Applies to nifedipine: compounding powder, oral capsule, oral tablet extended release
Recent data suggest that the use of short-acting nifedipine (the active ingredient contained in Adalat) in moderate to high doses in patients with coronary artery disease (particularly in the elderly) has been associated with an increase in total mortality. In addition, in general, approximately 20% of patients have experienced side effects, mostly due to the vasodilatory properties of the drug (headache, flushing, dizziness). These effects have usually been transient and mild in severity, and have been minimized by dose reduction or addition of a beta-blocker (if indicated).
A 59-year-old man with hypertension (BP of 160/110) developed a severe headache, right-sided paresthesia, and complete bilateral loss of vision 30 minutes after receiving his first dose of nifedipine (the active ingredient contained in Adalat) 20 mg orally. A CT scan confirmed the diagnosis of bilateral occipital lobe infarction resulting in cortical blindness with macular sparing. The authors of this case report believe that nifedipine may have caused a local cerebral vascular steal phenomenon or a global reduction in cerebral blood flow, and have located approximately four similar reports.
Nervous system side effects are the most common and have included headache (7% to 35%), weakness (10% to 12%), dizziness/lightheadedness/giddiness (3% to 27%), and tremor (1% or less to 8%). Paresthesia, insomnia, somnolence, and vertigo (3% or less); sleep disturbances and shakiness (2% or less); ataxia, decreased libido, hypertonia, hypesthesia, and migraine (1% or less); and dystonia, dysosmia, and dysgeusia have been reported. Rare cases of stroke associated with nifedipine-induced hypotension have been reported.
Nifedipine-induced hypotension may result in retinal, coronary, or cerebral ischemia in some patients, resulting in visual field defects, angina, or stroke. A single case report of profound hypotension and death associated with nifedipine (the active ingredient contained in Adalat) in a 17-year-old woman with primary pulmonary hypertension (PPH) has been reported. The patient had extraordinarily high right atrial pressures and depressed cardiac output, indicating caution when one is testing the efficacy of calcium channel blockers in patients with PPH.
A 34-year-old woman experienced torsades de pointes leading to ventricular fibrillation after a 20 mg sublingual dose of nifedipine was administered to treat a hypertensive emergency.
Atrioventricular block is an unusual side effect of nifedipine therapy.
Rare cases of nifedipine-associated noncardiac pulmonary edema in patients with pulmonary hypertension and left ventricular outflow obstruction syndromes, such as aortic stenosis and hypertrophic cardiomyopathy have been reported.
Although relatively minor, the negative inotropic side effect of nifedipine may be important in patients with a history of congestive heart failure.
Cardiovascular side effects can be significant and have included peripheral edema (7% to 29%), hypotension (less than 1% to 5%), palpitations (less than 1% to 7%), myocardial infarction (4%), congestive heart failure (2%), and noncardiogenic edema (0.6% to 8%). Arrhythmia, increased angina, tachycardia, and syncope (1% or less); substernal chest pain, atrial fibrillation, bradycardia, cardiac arrest, extrasystole, phlebitis, postural hypotension, and cutaneous angiectases (less than 1%); erythromelalgia (0.5%); ventricular arrhythmias and conduction disturbances (less than 0.5%); and atrial and ventricular dysrhythmias have been reported. Patients with hypovolemia and/or concomitant antihypertensive therapy are at increased risk of hypotension associated with nifedipine. Some patients with exertional angina pectoris have reported increased chest pain after taking nifedipine. This may, however, reflect progressive disease rather than drug effect. Ventricular fibrillation has rarely been reported.
Gastrointestinal (GI) side effects are common and have included nausea (2% to 11%); heartburn (11%); constipation (3.3% or less); abdominal pain, diarrhea, dry mouth, dyspepsia, and flatulence (3% or less); abdominal cramps (2% or less); eructation, gastroesophageal reflux, gingival hyperplasia, melena, taste perversion, and vomiting (1% or less); and dysphagia, esophagitis, GI disorder, GI hemorrhage, GI irritation, gum disorder, and gum hemorrhage (less than 1%). Rarely, bezoars have been reported in patients taking extended release nifedipine (the active ingredient contained in Adalat) as Procardia XL(R). Gastrointestinal obstruction resulting in hospitalization and surgery (including the need for bezoar removal) has been reported with Procardia XL(R), even in patients with no known gastrointestinal disease. Tablet adherence to the GI wall with ulceration has been reported with Procardia XL(R); some cases required hospitalization and intervention.
Nifedipine-associated hepatitis is dose-dependent, idiosyncratic, and thought to be due to hypersensitivity because it is often associated with fever, rash, eosinophilia, and arthritis. One case of alcoholic-like liver lesions, consisting of steatosis and Mallory bodies, has been associated with the use of nifedipine (the active ingredient contained in Adalat)
Some studies have shown that nifedipine may increase hepatic portal venous hypertension, which may be important in patients with severe liver disease. Frequent monitoring of liver function tests during nifedipine therapy is recommended in patients with underlying liver disease.
