Está en la página 1de 6

Calcium channel blockers

Calcium channel blockers


See also Hypertension p 243, Angina p 238
For drug interactions see Calcium channel blockers
p 889
Dihydropyridines

Amlodipine p 231
Clevidipine p 862
Felodipine p 232
Lercanidipine p 232
Nifedipine p 232
Nimodipine p 233
Non-dihydropyridines

Diltiazem p 231
Verapamil p 234
Mode of action

Block inward current of calcium into cells in


vascular smooth muscle, myocardium and cardiac
conducting system via L-type calcium channels.
Act on coronary arteriolar smooth muscle to
reduce vascular resistance and myocardial oxygen
requirements, relieving angina symptoms.
Dihydropyridines act mainly on arteriolar smooth
muscle to reduce peripheral vascular resistance
and BP. They have minimal effect on myocardial
cells.
Non-dihydropyridines: diltiazem and verapamil act
on cardiac and arteriolar smooth muscle. They
reduce cardiac contractility, heart rate and
conduction, with verapamil having the greater
effect. Diltiazem has a greater effect on arteriolar
smooth muscle than verapamil.

Pregnancy

Australian category C. Nifedipine is used to


suppress preterm labour and for hypertension in
pregnancy.
Breastfeeding

Limited data for diltiazem, nifedipine, nimodipine


and verapamil but they appear safe to use. No data
available for amlodipine, felodipine or
lercanidipine.
Adverse effects

Most listed adverse effects occur with all calcium


channel blockers.
Adverse effects vary between the calcium channel
blockers according to their relative effects on
vascular, myocardial and conducting tissue.
Dihydropyridines have more pronounced vasodilatory effects than diltiazem and verapamil.
Verapamil, and to a lesser extent, diltiazem, reduce
cardiac contractility, heart rate and conduction.
Common (>1%)

nausea, vasodilatory effects, including headache,


flushing, dizziness, hypotension, peripheral
oedema (below)
Infrequent (0.11%)

palpitations, tachycardia and chest pain with


dihydropyridines, see Precautions above; orthostatic hypotension, abdominal pain, dyspepsia,
diarrhoea, constipation (common with verapamil),
gingival hyperplasia (usually reversible), polyuria
(including nocturia), tinnitus, rash, itch
Rare (<0.1%)

Hypertension
Angina

taste disturbance, elevation of hepatic enzymes,


extrapyramidal reactions, gynaecomastia, hypersensitivity reactions, including Stevens-Johnson
syndrome, exfoliative dermatitis, angioedema and
vasculitis

Precautions

Peripheral oedema

Myasthenia-like neuromuscular diseasecalcium


channel blockers may increase risk of muscle
weakness and respiratory depression (most case
reports with verapamil).

Dihydropyridines commonly cause peripheral


oedema due to redistribution of extracellular fluid
(rather than fluid retention); this does not respond
to treatment with diuretics, which may put patient
at risk of volume depletion.

Indications

Cardiovascular

Contraindicated in cardiogenic shock.


Calcium channel blockers may further depress
myocardial function in patients with systolic heart
failure; diltiazem and verapamil are contraindicated (unless under specialist supervision); use
dihydropyridines with caution.
Angina may worsen when starting a dihydropyridine, increasing the dose or stopping abruptly
(possibly as a result of reflex cardiac stimulation,
which increases heart rate and contractility); less
likely with long-acting dihydropyridines,
controlled release products or use with a betablocker.
In aortic stenosis, dihydropyridines may cause
coronary hypoperfusion and systemic hypotension.

Comparative information
See Table 61 Comparison of calcium channel
blockers p 231
Practice points
vasodilatory adverse effects usually subside with
continued treatment (may require dose
reduction)

Hepatic

May require dose reduction in impairment.


