niCARdipine, are used concurrently. Monitor
patient for loss of clopidogrel efficacy.

Literature:

In a prospective, observational study of 200 patients with coronary artery disease undergoing percutaneous
coronary intervention, coadministration of clopidogrel and calcium channel blocking agents (n=45;
amlodipine, n=35; nifedipine, nitrendipine, and diltiazem, n=3; nisoldipine, n=1) significantly decreased
clopidogrel inhibitory effects as assessed by vasodilator-stimulated phosphoprotein (VASP)
phosphorylation assay. Platelet reactivity index (PRI) was significantly higher in patients receiving
clopidogrel and a calcium channel blocker (61%) compared to patients receiving clopidogrel alone (48%).
Similarly, decreased platelet inhibition by clopidogrel (PRI greater than 69%) was found in 40% of patients
given both drugs compared with 20% of those treated with clopidogrel alone (p=0.008). No significant effect
on platelet aggregation was seen in vitro when clopidogrel was combined with a calcium channel blocker,
suggesting the interaction is mediated by the CYP3A4 enzyme. Patients were followed for 6 months, and
those (25%) treated with clopidogrel and a calcium channel blocker experienced death from cardiovascular
causes, non fatal myocardial infarction, stent thrombosis, revascularization, or coronary artery bypass graft
compared with 8% of patients treated with clopidogrel alone (Siller-Matula et al, 2008).

In a post-hoc analysis of the prospective, randomized study of 900 Korean patients with coronary heart
disease undergoing percutaneous coronary intervention (PCI) with drug-eluting stents, concomitant use of
clopidogrel with aspirin and calcium channel blockers (CCB, n=239; amlodipine, 55%, n=132; diltiazem,
34.7%, n=83) significantly decreased the antiplatelet effect of clopidogrel as assessed by the VerifyNow
P2Y12 assay and significantly increased the rate of a composite of cardiac death, non-fatal myocardial
infarction, and ischemic stroke. In patients who received clopidogrel 75 mg/day and aspirin 100 mg/day, the
on-treatment platelet reactivity (OPR) at discharge significantly increased with concomitant CCB use as
compared with CCB non-use (mean OPR +/- standard error of the mean (SEM) 251.2+/-7.6 vs 225.6+/-5.1,
respectively; p=0.008). However, this difference was moderated in those patients who received cilostazol
200 mg/day in addition to the clopidogrel plus aspirin therapy (mean OPR +/- SEM at discharge, 214.5+/-
9.1 vs 203.4+/-5.6 for CCB users vs non-users; p=0.297). At the 6-month follow-up, these effects were
maintained. A composite of cardiac death, non-fatal myocardial infarction, and ischemic stroke was also
assessed at 6 months after PCI. This composite increased in patients who received clopidogrel and aspirin
with CCB use as compared with CCB non-use (4.9% vs 0.9%, respectively; p=0.016), but not in patients
who also received cilostazol (0% vs 1.8% for CCB users vs non-users; p=0.346) (Lee et al, 2011).

Reference(s):

Lee SP, Bae JW, Park KW et al: Inhibitory interaction between calcium channel blocker and clopidogrel. -
Efficacy of cilostazol to overcome it-. Circ J 2011; 75(11):2581-2589.

Siller-Matula JM, Lang I, Christ G et al: Calcium-channel blockers reduce the antiplatelet effect of
clopidogrel. J Am Coll Cardiol Nov 4, 2008; 52(19):1557-1563.

Copyright 2018 Truven Health Analytics LLC

2
Concurrent use of
CLOPIDOGREL and
NIFEDIPINE may result in
decreased antiplatelet effect and
increased risk of thrombotic
events.
(enzim berebut pemetabolisme,
Clopidogrel Hydrogen Sulfate
Excellent clopidogrel tidak aktif sehingga
+ Nifedipine Major
membutuhkan enzim pengaktivasi)
penggunaan nifedipine pada pasien
ini lama (continue) maka
sebaiknya digantikan brilinta, plan
ke dua yakni ditambahkan
cilostazol/asetosal.

Warning:
Concurrent use of CLOPIDOGREL and NIFEDIPINE may result in decreased antiplatelet effect and
increased risk of thrombotic events.

Clinical Management:
Coadministration of clopidogrel and NIFEdipine, a calcium channel blocker, may decrease the effect of
clopidogrel on platelet inhibition, and increase the risk of atherothrombotic events (Siller-Matula et al, 2008;
Lee et al, 2011). Use caution if these agents are used concurrently and monitor patients for loss of
clopidogrel efficacy.

Onset:
Not Specified

Severity:
Major

Documentation:
Excellent

Probable Mechanism:
inhibition of CYP3A4-mediated clopidogrel activation by NIFEdipine

Summary:

In 2 prospective studies, calcium channel blocking agents significantly decreased the effect of clopidogrel
on platelet activity by CYP3A4 inhibition of the activation of clopidogrel to its active metabolite, and
increased subsequent thrombotic events (Siller-Matula et al, 2008; Lee et al, 2011). The addition of
cilostazol may reduce these potentially harmful interactions (Lee et al, 2011). Caution is advised if
clopidogrel and calcium channel blockers, such as NIFEdipine are used concurrently. Patients may need to
be monitored for loss of clopidogrel efficacy.

Literature:

In a prospective, observational study of 200 patients with coronary artery disease undergoing percutaneous
coronary intervention, coadministration of clopidogrel and calcium channel blocking agents (n=45;
amlodipine, n=35; NIFEdipine, nitrendipine, and diltiazem, n=3; nisoldipine, n=1) significantly decreased
clopidogrel inhibitory effects as assessed by vasodilator-stimulated phosphoprotein (VASP)
phosphorylation assay. Platelet reactivity index (PRI) was significantly higher in patients receiving
clopidogrel and a calcium channel blocker (61%) compared to patients receiving clopidogrel alone (48%).
Similarly, decreased platelet inhibition by clopidogrel (PRI greater than 69%) was found in 40% of patients
given both drugs compared with 20% of those treated with clopidogrel alone (p=0.008). No significant effect
on platelet aggregation was seen in vitro when clopidogrel was combined with a calcium channel blocker,
suggesting the interaction is mediated by the CYP3A4 enzyme. Patients were followed for 6 months, and
those (25%) treated with clopidogrel and a calcium channel blocker experienced death from cardiovascular
causes, non fatal myocardial infarction, stent thrombosis, revascularization, or coronary artery bypass graft
compared with 8% of patients treated with clopidogrel alone (Siller-Matula et al, 2008).

In a post-hoc analysis of the prospective, randomized study of 900 Korean patients with coronary heart
disease undergoing percutaneous coronary intervention (PCI) with drug-eluting stents, concomitant use of
clopidogrel with aspirin and calcium channel blockers (CCB, n=239; amlodipine, 55%, n=132; diltiazem,
34.7%, n=83; NIFEdipine, n=7) significantly decreased the antiplatelet effect of clopidogrel as assessed by
the VerifyNow P2Y12 assay and significantly increased the rate of a composite of cardiac death, non-fatal
myocardial infarction, and ischemic stroke. In patients who received clopidogrel 75 mg/day and aspirin 100
mg/day, the on-treatment platelet reactivity (OPR) at discharge significantly increased with concomitant
CCB use as compared with CCB non-use (mean OPR +/- standard error of the mean (SEM) 251.2+/-7.6 vs
225.6+/-5.1, respectively; p=0.008). However, this difference was moderated in those patients who
received cilostazol 200 mg/day in addition to the clopidogrel plus aspirin therapy (mean OPR +/- SEM at
discharge, 214.5+/-9.1 vs 203.4+/-5.6 for CCB users vs non-users; p=0.297). At the 6-month follow-up,
these effects were maintained. A composite of cardiac death, non-fatal myocardial infarction, and ischemic
stroke was also assessed at 6 months after PCI. This composite increased in patients who received
clopidogrel and aspirin with CCB use as compared with CCB non-use (4.9% vs 0.9%, respectively;
p=0.016), but not in patients who also received cilostazol (0% vs 1.8% for CCB users vs non-users;
p=0.346) (Lee et al, 2011).

