In practice, the blood pressure goals set by hypertension management guidelines are not being achieved in majority of patients. One important reason for poor hypertension control rates is the inability of monotherapy to achieve blood pressure goals in many patients. Therefore, combination therapy is the need in nearly 2/3 rd of hypertensives to attain the target blood pressure levels.

One of the most common combination therapies for hypertension comprises a b blocker with a thiazide diuretic. Nebizide is a fixed dose combination of 5 mg nebivolol and 12.5 mg hydrochlorothiazide. Nebivolol is an outstanding, third generation highly selective b blocker with NO-mediated vasodilation whereas hydrochlorothiazide is a time-tested diuretic which has been used clinically for more than 45 years. Studies have shown the combination to offer additive BP reduction as compared to both monotherapies with no increase in adverse events. Further, the beneficial effects on lipids and glucose metabolism due to unique NO-mediated vasodilation with nebivolol can counteract the adverse effects of hydrochlorothiazide on lipids and glucose, thereby offering an advantage over other b blocker-diuretic combinations. In addition, the combination can also improve endothelial function on account of NO-mediated vasodilation with nebivolol and can yield added improvements in left ventricular function.

The recommended dose of NEBIZIDE is one tablet daily. In patients with severe renal impairment (CICr <30 mL/min) and moderate hepatic impairment, the initial dose of nebivolol should not exceed 2.5 mg of nebivolol in NEBIZIDE . NEBIZIDE is being made available across the country.

 

Cardiac arrhythmias are a major source of morbidity and mortality in the developing and the developed world. Although amiodarone is one of the oldest drugs with extensive evidence on its efficacy, its diverse adverse effect profile can limit its long-term use. Amongst other antiarrhythmic drugs, sotalol is a unique antiarhythmic drug. It is a class III antiarrhythmic; in addition to blocking the potassium channels, it is a non-selective b blocker.

Unlike amiodarone, sotalol has high bioavailability of 100%, no pharmacokinetic drug interactions and no need for any loading doses. Sotalol has been shown to be superior to amiodarone in ventricular arrhythmias and in supraventricular arrhythmias, sotalol has comparable efficacy with superior safety profile as compared to amiodarone. Sotalol has been demonstrated to be superior to b blockers in ventricular arrhythmias. Further, sotalol is also superior or at least comparable to class I drugs (procainamide, quinidine, propafenone, quinidine, mexiletinie, imipramine, piremenol) in ventricular and supraventricular arrhythmias. The major advantage of sotalol over amiodarone is that it does not exhibit multiorgan toxic side effects seen with long-term use of amiodarone

SOTALAR (sotalol) is available as 40 and 80 mg tablets and 10 mg/ml injections. SOTALAR tablets are indicated in life-threatening ventricular arrhythmias, non-sustained ventricular tachyarrhythmias, prophylaxis of supraventricular arrhythmias following cardiac surgery and for maintenance of sinus rhythm following conversion of atrial fibrillation or flutter. The initiation dose of SOTALAR tablets is 80 mg/day in single or two divided doses which can be increased at intervals of 2-3 days to 160-320 mg/day in two divided doses given at 12 hour intervals. SOTALAR injections are indicated in acute and life-threatening arrhythmias, programmed electrical stimulation in inducible ventricular and supraventricular arrhythmias and in those who are unable to take SOTALAR tablets. In acute arrhythmias, dosage for SOTALAR injections is 0.5-1.5 mg/kg. In programmed electrical stimulation, an initial bolus of 1.5 mg/kg of SOTALAR injection should be given, followed with maintenance infusion between 0.2-0.5 mg/kg/hour. For substitution in place of SOTALAR tablets, an infusion of SOTALAR injections between 0.2-0.5 mg/kg/hour should be used.

 

β blockers have been in clinical use for over 40 years and their usefulness for the management of cardiovascular diseases is well established. NEBICIP contains nebivolol, a novel, potent, third generation b blocker with the highest degree of b 1 selectivity amongst all currently available b blockers. Nebivolol also has a unique ability of stimulating nitric oxide (NO) production which causes vasodilation and improves endothelial function.

