Table 1. The classification, frequencies, mechanisms, and manifestations of undesired events, with examples and treatment options (frequencies in relation to the overall number of undesired events).
| Group | Type |
Frequency (Reference) |
Mechanism | Example |
Treatment options aside from discontinuation of the offending substance |
| Medication error | 20% (e1) | Medical appropriateness index too high, e.g., double prescription |
Prescription of the same drug with generic name and trade name |
– regular checking (computer-assisted if possible) of medications and of the patient‘s adherence to treatment (e25, e26) | |
| ADR | pharmacological (type A) |
72% (39) | PK: pharmacogenetic variants or PK-DI |
Irinotecan in carriers of the UGT1A1 variant |
– regular checking (computer-assisted if possible) of DI – therapeutic drug monitoring (TDM) |
| PD: multidimensional effects |
Cutaneous reaction to EGFR antagonists such as cetuximab |
– immune modulation with doxycycline (e29) | |||
| hypersensitivity (type B) |
6% (6) | Not allergic (pseudoallergy) |
Red man syndrome in response to vancomycin |
– H1 blockers (e.g., dimenhydrinate 62 mg i. v.) – H2 blockers (e.g., ranitidine 150 mg i. v.) – glucocorticoids (e.g., prednisolone 500 mg i. v.) – volume/norepinephrine as indicated – epinephrine (e.g., 0.5 mg i. m.) as indicated – ventilation/coniotomy as indicated |
|
| 0.4% | Type I (IgE) | Anaphylaxis in response to penicillins |
|||
| rare | Type II (IgG/IgM) | Hemolytic anemia or thrombocytopenia in response to penicillins |
– substitution of blood components | ||
| rare | Type III (IgG/IgM) | Nephritis in response to penicillins |
– glucocorticoids or other anti-inflammatory substances/immune modulators – volume |
||
| 1.6% | Type IV | DIA | – reverse isolation (protection of the patient from micro-organisms) – prophylactic antibiotic and antimycotic coverage (e.g., ampicillin + sulbactam 4 g/d + 0.5 g/d, ciprofloxacin 750 mg/d, fluconazole 200 mg/d) – growth factors such as filgrastim |
||
| DILI | – H1 blockers for pruritus | ||||
| DRESS (type IVb) | – antipyretic drugs for fever – H1 blockers for pruritus – glucocorticoids, plasmapheresis and/or high-dose intravenous immunoglobulins |
||||
| SJS/TEN (type IVc) | – reverse isolation as indicated – local treatment as an artifical cutaneous barrier, ‧possibly with the addition of glucocorticoids and antimicrobial drugs – systemic glucocorticoids, cyclosporine, intravenous ‧immunoglobulins – antibiotics if there is any evidence of infection – wound treatment analogous to that of burns (no early debridement!) – electrolyte and volume substitution – analgesia |
||||
| AGEP (type IVd), MPR | – H1 blockers for pruritus – in the early phase, glucocorticoids |
||||
ADR: adverse drug reactions, AGEP: acute generalized exanthematous pustulosis, DI: drug interactions, DIA: drug-induced agranulocytosis, DILI: drug-induced liver injury,
DIRI: drug-induced renal injury, DRESS: drug reaction with eosinophilia and systemic symptoms, EGFR: epidermal growth factor receptor,
IgG: immunglobulin G, IgM: immunglobulin M, i.m.: intramuscular; i.v.: intravenous, MPR: makulopapular rash, PD: pharmacodynamics, PK: pharmakokinetics,
SJS: Stevens-Johnson syndrome, TEN: toxic epidermal necrolysis, UGT: UDP-glucuronyltransferase