Reference(s):
Lee SP, Bae JW, Park KW et al: Inhibitory interaction between calcium channel blocker and clopidogrel. -
Efficacy of cilostazol to overcome it-. Circ J 2011; 75(11):2581-2589.

Siller-Matula JM, Lang I, Christ G et al: Calcium-channel blockers reduce the antiplatelet effect of
clopidogrel. J Am Coll Cardiol Nov 4, 2008; 52(19):1557-1563.

Copyright 2018 Truven Health Analytics LLC

3 Concurrent use of
ANTIDIABETIC AGENTS and
BETA-ADRENERGIC
BLOCKERS may result in
Acarbose + Bisoprolol hypoglycemia or hyperglycemia;
Good
Fumarate Moderate decreased symptoms of
hypoglycemia.
Mengurangi sensasi deg-deg an
(gejala hipoglikemi) -> (lakukan
monitoring GD secara rutin)

Warning:
Concurrent use of ANTIDIABETIC AGENTS and BETA-ADRENERGIC BLOCKERS may result in
hypoglycemia or hyperglycemia; decreased symptoms of hypoglycemia.

Clinical Management:

Concurrent use of antidiabetic agents with beta-blockers may increase or decrease the blood glucose
lowering effect of the antidiabetic agent, and may decrease or obscure signs and symptoms of
hypoglycemia. Increased frequency of glucose monitoring or dose adjustment of the antidiabetic agent may
be required (Prod Info TOUJEO® subcutaneous injection, 2015; Prod Info AMARYL® oral tablets, 2013).
Closely monitor for hypoglycemia with concurrent use, and if the beta-blocker is withdrawn, observe for
signs of loss of glycemic control (Prod Info Glynase® PresTab® oral micronized tablets, 2013).

Onset:
Delayed

Severity:
Moderate

Documentation:
Good

Probable Mechanism:
altered glucose metabolism and beta blockade

Summary:

Concomitant antidiabetic drugs and beta-blockers may lead to hypo- or hyperglycemia, or may obscure
symptoms of hypoglycemia (Prod Info TOUJEO® subcutaneous injection, 2015; Prod Info AMARYL® oral
tablets, 2013). Tachycardia, but not other symptoms of hypoglycemia, such as dizziness and sweating,
may be affected (Prod Info TENORMIN® oral tablets, 2012). Nonselective beta blockers can potentiate
insulin-induced hypoglycemia and interfere with recovery of serum glucose levels. Worsening
hyperglycemia may occur in patients with heart failure and diabetes (Prod Info COREG CR® extended-
release oral capsules, 2011). Increased frequency of glucose monitoring or dose adjustment of the
antidiabetic agent may be required (Prod Info TOUJEO® subcutaneous injection, 2015; Prod Info
AMARYL® oral tablets, 2013). Closely monitor for signs and symptoms of hypoglycemia with concurrent
use, and if the beta-blocker is withdrawn, observe for loss of glycemic control (Prod Info Glynase®
PresTab® oral micronized tablets, 2013).

Literature:

The choice of antihypertensive drug in elderly patients with diabetes who were taking either insulin or
sulfonylureas had little effect on the risk of hypoglycemia, but after adjustment for other risk factors, the
lowest risk was with cardioselective beta blockers and the highest with non-cardioselective beta blockers,
with other antihypertensive drugs having intermediate results (N=13,559) (Shorr et al, 1997).

Beta blockers, but not alpha blockade and ACE inhibitors, caused a deterioration in long-term glycemic
control in patients with hypertension and non-insulin dependent diabetes. Some adverse effects on the lipid
profile also occurred with beta blockade. These effects were especially apparent with propranolol.
Concurrent use of an alpha blocker with the beta blocker prevented the deterioration due to beta blockade
(Whitcroft et al, 1990).

Reference(s):

Product Information: AMARYL(R) oral tablets, glimepiride oral tablets . Sanofi-Aventis U.S. LLC (per FDA),
Bridgewater, NJ, Oct, 2013.

Product Information: COREG CR(R) extended-release oral capsules, carvedilol phosphate extended-
release oral capsules. GlaxoSmithKline, Research Triangle Park, NC, Jan, 2011.

Product Information: Glynase(R) PresTab(R) oral micronized tablets, glyburide oral micronized tablets.
Pharmacia & Upjohn Co (per FDA), New York, NY, Oct, 2013.

Product Information: TENORMIN(R) oral tablets, atenolol oral tablets. AstraZeneca Pharmaceuticals LP
(per FDA), Wilmington, DE, Oct, 2012.

Product Information: TOUJEO(R) subcutaneous injection, insulin glargine subcutaneous injection. sanofi-
aventis (per manufacturer), Bridgewater, NJ, Feb, 2015.

Shorr RI, Ray WA, Daugherty JR et al: Antihypertensives and the risk of serious hypoglycemia in older
persons using insulin or sulfonylureas. JAMA 1997; 278:40-43.

Whitcroft IA, Thomas JM, Rawsthorne A et al: Effects of alpha and beta adrenoceptor blocking drugs and
ACE inhibitors on long term glucose and lipid control in hypertensive non-insulin dependent diabetics.
Horm Metab Res Suppl 1990; 22:42-46.

Copyright 2018 Truven Health Analytics LLC

4 Concurrent use of
ANTIDIABETIC AGENTS and
SELECTED DIURETICS may
result in increased hyperglycemia
risk; increased insulin
Acarbose + Furosemide Fair
Moderate requirement.
(Furosemide (obat diuretik) dapat
menurunkan volume cairan
sehingga meningkatkan
hiperosmolar dalam tubuh ketika
 ditambahkan dengan Acarbose
(obat golongan anti glikemi).
Rekomendasi : monitor glukosa
darah.

Warning:
Concurrent use of ANTIDIABETIC AGENTS and SELECTED DIURETICS may result in increased
hyperglycemia risk; increased insulin requirement.

Clinical Management:

Certain diuretic agents may alter glucose tolerance or blood glucose levels, possibly predisposing the
patient to hyperglycemia or loss of glycemic control. Insulin requirements may be increased (Prod Info
TOUJEO® subcutaneous injection, 2015; Prod Info Tresiba subcutaneous injection solution, 2013),
decreased, or unchanged (Prod Info chlorthalidone oral tablets, 2004). If concomitant use of a diuretic and
an antidiabetic agent is required, monitor glucose levels more frequently, including upon withdrawal of the
diuretic (Prod Info XIGDUO(TM) XR oral extended release tablets, 2014; Prod Info GLUMETZA® oral
extended-release tablets, 2013). Dose adjustment of oral antidiabetic agents or insulin may be required
(Prod Info ACCURETIC(TM) oral tablets, 2015; Prod Info DYRENIUM® oral capsules, 2005; Prod Info
chlorthalidone oral tablets, 2004).

Onset:
Not Specified

Severity:
Moderate

Documentation:
Fair

Probable Mechanism:
altered glucose metabolism

Summary:

Certain diuretic agents may alter glucose tolerance or blood glucose levels, possibly predisposing the
patient to hyperglycemia or loss of glycemic control. Insulin requirements may be increased (Prod Info
TOUJEO® subcutaneous injection, 2015; Prod Info Tresiba subcutaneous injection solution, 2013),
decreased, or unchanged (Prod Info chlorthalidone oral tablets, 2004). If concomitant use of a certain
diuretic and an antidiabetic agent is required, monitor glucose levels more frequently, including upon
withdrawal of the diuretic (Prod Info XIGDUO(TM) XR oral extended release tablets, 2014; Prod Info
GLUMETZA® oral extended-release tablets, 2013). Dose adjustment of oral antidiabetic agents or insulin
may be required (Prod Info ACCURETIC(TM) oral tablets, 2015; Prod Info DYRENIUM® oral capsules,
2005; Prod Info chlorthalidone oral tablets, 2004).

Reference(s):

Product Information: ACCURETIC(TM) oral tablets, quinapril HCl hydrochlorothiazide oral tablets. Parke-
Davis (per FDA), New York, NY, Feb, 2015.

Product Information: DYRENIUM(R) oral capsules, triamterene oral capsules. Wellspring Pharmaceutical
Corporation, Ontario, Canada, Oct 1, 2005.

