What are the fever-inducing drugs (FIDs) that can be used under medical supervision?

Fever-Inducing Drugs (FIDs) for Medical Use

Fever-inducing drugs that can be used under medical supervision include amphotericin B, interferon-alpha, and certain bacterial extracts, which should only be administered with careful monitoring for adverse reactions and in specific therapeutic contexts.

Established Fever-Inducing Drugs

Amphotericin B

Amphotericin B is a well-documented fever-inducing medication that is primarily used as an antifungal agent:

• Commonly causes fever accompanied by shaking chills within 15-20 minutes of infusion 1
• Management of fever side effects:
  • Pre-medication with antipyretics (acetaminophen), antihistamines, or antiemetics
  • Meperidine (25-50mg IV) can decrease duration of shaking chills and fever
  • Administration on alternate days may decrease adverse reactions
  • Small doses of adrenal corticosteroids prior to or during infusion can help decrease febrile reactions 1

Interferon-alpha

Interferon-alpha is another medication with known pyrogenic effects:

• Used in treatment of viral hepatitis and certain cancers
• Fever is a common adverse reaction during administration
• Dosing may need adjustment in patients with renal impairment 2
• Careful monitoring of laboratory abnormalities (especially hemoglobin) is required during treatment

Therapeutic Fever Induction

Therapeutic fever induction has historical precedent and some emerging research applications:

• Pathogen Associated Molecular Pattern (PAMP) substances have been used to induce therapeutic fever in cancer patients 3
• A retrospective phase-1 study reported on the safety of fever induction using bacterial extracts and combinations of approved drugs in 131 patients (primarily with cancer)
• Adverse reactions were similar to those expected during a feverish infection and generally mild 3

Drug-Induced Fever as an Adverse Effect

Many medications can cause fever as an adverse effect rather than a therapeutic goal:

• Most commonly results from hypersensitivity reactions
• Typically occurs after 7-10 days of drug administration
• Persists while drug is continued and resolves after discontinuation
• Common culprits include penicillins, cephalosporins, antituberculars, quinidine, procainamide, methyldopa, and phenytoin 4
• Antimicrobial agents are responsible for the majority of drug-induced fever cases 5

Clinical Considerations for Therapeutic Fever Induction

When considering the use of fever-inducing drugs for therapeutic purposes:

1. Patient selection is critical:

   • Avoid in patients with severe cardiovascular disease
   • Use with caution in immunocompromised patients
   • Consider baseline organ function, especially renal function

2. Monitoring requirements:

   • Continuous vital sign monitoring during administration
   • Laboratory monitoring for electrolyte abnormalities
   • Assessment for signs of dehydration

3. Management of adverse effects:

   • Prophylactic antipyretics may be used to manage excessive fever
   • Ensure adequate hydration before, during, and after administration
   • Have emergency medications available for severe reactions

Special Populations

Immunocompromised Patients

• HIV-infected patients may require special consideration when using fever-inducing drugs
• Fluoroquinolones such as ciprofloxacin (500 mg per day) can be considered when prophylaxis is deemed necessary for travelers 6
• For HIV-infected patients with Salmonella gastroenteritis, antimicrobial therapy may be administered to prevent extraintestinal spread 6

Pediatric Patients

• Dosing adjustments required based on age and weight
• Careful monitoring for adverse effects
• Alternative agents may be needed for children under 8 years 6

Pregnant Women

• Many fever-inducing drugs are contraindicated in pregnancy
• Trimethoprim/sulfamethoxazole may be used for certain indications in pregnant women 6

Pitfalls and Caveats

• Fever-inducing drugs can mimic infectious processes, leading to unnecessary diagnostic procedures
• Distinguishing between drug-induced fever and infection can be challenging
• Serum procalcitonin levels and endotoxin activity assay can help discriminate between drug-induced fever and infection 6
• Drug-induced fever may persist for several days after drug discontinuation 6
• Neuroleptic malignant syndrome and serotonin syndrome are serious conditions that can present with drug-induced fever and require immediate intervention 6

Remember that therapeutic fever induction should only be performed under close medical supervision with appropriate monitoring and supportive care measures in place.