Elderly

Start treatment at a lower dose.

www.amh.net.au

AMH 2014

Calcium channel blockers


Table 61 Comparison of calcium channel blockers
Drug
Indications
Forms
Doses/day

Comments

Dihydropyridines
angina
hypertension

tablet

felodipine

hypertension

CR tablet

lercanidipine

hypertension

tablet

nifedipine

angina
hypertension
preterm labour (p 747)

tablet, CR tablet

2 (tablet)
1 (CR)

nimodipine

aneurysmal subarachnoid
haemorrhage

tablet, injection

6 (tablet)
continuous
infusion

amlodipine

effect on arterial pressure is similar to that


of other antihypertensives
may be used with beta-blockers in stable
angina
minimal effect on cardiac conduction
system and myocardial contractility
use with caution in systolic heart failure
(amlodipine or felodipine may be
considered if necessary)
peripheral vasodilation causes adverse
effects, eg peripheral oedema, flushing,
headache
mainly selective for the cerebral
vasculature

Non-dihydropyridines
diltiazem

angina
hypertension (CR)
AF

tablet, CR
capsule

verapamil

tablet, CR
tablet/capsule,
injection

angina
hypertension
SVT, AF, atrial flutter
prevention of cluster
headache (p 703)

used post-ACS and in stable angina when


3 or 4 (tablet) beta-blockers
are contraindicated or not
1 (CR)
tolerated
reduce heart rate and depress myocardial
contractility (verapamil more than
diltiazem)
2 or 3 (tablet)

contraindicated in systolic heart failure


1 (CR)
less peripheral vasodilation than
dihydropyridines

CR = controlled release

Amlodipine
Dihydropyridine
For additional information see Calcium channel
blockers p 230
For drug interactions see Calcium channel blockers
p 889, Amlodipine p 889
Indications
Hypertension (includes combinations with
olmesartan (p 257), olmesartan (p 257) with
hydrochlorothiazide, telmisartan (p 258), valsartan
(p 258), valsartan (p 258) with hydrochlorothiazide)
Angina
Combination with atorvastatin
Treatment of patients stabilised on atorvastatin and
at least 5 mg of amlodipine daily
Combination with perindopril
See Perindopril p 253
Hypertension if already maintained on perindopril
and amlodipine
Stable coronary heart disease if already maintained
on perindopril and amlodipine
Dosage
Adult, child >6 years, initially 2.55 mg once daily,
increasing if necessary after at least 12 weeks to a
maximum of 10 mg once daily.
Child <6 years, initially 0.10.2 mg/kg once daily,
increasing if necessary over 12 weeks to a
maximum of 0.4 mg/kg or 10 mg once daily.
Elderly, hepatic impairment
Adult, initially 2.5 mg once daily.
Combination with atorvastatin
For additional information see Atorvastatin p 290

Adult, 1 tablet once daily (of any strength).

tab, 5 mg, 30, Amlodipine (DO, GQ, RZ), PBS


tab, 5 mg (scored), 30, Amlo (ZP), Nordip (AL), Norvapine (PF),
Norvasc (PF), Ozlodip (RA), Amlodipine (CH, PF, SZ, TA, TW, TX),
PBS
tab, 10 mg, 30, Amlodipine (CH, DO, GQ, RZ, TW, TX), PBS
tab, 10 mg (scored), 30, Amlo (ZP), Nordip (AL), Norvapine
(PF), Norvasc (PF), Ozlodip (RA), Amlodipine (PF, SZ, TA), PBS