Product Information: GLUMETZA(R) oral extended-release tablets, metformin HCl oral extended-release
tablets. Santarus, Inc. (per Manufacturer), San Diego, CA, Jan, 2013.

Product Information: TOUJEO(R) subcutaneous injection, insulin glargine subcutaneous injection. sanofi-
aventis (per manufacturer), Bridgewater, NJ, Feb, 2015.

Product Information: Tresiba subcutaneous injection solution, insulin degludec subcutaneous injection
solution. Novo Nordisk A/S (per EMA), Bagsvaerd, Denmark, Oct, 2013.

Product Information: XIGDUO(TM) XR oral extended release tablets, dapagliflozin metformin HCl oral
extended release tablets. AstraZeneca Pharmaceuticals LP (per manufacturer), Wilmington, DE, Oct, 2014.

Product Information: chlorthalidone oral tablets, chlorthalidone oral tablets. Pliva,Inc, East Hanover, NJ,
Mar 1, 2004.

Copyright 2018 Truven Health Analytics LLC

5 Concurrent use of ACARBOSE

and NIFEDIPINE may result in
loss of glucose control.
(Monitor blood glucose, dan/atau
adjustment dosis)

Pada obat Ca Channel Blocker

menghambat pengeluaran (sekresi)
insulin dikarenakan mekansime
sekresi insulin membutuhkan Ca,
apabila Ca di blok maka sekresi
akan terhambat.

Molekul ATP yang terbentuk,

dibutuhkan untuk tahap
selanjutnya yakni proses
Acarbose + Nifedipine Fair mengaktifkan penutupan K
Moderate
channel pada membran sel.
Penutupan ini berakibat
terhambatnya pengeluaran ion K
dari dalam sel yang menyebabkan
terjadinya tahap depolarisasi
membran sel, yang diikuti
kemudian oleh tahap pembukaan
Ca channel. Keadaan inilah yang
memungkinkan masuknya ion Ca
ke dalam sel β sehingga
menyebabkan peningkatan kadar
ion Ca intrasel dan memicu
exocytosis insulin. Selanjutnya
molekul insulin masuk ke dalam
sirkulasi darah terikat dengan
reseptor. Ikatan insulin dan
 reseptornya membutuhkan GLUT-
4 glucose transporter untuk dapat
masuk ke dalam sel otot
danjaringan lemak, serta uptake
glukosa dengan efisien, yang
akhirnya menurunkan kadar
glukosa dalam plasma

Warning:
Concurrent use of ACARBOSE and NIFEDIPINE may result in loss of glucose control.

Clinical Management:

NIFEdipine tends to produce hyperglycemia. Concomitant administration of NIFEdipine and acarbose may
result in a loss of glucose control. Monitor blood glucose levels carefully. Consider dose adjustment to
maintain glucose control.

Onset:
Delayed

Severity:
Moderate

Documentation:
Fair

Probable Mechanism:
NIFEdipine-induced hyperglycemia

Summary:

NIFEdipine may produce hyperglycemia and may lead to loss of glucose control. When NIFEdipine and
acarbose are co-administered, monitoring of blood glucose levels is recommended (Prod Info Adalat® CC
Extended Release Tablets, 2004).

Reference(s):

Product Information: Adalat(R) CC Extended Release Tablets, nifedipine extended release tablets.
Schering Corporation, Kenilworth, NJ, USA, October, 2004.

Copyright 2018 Truven Health Analytics LLC

6 Concurrent use of
CANDESARTAN and
POTASSIUM-SPARING
DIURETICS may result in
Candesartan Cilexetil +
Fair increased risk of hyperkalemia.
Spironolactone Moderate

Berjalan di sistem RAAS (Renin

Angiotensin Aldosteron System)
sehingga berebut.
Warning:
Concurrent use of CANDESARTAN and POTASSIUM-SPARING DIURETICS may result in increased risk
of hyperkalemia .

Clinical Management:

Use of candesartan with potassium-sparing diuretics (such as amiloride, eplerenone, spironolactone, or

triamterene), potassium supplements, potassium-containing salt substitutes, or other drugs that raise
potassium levels may result in hyperkalemia. Monitor serum potassium levels (Prod Info ATACAND® oral
tablets, 2016).

Onset:
Not Specified

Severity:
Moderate

Documentation:
Fair

Probable Mechanism:
additive hyperkalemia

Summary:

Use of candesartan with potassium-sparing diuretics (such as amiloride, eplerenone, spironolactone, or

triamterene), potassium supplements, potassium-containing salt substitutes, or other drugs that raise
potassium levels may result in hyperkalemia. Monitor serum potassium levels (Prod Info ATACAND® oral
tablets, 2016).

Reference(s):

Product Information: ATACAND(R) oral tablets, candesartan cilexetil oral tablets. AstraZeneca LP (per
FDA), Wilmington, DE, Feb, 2016.

Copyright 2018 Truven Health Analytics LLC

7 Concurrent use of
CLOPIDOGREL and CYP3A4
METABOLIZED STATINS may
result in decreased formation of
Clopidogrel Hydrogen Sulfate
Excellent clopidogrel active metabolite
+ Simvastatin Moderate
resulting in high on-treatment
platelet reactivity.

Rebutan enzim pemetabolisme.

Warning:
Concurrent use of CLOPIDOGREL and CYP3A4 METABOLIZED STATINS may result in decreased
formation of clopidogrel active metabolite resulting in high on-treatment platelet reactivity.

Clinical Management:

If a patient develops high on-treatment platelet reactivity during treatment with clopidogrel and a statin
metabolized by CYP3A4 (ie, atorvastatin, lovastatin, or simvastatin), discontinue the statin and substitute a
statin that is not metabolized by CYP3A4 (ie, pravastatin or rosuvastatin) (Park et al, 2012).

Onset:
Not Specified

Severity:
Moderate

Documentation:
Excellent

Probable Mechanism:
competition with CYP3A4-mediated metabolism and inhibition of P-glycoprotein efflux transport of
clopidogrel by CYP3A4-metabolized statins

Summary:

Patients treated with clopidogrel, which is partially metabolized to its active metabolite by CYP3A4 and P-
glycoprotein efflux transport, may develop high on-treatment platelet reactivity with concomitant use of a
CYP3A4-metabolized statin (ie, atorvastatin, lovastatin, or simvastatin). In a clinical study, patients
undergoing percutaneous coronary intervention with high on-treatment platelet reactivity during concurrent
use of clopidogrel and atorvastatin demonstrated a significant reduction in platelet reactivity and enhanced
clinical response to clopidogrel after switching to pravastatin or rosuvastatin (both non-CYP3A4-
metabolized statins). If a patient develops high on-treatment platelet reactivity during concomitant treatment
with clopidogrel and a CYP3A4-metabolized statin (ie, atorvastatin, lovastatin, or simvastatin), consider
discontinuation of that statin, and substitution with a statin that is not metabolized by CYP3A4 (ie,
pravastatin or rosuvastatin) (Park et al, 2012).

Literature:

Patients undergoing percutaneous coronary intervention (PCI) with high on-treatment platelet reactivity
(HPR; defined as 20 micromoles adenosine diphosphate (ADP)-induced maximal platelet aggregation
(MPA) greater than 50%) received chronic atorvastatin 10 mg daily and clopidogrel 75 mg daily and then
were randomly assigned to receive 15 days of either rosuvastatin 10 mg (n=25) or pravastatin 20 mg
(n=25) daily instead of atorvastatin. After switching statins, MPA levels after stimuli with 20 and 5
micromolar ADP decreased by 6.6% (95% CI, 3.2%% to 10.1%; p less than 0.001) in the rosuvastatin
group and by 6.3% (95% CI, 2.5 to 10.2%; p=0.002) in the pravastatin group and the prevalence of HPR
decreased by 24% (p less than 0.001) (Park et al, 2012).

Reference(s):

Park Y, Jeong YH, Tantry US et al: Accelerated platelet inhibition by switching from atorvastatin to a non-
CYP3A4-metabolized statin in patients with high platelet reactivity (ACCEL-STATIN) study. Eur Heart J
Sep, 2012; 33(17):2151-2162.