Hepatic side effects have included increased GGT (less than 1%); transient elevations of liver function tests and rare cases of hepatitis (approximately 0.5%); allergic hepatitis (less than 0.5%); and jaundice.
Rare cases of immune-complex nephritis and nephrotic syndrome associated with nifedipine (the active ingredient contained in Adalat) therapy have been reported. A case of acute, reversible renal failure attributable to nifedipine administration in a patient with congestive heart failure has been reported.
Renal side effects have included kidney calculus (less than 1%) and new or worsened renal insufficiency (less than 0.5%). Patients who are at higher risk include the elderly and patients with preexisting renal or arteriosclerotic vascular disease. Use of nifedipine has also been associated with improved glomerular filtration rate and effective renal plasma flow in hypertensive patients with moderate renal dysfunction, regardless of its antihypertensive effect.
Hypersensitivity side effects have included allergic reaction (less than 1%), angioedema (mostly oropharyngeal edema with difficulty breathing in a few patients; less than 0.5%), and anaphylactic reaction. Cases of urticarial eruptions and erythema multiforme, often associated with other findings of hypersensitivity, have been reported.
Hematologic side effects have included purpura (1% or less); eosinophilia and lymphadenopathy (less than 1%); and thrombocytopenia, anemia, and leukopenia (less than 0.5%).
Dermatologic side effects have included rash and pruritus (3% or less); dermatitis, urticaria, and sweating (2% or less); alopecia (1% or less); angioedema, petechial rash, and photosensitivity reaction (less than 1%); and exfoliative dermatitis (less than 0.5%). Rare cases of erythromelalgia, pemphigus foliaceus, and pemphigoid nodularis have been reported. Exfoliative or bullous skin reactions (such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), photosensitivity reactions, and acute generalized exanthematous pustulosis have been reported during postmarketing experience.
A single case of pemphigus foliaceus associated with nifedipine, resolving after discontinuation of the drug, and recurring upon rechallenge has been reported. Prior to this case, only drugs with an active sulfhydryl group, such as penicillamine and captopril, were implicated in the development of pemphigus foliaceus.
Psychiatric side effects have included nervousness (2% or less to 7%); mood changes (7%); jitteriness (2% or less); anxiety, depression, and paroniria (1% or less); confusion (less than 1%); paranoid syndrome (less than 0.5%); and agitation and psychosis.
Other side effects have included edema (10% to 30%); flushing/heat sensation (less than 3% to 25%); fatigue (4% to 5.9%); asthenia (less than 1% to 4%); chest pain, leg pain, and pain (3% or less); difficulties in balance, fever, and chills (2% or less); facial edema, hot flashes, malaise, periorbital edema, rigors, and tinnitus (1% or less); and cellulitis, abnormal laboratory test (unspecified), neck pain, and pelvic pain (less than 1%). A single report of falsely elevated laboratory urinary vanillylmandelic acid (VMA) values by spectrophotometry during nifedipine (the active ingredient contained in Adalat) therapy has been reported.
At least one case of acute pulmonary edema during tocolytic therapy with oral nifedipine (the active ingredient contained in Adalat) has been reported. The patient developed pulmonary edema 3 days after starting nifedipine (two doses of 20 mg sublingually 30 minutes apart followed by 40 mg orally every 6 hours). Symptoms included dyspnea, orthopnea, tachypnea, and tachycardia which resolved following discontinuation of nifedipine.
Respiratory side effects have included dyspnea, cough, nasal congestion, sore throat, and wheezing (less than 1% to 6%); epistaxis and rhinitis (3% or less); pulmonary edema (2%); chest congestion (2% or less); and upper respiratory tract infection, respiratory disorder, and sinusitis (1% or less).
Metabolic side effects have included gout and increased weight (1% or less), weight loss (less than 1%), and hyperglycemia.
Musculoskeletal side effects have included muscle cramps (2% or less to 8%); leg cramps and arthralgia (3% or less); inflammation and joint stiffness (2% or less); back pain and myalgia (1% or less); arthritis, joint disorder, and myasthenia (less than 1%), and arthritis with ANA (+) (less than 0.5%).
Genitourinary side effects have included impotence, polyuria, and urinary frequency (3% or less); sexual difficulties (2% or less); breast pain, dysuria, hematuria, and nocturia (1% or less); and urogenital disorder, erectile dysfunction, and gynecomastia (less than 1%).
Ocular side effects have included blurred vision (2% or less); abnormal lacrimation and abnormal vision (1% or less); amblyopia, conjunctivitis, diplopia, eye disorder, and eye hemorrhage (less than 1%); and transient blindness (at the peak of plasma level; less than 0.5%).