calcium channel blockers

Contraindicated in:

Hypersensitivity (cross-sensitivity may occur);
Sick sinus syndrome;
2nd- or 3rd-degree heart block (unless artificial pacemaker is in place);
BP <90 mmHg (especially with diltiazem and verapamil);
Recent MI or pulmonary congestion (diltiazem only);
HF, severe ventricular dysfunction, or cardiogenic shock, unless associated with supraventricular tachyarrhythmias (diltiazem and verapamil only);
Concurrent use of IV beta blocker (IV diltiazem and verapamil only);
Advanced aortic stenosis (nicardipine only);
Concurrent use of strong CYP3A4 inhibitors (nimodipine only);
Concurrent use of strong CYP3A4 inducers (nifedipine and nimodipine only).

Use Cautiously in:

Severe hepatic impairment (dose ↓ recommended for most agents);
Severe renal impairment (dose ↓ of nicardipine may be necessary);
History of serious ventricular arrhythmias or HF;
History of porphyria (nifedipine);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk; extended-release nifedipine preferred during pregnancy;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children <18 yr (diltiazem, felodipine, nicardipine, nifedipine, nimodipine, nisoldipine), <6 yr (amlodipine);
Geri: Dose ↓/slower IV infusion rates recommended for most agents in older adults; ↑ risk of hypotension; consider age-related ↓ in body mass, ↓ hepatic/renal/cardiac function, concurrent drug therapy and other disease states in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema (with amlodipine, felodipine, nifedipine), ARRHYTHMIAS, HF, bradycardia, chest pain, hypotension, palpitations, syncope, tachycardia

Derm: ↑sweating, dermatitis, erythema multiforme, flushing (with nifedipine, nicardipine), photosensitivity, pruritus/urticaria, rash, STEVENS-JOHNSON SYNDROME (SJS)

EENT: blurred vision, disturbed equilibrium, epistaxis, tinnitus

Endo: gynecomastia, hyperglycemia

GI: ↑liver enzymes, anorexia, constipation, diarrhea, dry mouth, dyspepsia, GI obstruction (with nifedipine), gingival hyperplasia, nausea, ulcer (with nifedipine), vomiting

GU: dysuria, nocturia, polyuria, sexual dysfunction, urinary frequency

Hemat: anemia, leukopenia, thrombocytopenia

Metab: weight gain

MS: joint stiffness, muscle cramps

Neuro: abnormal dreams, anxiety, confusion, dizziness, drowsiness, dysgeusia, headache(with nifedipine, isradipine, felodipine), nervousness, paresthesia, psychiatric disturbances, tremor, weakness

Resp: cough, dyspnea

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including clarithromycin, nelfinavir, ritonavir, ketoconazole, itraconazole, posaconazole, voriconazole, conivaptan, and nefazodone, may ↑ levels and risk of toxicity; avoid concurrent use with nimodipine.
Strong CYP3A4 inducers, including carbamazepine, phenobarbital, phenytoin, and rifampin, may ↓ levels and effectiveness; avoid concurrent use with nifedipine and nimodipine.
Additive hypotension may occur with acute ingestion of alcohol, quinidine, fentanyl, nitrates, or other antihypertensives.
Antihypertensive effects may be ↓ by NSAIDs.
Diltiazem, nifedipine, and verapamil may ↑ levels and risk of toxicity of digoxin.
Concurrent use of diltiazem or verapamil with beta blockers, digoxin, clonidine, or ivabradine may ↑ risk of bradycardia.
Amlodipine, diltiazem, and verapamil may ↑ risk of myopathy with simvastatin and lovastatin; do not exceed simvastatin dose of 20 mg/day (with amlodipine) or 10 mg/day (with diltiazem or verapamil); do not exceed lovastatin dose of 20 mg/day (with diltiazem or verapamil).
Phenobarbital and phenytoin may ↓ levels and effectiveness of diltiazem.
Cimetidine and propranolol may ↑ levels and risk of toxicity of diltiazem, felodipine, nicardipine, or nifedipine.
Amlodipine, diltiazem, nicardipine, nifedipine, and verapamil may ↑ levels and risk of toxicity of carbamazepine, cyclosporine, tacrolimus, prazosin, or quinidine.
Verapamil may ↑ muscle-paralyzing effects of nondepolarizing neuromuscular blocking agents.
Effectiveness of verapamil may be ↓ by coadministration with vitamin D and calcium.
Verapamil may alter lithium levels.
Concurrent use of verapamil with erythromycin or clarithromycin may ↑ risk of hypotension and bradycardia.
Verapamil may ↑ levels and risk of toxicity of doxorubicin and paclitaxel.
Concurrent use of verapamil with aspirin may ↑ risk of bleeding.
↑risk of GI obstruction when nifedipine used concurrently with H2 blockers, opioids, NSAIDs, laxatives, anticholinergic drugs, levothyroxine, or neuromuscular blockers.
Concurrent use of verapamil with sirolimus, temsirolimus, or everolimus may ↑ levels of sirolimus, temsirolimus, everolimus, and verapamil; consider ↓ dose of sirolimus, temsirolimus, everolimus, and verapamil.

