Statins are the most effective drugs available for lowering LDL and have revolutionized cardiovascular medicine. However, despite the widespread use of statins, many patients do not attain LDL goals and this is especially true in high and very high-risk patients in whom the LDL goals are even lower. Therefore, there is a demand for more potent statins.

Rosuvastatin is the most potent statin for reducing LDL and was approved by US FDA in August 2003. Rosuvastatin monotherapy may allow patients to attain LDL goals earlier and may help avoid combination therapy or potential adverse effects of high-dose statin therapy. Further, rosuvastatin has several advantages over all other statins- highest affinity for HMG-CoA reductase, greater increase in HDL and fewer clinically significant drug interactions. In addition, rosuvastatin is the only statin to be approved by the US FDA for slowing the progression of atherosclerosis. The safety profile of rosuvastatin is similar to other statins.

Recently, the JUPITER trial which showed significant reduction in cardiovascular events with rosuvastatin in healthy people with normal LDL and high C-reactive protein has added a new perspective in primary prevention therapy for statins. These results have the potential to revise guidelines and can have a huge impact on clinical practice.

ROSULIP is currently available in two strengths: ROSULIP 5 (5 mg rosuvastatin) and ROSULIP 10 (10 mg rosuvastatin). The dosage range of ROSULIP is 5-40 mg once daily at any time of the day and independent of food.

 

Hypertension and hypercholesterolemia are the most common major risk factors for cardiovascular disease (CVD). Approximately 40% of patients with hypertension have been reported to have hypercholesterolemia. Alarmingly, in agreement with the western population, even in our country, a significant proportion of patients have both hypertension and dyslipidemia. An analysis revealed that hypercholesterolemia was present in 57% and hypertriglyceridemia in 30% of Indian patients while 37% of patients had LDL ≥ 130 mg/d l.

Both hypertension and dyslipidemia result in endothelial dysfunction and consequently lead to the development of atherosclerosis. Hence, there is a strong synergy between hypertension and dyslipidemia in the development of CVD. P resence of high cholesterol in men with SBP ≥ 160 mg/dl has shown to dramatically increase the risk of CVD by 10-fold . This dramatic rise in CVD is through the interplay of hypertension & dyslipidemia via the renin angiotensin aldosterone system (RAAS). Therefore, combining ARB and statin seems to be an ideal choice for the management of coexisting hypertension with hyperlipidemia.

CRESLIP , a combination of 40 mg telmisartan and 10 mg atorvastatin, has been launched by Cipla in November 2009 for the management of coexisting hypertension and hyperlipidemia.

Telmisartan is a highly selective angiotensin II receptor blocker which has shown to provide 24-hr BP control even in the last 6 hrs of the dosing interval. Besides, telmisartan also acts as a partial PPAR gamma agonist which imparts some important benefits with the molecule like antiatherosclerotic property, improvement in lipid profile, improvement in insulin sensitivity etc.

The second component of CRESLIP is the most widely used statin, atorvastatin. Atorvastatin has shown to improve lipid profile effectively in a wide range of patients. It has shown to reduce CV events & also exhibits antiatherosclerotic, antioxidant property etc

The recommended dosage is one tablet of CRESLIP once daily. The maximum dose should not exceed two tablets of CRESLIP once daily. Patients with depletion of intravascular volume should have their condition corrected or CRESLIP should be initiated under close medical supervision. In p atients with biliary obstructive disorders or hepatic impairment, CRESLIP should be given under close medical supervision.

February 2010

The global burden of cardiovascular disease (CVD) is increasing steadily. The problem is even worse in low-income and middle-income countries; 4/5 th of all cardiovascular-related events occur in these countries. It is expected that by 2010, 60% of world's heart disease would occur in India , which can have a huge impact on the economy of our country. Therefore, the need of the hour is to contain this epidemic of CVD in India .

Although efficacy of the recommended secondary CVD prevention therapies viz. statins, beta blockers, renin-angiotensin system (RAS) blockers and aspirin are well-known, there is underutilization of these therapies. Adding to this is the fact that adherence to drug therapy in chronic diseases like CVD is very low, which is responsible for adverse clinical outcomes. Both these factors can prove to be a hurdle in effective secondary prevention of CVD.

Studies have proven beyond doubt that utilization of statins, beta blockers, RAS blockers and aspirin yields significant mortality benefits as compared to non-utilization of all these four classes of drugs in patients with CVD. The introduction of STARPILL ; a revolutionary single tablet which contains all these four drug classes- aspirin 75 mg, atenolol 50 mg, losartan 50 mg and atorvastatin 10 mg would therefore represent an optimal, cost-effective tool to reduce the rising burden of CVD in India. STARPILL is indicated in patients at high risk of vascular disease. The recommended dose of STARPILL is one tablet once daily and the maximum dosage should not exceed two tablets once daily. Just taking one tablet of STARPILL daily can reduce the risk of mortality up to 90% in CVD patients.

 

Shock , is a serious, life-threatening medical condition wherein due to insufficient blood flow reaching the body tissues, multiorgan failure may result. The causes of shock can be classified as hypovolemic, vasodilatory and cardiogenic. Re-establishing perfusion to the organs is the primary goal of the management. Septic shock , the most severe form of sepsis accounts for 9 % admissions to intensive care unit and it's short-term mortality ranges from 40 -60 %. Volume resuscitation combined with vasopressor support remains the standard of care in management of septic shock and many consider dopamine to be the pressor of choice. Because of the fear of excessive vasoconstriction, noradrenaline is considered to be deleterious. But as per the guidelines for `Managememt of severe sepsis and septic shock' 2008 ,led by European Society of Intensive Care Medicine, the International Sepsis Forum, and the Society of Critical Care Medicine, noradrenaline or dopamine , both are the initial vasopressors of choice in the management of septic shock.

