CONTRAINDICATIONS / PRECAUTIONS
Quinolone hypersensitivity
Ciprofloxacin should not be used in patients with quinolone hypersensitivity. Serious and occasionally fatal hypersensitivity reactions have been reported in patients receiving quinolone therapy. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and pruritus. Severe hypersensitivity reactions characterized by rash, pyrexia or elevated body temperature, eosinophilia, angioedema, or other symptoms of an allergic reaction have been reported in patients receiving quinolone antibiotics. Ciprofloxacin should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management, including intubation, should be administered as indicated.
Corticosteroid therapy, organ transplant, tendinitis, tendinopathy, tendon pain, tendon rupture
Systemic quinolones have been associated with disabling and potentially irreversible serious adverse reactions such as tendinopathy, including tendinitis and tendon rupture requiring surgical repair or resulting in prolonged disability. These reactions can occur within hours to weeks after starting these agents in patients of any age, with or without pre-existing risk factors. Because of this risk for serious and potentially permanent side effects, quinolones should only be used for the treatment of uncomplicated urinary tract infection, acute bacterial exacerbation of chronic bronchitis, or acute bacterial sinusitis in cases where alternative treatment options cannot be used. Discontinue quinolones at the first sign of tendon inflammation or tendon pain as these are symptoms that may precede rupture of the tendon. Avoid quinolone use in patients with a history of tendon disorders or tendon rupture. Tendon rupture typically involves the Achilles tendon; however, ruptures of the hand, shoulder, biceps, thumb, and other tendons have also been reported. Tendinitis and tendon rupture can occur bilaterally. Rupture can occur during therapy or up to a few months after therapy has been stopped. The risk of tendon rupture is further increased in older adults (more than 60 years of age), those receiving concomitant corticosteroid therapy, and in organ transplant recipients (including kidney, heart, and lung transplants). Reasons for tendon ruptures also include physical activity or exercise, kidney failure, or tendon problems in the past. If patients experience tendon inflammation or pain, they should rest and refrain from exercise until the diagnosis of tendonitis or tendon rupture has been confidently excluded.
Apheresis, atrial fibrillation, AV block, bradycardia, cardiomyopathy, celiac disease, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, systemic lupus erythematosus (SLE), torsade de pointes
Use ciprofloxacin cautiously in patients who have cardiac arrhythmias or other cardiac disease that predisposes to cardiac arrhythmias. Fluoroquinolones have the potential to cause QT prolongation and possibly torsade de pointes (TdP) by blocking human cardiac potassium (K+) channel currents.[28775] [33146] The potency of this blockade varies among the quinolones, with ciprofloxacin appearing to have a lower potency than other quinolones such as levofloxacin.[33146] Based on cardiac studies, clinical trials, and postmarketing evaluations, the overall risk for TdP with ciprofloxacin is lower compared with other quinolones such as levofloxacin and moxifloxacin.[28419] [28775] [29833] [33144] [33145] [48869] [48871] [48872] Rare postmarketing cases of TdP have been reported, though no cardiovascular morbidity or deaths have been reported due to ciprofloxacin-associated QT prolongation.[29833] [33142] [33143] The unmonitored use of quinolones in patients with a stable ischemic heart and preserved left ventricular function is likely safe and the risk of QT prolongation and TdP is low.[33141] However, avoid the unmonitored use of quinolones in patients with known QT prolongation, patients with ongoing proarrhythmic conditions that may increase the risk of developing TdP (e.g., uncorrected hypokalemia or hypomagnesemia, significant bradycardia, congestive heart failure, acute myocardial ischemia, and atrial fibrillation), or patients receiving drugs that prolong the QT interval.[43378] [43411] Use ciprofloxacin with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, cerebrovascular accident, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.[28432] [28457] [56592] Silent mutations and genetic polymorphisms in potassium channels may further increase the risk of QT prolongation in patients taking quinolones.[33148] [33149] Ciprofloxacin, with ECG monitoring at treatment initiation, is preferable if a quinolone is desired in patients with risk factors for QT prolongation. If other quinolones are used, ECG and/or Holter monitoring during therapy is recommended.[33141]
Arteriosclerosis, cerebrovascular disease, neurotoxicity, peripheral neuropathy, psychiatric event, seizure disorder, stroke
Systemic quinolones have been associated with disabling and potentially irreversible serious neurotoxicity, including central nervous system effects, peripheral neuropathy, or psychiatric event. These reactions can occur within hours to weeks after starting these agents in patients of any age, with or without pre-existing risk factors. Because of this risk for serious and potentially permanent side effects, use quinolones for the treatment of uncomplicated urinary tract infection, acute bacterial exacerbation of chronic bronchitis, or acute bacterial sinusitis only in cases where alternative treatment options cannot be used. Avoid quinolone use in patients who have previously experienced peripheral neuropathy. Additionally, use quinolones with caution in patients with a known or suspected CNS disorder (e.g., severe cerebrovascular disease or arteriosclerosis, seizure disorder, reduced cerebral blood flow, altered brain structure, or stroke) or in the presence of other risk factors (e.g., certain drug therapy, renal dysfunction) that may predispose to seizures or lower seizure threshold. Discontinue quinolone therapy at the first signs or symptoms of neuropathy (e.g., pain, burning, tingling, numbness, and/or weakness, or other alterations in sensations such as light touch, pain, temperature, position sense, and vibratory sensation, and/or motor strength), central nervous system adverse events (seizures or convulsions, increased intracranial pressure (including pseudotumor cerebri), dizziness, or tremors), or psychiatric adverse events (toxic psychosis, hallucinations, paranoia, depression, suicidal thoughts or acts, confusion, delirium, disorientation, disturbances in attention, anxiety, agitation, nervousness, insomnia, nightmares, or memory impairment).
Myasthenia gravis
Avoid systemic quinolones, like ciprofloxacin, in patients with a history of myasthenia gravis. Quinolones may exacerbate the signs of myasthenia gravis and lead to life threatening weakness of the respiratory muscles. Serious postmarketing events, including deaths and the requirement for ventilatory support, have been associated with quinolone use in patients with myasthenia gravis. Because of this risk for serious and potentially permanent side effects, quinolones should only be used for the treatment of uncomplicated urinary tract infection, acute bacterial exacerbation of chronic bronchitis, or acute bacterial sinusitis in cases where alternative treatment options cannot be used.
Diabetes mellitus
Blood glucose disturbances, including symptomatic hyperglycemia and hypoglycemia, have been reported in patients receiving systemic ciprofloxacin. Hypoglycemia, sometimes resulting in coma, occurs more frequently in elderly patients or patients with diabetes mellitus who are receiving an oral hypoglycemic agent or insulin concomitantly with ciprofloxacin; carefully monitor blood glucose concentrations in these patients. Educate patients on the symptoms of hypoglycemia and how to treat if they experience hypoglycemia. Discontinue ciprofloxacin if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Patients with diabetes may also be at an increased risk of developing detachment of the retina.
Dialysis, renal disease, renal failure, renal impairment
Use systemic ciprofloxacin with caution in patients with renal disease. Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and partially cleared through the biliary system of the liver and through the intestine. These alternative pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. Some modification of dosage is recommended in patients with renal impairment, including those with severe renal dysfunction or renal failure, and in patients receiving dialysis.
Dehydration
Systemic ciprofloxacin should be used with caution in patients who have dehydration. Crystalluria related to systemic use has been reported only rarely in humans because human urine is usually acidic. Alkalinization of the urine should be avoided in patients receiving ciprofloxacin. Hydrate patients well; hydration may help prevent the formation of highly concentrated urine and prevent crystalluria.
Hepatic disease, hepatitis, hepatotoxicity, jaundice
Use caution when administering ciprofloxacin to patients at risk for or with a preexisting history of hepatic disease. Ciprofloxacin has been associated with severe hepatotoxicity, including hepatic necrosis and hepatic failure (both fatal and non-fatal). Ciprofloxacin-induced hepatotoxicity is often associated with hypersensitivity, has a rapid onset (1 to 39 days), and may be hepatocellular, cholestatic or mixed. Of note, most patients experiencing fatal outcomes have been over the age of 55 years; therefore, caution is advised in older adults. Immediately discontinue use if signs and symptoms of hepatitis (e.g., anorexia, jaundice, dark urine, pruritus, abdominal pain) develop during treatment.
Sunlight (UV) exposure
Patients receiving systemic ciprofloxacin and other fluoroquinolones have experienced phototoxic reactions. Moderate to severe photosensitivity/phototoxicity reactions can occur after being exposed to direct or indirect sunlight or to artificial ultraviolet light (e.g., sunlamps) during or after treatment with ciprofloxacin. Phototoxic reactions are characterized by an exaggerated sunburn reaction (e.g., burning, erythema, exudation, vesicles, blistering, edema) in areas exposed to light such as the face, the neck, extensor surfaces of the forearms, and dorsa of the hands. Patients should avoid direct or indirect artificial ultraviolet light or sunlight (UV) exposure (even when using sunscreens) during and for several days after ciprofloxacin therapy. Ciprofloxacin therapy should be discontinued immediately at the first signs of phototoxicity.
