CORALAN Contents

pulse). Ivabradine HCl Use in Patients with AV-block of 2nd Degree: Ivabradine is not recommended in patients with AV-block of 2nd degree. Use in Patients with a Low Heart Rate: Ivabradine must not be initiated in patients with a pre-treatment resting heart rate <60 bpm (see Contraindications). If during treatment, resting heart rate decreases persistently <50 bpm or the patient experiences symptoms related to bradycardia eg, dizziness, fatigue or hypotension, the dose must be titrated downward or treatment discontinued if heart rate is <50 bpm or symptoms of bradycardia persist (see Dosage & Administration). Combination with Other Antianginal Therapies: Concomitant use of ivabradine with heart rate-reducing calcium channel blockers eg, verapamil or diltiazem is not recommended (see Interactions). No safety issue has been raised on the combination of ivabradine with nitrates and dihydropyridine calcium channel blockers eg, amlodipine. Additional efficacy of ivabradine in combination with dihydropyridine calcium channel blockers has not been established. (See Pharmacology under Actions.) Chronic Heart Failure: Heart failure must be appropriately controlled before considering ivabradine treatment. The use of ivabradine is contraindicated in heart failure patients with NYHA functional classification III-IV, due to a lack of data on clinical efficacy and safety (see Contraindications). Caution is needed in patients with asymptomatic left ventricular dysfunction, as well as in heart failure patients with NYHA functional classification II due to a limited number of patients studied. Stroke: The use of ivabradine is not recommended immediately after a stroke since no data is available in these situations. Visual Function: Ivabradine influences on retinal function (see Pharmacology under Actions). To date, there is no evidence of a toxic effect of ivabradine on the retina, but the effects of long-term ivabradine treatment beyond 1 year on retinal function are currently not known. Cessation of treatment should be considered if any unexpected deterioration in visual function occurs. Caution should be exercised in patients with retinitis pigmentosa. Excipients: Since tablets contain lactose, patients with rare

Indicatio Symptomatic treatment of chronic stable angina pectoris in coronary ns artery disease in patients with normal sinus rhythm. Indicated in patients unable to tolerate or with a contraindication to the use of blockers or in combination with -blockers in patients inadequately controlled with an optimal -blocker dose and whose heart rate is >60 bpm. Contrain Hypersensitivity to ivabradine or to any excipients of Coralan; dications resting heart rate of <60 bpm prior to treatment; cardiogenic shock; acute myocardial infarction; severe hypotension (<90/50 mm Hg); severe hepatic insufficiency; sick sinus syndrome; sino-atrial block; heart failure patients with NYHA functional classification III-IV due to lack of data; pacemaker-dependent; unstable angina; AV-block of 3rd degree. Combination with strong cytochrome P-450 3A4 inhibitors eg, azole antifungals (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, oral erythromycin, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone (see Interactions, Pharmacokinetics under Actions). Use in pregnancy & lactation: There are no adequate data concerning the use of ivabradine in pregnant women. Animal reproduction studies have shown embryotoxic and teratogenic effects (see Toxicology under Actions). The potential risk for humans is unknown. Therefore, ivabradine is contraindicated during pregnancy. Animal studies indicate that ivabradine is excreted in milk. Therefore, ivabradine is contraindicated in breastfeeding women. Warning Cardiac Arrhythmias: Ivabradine is not effective in the treatment or prevention of cardiac arrhythmias and likely loses its efficacy when a s tachyarrhythmia occurs (eg, ventricular or supraventricular tachycardia). Ivabradine is therefore not recommended in patients with atrial fibrillation or other cardiac arrhythmias that interfere with sinus node function. It is recommended to regularly clinically monitor ivabradine-treated patients for the occurrence of atrial fibrillation (sustained or paroxysmal), which should also include ECG monitoring if clinically indicated (eg, in case of exacerbated angina, palpitations, irregular

hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Coralan. Special Patients with Hypotension: Limited data are available in patients Precauti with mild to moderate hypotension and ivabradine should therefore be used with caution in these patients. Ivabradine is contraindicated ons in patients with severe hypotension (blood pressure <90/50 mm Hg) (see Contraindications). Atrial Fibrillation - Cardiac Arrhythmias: There is no evidence of risk of (excessive) bradycardia on return to sinus rhythm when pharmacological cardioversion is initiated in patients treated with ivabradine. However, in the absence of extensive data, non-urgent DC-cardioversion should be considered 24 hrs after the last dose of ivabradine. Use in Patients with Congenital QT Syndrome or Treated with QT Prolonging Medicinal Products: The use of ivabradine in patients with congenital QT syndrome or treated with QT prolonging medicinal products should be avoided (see Interactions). If the combination appears necessary, close cardiac monitoring is needed. Use in Patients with Moderate Hepatic Insufficiency: Caution should be exercised when using ivabradine in patients with moderate hepatic insufficiency (see Dosage & Administration). Use in Patients with Severe Renal Insufficiency: Caution should be exercised when using ivabradine in patients with severe renal insufficiency (creatinine clearance <15 mL/min) (see Dosage & Administration). Effects on the Ability to Drive or Operate Machinery: A specific study to assess the possible influence of ivabradine on driving performance has been performed in healthy volunteers where no alteration of the driving performance was evidenced. Ivabradine has no influence on the ability to drive and use machines. However, ivabradine may cause transient luminous phenomena consisting mainly of phosphenes (see Adverse Reactions). The possible occurrence of such luminous phenomena should be taken into account when driving or using machines in situations where sudden variations in light intensity may occur, especially when driving at night.