Dopamine is widely used to improve systemic and hepatosplanchnic hemodynamics and oxygenation during sepsis. However studies have shown that noradrenaline may have beneficial effects on regional blood flow and metabolism whereas dopamine might have deleterious effects related to redistribution of blood flow away from intestinal mucosa or by decreasing directly cell redox state. In addition dopamine may impair hepatic energy balance. Tissue hypoxia in the splanchnic region is considered to be an important factor in the pathogenesis of multiorgan failure. Multiorgan failure is associated with high rate of mortality in these septic shock patients despite having achieved normal systemic hemodynamics. Thus use of noradrenaline may influence outcome favorably in septic shock patients.

Each ml. of INFUNOR injection contains noradrenaline base of 1mg. INFUNOR injection is recommended for the restoration of blood pressure in acute hypotensive states and acts predominantly by a direct effect on alpha-adrenergic receptors.

INFUNOR injection is a concentrated, potent drug which must be diluted in dextrose -containing solutions and given by I.V. infusion into a large vein .

Initial dose is 8 µg to 12 µg of noradrenaline base per minute followed by maintenance dose of 2 µg to 4 µg of base per minute.

HIGHLIGHTS

• Noradrenaline is sympathomimetic amine, which acts predominantly by a direct effect on alpha-adrenergic receptors
• Indicated in the management of acute hypotensive states
• Initial vasopressor of choice in the management of septic shock
• Beneficial effects on systemic as well as hepatosplanchnic hemodynamics

Cipla has become the first company in India to manufacture and market bosentan under the trade name BOSENTAS , a drug used to treat pulmonary arterial hypertension (PAH), a life-threatening condition.

PAH usually affects women in their 30s and 40s but can also affect others. The patient experiences breathlessness, is easily tired, feels tightness of chest and is always fatigued. Other common conditions like asthma present similar symptoms. As a result, PAH is often misdiagnosed and the right treatment is delayed.  Other causes are the collagen vascular diseases such as scleroderma, or systemic lupus erythematosus. Congenital heart diseases, chronic pulmonary thromboembolism, HIV infection, liver disease and diet drugs like fenfluramine and dexfenfluramine are also causes of pulmonary hypertension.

Though the exact cause of PAH is as yet unknown, patients have high levels of endothelin, a substance produced by the endothelial cells that line the blood vessels. Endothelin causes vasoconstriction, hypertrophy and fibrosis leading to vascular remodeling. 

BOSENTAS (bosentan) is an orally active dual endothelin receptor antagonist (ERA). Bosentan works by blocking the binding of endothelin (ET).  ET is produced and secreted by the endothelium, a monolayer of cells covering the inner surface of blood vessels.  Bosentan blocks both ETA and ETB receptors preventing the deleterious effects of endothelin.

Since its introduction in the USA (2001), Europe (2002) and other countries worldwide, bosentan has become a recommended treatment for pulmonary arterial hypertension (PAH) as reflected in current guidelines for PAH.

Bosentan, is currently licensed for the treatment of PAH, a chronic, life-threatening disorder.  In the United States, Bosentan is approved for treatment of PAH Functional Class III and IV to improve exercise capacity and decrease the rate of clinical worsening, and in the European Union (EU) it is approved for treatment of PAH Functional Class III to improve exercise capacity and symptoms, as well as PAH Functional Class II where some improvements have also been shown.  In the EU, Bosentan is also indicated to reduce the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease.

BOSENTAS is available in 62.5 and 125 mg tablets.  Treatment should be initiated with 62.5 mg twice daily for 4 weeks and then uptitrated to 125 mg twice daily.

Prescribing information

 

Coronary heart disease (CHD) has assumed epidemic proportions in India & by 2010, 60% of the world's heart disease is expected to occur in India . Chronic stable angina is the commonest initial manifestation of CHD. It is observed that despite an extensive use of conventional therapy, 85% of patients still complain of anginal symptoms. Also, the hemodynamic adverse events limit the use of current antianginal agents.

Ranolazine is the first agent to be approved for angina after almost a decade. Studies with ranolazine have established its efficacy both as a monotherapy & in combination with other antianginal agents. Ranolazine reduces anginal symptoms and improves the quality of life without any effect on hemodynamic parameters. It is well tolerated with its safety documented up to 3 years. Interestingly, it also exhibits antiarrhythmic properties. Recently, ranolazine has been approved as a first-line agent for management of angina by US FDA in November 2008. Taking the above into consideration Cipla has recently launched ranolazine under the brand name CORVELA .

It is recommended to initiate with 1 tablet of CORVELA (ranolazine extended release 500 mg) twice daily and increase it to maximum of 2 tablets of CORVELA twice daily, based on clinical symptoms. The maximum dose of CORVELA should be limited to 500 mg twice daily in patients on diltiazem, verapamil, and other moderate CYP3A inhibitors (eg. erythromycin, fluconazole). The dose should be down-titrated based on clinical response in patients concomitantly treated with P-gp inhibitors, such as cyclosporine.

CORVELA should not be taken with strong inhibitors of CYP3A (eg. ketoconazole, itraconazole, clarithromycin), with inducers of CYP3A (eg. rifampin, rifabutin, refapentin, phenytoin, phenobarbital, cabamazepine) & by patients with clinically significant hepatic impairment.