C. difficile-associated diarrhea, diarrhea, pseudomembranous colitis
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including ciprofloxacin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
Syphilis
While ciprofloxacin may be used to treat certain sexually transmitted diseases (STD), the drug may mask or delay the symptoms of incubating syphilis when given as part of an STD treatment regimen.
Aneurysm, aortic dissection, hypertension
Reserve systemic quinolones for use only when there are no alternative antibacterial treatments available in patients at risk for aortic dissection, including those with a history of aneurysm of the aorta or other blood vessels, peripheral atherosclerotic vascular diseases, hypertension, certain genetic conditions such as Marfan syndrome and Ehlers-Danlos syndrome, and elderly patients. Epidemiologic studies report an increased rate of aortic dissection within 2 months after quinolone use, particularly in elderly patients.
Geriatric
Systemic ciprofloxacin should be used cautiously in geriatric patients. Geriatric patients may be more susceptible to drug-associated hepatic and cardiac effects, including effects on the QT interval and aortic dissection, and may also be at increased risk for drug-associated tendon effects, especially in those receiving concomitant treatment with corticosteroids. Dosage adjustments are recommended for older adults with renal dysfunction, and renal function monitoring may be useful during therapy.[28764] [43411] [43570]Â [63841] According to the Beers Criteria, ciprofloxacin is considered a potentially inappropriate medication (PIM) in geriatric patients with a creatinine clearance less than 30 mL/minute due to an increased risk of CNS effects (e.g., seizures, confusion) and tendon rupture. Doses used to treat common infections typically require a reduction when the creatinine clearance is less than 30 mL/minute.[63923] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs); limit antibiotic use to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Monitor for GI side effects and hypersensitivity reactions. Fluoroquinolones may increase the risk of acute tendonitis, a prolonged QT interval, or the risk of hypoglycemia/hyperglycemia in adults 65 years or older. Per OBRA, use should be avoided in individuals with prolonged QTc intervals or who are receiving selected antiarrhythmic agents.[60742]
Children, infants, neonates
Caution is warranted when prescribing systemic ciprofloxacin for neonates, infants, children, and adolescents for infections not listed in the approved labeling. According to the FDA-approved product labeling, an increased incidence of adverse reactions compared to controls, including events related to joints and/or surrounding tissues, has been observed.[43411] Evidence supporting sustained injury to developing joints in humans is lacking at this time; however, the possibility of rare occurrences has not been excluded. One retrospective study compared the rate of tendon or joint disorders in more than 7,000 pediatric patients less than 19 years old who received ciprofloxacin, ofloxacin, or levofloxacin with more than 20,000 patients who received azithromycin. The incidence of potential tendon or joint disorders was found to be approximately 2% in both the quinolone and azithromycin groups, and verified disorders were reported in less than 1% in both groups. The authors state that this incidence is likely to reflect the background incidence of these disorders in pediatric patients.[33095] Ciprofloxacin did not have an effect on linear growth in very low birth weight infants who received the drug.[31446] Due to concerns of increasing bacterial resistance, the possibility of rare joint injury, and other possible serious adverse reactions (i.e., CNS effects, peripheral neuropathy), the American Academy of Pediatrics Committee on Infectious Diseases recommends reserving the use of systemic quinolones for infections caused by multidrug-resistant pathogens for which there is no safe and effective alternative, for the treatment of infections when parenteral therapy is not feasible and no other effective oral agent is available, and for the treatment of infections as an alternative to standard therapy because of concerns for antimicrobial resistance, toxicity, or characteristics of tissue penetration.[61410]
Contact lenses
Whenever clinical judgment dictates, examine patients receiving ophthalmic ciprofloxacin with the aid of magnification, such as slitlamp biomicroscopy, and where appropriate, fluorescein staining. Advise patients not to wear contact lenses if they have signs and symptoms of bacterial conjunctivitis.
Driving or operating machinery
Systemic ciprofloxacin can cause dizziness and light-headedness; therefore, patients should know how they react to the drug before driving or operating machinery or engaging in an activity requiring mental alertness or coordination.
Pregnancy
Based on case reports, case-control studies, and observational studies of ciprofloxacin administered during pregnancy, prolonged experience with systemic ciprofloxacin in pregnant women over several decades has not identified any drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Available studies have methodological limitations including small sample size and lack of specificity for ciprofloxacin. In a controlled, prospective, observational study of 200 women exposed to quinolones during gestation (68% first-trimester exposures and 52.5% ciprofloxacin exposures), in utero exposure was not associated with increased risk of major congenital malformations (2.2% for quinolones and 2.6% for controls). There were no musculoskeletal dysfunctions up to 1 year of age in the ciprofloxacin exposed children. Another prospective follow-up study reported on 549 pregnancies with quinolone exposure (93% first-trimester exposures and 70 ciprofloxacin first-trimester exposures) and malformation rates were within background incidence ranges with no specific patterns of congenital abnormalities or any clear adverse reactions due to in utero ciprofloxacin exposure. No differences in the rates of prematurity, spontaneous abortions, or low birth weight were seen in women exposed to ciprofloxacin during pregnancy; however, these small postmarketing epidemiology studies are insufficient to evaluate the risk for less common defects or to permit reliable definitive conclusions regarding the safety of ciprofloxacin in pregnant women and their developing fetuses.[26982] [26983] [43411] In a nested, case-control study (n = 87,020 controls; 8,702 cases) within the Quebec Pregnancy Cohort, quinolone use during early pregnancy was associated with an increased risk of spontaneous abortion (adjusted odds ratio (aOR) 2.72; 95% CI: 2.27 to 3.27; 160 exposed cases); residual confounding by severity of infection may be a potential limitation of this study.[62176] In a large population-based cohort study (n = 139,938 live births) assessing antibiotic exposure during the first trimester of pregnancy (n = 15,469 exposures) and the risk of major birth defects, quinolone use was associated with an increased risk of urinary system malformations (aOR 1.89; 95% CI: 1.09 to 3.28, 14 exposed cases).[62177] Ciprofloxacin and other quinolones have been shown to cause arthropathy in immature animals when administered directly.[43411] There are no adequate and well-controlled studies of ophthalmic ciprofloxacin use during human pregnancy; therefore, use ophthalmic ciprofloxacin during pregnancy only if the potential benefit justifies the potential risk to the fetus.[43892] [43893] No adequate and well-controlled studies with otic ciprofloxacin have been performed in pregnant women. Animal studies have not been conducted with otic ciprofloxacin. Because of the negligible systemic exposure associated with otic ciprofloxacin, it is expected to be of minimal risk for maternal and fetal toxicity when administered to pregnant women. Use caution when administering otic ciprofloxacin to a pregnant woman. [60436]
Breast-feeding
Ciprofloxacin is present in human breast milk after intravenous and oral administration. There is no information regarding the effects of ciprofloxacin on milk production or the breast-fed infant. Because of the potential for serious adverse reactions (e.g., arthropathy) in the breast-fed infant, for most indications a lactating woman may consider pumping and discarding breast milk during treatment with systemic ciprofloxacin and for an additional 2 days after the last dose. Alternatively, advise a woman that breast-feeding is not recommended during treatment with systemic ciprofloxacin and for an additional 2 days after the last dose. However, for inhalational anthrax (post-exposure), during an incident resulting in exposure to anthrax, the risk-benefit assessment of continuing breast-feeding while the mother (and potentially the infant) is receiving ciprofloxacin may be acceptable. Consider the developmental and health benefits of breast-feeding along with the monther's clinical need for ciprofloxacin and any potential adverse effects on the breast-fed child from ciprofloxacin or the underlying maternal condition. Ciprofloxacin may cause intestinal flora alteration of the breast-feeding infant. Monitor the breast-fed infant for loose or bloody stools and candidiasis (i.e., thrush, diaper rash).[43411] It is not known whether topically applied ciprofloxacin is excreted in human milk. Use caution when administering ophthalmic ciprofloxacin to a breast-feeding woman. Nursing infants of mothers receiving otic ciprofloxacin should not be affected. However, because of the potential for serious adverse reactions in nursing infants, discontinue breast-feeding or discontinue otic ciprofloxacin, taking into account the importance of the drug to the mother.[43891]Â [43892] [43893] [60436] Levofloxacin, sulfamethoxazole; trimethoprim, ceftazidime, cefepime, and piperacillin; tazobactam may be potential systemic alternatives to consider during breast-feeding. However, assess site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility before choosing an alternative agent. Previous American Academy of Pediatrics (AAP) recommendations considered ofloxacin, trimethoprim (in combination with sulfamethoxazole), and ceftazidime to be usually compatible with breast-feeding.[27500] Levofloxacin is the S-enantiomer of ofloxacin, and although it is excreted in breast milk, the estimated amount that a nursing infant would receive, 1.23 mg/day, is less than doses that have been used to treat an infant.[45938] Other beta-lactams, such as cefepime and piperacillin; tazobactam are generally considered compatible with breast-feeding.[46945] [46946] [46947] In a study of lactating women given 3 oral ciprofloxacin doses of 750 mg, ciprofloxacin breast milk concentrations were higher than serum concentrations with peak concentrations occurring in 2 hours and the lowest concentration occurring at 24 hours; the mean milk:serum ratio varied from 0.85 to 2.14.[31576]
DRUG INTERACTIONS
Abarelix: (Moderate) Since abarelix can cause QT prolongation, abarelix should be used cautiously with other drugs that are associated with QT prolongation, such as ciprofloxacin.
