Amlodipine information from DrugsUpdate
P - Contraindicated in pregnancy
L - Contraindicated in lactation
Amlodipine (as besylate, mesylate or maleate) is a long-acting calcium channel blocker (dihydropyridine class) used as an anti-hypertensive and in the treatment of angina. Like other calcium channel blockers, amlodipine acts by relaxing the smooth muscle in the arterial wall, decreasing peripheral resistance and hence reducing blood pressure; in angina it increases blood flow to the heart muscle.
Pharmacodynamics
Hemodynamics: Following administration of therapeutic doses to patients with hypertension, Amlodipine produces vasodilation resulting in a reduction of supine and standing blood pressures. These decreases in blood pressure are not accompanied by a significant change in heart rate or plasma catecholamine levels with chronic dosing. Although the acute intravenous administration of Amlodipine decreases arterial blood pressure and increases heart rate in hemodynamic studies of patients with chronic stable angina, chronic oral administration of Amlodipine in clinical trials did not lead to clinically significant changes in heart rate or blood pressures in normotensive patients with angina.
With chronic once daily oral administration, antihypertensive effectiveness is maintained for at least 24 hours. Plasma concentrations correlate with effect in both young and elderly patients. The magnitude of reduction in blood pressure with Amlodipine is also correlated with the height of pretreatment elevation; thus, individuals with moderate hypertension (diastolic pressure 105 to 114 mmHg) had about a 50% greater response than patients with mild hypertension (diastolic pressure 90 to 104 mmHg). Normotensive subjects experienced no clinically significant change in blood pressures (+1/-2 mmHg). In hypertensive patients with normal renal function, therapeutic doses f Amlodipine resulted in a decrease in renal vascular resistance and n increase in glomerular filtration rate and effective renal plasma flow without change in filtration fraction or proteinuria. As with other calcium channel blockers, hemodynamic measurements of cardiac function at rest and during exercise (or pacing) in patients with normal ventricular function treated with Amlodipine have enerally demonstrated a small increase in cardiac index without significant influence on dP/dt or on left ventricular end diastolic pressure or volume.
In hemodynamic studies, Amlodipine has not been associated with a negative inotropic effect when administered in the therapeutic dose range to intact animals and man, even when co-administered ith beta-blockers to man. Similar findings, however, have been observed in normals or well-compensated patients with heart failure with agents possessing significant negative inotropic effects.
Electrophysiologic Effects: Amlodipine does not change sinoatrial nodal function or atrioventricular conduction in intact animals or man. In patients with chronic stable angina, intravenous administration of 10 mg did not significantly alter A-H and H-V conduction and sinus node recovery time after pacing. Similar results were obtained in patients receiving Amlodipine and concomitant beta-blockers. In clinical studies in which Amlodipine was administered in combination with beta-blockers to patients with either hypertension or angina, no adverse effects on electrocardiographic parameters were observed. In clinical trials with angina patients alone, Amlodipine therapy did not alter electrocardiographic intervals or produce higher degrees of AV blocks.
Pharmacokinetics
Absorption
T max is 6 to 12 h.
Distribution
Bioavailability is 64% to 90%. About 93% is protein bound.
Metabolism
About 90% is converted to inactive metabolites in the liver.
Elimination
10% of the parent compound and 60% of the metabolites are excreted in the urine. Elimination is biphasic. T ½ is about 30 to 50 h.
Duration
24 h.
Special Populations
Hepatic Function Impairment
Clearance is decreased and AUC may increase about 40% to 60%. May require lower initial dose.
Elderly
Clearance is decreased and AUC may increase about 40% to 60%. May require lower initial dose.
Moderate to severe heart failure
Clearance is decreased and AUC may increase about 40% to 60%. May require lower initial dose.
Amlodipine Indications / Amlodipine Uses
In hypertension, Prinzmetal's angina, Stable angina.
Amlodipine Adverse Reactions / Amlodipine Side Effects
Headache, peripheral oedema, fatigue, somnolence, nausea, abdominal pain, flushing, dyspepsia, palpitations, dizziness. Rarely pruritus, rash, dyspnoea, asthenia, muscle cramps, hypotension, bradycardia, conductive system delay & CCF
Precautions
General
Since the vasodilation induced by Amlodipine is gradual in onset, acute hypotension has rarely been reported after oral administration. Nonetheless, caution as with any other peripheral vasodilator, should be exercised when administering Amlodipine, particularly in patients with severe aortic stenosis.
