Nifedipine: Difference between revisions

| pregnancy_AU_comment =  

| class = [[Calcium channel blocker]] ([[dihydropyridine]])

'''Nifedipine''', sold under the brand names '''Adalat''' and '''Procardia''' among others, is a [[calcium channel blocker]] medication used to manage [[angina]], [[hypertension|high blood pressure]], [[Raynaud's phenomenon]], and [[premature labor]]. It is one of the treatments of choice for [[Prinzmetal angina]]. It may be used to treat severe [[high blood pressure in pregnancy]]. Its use in preterm labor may allow more time for [[corticosteroid|steroids]] to improve the baby's lung function and provide time for transfer of the mother to a well qualified medical facility before delivery. It is a calcium channel blocker of the [[Dihydropyridine calcium channel blockers|dihydropyridine]] type. Nifedipine is taken by mouth and comes in fast- and slow-release formulations.

Common side effects include [[lightheadedness]], [[headache]], feeling tired, leg swelling, cough, and shortness of breath. Serious side effects may include [[hypotension|low blood pressure]] and [[heart failure]]. Nifedipine is considered safe in pregnancy and breastfeeding.

Nifedipine was patented in 1967, and approved for use in the United States in 1981. It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]]. It is available as a [[Generic drug|generic medication]].  In 2020, it was the 135th most commonly prescribed medication in the United States, with more than 4{{nbsp}}million prescriptions.

==Medical uses== <!--T:4-->

===High blood pressure=== <!--T:5-->

The approved uses are for the long-term treatment of [[hypertension]] and [[angina pectoris]]. In hypertension, recent clinical guidelines generally favour [[diuretic]]s and [[ACE inhibitor]]s, although calcium channel antagonists, along with [[Thiazide|thiazide diuretics]], are still favoured as primary treatment for patients over 55 and black patients.

Nifedipine given as [[sublingual administration]] has previously been used in [[Hypertensive emergency|hypertensive emergencies]]. It was once frequently prescribed on an as-needed basis to patients taking [[Monoamine oxidase inhibitor|MAOIs]] for real or perceived hypertensive crises. This was found to be dangerous, and has been abandoned. Sublingual administration of nifedipine promotes a hypotensive effect via peripheral vasodilation. It can cause an uncontrollable decrease in blood pressure, [[Tachycardia|reflex tachycardia]], and a ''steal phenomenon'' in certain vascular beds. There have been multiple reports in the medical literature of serious adverse effects with sublingual nifedipine, including [[Brain ischemia|cerebral ischemia/infarction]], [[myocardial infarction]], complete [[heart block]], and death. As a result of this, in 1985 the [[Food and Drug Administration|FDA]] reviewed all data regarding the safety and effectiveness of sublingual nifedipine for the management of hypertensive emergencies, and concluded that the practice should be abandoned because it was neither safe nor effective. An exception to the avoidance of this practice is in the use of nifedipine for the treatment of hypertension associated with [[autonomic dysreflexia]] in [[spinal cord injury]].

===Early labor=== <!--T:7-->

Nifedipine has been used frequently as a [[tocolytic]] (agent that delays premature labor). A [[Cochrane review]] has concluded that it has benefits over placebo or no treatment for prolongation of pregnancy. It also has benefits over [[beta-agonists]] and may also have some benefits over [[atosiban]] and [[magnesium sulfate]], although [[atosiban]] results in fewer maternal adverse effects. No difference was found in the rate of deaths among babies around the time of birth, while data on longer-term outcomes is lacking.

===Other=== <!--T:8-->

Other uses include painful spasms of the [[esophagus]] such as from [[cancer]] or [[tetanus]]. It is also used for the small subset of people with [[pulmonary hypertension]].

==Side effects== <!--T:14-->

Nifedipine rapidly lowers 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.

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 inhibition of [[CYP3A4]]-mediated metabolism.