Abemaciclib: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with ciprofloxacin is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Acalabrutinib: (Major) Decrease the acalabrutinib dose to 100 mg PO once daily if coadministered with ciprofloxacin. Coadministration may result in increased acalabrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Acalabrutinib is a CYP3A4 substrate; ciprofloxacin is a moderate CYP3A4 inhibitor. In physiologically based pharmacokinetic (PBPK) simulations, the Cmax and AUC values of acalabrutinib were increased by 2- to almost 3-fold when acalabrutinib was coadministered with moderate CYP3A inhibitors.
Acarbose: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including alpha-glucosidase inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Acetaminophen; Caffeine: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with ciprofloxacin may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of ciprofloxacin could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Ciprofloxacin is a moderate inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after magnesium salicylate. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with ciprofloxacin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ciprofloxacin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ciprofloxacin is a moderate inhibitor of CYP3A4.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. If ciprofloxacin is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like ciprofloxacin can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If ciprofloxacin is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Acetazolamide: (Minor) A large proportion of ciprofloxacin is normally excreted unchanged in the urine. If urinary alkalinizing agents such as carbonic anhydrase inhibitors are used concomitantly, the solubility of ciprofloxacin can be decreased because of alkaline urine. Patients should be monitored for crystalluria and nephrotoxicity.
Acetohexamide: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including sulfonylureas, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Ado-Trastuzumab emtansine: (Major) Avoid concomitant use of ado-trastuzumab emtansine with ciprofloxacin, as plasma exposure to the cytotoxic small molecule of ado-trastuzumab emtansine, DM1, may be increased. Treatment with ado-trastuzumab emtansine should be delayed until ciprofloxacin is cleared from the circulation (approximately 3 elimination half-lives), or an alternate medication with less potential to inhibit CYP3A4 should be considered. If co-administration is necessary, monitor for an increase in ado-trastuzumab emtansine-related adverse events. Ciprofloxacin is a moderate CYP3A4 inhibitor. While formal drug interaction studies have not been conducted, DM1 is mainly metabolized by CYP3A4 (and to a lesser extent, CYP3A5) in vitro. Coadministration may result in potentially increased DM1 exposure and toxicity.
Albiglutide: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including incretin mimetics, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Alfentanil: (Moderate) The plasma concentrations of alfentanil may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as hypotension, nausea, itching, and respiratory depression, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor and alfentanil is a CYP3A4 substrate.
Alfuzosin: (Moderate) Use caution when administering alfuzosin with ciprofloxacin due to the potential for QT prolongation. Alfuzosin may prolong the QT interval in a dose-dependent manner. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance.
Aliskiren: (Moderate) The plasma concentrations of aliskiren may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as decreased blood pressure, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor and aliskiren is a CYP3A4 substrate.
Aliskiren; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ciprofloxacin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure. (Moderate) The plasma concentrations of aliskiren may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as decreased blood pressure, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor and aliskiren is a CYP3A4 substrate.
Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ciprofloxacin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure. (Moderate) The plasma concentrations of aliskiren may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as decreased blood pressure, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor and aliskiren is a CYP3A4 substrate.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) The plasma concentrations of aliskiren may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as decreased blood pressure, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor and aliskiren is a CYP3A4 substrate.
Aliskiren; Valsartan: (Moderate) The plasma concentrations of aliskiren may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as decreased blood pressure, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor and aliskiren is a CYP3A4 substrate.
Alogliptin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including dipeptidyl peptidase-4 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Alogliptin; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including dipeptidyl peptidase-4 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Alogliptin; Pioglitazone: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including dipeptidyl peptidase-4 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including thiazolidinediones, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Alosetron: (Major) Avoid coadministration of alosetron and ciprofloxacin due to the potential for increased exposure and half-life of alosetron. Ciprofloxacin is a strong inhibitor of CYP1A2; alosetron is a CYP1A2 substrate. Coadministration of another strong CYP1A2 inhibitor increased the mean alosetron AUC by about 6-fold and prolonged the half-life by 3-fold.
Alpha-glucosidase Inhibitors: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including alpha-glucosidase inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Alprazolam: (Major) Avoid coadministration of alprazolam and ciprofloxacin due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Alprazolam is a CYP3A4 substrate and ciprofloxacin may be a CYP3A4 inhibitor but in vivo data are conflicting. Coadministration with other moderate CYP3A4 inhibitors increased alprazolam exposure by 1.6- to 1.98-fold.
Aluminum Hydroxide: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after products that contain aluminum hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain aluminum hydroxide.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after magnesium carbonate. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after products that contain aluminum hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain aluminum hydroxide.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after magnesium hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after products that contain aluminum hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain aluminum hydroxide.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after magnesium hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after products that contain aluminum hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain aluminum hydroxide.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after products that contain aluminum hydroxide. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids that contain aluminum hydroxide. (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after products that contain magnesium trisilicate. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
Amiodarone: (Major) Concomitant use of ciprofloxacin and amiodarone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with ciprofloxacin. Amisulpride causes dose- and concentration- dependent QT prolongation. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance.
Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ciprofloxacin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Atorvastatin: (Moderate) Closely monitor for signs and symptoms of myopathy and rhabdomyolysis and consider atorvastatin dosage adjustment in patients also taking ciprofloxacin. Coadministration of ciprofloxacin, a moderate CYP3A4 inhibitor, with atorvastatin, a CYP3A4 substrate, may increase atorvastatin exposure resulting in atorvastatin-related toxicity; the risk may be increased with higher statin doses. (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ciprofloxacin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Benazepril: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ciprofloxacin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Celecoxib: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ciprofloxacin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure. (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Amlodipine; Olmesartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ciprofloxacin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Valsartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ciprofloxacin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ciprofloxacin is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with ciprofloxacin. Clarithromycin is associated with an established risk for QT prolongation and TdP. Ciprofloxacin has a possible risk for QT prolongation and TdP and should be used cautiously with clarithromycin. (Minor) Concomitant use of ciprofloxacin and omeprazole may decrease the AUC and Cmax of ciprofloxacin, but the clinical significance of this interaction is unknown. Codministration of a single tablet dose of 500 mg ciprofloxacin and once-daily administration of 20 mg omeprazole pretreatment for 4 days resulted in a 16% reduction of mean Cmax and mean AUC of ciprofloxacin. A single 1000 mg oral dose of Cipro XR administered with omeprazole (40 mg once daily for 3 days) to 18 healthy volunteers resulted in a decrease in the ciprofloxacin mean AUC by 20% and Cmax by 23%. However, coadministration of a single 1000 mg oral dose of Proquin XR given 2 hours after the third dose of omeprazole (40 mg once daily for 3 days) to 27 healthy volunteers resulted in no changes in the ciprofloxacin AUC and Cmax. If ciprofloxacin is administered with omeprazole with magnesium, chelation of the ciprofloxacin would be expected; in general, it is recommended that ciprofloxacin be administered 2 hours before or 6 hours after any divalent cations like magnesium to help limit an interaction.
Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP and should be used cautiously and with close monitoring with anagrelide. In addition, anagrelide is partially metabolized by CYP1A2. Coadministration of anagrelide with drugs that inhibit CYP1A2, such as ciprofloxacin, could theoretically decrease the elimination of anagrelide and increase the risk of side effects or toxicity. Patients should be monitored for increased adverse effects if anagrelide is coadministered with ciprofloxacin.
Apomorphine: (Moderate) Use apomorphine and ciprofloxacin together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Rare cases of QT prolongation and torsade de pointes have been reported with ciprofloxacin during postmarketing surveillance.
Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use due to substantially increased exposure of aprepitant with ciprofloxacin use. If coadministration cannot be avoided, use caution and monitor for an increase in aprepitant-related adverse effects for several days after administration of a multi-day aprepitant regimen. Ciprofloxacin is a moderate CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of daily oral aprepitant (230 mg, or 1.8 times the recommended single dose) with another moderate CYP3A4 inhibitor increased the aprepitant AUC 2-fold; clinically meaningful changes in ECG, heart rate, or blood pressure did not occur. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions.
