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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 severe clinical significance or those considered life-threatening which have not yet been classified will be reviewed.

Table 5. LMWH Drug-Drug Interactions1
Target DrugInteracting DrugInteractionRecommendationClinical Significance Level
LMWHsdefibrotideenhances LMWH pharmacologic effects, increasing bleeding riskavoid concurrent usecontraindicated
LMWHsdrugs 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: apixaban, edoxaban, rivaroxaban, NSAIDs, thrombolytic agents

moderate: aspirin

LMWHsmifepristoneconcurrent use of anticoagulants is contraindicated due to the risk of serious bleeding when mifepristone is used for the termination of pregnancyavoid concurrent usecontraindicated
LMWHsSSRIs, SNRIscombined use may increase bleeding event risk (e.g., ecchymosis, epistaxis, hematoma, petechiae, life-threatening hemorrhages, GI bleeding) as SSRIs and SNRIs may mechanistically interfere with platelet function since serotonin contributes to hemostasispatients 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: SNRIs

moderate: SSRIs

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