NIFEDIPINE

'Nifedipine' (brand name 'Adalat', 'Nifedical', and 'Procardia') is a dihydropyridine calcium channel blocker. Its main uses are in angina pectoris (especially Prinzmetal's angina) and hypertension, although a large number of other uses have recently been found for this agent, such as Raynaud's phenomenon, premature labor, and painful spasms of the esophagus in cancer and tetanus patients. It is also commonly used for the small subset of pulmonary hypertension patients whose symptoms respond to calcium channel blockers.

Contents

Dosing

Uses

Approved uses

Off-label uses

History

References

External link

Dosing

Nifedipine rapidly lowers the blood pressure, and patients are commonly warned they may feel dizzy or faint after taking the first few doses. Tachycardia (fast heart rate) may occur as a reaction. These problems are much less frequent in the sustained-release preparations of nifedipine (such as Adalat OROS). A more novel release system is GITS (Gastro-Intestinal Therapeutic System), which - according to Bayer - provides 24-hour continuous release through an osmotic push system. Recent trials with GITS include INSIGHT (for blood pressure)^[1] and ACTION (for angina).^[2]
Extended release formulations of nifedipine should be taken on an empty stomach, and patients are warned not to consume anything containing grapefruit or grapefruit juice, as they raise blood nifedipine levels. There are several possible mechanisms, including the lowering of CYP3A4 activity.^[3]

Uses

Approved uses

The approved uses for nifedipine are the long-term treatment of hypertension (high blood pressure) and angina pectoris. In hypertension, recent clinical guidelines generally favour diuretics and ACE inhibitors, although calcium channel antagonists are still favoured as primary treatment for older black patients.^[4]
Sublingual nifedipine has previously been used in hypertensive emergencies. This was found to be dangerous, and has been abandoned.^[5][6]

Off-label uses

Nifedipine has been used frequently as a tocolytic (agent that delays premature labor). A Cochrane review has concluded that it is comparable with magnesium sulfate and beta-agonists (such as ritodrine) with fewer side-effects.^[7] Its role ''vis à vis'' atosiban is not established.
Raynaud's phenomenon is often treated with nifedipine. A 2005 meta-analysis showed modest benefits (33% decrease in attack severity, 2.8-5 reduction in absolute number of attacks per week); it does conclude that most included studies used low doses of nifedipine.^[8]
Topical nifedipine has been shown to be as effective as topical nitrates for anal fissures.^[9]

History

Nifedipine (initially BAY a1040) was developed by the German pharmaceutical company Bayer, with most initial studies being performed in the early 1970s.^[10]
The use of nifedipine and related calcium channel antagonists was reduced much in response to 1995 trials that mortality was increased in patients with coronary artery disease who took nifedipine.^[11] This study was a meta-analysis, and demonstrated harm mainly in short-acting forms of nifedipine (that could cause large fluctations in blood pressure) and at high doses of 80 mg a day and more.^[12]

References

1. Morbidity and mortality in patients randomised 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), Brown MJ, Palmer CR, Castaigne A, ''et al'', , , Lancet, 2000
2. Safety of nifedipine GITS in stable angina: the ACTION trial, Poole-Wilson PA, Kirwan BA, Vokó Z, de Brouwer S, van Dalen FJ, Lubsen J, , , Cardiovas Drugs Ther, 2006
3. Grapefruit juice-nifedipine interaction: possible involvement of several mechanisms, Odou P, Ferrari N, Barthélémy C, ''et al'', , , Journal Clinical Pharm Ther, 2005
4. ''Hypertension: management of hypertension in adults in primary care''. Clinical guideline CG34. National Institute for Health and Clinical Excellence (NICE), June 2006. Fulltext index. ISBN 1-86016-285-1.
5. Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudoemergencies?, Grossman E, Messerli FH, Grodzicki T, Kowey P, , , JAMA, 1996
6. Clinical review: the management of hypertensive crises, Varon J, Marik PE, , , Critical care (London, England), 2003
7. Calcium channel blockers for inhibiting preterm labour, King JF, Flenady VJ, Papatsonis DN, Dekker GA, Carbonne B, , , Cochrane database of systematic reviews (Online), 2003
8. Calcium channel blockers for primary Raynaud's phenomenon: a meta-analysis, Thompson AE, Pope JE, , , Rheumatology (Oxford, England), 2005
9. Topical nifedipine vs. topical glyceryl trinitrate for treatment of chronic anal fissure, Ezri T, Susmallian S, , , Dis. Colon Rectum, 2003
10. [Pharmacology of 4-(2'-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester (Nifedipine, BAY a 1040)], Vater W, Kroneberg G, Hoffmeister F, ''et al'', , , Arzneimittel-Forschung, 1972
11. Nifedipine. Dose-related increase in mortality in patients with coronary heart disease, Furberg CD, Psaty BM, Meyer JV, , , Circulation, 1995
12. Nifedipine and mortality. Grave defects in the dossier, Opie LH, Messerli FH, , , Circulation, 1995

External link

★ Official site (Bayer)

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