Aripiprazole: (Moderate) Caution is advised when administering aripiprazole with ciprofloxacin, as use of these drugs together may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. In addition, rare cases of QT prolongation and TdP have been reported with ciprofloxacin during post-marketing surveillance.
Arsenic Trioxide: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering arsenic trioxide with ciprofloxacin. If possible, use of ciprfloxacin should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported.
Artemether; Lumefantrine: (Major) Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, such as ciprofloxacin, coadministration may result in additive QT prolongation. Concomitant use of artemether; lumefantrine with other drugs that prolong the QT interval should be avoided. Consider ECG monitoring if ciprofloxacin must be used with or after artemether; lumefantrine treatment. (Major) Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, such as ciprofloxacin, coadministration may result in additive QT prolongation. Concomitant use of artemether; lumefantrine with other drugs that prolong the QT interval should be avoided. Consider ECG monitoring if ciprofloxacine must be used with or after artemether; lumefantrine treatment.
Asenapine: (Major) Asenapine has been associated with QT prolongation. According to the manufacturer, asenapine should not be used with other agents also known to have this effect. Ciprofloxacin is associated with a possible risk for QT prolongation and torsade de pointes; therefore, caution is advised during combination therapy. In addition, in vitro studies indicate that CYP1A2 is a primary metabolic pathway of asenapine. In theory, inhibitors of this isoenzyme such as ciprofloxacin may decrease the elimination of asenapine.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concomitant use of codeine with ciprofloxacin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ciprofloxacin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ciprofloxacin is a moderate inhibitor of CYP3A4. (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Aspirin, ASA; Caffeine: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with ciprofloxacin may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of ciprofloxacin could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Ciprofloxacin is a moderate inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with ciprofloxacin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ciprofloxacin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ciprofloxacin is a moderate inhibitor of CYP3A4.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Crystalluria related to ciprofloxacin has been reported only rarely in humans because human urine is usually acidic. Avoid alkalinity of the urine in patients receiving ciprofloxacin when possible. A large proportion of ciprofloxacin is normally excreted unchanged in the urine. If sodium bicarbonate is used concomitantly, the solubility of ciprofloxacin might be decreased because of alkaline urine. Patients should be monitored for crystalluria, proper urination,and altered kidney function. Hydrate patients well to prevent the formation of highly concentrated urine.
Aspirin, ASA; Omeprazole: (Minor) Concomitant use of ciprofloxacin and omeprazole may decrease the AUC and Cmax of ciprofloxacin, but the clinical significance of this interaction is unknown. Codministration of a single tablet dose of 500 mg ciprofloxacin and once-daily administration of 20 mg omeprazole pretreatment for 4 days resulted in a 16% reduction of mean Cmax and mean AUC of ciprofloxacin. A single 1000 mg oral dose of Cipro XR administered with omeprazole (40 mg once daily for 3 days) to 18 healthy volunteers resulted in a decrease in the ciprofloxacin mean AUC by 20% and Cmax by 23%. However, coadministration of a single 1000 mg oral dose of Proquin XR given 2 hours after the third dose of omeprazole (40 mg once daily for 3 days) to 27 healthy volunteers resulted in no changes in the ciprofloxacin AUC and Cmax. If ciprofloxacin is administered with omeprazole with magnesium, chelation of the ciprofloxacin would be expected; in general, it is recommended that ciprofloxacin be administered 2 hours before or 6 hours after any divalent cations like magnesium to help limit an interaction.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. If ciprofloxacin is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like ciprofloxacin can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If ciprofloxacin is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and ciprofloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Atorvastatin: (Moderate) Closely monitor for signs and symptoms of myopathy and rhabdomyolysis and consider atorvastatin dosage adjustment in patients also taking ciprofloxacin. Coadministration of ciprofloxacin, a moderate CYP3A4 inhibitor, with atorvastatin, a CYP3A4 substrate, may increase atorvastatin exposure resulting in atorvastatin-related toxicity; the risk may be increased with higher statin doses.
Atorvastatin; Ezetimibe: (Moderate) Closely monitor for signs and symptoms of myopathy and rhabdomyolysis and consider atorvastatin dosage adjustment in patients also taking ciprofloxacin. Coadministration of ciprofloxacin, a moderate CYP3A4 inhibitor, with atorvastatin, a CYP3A4 substrate, may increase atorvastatin exposure resulting in atorvastatin-related toxicity; the risk may be increased with higher statin doses.
Avanafil: (Major) Do not exceed an avanafil dose of 50 mg once every 24 hours in patients receiving ciprofloxacin. Coadministration may increase avanafil exposure. Avanafil is a sensitive CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the avanafil AUC by 3-fold and prolonged the half-life to approximately 8 hours.
Avapritinib: (Major) Avoid coadministration of avapritinib with ciprofloxacin due to the risk of increased avapritinib-related adverse reactions. If concurrent use is unavoidable, reduce the starting dose of avapritinib from 300 mg PO once daily to 100 mg PO once daily in patients with gastrointestinal stromal tumor or from 200 mg PO once daily to 50 mg PO once daily in patients with advanced systemic mastocytosis. Avapritinib is a CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. Coadministration of avapritinib 300 mg PO once daily with a moderate CYP3A4 inhibitor is predicted to increase the AUC of avapritinib by 210% at steady-state.
Azithromycin: (Major) Concomitant use of azithromycin and ciprofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bacillus Calmette-Guerin Vaccine, BCG: (Major) Ciprofloxacin may interfere with the effectiveness of Bacillus Calmette-Guerin Live, BCG. The TheraCys product is made from the Connaught strain of Bacillus Calmette and Guerin, which is an attenuated strain of Mycobacterium bovis. Sensitivity of the Connaught strain to several antibiotics was tested in vitro. Bacteria were susceptible to ciprofloxacin. Urinary concentrations of these antibiotics could interfere with the therapeutic effectiveness of BCG. Furthermore, the minimum inhibitory concentrations associated with each drug render them potentially useful for the treatment of systemic BCG reactions or infections. Although the TICE BCG product is obtained from a different strain (Tice strain), similar antimicrobial sensitivities may occur. Postpone instillation of BCG if the patient is receiving antibiotics. BCG Live should not be used in patients with an active infection (see Contraindications).[
Bedaquiline: (Major) Coadministration of bedaquiline with other QT prolonging drugs, such as ciprofloxacin, may result in additive or synergistic prolongation of the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
Bendamustine: (Major) Consider the use of an alternative therapy if ciprofloxacin treatment is needed in patients receiving bendamustine. Ciprofloxacin may increase bendamustine exposure, which may increase the risk of adverse reactions (e.g., myelosuppression, infection, hepatotoxicity). Bendamustine is a CYP1A2 substrate and ciprofloxacin is a CYP1A2 inhibitor.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with ciprofloxacin may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of ciprofloxacin in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4. Ciprofloxacin is an inhibitor of CYP3A4.
Bepridil: (Major) Bepridil is associated with a well-established risk of QT prolongation and torsades de pointes. Patients receiving other drugs which have the potential for QT prolongation, such as ciprofloxacin, have an increased risk of developing proarrhythmias during bepridil therapy.
Betamethasone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and ciprofloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and ciprofloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Boceprevir: (Moderate) Close clinical monitoring is advised when administering ciprofloxacin with boceprevir due to an increased potential for boceprevir-related adverse events. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of ciprofloxacin and boceprevir. Ciprofloxacin is an inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may be elevated.
Bortezomib: (Minor) Plasma concentrations of bortezomib may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as gastrointestinal side effects, hypotension, or peripheral neuropathy, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while bortezomib is a CYP3A4 substrate.
Bosentan: (Moderate) Coadministration of bosentan, a CYP3A4 substrate, with ciprofloxacin, a CYP3A4 inhibitor, may increase the plasma concentrations of bosentan. No dosage adjustment of bosentan is needed, however, the potential for increased bosentan effects, such as hepatic injury or decreased blood pressure, should be monitored.
Bosutinib: (Major) Avoid concomitant use of bosutinib and ciprofloxacin; bosutinib plasma exposure may be significantly increased resulting in an increased risk of bosutinib adverse events (e.g., myelosuppression, GI toxicity). Bosutinib is a CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. In a cross-over trial in 18 healthy volunteers, the Cmax and AUC values of bosutinib were increased 1.5-fold and 2-fold, respectively, when bosutinib 500 mg PO was administered with a single dose of a moderate CYP3A4 inhibitor.
Brentuximab vedotin: (Moderate) Clinical monitoring for adverse effects, such as peripheral neuropathy or gastrointestinal side effects, is recommended during coadministration of brentuximab vedotin and ciprofloxacin. Plasma concentrations of monomethyl auristatin E (MMAE), one of the 3 components released from brentuximab vedotin, may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while MMAE is a CYP3A4 substrate.