Combination products
tab, amlodipine 5 mg, atorvastatin 10 mg, 30, Cadatin 5/10
(PF), Caduet 5/10 (PF), PBS-R1
tab, amlodipine 5 mg, atorvastatin 20 mg, 30, Cadatin 5/20
(PF), Caduet 5/20 (PF), PBS-R1
tab, amlodipine 5 mg, atorvastatin 40 mg, 30, Cadatin 5/40
(PF), Caduet 5/40 (PF), PBS-R1
tab, amlodipine 5 mg, atorvastatin 80 mg, 30, Cadatin 5/80
(PF), Caduet 5/80 (PF), PBS-R1
tab, amlodipine 10 mg, atorvastatin 10 mg, 30, Cadatin 10/10
(PF), Caduet 10/10 (PF), PBS-R1
tab, amlodipine 10 mg, atorvastatin 20 mg, 30, Cadatin 10/20
(PF), Caduet 10/20 (PF), PBS-R1
tab, amlodipine 10 mg, atorvastatin 40 mg, 30, Cadatin 10/40
(PF), Caduet 10/40 (PF), PBS-R1
tab, amlodipine 10 mg, atorvastatin 80 mg, 30, Cadatin 10/80
(PF), Caduet 10/80 (PF), PBS-R1
1

patients with hypertension and/or angina meeting the


criteria in the PBS General Statement for Lipid-Lowering
Drugs

Diltiazem
Non-dihydropyridine
For additional information see Calcium channel
blockers p 230
See also Atrial fibrillation p 276
For drug interactions see Calcium channel blockers
p 889, Diltiazem p 889
Indications

Angina
Hypertension (controlled release)
Accepted

AF or atrial flutter (ventricular rate control)

AMH 2014

www.amh.net.au

Calcium channel blockers


Precautions
Cardiovascular
Contraindicated in severe bradycardia, sick sinus
syndrome, second- or third-degree atrioventricular
block (without pacemaker); hypotension (systolic BP
<90 mm Hg); AF or atrial flutter associated with an
accessory conduction pathway (eg Wolff-ParkinsonWhite syndrome).
Diltiazem may worsen first-degree atrioventricular
block, but risk is less than with verapamil.
Other drugs
Treatment with drugs that slow cardiac conduction,
cause bradycardia or arrhythmias may potentiate
the adverse cardiac effects of diltiazem; use
combinations, eg with beta-blockers, carefully and
monitor cardiac function.
Adverse effects
Common (>1%)

Counselling

bradycardia

Hypertension (includes combination with


enalapril (p 252))

Infrequent (0.11%)
atrioventricular block, development or worsening of
heart failure
Dosage
Angina, AF, atrial flutter
Conventional product, adult, initially 30 mg 3 or
4 times daily; increase as required; maximum
360 mg daily in 3 or 4 divided doses.
Controlled release products, adult, initially 180 mg
once daily; increase as required up to 360 mg once
daily.
Hypertension
Controlled release products, adult, initially 180240 mg
once daily; increase as required up to 360 mg once
daily.
Dose conversion
When converting to controlled release product, use
the strength nearest the total daily dose of
conventional product.
Counselling
Swallow the capsules whole; do not open or chew
them.
tab, 60 mg (scored), 90, Cardizem (AV), Coras (AL), Dilzem
(TA), Vasocardol (AV), Diltiazem (CH, SZ, TW, TX), PBS
cap, 180 mg (controlled release), 30, Cardizem CD (AV),
Vasocardol CD (AV), Diltiazem CD (SZ, TX), PBS
cap, 240 mg (controlled release), 30, Cardizem CD (AV),
Vasocardol CD (AV), Diltiazem CD (SZ, TX), PBS
cap, 360 mg (controlled release), 30, Cardizem CD (AV),
Vasocardol CD (AV), Diltiazem CD (SZ), PBS

Felodipine
Dihydropyridine
For additional information see Calcium channel
blockers p 230
For drug interactions see Calcium channel blockers
p 889, Felodipine p 890
Indications
Hypertension (includes combination with ramipril
(p 254))
Dosage
Adult, initially 5 mg once daily; maintenance dose
510 mg once daily; maximum dose 20 mg once
daily.
Elderly, hepatic impairment

Swallow tablet whole; do not crush or chew.