Drug-Natural Products:

Verapamil↑ caffeine levels with caffeine-containing herbs (cola nut, guarana, mate, tea, coffee).
St. John's wort may significantly ↓ levels and effectiveness; concurrent use is contraindicated.

Drug-Food:

Grapefruit juice may ↑ levels and risk of toxicity of felodipine, nifedipine, nimodipine, nicardipine, nisoldipine, and verapamil; avoid concurrent use with nifedipine and nimodipine.

Availability ⬆ ⬇

Amlodipine

(Generic available)

Tablets: 2.5 mg; 5 mg; 10 mg
Oral solution (Norliqva) peppermint flavor: 1 mg/mL
Oral suspension (Katerzia): 1 mg/mL
In combination with:
aliskiren/hydrochlorothiazide (Amturnide), atorvastatin (Caduet), benazepril (generic only), olmesartan (Azor), olmesartan/hydrochlorothiazide (Tribenzor), telmisartan, telmisartan/indapamide (Widaplik), valsartan (Exforge), and valsartan/hydrochlorothiazide (Exforge HCT). See Combination Drugs.

Diltiazem

(Generic available)

Tablets: 30 mg; 60 mg; 90 mg; 120 mg
Extended-release capsules (Cardizem CD, Tiazac, Cartia XT): 120 mg; 180 mg; 240 mg; 300 mg; 360 mg; 420 mg
Extended-release tablets (Cardizem LA): 120 mg; 180 mg; 240 mg; 300 mg; 360 mg; 420 mg
Solution for injection: 5 mg/mL

Felodipine

(Generic available)

Extended-release tablets: 2.5 mg; 5 mg; 10 mg

Isradipine

(Generic available)

Capsules: 2.5 mg; 5 mg

Nicardipine

(Generic available)

Capsules: 20 mg; 30 mg
Premixed infusion: 20 mg/200 mL dextrose 4.8% in water or 0.86% NaCl; 40 mg/200 mL 0.83% NaCl
Solution for injection: 2.5 mg/mL

Nifedipine

(Generic available)

Capsules: 5 mg; 10 mg; 20 mg
Tablets: 10 mg
Extended-release tablets (Nifedical XL, Procardia XL): 10 mg, ; 20 mg; 30 mg; 60 mg; 90 mg

Nimodipine

(Generic available)

Capsules: 30 mg
Oral solution: 6 mg/mL

Nisoldipine

(Generic available)

Extended-release tablets: 20 mg; 30 mg; 40 mg
Geomatrix extended-release tablets: 8.5 mg; 17 mg; 25.5 mg; 34 mg

Verapamil

(Generic available)

Immediate-release tablets: 40 mg; 80 mg; 120 mg
Extended-release capsules: 120 mg; 180 mg; 240 mg; 360 mg
Extended-release capsules (Verelan PM): 100 mg; 200 mg; 300 mg
Extended-release tablets: 120 mg; 180 mg; 240 mg
Solution for injection: 2.5 mg/mL
In combination with:
trandolapril (Tarka); see Combination Drugs.

Route/Dosage ⬆ ⬇

Amlodipine

PO (Adults ): 5–10 mg once daily; Fragile or small patients or patients already receiving other antihypertensives: Initiate at 2.5 mg/day; ↑ as required/tolerated (up to 10 mg/day) as an antihypertensive therapy with 2.5 mg/day in patients with hepatic impairment.
PO Geriatric Patients ): Hypertension: Initiate therapy at 2.5 mg/day; ↑ as required/tolerated (up to 10 mg/day); Angina: Initiate therapy at 5 mg/day; ↑ as required/tolerated (up to 10 mg/day).
PO (Children 6–17 yr): 2.5–5 mg once daily.

Hepatic Impairment

PO (Adults ): Hypertension: Initiate therapy at 2.5 mg/day; ↑ as required/tolerated (up to 10 mg/day); Angina: Initiate therapy at 5 mg/day; ↑ as required/tolerated (up to 10 mg/day).

