NICARDIPINE HYDROCHLORIDE INJECTION – A SPECIALTY DRUG - Taj Pharmaceuticals Limited by Taj Pharma

NICARDIPINE HYDROCHLORIDE INJECTION – A SPECIALTY DRUG Author: Sangeeta R. Mergu (M.Pharm.)

 TAJ PHARMA is one of the leading generic pharmaceutical company in India, always ready to meet the challenges of the dynamic global pharmaceutical industry with its numerous and wide-ranging issues – from complex research, development and regulatory conditions to rapidly changing consumer demands. Taj Pharmaceuticals Ltd India | Taj Pharma | Taj Pharmaceuticals Mumbai, Company Overview of Taj Pharmaceuticals Limited |Taj Pharmaceuticals Limited Taj Pharmaceutical an Industrial conglomerate, having diversified interest in Pharmaceuticals and healthcare, Chemicals, API and Agro commodities mainly offers unique opportunities for all its associates to grow in capacity as one of a significant part in curing lives worldwide and building a disease-free nation. Taj Pharma is having more than 600+ brands in different divisions and multiple subsidiaries to meet up most of the requirements of buyers in our industry along with a very efficient staff management capacity.

Index of Contents  About Taj Pharma  Hypertension  Nicardipine Hydrochloride  Why Nicardipine a Specialty Drug?  Nicardipine Finished Products (Export)  Drug indications  Mechanism of Action  Pharmacokinetics  Alternative Drugs  Taj Pharma as Generics Manufacturer  Conclusion and Future Scope  References Taj Pharmaceuticals Ltd India | Taj Pharma | Taj Pharmaceuticals Mumbai, Company Overview of Taj Pharmaceuticals Limited |Taj Pharmaceuticals Limited Taj Pharmaceutical an Industrial conglomerate, having diversified interest in Pharmaceuticals and healthcare, Chemicals, API and Agro commodities mainly offers unique opportunities for all its associates to grow in capacity as one of a significant part in curing lives worldwide and building a disease-free nation. Taj Pharma is having more than 600+ brands in different divisions and multiple subsidiaries to meet up most of the requirements of buyers in our industry along with a very efficient staff management capacity.

About Taj Pharma  Today, we market more than 100+ branded and 500+ generics compositions to consumers in more than 28 countries and territories across the globe (1).  Therapeutic categories of our products offers an extensive range of dosage forms and delivery systems including oral solids, controlled-release, steriles, injectables, topicals, liquids, transdermals, semi-solids and high-potency products (1).  Our Generics portfolio offers over 600+ products in the major therapeutic areas of gastro-intestinal, cardiovascular, pain management, oncology, antiinfectives, paediatrics and dermatology (1).  Brands like Alzocum®, Benacof, Wallbrurate®, Coversec®, Cadrol®, Humogen®, Merokem®etc. enjoy leadership positions in several key markets, including India, Russia & other CIS countries (1).

Taj Pharmaceuticals Ltd India | Taj Pharma | Taj Pharmaceuticals Mumbai, Company Overview of Taj Pharmaceuticals Limited |Taj Pharmaceuticals Limited Taj Pharmaceutical an Industrial conglomerate, having diversified interest in Pharmaceuticals and healthcare, Chemicals, API and Agro commodities mainly offers unique opportunities for all its associates to grow in capacity as one of a significant part in curing lives worldwide and building a disease-free nation. Taj Pharma is having more than 600+ brands in different divisions and multiple subsidiaries to meet up most of the requirements of buyers in our industry along with a very efficient staff management capacity.

Hypertension  High blood pressure is a common condition but if not treated, it can cause damage to the heart, brain, blood vessels, kidneys leading to heart disease, stroke, heart failure, heart attack and many other problems (2).  Nicardipine is used to treat high blood pressure (hypertension) as well as angina pectoris (chest pain) (2).  Being a calcium channel blocker, it lowers the blood pressure and relaxes the blood vessels so that the heart does not need to pump hard, thereby controlling chest pain as it increases the blood and oxygen supply to the heart (2).

Nicardipine Hydrochloride  Nicardipine Hydrochloride is the hydrochloride salt form of nicardipine, a synthetic derivative of nitrophenyl-pyridine and potent calcium-channel blocker (3).  Nicardipine (Nifedipine Family) blocks calcium ions from certain cell walls and inhibits contraction of coronary and peripheral arteries, resulting in lower oxygen requirements for heart muscle and decreased arterial contraction and spasm (3).  It is used clinically as a cerebral and coronary vasodilator (3).

Why Nicardipine A Specialty Drug? Intravenous Nicardipine is a specialty drug for the following reasons:  Nicardipine has a selective arterial vasodilator mode of action (6, 7, 9).