Avoid grapefruit juice as it may increase the risk of
side effects with felodipine.
tab, 2.5 mg (controlled release), 30, Felodur ER (AP), Fendex ER
(AL), Plendil ER (AP), PBS
tab, 5 mg (controlled release), 30, Felodil XR (AS), Felodur ER
(AP), Fendex ER (AL), Plendil ER (AP), PBS
tab, 10 mg (controlled release), 30, Felodil XR (AS), Felodur ER
(AP), Fendex ER (AL), Plendil ER (AP), PBS

Lercanidipine
Dihydropyridine
For additional information see Calcium channel
blockers p 230
For drug interactions see Calcium channel blockers
p 889, Lercanidipine p 890
Indications

Precautions

Treatment with cyclosporinmanufacturer contraindicates combination.


Renal

Use cautiously in severe impairment (manufacturer contraindicates use when CrCl <12 mL/minute).
Hepatic

Use cautiously in severe impairment (manufacturer contraindicates use).


Dosage

Adult, initially 10 mg once daily; if necessary,


increase after at least 2 weeks. Maximum 20 mg
once daily.
Counselling

This medicine is absorbed best if you take it at least


15 minutes before a meal.
tab, 10 mg (scored), 28, Ledip (RA), Lercadip (AB), Lercan (AB),
Zanidip (AB), Zircol (AL), Lercanidipine (CH, GQ, SZ, TX, TW),
PBS
tab, 20 mg, 28, Lercadip (AB), Lercan (AB), Zanidip (AB), PBS
tab, 20 mg (scored), 28, Ledip (RA), Zircol (AL), Lercanidipine
(CH, GQ, SZ, TX, TW), PBS

Nifedipine
Dihydropyridine
For additional information see Calcium channel
blockers p 230
For drug interactions see Calcium channel blockers
p 889, Nifedipine p 890
Indications

Hypertension
Angina
Accepted

Preterm labour (see Nifedipine p 747)


Precautions

Severe GI stenosisuse controlled release tablet


cautiously; tablet is non-deformable.

Adult, initially 2.5 mg once daily.


www.amh.net.au

AMH 2014

Calcium channel blockers


Dosage
Adult

Conventional tablet, initially 1020 mg twice daily,


increase to 2040 mg twice daily.
Controlled release tablet, initially 20 mg or 30 mg
once daily, increase to a maximum of 90 mg once
daily (angina) or 120 mg once daily (hypertension).
To change from conventional tablets to controlled
release, choose the nearest daily dose initially, then
adjust according to response, eg if converting from
20 mg twice daily conventional tablets, choose
30 mg once daily controlled release.
Child

Initially 0.250.5 mg/kg daily in 1 or 2 doses


depending on product used; maximum 3 mg/kg
(not to exceed 120 mg daily in 1 or 2 doses).
See above for changing from conventional to
controlled release tablets.
Counselling

Conventional tablet: do not stop taking this medicine


suddenly unless your doctor tells you to.
Controlled release tablet: swallow whole; do not
crush or chew.
Avoid grapefruit juice as it may increase the risk of
side effects with nifedipine.
Practice points

if using nifedipine without a beta-blocker to


treat angina, controlled release tablets are more
appropriate than conventional tablets as they do
not appear to worsen angina
tab, 10 mg, 60, Adalat (BN), Adefin 10 (AL), PBS
tab, 20 mg, 60, Adalat (BN), Adefin 20 (AL), Nifehexal (SZ), PBS
tab, 20 mg (controlled release), 30, Adalat Oros (BN), PBS
tab, 30 mg (controlled release), 30, Adalat Oros (BN), Addos
XR (AS), Adefin XL (AL), Nifedipine (AS), PBS
tab, 60 mg (controlled release), 30, Adalat Oros (BN), Addos
XR (AS), Adefin XL (AL), Nifedipine (AS), PBS

Nimodipine
Dihydropyridine
For additional information see Calcium channel
blockers p 230
For drug interactions see Calcium channel blockers
p 889, Nimodipine p 890
Mode of action

Unclear; may reduce influx of calcium into


neurones and vascular smooth muscle cells;
prevents ischaemic damage from cerebral
vasospasm.
Indications

