the risk for acute and/or chronic nephrotoxicity.vorapaxarMonitor Closely (1)ibuprofen, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur.voriconazoleMinor (1)voriconazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.vortioxetineMonitor Closely (1)ibuprofen, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.warfarinMonitor Closely (1)ibuprofen, warfarin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Drugs with antiplatelet properties may increase anticoagulation effect of warfarin.willow barkMinor (1)ibuprofen will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.xylometazolineMonitor Closely (1)diphenhydramine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.yohimbineMonitor Closely (1)diphenhydramine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.zafirlukastMinor (1)zafirlukast will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.zanubrutinibMonitor Closely (1)ibuprofen, zanubrutinib. Either increases effects of the other by anticoagulation. Modify Therapy/Monitor Closely. Zanubrutinib-induced cytopenias increases risk of hemorrhage. Coadministration of zanubritinib with antiplatelets or anticoagulants may further increase this risk.ziconotideMonitor Closely (1)diphenhydramine and ziconotide both increase sedation. Use Caution/Monitor.ziprasidoneMonitor Closely (4)diphenhydramine decreases levels of ziprasidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. diphenhydramine decreases levels of ziprasidone by pharmacodynamic antagonism. Use Caution/Monitor. ziprasidone increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. diphenhydramine and ziprasidone both increase sedation. Use Caution/Monitor.zotepineMonitor Closely (4)diphenhydramine decreases levels of zotepine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. diphenhydramine and zotepine both increase sedation. Use Caution/Monitor. ibuprofen decreases effects of zotepine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis. diphenhydramine decreases levels of zotepine by pharmacodynamic antagonism. Use Caution/Monitor. Frequency Not Defined Diphenhydramine Sedation Confusion Anticholinergic effects May decrease cognitive function in geriatric patients Xerostomia Pharyngeal and nasal mucosa dryness Thick sputum Ibuprofen Nausea Vomiting Epigastric pain Rash Edema Tinnitus Contraindications Hypersensitivity to NSAIDs or aspirin Active GI bleeding disorder Breastfeeding Unless you have time for a full night's sleep In children <12 years of age Right before or after heart surgery Concomitant administration with any other product containing diphenhydramine, even one used on skin Experience sleeplessness without pain Cautions Asthma (bronchial), cardiac disease, CHF, hepatic/renal impairment, hypertension Avoid driving or operating machinery When using this product avoid alcoholic beverages, do not drive motor vehicle or operate machinery, take with food or milk if stomach upset occurs, drowsiness may occur Diphenhydramine: Caution in narrow-angle glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, or bladder neck obstruction If pregnant or breastfeeding, ask a health professional before use; it is especially important not to use ibuprofen at 20 weeks or later in pregnancy unless definitely directed to do so by a doctor; it may cause problems in the unborn child or complications during delivery Before taking this medication the patient should first ask a doctor if history of stomach bleeding, experienced problems or serious side effects from taking pain relievers or fever reducers, history of stomach problems, including heartburn, history of high blood pressure, heart disease, liver cirrhosis, kidney disease, asthma, or stroke, taking diuretic, history of breathing problems, including emphysema or chronic bronchitis, diagnosed with glaucoma, difficulty urinating due to enlarged prostate gland Ask physician or pharmacist before taking this medication if taking sedatives or tranquilizers, or any other sleep-aid, under a doctor's care for any continuing medical illness, taking any other antihistamines, taking aspirin for heart attack or stroke, because ibuprofen may decease this benefit of aspirin, taking any other drug Patient should discontinue use if experiencing pain that gets worse or last more than 10 days, sleeplessness persists continuously for more than 2 weeks; insomnia may be a symptom of a serious underlying medical illness; if redness or swelling is present in the painful area, any new symptoms appear Cardiovascular risk NSAIDs, except aspirin, increase risk of heart attack, heart failure, and stroke; these can be fatal; the risk is higher if you use more than directed or for longer than directed Risk may increase with duration of use Patients with risk factors for or existing cardiovascular disease may be at greater risk NSAIDs are contraindicated for perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (increased risk of MI & stroke) Gastrointestinal risk NSAIDs increase risk of serious GI adverse events including bleeding, ulceration, & perforation of the stomach or intestines, which can be fatal Risk of severe stomach bleeding is higher if you have had stomach ulcers or bleeding problems, take a blood thinning (anticoagulant) or steroid drug, are age 60 or older, take other drugs containing prescription or nonprescription NSAIDs [aspirin, ibuprofen, naproxen, or others], take more or for a longer time than directed, have 3 or more alcoholic drinks every day while using this product GI adverse events may occur at any time during use & without warning symptoms Elderly patients are at greater risk for serious GI events The patient should discontinue use if experiencing signs of stomach bleeding, including feeling faint, having bloody or black stools, vomiting blood, experiencing stomach pain that does not get better, or when experiencing symptoms of heart problems or stroke, including chest pain, trouble breathing, leg swelling, slurred speech, weakness in one part or side of body Pregnancy Category Ask healthcare professional before use; important not to use ibuprofen during the last 3 months of pregnancy unless definitely directed to do so by a physician because it may cause problems in the unborn child or complications during delivery The Quebec Pregnancy Registry identified 4705 women who had spontaneous abortions by 20 weeks gestation; each case was matched to 10 control subjects (n=47,050) who had not had spontaneous abortions; exposure to nonaspirin NSAIDs during pregnancy was documented in approximately 7.5% of cases of spontaneous abortions and in approximately 2.6% of controls. (CMAJ, September 6, 2011; DOI:10.1503/cmaj.110454) Lactation Diphenhydramine: Enters breast milk; may decrease breast milk production; contraindicated with breastfeeding Ibuprofen: No lactation studies have been conducted with ibuprofen; however, limited published literature reports that, following oral administration, ibuprofen is present in human milk at relative infant doses of 0.06-0.6% of the maternal weight-adjusted daily dose; no information is available on effects of ibuprofen on milk production or on a breastfed infant; not recommended (AAP Committee states "compatible with nursing")Pregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Diphenhydramine: Histamine H1-receptor antagonist with low-to-moderate antihistamine properties and moderate-to-high anticholinergic/antiemetic properties Ibuprofen: Inhibits synthesis of prostaglandins in body tissues by inhibiting cyclooxygenase; at least 2 isoenzymes, cyclooxygenase-1 (COX-1) & -2 (COX-2) No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print