A review of the gastrointestinal therapeutic system (GITS) formulation and its effectiveness in the delivery of antihypertensive drug treatment (focus on nifedipine GITS)

Abstract

Hypertension treatment guidelines do not discriminate within drug classes and, furthermore, do not consider whether or not all of the formulations of any given drug licensed for once-daily administration can be considered to be therapeutically interchangeable. This article focuses on this issue with respect to nifedipine and the development of the gastrointestinal therapeutic system (GITS) formulation. Nifedipine GITS is regarded as the gold standard once-daily formulation of nifedipine and, as such, it is anticipated that alternative formulations will be therapeutically equivalent to nifedipine GITS. In general, this depends on demonstrating pharmacokinetic bioequivalence. This article is intended to focus attention on generic substitution and, in particular, on aspects of the scientific basis for the substitution of generic products in place of branded products. Such substitution is required for cost-saving or cost-containment reasons and is justified on the basis that the generic (substitute) drug is “therapeutically” equivalent to the branded drug. Unfortunately, there are serious shortcomings in the current methods of assessment insofar as they are typically based on statistical comparisons of average pharmacokinetic parameter values, using arbitrary comparative criteria. This article illustrates the shortcomings of the current approaches to generic substitution and concludes that, in regulatory terms, either more rigorous pharmacokinetic criteria are required or pharmacodynamic indices should be added to reinforce the regulatory criteria. Generic substitution is a balancing act but, at the moment, the cost issue is dominant. To restore the balance, equivalent efficacy must be confirmed. At present, therefore, in the absence of such regulatory rigor, the obvious course is to prefer the branded product, the therapeutic efficacy of which (including outcome benefits) has been established.

Nifedipine GITS/Candesartan Combination Therapy Lowers Blood Pressure Across Different Baseline Systolic and Diastolic Blood Pressure Categories: DISTINCT Study Subanalyses

“…Nifedipine and candesartan cilexetil are both effective monotherapies for lowering BP 16, 17, 18, 19. The nifedipine GITS formulation offers, in addition, the advantage of controlled drug release, making it suitable for once‐daily administration, and an observational study suggests that candesartan reduces the risk of cardiovascular disease and heart failure in comparison with another angiotensin receptor blocker (ARB), losartan 16, 18.…”

“…[16][17][18][19] The nifedipine GITS formulation offers, in addition, the advantage of controlled drug release, making it suitable for once-daily administration, and an observational study suggests that candesartan reduces the risk of cardiovascular disease and heart failure in comparison with another angiotensin receptor blocker (ARB), losartan. 16,18 A placebo arm was included in DIS-TINCT in accordance with the International Conference on Harmonisation guideline for evaluation of fixed-dose combination products for the treatment of hypertension and similar to other multifactorial trials of combination antihypertensive therapies. [20][21][22][23] DIS-TINCT demonstrated that initial combination therapy with nifedipine GITS/candesartan cilexetil was more effective in lowering BP and meeting target BP goals (SBP <140 and DBP <90 mm Hg) vs respective monotherapies at the same doses in participants with hypertension.…”

Undigested Pills in Stool Mimicking Parasitic Infection

“…Nifedipine is a calcium channel blocker given for treatment of hypertension and chronic angina, with frequent dosing in the past [ 3 ]. An extended release formulation of nifedipine was developed to achieve once-daily dosing using the gastrointestinal therapeutic system (GITS) [ 4 ].…”

COMPARATIVE IN VITRO EVALUATION OF DIFFERENT BRANDS OF NIFEDIPINE 20mg RETARD TABLET PRODUCTS MARKETED IN ADDIS ABABA, ETHIOPIA

“…The primary goal of antihypertensive therapy is to control blood pressure and reduce the long-term risk of cardiovascular morbidity and mortality. Different classes of medication are available for the management of hypertension 4,5,6 . Nifedipine [Dimethyl-2,6-methyl-4-( 2-nitrophenyl)-1, 4-dihydropyridine-3, 5-dicarboxylate] (Fig 1) is a calcium channel blocking agent which is commonly employed in the management of systemic hypertension and angina pectoris 7 .…”

“…°C. Aliquot samples of 10 ml were withdrawn at pre scheduled intervals(1,3,4,6, and 12 h) and replaced with an equal volume of fresh dissolution medium which was kept at 37±0.5 °C to maintain sink condition. Each filtered sample was analyzed for drug content at  max of 329 nm using a UV/Visible Spectrophotometer.…”