Nicardia® XL (Nifedipine Extended Release): Technologically Advanced GITS Formulation Ensures Robust Efficacy and Assured Safety
Abstract
Nifedipine is a classical dihydropyridine calcium channel blocker (CCB) indicated for the management of hypertension, vasospastic angina and chronic stable angina. Prestigious regulatory bodies like USFDA, EMA, CDSCO and TGA have approved long-acting Nifedipine for the management of hypertension and angina. Nifedipine was 1st introduced in United States as Adalat® (Bayer) in 1981 and in India as Nicardia® (J. B. Chemicals & Pharmaceuticals) in 1985.
Conventional Nifedipine shows the rapid onset and short duration of action which results in prompt and marked hypotensive effect but exhibits reflex SNS activation leading to flushing, tachycardia, worsening myocardial ischemia, and cerebrovascular ischemia. Nifedipine gastrointestinal therapeutic system (GITS) formulation addresses many of the concerns surrounding the older formulations of Nifedipine. Nifedipine GITS is a gold standard once-daily formulation of Nifedipine which allows relatively constant plasma drug concentrations over 24 hours. Nifedipine GITS provides a controlled release and gradual onset of action of Nifedipine, avoiding the reflex SNS activation resulting in improved tolerability and compliance.
Clinical studies suggest that long-acting formulations of Nifedipine have slightly greater antihypertensive actions than Amlodipine. Nifedipine was also found to be more efficient than other CCBs like Amlodipine, Nicardipine, and Isradipine in resistant hypertensive patients. The addition of Nifedipine GITS to the conventional treatment of angina pectoris is safe and reduces the need for coronary angiography and interventions.
Several landmark trials have demonstrated that long-acting Nifedipine improves endothelial function and arterial stiffness and reduces albuminuria, LV hypertrophy, atherosclerotic plaques and cardiovascular and cerebrovascular complications.
This comprehensive review focuses on the superiority of the Nifedipine GITS formulation over the conventional Nifedipine and elaborates on the role of long-acting Nifedipine as a CCB of choice for the management of hypertension, resistant hypertension, angina pectoris and coronary artery disease.
Keywords – Calcium Channel Blockers, Nifedipine, Long-Acting Nifedipine, Nifedipine GITS, Nifedipine Extended Release, Nicardia XL.
Keywords:
Calcium Channel Blockers, Nifedipine, Long-Acting Nifedipine, Nifedipine GITS, Nifedipine Extended Release, Nicardia XLDOI
https://doi.org/10.22270/jddt.v12i4-S.5483References
Hypertension, Standard treatment guidelines, Ministry of health & family welfare government of India;
https://nhm.gov.in/images/pdf/guidelines/nrhm-guidelines/stg/Hypertension_full.pdf (Accessed on 29th June 2022)
Sivasubramanian Ramakrishnan, Geevar Zachariah, Kartik Gupta et al. Prevalence of hypertension among Indian adults: Results from the great India blood pressure survey. Indian Heart Journal 2019; 71(4):309-313
Word Health Organization. https://www.who.int/news/item/25-08-2021-more-than-700-million-people-with-untreated-hypertension (Accessed on 29th June 2022)
Thomas Unger, Claudio Borghi , Fadi Charchar et al. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. J Hypertens 2020 Jun; 38(6):982-1004
John M Flack, Bemi Adekola. Blood pressure and the new ACC/AHA hypertension guidelines. Trends Cardiovasc Med 2020 Apr; 30(3):160-164.
Tafadzwa Priscilla Goverwa, Nyasha Masuka, Mufuta Tshimanga et al. Uncontrolled hypertension among hypertensive patients on treatment in Lupane District, Zimbabwe, 2012. BMC Res Notes. 2014; 7:703. doi: 10.1186/1756-0500-7-703
Aberhe W, MariyeT, Bahrey D et al. Prevalence and factors associated with uncontrolled hypertension among adult hypertensive patients on follow-up at Northern Ethiopia, 2019: cross-sectional study. Pan Afr Med J. 2020; 36: 187. doi: 10.11604/pamj.2020.36.187.23312
John Wilkins; William M. Schultz. The Evaluation and Treatment of Drug-Resistant Hypertension. American College of Cardiology; https://www.acc.org/latest-in-cardiology/articles/2019/07/23/08/42/the-evaluation-and-treatment-of-drug-resistant-hypertension (Accessed on 29th June 2022).
