Ceftriaxone/lidocaine Disease Interactions

Antiarrhythmic agents can induce severe hypotension (particularly with IV administration) or induce or worsen congestive heart failure (CHF). Patients with primary cardiomyopathy or inadequately compensated CHF are at increased risk. Antiarrhythmic agents should be administered cautiously and dosage and/or frequency of administration modified in patients with hypotension or adequately compensated CHF. Alternative therapy should be considered unless these conditions are secondary to cardiac arrhythmia.

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

Hyperbilirubinemic neonates, especially premature, should not be treated with ceftriaxone for injection. Studies have shown that ceftriaxone can displace bilirubin from its binding to serum albumin, leading to possible risk of bilirubin encephalopathy in these patients.

Lidocaine is rapidly and extensively metabolized by the liver. Less than 10% is eliminated unchanged in the urine. Several inactive and two active forms (MEGX and GX) have been identified. MEGX and GX exhibit antiarrhythmic and convulsant properties. GX accumulates during prolonged intravenous lidocaine infusion. The pharmacokinetic disposition of lidocaine is altered by changes in hepatic function, including hepatic blood flow. Therapy with lidocaine should be administered cautiously and dosing modifications for repeated or loading and maintenance doses may be necessary. Clinical monitoring of cardiac (continuous ECG) is required and serum metabolite concentrations and monitoring hepatic function are recommended.

Lidocaine is primarily eliminated by the kidney. Less than 10% is eliminated unchanged in the urine. Two active metabolites (MEGX and GX) have been identified that exhibit antiarrhythmic and convulsant properties. GX accumulates during prolonged intravenous lidocaine infusion. Serum concentrations of lidocaine and the active metabolites are increased and the half-life prolonged in patients with renal impairment. Therapy with lidocaine should be administered cautiously and dosing modified for repeated or maintenance doses in patients with compromised renal function. Clinical monitoring of cardiac function (continual ECG) is required and serum metabolite concentrations and monitoring renal function are recommended.

Seizures have occurred during lidocaine therapy and have been associated with the rapid administration of a large intravenous doses or accumulation of active metabolites with maintenance therapy. Therapy with lidocaine should be administered cautiously to patients with or predisposed to seizure disorders. Clinical monitoring of cardiac (continuous ECG) is required, and serum metabolite concentrations are recommended.

The use of lidocaine is contraindicated in patients with Stokes-Adam syndrome, Wolff-Parkinson White syndrome, or second- or third-degree AV block in the absence of a functional artificial pacemaker, or congenital QT prolongation.

Electrolyte imbalance can alter the therapeutic effectiveness of antiarrhythmic agents. Hypokalemia and hypomagnesemia can reduce the effectiveness of antiarrhythmic agents. In some cases, these disorders can exaggerate the degree of QTc prolongation and increase the potential for torsade de pointes. Hyperkalemia can potentiate the toxic effects of antiarrhythmic agents. Electrolyte imbalance should be corrected prior to initiating antiarrhythmic therapy. Clinical monitoring of cardiac function and electrolyte concentrations is recommended.

Ceftriaxone can precipitate in the gallbladder. Sonographic abnormalities and symptoms of gallbladder disease have been reported. Therapy with ceftriaxone should be administered cautiously in patients with preexisting disease of the gallbladder, biliary tract, or liver. Serial abdominal ultrasonography may be appropriate during therapy. The drug should be discontinued in patients who develop signs and symptoms suggestive of gallbladder disease while being treated with ceftriaxone.

Cases of pancreatitis, possibly secondary to biliary obstruction, have been reported rarely in patients treated with ceftriaxone. Most patients presented with risk factors for biliary stasis and biliary sludge (preceding major therapy, severe illness, total parenteral nutrition). A cofactor role of ceftriaxone-related biliary precipitation cannot be ruled out.

Alterations in prothrombin times have rarely occurred in patients treated with ceftriaxone. Patients with impaired vitamin K synthesis or low vitamin K stores, such a patients with chronic hepatic disease and malnutrition, require monitoring of prothrombin time during treatment. Vitamin K administration (10 mg per week) might be needed if prothrombin time is prolonged before or during therapy.

Ceftriaxone is eliminated by both renal and hepatobiliary excretion. At usual dosages (i.e. 1 to 2 g/day), adjustments are generally not necessary in either renal or hepatobiliary impairment. However, serum drug concentrations should be monitored periodically, and the dosage decreased accordingly if drug accumulation occurs. In patients with both hepatic and severe renal impairment, ceftriaxone dosage should not exceed 2 grams per day without close monitoring of serum concentrations.

Cases of hepatitis have been reported with the use of certain cephalosporins. Transient rise in AST, ALT, and alkaline phosphatase levels have also been observed. Caution and monitoring are recommended when these agents are prescribed to patients with hepatic disorders.

Cephalosporins have been implicated in triggering seizures. Nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported with cephalosporins particularly in patients with a history of epilepsy and/or when recommended dosages of cephalosporins were exceeded due to renal dysfunction. Dosage should be adjusted based on the degree of renal function. Anticonvulsant therapy should be continued in patients with known seizure disorders. If CNS adverse reactions including seizures occur, patients should undergo a neurological evaluation to determine whether treatment should be discontinued.