Brexpiprazole: (Moderate) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Ciprofloxacin is a moderate inhibitor of CYP3A4. If ciprofloxacin is used in combination with brexpiprazole and a moderate to strong CYP2D6 inhibitor, the brexpiprazole dose should be adjusted and the patient should be carefully monitored for brexpiprazole-related adverse reactions. A reduction of the brexpiprazole dose to 25% of the usual dose is also recommended in patients who are poor metabolizers of CYP2D6 and are receiving a moderate CYP3A4 inhibitor.
Brigatinib: (Major) Avoid coadministration of brigatinib with ciprofloxacin if possible due to increased plasma exposure of brigatinib; an increase in brigatinib-related adverse reactions may occur. If concomitant use is unavoidable, reduce the dose of brigatinib by approximately 40% without breaking tablets (i.e., from 180 mg to 120 mg; from 120 mg to 90 mg; from 90 mg to 60 mg); after discontinuation of ciprofloxacin, resume the brigatinib dose that was tolerated prior to initiation of ciprofloxacin. Brigatinib is a CYP3A4 substrate; ciprofloxacin is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase the AUC of brigatinib by approximately 40%.
Bromocriptine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of ciprofloxacin. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; ciprofloxacin is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Budesonide: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Budesonide; Formoterol: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Bupivacaine Liposomal: (Moderate) Clinical monitoring for adverse effects, such as cardiotoxic effects, hypotension, or CNS toxicity, is recommended during coadministration as plasma concentrations of bupivacaine may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while bupivacaine is a CYP3A4 substrate.
Bupivacaine: (Moderate) Clinical monitoring for adverse effects, such as cardiotoxic effects, hypotension, or CNS toxicity, is recommended during coadministration as plasma concentrations of bupivacaine may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while bupivacaine is a CYP3A4 substrate.
Bupivacaine; Epinephrine: (Moderate) Clinical monitoring for adverse effects, such as cardiotoxic effects, hypotension, or CNS toxicity, is recommended during coadministration as plasma concentrations of bupivacaine may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while bupivacaine is a CYP3A4 substrate.
Bupivacaine; Lidocaine: (Moderate) Clinical monitoring for adverse effects, such as cardiotoxic effects, hypotension, or CNS toxicity, is recommended during coadministration as plasma concentrations of bupivacaine may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while bupivacaine is a CYP3A4 substrate. (Moderate) Concomitant use of systemic lidocaine and ciprofloxacin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ciprofloxacin inhibits both of these isoenzymes. In a study of healthy volunteers (n = 9), concomitant use of lidocaine (1.5mg/kg IV) and ciprofloxacin (500 mg twice daily) resulted in an increase of lidocaine Cmax and AUC by 12% and 26%, respectively.
Bupivacaine; Meloxicam: (Moderate) Clinical monitoring for adverse effects, such as cardiotoxic effects, hypotension, or CNS toxicity, is recommended during coadministration as plasma concentrations of bupivacaine may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while bupivacaine is a CYP3A4 substrate. (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Buprenorphine: (Major) Concomitant use of buprenorphine and ciprofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use can also increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when ciprofloxacin is added after a stable buprenorphine dose is achieved. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping ciprofloxacin, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If ciprofloxacin is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a CYP3A4 substrate and ciprofloxacin is a CYP3A4 inhibitor.
Buprenorphine; Naloxone: (Major) Concomitant use of buprenorphine and ciprofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use can also increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when ciprofloxacin is added after a stable buprenorphine dose is achieved. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping ciprofloxacin, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If ciprofloxacin is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a CYP3A4 substrate and ciprofloxacin is a CYP3A4 inhibitor.
Buspirone: (Moderate) Close clinical monitoring is recommended if buspirone is administered with ciprofloxacin; buspirone dose reductions may be required. The plasma concentrations of buspirone may be elevated when administered concurrently with ciprofloxacin. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. Ciprofloxacin is an inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of buspirone. These drugs used in combination may result in elevated buspirone plasma concentrations, causing an increased risk for buspirone-related adverse events.
Butalbital; Acetaminophen; Caffeine: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with ciprofloxacin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ciprofloxacin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ciprofloxacin is a moderate inhibitor of CYP3A4. (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Cabotegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with ciprofloxacin as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance.
Caffeine: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Caffeine; Sodium Benzoate: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Calcium Acetate: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium Carbonate: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium Carbonate; Risedronate: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium Carbonate; Simethicone: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium Chloride: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium Gluconate: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Calcium; Vitamin D: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Canagliflozin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including SGLT2 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Canagliflozin; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including SGLT2 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Carbamazepine: (Major) Serum carbamazepine concentrations should be monitored closely during coadministration with ciprofloxacin; reduced carbamazepine doses may be necessary. Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Drugs known to inhibit CYP3A4, such as ciprofloxacin, may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations.
Carbetapentane; Guaifenesin; Phenylephrine: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain zinc. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc.
Carbetapentane; Phenylephrine: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain zinc. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc.
Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Carbonic anhydrase inhibitors: (Minor) A large proportion of ciprofloxacin is normally excreted unchanged in the urine. If urinary alkalinizing agents such as carbonic anhydrase inhibitors are used concomitantly, the solubility of ciprofloxacin can be decreased because of alkaline urine. Patients should be monitored for crystalluria and nephrotoxicity.
Cariprazine: (Moderate) Monitor for adverse effects, such as CNS effects and extrapyramidal symptoms, during coadministration of cariprazine and ciprofloxacin. Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Ciprofloxacin is a CYP3A4 inhibitor and may reduce the hepatic metabolism of CYP3A4 substrates, although the impact of moderate CYP3A4 inhibitors on cariprazine metabolism has not been studied.
Celecoxib: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Celecoxib; Tramadol: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Ceritinib: (Major) Avoid coadministration of ceritinib with ciprofloxacin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance.
Chlordiazepoxide: (Major) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity.
Chlordiazepoxide; Amitriptyline: (Major) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity.
Chlordiazepoxide; Clidinium: (Major) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity.
Chloroquine: (Major) Avoid coadministration of chloroquine with ciprofloxacin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with ciprofloxacin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ciprofloxacin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ciprofloxacin is a moderate inhibitor of CYP3A4.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with ciprofloxacin may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of ciprofloxacin could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Ciprofloxacin is a moderate inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with ciprofloxacin may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of ciprofloxacin could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Ciprofloxacin is a moderate inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Chlorpheniramine; Pseudoephedrine: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain zinc. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc.
Chlorpromazine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering chlorpromazine with ciprofloxacin. Phenothiazines have been associated with a risk of QT prolongation and/or TdP. This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Administration of chlorpromazine with ciprofloxacin may cause additive QT prolongation and could lead to TdP, and therefore concurrent use is generally not recommended.
Chlorpropamide: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including sulfonylureas, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Cholera Vaccine: (Major) Avoid the live cholera vaccine in patients that have received ciprofloxacin within 14 days prior to vaccination. Concurrent administration of the live cholera vaccine with antibiotics active against cholera, such as ciprofloxacin, may diminish vaccine efficacy and result in suboptimal immune response. A duration of fewer than 14 days between stopping antibiotics and vaccination might also be acceptable in some clinical settings if travel cannot be avoided before 14 days have elapsed after stopping antibiotics.
Choline Salicylate; Magnesium Salicylate: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after magnesium salicylate. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
Chromium: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Cilostazol: (Major) Reduce cilostazol dose to 50 mg PO twice daily when administered with ciprofloxacin. Coadministration of moderate CYP3A4 inhibitors, such as ciprofloxacin, can increase exposure to cilostazol, a CYP3A4 substrate.
Cisapride: (Contraindicated) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Because of the potential for TdP, use of ciprofloxacin is contraindicated with cisapride.
Citalopram: (Major) Concomitant use of citalopram and ciprofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clarithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with ciprofloxacin. Clarithromycin is associated with an established risk for QT prolongation and TdP. Ciprofloxacin has a possible risk for QT prolongation and TdP and should be used cautiously with clarithromycin.
Clindamycin; Tretinoin: (Major) Avoid the concomitant use of tretinoin with other drugs known to cause photosensitivity, such as ciprofloxacin. Concomitant use with other photosensitizing agents may increase the risk of a photosensitivity reaction.
Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with ciprofloxacin. QT prolongation and torsade de pointes (TdP) have been reported in patients receiving clofazimine in combination with QT prolonging medications. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance.
Clonazepam: (Moderate) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of clonazepam and increase the potential for benzodiazepine toxicity.
Clorazepate: (Moderate) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of clorazepate and increase the potential for benzodiazepine toxicity. Clorazepate is a pro-drug converted to N-desmethyldiazepam in the GI tract; N-desmethyldiazepam is metabolized by CYP3A4.