Stacie L. Daugherty, J. David Powers, David J. Magid, Incidence and Prognosis of Resistant Hypertension in Hypertensive Patients. Circulation. 2012 Apr 3; 125(13):1635–1642.
Akram Al-Makki , Donald DiPette, Paul K. Whelton et al. Hypertension Pharmacological Treatment in Adults: A World Health Organization Guideline Executive Summary. Hypertension. 2022; 79:293–301
Peter A Meredith, Henry L Elliott. A review of the gastrointestinal therapeutic system (GITS) formulation and its effectiveness in the delivery of antihypertensive drug treatment (focus on nifedipine GITS). Integrated Blood Pressure Control 2013; 6:79–87
Rita G. McKeever; Richard J. Hamilton. Calcium Channel Blockers. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK482473/ (Accessed on 29th June 2022).
Morgan E Snider, Donald S Nuzum, and Angie Veverka. Long-acting nifedipine in the management of the hypertensive patient. Vasc Health Risk Manag. 2008 Dec; 4(6):1249–1257.
Imai Y, Abe K, Sasaki S et al. Pharmacokinetics and pharmacodynamics of conventional and slow release forms of nifedipine in essential hypertensive patients. The Tohoku Journal of Experimental Medicine 1986; 148(4): 421–438.
Meredith PA, Elliott HL. A review of the gastrointestinal therapeutic system (GITS) formulation and its effectiveness in the delivery of antihypertensive drug treatment (focus on nifedipine GITS). Integr Blood Press Control. 2013; 6:79-87.
Grundy JS, Foster RT. The nifedipine gastrointestinal therapeutic system (GITS). Evaluation of pharmaceutical, pharmacokinetic and pharmacological properties. Clin Pharmacokinet. 1996; 30(1):28-51.
Chung M, Reitberg DP. Gaffney M. et al. Clinical pharmacokinetics of nifedipine gastro intestinal therapeutic system. A controlled-release formulation of nifedipine. Am J Med 1987; 83 Suppl. 6B:10-4
Snider ME, Nuzum DS, Veverka A. Long-acting nifedipine in the management of the hypertensive patient. Vasc Health Risk Manag. 2008; 4(6):1249-1257.
Robert M. Carey, David A. Calhoun, George L. Bakris. Resistant Hypertension: Detection, Evaluation, and Management. A Scientific Statement From the American Heart Association. Hypertension. 2018;72:e53-e90.
Champlain J, Karas M, Nguyen P, et al. Different effects of nifedipine and amlodipine on circulating catecholamine levels in essential hypertensive patients. J Hypertens. 1998; 16:1357–69.
Jidong Zhang, Yan Wang, Haijuan Hu et al. Early intervention of long-acting nifedipine GI TS reduces brachial–ankle pulse wave velocity and improves arterial stiffness in Chinese patients with mild hypertension: a 24-week, single-arm, open-label, prospective study. Drug Design, Development and Therapy 2016; 10:3399–3406.
Byyny RL, Shannon T, Schwartz LA et al. Efficacy and safety of nifedipine coat-core versus amlodipine in patients with mild to moderate essential hypertension: comparison of 24-hour mean ambulatory diastolic blood pressure. J Cardiovasc Pharmacol Ther. 1997; 2:77–84. doi: 10.1177/107424849700200201
Kuga K, Xu DZ, Ohtsuka M et al. Comparison of daily anti-hypertensive effects of amlodipine and nifedipine coat-core using ambulatory blood pressure monitoring: utility of “hypobaric curve” and “hypobaric area.” Clin Exp Hypertens. 2011; 33:231–239. doi: 10.3109/10641963.2011.583968.
Tanaka T, Miura S, Tanaka M. et al. Efficacies of controlling morning blood pressure and protecting the kidneys by treatment with valsartan and nifedipine CR or valsartan and amlodipine (MONICA study). J Clin Med Res. 2013; 5:432–440. doi:10.4021/jocmr1563w
Gavras I, Mulinari R, Gavras H, et a. Antihypertensive effectiveness of the nifedipine gastrointestinal therapeutic system. Am J Med, 1987; 83(suppl 6B):20–3.
Frishman WH, Garofalo JL, Rothschild A, et al. The nifedipine gastrointestinal therapeutic system in the treatment of hypertension. Am J Cardiol, 1989; 64:65F–9F.
George Thomas and Mahboob Rahman. Resistant Hypertension in CKD. CJASN 2021; 16: 467–469.
