(dil tye' a zem)
P : Contraindicated in pregnancy
L : Contraindicated in lactation
Diltiazem hydrochloride is a calcium ion cellular influx inhibitor (slow channel blocker or calcium antagonist). Chemically, diltiazem hydrochloride is 1,5-Benzothiazepin-4(5H)-one, 3(acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-, monohydrochloride,(+)-cis-.
Diltiazem hydrochloride is a white to off-white crystalline powder with a bitter taste. It is soluble in water, methanol, and chloroform. It has a molecular weight of 450.98. Each tablet of Diltiazem contains 30 mg, 60 mg, 90 mg, or 120 mg diltiazem hydrochloride. Also contains: colloidal silicon dioxide, D&C Yellow #10 Aluminum Lake, FD&C Blue #1 Aluminum Lake (30 mg and 90 mg), FD&C Yellow #6 Aluminum Lake (60 mg and 120 mg), hydroxypropyl cellulose, hypromellose, lactose, magnesium stearate, methylparaben, microcrystalline cellulose, and polyethylene glycol.
Indication(s) & Dosage
Diltiazem is indicated for the management of chronic stable angina and angina due to coronary artery spasm.
Adult: Initially, 60 mg tid, increased to 360 mg daily or up to 480 mg daily, if necessary. Renal impairment: Dosage adjustment may be needed. Initial dose of 120 mg daily, as a single dose or in 2 divided doses depending on the formulation and titrated carefully as required. Do not increase dose if the heart rate drops <50 beats/min. Hepatic impairment: Dosage adjustment may be needed. Initial dose of 120 mg daily, as a single dose or in 2 divided doses depending on the formulation and titrated carefully as required. Do not increase dose if the heart rate drops <50 beats/min. Oral Hypertension Adult: Initially, 60-120 mg bid increased if needed. Max: 360 mg daily. Renal impairment: Dosage adjustment may be needed. Initial dose of 120 mg daily, as a single dose or in 2 divided doses depending on the formulation and titrated carefully as required. Do not increase dose if the heart rate drops <50 beats/min. Hepatic impairment: Dosage adjustment may be needed. Initial dose of 120 mg daily, as a single dose or in 2 divided doses depending on the formulation and titrated carefully as required. Do not increase dose if the heart rate drops <50 beats/min.
Cardiac arrhythmias Adult: Initially, 250 mcg/kg by bolus IV Inj over 2 mins, if necessary, after 15 min, may administer another dose of 350 mcg/kg. Individualsie subsequent doses. In patients with atrial fibrillation or flutter: 5-10 mg/hr infusion, increased in increments of 5 mg/hr up to a rate of 15 mg/hr continued for 24 hr. Renal impairment: Dosage adjustment may be needed. Hepatic impairment: Dosage adjustment may be needed.
Normal release prep: May be taken with or without food. Admin instructions for modified release prep may vary according to brands, refer to literatures.
Altered mental status, shock, bradycardia, hypotension, ECG changes, arrhythmias, heart block, cardiac arrest and heart failure.
Management: Treatment is supportive and symptomatic. Gastric lavage and administration of activated charcoal may help to reduce drug absorption. Haemodialysis and peritoneal unlikely to be useful. Charcoal haemoperfusion may be useful.
Diltiazem is contraindicated in patients with sick sinus syndrome except in the presence of a functioning ventricular pacemaker, (2) patients with second- or third-degree AV block except in the presence of a functioning ventricular pacemaker, (3) patients with hypotension (less than 90 mm Hg systolic), (4) patients who have demonstrated hypersensitivity to the drug, and (5) patients with acute myocardial infarction and pulmonary congestion documented by x-ray on admission.
1. Cardiac Conduction. Diltiazem prolongs AV node refractory periods without significantly prolonging sinus node recovery time, except in patients with sick sinus syndrome. This effect may rarely result in abnormally slow heart rates (particularly in patients with sick sinus syndrome) or second- or third-degree AV block (six of 1243 patients for 0.48%). Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. A patient with Prinzmetal's angina developed periods of asystole (2 to 5 seconds) after a single dose of 60 mg of diltiazem.
Elderly. Hepatic or renal impairment; impaired left ventricular function; prolonged AV periods; DM; hypotension. Avoid abrupt withdrawal and long-term use. Patients with sick-sinus syndrome, preexisting AV block, bradycardia and those taking beta-blockers or digitalis are at risk of developing AV block, bradycardia, asystole or sinus arrest.
