Angiozem

Angiozem

diltiazem

Manufacturer:

Yu Sheng

Distributor:

Littman
Full Prescribing Info
Contents
Diltiazem HCl.
Action
Antiangina.
Pharmacology: The therapeutic benefits achieved with diltiazem are related to its ability to inhibit the influx of calcium ions during membrane depolarization of cardiac and vascular smooth muscle.
Mechanism of Action: Diltiazem acts in the following ways: Angina Due to Coronary Artery Spasm: Diltiazem has been shown to be a potent dilator of coronary arteries both epicardial and subendocardial. Spontaneous and ergonovine-induced coronary artery spasms are inhibited by diltiazem.
Exertional Angina: Diltiazem has been shown to produce increase in exercise tolerance, probably due to its ability to reduce myocardial oxygen demand. This is accomplished via reductions in heart rate and systemic blood pressure at submaximal and maximal exercise workloads. In animal models, diltiazem interferes with the slow inward (depolarizing) current in excitable tissue. It causes excitation-contraction uncoupling in various myocardial tissues without changes in the configuration of the action potential. Diltiazem produces relaxation of coronary vascular smooth muscle and dilation of both large and small coronary arteries. The resultant increases in coronary blood flow (epicardial and subendocardial) occur in ischemic and non-ischemic models, and are accompanied by dose-dependent decreases in blood pressure and decreases in peripheral resistance.
Indications/Uses
Management of chronic stable angina and angina due to coronary artery spasm. Alone or in combination, it is also used for the treatment of hypertension.
Dosage/Direction for Use
Angina Pectoris: Initially, 30 mg 3 or 4 times a day, the dosage being increased gradually at 1- or 2-day intervals as needed and tolerated, or as prescribed by the physician.
Hypertension: 60 mg 3 times a day.
Contraindications
Patients with sick sinus syndrome except in the presence of a functioning ventricular pacemaker; 2nd- or 3rd-degree AV block except in the presence of a functioning ventricular pacemaker; hypotension (<90 mm Hg systolic); hypersensitivity to Angiozem; and acute myocardial infarction and pulmonary congestion documented by x-ray on admission.
Use in lactation: Diltiazem should not be given to nursing women until more information becomes available concerning its safety on infants.
Warnings
Cardiac Conduction: Diltiazem prolongs AV node refractory period without significantly prolonging sinus node recovery time, except in patients with sick sinus syndrome. This effect may rarely result in abnormal slow heart rates (particularly in patients with sick sinus syndrome) or 2nd- or 3rd-degree AV block (13 of 3290 patients or 0.4%). Concomitant use of diltiazem with β-blockers or digitalis may result in additive effects on cardiac conduction. A patient with Prinzmetal's angina developed periods asystole (2-5 sec) after a single dose of 60 mg of diltiazem. (See Adverse Reactions.)
Congestive Heart Failure: Although diltiazem has a negative inotropic effect in isolated animal tissue preparations, hemodynamic studies in humans with normal ventricular function have not shown a reduction in cardiac index nor consistent negative effects on contractility (dp/dt). An acute study of oral diltiazem in patients with impaired ventricular function (ejection fraction 24±6%) showed improvement in indices of ventricular function without significant decrease in contractile function (dp/dt). Worsening of congestive heart failure has been reported in patients with preexisting impairment of ventricular function. Hypotension: Decreases in blood pressure associated with diltiazem therapy may occasionally result in symptomatic hypotension.
Special Precautions
General: Diltiazem is extensively metabolized by the liver and excreted by the kidneys and in bile. As with any drug given over prolonged periods, laboratory parameter 8 of renal and hepatic functions should be monitored at regular intervals.
Angiozem should be used with caution in patients with impaired renal or hepatic function. In subacute and chronic dog and rat studies designed to produce toxicity, high doses of diltiazem were associated with hepatic damage. In special subacute hepatic studies, oral doses of ≥125 mg/kg in rats were associated with histological changes in the liver which were reversible when the drug was discontinued. In dogs, doses of 20 mg/kg were also associated with hepatic changes; however, these changes were reversible with continued dosing.
Dermatological events (see Adverse Reactions) may be transient and may disappear despite continued use of diltiazem. However, skin eruptions progressing to erythema multiforme and/or exfoliative dermatitis have also been infrequently reported. Should a dermatologic reaction persist, Angiozem should be discontinued.
Use In Pregnancy & Lactation
Use in lactation: Diltiazem should not be given to nursing women until more information becomes available concerning its safety on infants.
Adverse Reactions