Clozapine: (Major) If co-administration of clozapine and a potent inhibitor of CYP1A2 such as ciprofloxacin is necessary, the manufacturer of clozapine recommends using one-third of the usual clozapine dose. If the inhibitor is discontinued, increase the clozapine dose based on clinical response. One study of 7 schizophrenic patients has shown that concurrent therapy with ciprofloxacin (250 mg twice daily) versus placebo resulted in increased clozapine plasma concentrations (29%) and N-desmethylclozapine plasma concentrations (31%). One case study has reported elevated clozapine plasma concentrations (by 80%) during ciprofloxacin coadministration at doses of 500 mg twice daily. In addition, rare cases of QT prolongation and torsade de pointes (TdP) have been reported with both ciprofloxacin and clozapine. Elevated plasma concentrations of clozapine occurring through inhibition of CYP1A2, CYP3A4, or CYP2D6 may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. If quinolone administration is indicated during clozapine therapy, an alternative fluoroquinolone with minimal inhibitory effects on CYP1A2, CYP2D6, or CYP3A4 should be considered.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with chronic ciprofloxacin therapy due to the risk of cobimetinib toxicity. If concurrent short-term (14 days or less) use of ciprofloxacin is unavoidable, reduce the dose of cobimetinib to 20 mg once daily for patients normally taking 60 mg daily; after discontinuation of ciprofloxacin, resume cobimetinib at the previous dose. Use an alternative to ciprofloxacin in patients who are already taking a reduced dose of cobimetinib (40 or 20 mg daily). Cobimetinib is a CYP3A substrate in vitro, and ciprofloxacin is a moderate inhibitor of CYP3A. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with a strong CYP3A4 inhibitor increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7).
Codeine: (Moderate) Concomitant use of codeine with ciprofloxacin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ciprofloxacin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ciprofloxacin is a moderate inhibitor of CYP3A4.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with ciprofloxacin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ciprofloxacin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ciprofloxacin is a moderate inhibitor of CYP3A4.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with ciprofloxacin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ciprofloxacin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ciprofloxacin is a moderate inhibitor of CYP3A4.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of ciprofloxacin and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) Concomitant use of codeine with ciprofloxacin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ciprofloxacin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ciprofloxacin is a moderate inhibitor of CYP3A4.
Codeine; Promethazine: (Moderate) Concomitant use of ciprofloxacin and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) Concomitant use of codeine with ciprofloxacin may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ciprofloxacin could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ciprofloxacin is a moderate inhibitor of CYP3A4.
Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and ciprofloxacin unless the use of both agents is imperative. Ciprofloxacin can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate inhibitor like ciprofloxacin in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
Cortisone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Crizotinib: (Major) Avoid coadministration of crizotinib with ciprofloxacin due to the risk of QT prolongation; crizotinib exposure may also increase. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Also monitor for an increase in crizotinib-related adverse reactions. Crizotinib is a CYP3A substrate that has been associated with concentration-dependent QT prolongation. Ciprofloxacin is a moderate CYP3A4 inhibitor that has had rare cases of QT prolongation and torsade de pointes (TdP) reported during postmarketing surveillance.
Cyclosporine: (Moderate) Monitor renal function during concomitant therapy. Cyclosporine serum concentrations should be monitored and suitable dosage adjustments made. Coadministration of ciprofloxacin and cyclosporine may result in elevated plasma cyclosporine concentrations. Cyclosporine is extensively metabolized by CYP3A4; ciprofloxacin is an inhibitor of CYP3A4. Additionally, some quinolones, including ciprofloxacin, have been associated with transient elevations in serum creatinine in patients receiving concomitant cyclosporine and ciprofloxacin therapy and may potentiate renal dysfunction. Cases of nephrotoxicity with and without increases in cyclosporine concentrations during concurrent cyclosporine and ciprofloxacin treatment have been reported.
Daclatasvir: (Moderate) According to the manufacturer, concurrent administration of daclatasvir, a CYP3A4 substrate, with ciprofloxacin, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Dapagliflozin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including SGLT2 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Dapagliflozin; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including SGLT2 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including dipeptidyl peptidase-4 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including SGLT2 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Dapsone: (Moderate) Clinical monitoring for adverse effects, such as hemolytic anemia, methemoglobinemia, or peripheral neuropathy, is recommended during coadministration of dapsone and ciprofloxacin. Plasma concentrations of dapsone may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while dapsone is a CYP3A4 substrate.
Darifenacin: (Moderate) Clinical monitoring for adverse effects, such as anticholinergic effects, is recommended during coadministration of darifenacin and ciprofloxacin. The plasma concentrations of darifenacin may be elevated when administered concurrently with ciprofloxacin. Ciprofloxacin is a CYP3A4 inhibitor, while darifenacin is a CYP3A4 substrate.
Darunavir: (Moderate) Caution is warranted when darunavir is administered with ciprofloxacin as there is a potential for elevated concentrations of darunavir. Clinical monitoring for adverse effects is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while darunavir is a CYP3A4 substrate.
Darunavir; Cobicistat: (Moderate) Caution is warranted when darunavir is administered with ciprofloxacin as there is a potential for elevated concentrations of darunavir. Clinical monitoring for adverse effects is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while darunavir is a CYP3A4 substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when darunavir is administered with ciprofloxacin as there is a potential for elevated concentrations of darunavir. Clinical monitoring for adverse effects is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while darunavir is a CYP3A4 substrate.
Dasatinib: (Moderate) Ciprofloxacin should be used with caution in patients receiving dasatinib as concurrent use may increase the risk of QT prolongation. Rare cases of QT prolongation and torsade de pointes have been reported with ciprofloxacin during postmarketing surveillance. Additionally, in vitro studies have shown that dasatinib has the potential to prolong the QT interval.
Deflazacort: (Major) Decrease deflazacort dose to one-third of the recommended dosage when coadministered with ciprofloxacin. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort. Deflazacort is a CYP3A4 substrate; ciprofloxacin is a moderate inhibitor of CYP3A4. Also, quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving ciprofloxacin as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance.
Delavirdine: (Moderate) The plasma concentrations of delavirdine may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects is recommended during coadministration. Delavirdine is a CYP3A4 substrate and ciprofloxacin is an inhibitor of CYP3A4.
Desflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with ciprofloxacin. Halogenated anesthetics can prolong the QT interval. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval.
Deutetrabenazine: (Moderate) Use ciprofloxacin with caution in patients receiving other drugs that prolong the QT interval. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dexamethasone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Dextromethorphan; Quinidine: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering quinidine with ciprofloxacin. Quinidine is associated with QT prolongation and TdP. The manufacturer of dextromethorphan; quinidine recommends an ECG in patients taking it in combination with other drugs known to prolong the QTc, such as ciprofloxacin.
Diazepam: (Moderate) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of diazepam and increase the potential for benzodiazepine toxicity. Ciprofloxacin has been shown to decrease the clearance and increase the half-life of diazepam. However, no significant changes were observed in digit symbol substitution psychometric tests, tapping rate and short memory, or concentration, vigilance, and tension.
Diclofenac: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Diclofenac; Misoprostol: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Didanosine, ddI: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after didanosine tablets or powder for oral solution. Ciprofloxacin absorption may be reduced as it can chelate with the buffering agents contained in didanosine tablets and powder. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with ciprofloxacin.
Diflunisal: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with ciprofloxacin may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of ciprofloxacin could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If ciprofloxacin is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Ciprofloxacin is a moderate inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Diltiazem: (Moderate) Caution and monitoring is warranted with the use of ciprofloxacin and diltiazem. Monitor for adverse events such as a decrease in blood pressure or heart rate. Coadministration of ciprofloxacin, a CYP3A4 inhibitor, with diltiazem, a CYP3A4 substrate, may result in elevated diltiazem serum concentrations.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including dipeptidyl peptidase-4 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Diphenhydramine; Ibuprofen: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Diphenhydramine; Naproxen: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Disopyramide: (Major) Both disopyramide and ciprofloxacin are associated with a possible risk for QT prolongation and torsade de pointes (TdP); therefore, caution is advised when administering these medications concurrently.
Disulfiram: (Moderate) The plasma concentrations of disulfiram may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while disulfiram is a CYP3A4 substrate.
Docetaxel: (Moderate) The plasma concentrations of docetaxel may be elevated when administered concurrently with ciprofloxacin. Clinical monitoring for adverse effects, such as myelosuppression and neurologic toxicity, is recommended during coadministration. Ciprofloxacin is a CYP3A4 inhibitor, while docetaxel is a CYP3A4 substrate.
Dofetilide: (Major) Coadministration of dofetilide and ciprofloxacin is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance.
Dolasetron: (Moderate) Administer dolasetron with caution in combination with ciprofloxacin as concurrent use may increase the risk of QT prolongation. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with ciprofloxacin as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance.
Donepezil: (Moderate) Ciprofloxacin should be used with caution in patients receiving donepezil. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during both donepezil and ciprofloxacin therapy.
Donepezil; Memantine: (Moderate) Ciprofloxacin should be used with caution in patients receiving donepezil. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during both donepezil and ciprofloxacin therapy.
