Cartia XT (diltiazem)

A 58-year-old man with hypertension, coronary artery disease, and hypercholesterolemia developed acute and generalized extremity weakness and chest pain while receiving diltiazem, lovastatin, nitrates, and enalapril. The patient's muscles were tender to palpation. An ECG was unchanged. With normal liver and thyroid function tests, lovastatin was discontinued, but the patient's creatine phosphokinase (CPK) levels remained elevated (all CPK-MM) and the patient's symptoms persisted. There was no evidence of a connective tissue disease, rhabdomyolysis, or renal failure. The patient refused muscle biopsy. Upon discontinuation of diltiazem, the signs and symptoms of myopathy rapidly resolved, even after lovastatin was readministered. All signs and symptoms recurred upon rechallenge with diltiazem.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have any of these serious side effects: fast or slow heartbeats; feeling light-headed, fainting; fever, sore throat, and headache with a severe blistering, peeling, and red skin rash; feeling short of breath, even with mild exertion; swelling, rapid weight gain; or nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes). Less serious side effects may include: stuffy nose; skin rash or itching; dizziness, headache, tired feeling; nausea; or warmth, itching, redness, or tingly feeling under your skin. This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Hepatic side effects reported in 1% of patients have included mild and transient increases in liver function tests. Rarely, granulomatous hepatitis and hepatorenal failure have been reported. Extremely rarely, acute hepatitis has been reported. A case of jaundice associated with elevated serum transaminases has been reported.

One patient developed both renal and hepatic failure while taking diltiazem. Although the drug was discontinued and renal and hepatic function were improving, the patient developed cardiogenic shock and died. A 61-year-old man with hypertension and angina pectoris presented with fever and a generalized rash associated with hepatomegaly, a mild leukocytosis, thrombocytopenia, and elevated liver function tests. An infectious etiology was not found. After all of the patient's medications were continued except for diltiazem, his signs and symptoms resolved within six days. A macrophage inhibitory factor test and mast cell degranulation test done in the presence of diltiazem were positive.

Metabolic side effects have been reported rarely. These have included insulin resistance and diabetes-like symptoms. A case of attenuated hypoglycemia and symptoms of hypoglycemia has been reported. A case of polyuria, polydipsia, and elevated blood glucose has been reported. A case of frank hyperosmolar nonketotic hyperglycemic coma has been reported. A case of insulinoma has been reported. At least one case of metabolic acidosis and hyperkalemia has been reported.

A 72-year-old man with coronary artery disease and esophagitis developed a urticarial rash and jaundice associated with elevated serum transaminases, metabolic acidosis, and hyperkalemia. The patient died of cardiogenic shock complicated by pulmonary edema. A 46-year-old woman with insulinoma demonstrated suppressed serum insulin levels after diltiazem 44 mg intravenously was administered. The patient was subsequently treated with orally administered diltiazem, with a significant decrease in the frequency of hypoglycemic attacks.

Renal side effects have rarely included acute renal failure.

A 53-year-old man, with hypertension and ischemic heart disease, developed a rash and acute renal failure associated with elevated liver function tests following a single dose of diltiazem. Several case reports have been published describing renal failure, which appear to be related to diltiazem. A 72-year-old man with coronary artery disease and esophagitis developed a urticarial rash and jaundice associated with elevated serum transaminases, metabolic acidosis, and hyperkalemia. The patient died of cardiogenic shock complicated by pulmonary edema.

Dermatological side effects have been reported rarely. These have included exfoliative dermatitis (10%) and toxic epidermal necrolysis (1%). Rarely, acute generalized exanthematous pustular dermatitis, subacute cutaneous, and lupoid lesions have been reported. At least six cases of photodistributed hyperpigmentation have been reported. At least three cases of acute generalized exanthematous pustular dermatitis have been reported.

Cardiovascular side effects have been reported the most frequently. These have included asymptomatic hypotension (4% to 13%), symptomatic hypotension (3% to 13%), flushing (2%), edema (2%), and atrioventricular heart block (1% to 3%). Cardiovascular side effects reported in 1% of patients have included sinoatrial depression, atrioventricular depression, sinoatrial heart block, and bradycardia. Several cases of sinus arrest, atrioventricular dissociation, and junctional bradycardia have been reported. A case of nodal bigeminy progressing to complete heart block has also been reported.

Nodal bigeminy progressing to complete heart block has been reported in one cardiac patient who ingested a large amount of diltiazem in a suicide attempt.

Diltiazem is contraindicated in patients with sick sinus syndrome or in patients with second- or third-degree AV block without a functioning ventricular pacemaker, in patients with cardiogenic shock or hypotension (systolic blood pressure less than 90 mm Hg), in patients with atrial fibrillation or flutter associated with the Wolff-Parkinson-White syndrome or an accessory pathway, in patients with ventricular tachycardia, and in patients with acute myocardial infarction and pulmonary congestion.

Diltiazem prolongs AV node refractory periods without significantly prolonging sinus node recovery time, except in patients with sick sinus syndrome. This effect may rarely result in abnormally slow heart rates (particularly in patients with sick sinus syndrome) or second- or third-degree AV block (13 of 3290 patients or 0.40%). Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. A patient with Prinzmetal's angina developed periods of asystole (2 to 5 seconds) after a single dose of 60 mg of diltiazem.

Mild elevations of transaminases with and without concomitant elevation in alkaline phosphatase and bilirubin have been observed in clinical studies. Such elevations were usually transient and frequently resolved even with continued diltiazem treatment. In rare instances, significant elevations in enzymes such as alkaline phosphatase, LDH, SGOT, SGPT, and other phenomena consistent with acute hepatic injury have been noted. These reactions tended to occur early after therapy initiation (1 to 8 weeks) and have been reversible upon discontinuation of drug therapy. The relationship to diltiazem is uncertain in some cases, but probable in some.

Nervous system side effects reported in 7% of patients have included dizziness and headache. Dysosmia, dysgeusia, and sensory loss have been reported. At least one case of acute Parkinsonism has been reported. At least two cases of hyperactive symptoms or akathisia have been reported. Myoclonus has also been reported.