Diltiazem

PO (Adults ): Immediate release: 30–120 mg 3–4 times daily. Extended release: 120–240 mg once daily (up to 360 mg/day); Concurrent use of simvastatin: Diltiazem dose should not exceed 240 mg/day, and simvastatin dose should not exceed 10 mg/day.
IV (Adults ): 0.25 mg/kg; may repeat in 15 min with a dose of 0.35 mg/kg. May follow with continuous infusion at 10 mg/hr (range 5–15 mg/hr) for up to 24 hr.

Felodipine

PO (Adults ): 5 mg/day initially (2.5 mg/day in older adults). May ↑ every 2 wk. Usual daily dose is 5–10 mg (not to exceed 20 mg/day).

Isradipine

PO (Adults ): 2.5 mg twice daily; may ↑ every 2–4 wk by 5 mg/day (not to exceed 20 mg/day).

Nicardipine

PO (Adults ): Immediate release: 20 mg 3 times daily; may ↑ every 3 days (range 20–40 mg 3 times daily). Extended release: 30 mg twice daily (up to 60 mg twice daily).
IV (Adults ): Substitute for PO nicardipine: If PO dose is 20 mg every 8 hr, then infusion rate is 0.5 mg/hr; if PO dose is 30 mg every 8 hr, then infusion rate is 1.2 mg/hr; if PO dose is 40 mg every 8 hr, then infusion rate is 2.2 mg/hr. Patients not receiving PO nicardipine: Initiate therapy at 5 mg/hr; may ↑ by 2.5 mg every 5–15 min as needed (up to 15 mg/hr).

Nifedipine

PO (Adults ): Immediate release: 10–30 mg 3 times daily (not to exceed 180 mg/day); Extended release: 30–90 mg once daily (not to exceed 90–120 mg/day).

Nimodipine

PO (Adults ): 60 mg every 4 hr for 21 days; therapy should be started within 96 hr of subarachnoid hemorrhage.

Nisoldipine

PO (Adults ): 20 mg once daily; may ↑ by 10 mg/day every 7 days (range 20–40 mg/day; not to exceed 60 mg/day).

Verapamil

PO (Adults ): 80–120 mg 3 times daily; ↑ as needed. Patients with poor ventricular function or hepatic impairment, or older adults: Immediate release: 40 mg 3 times daily initially. Extended release: 120–240 mg once daily; may ↑ as needed (range 240–480 mg/day).
PO Geriatric Patients ): Immediate release: 40 mg 3 times daily initially.
PO (Children <15 yr): 4–8 mg/kg/day in divided doses
IV (Adults ): 5–10 mg (75–150 mcg/kg); may repeat with 10 mg after 30 min.
IV (Children 1–15 yr): 100–300 mcg/kg; may repeat after 30 min (initial dose not to exceed 5 mg; repeat dose not to exceed 10 mg).
IV (Children <1 yr): 100–200 mcg/kg.

US Brand Names ⬆ ⬇

amLODIPine: Katerzia, Norliqva, Norvasc,

diltiazem: Cardizem, Cardizem CD, Cardizem LA, Cartia XT, ~~Taztia XT,~~ Tiazac,

isradipine: ~~DynaCirc,~~

niCARdipine: Cardene IV,

NIFEdipine: ~~Adalat CC,~~ ~~Afeditab CR,~~ Procardia, Procardia XL,

niMODipine: Nymalize,

nisoldipine: Sular,

verapamil: ~~Calan,~~ ~~Calan SR,~~ ~~Verelan,~~ Verelan PM

Action ⬆ ⬇

Inhibits the transport of calcium into myocardial and vascular smooth muscle cells, resulting in inhibition of excitation-contraction coupling and subsequent contraction.

Diltiazem, verapamil

Decrease SA and AV conduction and prolong AV node refractory period in conduction tissue.

Therapeutic effects:

Systemic vasodilation resulting in decreased BP.
Coronary vasodilation resulting in decreased frequency and severity of attacks of angina.

Nimodipine

Prevention of vascular spasm after subarachnoid hemorrhage, resulting in decreased neurologic impairment.

Diltiazem, verapamil

Reduction of ventricular rate during atrial fibrillation or flutter.

Classifications ⬆ ⬇

Therapeutic Classification: antianginals, antiarrhythmics, antihypertensives

Pharmacokinetics ⬆ ⬇

Absorption: Amlodipine: Well absorbed after oral administration (64–90%); Diltiazem and verapamil: Well absorbed after oral administration but rapidly metabolized; Felodipine, isradipine, nicardipine, nimodipine, and nisoldipine: Well absorbed after oral administration but extensively metabolized, resulting in ↓ bioavailability; Nifedipine: Well absorbed after oral administration but rapidly metabolized, resulting in ↓ bioavailability (45–70%); bioavailability is ↑ (80%) with extended-release forms.