Headache, ankle oedema, hypotension, dizziness, fatigue, flushing, nausea, GI discomfort, gingival hyperplasia, rashes, erythema multiforme, exfoliative dermatitis, photosensitivity, occasionally hepatitis. Potentially Fatal: AV block, bradycardia, asystole, sinus arrest.
Due to the potential for additive effects, caution and careful titration are warranted in patients receiving Diltiazem concomitantly with any agents known to affect cardiac contractility and/or conduction . Pharmacologic studies indicate that there may be additive effects in prolonging AV conduction when using beta-blockers or digitalis concomitantly with Diltiazem .
Administration of Diltiazem concomitantly with propranolol in five normal volunteers resulted in increased propranolol levels in all subjects, and bioavailability of propranolol was increased approximately 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 .
Buspirone. In nine healthy subjects, diltiazem significantly increased the mean buspirone AUC 5.5-fold and Cmax 4.1-fold compared to placebo. The T1/2 and Tmax of buspirone were not significantly affected by diltiazem. Enhanced effects and increased toxicity of buspirone may be possible during concomitant administration with diltiazem. Subsequent dose adjustments may be necessary during coadministration, and should be based on clinical assessment. Carbamazepine. Concomitant administration of diltiazem with carbamazepine has been reported to result in elevated serum levels of carbamazepine (40% to 72% increase) resulting in toxicity in some cases. Patients receiving these drugs concurrently should be monitored for a potential drug interaction.
Cimetidine. A study in six healthy volunteers has shown a significant increase in peak diltiazem plasma levels (58%) and area-under-the-curve (53%) after a 1-week course of cimetidine at 1200 mg per 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 the diltiazem dose may be warranted.
Cyclosporine. A pharmacokinetic interaction between diltiazem and cyclosporine has been observed during studies involving renal and cardiac transplant patients. In renal and cardiac transplant recipients, a reduction of cyclosporine trough dose ranging from 15% to 48% was necessary to maintain concentrations similar to those seen prior to the addition of diltiazem. If these agents are to be administered concurrently, cyclosporine concentrations should be monitored, especially when diltiazem therapy is initiated, adjusted, or discontinued. The effect of cyclosporine on diltiazem plasma concentrations has not been evaluated.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Serum levels may be elevated if taken with food.
Category C: Either studies in animals have revealed adverse effects on the foetus and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
Intravenous or Oral: Store at 15-30°C.
The therapeutic benefits achieved with Diltiazem are believed to be related to its ability to inhibit the influx of calcium ions during membrane depolarization of cardiac and vascular smooth muscle.
Mechanisms of Action
2. Exertional Angina. Diltiazem has been shown to produce increases 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 at drug levels which cause little or no negative inotropic effect. The resultant increases in coronary blood flow (epicardial and subendocardial) occur in ischemic and nonischemic models and are accompanied by dose-dependent decreases in systemic blood pressure and decreases in peripheral resistance.
Diltiazem relaxes coronary vascular smooth muscles by inhibiting influx of calcium ions during depolarisation of the vascular smooth muscles and myocardium. It increases myocardial O2 delivery in patients with vasospastic angina and inhibits cardiac conduction, particularly at the SA and AV nodes.
Absorption: Rapidly and almost completely absorbed from the GI tract. Distribution: Enters breast milk. Protein-binding: 80%. Metabolism: Hepatic: Extensive first-pass effect; yields desacetyldiltiazem. Excretion: Via urine, via bile; 3-5 hrs.
C08DB01 - diltiazem; Belongs to the class of benzothiazepine derivative selective calcium-channel blockers with direct cardiac effects. Used in the treatment of cardiovascular diseases.
|Brand Name||Manufacturer/Marketer||Composition||Dosage Form||Pack Size & Price|
|CARDIL||IBN SINA Pharmaceutical Industry Ltd.||Diltiazem hydrochloride 30mg, 60mg||Tablet||30mg x 100's, 60mg x 100's: 225.00 IP, 400.00 IP|
|CARDIZEM||Drug International Ltd||Diltiazem hydrochloride 30mg, 60mg||Tablet||30mg x 100's, 60mg x 100's: 300.00 & 500.00 MRP|
|CARDIZEM-SR||Drug International Ltd||Diltiazem hydrochloride 90mg, 120mg Sustained Release Capsule||Capsule||50's each: 250.00 & 400.00 MRP|
|DIAL||Nipa Pharmaceuticals Ltd.||Diltiazem hydrochloride 60mg||Tablet||60mg x 100's: 380.00 MRP|
|DILTIZEM 90||Square Pharmaceuticals Ltd.||Diltiazem 90mg||Tablet||4x10's: 225.20 MRP|
|EVASCON||Renata Limited||Diltiazem hydrochloride 30mg, 60mg||Tablet||30mg x 100's, 60mg x 100's: 202.00 & 385.00 MRP|
Why this medication is prescribed?