The following represent occurrences observed in clinical studies of angina patients. In many cases, the relationship to diltiazem has not been established. The most common occurrences from these studies as well as their frequency of presentation are: Edema (2.4%), headache (2.1%), nausea (1.9%) dizziness (1.5%), rashes (1.3%), asthenia (1.2%). Ankle edema, hypotension, flushing and gastrointestinal disturbances (including anorexia, vomiting, constipation or diarrhea, taste disturbances and weight gain) may occur. Rashes, possibly due to hypersensitivity, are normally mild and transient, but in a few cases, erythema multiforme or exfoliative dermatitis has developed. Transient elevations in liver enzyme values, and occasionally hepatitis, have been reported.
The following events were reported infrequently (<1%):
Cardiovascular: Angina, arrhythmia, AV block (1st degree), AV block (2nd or 3rd degree, see Warnings), bradycardia, bundle-branch block, congestive heart failure, ECG abnormality, flushing, hypotension, palpitations, syncope.
CNS: Abnormal dreams, amnesia, depression, gait abnormality, hallucinations, insomnia, nervousness, paresthesia, personality change, somnolence, tremor.
Gastrointestinal: Anorexia, constipation, diarrhea, dysgeusia, dyspepsia, mild elevations of alkaline phosphatase, SGOT, SGPT and LDH.
Dermatological: Petechiae, photosensitivity, pruritus, urticaria.
Others: Amblyopia, CPK elevation, dry mouth, dyspnea, epistaxis, eye irritation, hyperglycemia, hyperuricemia, impotence and muscle cramps, nasal congestion, nocturia, osteoarticular pain, polyuria, sexual difficulties, tinnitus.
Drug Interactions
Due to the potential for additive effects, caution and careful titration are warranted in patients receiving diltiazem concomitantly with other agents known to affect the cardiac contractility and/or conduction (see Warnings). Pharmacologic studies indicate that there may be additive effects in prolonging AV conduction when using β-blockers or digitalis concomitantly with diltiazem (see Warnings). As with all drugs, care should be exercised when treating patients with multiple medications. Diltiazem undergoes biotransformation by cytochrome P-450 mixed function oxidase. Co-administration of diltiazem with other agents which follow the same route of biotransformation may result in the competitive inhibition of metabolism. Especially in patients with renal and/or hepatic impairment, dosage of similarly metabolized drugs, particularly those of low therapeutic ratio, may require adjustment when starting or stopping concomitantly administered diltiazem to maintain optimum therapeutic blood levels.
Beta-Blockers: Controlled and uncontrolled domestic studies suggest that concomitant use of diltiazem and β-blockers is usually well tolerated. But available data are not sufficient to predict the effects of concomitant treatment in patients with left ventricular dysfunction or cardiac conduction abnormalities. Administration of diltiazem concomitantly with propranolol in 5 normal volunteers resulted in increased propranolol levels in all subjects and bioavailability of propranolol was increased approximately by 50%. In vitro, propranolol appears to be displaced from its binding sites by diltiazem. If combination therapy is initiated or withdrawn in conjunction with propranolol, an adjustment in the propranolol dose may be warranted.
Cimetidine: A study in 6 healthy volunteers has shown a significant increase in peak diltiazem plasma levels (58%) and AUC (53%) after a 1-week course of cimetidine at 1200 mg/day and a single dose of diltiazem 60 mg. Ranitidine produced smaller, nonsignificant increases. The effect may be mediated by cimetidine's known inhibition of hepatic cytochrome P-450, the enzyme system responsible for the first-pass metabolism of diltiazem. Patients currently receiving diltiazem therapy should be carefully monitored for a change in pharmacological effect when initiating and discontinuing therapy with cimetidine. An adjustment in diltiazem dose may be warranted.
Anesthetics: The depression of cardiac contractility, conductivity and automaticity as well as the vascular dilation associated with anesthetics may be potentiated by calcium-channel blockers. When used concomitantly, anesthetics and calcium blockers should be titrated carefully.
Cyclosporin: A pharmacokinetic interaction between diltiazem and cyclosporin has been observed during studies involving renal and cardiac transplant patients. In renal and cardiac transplant recipients, a reduction of cyclosporin dose ranging from 15-48% was necessary to maintain cyclosporin through concentrations similar to those seen prior to the addition of diltiazem. If these agents are to be administered concurrently, cyclosporin concentrations should be monitored especially when diltiazem therapy is initiated, adjusted or discontinued. The effect of cyclosporin-diltiazem plasma concentrations has not been evaluated.
Carbamazepine: Concomitant administration of diltiazem with carbamazepine has been reported to result in elevated serum levels of carbamazepine (40-72% increase), resulting in toxicity in some cases. Patients receiving these drugs concurrently should be monitored for a potential drug interaction.
Storage
Store at temperatures not exceeding 30°C.
MIMS Class
ATC Classification
C08DB01 - diltiazem ; Belongs to the class of benzothiazepine derivative selective calcium-channel blockers with direct cardiac effects. Used in the treatment of cardiovascular diseases.
Presentation/Packing
Tab 30 mg x 100's. 60 mg x 100's.
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