The P-I-E-N-O Parkinsn's List Drug Database
amlodipine / NorvascTM
BLOOD PRESSURE:
Description: Amlodipine is an oral calcium-channel blocker. It is used for the treatment of hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina, however, it is also under investigation for the treatment of heart failure. Amlodipine is a potent peripheral vasodilator, similar to nifedipine and other members of the dihydropyridine class, although amlodipine has the longest half-life of the group, thus allowing for once-daily dosing. Amlodipine was approved by the FDA in July 1992. As of May 1995, it is currently under review for treatment of heart failure.
Mechanism of Action: Amlodipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes. Serum calcium levels remain unchanged. Amlodipine inhibits this influx, and the resultant decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, resulting in dilation of the coronary and systemic arteries. As with other calcium-channel blockers of the dihydropyridine class, amlodipine exerts its effects mainly on arteriolar vasculature. It has no significant effect on sinus node function or cardiac conduction, nor does it possess negative inotropic effects at clinical doses. Because it has a gradual onset, reflex tachycardia does not occur, a side effect that is common with other peripheral vasodilators. Amlodipine therapy usually does not affect hemodynamic parameters in patients with normal ventricular function and has not worsened heart failure in patients with well-compensated heart failure (i.e., NYHA Class II and Class III); however, the drug should be used cautiously in patients with NYHA Class IV heart failure.
Amlodipine reduces coronary vasculature resistance and increases coronary blood flow. These actions increase oxygen delivery to the myocardial tissue. Myocardial oxygen consumption is also reduced. Thus, amlodipine's beneficial effects in the treatment of angina are a result of multiple actions.
Pharmacokinetics: Amlodipine is slowly but almost completely absorbed after oral administration. Oral bioavailability ranges from 52-88%. Peak plasma concentrations are achieved between 6-9 hours post-dose, and maximum hypotensive effects are correspondingly delayed. Food does not appear to influence these parameters significantly. The drug is approximately 93% bound to plasma proteins, but drug interactions secondary to displacement from binding sites have not been documented. Amlodipine is extensively metabolized to inactive compounds, and 10% of the parent compound and 60% of the inactive metabolites are excreted in the urine. Elimination of the drug is biphasic, with a 30- to 50-hour terminal elimination half-life, which is much longer than other currently available calcium-channel antagonists of the dihydropyridine class. Steady-state levels of amlodipine are achieved after 7-8 days of daily dosing.
CONTRAINDICATIONS/PRECAUTIONS: Amlodipine should be used with caution in patients with heart failure or cardiogenic shock because of the risk of a slight negative inotropic effect. Although clinical studies have shown that amlodipine did not worsen heart failure in patients with NYHA Class II or III heart failure, amlodipine should nevertheless be used cautiously in patients with heart failure.
Amlodipine decreases peripheral resistance and can worsen hypotension. Amlodipine should not be used in patients with systolic blood pressures of less than 90 mm Hg (i.e., severe hypotension). Amlodipine should be used with caution in patients with mild to moderate hypotension. Blood pressure should be monitored carefully in all patients receiving amlodipine.
Since amlodipine has an extremely long elimination half-life and is eliminated hepatically, amlodipine should be used cautiously in patients with hepatic disease. Accumulation could occur, leading to exaggerated hemodynamic effects. Amlodipine should be used cautiously in patients at risk of developing hypotension.
Amlodipine is relatively contraindicated in patients with advanced aortic stenosis because the drug can worsen the abnormal pressure gradient associated with this condition.
Rarely, an increased frequency, duration, and/or intensity of angina or acute myocardial infarction have occurred during amlodipine therapy, particularly in patients with severe obstructive coronary artery disease. Patients should be monitored for worsening angina when amlodipine therapy is begun.
Amlodipine is classified as a pregnancy category C drug. Amlodipine has been shown to be fetotoxic in laboratory animals. No adequate or well-controlled studies have been done in humans. Amlodipine should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.
DRUG INTERACTIONS: No clinically significant drug-drug interactions have been noted with amlodipine. In vitro studies have not shown any effect of amlodipine on the protein binding of other agents. Concomitant administration of cimetidine with amlodipine did not change the pharmacokinetics of amlodipine. Prothrombin time is not altered when amlodipine is given to patients receiving warfarin therapy. Amlodipine has been safely administered with digoxin, angiotensin-converting enzyme inhibitors, long-acting nitrates, thiazide diuretics, and ý-adrenergic blocking agents. No drug interactions are noted at this time.
ADVERSE REACTIONS: Amlodipine therapy is generally well tolerated at doses of up to 10 mg/day. Most of the reported reactions are of mild to moderate severity and are related to the drug's vasodilatory effect on the periphery. Headache and edema are reported most frequently. Dizziness, flushing, and palpitations also occur and appear to be dose-related. Other adverse reactions that have been reported and do not appear to be dose-related include fatigue, nausea/vomiting, abdominal pain, and drowsiness.
Although calcium-channel blockers are effective drugs for treating angina, worsening of angina has occurred in as many as 10% of patients receiving nifedipine for angina pectoris. This may be a result of excessive hypotension, myocardial steal, or a reflex increase in myocardial contractility. Since amlodipine is similar to nifedipine in structure and actions, patients with angina should be observed for worsening symptoms when amlodipine therapy is begun. The following adverse effects have been reported during amlodipine administration, but a causal relationship has not been established: sinus bradycardia, angina, peripheral ischemia, syncope, postural dizziness, orthostatic hypotension, paresthesias, tremor, vertigo, blurred vision, anorexia, constipation, diarrhea, dysphagia, and flatulence.
PATIENT INFORMATION:
What do amlodipine tablets do?
Amlodipine (NorvascTM ) is a calcium-channel blocker. It affects the amount of calcium found in your heart and muscle cells. This results in relaxation of blood vessels, which can reduce the amount of work the heart has to do. Amlodipine lowers high blood pressure (hypertension). It also relieves different types of chest pain (angina). It is not a cure. Generic amlodipine tablets are not yet available.
What should my doctor, dentist, or pharmacist know before I take amlodipine?
They need to know if you have any of these conditions:
How should I take this medicine?
Take amlodipine tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. You can take the tablets with or without food. Take your doses at regular intervals. Do not take your medicine more often then directed. Do not stop taking except on your doctor's advice.
Special precautions for use in children:
This medicine is not for children.
Elderly patients over 65 years old may have a stronger reaction to this medicine and need smaller doses.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact with amlodipine?
To date there have been no interactions recorded between amlodipine and other medicines.
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking amlodipine?
Serious side effects with amlodipine include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with amlodipine include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take amlodipine?
Check your blood pressure and pulse rate regularly; this is important while you are taking amlodipine. Ask your doctor what your blood pressure and pulse rate should be and when you should contact him or her.
You may feel dizzy or lightheaded. Do not drive, use machinery, or do anything that needs mental alertness until you know how amlodipine affects you. To reduce the risk of dizzy or fainting spells, do not sit or stand up quickly, especially if you are an older patient. Avoid alcoholic drinks; they can make you more dizzy, increase flushing and rapid heartbeats.
Do not suddenly stop taking amlodipine. Ask your doctor how you can gradually reduce the dose.
If you are going to have surgery, tell your doctor or dentist that you are taking amlodipine.
Where can I keep my medicine? Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30 C (59 and 86F). Protect from light. Keep container tightly closed. Throw away any unused medicine after the expiration date.
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