Beta-Blocker Withdrawal
Amlodipine is not a beta-blocker and therefore gives no protection against the dangers of abrupt beta-blocker withdrawal; any such withdrawal should be by gradual reduction of the dose of beta-blocker.
Patients with Hepatic Failure
Since Amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t1/2) is 56 hours in patients with impaired hepatic function, caution should be exercised when administering Amlodipine to patients with severe hepatic impairment.
Special Precautions
Impaired liver or renal function, CHF, sick- sinus sundrome, severe ventricular dysfunction, hypertropic cardiomyopathy, severe aortic stenosis. Caution when used in patients with idiopathic hypertrophic subaortic stenosis. Elderly, children, pregnancy & lactation.
Other Drug Interactions
In vitro data indicate that Amlodipine has no effect on the human plasma protein binding of digoxin, phenytoin, warfarin, and indomethacin.
Effect of Other Agents on Amlodipine
Cimetidine: Co-administration of Amlodipine with cimetidine did not alter the pharmacokinetics of Amlodipine.
Grapefruit juice: Co-administration of 240 mL of grapefruit juice with a single oral dose of Amlodipine 10 mg in 20 healthy volunteers had no significant effect on the pharmacokinetics of Amlodipine.
Maalox1 (antacid): Co-administration of the antacid Maalox with a single dose of Amlodipine had no significant effect on the pharmacokinetics of Amlodipine.
Sildenafil: A single 100 mg dose of sildenafil (Viagra®2) in subjects with essential hypertension had no effect on the pharmacokinetic parameters of Amlodipine. When Amlodipine and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect.
Effect of Amlodipine on Other Agents
Atorvastatin: Co-administration of multiple 10 mg doses of Amlodipine with 80 mg of atorvastatin resulted in no significant change in the steady state pharmacokinetic parameters of atorvastatin.
Digoxin: Co-administration of Amlodipine with digoxin did not change serum digoxin levels or digoxin renal clearance in normal volunteers.
Ethanol (alcohol): Single and multiple 10 mg doses of Amlodipine had no significant effect on the pharmacokinetics of ethanol.
Warfarin: Co-administration of Amlodipine with warfarin did not change the warfarin prothrombin response time.
In clinical trials, Amlodipine has been safely administered with thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, nonsteroidal anti-inflammatory drugs, antibiotics, and oral hypoglycemic drugs.
Other Interactions
Information Not Available
Dosage
Adults
PO 5 to 10 mg every day.
Elderly
PO Initially 2.5 mg every day.
Hepatic Impairment
PO Initially 2.5mg every day.
Food(before/after)
Take with or without food
List of Contraindications
Amlodipine and Pregnancy
Category C:No evidence of teratogenicity or other embryo/fetal toxicity was found when pregnant rats or rabbits were treated orally with Amlodipine maleate at doses up to 10 mg Amlodipine/kg/day respectively 8 times* and 23 times* the maximum recommended human dose of 10 mg on a mg/m2 basis) during their respective periods of major organogenesis. However, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold) in rats receiving Amlodipine maleate at a dose equivalent to 10 mg Amlodipine/kg/day for 14 days before mating and throughout mating and gestation. Amlodipine maleate has been shown to prolong both the gestation period and the duration of labor in rats at this dose. There are no adequate and well-controlled studies in pregnant women. Amlodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. *Based on patient weight of 50 kg.
Amlodipine and Lactation
It is not known whether Amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while Amlodipine is administered.
Amlodipine and Children
The effect of Amlodipine on blood pressure in patients less than 6 years of age is not known.
Amlodipine and Geriatic
Clinical studies of Amlodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients have decreased clearance of Amlodipine with a resulting increase of AUC of approximately 40 to 60%, and a lower initial dose may be required
Amlodipine and Other Contraindications
Known hypersensitivity to dihydropyridnes.
Storage
Store in tightly closed container in cool location at 59° to 86°F.
Lab interference
Store in tightly closed container in cool location at 59° to 86°F.
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