Adverse Drug Reaction s

Coralan has been studied in clinical trials involving nearly 5000 participants. Approximately 2900 patients have been treated with ivabradine in phase II-III studies. The most common undesirable effects with ivabradine are dose-dependent and related to the pharmacological effect of the medicinal product. The following adverse effects or events have been reported during clinical trials. Eye Disorders: Very common (>1/10): Luminous phenomena (phosphenes): Reported by 14.5% of patients, described as a transient enhanced brightness in a limited area of the visual field. They are usually triggered by sudden variations in light intensity. The onset of phosphenes is generally within the first 2 months of treatment after which they may occur repeatedly. Phosphenes were generally reported to be of mild to moderate intensity. All phosphenes resolved during or after treatment, of which a majority (77.5%) resolved during treatment. Fewer than 1% of patients changed their daily routine or discontinued the treatment in relation with phosphenes. Common (>1/100, <1/10): Blurred vision. Cardiovascular Disorders: Common (>1/100, <1/10): Bradycardia: 3.3% of patients particularly within the first 2-3 months of treatment initiation. 0.5% of patients experienced a severe bradycardia 40 bpm; AV 1st degree block; ventricular extrasystoles. Uncommon (>1/1000, <1/100): Palpitations, supraventricular extrasystoles. The following events reported during clinical trials were of similar incidence than comparators and/or possibly related to the underlying disease: Sinus arrhythmia, unstable angina, aggravated angina pectoris, atrial fibrillation, myocardial ischaemia, myocardial infarction and ventricular tachycardia. Gastrointestinal Disorders: Uncommon (>1/1000, <1/100): Nausea, constipation and diarrhoea. General Disorders: Common (>1/100, <1/10): Headache, generally during the 1st month of treatment; dizziness, possibly related to bradycardia. Uncommon (>1/1000, <1/100): Vertigo, dyspnoea, muscle cramps. Investigations: Uncommon (>1/1000, <1/100): Hyperuricaemia, eosinophilia, elevated creatinine in blood.

Mechani Antiangina. Pharmacotherapeutic Group: Other cardiac preparations, sm of ATC code: C01EB17. Action Pharmacology: Pharmacodynamics: Ivabradine is a pure heart ratelowering agent, acting by selective and specific inhibition of the cardiac pacemaker If current that controls the spontaneous diastolic depolarisation in the sinus node and regulates heart rate. The cardiac effects are specific to the sinus node with no effect on intraatrial, atrioventricular or intraventricular conduction times, nor on myocardial contractility or ventricular repolarisation. Ivabradine can interact also with the retinal current Ih which closely resembles cardiac If. It participates in the temporal resolution of the visual system, by curtailing the retinal response to bright light stimuli. Under triggering circumstances (eg, rapid changes in luminosity), partial inhibition of Ih by ivabradine underlies the luminous phenomena that may be occasionally experienced by patients. Luminous phenomena (phosphenes) are described as a transient enhanced brightness in a limited area of the visual field (see Adverse Reactions). The main pharmacodynamic property of ivabradine in humans is a specific dose-dependent reduction in heart rate. Analysis of heart rate reduction with doses up to 20 mg twice daily indicates a trend towards a plateau effect which is consistent with a reduced risk of severe bradycardia <40 beats/min (bpm) (see Adverse Reactions). At usual recommended doses, heart rate reduction is approximately 10 bpm at rest and during exercise. This leads to a reduction in cardiac workload and myocardial oxygen consumption. Ivabradine does not influence intracardiac conduction, contractility (no negative inotropic effect) or ventricular repolarisation: In clinical electrophysiology studies, ivabradine had no effect on atrioventricular or intraventricular conduction times or corrected QT intervals; in patients with left ventricular dysfunction [left ventricular ejection fraction (LVEF) between 30% and 45%], ivabradine did not have any deleterious influence on LVEF. The antianginal and anti-ischaemic efficacy of Coralan was studied in 4 double-blind randomised trials (2 versus placebo, and 1 each versus atenolol and amlodipine). These trials included a total of 3222 patients with chronic stable angina pectoris, of whom 2168 received ivabradine.

Ivabradine 5 mg twice daily was shown to be effective on exercise test parameters within 3-4 weeks of treatment. Efficacy was confirmed with 7.5 mg twice daily. In particular, the additional benefit over 5 mg twice daily was established in a referencecontrolled study versus atenolol: Total exercise duration at trough was increased by about 1 min after 1 month of treatment with 5 mg twice daily and further improved by almost 25 sec after an additional 3-month period with forced titration to 7.5 mg twice daily. In this study, the antianginal and anti-ischaemic benefits of ivabradine were confirmed in patients 65 years. The efficacy of 5 and 7.5 mg twice daily was consistent across studies on exercise test parameters (total exercise duration, time to limiting angina, time to angina onset and time to 1 mm ST segment depression) and was associated with a decrease of about 70% in the rate of angina attacks. The twice-daily dosing regimen of ivabradine gave uniform efficacy over 24 hrs. In a 725 patients randomised placebo-controlled study, ivabradine did not show additional efficacy on top of amlodipine at the trough of drug activity (12 hrs after oral intake) while an additional efficacy was shown at peak (3-4 hrs after oral intake). Ivabradine efficacy was fully maintained throughout the 3- or 4month treatment periods in the efficacy trials. There was no evidence of pharmacological tolerance (loss of efficacy) developing during treatment nor of rebound phenomena after abrupt treatment discontinuation. The antianginal and anti-ischaemic effects of ivabradine were associated with dose-dependent reductions in heart rate and with a significant decrease in rate pressure product (heart rate x systolic blood pressure) at rest and during exercise. The effects on blood pressure and peripheral vascular resistance were minor and not clinically significant. A sustained reduction of heart rate was demonstrated in patients treated with ivabradine for at least 1 year (n=713). No influence on glucose or lipid metabolism was observed. The antianginal and anti-ischaemic efficacy of ivabradine was preserved in diabetic patients (n=457) with a similar safety profile as compared to the overall population. Pharmacokinetics: Under physiological conditions, ivabradine is rapidly released from tablets and is highly water-soluble (>10 mg/mL). Ivabradine is the S-enantiomer with no bioconversion

