Procainamide Hydrochloride (Page 2 of 4)

PRECAUTIONS

Blood-Pressure and ECG Monitoring

Blood pressure should be monitored with the patient supine during parenteral, especially intravenous, administration of PA (see DOSAGE AND ADMINISTRATION). There is a possibility that relatively high although transient plasma levels of PA may be attained and cause hypotension before the PA can be distributed from the plasma volume to its full apparent volume of distribution which is approximately 50 times greater. Therefore, caution should be exercised to avoid overly rapid administration of PA. If the blood pressure falls 15 mm Hg or more, PA administration should be temporarily discontinued. Electrocardiographic (ECG) monitoring is advisable as well, both for observation of the progress and response of the arrhythmia under treatment, and for early detection of any tendency to excessive widening of the QRS complex, prolongation of the P-R interval, or any signs of heart block (see OVERDOSAGE). Parenteral therapy with PA should be limited to use in hospitals in which monitoring and intensive supportive care are available, or to emergency situations in which equivalent observation and treatment can be provided.

General

Immediately after initiation of PA therapy, patients should be closely observed for possible hypersensitivity reactions. In conversion of atrial fibrillation to normal sinus rhythm by any means, dislodgement of mural thrombi may lead to embolization, which should be kept in mind.

After achieving and maintaining therapeutic plasma concentrations and satisfactory electrocardiographic and clinical responses, continued frequent periodic monitoring of vital signs and electrocardiograms is advised. If evidence of QRS widening of more than 25 percent or marked prolongation of the Q-T interval occurs, concern for overdosage is appropriate, and interruption of the PA infusion is advisable if a 50 percent increase occurs. Elevated serum creatinine or urea nitrogen, reduced creatinine clearance or history of renal insufficiency, as well as use in older patients (over age 50), provide grounds to anticipate that less than the usual dosage or infusion rate may suffice, since the urinary elimination of PA and NAPA may be reduced, leading to gradual accumulation beyond normally-predicted amounts. If facilities are available for measurement of plasma PA and NAPA, or acetylation capability, individual dose adjustment for optimal therapeutic levels may be easier, but close observation of clinical effectiveness is the most important criterion.

Information for Patients

The patient should be encouraged to disclose any past history of drug sensitivity, especially to procaine or other local anesthetic agents, or aspirin, and to report any history of kidney disease, congestive heart failure, myasthenia gravis, liver disease, or lupus erythematosus.

The patient should be counseled to report any symptoms of arthralgia, myalgia, fever, chills, skin rash, easy bruising, sore throat or sore mouth, infections, dark urine or icterus, wheezing, muscular weakness, chest or abdominal pain, palpitations, nausea, vomiting, anorexia, diarrhea, hallucinations, dizziness, or depression.

Laboratory Tests

Laboratory tests such as complete blood count (CBC), electrocardiogram and serum creatinine or urea nitrogen may be indicated depending on the clinical situation, and periodic rechecking of the CBC and ANA may be helpful in early detection of untoward reactions.

Drug Interactions

If other antiarrhythmic drugs are being used, additive effects on the heart may occur with PA administration, and dosage reduction may be necessary (see WARNINGS).

Anticholinergic drugs administered concurrently with PA may produce additive antivagal effects on A-V nodal conduction, although this is not as well documented for PA as for quinidine.

Patients taking PA who require neuromuscular blocking agents such as succinylcholine may require less than usual doses of the latter, due to PA effects on reducing acetylcholine release.

Drug/Laboratory Test Interactions

Suprapharmacologic concentrations of lidocaine and meprobamate may inhibit fluorescence of PA and NAPA, and propranolol shows a native fluorescence close to the PA/NAPA peak wavelengths, so that tests which depend on fluorescence measurement may be affected.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed.

Teratogenic Effects: Pregnancy Category C

Animal reproduction studies have not been conducted with PA. It also is not known whether PA can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. PA should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Both PA and NAPA are excreted in human milk, absorbed by the nursing infant. Because of the potential for serious adverse reactions in nursing infants, a decision to discontinue nursing or the drug should be made, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

ADVERSE REACTIONS

Cardiovascular System: Hypotension and serious disturbances of cardiorhythm such as ventricular asystole or fibrillation are more common with intravenous administration of PA than with intramuscular administration. Because PA is a peripheral vasodilator in concentrations higher than the usual therapeutic range, transient high plasma levels which may occur especially during intravenous administration may produce temporary but at times severe lowering of blood pressure (see OVERDOSAGE and PRECAUTIONS).

Multisystem: A lupus erythematosus-like syndrome of arthralgia, pleural or abdominal pain, and sometimes arthritis, pleural effusion, pericarditis, fever, chills, myalgia, and possibly related hematologic or skin lesions (see below) is fairly common after prolonged PA administration, perhaps more often in patients who are slow acetylators (See Boxed Warning and PRECAUTIONS). While some series have reported less than 1 in 500, others have reported the syndrome in up to 30 percent of patients on long term oral PA therapy. If discontinuation of PA does not reverse the lupoid symptoms, corticosteroid treatment may be effective.

Hematologic: Neutropenia, thrombocytopenia, or hemolytic anemia may rarely be encountered. Agranulocytosis has occurred after repeated use of PA, and deaths have been reported. (See Boxed Warning, WARNINGS section.)

Skin: Angioneurotic edema, urticaria, pruritus, flushing, and maculopapular rash have also occurred.

Gastrointestinal System: Anorexia, nausea, vomiting, abdominal pain, diarrhea or bitter taste may occur in 3 to 4 percent of patients taking oral procainamide.

Nervous System: Dizziness or giddiness, weakness, mental depression and psychosis with hallucinations have been reported.

Elevated Liver Enzymes: Elevations of transaminase with and without elevations of alkaline phosphatase and bilirubin have been reported. Some patients have had clinical symptoms (e.g., malaise, right upper quadrant pain). Deaths from liver failure have been reported.

OVERDOSAGE

Progressive widening of the QRS complex, prolonged Q-T and P-R intervals, lowering of the R and T waves, as well as increasing A-V block, may be seen with doses which are excessive for a given patient. Increased ventricular extrasystoles, or even ventricular tachycardia or fibrillation may occur. After intravenous administration but seldom after oral therapy, transient high plasma levels of PA may induce hypotension, affecting systolic more than diastolic pressures, especially in hypertensive patients. Such high levels may also produce central nervous depression, tremor, and even respiratory depression.

Plasma levels above 10 mcg/mL are increasingly associated with toxic findings, which are seen occasionally in the 10 to 12 mcg/mL range, more often in the 12 to 15 mcg/mL range, and commonly in patients with plasma levels greater than 15 mcg/mL.

Treatment of overdosage or toxic manifestations includes general supportive measures, close observation, monitoring of vital signs and possibly intravenous pressor agents and mechanical cardiorespiratory support. If available, PA and NAPA plasma levels may be helpful in assessing the potential degree of toxicity and response to therapy. Both PA and NAPA are removed from the circulation by hemodialysis but not peritoneal dialysis. No specific antidote for PA is known.