Prevention and treatment of ischaemic neurological deficits following aneurysmal subarachnoid haemorrhage

drugs that affect CYP3A4 may affect nimodipines


clearance and activity, see Table B4 Drugs and
CYP enzymes p 974.
Treatment with disulfiram or metronidazole may
cause reactions with ethanol (p 866) as nimodipine
infusion contains ethanol (about 25%).
Hepatic

Requires lower dosage in hepatic impairment;


monitor BP and pulse rate.
Adverse effects
Rare (<0.1%)

ileus
Dosage

Refer to local protocols. Start nimodipine as soon as


possible or within 4 days of subarachnoid
haemorrhage; duration of treatment usually up to
21 days.
Oral

Adult, 60 mg every 4 hours.


Hepatic impairment, 30 mg every 4 hours.
IV infusion

Co-infuse with a compatible solution, eg glucose


5%, sodium chloride 0.9%, dextran 40.
Adult >70 kg, 1 mg/hour for the first 2 hours; give
co-infusion solution at a rate of 20 mL/hour.
If well tolerated (ie BP stable), increase dosage up
to 2 mg/hour (with an increase in the rate of coinfusion solution to 40 mL/hour).
Adult <70 kg or labile BP or hepatic impairment,
initially 0.5 mg/hour; give co-infusion solution at a
rate of 10 mL/hour. Maximum 1 mg/hour.
Administration advice

Give infusion via a central catheter using an


infusion pump.
Do not use PVC giving sets because of the loss of
nimodipine and contamination by plasticisers; use
polyethylene sets.
Counselling

Tablets: avoid grapefruit juice as it may increase the


risk of side effects with nimodipine.
Practice points

high morbidity and mortality after aneurysmal


subarachnoid haemorrhage is associated with
neurological damage from bleeding (initial and
recurrent) and cerebral ischaemia due to reactive
vasospasm; early medical treatment aims to
prevent vasospasm and re-bleeding and to
stabilise the patient for surgery
tab, 30 mg, 100, Nimotop (BN)
inj, 0.2 mg/mL, 50 mL, 5, Nimotop (BN)

Precautions

Ethanol contentinfusing at 2 mg/hour for 24 hours


will deliver about 50 g ethanol.
Cerebral oedema or severely raised intracranial pressure
manufacturer suggests cautious use with close
monitoring.
Hypotensionrisk of aggravation.
Other drugs

The manufacturer contraindicates use of oral


nimodipine with rifampicin, phenobarbitone,
phenytoin or carbamazepine, as treatment with
AMH 2014

www.amh.net.au

Calcium channel blockers

Verapamil
Non-dihydropyridine
For additional information see Calcium channel
blockers p 230
See also Tachyarrhythmias p 276, Migraine p 701
For drug interactions see Calcium channel blockers
p 889, Verapamil p 890
Indications

SVT
AF or atrial flutter (ventricular rate control)
Hypertension, including combination with
trandolapril
Angina
Accepted

Prophylaxis of cluster headache


Precautions
Cardiovascular

Contraindicated in severe bradycardia, sick sinus


syndrome, second- or third-degree atrioventricular
block (without pacemaker); hypotension (systolic
BP <90 mm Hg); AF or atrial flutter associated with
an accessory conduction pathway (eg WolffParkinson-White syndrome), wide complex
tachycardia or ventricular tachycardia.
Verapamil may worsen first-degree atrioventricular block (greater risk than with diltiazem).
Other drugs