Nebivolol has demonstrated antihypertensive efficacy similar to that of other b blockers and other classes of antihypertensive drugs. Furthermore, nebivolol has been shown to significantly reduce the mortality and morbidity in elderly patients with chronic heart failure (CHF). In addition, nebivolol maintains or improves left ventricular function in patients with hypertension and also has anti-anginal efficacy.

NEBICIP is available in two strengths, NEBICIP 2.5 and NEBICIP 5 . It is indicated in hypertension and in elderly patients (age ≥ 70 years) with stable mild and moderate CHF. The recommended starting dose in hypertension is one tablet of NEBICIP 5 once daily, with or without food, which can be increased at 2-week intervals up to 40 mg. In severe renal impairment (CICr < 30 ml/min) and moderate hepatic impairment, recommended initial dose is one tablet of NEBICIP 2.5 once daily; upward titration should be performed cautiously if needed. In CHF, the initial dose is half-tablet of NEBICIP 2.5 , to be increased to one tablet of NEBICIP 2.5 once daily, then to one tablet of NEBICIP 5 once daily and then to 10 mg once daily.

 

Since activation of renin angiotensin system (RAS) plays a key role in the progression of renal and cardiovascular diseases, inhibitors of RAS [angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)] are now first-line treatments for progressive renal disease and hypertensive target organ damage.

The primary rationale justifying the use of ACE inhibitor and ARB combination is to ensure a more specific and complete RAS blockade. Clinical studies have demonstrated that ACE inhibitors and ARBs have specific renoprotective effects independent of BP reduction which include reduced risk of ESRD, reduced proteinuria and increased serum albumin levels and improvement in survival.

Amongst ACE inhibitors, ramipril has an extensive body of evidence regarding its clinical efficacy and safety. Amongst ARBs, telmisartan is an extensively used ARB on account of its unique properties. Hence, telmisartan and ramipril represents promising combination for providing renoprotection in high-risk hypertensives viz., hypertensives with diabetic and non-diabetic chronic kidney disease and diabetic hypertensives.

 CRESAR-R is the fixed-dose combination of telmisartan and ramipril from Cipla available in two strengths, CRESAR-R 2.5 (telmisartan 40 mg plus ramipril 2.5 mg) and CRESAR-R 5 (telmisartan 40 mg plus ramipril 5 mg). The usual recommended dosage is one tablet of CRESAR-R 2.5 or CRESAR-R 5 . In severe renal impairment or haemodialysis, a lower starting dose of one tablet of CRESAR-R 2.5 once daily should be used which may be titrated upward to a maximum of one tablet of CRESAR R 5 once daily . In mild to moderate hepatic impairment, dosage should not exceed one tablet of CRESAR-R 2.5/5 once daily.

 

Any disturbance in the blood coagulation system can lead to thrombosis which can clinically manifest as deep vein thrombosis (DVT), pulmonary embolism, unstable angina and myocardial infarction (MI). In such conditions, it is therefore prudent to use an anticoagulant in order to prevent the thrombotic sequelae. Although warfarin is the best amongst oral anticoagulants, it has a slow anticoagulant effect and a narrow therapeutic range. Low molecular weight heparins (LMWHs) have a rapid anticoagulant effect as compared to warfarin and offer several advantages over unfractionated heparin.

Enoxaparin is a unique chemical entity amongst LMWHs and has an extensive body of evidence on clinical efficacy and safety. Enoxaparin offers several advantages over unfractionated heparin including greater risk reduction of clinical events with safety profile similar to heparin. Enoxaparin is the only low-molecular-weight heparin to be approved by the US FDA in 7 indications for the prophylaxis and treatment of thromboembolic disease.

Enclex (Enoxaparin) is available in pre-filled syringes in two strengths, Enclex 40 and Enclex 60. Enclex is indicated for the prophylaxis of complications of unstable angina and non-Q wave MI, in the treatment of acute ST elevation MI, prophylaxis of DVT and in the treatment of acute DVT.

 

Epidemiological data has revealed that every 1 out of 5 Indian has hypertension and it is therefore of utmost importance to manage hypertension. More than 2/3 rd hypertensive patients require two or more drugs from different classes to achieve the target BP goals and hence, the use of fixed dose combinations may be more convenient.