Copyright 2018 Truven Health Analytics LLC

 DRUG COMPATIBILITY

A. Y-Site Test Details = contohnya : 3 way

No. Nama Obat Rating
1 Furosemide + Nicardipine Hydrochloride
Incompatible
Rekomendasi : waktu
pemberian di pisah atau
dipindah line lain (di
tangan kanan dan kanan
kiri)
2 Furosemide + Ranitidin Hydrochloride
Compatible
3 Nicardipine Hydrochloride + Ranitidine
Caution : Variable
Hydrochloride

Furosemide
Intravenous

 (Injection) Administer up to 80 mg IV slowly over 1 to 2 minutes [6]

 (Injection) May be given undiluted [6]
 (High-dose infusion) Add to NS, LR, or D5W after pH has been adjusted to above 5.5 and infuse at
a rate not greater than 4 mg/min [6]
 (Pediatrics, 17 years or less) Dilute in at least an equal volume of intravenous fluid and give at a
rate no greater than 1 mg/kg/2 minutes with an infusion not exceeding 10 minutes [15]
 (Pediatrics, 17 years or less) May give undiluted by slow intravenous push at a rate of 1 mg/kg over
at least 1 to 2 minutes [15]

Subcutaneous

 Doses of furosemide as bolus or continuous subQ infusion with an elastomeric pump ranged from
40 to 140 mg/day for a duration ranging from 3 days to 8 months. All patients used a butterfly
needle of 25 or 23 gauge . Injection sites in the pectoral region were better tolerated compared with
those in the extremities (study dosage) [8].
 Continuous subQ furosemide administration for 4 or 5 days (96 mL at 1 mL/hr or 250 mL at 2 ml/hr
depending on pump volume and preset flow rate) utilizing an elastomeric pump has been used in
an outpatient setting. Pumps were connected to a catheter (Abbocath 20 to 22 gauge) implanted
subcutaneously in the chest or abdominal tissue. The calculated dose was given in D5W (study
dosage) [16].
 Nicardipin HCl

Intravenous

 Ampules must be diluted with NS, D5W, or other compatible solution to a final concentration of 0.1
mg/mL [9]
 Diluted solution is stable at room temperature for 24 hr [9]
 Administer as a slow, continuous infusion; do not administer through small veins (e.g. those on the
dorsum of the hand or wrist); change the infusion site every 12 hours if a peripheral vein is
used [7][8][9]

Ranitidine HCl

Intramuscular

 No dilution is necessary [5].

Intravenous

 (Injection for intermittent bolus) Dilute ranitidine 50 mg (2 mL) in NS or other compatible IV solution
to a concentration no greater than 2.5 mg/mL (20 mL) and inject at a rate no greater than 4 mL/min
(usually 5 minutes) [5].
 (Injection for intermittent infusion) Dilute ranitidine 50 mg (2 mL) in D5W or other compatible IV
solution to a concentration no greater than 0.5 mg/mL (100 mL) and infuse at a rate no greater than
5 to 7 mL/min (usually 15 to 20 minutes) [5].
 (Injection for continuous infusion) Dilute in D5W or other compatible IV solution and infuse at a rate
of 6.25 mg/hr [5].
 (Injection for continuous infusion) For Zollinger-Ellison patients, dilute in D5W or other compatible
IV solution to a concentration no greater than 2.5 mg/mL; start infusion at a rate of 1 mg/kg/hr [5].
 Stable for 48 hours at room temperature when added to or diluted with most commonly used IV
solutions [5]

Furosemide + Nicardipine Hydrochloride

Drug 1 Drug 2 Status Information Test Parameters
Furosemide Nicardipine Physical Reference: 2062
10mg/mL`in` hydrochloride Compatibility:Physically
Undiluted 1mg/mL`in` D5W- incompatible. Study Period:4 hours.
Incompatible Precipitation appeared
Dextrose 5%
American Regent immediately upon Method:Visual
Wyeth Laboratories mixing. observation.

Storage:Room Container:Simulated
temperature of 27 °C Y-site administration
exposed to fluorescent using glass vials.
light.
Drug 1 Drug 2 Status Information Test Parameters
Furosemide Nicardipine Physical Reference: 8632
3mg/mL`in` D5W- hydrochloride Compatibility:Physically
Dextrose 5% 0.1mg/mL`in` D5W- incompatible. White Study Period:4 hours.
Incompatible cloudy precipitation
Dextrose 5%
American Regent appeared upon mixing. Method:Visual
Wyeth Laboratories observation and
Storage:Ambient electronic
conditions near 23 °C measurement of haze
exposed to fluorescent and particulates. The
light. methods used in this
testing have been
described in the
published articles cited
below and have also
been used in
numerous other
published drug
compatibility studies:
1. Trissel LA, Martinez
JF. Physical
compatibility of
melphalan with
selected drugs during
simulated Y-site
administration. Am J
Hosp Pharm 1993;
50:2359-63. 2. Trissel
LA, Bready BB.
Turbidimetric
assessment of the
compatibility of taxol
with selected other
drugs during simulated
Y-site injection. Am J
Hosp Pharm
1992;49:1716-9. 3.
Trissel LA and
Martinez JF.
Turbidimetric
assessment of the
compatibility of taxol
with selected other
drugs during simulated
Y-site injection, Part 2.
Am J Hosp Pharm
1993; 50:300-4. 4.
Trissel LA, Gilbert DL,
Martinez JF.
Incompatibility and
compatibility of
amphotericin B
cholesteryl sulfate
complex with selected
other drugs during
simulated Y-site
administration. Hosp
Pharm 1998; 33:284-
92.

Container:Simulated
Y-site administration
using glass test tubes.
 Furosemide + Ranitidin Hydrochloride
Drug 1 Drug 2 Status Information Test Parameters
Furosemide Ranitidine Physical Reference: 2062
10mg/mL`in` hydrochloride Compatibility:Physically
Undiluted 1mg/mL`in` D5W- compatible. No visible Study Period:4 hours.
Compatible haze or particulate
Dextrose 5%
American Regent formation, color change, Method:Visual
Glaxo or gas evolution. observation.

Storage:Room Container:Simulated Y-
temperature of 27 °C site administration
exposed to fluorescent using glass vials.
light.
Drug 1 Drug 2 Status Information Test Parameters
Furosemide Ranitidine Physical Reference: 8842
5mg/mL`in` D5W- hydrochloride Compatibility:Physically
Dextrose 5% 2mg/mL`in` D5W- compatible. No changes Study Period:4 hours.
Compatible in measured haze or
Dextrose 5%
American Regent turbidity, particulates, or Method:Visual
Glaxo Wellcome Inc. color were found. observation and
electronic assessment.
Storage:Ambient room
temperature near 23 °C Container:Simulated Y-
exposed to normal site administration
fluorescent light. using glass test tubes.
Drug 1 Drug 2 Status Information Test Parameters
Furosemide Ranitidine Physical Reference: 8842
5mg/mL`in` Normal hydrochloride Compatibility:Physically
saline- Sodium 2mg/mL`in` Normal compatible. No changes Study Period:4 hours.
Compatible in measured haze or
chloride 0.9% saline- Sodium
chloride 0.9% turbidity, particulates, or Method:Visual
American Regent color were found. observation and
Glaxo Wellcome Inc. electronic assessment.
Storage:Ambient room
temperature near 23 °C Container:Simulated Y-
exposed to normal site administration
 fluorescent light. using glass test tubes.
Drug 1 Drug 2 Status Information Test Parameters
Furosemide Ranitidine Physical Reference: 8842
5mg/mL`in` hydrochloride Compatibility:Physically
Dextrose 5% in 2mg/mL`in` compatible. No changes Study Period:4 hours.
Compatible in measured haze or
sodium chloride Dextrose 5% in
0.9% sodium chloride turbidity, particulates, or Method:Visual
0.9% color were found. observation and
American Regent electronic assessment.
Glaxo Wellcome Inc. Storage:Ambient room
temperature near 23 °C Container:Simulated Y-
exposed to normal site administration
fluorescent light. using glass test tubes.
Drug 1 Drug 2 Status Information Test Parameters
Furosemide Ranitidine Physical Reference: 8842
5mg/mL`in` hydrochloride Compatibility:Physically
Dextrose 5% in 2mg/mL`in` compatible. No changes Study Period:4 hours.
Compatible in measured haze or
sodium chloride Dextrose 5% in
0.45% sodium chloride turbidity, particulates, or Method:Visual
0.45% color were found. observation and
American Regent electronic assessment.
Glaxo Wellcome Inc. Storage:Ambient room
temperature near 23 °C Container:Simulated Y-
exposed to normal site administration
fluorescent light. using glass test tubes.
 Nicardipine Hydrochloride + Ranitidine Hydrochloride
Drug 1 Drug 2 Notes:Variable compatibility results have been reported
for this drug combination possibly depending on drug
Nicardipine Ranitidine
concentrations and/or testing methodologies.
hydrochloride hydrochloride
Status Information Test Parameters
0.1mg/mL`in` 0.5mg/mL`in` Physical Reference: 0235
D5W-Dextrose D5W-Dextrose Compatibility:Physicall
5% 5%
Compatibl y compatible. No Study Period:24
e visible haze or hours.
Dupont Critical Glaxo particulate formation,
Care color change, or gas Method:Visual
evolution. observation.

