DESCRIPTION

Terfenadine (Seldane) is a nonsedating antihistamine (H₁) medication.

FORMS AND USES

• Typical adult dose is 60 mg orally.
• Terfenadine was removed from the United States market in 1997.

TOXIC DOSE

The parent form (terfenadine) is the toxic species; metabolites are less toxic.

PATHOPHYSIOLOGY

Torsade de pointes have been reported when terfenadine was used concomitantly with drugs that interfere with hepatic cytochrome P450 enzyme.

EPIDEMIOLOGY

Torsade de pointes have been reported to occur when terfenadine was taken in an intentional overdose, taken in dosage higher than the recommended dosage, in patients with cirrhosis or a history of alcohol abuse, and during use with a contraindicated medication.

CAUSES

• Toxicity is usually caused by drug interaction.
• Child neglect or abuse should be considered if the patient is less than 1 year of age, suicide attempt if the patient is over 6 years of age.

DRUG AND DISEASE INTERACTIONS

Drug interactions occur with ketoconazole, itraconazole, metronidazole, fluconazole, miconazole, and macrolide antibiotics (e.g., erythromycin), all of which increase terfenadine levels by interfering with terfenadine metabolism.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• DRUG AND DISEASE INTERACTIONS

A meticulous patient history including concomitant medications is important because a drug interaction is the most likely cause of toxicity.

DIFFERENTIAL DIAGNOSIS

Terfenadine-induced toxicity should be considered in the differential diagnosis of syncope, seizures, ventricular tachydysrhythmia, or prolonged QTc on ECG.

SIGNS AND SYMPTOMS

Cardiovascular

Syncope, seizures, ventricular tachydysrhythmia, prolonged QTc on ECG, and torsade de pointes may occur.

Neurologic

Lightheadedness and syncope may occur secondary to cardiac effects.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• Serum electrolytes, complete blood count, BUN, and creatinine to assess causes of syncope
• ECG and cardiac monitoring to detect cardiac effects
• Serum acetaminophen and aspirin levels in overdose setting to detect occult ingestion.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Cardiovascular
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests

Treatment should focus on supportive cardiac care and treatment of ventricular tachydysrhythmias.

DIRECTING PATIENT COURSE

The health-care professional should call the poison control center when:

• Severe or persistent effects develop.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

The patient should be referred to a health-care facility when:

• Suicide or homicide attempt is possible.
• Toxic effects develop.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Patients with syncope or prolonged QTc on the ECG should be admitted to an intensive care setting, with continuous cardiac monitoring until at least 24 hours after the patient has been asymptomatic and the QTc has returned to baseline.

DECONTAMINATION

Out of Hospital

Ipecac-induced emesis should be avoided.

In Hospital

One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.

ANTIDOTES

There is no specific antidote for terfenadine poisoning.

ADJUNCTIVE TREATMENT

• Intravenous magnesium sulfate has been successful in the management of torsade de pointes.
• Isoproterenol, cardioversion, and temporary cardiac pacing may also be necessary.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT

PATIENT MONITORING

Patients should be placed on a cardiac monitor and an ECG obtained.

EXPECTED COURSE AND PROGNOSIS

Complete recovery is anticipated unless sequelae of hypotension intercede.

DISCHARGE CRITERIA/INSTRUCTIONS

Asymptomatic patients with normal ECG results may be discharged following decontamination, 6 hour observation period, and psychiatric evaluation, if needed.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

• Physicians should avoid combining terfenadine with drugs that interfere with terfenadine metabolism [ketoconazole, itraconazole, metronidazole, fluconazole, miconazole, macrolide antibiotics (e.g., erythromycin)], cause torsade de pointes, or prolong QTc (e.g., quinidine, procainamide, disopyramide, sotalol, haloperidol, thioridazine, probucol, pentamidine).
• Terfenadine should be avoided in patients with congenital long QT syndrome.

Poisoning primarily by systemic agents: antiallergic and antiemetic drugs.

See Also: SECTION II, Ventricular dysrhythmia chapter.

RECOMMENDED READING

Safety of terfenadine and astemizole. Med Lett Drugs Ther 1992;34:9-10.

Author: Steven A. Seifert

Reviewer: Richard C. Dart