 It is suitable for emergencies because it effectively lowers the BP with minimal adverse effects in severe blood pressure elevation by achieving rapid dose-related increases in plasma concentrations (6, 7, 9).  It has unique pharmacological effects wherein the drug selectively reduces systemic and coronary resistance thereby increasing coronary blood flow (6, 7, 9).  It is also used for paediatric hypertension (6, 7, 9). Taj Pharmaceuticals Ltd India | Taj Pharma | Taj Pharmaceuticals Mumbai, Company Overview of Taj Pharmaceuticals Limited |Taj Pharmaceuticals Limited Taj Pharmaceutical an Industrial conglomerate, having diversified interest in Pharmaceuticals and healthcare, Chemicals, API and Agro commodities mainly offers unique opportunities for all its associates to grow in capacity as one of a significant part in curing lives worldwide and building a disease-free nation. Taj Pharma is having more than 600+ brands in different divisions and multiple subsidiaries to meet up most of the requirements of buyers in our industry along with a very efficient staff management capacity.

Nicardipine Finished Products (Export) Sr. No.

Product Name

Strength

Brand Name

Manufacturer

Nicardipine Hydrochloride Capsules

20 mg/30 mg

MYLAN

Nicardipine Hydrochloride Sustained Release Capsules

30 mg/45 mg/ 60 mg

CARDENE SR

EKR THERAPEUTICS

Nicardipine Hydrochloride Injection

25 mg/10 ml (2.5 mg/ml)

SANDOZ

Nicardipine Hydrochloride Injection

40 mg/200 ml (0.2 mg/ml)

CARDENE I.V.

BAXTER HEALTHCARE

Drug Indication Intravenous Nicardipine is indicated for the treatment of acute life-threatening hypertension, particularly in the event of:  Malignant arterial hypertension/Hypertensive encephalopathy  Aortic dissection, when short-acting beta blocker therapy is not suitable, or in combination with a beta-blocker when beta-blockade alone is not effective  Severe pre-eclampsia, when other intravenous antihypertensive agents are not recommended or are contraindicated  Nicardipine is also indicated for the treatment of postoperative hypertension (3).

Mechanism of Action ď ąNicardipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum (5). ď ąThe decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload (5).

Pharmacokinetics  Absorption: • Nicardipine is completely absorbed but it is subjected to saturable first pass metabolism and the systemic bioavailablity is 35% following a 30 mg oral dose at steady state (3, 4). • Following infusion of Cardene I.V., nicardipine plasma concentrations rapidly increase in dose-related manner and after first few hours reach steady state at 24 – 48 hours, and later on decline tri-exponentially (3, 4).

Continued…  Distribution: • Total plasma clearance (Cl) is 0.4 L/Hr*kg (following infusion). • The apparent volume of distribution is 8.3 L/kg (3).

 Metabolism: • Nicardipine HCl is extensively metabolised by the liver (3, 4).  Elimination: • Urine (oral: 60% as metabolites; IV: 49% as metabolites; <1% as unchanged drug); feces (oral: 35%; IV: 43%).

Alternative Drugs  Clivedipine: • Ultrashort-acting, I.V. administered, dihydropyridine calcium channel blocker which works as an arterial selective vasodilator. • Like nicardipine, it could be used if nitroglycerin does not control the blood pressure (8, 9).

Taj Pharma as Generics Manufacturer • As a leading generics manufacturer, Taj Pharma has manufactured various formulations in the dosage form of parenterals or injections which include various therapeutic classes of cardiovascular (CVS) drugs. • These formulations are in a lead in export markets and the examples include injections of various drugs like DOBUTAMINE, LABETALOL, DOPAMINE, ISOXSUPRINE etc. • Nicardipine HCl being a specialty drug of the CVS category, production of this drug in the form of injection is the target in near future.

Conclusion and Future Scope • Nicardipine appears to be better tolerated as it produces slower and more prolonged decrease in blood pressure than other drugs like Nifedipine (6, 7, 8, 9). • Although nicardipine is not the primary choice of drug, it is very useful when no other CVS drugs are effective (6, 7, 8, 9). • Compared to nifedipine, oral nicardipine is safer as effective a drug for initial treatment of urgent hypertension (6, 7, 8, 9). • There is a huge scope of research and advancement in nicardipine as a CVS drug to develop it as a primary choice of drug by modulating it drawbacks.

References 1. 2. 3. 4. 5. 6.

Taj Pharmaceuticals Ltd https://tajpharma.com. Medline Plus Drug Information. PubChem. Drugs.com. DrugBank. Ehud Grossman, Franz H. Messerli, in Comprehensive Hypertension, 2007. 7. Liem P. Nguyen MD, Neal S. Gerstein MD, FASE, in Essentials of Cardiac Anesthesia for Noncardiac Surgery, 2019. 8. Cardiac Intensive Care (Second Edition), 2010. 9. Science Direct.