Kuga K, Xu DZ, Ohtsuka M, et al. Comparison of daily anti-hypertensive effects of amlodipine and nifedipine coat-core using ambulatory blood pressure monitoring: utility of “hypobaric curve” and “hypobaric area.”Clin Exp Hypertens. 2011; 33:231–239.
Bryan Williams, Giuseppe Mancia, Wilko Spiering et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal 2018; 39:3021–3104.
Adebayo JA, Nwafor JI, Lawani LO et al. Efficacy of nifedipine versus hydralazine in the management of severe hypertension in pregnancy: A randomised controlled trial. Niger Postgrad Med J 2020; 27:317-24.
THE ENCORE INVESTIGATORS: Effect of nifedipine and cerivastatin on coronary endothelial function in patients with coronary artery disease. The ENCORE I study. Circulation 2003; 107:422 -428.
Brown MJ, Palmer CR, Castaigne A, et al. Morbidity and mortality in patients randomized to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the international nifedipine GITS study: intervention as a goal in hypertension treatment (INSIGHT). Lancet 2000; 356:366–72.
Mancia G, Omboni S, Parati G. Twenty-four hour ambulatory blood pressure in the International Nifedipine GITS Study Intervention as a Goal in Hypertension Treatment (INSIGHT). J Hypertens 2002; 20:545–53.
Mancia G, Ruilope LM, Palmer CR. Effects of nifedipine GITS and diuretics in isolated systolic hypertension – a subanalysis of the INSIGHT study. Blood Press, 2004; 13:310–5.
LICHTLEN PR, HUGENHOLTZ PG, RAFFLENBEUL W et al. Retardation of angiographic progression of coronary artery disease by nifedipine. Lancet 1990; 335:1109 -1113.
Katherine F. Croom and Keri Wellington. Modified-Release Nifedipine. A Review of the Use of Modified-Release Formulations in the Treatment of Hypertension and Angina Pectoris. Drugs 2006; 66 4):497-528.
Philip A Poole-Wilson , Jacobus Lubsen, Bridget-Anne Kirwan et al. Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial. Lancet 2004; 364(9437):849-57
Devereux Rb, Palmieri V, Sharpe N et al. Effects of once-daily angiotensin-converting enzyme inhibition and calcium channel blockade-based antihypertensive treatment regimens on left ventricular hypertrophy and diastolic filling in hypertension. The prospective randomized enalapril study evaluating regression of ventricular enlargement (PRESERVE) trial. Circulation 2001; 104:1248 -1254.
Houston Mc, Olafsson L, Burger Mc, Lichtenstein Mj: Effects of nifedipine GITS and atenolol monotherapy on serum lipids in mild to moderate hypertension. Clin. Res. 1990; 38:A542.
Kazumi T, Yoshino G, Okutani T et al. Plasma lipoprotein and apolipoprotein concentrations and glycemic control during short-term treatment with nifedipine in hypertensive patients with Type II diabetes mellitus. Curr. Ther. Res. 1989; 46:951 -958.
Sasaki J, Arakawa K: Effect of nifedipine on serum lipids, lipoproteins, and apolipoproteins in patients with essential hypertension. Curr. Ther. Res. 1987; 41:845 -851.
Kwo-Chang Ueng, Ming-Cheng Lin, Kuei-Chuan Chan et al. Nifedipine gastrointestinal therapeutic system: an overview of its antiatherosclerotic effects. Expert Opin Drug Metab Toxicol 2007; 3(5):769-80.
Fogari R, Mugellini A, Zoppi A, et al. Differential effects of lercanidipine and nifedipine GITS on plasma norepinephrine in chronic treatment of hypertension. Am J Hypertens. 2003; 16:596–9.
Toal CB. Formulation-dependent pharmacokinetics - does the dosage form matter for nifedipine? J Cardiovasc Pharmacol. 2004; 44:82–6.
Wenzel RR, Allegranza G, Binggeli C, et al. Differential activation of cardiac and peripheral sympathetic nervous system by nifedipine:role of pharmacokinetics. J Am Coll Cardiol, 1997; 29:1607–14.
Toal Cb, Mahon Wa, Barnes C et al. Nifedipine gastrointestinal therapeutic system (GITS) for hypertensive patients in a primary care setting: results of the extended release adalat Canadian trial (EXACT). The EXACT investigators. Clin. Ther. 1997; 19:924 -935.
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