Drug-induced Bleeding

Johnathan W. Hamrick, PharmD; Diane Nykamp, PharmD

US Pharmacist. 2015;40(12):17-21.

Conclusion

Bleeding as a result of medication therapy is a severe complication that has a negative impact on patient safety. In many cases, bleeding is not easily identified as a drug-induced problem. Pharmacists can play a pivotal role in minimizing the development of druginduced bleeding by being aware of the contributing risk factors and medications.

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Table 1. Drugs That Increase Bleeding Risk
Drug Class	Specific Agents
Anticoagulants	Argatroban, bivalirudin, desirudin, heparin, lepirudin, warfarin
Antiplatelets	Aspirin, cilostazol, clopidogrel, dipyridamole, prasugrel, ticlopidine
NOAs	Apixaban, dabigatran, edoxaban, rivaroxaban
NSAIDs	Low risk: celecoxib, etodolac, ibuprofen, meloxicam, nabumetone, salsalate High risk: flurbiprofen, indomethacin, ketorolac, meclofenamate, naproxen, oxaprozin, piroxicam
SNRIs	Desvenlafaxine, duloxetine, venlafaxine
SSRIs	Citalopram, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline

NOA: novel oral anticoagulant; NSAID: nonsteroidal anti-inflammatory drug; SNRI: selective norepinephrine reuptake inhibitor; SSRI: selective serotonin reuptake inhibitor.
Source: References 1–3.

Table 2. Drugs That Commonly Cause Constipation
Antacids (aluminum hydroxide, calcium carbonate)
Anticholinergics (e.g., benztropine, glycopyrrolate)
Anticonvulsants (e.g., carbamazepine, divalproate)
Antihistamines (e.g., diphenhydramine, loratadine)
Antimotility agents (diphenoxylate, loperamide)
Antimuscarinics (e.g., darifenacin, oxybutynin, solifenacin, tolterodine)
Antipsychotics (e.g., clozapine, olanzapine, quetiapine)
Atropine
Barium sulfate
Benzodiazepines (alprazolam, estazolam)
Calcium channel blockers (e.g., diltiazem, verapamil)
Clonidine
Diuretics (furosemide, hydrochlorothiazide)
GI antispasmodics (dicyclomine, hyoscyamine)
Iron preparations
Memantine
Muscle relaxants (cyclobenzaprine, metaxalone)
Opiates (e.g., codeine, meperidine, morphine)
Sedative-hypnotics (phenobarbital, zolpidem)
Sucralfate
Tricyclic antidepressants (e.g., amitriptyline)
Vincristine

GI: gastrointestinal.
Source: References 12, 13.

Table 3. Natural Medicines That Affect Platelet Aggregation
Agent	Response
Arnica	Concomitant use with other anticoagulant/antiplatelet drugs may potentiate bleeding
Chondroitin	Concomitant use with other anticoagulant/antiplatelet drugs may potentiate bleeding
Coenzyme Q₁₀	Concomitant use with warfarin may reduce anticoagulant effects
Fish oil	Use of >3 g/day may potentiate bleeding. Concomitant use with other anticoagulant/antiplatelet drugs may potentiate bleeding
Garlic	Use may increase risk of bleeding. Concomitant use with other anticoagulant/antiplatelet drugs may potentiate bleeding
Ginkgo	Concomitant use with other anticoagulant/antiplatelet drugs may potentate bleeding
Green tea	Conflicting reports
Guarana	Conflicting reports
Vitamin E	High doses^a may increase risk of bleeding. Concomitant use with other anticoagulant/antiplatelet drugs may potentiate bleeding

^aData regarding what constitutes a high dose are conflicting.
Source: Reference 14.

Table 4. Drug-Drug Interactions That Increase Bleeding Risk
Agent	Bleeding Risk Enhanced by These Drugs
Citalopram	Ibritumomab, pentosan polysulfate sodium, tositumomab
Clopidogrel	CYP2C19 inhibitors: azole antifungals, cimetidine, etravirine, felbamate, fluoxetine, fluvoxamine, PPIs
Dabigatran	Ibritumomab, obinutuzumab, omacetaxine, prostacyclin analogues, ticagrelor, tositumomab, vorapaxar
Heparin	Dextran, dipyridamole, hydroxychloroquine, glycoprotein IIb/IIIa antagonists, systemic salicylates/NSAIDs
Ketorolac	Pentoxifylline, prednisone
Piroxicam	Deferasirox, obinutuzumab, omacetaxine, tositumomab, treprostinil
Rivaroxaban	Deferasirox, ibritumomab, prostacyclin analogues, tositumomab, vorapaxar
Venlafaxine	Obinutuzumab, pentosan polysulfate sodium
Warfarin	Acarbose, acetaminophen (most likely with doses >2 g/day on consecutive days), amiodarone, amoxicillin/clavulanate, azole antifungals, ciprofloxacin, citalopram, clarithromycin, fenofibrate, fluorouracil, fluvastatin, fluvoxamine, gemfibrozil, isoniazid, orlistat, protease inhibitors, simvastatin