Amlopres-NB is a fixed dose combination of 5 mg amlodipine and 5 mg nebivolol. Amlopres-NB can offer several benefits viz. additive BP reduction with an improved left ventricular function, NO mediated improvement in endothelial function, added anti-atherosclerotic effects and an excellent safety profile permitting its use in various classes of hypertensive patients. The recommended dosage of Amlopres-NB is one tablet once daily. In elderly patients (age above 65 years) and in patients with renal impairment, the dosage of Amlopres-NB is half tablet once daily which can be increased to one tablet once daily, if adequate blood pressure reduction is not achieved.

Obesity is a major health problem affecting not only the developed but also developing countries. India too is currently experiencing an increasing obesity epidemic. Around 20 million Indians are either obese or abdominally obese and by 2025, the expected number is 68 million.

This is indeed an alarming scenario since obesity not only increases mortality risk but also predisposes individuals to numerous comorbidities including type 2 diabetes, hypertension, heart disease, dyslipidaemia, osteoarthritis, gall bladder disease, sleep apnea and cancer.

Riomont (rimonabant) is a novel anti-obesity drug, which acts on the newly discovered endocannabinoid system. It is a selective cannabinoid receptor-1 (CB 1 ) antagonist, and modulates food intake, energy balance and body composition through both central and peripheral effects, and also improves glucose and lipid metabolism.

Clinical trials have shown that rimonabant causes significant and clinically meaningful reduction in weight , which is approximately four-fold greater compared to lifestyle modification alone. Importantly, weight loss achieved with rimonabant is maintained over time. Rimonabant also results in a remarkable reduction in waist circumference , which translates into a 25-30% reduction in visceral fat.

Further, rimonabant also causes a dramatic increase in HDL (high density lipoprotein) of 15-28%. This increase is greater than the average increase seen with placebo and similar to that seen with nicotinic acid. The decrease in triglycerides with rimonabant is in the rage of 9-16%. The drug also causes a favourable shift in the size of LDL (low density lipoprotein) particles. It also has been shown to significantly reduce glycosylated hemoglobin and improve insulin sensitivity.

Rimonabant has a favourable safety profile and is generally well tolerated. The most frequent adverse events are nausea, dizziness, diarrhoea and insomnia, each occurring 1-9% more frequently than with placebo. Side effects leading to drug discontinuation occurred in 13-16% patients with rimonabant vs 6-9% with placebo; and mainly included psychiatric disorders (depressed mood, anxiety and agitation), nausea and dizziness.

Riomont is indicated as an adjunct to diet and exercise for the treatment of obese patients (BMI ≥30 kg/m 2 ), or overweight patients (BMI > 27 kg/m 2 ) with associated risk factor(s) such as type 2 diabetes or dyslipidaemia. In adults, the recommended dosage is one 20 mg tablet daily to be taken in the morning before breakfast . Patients should be instructed not to increase their dose of rimonabant.

 Thus, manipulation of the endocannabinoid system with rimonabant is an intriguing new approach that addresses obesity as well as produces favourable changes in cardiometabolic risk.

 

Despite the increasing number of antihypertensive medications, epidemiological data have shown that fewer that one-third of hypertensive patients achieve BP goal of < 140/90 mm Hg. Hence, 90 out of 100 patients with hypertension may have inadequately controlled blood pressure. Thus there is a need for more potent and effective agents to control hypertension.

Amongst the various causes of hypertension, the renin-angiotensin system (RAS) is a major determinant of blood pressure and intravascular volume.

OLMECIP (Olmesartan medoxomil) is a new potent agent that acts on RAS by preventing the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT 1 receptor in the vascular smooth muscle. Its action is, therefore, independent of the pathways for angiotensin II synthesis. It shows ‘insurmountable' binding profile with more than a 12,500-fold greater affinity for the AT 1 receptor than for the AT 2 receptor.

OLMECIP shows powerful effects on blood pressure (BP) causing double-digit blood pressure reduction. It has a prolonged terminal elimination half-life of 12-18 hours, which is longer that most other AT 1 receptor antagonist. This favorable pharmacokinetic profile, coupled with its ‘insurmountable' receptor binding, allows the drug to be administered on a once-daily basis.

