Nifedipine

Adalat ®

Nifedipine (brand names Adalat, Nifediac, Nifedical, and Procardia) is a dihydropyridine calcium channel blocker. Its main uses are as an antianginal (especially in Prinzmetal’s angina) and antihypertensive, 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.

Dosing
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 (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, along with thiazide diuretics, are still favoured as primary treatment for over 55’s and black patients.[4]

Sublingual nifedipine has previously been used in hypertensive emergencies. This was found to be dangerous, and has been abandoned. Sublingual nifedipine causes blood-pressure lowering through peripheral vasodilation. It can cause an uncontrollable decrease in blood pressure, 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 cerebral ischemia/infarction, myocardial infarction, complete heart block, and death. As a result of this, the FDA reviewed all data regarding the safety and efficacy of sublingual nifedipine for hypertensive emergencies in 1995, and concluded that the practice should be abandoned because it was neither safe nor efficacious. [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]

Nifedipine is also used in high-altitude medicine to treat high altitude pulmonary edema.[10]

Oral nifedipine has also been found to cause iron loss in the urine of small animals.[11] A NIH NIDDK study[12] is currently seeing if the drug can increase the removal of iron into the urine in humans as well, thus becoming a possible treatment for iron overload.

Overdosage
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 loss of consciousness. The drug may be quantitated in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients or to assist in a medicolegal death investigation. Analytical methods usually involve gas or liquid chromatography and specimen concentrations are usually in the 100-1000 μg/L range.[13][14]

History
Nifedipine (initially BAY a1040) was developed by the German pharmaceutical company Bayer, with most initial studies being performed in the early 1970s.[15]

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.[16] 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.[17]