Storage:Room Container:Simulate
temperature exposed to d Y-site
fluorescent light. administration
using glass tubes.

Drug 1 Drug 2 Notes:Variable compatibility results have been reported

for this drug combination possibly depending on drug
Nicardipine Ranitidine
concentrations and/or testing methodologies.
hydrochlorid hydrochloride
e 2mg/mL`in` Status Information Test Parameters
0.1mg/mL`in` D5W-Dextrose Physical Reference: 8629
D5W- 5% Compatibility:Physical
Dextrose 5%
Incompatibl ly incompatible. White Study Period:4
GlaxoSmithKli cloudy precipitation
e hours.
Wyeth ne appeared upon mixing.
Laboratories Method:Visual
Storage:Ambient observation and
conditions near 23 °C electronic
exposed to fluorescent measurement of
light. haze and
particulates. The
methods used in
this testing have
been described in
the published
articles cited below
and have also been
used in numerous
other published
drug compatibility
studies: 1. Trissel
LA, Martinez JF.
Physical
compatibility of
melphalan with
selected drugs
during simulated
Y-site
administration. Am
J Hosp Pharm
1993; 50:2359-63.
2. Trissel LA,
Bready BB.
Turbidimetric
assessment of the
compatibility of
taxol with selected
other drugs during
simulated Y-site
injection. Am J
Hosp Pharm
1992;49:1716-9. 3.
Trissel LA and
Martinez JF.
Turbidimetric
assessment of the
compatibility of
taxol with selected
other drugs during
simulated Y-site
injection, Part 2.
Am J Hosp Pharm
1993; 50:300-4. 4.
Trissel LA, Gilbert
DL, Martinez JF.
 Incompatibility
and compatibility
of amphotericin B
cholesteryl sulfate
complex with
selected other
drugs during
simulated Y-site
administration.
Hosp Pharm 1998;
33:284-92.

Container:Simulat
ed Y-site
administration
using glass test
tubes.

Drug 1 Drug 2 Notes:Variable compatibility results have been reported

for this drug combination possibly depending on drug
Nicardipine Ranitidine
concentrations and/or testing methodologies.
hydrochloride hydrochloride
Status Information Test Parameters
1mg/mL`in` 1mg/mL`in` Physical Reference: 2062
D5W-Dextrose D5W-Dextrose Compatibility:Physicall
5% 5%
Compatibl y compatible. No Study Period:4
e visible haze or hours.
Wyeth Glaxo particulate formation,
Laboratories color change, or gas Method:Visual
evolution. observation.

Storage:Room Container:Simulate
temperature of 27 °C d Y-site
exposed to fluorescent administration
light. using glass vials.
 B. Admixture Test Details > 50 cc -> dicampur di cairan infuse nya
No. Nama Obat Rating
1 Furosemide + Nicardipine Hydrochloride
Not Tested
2 Furosemide + Ranitidin Hydrochloride
Compatible
3 Nicardipine Hydrochloride + Ranitidine
Not Tested
Hydrochloride

Furosemide + Ranitidine Hydrochloride

Test
Drug 1 Drug 2 Status Information
Parameters
Furosemide Ranitidine Physical Reference: 1515
0.4mg/mL hydrochloride Compatibility:Physically
0.05mg/mL (50 compatible. No visible Study Period:24
Compatible D5W- haze or particulate
Manufacturer mcg/mL) hours.
Dextrose formation, color change,
Unspecified
5%Manufacturer or gas evolution.
Glaxo Method:Visual
Unspecified
observation and
Chemical HPLC analysis of
Stability:Chemically ranitidine
stable. Adequate hydrochloride.
ranitidine hydrochloride
concentration was Container:Not
retained for 24 hours. specified.
Furosemide was not
analyzed.

Storage:Room
temperature of 25 °C
exposed to fluorescent
light.
 Test
Drug 1 Drug 2 Status Information
Parameters
Furosemide Ranitidine Physical Reference: 1515
0.4mg/mL hydrochloride Compatibility:Physically
2mg/mL compatible. No visible Study Period:24
Compatible D5W- haze or particulate
Manufacturer hours.
Dextrose formation, color change,
Unspecified Glaxo
5%Manufacturer or gas evolution.
Method:Visual
Unspecified
observation and
Chemical HPLC analysis of
Stability:Chemically ranitidine
stable. Adequate hydrochloride.
ranitidine hydrochloride
concentration was Container:Not
retained for 24 hours. specified.
Furosemide was not
analyzed.

Storage:Room
temperature of 25 °C
exposed to fluorescent
light.
Test
Drug 1 Drug 2 Status Information
Parameters
Furosemide Ranitidine Physical Reference: 1479
1mg/mL hydrochloride Compatibility:Physically
0.5mg/mL compatible. No visible Study Period:Up
Compatible haze or particulate
Hoechst to 72 hours.
Normal saline- formation, color change,
Glaxo
Sodium chloride or gas evolution. Method:Visual
0.9%Manufacturer
observation.
Unspecified Storage:Room
temperatures of 15 and Container:Glass
30 °C. containers.
C. Syringe Test Details <=50cc dicampur dalam syringe
No. Nama Obat Rating
1 Furosemide + Nicardipine Hydrochloride
Not Tested
2 Furosemide + Ranitidin Hydrochloride
Not Tested
3 Nicardipine Hydrochloride + Ranitidine
Not Tested
Hydrochloride
 DOSING

A. Furosemide

Chronic kidney disease, Hypoalbuminemic

 40 mg IV bolus with or without albumin 20% 10 mg IV bolus [3]

Congestive heart failure - Edema

 (Tablets, oral solution) Initial, 20 to 80 mg orally as a single dose; may repeat the same dosage 6
to 8 hours later, or increase by 20 to 40 mg and administer no sooner than 6 to 8 hours following
previous dose; titrate to effect, up to 600 mg/day with clinically severe edematous states;
individualized dosage may then be given once or twice daily (eg, at 8 am and 2 pm); for best
results, consider administering on 2 to 4 consecutive days each week (FDA dosage) [4][5]
 (Injection) Initial, 20 to 40 mg IM or slow IV, over 1 to 2 minutes; may repeat same dosage 2
hours later or increase by 20 mg no sooner than 2 hours following previous dose; titrate to effect;
individualized dosage may then be given once or twice daily (FDA dosage) [6]
 (Oral) Chronic heart failure with evidence of fluid retention, 20 to 40 mg orally once or twice daily;
diuretic resistance may be overcome with IV administration or addition of a different diuretic class
(eg, thiazide); MAX 600 mg/day (guideline dosage) [7].
 (Injection) Acute decompensated heart failure receiving chronic oral diuretics, begin continuous IV
infusion or intermittent IV bolus injections at equal to or greater than the chronic oral daily dose
and adjust based on response (guideline dosage) [7].
 (Injection) Acute decompensated heart failure with inadequate diuresis, regimen may be
intensified with higher doses, more frequent dosing, continuous infusion, or addition of a second
(eg, thiazide) diuretic (guideline dosage) [7]
 (Injection) Alternative to IV administration, 40 to 140 mg/day as bolus or continuous subQ infusion
with an elastomeric pump for 3 days to 8 months. Injection sites in the pectoral region were better
tolerated compared with those in the extremities (off-label dosage) [8].