Further, OLMECIP has a consistent 24-hour BP control which is clinically important in controlling the early morning surge in BP that appears to contribute to an increased risk of cardiovascular events during that time.

The antihypertensive effect of OLMECIP is seen within 1 week of treatment initiation with near-maximal effects being seen at 2 weeks. This offers the opportunity to achieve early BP control without the need for prolonged dose-titration schedules.

INDICATION
OLMECIP is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.

DOSAGE AND ADMINISTRATION
The usual recommended starting dose of OLMECIP is 20 mg once daily when used as monotherapy in patients who are not volume-contracted. For patients requiring further reduction in blood pressure after 2 weeks of therapy, the dose of OLMECIP may be increased to 40 mg. Doses above 40 mg do not appear to have greater effect. Twice-daily dosing offers no advantage over the same total dose given once daily.

STRENGTHS AVAILABLE:
OLMECIP 20
Olmesartan medoxomil 20 mg tablets

OLMECIP 40
Olmesartan medoxomil 40 mg tablets

ALSO AVAILABLE AS:
OLMECIP-H
Olmesartan medoxomil 20 mg and Hydrochlorothiazide 12.5 mg tablets

 

Although the management of arrhythmias involve a combination of pharmacological as well as non-pharmacological options, in India , antiarrhythmic drugs play a major role mainly due to the high cost of the non-pharmacological measures. Amongst the antiarrhythmic drugs, amiodarone is one of the oldest and most frequently used drug for the management of cardiac arrhythmias.

Tachyra (Amiodarone) is available as 100 and 200 mg tablets and is indicated for the management of tachyarrhythmias associated with Wolff-Parkinson-White Syndrome, atrial flutter and fibrillation, all types of tachyarrhythmias of paroxysmal nature including supraventricular, nodal and ventricular tachycardias, ventricular fibrillation, when other drugs cannot be used. The recommended dosage regimen of Tachyra comprises an initial dose of 200 mg three times a day for 1 week which should then be reduced to 200 mg twice daily for a further week, followed subsequently with a maintenance dose of 200 mg daily, or less if appropriate.

 

Dytor Plus is a fixed-dose combination of torsemide and spironolactone, launched for the first time in the world. It is indicated for the relief of edema associated with secondary hyperaldosteronism in liver cirrhosis, congestive heart failure and nephrotic syndrome. It is also indicated in hypertension with hyperaldosteronism.

Torsemide is a powerful loop diuretic that blocks the Na + /K + /Cl - transporter in the loop of Henle and exhibits various advantages over frusemide viz. greater potency, longer duration of action, more complete and predictable bioavailability, lesser kaliuresis and no risk of drug accumulation. Spironolactone is a potassium sparing diuretic and a specific aldosterone antagonist, which competitively binds to receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule of the nephron. It causes diuresis and natriuresis, while retaining potassium.

In liver cirrhosis, torsemide plus spironolactone combination causes significantly greater diuresis, natriuresis and free water clearance, with lesser patients requiring upward dose titration as compared to frusemide plus spironolactone combination. It has also been shown reduction in body weight, ascites, edema, abdominal girth and ankle circumference. In CHF, torsemide plus spironolactone combination may provide significant reduction in mortality and hospitalization rates and increased efficacy in relieving edema. Studies have shown that both torsemide and spironolactone reduce myocardial fibrosis and left ventricular remodeling in CHF. Torsemide and spironolactone combination can also help to tackle diuretic resistance as this combination results in dual blockade of the nephron, at the loop of Henle as well as at the distal convoluted tubule and achieve edema relief. In nephrotic syndrome, torsemide in combination with spironolactone significantly reduced body weight, proteinuria by almost 50% and relieved peripheral edema. When spironolactone therapy is combined with torsemide, the hyperkalemia and hypermagnesemia caused by spironolactone can be attenuated by the hypokalemia and hypomagnesemia caused by torsemide, respectively and vice versa

Dytor Plus is available in two strengths: Dytor Plus 10 (torsemide 10 mg + spironolactone 50 mg) and Dytor Plus 20 (torsemide 20 mg + spironolactone 50 mg).

