Potential drug-drug interaction between interferon alfa-2b and gemfibrozil in a patient with malignant melanoma.
BACKGROUND
In the United States, patients with high-risk stage II or III melanoma are often treated with adjuvant interferon (IFN) therapy for 1 year after surgery. Adverse events associated with IFN alfa-2b use are primarily constitutional symptoms. However, hypertriglyceridemia requiring treatment has been reported.


OBJECTIVE
The aim of this report was to describe a potential drug-drug interaction between IFN alfa-2b and gemfibrozil in a patient with malignant melanoma. The possible mechanism of this potential interaction was examined.


METHODS
This report presents the case of a 43-year-old male patient weighing 101 kg with newly diagnosed stage III melanoma of the left arm, with metastasis to the supraclavicular node. The patient presented to the University of California Irvine Medical Center, Orange, California with severe gastrointestinal (GI) symptoms and elevated hepatic enzyme concentrations at week 48 of 104 of adjuvant treatment of malignant melanoma (IFN alfa 11 MU SC TIW in combination with the investigational melanoma vaccine melanoma theraccine 1.25 mL [I mL lysate + 0.25 mL vaccine adjuvant] given SC at weeks 1, 2, 3, 4, 8, 16, 24, 32, 40, and 48 and then every 8 weeks until week 104), and IFN-induced hypertriglyceridemia (gemfibrozil 600 mg PO BID). The patient had no history of cardiovascular or GI disease and was not receiving any concomitant medication. The possible mechanism of this potential IFN alfa-gemfibrozil interaction as related to the cytochrome P450 (CYP) enzyme system was assessed.


RESULTS
In this case of a possible drug-drug interaction between IFN alfa 11 MU TIW and gemfibrozil 600 mg BID in a patient undergoing treatment for IFN-induced hypertriglyceridemia, the Naranjo Adverse Drug Reactions (ADR) Probability Scale score was 7 (ie, ADR possibly related to treatment).


CONCLUSIONS
Both IFN and gemfibrozil inhibit the activity of the hepatic enzymes CYP1A2 and CYP2C19. A possible drug-drug interaction between IFN alfa 11 MU TIW and gemfibrozil 600 mg BID was reported in a patient undergoing treatment for IFN-induced hypertriglyceridemia.
Wong
Siu-Fun
SF
Western University College of Pharmacy, Pomona, California 91766-1854, USA. siuwong@westernu.edu
Jakowatz
James G
JG
Taheri
Reza
R
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D004347:Drug Interactions; D015248:Gemfibrozil / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D015228:Hypertriglyceridemia / Q000139:chemically induced / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D000960:Hypolipidemic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015248:Gemfibrozil