As calcium channel blocker, nifedipine has a risk of causing [[gingival hyperplasia]]

==Overdose== <!--T:17-->

A number of persons have developed toxicity due to acute overdosage with nifedipine, either accidentally or intentionally, and via either oral or [[parenteral administration]]. The adverse effects include lethargy, bradycardia, marked hypotension and [[unconsciousness|loss of consciousness]]. The drug may be quantified in blood or plasma to confirm a diagnosis of poisoning, or to assist in a medicolegal investigation following death. Analytical methods usually involve gas or liquid [[chromatography]] and specimen concentrations are usually in the 100-1000 μg/L range.

==Mechanism of action== <!--T:18-->

Nifedipine is a [[calcium channel blocker]]. Although nifedipine and other [[dihydropyridines]] are commonly regarded as specific to the [[L-type calcium channel]], they also possess nonspecific activity towards other [[voltage-dependent calcium channels]].

Nifedipine has additionally been found to act as an [[receptor antagonist|antagonist]] of the [[mineralocorticoid receptor]], or as an [[antimineralocorticoid]].

==History== <!--T:20-->

Nifedipine (initially BAY a1040, then Adalat) was developed by the German pharmaceutical company [[Bayer]], with most initial studies being performed in the early 1970s.

The use of nifedipine and related calcium channel antagonists was much reduced in response to 1995 trials that mortality was increased in patients with [[coronary artery disease]] who took nifedipine. This study was a meta-analysis, and demonstrated harm mainly in short-acting forms of nifedipine (that could cause large fluctuations in blood pressure) and at high doses of 80&nbsp;mg a day and more.

Adalat was the first German pharmaceutical to be awarded the prestigious [[Prix Galien]] in 1980. In the same year, [[Ahmed Hegazy (pharmacist)|Ahmed Hegazy]] <!--(1939-2021) -->submitted his invention (in collaboration with Klaus-Dieter Rämsch) of an extended release, solid medicinal preparation of nifedipine to the German Patent Office in Munich, patenting the “use of nifedipine crystals with a specific surface area of 1-4 m2/g for the production of solid medicinal formulations for achieving long-lasting blood levels for the oral treatment of hypertension by administration 1 to 2 times”, an invention that became known as ''Adalat retard'' from Bayer (see letter Dr Schauerte). In that formulation, the active ingredient is released over a period of up to 36 hours. With the increasing incidence of heart disease in that period—heart failure became the first cause of death in West Germany—and the new  formulation, the medication replaced [[Aspirin]] in the 1990s as the biggest single product of Bayer. As Alexander Mey noted, "[d]iese Maßnahmen führten dazu, dass der Umsatz im Jahr 2000 auf 1,7 Mrd. US-$ stieg, obwohl das Präparat bereits ein Vierteljahrhundert am Markt war."<!--"These measures resulted in sales increasing to US$1.7 billion in 2000, even though the preparation had already been on the market for a quarter of a century."--> On 14 October 1991, Hegazy was awarded the Otto Bayer Medal—no relation to the company founder—for his work solubilizing poorly soluble active ingredients such as nifedipine, a prize, that the Bayer Group has been using to honor excellent research since 1984. By 2020, 528 researchers had received the award. A 1995 US lawsuit, in which Hegazy defended his patent, found that Pfizer's Procardia XL product was also based on his European patent No. [https://patentimages.storage.googleapis.com/8c/e7/6b/65e124ccf4f4bd/EP0047899B2.pdf 0047899], United States Patent [https://patentimages.storage.googleapis.com/80/e0/2f/1e0ab56b05b557/US5264446.pdf 5264446].

== Society and culture == <!--T:22-->

In India, nifedipine is manufactured by JB Chemicals, and comes in brands Nicardia Retard (Nifedipine 10&nbsp;mg, 20&nbsp;mg tablets) and Nicardia XL 30/60, which are Nifedipine Extended Release tablets.

In Switzerland, nifedipine is sold only as a generic version of extended release formulation, under the names Nifedipin Mepha and Nifedipin Spirig.

== See also == <!--T:24-->

== External links == <!--T:25-->