Dosage must be individualized. The recommended usual initial dose is 1 to 2 tablets of Dytor Plus 10 . The usual dose range is 1 to 4 tablets of Dytor Plus 10 per day (10-40 mg torsemide and 200 mg of spironolactone). In severe cases of edema, where a greater amount of loop diuretic is desired, Dytor Plus 20 may be given in the range of 1 to 4 tablets per day (20-80 mg torsemide and 200 mg of spironolactone). In certain patients, lower dosage (half tablet of Dytor Plus 10 ) may be adequate. To facilitate dosage convenience, Dytor Plus tablets are scored.

 

Cresar (Telmisartan) is an angiotensin type 1 (AT 1 ) receptor blocker mainly indicated for the management of hypertension.

Telmisartan is an ARB with dual function i.e. it inhibits AT 1 receptor and acts as a partial agonist of peroxisome proliferator activated receptor-gamma (PPAR g ). Telmisartan has the longest elimination half-life as compared to all other ARBs, leading to sustained duration of action particularly at the end of the dosing interval as compared to losartan. Telmisartan once daily elicits a smooth, consistent, clinically relevant reduction in BP throughout a 24-hour period.

In hypertension, telmisartan is superior to losartan, valsartan and ramipril in reducing the 24-hour ambulatory BP as well as the BP in the last 6 hours of dosing interval. Telmisartan is also at least as effective as other classes of antihypertensive drugs like calcium channel blockers, beta-blockers and ACE inhibitors. Telmisartan effectively reduces BP and proteinuria in patients with nephropathy in moderate or severe stages of renal insufficiency. Also, telmisartan offers renoprotection that is clinically equivalent to enalapril in patients at high risk for cardiovascular events. As a result of its PPAR g activation, telmisartan improves insulin sensitivity, reduces lipids and exerts antiatherosclerotic benefits.

In diabetic hypertensives, telmisartan significantly improved plasma lipids, decreased fasting insulin levels, fasting plasma glucose and HBA 1c levels. Serum adiponectin levels were significantly increased and CRP levels were decreased with telmisartan. Telmisartan exhibits placebo-like tolerability. The incidence of cough with telmisartan is significantly less than that seen with lisinopril and comparable to placebo. The adverse experiences have generally been mild and transient.

The usual starting dose is 40 mg once daily. Some patients may derive benefit with 20 mg. Most of the antihypertensive effect is apparent within two weeks and maximal reduction is generally attained after four weeks. When additional BP reduction beyond that achieved with 80 mg telmisartan is required, a diuretic may be added. I n patients with severe renal impairment or haemodialysis, a lower starting dose of 20 mg is recommended. In patients with mild to moderate hepatic impairment, dosage should not exceed 40 mg once daily.

Cresar is available in two strengths: Cresar 20 (telmisartan 20 mg) and Cresar 40 (telmisartan 40 mg).

 

Cresar-H is a fixed-dose combination of telmisartan (angiotensin receptor blocker) and hydrochlorothiazide (thiazide diuretic). This fixed-dose combination provides a balanced and synergistic antihypertensive effect in controlling blood pressure in hypertension along with a significant regression of left ventricular hypertrophy. Also, this combination is efficacious in a wide range of patient population - young as well as the elderly and in patients with low as well as high levels of renin.

The efficacy of Cresar-H combination has been well established over the monotherapy, as compared to losartan/HCTZ & enalapril /HCTZ

The combination of telmisartan-hydrochlorothiazide is well tolerated and the efficacy is maintained over 3 years. Cresar-H exhibits an improved safety profile, whereby hypokalemia associated with hydrochlorothiazide is attenuated by coadministration of telmisartan. Cresar-H improves patient compliance.

The usual initial dosage is one tablet of Cresar-H daily. The dose may be increased, if necessary, to two tablets of Cresar -H daily. In patients with renal impairment, t he usual dose is followed as long as the patient's creatinine clearance is >30 mL/min. In patients with more severe renal impairment, Cresar-H is not recommended. In p atients with hepatic impairment, Cresar-H is not recommended for patients with severe hepatic impairment. Patients with biliary obstructive disorders or hepatic insufficiency should have treatment started under close medical supervision.

Cresar-H is available as Cresar-H tablets (Telmisartan 40 mg + Hydrochlorothiazide 12.5 mg).