demonstrated in vivo. The N-desmethylated derivative of ivabradine has been identified as the main active metabolite in humans. Absorption and Bioavailability: Ivabradine is rapidly and almost completely absorbed after oral administration with a peak plasma level reached in about 1 hr under fasting condition. The absolute bioavailability of the film-coated tablets is around 40%, due to firstpass effect in the gut and liver. Food delayed absorption by approximately 1 hr and increased plasma exposure by 20-30%. The intake of the tablet during meals is recommended in order to decrease intraindividual variability in exposure (see Dosage & Administration). Distribution: Ivabradine is approximately 70% plasma proteinbound and the volume of distribution at steady-state is close to 100 L in patients. The maximum plasma concentration following chronic administration at the recommended dose of 5 mg twice daily is 22 ng/mL (CV=29%). The average plasma concentration is 10 ng/mL (CV=38%) at steady-state. Biotransformation: Ivabradine is extensively metabolised by the liver and the gut by oxidation through cytochrome P-450 3A4 (CYP3A4) only. The major active metabolite is the N-desmethylated derivative (S 18982) with an exposure about 40% of that of the parent compound. The metabolism of this active metabolite also involves CYP3A4. Ivabradine has low affinity for CYP3A4, shows no clinically relevant CYP3A4 induction or inhibition and is therefore unlikely to modify CYP3A4 substrate metabolism or plasma concentrations. Inversely, potent inhibitors and inducers may substantially affect ivabradine plasma concentrations (see Interactions). Elimination: Ivabradine is eliminated with a main half-life of 2 hrs (70-75% of the AUC) in plasma and an effective half-life of 11 hrs. The total clearance is about 400 mL/min and the renal clearance is about 70 mL/min. Excretion of metabolites occurs to a similar extent via faeces and urine. About 4% of an oral dose is excreted unchanged in urine. Linearity/Non-linearity: The kinetics of ivabradine is linear over an oral dose range of 0.5-24 mg. Special Populations: Elderly: No pharmacokinetic differences (AUC

and Cmax) have been observed between elderly ( 65 years) or very elderly patients ( 75 years) and the overall population (see Dosage & Administration). Renal Insufficiency: The impact of renal impairment (creatinine clearance from 15-60 mL/min) on ivabradine pharmacokinetic is minimal, in relation with the low contribution of renal clearance (about 20%) to total elimination for both ivabradine and its main metabolite S 18982 (see Dosage & Administration). Hepatic Impairment: In patients with mild hepatic impairment (Child Pugh score up to 7) unbound AUC of ivabradine and the main active metabolite were about 20% higher than in subjects with normal hepatic function. Data are insufficient to draw conclusions in patients with moderate hepatic impairment. No data are available in patients with severe hepatic impairment (see Dosage & Administration and Contraindications). Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship: PK/PD relationship analysis has shown that heart rate decreases almost linearly with increasing ivabradine and S 18982 plasma concentrations for doses of up to 15-20 mg twice daily. At higher doses, the decrease in heart rate is no longer proportional to ivabradine plasma concentrations and tends to reach a plateau. High exposures to ivabradine that may occur when ivabradine is given in combination with strong CYP3A4 inhibitors may result in an excessive decrease in heart rate, although this risk is reduced with moderate CYP3A4 inhibitors (see Contraindications, Warnings, Precautions and Interactions). Toxicology: Preclinical Safety Data: Reproductive toxicity studies showed no effect of ivabradine on fertility in male and female rats. When pregnant animals were treated during organogenesis at exposures close to therapeutic doses, there was a higher incidence of foetuses with cardiac defects in the rat and a small number of foetuses with ectrodactylia in the rabbit. In dogs, given ivabradine (doses of 2, 7 or 24 mg/kg/day) for 1 year, reversible changes in retinal function were observed but were not associated with any damage to ocular structures. These data are consistent with the pharmacological effect of ivabradine related to its interaction with hyperpolarisation-activated Ih currents in the retina, which share extensive homology with the cardiac pacemaker If current.

