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AmLODIPine


General


Pronunciation

(am LOE di peen)


Brand Names: U.S.

  • Norvasc

Indications


Use: Labeled Indications

Coronary artery disease (CAD):

Chronic stable angina: Treatment of symptomatic chronic stable angina. May be used alone or in combination with other antianginal agents.

Vasospastic angina (Prinzmetal or variant angina): Treatment of confirmed or suspected vasospastic angina. May be used alone or in combination with other antianginal agents.

Angiographically documented CAD: Reduce the risk of hospitalization secondary to angina and to reduce the risk of a coronary revascularization procedure in patients with recently documented CAD by angiography (without heart failure or an ejection fraction of <40%).

The ACCF/AHA 2013 guidelines for management of heart failure state that, with the exception of amlodipine, calcium channel blockers should be avoided and withdrawn whenever possible in patients with heart failure with reduced ejection fraction (HFrEF). While amlodipine, like other calcium channel blockers, has no benefit on functioning or survival, it may be used for the treatment of hypertension or ischemic heart disease in patients with HFrEF (ACCF/AHA [Yancy 2013]).

Hypertension: Treatment of hypertension. May be used alone or in combination with other antihypertensive agents

The 2014 guideline for the management of high blood pressure in adults (JNC 8) recommends initiation of pharmacologic treatment to lower blood pressure for the following patients (JNC8 [James 2013]):

- Patients ≥60 years of age, with systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg. Goal of therapy is SBP <150 mm Hg and DBP <90 mm Hg.

- Patients <60 years of age, with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

- Patients ≥18 years of age with diabetes, with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

- Patients ≥18 years of age with chronic kidney disease (CKD), with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

In patients with chronic kidney disease (CKD), regardless of race or diabetes status, the use of an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) as initial therapy is recommended to improve kidney outcomes. In the general nonblack population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic, calcium channel blocker, ACEI, or ARB. In the general black population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic or a calcium channel blocker instead of an ACEI or ARB.


Contraindications


Hypersensitivity to amlodipine or any component of the formulation


Dosing and Administration


Dosing: Adult

Coronary artery disease (CAD) (chronic stable angina, vasospastic angina, angiographically documented CAD [without heart failure or ejection fraction <40%]): Oral: 5 to 10 mg once daily

Hypertension: Oral: Initial: 5 mg once daily or 2.5 mg once daily in small or frail patients, or when adding amlodipine to other antihypertensive therapy; maximum dose: 10 mg once daily. In general, titrate every 7 to 14 days. Titrate more rapidly, however, if clinically warranted, provided the patient is assessed frequently. Usual dosage range (ASH/ISH [Weber 2014]): 5 to 10 mg once daily. Target dose (JNC8 [James 2013]): 10 mg once daily.


Dosing: Geriatric

Dosing should start at the lower end of dosing range and titrated to response due to possible increased incidence of hepatic, renal, or cardiac impairment. Elderly patients also show decreased clearance of amlodipine.

Coronary artery disease (CAD) (chronic stable angina, vasospastic angina, angiographically documented CAD without heart failure or ejection fraction <40%): Oral: Initial: 5 mg once daily

Hypertension: Oral: Initial: 2.5 mg once daily; maximum dose: 10 mg once daily. In general, titrate every 7 to 14 days. Titrate more rapidly, however, if clinically warranted, provided the patient is assessed frequently. Usual dosage range (ASH/ISH [Weber 2014]): 5 to 10 mg once daily. Target dose (JNC8 [James 2013]): 10 mg once daily.


Dosing: Pediatric

Hypertension: Children ≥6 years and Adolescents: Oral: 2.5 to 5 mg once daily


Dosing: Renal Impairment

No dosage adjustment necessary (Doyle 1989; Kungys 2003).

End-stage renal disease (ESRD) on dialysis: Hemodialysis and peritoneal dialysis do not enhance elimination; supplemental dose is not necessary (Kungys 2003).


Dosing: Hepatic Impairment

Coronary artery disease (CAD) (chronic stable angina, vasospastic angina, angiographically documented CAD without heart failure or ejection fraction <40%): Initial: 5 mg once daily; titrate slowly in patients with severe hepatic impairment.

Hypertension: Initial: 2.5 mg once daily; titrate slowly in patients with severe hepatic impairment.