Diltiazem is used to treat high blood pressure and to control angina. Diltiazem is in a class of medications called calcium-channel blockers. It works by relaxing the blood vessels so the heart does not have to pump as hard. It also increases the supply of blood and oxygen to the heart.
How this medicine should be used?
Diltiazem may come as a tablet, an extended-release tablet, and an extended-release capsule to take by mouth. The regular tablet is usually taken three or four times a day. The extended-release capsule and tablet are usually taken one or two times a day. Ask your Doctor if you should take diltiazem with or without food, because instructions may vary with each product. Take diltiazem at around the same time every day. Follow the directions on your prescription label carefully, and ask your Doctor to explain any part you do not understand. Take diltiazem exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Swallow the extended-release capsules and tablets whole; do not chew or crush them.Your doctor will probably start you on a low dose of diltiazem and gradually increase your dose, not more than once every 7 to 14 days if you are taking the extended-release tablet or capsule and not more than once every 1 to 2 days if you are taking the regular tablet.
If taken regularly, diltiazem may control chest pain, but it does not stop chest pain once it starts. Your doctor may give you a different medication to take when you have chest pain.
Diltiazem controls high blood pressure and chest pain but does not cure them. It may take up to 2 weeks before you feel the full benefit of diltiazem. Continue to take diltiazem even if you feel well. Do not stop taking diltiazem without talking to your doctor.
Diltiazem is also sometimes used to treat certain types of arrhythmias. Talk to your doctor about the risks of using this medication for your condition.
This medication may be prescribed for other uses; ask your Doctor for more information.
What special precautions to follow?
Before taking diltiazem,
- inform your Doctor if you are allergic to diltiazem, any other medications, or any of the ingredients in diltiazem. Ask your Doctor for a list of the ingredients.
- inform your Doctor what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: atazanavir; benzodiazepines such as midazolam and triazolam; beta blockers such as atenolol, labetalol, metoprolol, nadolol, and propranolol; buspirone; carbamazepine; cimetidine; cyclosporine; digoxin; lovastatin; quinidine; and rifampin. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with diltiazem, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
- tell your doctor if you have or have ever had a myocardial infarction; a narrowing or blockage of your digestive system or any other condition that causes food to move through your digestive system more slowly; low blood pressure; or heart, liver, or kidney disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking diltiazem, consult your doctor.
- if you are having surgery, including dental surgery, tell your doctor or dentist that you are taking diltiazem.
What special dietary instructions to follow?
If your doctor prescribes a low-salt or low-sodium diet, follow these directions carefully.
What to do if I forget a dose?
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?
- dizziness or lightheadedness
- slow heartbeat
- nasal congestion
- swelling of the face, eyes, lips, tongue, hands, arms, feet, ankles, or lower legs
- difficulty breathing or swallowing
- yellowing of the skin or eyes
- extreme tiredness
- unusual bleeding or bruising
- lack of energy
- loss of appetite
- pain in the upper right part of the stomach
- flu-like symptoms
- increase in frequency or severity of chest pain
If you experience a serious side effect, you or your doctor may send a report to the Office of Directorate General, Drugs Administration.
What storage conditions are needed for this medicine?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture. Throw away any medication that is outdated or no longer needed. Talk to your Doctor about the proper disposal of your medication.
In case of emergency/overdose
In case of overdose, consult your Doctor. If the victim has collapsed or is not breathing, consult local medical emergency services..
Symptoms of overdose may include:
- slow, fast, or irregular heartbeat
- difficulty breathing
- increased sweating
What other information to know?
Keep all appointments with your doctor and the laboratory. Your blood pressure should be checked regularly to determine your response to diltiazem.
Your doctor may ask you to check your pulse daily and will tell you how fast it should be. If your pulse is slower than it should be, consult your doctor for directions on taking diltiazem that day. Ask your Doctor to teach you how to check your pulse.
Do not let anyone else take your medication.
It is important for you to keep a written list of all of the prescription and nonprescription medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
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