Other long-term repeat dose and carcinogenicity studies revealed no clinically relevant changes. MIMS Class Anti-Anginal Drugs

GENERIC NAME: CAPTOPRIL BRAND NAME: CAPOTEN DRUG CLASS AND MECHANISM: Captopril is an oral drug and a member of a class of drugs called angiotensin converting enzyme (ACE) inhibitors.ACE inhibitors are used for treating high blood pressure, heart failure, and for preventing kidney failure due to high blood pressure and diabetes. Other ACE inhibitors include enalapril (Vasotec), quinapril (Accupril), ramipril(Altace), fosinopril (M onopril), benazepril (Lotensin), lisinopril (Zestril, Prinivil), moexipril (Univasc) and trandolapril (Mavik). Angiotensin II is a very potent chemical that causes the muscles surrounding blood vessels to contract, thereby narrowing the vessels. The narrowing of the vessels increases the pressure within the vessels causing high blood pressure (hypertension). Angiotensin II is formed from angiotensin I in the blood by the enzyme angiotensin converting enzyme or ACE. ACE inhibitors are medications that slow (inhibit) the activity of the enzyme ACE and decrease the production of angiotensin II. As a result, blood vessels enlarge or dilate, and blood pressure is reduced. The lower blood pressure makes it easier for the heart to pump blood and can improve the function of a failing heart. In addition, progression of the blood vessel disease within the kidney caused by high blood pressure or diabetes is slowed. The FDA approved captopril in April 1981. PRESCRIPTION: Yes GENERIC AVAILABLE: Yes PREPARATIONS: Tablets: 12.5, 25, 50, 100 mg STORAGE: Captopril should be stored at room temperature, 15 to 30 C (59 to 86 F) and away from moisture. PRESCRIBED FOR: Captopril is used alone or in combination with other drugs for the treatment of high blood pressure and heart failure. Captopril also is used for improving survival and preventing heart failure and hospitalizations for heart failure after a heart attack. Like other ACE inhibitors, captopril may slow the progression of kidney failure in patients with diabetes or high blood pressure. DOSING: The recommended dose of captopril is 25-150 mg two or three times daily. The maximum dose is 450 mg daily. It should be taken on an empty stomach one hour before or two hours after meals since absorption of captopril is reduced when it is taken with food. DRUG INTERACTIONS: The use of ACE inhibitors with potassium supplements, salt substitutes or diuretics , for example, spironolactone(Aldactone), that

increase potassium in the blood may lead to excessive potassium levels (hyperkalemia). Potassium levels should be monitored whenever ACE inhibitors are used in combination with these drugs. There have been reports of increased lithium (Eskalith, Lithobid) levels when lithium is used in combination with ACE inhibitors. The reason for this interaction is not known, but the increased levels may lead to toxicity from lithium. There have been reports that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) such as ibuprofen (Advil, Children's Advil/Motrin, Medipren, Motrin, Nuprin, PediaCare Fever, etc.), indomethacin(Indocin, Indocin-SR), and naproxen (Anaprox, Naprelan, Naprosyn, Aleve) may reduce the effects of ACE inhibitors. PREGNANCY: ACE inhibitors, including captopril, can be harmful to the fetus and should not be taken by pregnant women. NURSING MOTHERS: Captopril is secreted in breast milk. Therefore it should be avoided by nursing mothers. SIDE EFFECTS: Captopril generally is well tolerated, and side effects are usually mild and transient. A dry, persistent cough has been reported commonly with the use of captopril and other ACE inhibitors. Coughing resolves after discontinuing the drug. Other side effects include abdominal pain, constipation, diarrhea, rash, dizziness, fatigue, headache, loss of taste, loss of appetite, nausea, vomiting, fainting and numbness or tingling in the hands or feet. Captopril and other ACE inhibitors also may cause kidney failure and increased levels of potassium in the blood. Serious but, fortunately, very rare side effects are liver failure and angioedema (swelling of lips and throat that can obstruct breathing). USES: Captopril is used to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. It is also used to treat heart failure, protect the kidneys from harm due to diabetes, and to improve survival after a heart attack.Captopril is an ACE inhibitor and works by relaxing blood vessels so that blood can flow more easily. HOW TO USE: Take this medication by mouth on an empty stomach (at least 1 hour before meals) as directed by your doctor, usually two to three times a day.The dosage is based on your medical condition and response to treatment.Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same times each day. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick.For the treatment of high blood pressure, it may take up to 2 weeks before you get the full benefit of this medication. For the treatment of heart failure, it may take weeks to months before you get the full benefit of this medication. Tell your doctor if your condition does not improve or if it worsens (such as your blood pressure readings remain high or increase).