Administration

Oral: Administer without regard to meals.


Storage

Store at 15 � �C to 30 � �C (59 � �F to 86 � �F).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Norvasc: 2.5 mg, 5 mg, 10 mg

Generic: 2.5 mg, 5 mg, 10 mg


Extemporaneously Prepared

A 1 mg/mL oral suspension may be made with tablets and either a 1:1 mixture of simple syrup and 1% methylcellulose or a 1:1 mixture of Ora-Plus � � and Ora-Sweet � �. Crush fifty 5 mg tablets in a mortar and reduce to a fine powder. Add small portions of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 250 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 250 mL. Label "shake well " � and "refrigerate " �. Stable for 56 days at room temperature or 91 days refrigerated.

Nahata MC, Morosco RS, and Hipple TF, Stability of Amlodipine Besylate in Two Liquid Dosage Forms," J Am Pharm Assoc (Wash) 1999, 39(3):375-7.[PMID: 10363465]

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs. Management: Concurrent use of felodipine or nisoldipine with itraconazole is specifically contraindicated. Frequent monitoring is warranted with any such combination; calcium channel blocker dose reductions may be required. Exceptions: Fluconazole; Isavuconazonium Sulfate. Consider therapy modification

Antihepaciviral Combination Products: May increase the serum concentration of AmLODIPine. Management: Reduce amlodipine dose by at least 50% and monitor for increased amlodipine effects (eg, hypotension) if an antihepaciviral combination product is initiated. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Monitor therapy

CarBAMazepine: May increase the metabolism of Calcium Channel Blockers (Dihydropyridine). Management: Consider calcium channel blocker (CCB) dose adjustments or alternative therapy in patients receiving concomitant carbamazepine. Nimodipine Canadian labeling contraindicates concurrent use with carbamazepine. Consider therapy modification

Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CycloSPORINE (Systemic): May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Monitor therapy

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Efavirenz: May decrease the serum concentration of Calcium Channel Blockers. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

Fluconazole: May increase the serum concentration of Calcium Channel Blockers. Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fosphenytoin: Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Consider therapy modification

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Grapefruit Juice: May increase the serum concentration of AmLODIPine. Management: The Canadian product Viacoram (perindopril/amlodipine) states that concurrent grapefruit juice is not recommended. US labeling for similar amlodipine-containing combination products states that there is no evidence of a significant interaction. Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

HYDROcodone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of HYDROcodone. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification

Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification

Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy

Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nafcillin: May increase the metabolism of Calcium Channel Blockers. Consider therapy modification

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Phenytoin: Calcium Channel Blockers may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers. Management: Avoid use of nimodipine or nifedipine with phenytoin. Monitor for phenytoin toxicity and/or decreased calcium channel blocker effects with any concurrent use. Consider therapy modification

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

QuiNIDine: Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Rifamycin Derivatives: May decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. Consider therapy modification

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Simvastatin: AmLODIPine may increase the serum concentration of Simvastatin. Management: Avoid the concurrent use of amlodipine with simvastatin when possible. If used together, avoid doses of simvastatin greater than 20 mg/day (for adults). Consider therapy modification

St Johns Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy


Monitoring Parameters

Heart rate, blood pressure


Adverse Reactions


>10%:

Cardiovascular: Peripheral edema (2% to 11% dose related; female 15%; male 6%; HF patients 27% to 28% [Packer 1996; Packer 2013])

Respiratory: Pulmonary edema (HF patients 7% to 15% [Packer 1996; Packer 2013])

1% to 10%:

Cardiovascular: Palpitations ( ≤5%, dose related), flushing ( ≤3%, dose related, more frequent in females)

Central nervous system: Fatigue (5%), dizziness (1% to 3%, dose related), male sexual disorder ( ≤2%), drowsiness (1%)

Dermatologic: Pruritus ( ≤2%), skin rash ( ≤2%)

Gastrointestinal: Nausea (3%), abdominal pain (2%)

Neuromuscular & skeletal: Muscle cramps ( ≤2%), weakness ( ≤2%)

Respiratory: Dyspnea ( ≤2%)