Edema
 (Tablets, oral solution) Initial, 20 to 80 mg orally as a single dose; may repeat the same dosage 6
to 8 hours later, or increase by 20 to 40 mg and administer no sooner than 6 to 8 hours following
previous dose; titrate to effect, up to 600 mg/day with clinically severe edematous states;
individualized dosage may then be given once or twice daily (eg, at 8 am and 2 pm); for best
results, consider administering on 2 to 4 consecutive days each week [4][5]
 (Injection) Initial, 20 to 40 mg IM or slow IV, over 1 to 2 minutes; may repeat same dosage 2
hours later or increase by 20 mg no sooner than 2 hours following previous dose; titrate to effect;
individualized dosage may be then be given once or twice daily [6]

Edema - Renal failure

 (Tablets, oral solution) Initial, 20 to 80 mg orally as a single dose; may repeat the same dosage 6
to 8 hours later, or increase by 20 to 40 mg and administer no sooner than 6 to 8 hours following
previous dose; titrate to effect, up to 600 mg/day with clinically severe edematous states;
individualized dosage may then be given once or twice daily (eg, at 8 am and 2 pm); for best
results, consider administering on 2 to 4 consecutive days each week [4][5]
 (Injection) Initial, 20 to 40 mg IM or slow IV, over 1 to 2 minutes; may repeat same dosage 2
hours later or increase by 20 mg no sooner than 2 hours following previous dose; titrate to effect;
individualized dosage may then be given once or twice daily [6]

Hypertension
 Initial, 80 mg orally daily (divided twice daily in equal doses); individualize based upon patient
response (FDA dosage) [4][5]
 Concomitant medication, reduce dosage of other antihypertensive agents by at least 50% when
furosemide is added to a regimen, further reduction in dosage or discontinuation of other agents
may be necessary (FDA dosage) [4][5].
 Usual dosage range, 20 to 80 mg orally daily in 2 divided doses (guideline dosage) [9]

Nasal polyp; Prophylaxis

 2 puffs twice daily (total daily dose, 300 mcg) for 2 months after endoscopic sinus surgery for
chronic rhinosinusitis associated with polyposis (off-label dosage) [10]
 2 puffs per nostril daily (50 mcg per puff) for 1 month after ethmoidal cleaning, then no treatment
for 2 months, for the first 2 postoperative years; then administer for 1 month and interrupt for 4
months over years 3 through 5; administer for 1 month and interrupt for 6 months for year 6 (off-
label dosage) [11]

Pulmonary edema, acute; Adjunct

 Initial, 40 mg IV slowly, over 1 to 2 minutes; after 1 hour, may increase to 80 mg IV over 1 to 2
minutes [6]
B. Nicardipine Hydrochloride

Normal Dosage
Dosage in Renal Failure
Dosage in Hepatic Insufficiency
Dosage in Geriatric Patients
Dosage in Other Disease States

Normal Dosage
Nicardipine
Nicardipine Hydrochloride
Nicardipine
Arteriosclerotic vascular disease
See Drug Consult reference: Calcium Channel Blocker Therapy of
Atherosclerosis
Nicardipine Hydrochloride
Intra-arterial route
Intrathecal route
Intravenous route
Oral route
Cerebrovascular accident, acute - Hypertension
Intra-arterial route
Subarachnoid hemorrhage - Vasospasm
1) Off-label Dosage
a) Dose: 0.83 mg/mL in distilled water infused intra-arterially, as 0.5 to 1
mL bolus over 60 seconds (0.415 to 0.83 mg/min); titrated to changes in
systolic blood pressure (SBP), stopped when SBP decreased 30% or
more, restarted when SBP recovered to within 20% of preinfusion value,
and terminated when angiographic imaging of severely affected vessel
 segment demonstrated 60% or more recovery of normal diameter, used
in a study [4]
Intrathecal route
Subarachnoid hemorrhage - Vasospasm
1) Off-label Dosage
a) Dose: 2 mg diluted in 10 mL NS intrathecally every 8 hours, after
withdrawal of 10 mL of cerebrospinal fluid and cisternal drain clamped for
1 hour, used in 1 study [5] OR 4 mg intrathecally every 12 hours, used in
1 study [6]
Intravenous route
Electroconvulsive therapy
Hypertension
Hypertension, Postoperative
Malignant hypertension
Subarachnoid hemorrhage - Vasospasm
Electroconvulsive therapy
1) Off-label Dosage
a) Dosage: 2.5 mg IV over 10 to 15 seconds administered 4 minutes prior
to anesthesia induction. Simultaneously administer labetalol 10 mg IV
over 10 to 15 seconds 4 minutes prior to anesthesia induction [11].
Hypertension
1) Patients Not Currently Receiving Nicardipine Hydrochloride Oral
Therapy
a) Initial dosage: 5 mg/hr IV infusion and increase the infusion rate by 2.5
mg/hr every 5 minutes (rapid titration) to every 15 minutes (gradual
titration) [14][15][16].
b) Maximum dosage: 15 mg/hr [14][15][16]
c) Once the desired blood pressure response is achieved, the
niCARdipine hydrochloride infusion rate may be decreased to 3 mg/hr,
and the rate of infusion adjusted as needed to maintain desired
response [14][15][16].
2) Conversion from Oral to Intravenous Nicardipine Hydrochloride
a) The following table may be used to determine the equivalent
intravenous niCARdipine hydrochloride infusion rate for patients currently
receiving oral niCARdipine hydrochloride therapy [14][15][16]:
Oral NiCARdipine Dose Equivalent IV Infusion Rate
20 mg every 8 hours 0.5 mg/hr
30 mg every 8 hours 1.2 mg/hr
40 mg every 8 hours 2.2 mg/hr

3) Conversion from Intravenous Nicardipine Hydrochloride to Oral

Antihypertensive Agents
a) Oral Antihypertensive Agent Other than Nicardipine Hydrochloride
 1) Initiate oral antihypertensive therapy (other than niCARdipine
hydrochloride capsules) when the intravenous niCARdipine hydrochloride
is discontinued [14][15][16].
b) Oral Nicardipine Hydrochloride
1) Initiate treatment with immediate-release niCARdipine hydrochloride
oral capsules 1 hour before the intravenous niCARdipine hydrochloride is
discontinued [14][15][16].
Hypertension, Postoperative
1) Patients Not Currently Receiving Nicardipine Hydrochloride Oral
Therapy
a) Dosage: Initiate at 5 mg/hr IV infusion and increase the infusion rate
by 2.5 mg/hr every 5 minutes (rapid titration) to every 15 minutes
(gradual titration) up to a maximum to 15 mg/hr until desired blood
pressure control is achieved. Once the desired blood pressure response
is achieved, the niCARdipine hydrochloride infusion rate may be
decreased to 3 mg/hr, and the rate of infusion adjusted as needed to
maintain desired response [14][15][16]. If unacceptable hypotension or
tachycardia occurs, discontinue the infusion. Restart the infusion at low
doses, such as 3 to 5 mg/hr [14][15].
2) Conversion from Oral to Intravenous Nicardipine Hydrochloride
a) The following table may be used to determine the equivalent
intravenous niCARdipine hydrochloride infusion rate for patients currently
receiving oral nicardipine hydrochloride therapy [14][15][16]:
Oral NiCARdipine Dose Equivalent IV Infusion Rate
20 mg every 8 hours 0.5 mg/hr
30 mg every 8 hours 1.2 mg/hr
40 mg every 8 hours 2.2 mg/hr