GENERIC NAME: PENTOXIFYLLINE BRAND NAME: TRENTAL DRUG CLASS AND MECHANISM: Pentoxifylline is an oral drug used for treating by peripheral arterial symptoms of intermittent claudication caused disease (PAD). PAD is caused by the build-up of cholesterol plaques in arteries of the legs. Plaque blocks arteries, reducing the flow of oxygen-carrying blood through the arteries to the muscles. This causes pain uponwalking and reduces mobility. PAD is similar to coronary artery disease in which plaque builds up in heart arteries, causing chest pain (angina) because of a reduced supply of oxygen to the heart's muscle. Pentoxifylline, through unknown mechanisms, decreases the "stickiness" (viscosity) of blood and thereby improves its flow through arteries. This increases the flow of blood and oxygen to muscles and helps patients with intermittent claudication. The FDA approved pentoxifylline in August 1984. PRESCRIPTION: Yes GENERIC AVAILABLE: Yes PREPARATIONS: Tablets: 400 mg STORAGE: Pentoxifylline should be stored at room temperature between 15-30 C (59- 86 F), in a light resistant container. PRESCRIBED FOR: Pentoxifylline is used for the treatment of intermittent claudication caused by peripheral artery disease. DOSING: The recommended dose of Pentoxifylline is 400 mg three times daily with meals. DRUG INTERACTIONS: Pentoxifylline reduces the breakdown oftheophylline (Theo-Dur, Respbid, Slo-Bid, Theo-24, Theolair, Uniphyl, SloPhyllin) in the liver, increasing blood levels and side effects of theophylline. Combining pentoxifylline with warfarin (Coumadin) may increase the risk of bleeding. The mechanism for this interaction is unknown. PREGNANCY: Pentoxifylline has not been adequately studied in pregnant women. NURSING MOTHERS: Pentoxifylline is excreted in breast milk and may cause adverse effects in the infant. SIDE EFFECTS: Common adverse effects blurred vision, include nausea, vomiting,dizziness, headache, diarrhea, agitation, insomnia and drowsiness. Rarely, patients may experience abnormal heart beats,elevation of liver function tests, jaundice, and hepatitis. USES: This medication is used to improve the symptoms of a certain blood flow problem in the legs/arms (intermittent claudication due to occlusive artery disease). Pentoxifylline can decrease the muscle aching/pain/cramps during exercise, including walking, that occur with intermittent claudication. Pentoxifylline belongs to a class of drugs known as hemorrheologic agents. It works by helping blood flow more easily through narrowed arteries. This increases the amount of oxygen that can be delivered by the blood when the muscles need more (such as during exercise) thereby increasing walking distance and duration.

GENERIC NAME: SPIRONOLACTONE BRAND NAME: ALDACTONE DRUG CLASS AND MECHANISM: One of the main functions of the kidneys is to retain salt (sodium chloride) and water in the body. In patients with heart failure and cirrhosis, increased levels of a hormone produced by the adrenal glands, called aldosterone, causes salt and fluid to be retained by the kidneys. (At the same time, it also causes the kidneys to eliminate potassium.) The body becomes overloaded with salt and water, and this worsens the heart failure. Spironolactone inhibits the action of aldosterone thereby causing the kidneys to excrete salt and fluid in the urine while retaining potassium. Therefore, spironolactone is classified as a potassium-sparing diuretic, a drug that promotes the output of urine (diuretic) while allowing the kidneys to hold onto potassium. The FDA approved spironolactone in October 1985. PRESCRIPTION: Yes GENERIC AVAILABLE: Yes PREPARATIONS: Tablets 25, 50, and 100 mg STORAGE: Spironolactone should be stored at room temperature, below 25 C (77 F). PRESCRIBED FOR: Spironolactone removes excess fluid from the body incongestive heart failure, cirrhosis of the liver, and kidney disease. It can also be used in combination with other drugs to treat elevated blood pressureand for treating diuretic-induced low potassium (hypokalemia). Spironolactone also is used to counteract the effects of excessive adrenal aldosterone production (hyperaldosteronism). Aldosterone overproduction can occur from a tumor in the adrenal gland or enlarged adrenal glands (hyperplasia of the adrenal glands). DOSING: Spironolactone may be taken with or without food. The dosage range is 25-400 mg daily in single or divided doses. DRUG INTERACTIONS: Spironolactone can lower blood sodium levels while raising blood potassium levels. Excessively high blood potassium levels can lead to potentially life-threatening abnormalities in the rhythm of the heart. Therefore, spironolactone usually is not administered with other agents that can raise blood potassium levels, such as potassium supplements,angiotensin converting enzyme (ACE) inhibitors [for example, enalapril(Vasotec)], indomethacin (Indocin), or other potassiumsparing diuretics. Spironolactone can cause elevation of blood digoxin (Lanoxin) to toxic levels, requiring adjustment of the digoxin dosage. PREGNANCY: There are no adequate studies in pregnant women. Spironolactone may be harmful if used for treating gestational hypertension (high blood pressure during pregnancy). NURSING MOTHERS: An active metabolite of spironolactone is secreted in breast-milk. To avoid adverse effects in the newborn, mothers should avoidbreastfeeding while taking spironolactone. SIDE EFFECTS: Side effects of spironolactone include headache, diarrhea, cramps, drowsiness, rash, nausea, vomiting, impotence, irregular menstrual periods, and irregular hair growth. Fluid and electrolytes imbalance (for