Doxorubicin Liposomal: (Major) Avoid coadministration of ciprofloxacin with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Ciprofloxacin is a moderate CYP3A4 inhibitor, and doxorubicin is a major substrate of CYP3A4. Concurrent use of CYP3A4 inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of ciprofloxacin with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Ciprofloxacin is a moderate CYP3A4 inhibitor, and doxorubicin is a major substrate of CYP3A4. Concurrent use of CYP3A4 inhibitors with doxorubicin has resulted in clinically significant interactions.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with ciprofloxacin is necessary, and closely monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP3A4 substrate; ciprofloxacin is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Dronedarone: (Contraindicated) Concurrent use of dronedarone and ciprofloxacin is contraindicated. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. The concomitant use of dronedarone with other drugs that prolong the QTc, such as ciprofloxacin, may induce Torsade de Pointes (TdP) and is contraindicated.
Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as ciprofloxacin. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance. If coadministration cannot be avoided, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect.
Dulaglutide: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including incretin mimetics, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Duloxetine: (Major) Coadministration of duloxetine and potent inhibitors of CYP1A2, such as ciprofloxacin, should be avoided. Duloxetine is partially metabolized by CYP1A2. One study involving a potent CYP1A2 inhibitor in concomitant use with duloxetine showed that duloxetine exposure was significantly increased.
Duvelisib: (Moderate) Monitor for increased toxicity of duvelisib if coadministered with ciprofloxacin. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; ciprofloxacin is a moderate CYP3A inhibitor.
Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with ciprofloxacin as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during post-marketing surveillance.
Efavirenz; Emtricitabine; Tenofovir: (Moderate) Consider alternatives to efavirenz when coadministering with ciprofloxacin as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during post-marketing surveillance.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with ciprofloxacin as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during post-marketing surveillance.
Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with ciprofloxacin may cause the plasma concentrations of elbasvir and grazoprevir to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Ciprofloxacin is a moderate inhibitor of CYP3A; both elbasvir and grazoprevir are metabolized by CYP3A. If these drugs are used together, closely monitor for signs of hepatotoxicity.
Eletriptan: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with ciprofloxacin. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and ciprofloxacin is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor patients closely for tezacaftor; ivacaftor-related adverse reactions if coadministration with ciprofloxacin is necessary. Pharmacokinetic data suggest that no dose adjustment is necessary if tezacaftor; ivacaftor is coadministered with ciprofloxacin. However, because ciprofloxacin is a moderate CYP3A inhibitor, there is a potential for increased tezacaftor; ivacaftor exposure and adverse reactions with concurrent use of ciprofloxacin. Of note, FDA-approved labeling generally recommends tezacaftor; ivacaftor dosage adjustment when coadministered with a moderate CYP3A inhibitor (1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days).
Eliglustat: (Major) Coadministration of eliglustat and ciprofloxacin is contraindicated in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with ciprofloxacin and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with moderate CYP3A inhibitors, such as ciprofloxacin, increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A. Both eliglustat and ciprofloxacin can independently prolong the QT interval, and coadministration increases this risk.
Eltrombopag: (Moderate) Eltrombopag is metabolized by CYP1A2. The significance of administering inhibitors of CYP1A2, such as ciprofloxacin, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
Empagliflozin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including SGLT2 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including dipeptidyl peptidase-4 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including SGLT2 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including dipeptidyl peptidase-4 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including SGLT2 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Empagliflozin; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including SGLT2 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Caution is advised when administering rilpivirine with ciprofloxacin as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance.
Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering rilpivirine with ciprofloxacin as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance.
Enalapril; Felodipine: (Moderate) Concurrent administration of felodipine with ciprofloxacin may result in elevated felodipine plasma concentrations. This increase in felodipine concentration may lead to increased therapeutic and adverse effects, such as lower blood pressure, dizziness, and headache. Felodipine is metabolized by the hepatic isoenzyme CYP3A4; ciprofloxacin is an inhibitor of this enzyme. If coadministration of these drugs is warranted, do so with caution and careful monitoring.
Encorafenib: (Major) Avoid coadministration of encorafenib and ciprofloxacin due to increased encorafenib exposure and QT prolongation. If concurrent use cannot be avoided, reduce the encorafenib dose to one-half of the dose used prior to the addition of ciprofloxacin. Monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. If ciprofloxacin is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of ciprofloxacin. Encorafenib is a CYP3A4 substrate that has been associated with dose-dependent QT prolongation; ciprofloxacin is a moderate CYP3A4 inhibitor that has been associated with rare cases of QT prolongation and torsade de pointes (TdP) during postmarketing surveillance. Coadministration of a moderate CYP3A4 inhibitor with a single 50 mg dose of encorafenib (0.1 times the recommended dose) increased the encorafenib AUC and Cmax by 2-fold and 45%, respectively.
Enflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with ciprofloxacin. Halogenated anesthetics can prolong the QT interval. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval.
Enteral Feedings: (Major) Enteral feedings may decrease the serum concentrations of quinolone antimicrobials. The enteral formulation Ensure significantly decreased the serum concentrations of ciprofloxacin, levofloxacin, and ofloxacin tablets by 83%, 61%, and 46%, respectively, when they were crushed and mixed with 240 ml of Ensure. One study showed that enteral feedings given concurrently with ciprofloxacin via the oral or jejunostomy routes decreased the mean bioavailability of ciprofloxacin by 27 to 67%; however, ciprofloxacin serum concentrations after coadministration with enteral feedings via a gastrostomy tube were similar to concentrations following administration of ciprofloxacin on an empty stomach. Administration of ciprofloxacin and enteral feedings together through a nasogastric (NG) tube decreased the gastrointestinal absorption of ciprofloxacin minimally; MIC values remained high for many pathogenic bacteria. Ciprofloxacin should be taken either 2 hours before or 6 hours after enteral feedings.
Entrectinib: (Major) Avoid coadministration of entrectinib with ciprofloxacin due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If ciprofloxacin is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of ciprofloxacin. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; ciprofloxacin is a moderate CYP3A4 inhibitor that has been associated with rare cases of QT prolongation and torsade de pointes (TdP) during postmarketing surveillance. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Eplerenone: (Major) Do not exceed an eplerenone dose of 25 mg PO once daily if given concurrently with a CYP3A4 inhibitor in a post-myocardial infarction patient with heart failure. In patients with hypertension receiving a concurrent CYP3A4 inhibitor, initiate eplerenone at 25 mg PO once daily; the dose may be increased to a maximum of 25 mg PO twice daily for inadequate blood pressure response. In addition, measure serum creatinine and serum potassium within 3 to 7 days of initiating a CYP3A4 inhibitor and periodically thereafter. Eplerenone is a CYP3A4 substrate. Ciprofloxacin is a CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors increased eplerenone exposure by 100% to 190%. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
Ergotamine; Caffeine: (Moderate) Reduction or limitation of the caffeine dosage in medications and limitation of caffeine in beverages and food may be necessary during concurrent ciprofloxacin therapy. Ciprofloxacin can decrease the clearance of caffeine. Caffeine toxicity may occur and can manifest as nausea, vomiting, anxiety, tachycardia, or seizures. Ciprofloxacin is a CYP1A2 inhibitor and caffeine is a CYP1A2 substrate.
Eribulin: (Major) Concurrent use of eribulin and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Eribulin has been associated with QT prolongation, and ciprofloxacin is associated with a posssible risk for QT prolongation and TdP.
Erlotinib: (Major) Avoid coadministration of erlotinib with ciprofloxacin if possible due to the increased risk of erlotinib-related adverse reactions. If concomitant use is unavoidable and severe reactions occur, reduce the dose of erlotinib by 50 mg decrements. Erlotinib is primarily metabolized by CYP3A4 and to a lesser extent by CYP1A2. Ciprofloxacin is a CYP3A4 and CYP1A2 inhibitor. Coadministration with ciprofloxacin increased erlotinib exposure by 39% and increased the erlotinib Cmax by 17%.
Ertugliflozin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including SGLT2 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Ertugliflozin; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including SGLT2 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including dipeptidyl peptidase-4 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including SGLT2 inhibitors, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Erythromycin: (Major) Concomitant use of ciprofloxacin and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Erythromycin; Sulfisoxazole: (Major) Concomitant use of ciprofloxacin and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Escitalopram: (Moderate) Concomitant use of ciprofloxacin and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Esomeprazole: (Minor) Use caution when administering ciprofloxacin and esomeprazole concurrently. Ciprofloxacin is an inhibitor of CYP3A, and esomeprazole is partially metabolized by CYP3A. Coadministration of ciprofloxacin with CYP3A substrates, such as esomeprazole, can theoretically increase esomeprazole exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
Estazolam: (Moderate) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of estazolam and increase the potential for benzodiazepine toxicity.
