4. Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens, which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically relevant for LMWHs are summarized in Table 5. Only those drug-drug interactions classified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.
| Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level |
|---|---|---|---|---|
| LMWHs | defibrotide | enhances LMWH pharmacologic effects, increasing bleeding risk | avoid concurrent use | contraindicated (DrugReax); 1-severe (CP) |
| LMWHs | drugs affecting hemostasis (e.g., anticoagulants, NSAIDs) | combined use may produce additive prolongation of bleeding time and increased bleeding risk, including gastrointestinal bleeding; prolonged bleeding risk may persist for several days following LMWH discontinuation; spinal, epidural hematomas reported with enoxaparin use in patients receiving spinal or epidural anesthesia (many also receiving drugs that affect hemostasis like NSAIDs) | avoid combination, if possible; discontinue drugs that affect hemostasis prior to initiating LMWH therapy; non-acetylated salicylate may be administered in conjunction with LMWH to avoid antiplatelet activity; acetaminophen, narcotic analgesics additional alternative analgesics for use in patients without inflammatory pain requiring LMWH therapy; if coadministration necessary, monitor closely for clinical, laboratory bleeding complications | major (DrugReax) apixaban: 1-severe (CP); other DOACs: 2- major (CP) |
| LMWHs | SSRIs, SNRIs | combined use may increase bleeding event risk (e.g., ecchymosis, epistaxis, hematoma, petechiae, life-threatening hemorrhages) as SSRIs and SNRIs may mechanistically interfere with platelet function since serotonin contributes to hemostasis | patients requiring adjunctive therapy should be closely monitored for bleeding, with treatment adjustments as necessary, when doses are modified or therapy is initiated or discontinued | major (DrugReax); 2-major (CP) |
Legend:
- +CP = Clinical Pharmacology
- DOACs = direct oral anticoagulants
- LMWHs = low-molecular-weight heparins
- NSAIDs = nonsteroidal anti-inflammatory drugs
- SNRIs = serotonin-norepinephrine reuptake inhibitors
- SSRIs = selective serotonin reuptake inhibitors