example, low sodium, low magnesium, and high potassium) may occur, so patients should be monitored carefully. Enlargement of the breasts (gynecomastia) may also occur and is related to dose and duration of therapy. It usually reverses upon discontinuation of spironolactone. USES: Spironolactone is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. It is also used to treat swelling (edema) caused by certain conditions (e.g.,congestive heart failure) by removing excess fluid and improving symptoms such as breathing problems.This medication is also used to treat low potassium levels and conditions in which the body is making too much of a natural chemical (aldosterone).Spironolactone is known as a "water pill" (potassium-sparing diuretic).OTHER This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.This medication has also been used to treat excessive hair growth (hirsutism) in women with polycystic ovary disease. GENERIC NAME: DIGOXIN BRAND NAME: LANOXIN DRUG CLASS AND MECHANISM: Digoxin increases the strength and vigor of heart contractions, and is useful in the treatment of heart failure. It is extracted from the leaves of a plant called digitalis lanata. Digoxin increases the force of contraction of the muscle of the heart by inhibiting the activity of an enzyme (ATPase) that controls movement of calcium, sodium andpotassium into heart muscle. Calcium controls the force of contraction. Inhibiting ATPase increases calcium in heart muscle and therefore increases the force of heart contractions. Digoxin also slows electrical conduction between the atria and the ventricles of the heart and is useful in treatingabnormally rapid atrial rhythms such as atrial fibrillation, atrial flutter, and atrial tachycardia. (Abnormally rapid atrial rhythms can be caused by heart attacks, excessive thyroid hormones, alcoholism, infections, and many other conditions.) During rapid atrial rhythms, electrical signals from the atria cause rapid contractions of the ventricles. Rapid ventricular contractions are inefficient in pumping blood containing oxygen and nutrients to the body, causing symptoms of weakness, shortness of breath, dizziness, and evenchest pain. Digoxin alleviates these symptoms by blocking the electrical conduction between the atria and ventricles, thus slowing ventricular contractions. The FDA approved digoxin in 1975. PRESCRIPTION: Yes GENERIC AVAILABLE: Yes PREPARATIONS: Tablets: 0.125, and 0.25 mg; Elixir: 0.05, 0.25, and 0.1 mg/ml. STORAGE: Digoxin should be stored at room temperature, 59-86 F (15-30 C) and protected from light. PRESCRIBED FOR: Digoxin is used for mild to moderate congestive heart failure and for treating an abnormal heart rhythm called atrial fibrillation.

DOSING: Digoxin may be taken with or without food. Digoxin is primarily eliminated by the kidneys; therefore, the dose of digoxin should be reduced in patients with kidney dysfunction. Digoxin blood levels are used for adjusting doses in order to avoid toxicity. The usual starting dose is 0.0625-0.25 mg daily depending on age and kidney function. The dose may be increased every two weeks to achieve the desired response. DRUG INTERACTIONS: Drugs such as verapamil (Calan, Verelan, Verelan PM, Isoptin, Isoptin SR, Covera-HS), quinidine (Quinaglute, IndocinQuinide),amiodarone (Cordarone), indomethacin (Indocin, SR), alprazolam(Xanax, Xanax XR, Niravam), spironolactone (Aldactone), and itraconazole(Sporanox) can increase digoxin levels and the risk of toxicity. The co-administration of digoxin and beta-blockers [for example propranolol(Inderal, Inderal LA) or calcium channel blockers (for example, verapamil), which also reduces heart rate, can cause serious slowing of the heart rate. USES: Digoxin is used to treat heart failure, usually along with other medications. It is also used to treat a certain type of irregular heartbeat (chronic atrial fibrillation). Treating heart failure may help maintain your ability to walk and exercise and may improve the strength of your heart. Treating an irregular heartbeat can decrease the risk for blood clots, an effect that may reduce your risk for a heart attack or stroke.Digoxin belongs to a class of medications called cardiac glycosides. It works by affecting certain minerals (sodium and potassium) inside heart cells. This reduces strain on the heart and helps it maintain a normal, steady, and strong heartbeat. VASTAREL Contents Indications Dosage Trimetazidine Long-term treatment of coronary insufficiency; angina pectoris. 60 mg/24 hrs, equivalent to 3 tabs/day. Tablets should be taken orally in 3 doses with meals. Use in pregnancy & lactation: Studies in animal have not demonstrated a teratogenic effect, however in the absence of clinical data and for safety reasons, prescription should be avoided during pregnancy. In the absence of data on excretion in breast milk, breastfeeding is not recommended during treatment. Rare cases of gastrointestinal disorders. Click to view ADR Monitoring Website Since non-interaction with MAOIs has not been established,

Administration Should be taken with food Special Precautions

Adverse Drug Reactions Drug

Interactions

trimetazidine should not be co-administered with these agents. No other drug interactions have been reported. View more drug interactions with Vastarel 20 Trimetazidine diHCl is 1-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride. Metabolic anti-ischemic agent. Trimetazidine is a metabolic agent, a specific and selective inhibitor of the 3-KAT. This inhibition of -oxidation allows a recoupling of glycolysis and an increase in glucose oxidation for better energy production under ischemic conditions. Pharmacology: By preserving the energy metabolism in cells exposed to hypoxia or ischemia, trimetazidine prevents a decrease in intracellular ATP levels, thereby ensuring the proper functioning of ionic pumps and transmembranous sodium-potassium flow whilst maintaining cellular homeostasis. In animals, trimetazidine has been shown to help maintain energy metabolism in the heart during episodes of ischemia and hypoxia, to reduce intracellular acidosis and alterations in transmembranous ion flow caused by ischemia, to decrease the migration and infiltration of polynuclear neutrophils in ischemic and reperfused cardiac tissue, to also reduce the size of experimental infarction and to exert this action in the absence of any direct hemodynamic effect. In man, controlled studies in angina patients have shown that trimetazidine increases coronary reserve, thereby delaying the onset of ischemia associated with exercise, starting from the 15th day of treatment, significantly decreases the frequency of angina attacks and leads to a significant decrease in the use of nitrates. Pharmacokinetics: After oral administration, absorption of trimetazidine is rapid and the plasma peak is reached in <2 hrs. After a single oral dose of 20 mg of trimetazidine, the peak plasma concentration is about 55 ng/mL. The apparent volume of distribution is 4.8 L/kg which suggests good tissue diffusion. Elimination of trimetazidine is principally urinary; the mean half-life is 6 hrs.

