Drugs Associated with HHV-6 Reactivation:
IN VIVO (DIHS, DRESS, AHS, SJS, and TEN):
| Drug | Associations | References | Notes |
| allopurinol | DIHS, DRESS, SJS | 1-7 | Enzyme inhibitor used for gout; may cause a drop in circulating B cells 8. |
| carbamazepine | AHS, DIHS, DRESS, SJS, TEN | 3, 9-21 | Anticonvulsant and HDAC inhibitor. Associated with transient hypogammaglobulinemia 14, 17. |
| dapsone | AHS, DIHS, DRESS | 3, 22 | Antibiotic and anti-malarial drug. |
| ibuprofen | DIHS, DRESS | 12, 23 | Non-steroidal anti-inflammatory drug; one case was in association with diclofenac 23. |
| lamotrigine | AHS, DIHS, DRESS | 24, 25 | Anticonvulsant. |
| mexiletine | DIHS | 3, 26, 27 | Class 1B anti-arrhythmic. |
| minocycline | DIHS, DRESS | 5, 28, 29 | Broad spectrum tetracycline antibiotic. |
| naproxen | DRESS | 30 | Non-steroidal anti-inflammatory drug that inhibits both COX-1 and COX-2 enzymes. |
| phenytoin | AHS, DIHS | 10, 31-33 | Cross-sensitive with carbamazepine and phenobarbital 18. |
| phenobarbital | AHS, DIHS, DRESS | 3, 10, 28, 31, 32, 34-37 | Barbituate and anticonvulsant known to induce EBV in Raji cells; cross-sensitive with carbamazepine and phenytoin 18. |
| sodium valproate | AHS, DIHS | 38 | Anticonvulsant, HDAC inhibitor and rare cause of DIHS. Three cases have been reported, but in two of them HHV-6 was not tested 39, 40. |
| sulfasalazine | DIHS, DRESS, | 30, 41-43 | Anti-inflammatory that is not an immunosuppressant; used in inflammatory bowel disease and rheumatoid arthritis. |
| trichloroethylene | DIHS | 44, 45 | HDAC inhibitor and industrial solvent previously used as an anesthetic and inhaled obstetrical analgesic. |
| trimethoprim-sulfamethoxazole | DIHS, DRESS | 46, 47 | Sulfonamide antibiotic. |
| vancomycin | DRESS | 48, 49 | In one case teicoplanin was also reactive 49. |
| zonisamide | AHS, DIHS, TEN | 3, 10, 50, 51 | Sulfonamide anticonvulsant. |
IN VITRO:
| Drug | References | Notes |
| 12-O-tetradecanoylphorbol-13-acetate (TPA) | 52-54 | Diester of phorbol and potent tumor promoter, used in laboratories to activate herpesviruses, stimulate division of B cells, and activate signal transduction enzyme protein kinase C. |
| amoxicillin | 5 | β-lactam antibiotic. |
| calcium ionophore, A23187 | 54 | Ion carrier also known as calimycin or calcium ionophore; used in the laboratory to reactivate latent herpesviruses. |
| hydrocortisone | 53, 55 | Cortisol, a steroid hormone produced by the adrenal gland; used in the laboratory to reactivate herpesviruses. |
| sodium n-butyrate | 54 | HDAC inhibitor; used in the lab to alter gene expression or activate herpesviruses. |
| trichostatin A | 53 | HDAC inhibitior; closely related Vorinostat is FDA approved for the treatment of cutaneous T cell lymphoma. |
| valproic acid and carbamazapine | 56 | HDAC inhibitors; evidence conflicting because valproic acid was also shown to inhibit HHV-6B replication in one of three cell lines 57. VPA inhibits EBV, but enhances HHV-8 replication in vitro 58. |
Key Papers: HHV-6 & Drug-Induced Hypersensitivity Syndrome
REFERENCES
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