<1% (Limited to important or life-threatening): Acute interstitial nephritis (Ejaz 2000), anorexia, atrial fibrillation, bradycardia, cholestasis, conjunctivitis, depression, diarrhea, difficulty in micturition, diplopia, dysphagia, epistaxis, erythema multiforme, exfoliative dermatitis, extrapyramidal reaction, eye pain, female sexual disorder, gingival hyperplasia, gynecomastia, hepatitis, hot flash, hyperglycemia, hypersensitivity angiitis, hypersensitivity reaction, hypoesthesia, increased serum transaminases, increased thirst, insomnia, leukopenia, maculopapular rash, myalgia, nocturia, orthostatic hypotension, osteoarthritis, pancreatitis, paresthesia, peripheral ischemia, peripheral neuropathy, phototoxicity, purpura, rigors, tachycardia, thrombocytopenia, tremor, vasculitis, ventricular tachycardia, weight gain


Warnings/Precautions


Special Populations: Hepatic Function Impairment

AUC may increase ~40% to 60%.


Special Populations: Elderly

AUC may increase ~40% to 60%.


Special Populations Note

Moderate to severe heart failure: AUC may increase ~40% to 60%.


Warnings/Precautions

Concerns related to adverse effects:

- Angina/MI: Increased angina and/or MI have occurred with initiation or dosage titration of dihydropyridine calcium channel blockers. Reflex tachycardia may occur resulting in angina and/or MI in patients with obstructive coronary disease, especially in the absence of concurrent beta-blockade.

- Hypotension: Symptomatic hypotension can occur; acute hypotension upon initiation is unlikely due to the gradual onset of action. Blood pressure must be lowered at a rate appropriate for the patients clinical condition.

- Peripheral edema: The most common side effect is peripheral edema; occurs within 2 to 3 weeks of starting therapy.

Disease-related concerns:

- Aortic stenosis: Use amlodipine with extreme caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.

- Hepatic impairment: Use with caution in patients with hepatic impairment; may require lower starting dose; titrate slowly in patients with severe hepatic impairment.

- Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use amlodipine with caution in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (ACCF/AHA [Gersh 2011]).

Special populations:

- Elderly: Initiate at a lower dose in the elderly.

Other warnings/precautions:

- Titration: Peak antihypertensive effect is delayed; dosage titration should occur after 7 to 14 days on a given dose.


Pregnancy Risk Factor

C


Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. Untreated chronic maternal hypertension is associated with adverse events in the fetus, infant, and mother. If treatment for hypertension during pregnancy is needed, other agents are preferred (ACOG 2013).


Actions


Pharmacology

Inhibits calcium ion from entering the "slow channels " � or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization, producing a relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina. Amlodipine directly acts on vascular smooth muscle to produce peripheral arterial vasodilation reducing peripheral vascular resistance and blood pressure.


Absorption

Well absorbed (Meredith 1992)


Distribution

Mean Vd:

Children >6 years: Similar to adults on a mg per kg basis; Note: Weight-adjusted Vd in younger children (<6 years of age) may be greater than in older children (Flynn 2006)

Adults: 21 L/kg (Scholz 1997)


Metabolism

Hepatic (~90%) to inactive metabolites


Excretion

Urine (10% of total dose as unchanged drug, 60% of total dose as metabolites)

Clearance: May be decreased in patients with hepatic insufficiency or moderate to severe heart failure; weight-adjusted clearance in children >6 years of age is similar to adults; Note: Weight-adjusted clearance in younger children (<6 years of age) may be greater than in older children (Flynn 2006)


Onset of Action

Antihypertensive effect: Significant reductions in blood pressure at 24 to 48 hours after first dose; slight increase in heart rate within 10 hours of administration may reflect some vasodilating activity (Donnelly 1993)


Time to Peak

Plasma: 6 to 12 hours


Duration of Action

Antihypertensive effect: At least 24 hours (Donnelly 1993); has been shown to extend to at least 72 hours when discontinued after 6 to 7 weeks of therapy (Biston 1999)


Half-Life Elimination

Terminal (biphasic): 30 to 50 hours; increased with hepatic dysfunction


Protein Binding

~93%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience fatigue, loss of strength and energy, flushing, nausea, or abdominal pain. Have patient report immediately to prescriber severe dizziness, passing out, angina, tachycardia, arrhythmia, shortness of breath, excessive weight gain, muscle rigidity, tremors, abnormal movements, or swelling of arms or legs (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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