Description Mechanism of Action

MIMS Class

Anti-Anginal Drugs

GENERIC NAME: OMEPRAZOLE, OMEPRAZOLE/SODIUM BICARBONATE BRAND NAME: PRILOSEC, ZEGERID DRUG CLASS AND MECHANISM: Omeprazole is in a class of drugs called proton pump inhibitors (PPI) that block the production of acid by the stomach. Other drugs in the class include lansoprazole (Prevacid),rabeprazole (Aciphex), pantoprazole (Protonix) , and esomeprazole (Nexium). Proton pump inhibitors are used for the treatment of conditions such as ulcers, gastroesophageal reflux disease (GERD) and the Zollinger-Ellison syndrome, which are all caused by stomach acid. Omeprazole, like otherproton-pump inhibitors, blocks the enzyme in the wall of the stomach that produces acid. By blocking the enzyme, the production of acid is decreased, and this allows the stomach and esophagus to heal. Zegerid contains omeprazole and an antacid (sodium bicarbonate). The FDA approved omeprazole in September 1989. GENERIC AVAILABLE: Yes (Prilosec) PRESCRIPTION: Yes; No (Prilosec OTC, Zegerid OTC) PREPARATIONS: Capsules: 10, 20 and 40 mg. Tablets: 20 mg (Prilosec OTC). Powder for oral suspension: 20 and 40 mg STORAGE: Capsules should be stored at 15 to 30 C (59 to 86 F) and tablets at 20 to 25 C (68 to 77 F). They should be kept away from moisture and light. PRESCRIBED FOR: Omeprazole is used for treating acid-induced inflammation and ulcers of the stomach and duodenum; gastroesophageal reflux disease (GERD); erosive esophagitis, heartburn; prevention of upper gastrointestinal bleeding in critically ill patients; and Zollinger-Ellison Syndrome. It also is used in combination with antibiotics for eradicating H. pylori infection of the stomach. DOSING: For ulcers, GERD, erosive esophagitis and eradication of H. pylorithe recommended dose for adults is 20-40 mg daily. Ulcer healing usually occurs within 4-8 weeks. H. pylori infections are treated for 10-28 days. The usual dose for prevention of upper gastrointestinal bleeding in critically ill patients is 40 mg daily for 14 days. Prilosec OTC is used for treating heartburn for up to two weeks, and the usual dose is 20 mg daily. For the management of Zollinger-Ellison Syndrome the starting dose for adults is 60 mg daily, and the dose is adjusted based on either the response of symptoms or the actual measurement of acid production. Doses greater than 80 mg should be divided. Doses up to 120 mg three times a day have been used in the treatment of Zollinger-Ellison Syndrome. For maximal efficacy, omeprazole tablets should be taken before meals, swallowed whole and should not be crushed, chewed or opened. DRUG INTERACTIONS: Omeprazole potentially can increase the concentrations in blood of diazepam (Valium), warfarin (Coumadin), andphenytoin (Dilantin) by decreasing the elimination of these drugs by the liver. The absorption of certain drugs may be affected by stomach acidity. Therefore, omeprazole as well as other PPIs reduce the absorption and concentration in

blood of ketoconazole (Nizoral) and increase the absorption and concentration in blood of digoxin (Lanoxin). This may reduce the effectiveness of ketoconazole or increase digoxin toxicity. USES: Omeprazole is used to treat certain stomach and esophagus problems (such as acid reflux, ulcers). It works by decreasing the amount of acid your stomach makes. It relieves symptoms such as heartburn, difficulty swallowing, and persistent cough. This medication helps heal acid damage to the stomach and esophagus, helps prevent ulcers, and may help preventcancer of the esophagus. Omeprazole belongs to a class of drugs known as proton pump inhibitors (PPIs).If you are self-treating with this medication, over-the-counter omeprazole products are used to treat frequent heartburn (occurring 2 or more days a week). Since it may take 1 to 4 days to have full effect, these products do not relieve heartburn right away.For over-the-counter products, carefully read the package instructions to make sure the product is right for you. Check the ingredients on the label even if you have used the product before. The manufacturer may have changed the ingredients. Also, products with similar brand names may contain different ingredients meant for different purposes. Taking the wrong product could harm you. GENERIC NAME: CALCIUM CARBONATE BRAND NAME: CALTRATE 600, CALTRATE 600 PLUS D, CALTRATE 600 PLUS DRUG CLASS AND MECHANISM: Calcium is the fifth most abundant element in the body. Calcium is an important structural component of bone and teeth and also is necessary for the normal function of all muscles (skeletal, heart, and smooth muscles) and nerves as well as the normal clotting of blood. Prolonged, inadequate intake of calcium causes weak bones (osteoporosis). Products containing calcium carbonate are used to increase the intake of calcium in individuals whose diets are low in calcium. The National Institutes of Health recommend 1000 to 1500 mg of calcium per day as part of a regimen to prevent the loss of bone that is associated with aging. Calcium carbonate products contain 40% calcium (absorbable calcium). Therefore, a 1500 mg tablet of calcium carbonate provides 600 mg of calcium. PRESCRIPTION: no GENERIC AVAILABLE: yes PREPARATIONS: Caltrate 600 tablets (600 mg calcium); Caltrate 600 plus D tablets (600 mg calcium plus 200 IU vitamin D), Caltrate 600 plus tablets (600 mg calcium plus 200 IU vitamin D and other minerals); Caltrate 600 chewable tablets. STORAGE:Tablets should be stored at room temperature, 2-25C (36-77F). PRESCRIBED FOR: Calcium-containing products are used as part of a regimen for preventing and treating osteoporosis in individuals with low levels of calcium in their diets. Such regimens also may include vitamin D, estrogen replacement therapy, and specific medications for treating osteoporosis, for example, alendronate.