3) Conversion from Intravenous Nicardipine Hydrochloride to Oral

Antihypertensive Agents
a) Oral Antihypertensive Agent Other than Nicardipine Hydrochloride
1) Initiate oral antihypertensive therapy (other than niCARdipine
hydrochloride capsules) when the intravenous niCARdipine hydrochloride
is discontinued [14][15][16].
b) Oral Nicardipine Hydrochloride
1) Initiate treatment with immediate-release niCARdipine hydrochloride
oral capsules 1 hour before the intravenous niCARdipine hydrochloride is
discontinued [14][15][16].
Malignant hypertension
1) Guideline Dosage
a) Initial dosage: 5 mg/hour IV infusion [1]
b) Titration: Increase by 2.5 mg/hour every 5 minutes as needed [1]
c) Maximum dosage: 15 mg/hour [1]
d) With a compelling condition (ie, aortic dissection, severe preeclampsia
or eclampsia, or pheochromocytoma crisis): Decrease systolic blood
 pressure (SBP) to less than 140 mm Hg over the first hour and to less
than 120 mm Hg for aortic dissection [1].
e) Without a compelling indication: Reduce SBP by no more than 25%
within the first hour. If patient is stable, may further reduce to 160/100
mm Hg over the next 2 to 6 hours, then carefully to normal over the
following 24 to 48 hours [1]
Subarachnoid hemorrhage - Vasospasm
1) Off-label Dosage
a) Dose: 0.15 mg/kg/hr continuous IV infusion for up to 14 days following
hemorrhage to prevent symptomatic vasospasm, used in a clinical
study [3]
Oral route
Hypertension
Stable angina, chronic
Hypertension
1) Immediate-release Capsules
a) Initial dosage: 20 mg orally 3 times daily; adjust no sooner than every
3 days to maintenance dosage [12].
b) Maintenance dosage: 20 to 40 mg 3 times daily [12].
2) Sustained-release Capsules
a) Initial dosage: 30 mg orally twice daily. Titrate no sooner than every 3
days to maintenance dosage [12].
b) Maintenance dosage: 30 to 60 mg orally twice daily [12]
c) For patients who are currently receiving niCARdipine hydrochloride
immediate-release (IR) capsules, initiate niCARdipine hydrochloride SR
capsules at the same total niCARdipine hydrochloride IR daily dose and
adjust dose to achieve desired blood pressure [12].
Stable angina, chronic
1) Immediate-release Capsules
a) Initial dosage: 20 mg orally 3 times daily [12]
b) Titration: Adjust no sooner than every 3 days [12]
c) Maintenance dosage: 20 to 40 mg orally 3 times daily [12].
Cerebrovascular accident, acute - Hypertension
a) Guideline Dosage, Intracerebral Hemorrhage with Systolic Blood Pressure
Greater than 220 mm Hg
1) Initial dosage: 5 mg/hour IV infusion [1]
2) Titration: Increase by 2.5 mg/hour every 5 minutes as needed [1]
3) Maximum dosage: 15 mg/hour [1]

Dosage in Renal Failure

A) Nicardipine Hydrochloride
1) Intravenous
a) Titrate infusion gradually [14][15][16].
2) Oral
 a) (Immediate-release) Initial, 20 mg orally 3 times daily, titrate cautiously [64]
b) (Sustained-release) Initial, 30 mg orally twice daily, titrate cautiously [65]

Dosage in Hepatic Insufficiency

A) Nicardipine Hydrochloride
1) Intravenous
a) Consider lower initial dosages and titrate infusion gradually [14][15][16].
2) Oral, Immediate-release
a) Severe impairment: Initial, 20 mg orally twice daily; adjust based on clinical findings and
maintain twice daily schedule [12]

Dosage in Geriatric Patients

A) Nicardipine Hydrochloride
1) Intravenous
a) Consider lower initial dosages [14][15][16].

Dosage in Other Disease States

A) Nicardipine Hydrochloride
1) Intravenous
a) Heart Failure
1) Titrate infusion gradually [14][15][16].
b) Hypotension of Tachycardia
1) In patients who develop hypotension or tachycardia, discontinue the IV niCARdipine
hydrochloride infusion. After blood pressure and heart rate stabilize, the niCARdipine
hydrochloride infusion may be reinitiated at a low dose (eg, 3 to 5 milligrams/hour) and titrated to
maintain blood pressure [14][15].
C. Ranitidine Hydrochloride

Normal Dosage
Dosage in Renal Failure
Dosage in Hepatic Insufficiency
Dosage Adjustment During Dialysis