Treatment with antiarrhythmics increases risk of


heart failure, bradycardia and proarrhythmic
effect; avoid such combinations if possible.
Treatment with drugs that cause bradycardia may
further decrease heart rate and cause hypotension;
monitor cardiac function.
Treatment with beta-blockers increases risk of
severe bradycardia, heart block and left ventricular
failure; avoid combination (unless under specialist
supervision).
The manufacturer of dabigatran contraindicates
combination with verapamil in certain circumstances, see Dabigatran p 314.
Adverse effects
Common (>1%)

constipation, bradycardia
Infrequent (0.11%)

atrioventricular block, development or worsening


of heart failure
Rare (<0.1%)

ileus
Dosage
Angina

Conventional tablet, adult, initially 80 mg 2 or


3 times daily; maintenance dose, 160 mg 2 or
3 times daily.
Controlled release capsule, adult, initially 160240 mg
once daily, increasing if necessary to a maximum of
480 mg once daily.
Controlled release tablet, adult, initially 180240 mg
once daily, increasing if necessary to a maximum of
240 mg twice daily. Give daily doses >240 mg in
2 doses.

www.amh.net.au

SVT, AF or atrial flutter


IV injection

Refer to local protocols.


Adult, 2.510 mg over 23 minutes.
Oral

Conventional tablet, adult, initially 4080 mg 2 or


3 times daily; maintenance dose, 160 mg 2 or
3 times daily.
Controlled release capsule, initially 160240 mg
once daily, increasing if necessary to a
maximum of 480 mg once daily.
Controlled release tablet, initially 120240 mg once
daily, increasing if necessary to a maximum of
240 mg twice daily. Give daily doses >240 mg in
2 doses.
Hypertension

Conventional tablet, adult, initially 80 mg 2 or 3 times


daily; maintenance dose, 160 mg 2 or 3 times daily.
Controlled release capsule, adult, initially 160240 mg
once daily, increasing if necessary to a maximum of
480 mg once daily.
Controlled release tablet, adult, initially 120180 mg
once daily; usual maintenance dose 240 mg once
daily; increase if necessary to a maximum of 240 mg
twice daily. Give daily doses >240 mg in 2 doses.
Controlled release verapamil with
trandolapril
For additional information see Trandolapril p 255

Do not start treatment with these products; it is


important to titrate the dose of both drugs first.
Adult, 1 tablet once daily (of either strength).
Prophylaxis of cluster headache

Use under specialist supervision; individualise


dose according to response. Monitor ECG
regularly.
Adult, initially 240 mg daily; usual range
240960 mg daily in 14 doses depending on
formulation.
Administration advice

Give IV injections slowly under continuous ECG


and BP monitoring over 23 minutes; rapid IV
administration may result in hypotension,
bradycardia, heart block and asystole.
Counselling

Controlled release capsules: swallow whole (do not


crush or chew), or you can open the capsule and
sprinkle the contents in soft food; take immediately
without chewing, followed by a glass of water.
Verapamil may increase the effects of alcohol so
that you are more easily affected and the effects last
longer. Limit your alcohol intake until you know
whether you are affected like this.
Avoid grapefruit juice as it may increase the risk of
side effects with verapamil.
tab, 40 mg, 100, Isoptin (AB), PBS
tab, 40 mg (scored), 100, Anpec (AL), PBS
tab, 80 mg (scored), 100, Anpec (AL), Isoptin (AB), PBS
tab, 120 mg (scored), 100, Isoptin (AB), PBS
tab, 180 mg (controlled release, scored), 30, Cordilox SR (AB),
Isoptin SR (AB), PBS
tab, 240 mg (controlled release, scored), 30, Cordilox SR (AB),
Isoptin SR (AB), PBS
cap, 160 mg (controlled release), 30, Veracaps SR (AS), PBS
cap, 240 mg (controlled release), 30, Veracaps SR (AS), PBS
inj, 2.5 mg/mL, 2 mL, 5, Isoptin (AB), PBS

AMH 2014

Calcium channel blockers


Combination products
tab, verapamil (controlled release) 180 mg, trandolapril 2 mg,
28, Tarka 2/180 (AB), PBS-R1
tab, verapamil (controlled release) 240 mg, trandolapril 4 mg,
28, Tarka 4/240 (AB), PBS-R1
1

hypertension inadequately controlled by either drug alone

AMH 2014

www.amh.net.au