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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 (0.1–1%)
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 disease—calcium
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 6–1 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.
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Calcium channel blockers
Table 6–1 Comparison of calcium channel blockers
Drug
Indications
Forms
Doses/day
Comments
Dihydropyridines
• angina
• hypertension
tablet
felodipine
hypertension
CR tablet
1
lercanidipine
hypertension
tablet
1
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
1
• 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 2.5–5 mg once daily,
increasing if necessary after at least 1–2 weeks to a
maximum of 10 mg once daily.
Child <6 years, initially 0.1–0.2 mg/kg once daily,
increasing if necessary over 1–2 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)
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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 (0.1–1%)
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 180–240 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
5–10 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 cyclosporin—manufacturer 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 stenosis—use controlled release tablet
cautiously; tablet is non-deformable.
Adult, initially 2.5 mg once daily.
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Calcium channel blockers
Dosage
Adult
Conventional tablet, initially 10–20 mg twice daily,
increase to 20–40 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 0.25–0.5 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 nimodipine’s
clearance and activity, see Table B–4 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 content—infusing 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.
Hypotension—risk of aggravation.
Other drugs
The manufacturer contraindicates use of oral
nimodipine with rifampicin, phenobarbitone,
phenytoin or carbamazepine, as treatment with
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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 (0.1–1%)
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 160–240 mg
once daily, increasing if necessary to a maximum of
480 mg once daily.
Controlled release tablet, adult, initially 180–240 mg
once daily, increasing if necessary to a maximum of
240 mg twice daily. Give daily doses >240 mg in
2 doses.
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SVT, AF or atrial flutter
IV injection
Refer to local protocols.
Adult, 2.5–10 mg over 2–3 minutes.
Oral
Conventional tablet, adult, initially 40–80 mg 2 or
3 times daily; maintenance dose, 160 mg 2 or
3 times daily.
Controlled release capsule, initially 160–240 mg
once daily, increasing if necessary to a
maximum of 480 mg once daily.
Controlled release tablet, initially 120–240 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 160–240 mg
once daily, increasing if necessary to a maximum of
480 mg once daily.
Controlled release tablet, adult, initially 120–180 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
240–960 mg daily in 1–4 doses depending on
formulation.
Administration advice
Give IV injections slowly under continuous ECG
and BP monitoring over 2–3 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
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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
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