Distribution: Amlodipine, diltiazem, isradipine, nicardipine, verapamil: Well distributed to tissues; nimodipine: Crosses the blood-brain barrier.

Metabolism/Excretion: All agents are mostly metabolized by the liver; ≤10% excreted unchanged by kidneys.

Half-Life: Amlodipine: 30–50 hr; diltiazem: 3.5–9 hr; felodipine: 11–16 hr; isradipine: 8 hr; nicardipine: 2–4 hr; nifedipine: 2–5 hr; nimodipine: 1–2 hr; verapamil: 4.5–12 hr.

Canadian Brand Names ⬆ ⬇

diltiazem: Tiazac XC,

felodipine: Plendil,

NIFEdipine: Adalat XL,

niMODipine: Nimotop

Time/Action Profile ⬆ ⬇

( cardiovascular effects)

ROUTE	ONSET	PEAK	DURATION
Amlodipine PO	unknown	6–9	24 hr
Diltiazem PO	30 min	2–3 hr	6–8 hr
Diltiazem PO-CD	unknown	14 days‡	24 hr
Diltiazem PO-XR	unknown	14 days‡	24 hr
Diltiazem IV	2–5 min	unknown	unknown
Felodipine PO	1 hr	2–4 hr	up to 24 hr
Isradipine PO	<2 hr	2–3 hr	12 hr
Nicardipine PO	20 min	1–2 hr	8 hr
Nicardipine IV	within min	45 min	50 hr‡
Nifedipine PO	20 min	unknown	6–8 hr
Nifedipine PO-ER	unknown	unknown	24 hr
Nimodipine PO	unknown	1 hr	unknown
Nisoldipine	unknown	6–12 hr	24 hr
Verapamil PO	1–2 hr	30–90 min	3–7 hr
Verapamil PO-ER	unknown	5–7 hr	24 hr
Verapamil IV	1–5 min	3–5 min	2 hr

‡Maximum antihypertensive effect with chronic therapy.

‡After discontinuation.

Single dose; effects from multiple doses may not be evident for 24–48 hr.

Antiarrhythmic effects; hemodynamic effects begin 3–5 min after injection and persist for 10–20 min.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of the medication. Instruct patient to take medication as directed, even if feeling well. Take missed doses as soon as possible unless almost time for next dose; do not double doses. May need to be discontinued gradually. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
- Advise patients taking felodipine, nifedipine, nimodipine, nisoldipine, nicardipine, and verapamil to avoid drinking grapefruit juice during therapy.
- Instruct patient on technique for monitoring pulse. Instruct patient to contact health care provider if HR <50 bpm.
- Caution patient to change positions slowly to minimize orthostatic hypotension.
- Advise patient to notify health care provider if rash, irregular heartbeat, dyspnea, swelling of hands and feet, pronounced dizziness, nausea, constipation, or hypotension occurs or if headache is severe or persistent.
- May cause drowsiness or dizziness. Advise patient to avoid driving or other activities requiring alertness until response to the medication is known.
- Teach patient and family about risk for falls and how to ↓ risk in the home.
- Instruct patient on importance of maintaining good dental hygiene and seeing dentist frequently for teeth cleaning to prevent tenderness, bleeding, and gingival hyperplasia (gum enlargement).
- Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to avoid concurrent use of alcohol or OTC medications and herbal products, especially NSAIDs and cold preparations, without consulting health care provider.
- Caution patient to wear protective clothing and use sunscreen to prevent photosensitivity reactions.
Angina: Instruct patient on concurrent nitrate or beta blocker therapy to continue taking both medications as directed and use SL nitroglycerin as needed for anginal attacks.
- Inform patient taking isradipine or nifedipine that anginal attacks may occur 30 min after administration as a result of reflex tachycardia. This is usually temporary and is not an indication for discontinuation.
- Advise patient to contact health care provider if chest pain does not improve, worsens after therapy, or occurs with diaphoresis or if shortness of breath or persistent headache occurs.
- Caution patient to discuss exercise restrictions with health care provider before exertion.
Hypertension: Encourage patient to comply with other interventions for hypertension (weight reduction, low-sodium diet, smoking cessation, moderation of alcohol consumption, regular exercise, stress management). Medication controls but does not cure hypertension.
- Instruct patient and family in proper technique for monitoring BP. Advise patient to take BP weekly and to report significant changes to health care provider.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

section name header

Indications ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Classifications ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Canadian Brand Names ⬆ ⬇

Time/Action Profile ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Pronunciation ⬆