DOSING: The usual recommended dose of Caltrate for adults is one tablet twice a day with meals. DRUG INTERACTIONS:Calcium products bind to quinolone (e.g.,Ciprofloxacin) and tetracycline (e.g., Sumycin) antibiotics in the intestine and can prevent their absorption into the body. To prevent this interaction, doses of quinolone and tetracycline antibiotics should be separated by three or more hours from doses of calcium. Calcium carbonate-containing products reduce acidity in the stomach, though there may be a rebound phenomenon which causes a greater than normal amount of acid to be produced after the initial acid-reducing effects of the calcium wear off. The reduction of acid decreases the absorption of iron from the intestine. Therefore, doses of calcium and iron should be separated by a several hours. Calcium products also bind to Kayexalate (a drug used to treat high levels of potassium) in the intestine and, therefore, may interfere with the action of Kayexalate. Doses of Kayexalate and calcium products should be separated by several hours. PREGNANCY:Use of calcium supplements during pregnancy appears to be safe, but such use should be done under the supervision of a healthcare provider. NURSING MOTHERS: Calcium supplements are safe when used by nursing mothers. SIDE EFFECTS: Calcium products rarely cause an upset stomach. However, excessive intake or absorption of calcium may lead to increased levels of calcium in the blood (hypercalcemia) which may cause nausea, vomiting, decreased appetite, abdominal pain, dry mouth and thirst. Severe hypercalcemia may cause confusion, delirium, stupor and coma. GENERIC NAME: MELOXICAM BRAND NAME: MOBIC DRUG CLASS AND MECHANISM: Meloxicam is in a class of drugs callednonsteroidal anti-inflammatory drugs (NSAIDs) and are used to treat pain and/or inflammation. Prostaglandins are chemicals that contribute to inflammation within joints, and it is the inflammation that leads to the common symptoms of pain, tenderness and swelling associated with arthritis. Meloxicam blocks the enzymes that make prostaglandins (cyclooxygenase 1 and 2) and reduces the levels of prostaglandins. As a result, inflammation and its accompanying symptoms are reduced. Meloxicam was approved for use in April 2000. GENERIC AVAILABLE: yes PRESCRIPTION: yes PREPARATIONS: Meloxicam is available as a yellow, round, biconvex, uncoated tablet containing meloxicam 7.5 mg or as a yellow, oblong, biconvex, uncoated tablet containing meloxicam 15 mg. STORAGE: Meloxicam should be stored in a dry place at room temperature, 1530C (59-86F).

PRESCRIBED FOR: Meloxicam is used to treat tenderness, swelling and pain caused by the inflammation of osteoarthritis and rheumatoid arthritis. DOSING: The lowest effective dose should be used for each patient. Meloxicam therapy usually is started at 7.5 mg daily. Some patients require a dose of 15 mg daily, but this dose should be taken only under the direction of a physician. Meloxicam may be taken with or without food. DRUG INTERACTIONS: In studies where meloxicam was administered withcimetidine (Tagamet), digoxin (Lanoxin), and methotrexate (Rheumatrex), there were no drug interactions. Meloxicam may interfere with a class of drugs called ACE inhibitors, e.g., captopril (Capoten) and ramipril (Altace) or the water pill, furosemide (Lasix), that are used for controlling high blood pressure,. This may lead to an increase in blood pressure, and as a result, the dose of ACE inhibitor or Lasix may need to be changed when starting or stopping meloxicam. Meloxicam should be avoided by patients with a history of asthma attacks,hives or other allergic reactions to aspirin or other NSAIDs. If aspirin is taken with meloxicam there may be an increased risk for developing an ulcer. Persons who have more than 3 alcoholic beverages per day may be at increased risk of developing stomach ulcers when taking meloxicam or other NSAIDs. Cholestyramine (Questran), colestipol (Colestid) and colesevelam (Welchol) may decrease the effectiveness of meloxicam by preventing its absorption from the intestine. Lithium (Eskalith or Lithobid) blood levels may increase or decrease after meloxicam therapy starts or stops. Therefore, both the patient taking lithium and the blood level of lithium need to be evaluated when starting or stopping meloxicam. Meloxicam should be used with caution in combination with blood thinning medications such as warfarin (Coumadin) because of an increased risk of bleeding. SIDE EFFECTS: In general, the most common side effects with NSAIDs are related to the gastrointestinal tract (GI) and include nausea, vomiting,abdominal pain, diarrhea and gas. To prevent these common side effects, it is recommended that most NSAIDs be taken with food or milk. NSAIDs may cause ulcers in the stomach and/or small intestine. A few NSAIDs are designed to be less damaging to the stomach and small intestine, and, therefore, they may be taken with or without food. Meloxicam is an example of one of these NSAIDs, but, nevertheless, it should be taken cautiously without food. NSAIDs have been associated with an increased risk of blood clots that can cause strokes and heart attacks. NSAIDs also may interfere with the function of the kidneys or injure the kidneys. Other less common side effects of meloxicam are headache, fatigue related to anemia (low red blood cell count), joint pain, back pain, insomnia, itching, skin rash, bladder infection and upper respiratory tract infection.