Normal Dosage
Important Note
Ranitidine
Ranitidine Hydrochloride
Important Note
Ranitidine Hydrochloride
Beers Criteria: Use caution or avoid use as potentially inappropriate in older
adults [1].
Ranitidine
Stress ulcer; Prophylaxis
See Drug Consult reference: H2-Antagonists - Continuous Infusion for Stress
Ulcer Prophylaxis
Ranitidine Hydrochloride
Intramuscular route
Intravenous route
Oral route
Administration of drug or medicament via enteral tube
Intramuscular route
Duodenal ulcer disease
Gastric hypersecretion
Zollinger-Ellison syndrome
Duodenal ulcer disease
 1) Intractable Duodenal Ulcers
a) Usual dosage: 50 mg IM every 6 to 8 hours [4]
See Drug Consult reference: Class Comparison: H2 Receptor
Antagonists (Selected)
Gastric hypersecretion
1) Usual dosage: 50 mg IM every 6 to 8 hours [4]
See Drug Consult reference: Class Comparison: H2 Receptor
Antagonists (Selected)
Zollinger-Ellison syndrome
1) Usual dosage: 50 mg IM every 6 to 8 hours [4]
See Drug Consult reference: Class Comparison: H2 Receptor
Antagonists (Selected)
Intravenous route
Duodenal ulcer disease
Gastric hypersecretion
Stress ulcer; Prophylaxis
Zollinger-Ellison syndrome
Duodenal ulcer disease
1) Intermittent IV Bolus, Intractable Duodenal Ulcers
a) Usual dosage: 50 mg intermittent IV bolus every 6 to 8 hours [4]
b) Administration: Give by bolus (concentration no greater than 2.5
mg/mL) at a rate up to 4 mL/min [4]
c) Dosage titration: May increase frequency of dosing based on patient
needs [4]
d) Maximum dosage: 400 mg/day [4]
2) Intermittent IV Infusion, Intractable Duodenal Ulcers
a) Usual dosage: 50 mg intermittent IV infusion every 6 to 8 hours [4]
b) Administration: Give by infusion (concentration no greater than 0.5
mg/mL) at a rate no greater than 5 to 7 mL/min [4]
c) Dosage titration: May increase frequency of dosing based on patient
needs [4]
d) Maximum dosage: 400 mg/day [4]
3) Continuous Infusion, Intractable Duodenal Ulcers
a) Usual dosage, intractable duodenal ulcers: 6.25 mg/hr continuous IV
infusion [4]
See Drug Consult reference: Class Comparison: H2 Receptor
Antagonists (Selected)
Gastric hypersecretion
1) Intermittent IV Bolus
a) Usual dosage: 50 mg intermittent IV bolus every 6 to 8 hours [4]
b) Administration: Give by bolus (concentration no greater than 2.5
mg/mL) at a rate up to 4 mL/min [4]
c) Dosage titration: May increase frequency of dosing based on patient
needs [4]
 d) Maximum dosage: 400 mg/day [4]
2) Intermittent IV Infusion
a) Usual dosage: 50 mg intermittent IV infusion every 6 to 8 hours [4]
b) Administration: Give by infusion (concentration no greater than 0.5
mg/mL) at a rate no greater than 5 to 7 mL/min [4]
c) Dosage titration: May increase frequency of dosing based on patient
needs [4]
d) Maximum dosage: 400 mg/day [4]
3) Continuous IV Infusion
a) Usual dosage: 6.25 mg/hr continuous IV infusion [4]
See Drug Consult reference: Class Comparison: H2 Receptor
Antagonists (Selected)
Stress ulcer; Prophylaxis
1) Intravenous bolus injections of ranitidine (50 milligrams every 6
hours) have been shown to be as effective as intravenous infusion
regimens (125 or 250 micrograms/kilogram/hour) in controlling gastric
pH in critically ill patients on a ventilator. However, pH control was
achieved more quickly with bolus injections as opposed to infusions
(mean pH of 7 achieved within 6 hours with boluses and at 12 and 8
hours with infusions of 125 micrograms/kilogram/hour and 250
micrograms/kilogram/hour, respectively). No advantage of the higher
dose infusion was observed in controlling the gastric pH. It is suggested
that ranitidine be given as a single 50 milligram intravenous bolus as
initial therapy to achieve rapid therapeutic serum levels, and followed
with intravenous infusion of 125 micrograms/kilogram/hour [26].
Zollinger-Ellison syndrome
1) Intermittent IV Bolus
a) Usual dosage: 50 mg intermittent IV bolus every 6 to 8 hours [4]
b) Administration: Give by bolus (concentration no greater than 2.5
mg/mL) at a rate up to 4 mL/min [4]
c) Dosage titration: May increase frequency of dosing based on patient
needs [4]
d) Maximum dosage: 400 mg/day [4]
2) Intermittent IV Infusion
a) Usual dosage: 50 mg intermittent IV infusion every 6 to 8 hours [4]
b) Administration: Give by infusion (concentration no greater than 0.5
mg/mL) at a rate no greater than 5 to 7 mL/min [4]
c) Dosage titration: May increase frequency of dosing based on patient
needs [4]
d) Maximum dosage: 400 mg/day [4]
3) Continuous IV Infusion
a) Usual dosage: 1 mg/kg/hr continuous IV infusion [4]
b) Dosage titration: If after 4 hours, gastric acid output is greater than
10 mEq/hr or patient becomes symptomatic, dose may be increased in
 0.5-mg/kg/hr increments; dosages up to 2.5 mg/kg/hr and rates as high
as 220 mg/hr have been used [4]
See Drug Consult reference: Class Comparison: H2 Receptor
Antagonists (Selected)
Oral route
Duodenal ulcer disease
Duodenal ulcer disease, Maintenance
Erosive esophagitis
Gastric hypersecretion
Gastric ulcer
Gastric ulcer, Maintenance
Gastroesophageal reflux disease
Indigestion, Non-ulcer
Zollinger-Ellison syndrome
Duodenal ulcer disease
1) Capsules or Tablets
a) Usual dosage: 150 mg orally twice daily [3]
b) Alternate regimen: 300 mg orally once daily after the evening meal
or at bedtime [3]
c) Concomitant medications: Antacids may be administered as needed
for pain relief [3]
2) Oral Solution
a) Usual dosage: 150 mg/10 mL orally twice daily [2]
b) Alternate regimen: 300 mg /20 mL orally once daily after the evening
meal or at bedtime [2]
c) Concomitant medications: Antacids may be administered as needed
for pain relief [2]
See Drug Consult reference: Class Comparison: H2 Receptor
Antagonists (Selected)
Duodenal ulcer disease, Maintenance
1) Capsules and Tablets
a) Usual dosage: 150 mg orally once daily at bedtime [3]
2) Oral Solution
a) Usual dosage: 150 mg/10 mL orally once daily at bedtime [2]
See Drug Consult reference: Class Comparison: H2 Receptor
Antagonists (Selected)
Erosive esophagitis
1) Capsules and Tablets
a) Usual dosage (initial treatment): 150 mg orally 4 times a day [3]
b) Usual dosage (maintenance treatment): 150 mg orally twice daily [3]
c) Concomitant medications: Antacids may be administered as needed
for pain relief [3]
2) Oral Solution
 a) Usual dosage (initial treatment): 150 mg/10 mL orally 4 times a
day [2]
b) Usual dosage (maintenance treatment): 150 mg/10 mL orally twice
daily [2]
c) Concomitant medications: Antacids may be administered as needed
for pain relief [2]
See Drug Consult reference: Class Comparison: H2 Receptor
Antagonists (Selected)
Gastric hypersecretion
1) Capsules or Tablets
a) Usual dosage: 150 mg orally twice daily; may administer more
frequently based on individual patient needs; up to 6 g/day have been
used in patients with severe disease [3]
b) Concomitant medications: Antacids may be administered as needed
for pain relief [3]
2) Oral Solution
a) Usual dosage: 150 mg/10 mL orally twice daily; may administer more
frequently based on individual patient needs; up to 6 g/day have been
used in patients with severe disease [2]
b) Concomitant medications: Antacids may be administered as needed
for pain relief [2]
See Drug Consult reference: Class Comparison: H2 Receptor
Antagonists (Selected)
Gastric ulcer
1) Capsules or Tablets
a) Usual dosage: 150 mg orally twice daily [3]
b) Concomitant medications: Antacids may be administered as needed
for pain relief [3]
2) Oral Solution
a) Usual dosage: 150 mg/10 mL orally twice daily [2]
b) Concomitant medications: Antacids may be administered as needed
for pain relief [2]
See Drug Consult reference: Class Comparison: H2 Receptor
Antagonists (Selected)
Gastric ulcer, Maintenance
1) Capsules and Tablets
a) Usual dosage: 150 mg orally once daily at bedtime [3]
2) Oral Solution
a) Usual dosage: 150 mg/10 mL orally once daily at bedtime [2]
See Drug Consult reference: Class Comparison: H2 Receptor
Antagonists (Selected)
Gastroesophageal reflux disease
1) Capsules or Tablets
 a) Usual dosage: 150 mg orally twice daily [3]
b) Concomitant medications: Antacids may be administered as needed
for pain relief [3]
2) Oral Solution
a) Usual dosage: 150 mg/10 mL orally twice daily [2]
b) Concomitant medications: Antacids may be administered as needed
for pain relief [2]
See Drug Consult reference: Class Comparison: H2 Receptor
Antagonists (Selected)
Indigestion, Non-ulcer
1) Treatment
a) Usual dosage: 150 mg orally [8].
b) Maximum dosage: 300 mg in 24 hours [8]
2) Prophylaxis
a) Usual dosage: 150 mg orally taken 30 to 60 minutes before eating or
drinking [8].
b) Maximum dosage: 300 mg in 24 hours [8]
See Drug Consult reference: Class Comparison: H2 Receptor
Antagonists (Selected)
Zollinger-Ellison syndrome
1) Capsules or Tablets
a) Usual dosage: 150 mg orally twice daily; may administer more
frequently based on individual patient needs; up to 6 g/day have been
used in patients with severe disease [3]
b) Concomitant medications: Antacids may be administered as needed
for pain relief [3]
2) Oral Solution
a) Usual dosage: 150 mg/10 mL orally twice daily; may administer more
frequently based on individual patient needs; up to 6 g/day have been
used in patients with severe disease [2]
b) Concomitant medications: Antacids may be administered as needed
for pain relief [2]
See Drug Consult reference: Class Comparison: H2 Receptor
Antagonists (Selected)
Administration of drug or medicament via enteral tube
See Drug Consult reference: Enteral Feeding Tubes and Medication Delivery
General Dosage Information
a) Ranitidine injection may be used as an alternative to the oral dosage form for short-
term use in patients who are unable to take oral medication [4].

Dosage in Renal Failure

A) Ranitidine Hydrochloride
1) Oral
 a) CrCl less than 50 mL/min: 150 mg orally or 10 mL of a 15 mg/mL oral solution every 24
hours [2][3]; if patient's condition requires, may increase dosing interval to every 12 hours or
further with caution [2][3]
b) CrCl less than 30 mL/min or plasma creatinine concentrations exceed 300 micromoles/L: 75
mg orally twice daily [69][70]
c) Renal transplant, serum creatinine 1.7 mg/dL: 150 mg orally once daily for 7 days was safely
used [71]
2) Intravenous
a) CrCl less than 50 mL/min: 50 mg IV every 18 to 24 hours; if patient's condition requires, may
increase dosing interval to every 12 hours or further with caution [4]
b) GFR 20 mL/min or less: Administer one-half the daily dose [72]

Dosage in Hepatic Insufficiency

A) Ranitidine Hydrochloride
1) Cirrhosis: Dose adjustment is not necessary [73].

Dosage Adjustment During Dialysis

A) Ranitidine Hydrochloride
1) Hemodialysis
a) Adjust schedule to administer ranitidine at the end of dialysis [4][2][3].
2) Peritoneal Dialysis
a) Doses of 150 mg once daily are sufficient [74].
3) Hemofiltration
a) Dose supplementation is not required [75].