Eszopiclone: (Moderate) Patients should be advised of the potential for next-day psychomotor and/or memory impairment during co-administration of eszopiclone and CYP3A4 inhibitors, such as ciprofloxacin. CYP3A4 is a primary metabolic pathway for eszopiclone, and increased systemic exposure to eszopiclone increases the risk of next-day impairment, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Ethosuximide: (Moderate) Close clinical monitoring is advised when administering ethosuximide with ciprofloxacin due to an increased potential for ethosuximide-related adverse events. If ethosuximide dose adjustments are made, re-adjust the dose upon completion of ciprofloxacin treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of ethosuximide. Ethosuximide is metabolized by the hepatic isoenzyme CYP3A4; ciprofloxacin inhibits this isoenzyme. Coadministration may result in elevated ethosuximide plasma concentrations.
Etodolac: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Etonogestrel: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as ciprofloxacin may increase the serum concentration of etonogestrel.
Etonogestrel; Ethinyl Estradiol: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as ciprofloxacin may increase the serum concentration of etonogestrel.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with ciprofloxacin is necessary. The dose of everolimus may need to be reduced. Everolimus is a sensitive CYP3A4 substrate and a P-glycoprotein (P-gp) substrate. Ciprofloxacin is a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4/P-gp inhibitors increased the AUC of everolimus by 3.5 to 4.4-fold.
Exenatide: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including incretin mimetics, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Ezetimibe; Simvastatin: (Moderate) Monitor for evidence of myopathy, including rhabdomyolysis, during coadministration of ciprofloxacin and simvastatin. There are case reports of rhabdomyolysis in patients stabilized on a simvastatin regimen after the addition of ciprofloxacin. Ciprofloxacin may increase simvastatin exposure. Simvastatin is a substrate for CYP3A; ciprofloxacin is a moderate CYP3A inhibitor.
Ezogabine: (Moderate) Use caution when coadministering ezogabine with ciprofloxacin. Ezogabine and ciprofloxacin have both been associated with QT prolongation.
Famotidine; Ibuprofen: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Felodipine: (Moderate) Concurrent administration of felodipine with ciprofloxacin may result in elevated felodipine plasma concentrations. This increase in felodipine concentration may lead to increased therapeutic and adverse effects, such as lower blood pressure, dizziness, and headache. Felodipine is metabolized by the hepatic isoenzyme CYP3A4; ciprofloxacin is an inhibitor of this enzyme. If coadministration of these drugs is warranted, do so with caution and careful monitoring.
Fenoprofen: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. If ciprofloxacin is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If ciprofloxacin is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
Ferric Maltol: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain iron. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
Finerenone: (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or ciprofloxacin; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased overall exposure to finerenone by 248%.
Fingolimod: (Moderate) Cautious use of fingolimod with ciprofloxacin is advised, as ciprofloxacin is associated with a possible risk for QT prolongation and torsade de pointes. Fingolimod initiation results in decreased heart rate and may prolong QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking ciprofloxacin. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
Flecainide: (Major) Concomitant use of ciprofloxacin and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Flibanserin: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as ciprofloxacin, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Fluconazole: (Moderate) Concomitant use of ciprofloxacin and fluconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fludrocortisone: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Fluocinolone; Hydroquinone; Tretinoin: (Major) Avoid the concomitant use of tretinoin with other drugs known to cause photosensitivity, such as ciprofloxacin. Concomitant use with other photosensitizing agents may increase the risk of a photosensitivity reaction.
Fluoxetine: (Moderate) Concomitant use of ciprofloxacin and fluoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluphenazine: (Minor) Both fluphenazine and ciprofloxacin are associated with a possible risk for QT prolongation; therefore, caution is advised when administering these medications concurrently.
Flurazepam: (Moderate) Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of flurazepam and increase the potential for benzodiazepine toxicity.
Flurbiprofen: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Flutamide: (Moderate) Coadministration of ciprofloxacin and flutamide could lead to increases in the serum concentrations of flutamide. Ciprofloxacin has been shown to inhibit CYP1A2 and CYP3A4 and flutamide is a substrate of these enzymes.
Fluvoxamine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and ciprofloxacin. Cases of QT prolongation and TdP have been reported during postmarketing use of both fluvoxamine and ciprofloxacin.
Food: (Major) Do not administer oral ciprofloxacin with dairy products (e.g., milk, yogurt) or calcium-fortified juices alone; however, oral ciprofloxacin may be taken with a meal that contains these products. The absorption of oral ciprofloxacin may be decreased if taken with calcium-containing foods or beverages.
Fosamprenavir: (Minor) Concomitant use of ciprofloxacin and fosamprenavir may result in increased amprenavir, the active metabolite of fosamprenavir, concentrations. Ciprofloxacin is a CYP3A4 inhibitor and amprenavir is a CYP3A4 substrate.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as ciprofloxacin. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Rare cases of QT prolongation and TdP have also been reported with ciprofloxacin during postmarketing surveillance. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment. In addition, use of ciprofloxacin with foscarnet may increase the risk of seizures. Since foscarnet is not metabolized by the liver and since renal dysfunction was not present, it is unlikely that drug accumulation is responsible for seizures. An additive effect is proposed since seizures have been associated with ciprofloxacin and foscarnet independently.
Fosphenytoin: (Moderate) Use ciprofloxacin and fosphenytoin together with caution as ciprofloxacin has been reported to both increase and decrease phenytoin concentrations. Monitor phenytoin serum concentrations and response to therapy during and shorty after coadministration to avoid the loss of seizure control associated with decreased phenytoin levels and to prevent overdose-related adverse events upon the discontinuation of ciprofloxacin.
Fostemsavir: (Moderate) Use ciprofloxacin and fostemsavir together with caution due to the potential for QT prolongation. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and ciprofloxacin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance.
Gilteritinib: (Moderate) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and ciprofloxacin is necessary. Gilteritinib has been associated with QT prolongation. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance.
Glasdegib: (Major) Avoid coadministration of glasdegib with ciprofloxacin due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance.
Glimepiride: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including sulfonylureas, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Glimepiride; Rosiglitazone: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including sulfonylureas, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including thiazolidinediones, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Glipizide: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including sulfonylureas, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Glipizide; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including sulfonylureas, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Glyburide: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including sulfonylureas, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Glyburide; Metformin: (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including metformin, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur. (Moderate) Monitor blood glucose carefully when systemic quinolones and antidiabetic agents, including sulfonylureas, are coadministered. Discontinue the quinolone if a hypoglycemic reaction occurs and initiate appropriate therapy immediately. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Hypoglycemia, sometimes resulting in coma, can occur.
Goserelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving ciprofloxacin. Androgen deprivation therapy may prolong the QT/QTc interval. Rare cases of QT prolongation and torsade de pointes (TdP) have also been reported with ciprofloxacin during postmarketing surveillance.
Granisetron: (Moderate) Use granisetron with caution in combination with ciprofloxacin due to the risk of QT prolongation. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance. Granisetron has been associated with QT prolongation.
Green Tea: (Moderate) Some, but not all, green tea products contain caffeine. Ciprofloxacin can inhibit the hepatic clearance of caffeine and theobromine which are commonly found in coffee and tea. Caffeine toxicity can result and can manifest as nausea/vomiting, nervousness, anxiety, tachycardia, or seizures.
Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Guanfacine: (Major) Ciprofloxacin may significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends decreasing the guanfacine dosage to half the recommended dose if these agents are taken together. Specific recommendations for immediate-release (IR) guanfacine are not available. Monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia. Upon ciprofloxacin discontinuation, the guanfacine ER dosage should be increased back to the recommended dose. Guanfacine is primarily metabolized by CYP3A4, and ciprofloxacin is a moderate CYP3A4 inhibitor.
Halobetasol; Tazarotene: (Moderate) Use tazarotene with caution in patients who are also taking drugs known to be photosensitizers, such as ciprofloxacin, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Halofantrine: (Major) Quinolones have been associated with QT prolongation and in rare cases, torsades de pointes. Of the quinolones, ciprofloxacin has the least potential for causing QT prolongation at usual dosages. Halofantrine has the potential to prolong the QT interval and should be used in caution when administered with ciprofloxacin.
Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with ciprofloxacin. Halogenated anesthetics can prolong the QT interval. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval.
Haloperidol: (Moderate) Caution is advisable when combining haloperidol concurrently with ciprofloxacin as concurrent use may increase the risk of QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance.
Halothane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with ciprofloxacin. Halogenated anesthetics can prolong the QT interval. Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval.
Hetastarch; Dextrose; Electrolytes: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium. (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain magnesium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving ciprofloxacin. Androgen deprivation therapy may prolong the QT/QTc interval. Rare cases of QT prolongation and torsade de pointes (TdP) have also been reported with ciprofloxacin during postmarketing surveillance.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing.
Hydrocodone; Phenylephrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ciprofloxacin is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ciprofloxacin can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ciprofloxacin is discontinued, hydrocodone plasma concentrations will decrease resulting in reduc