خواص دارویی و گیاهی
A total of 538 drugs are known to interact with ciprofloxacin.
Show all medications in the database that may interact with ciprofloxacin.
Type in a drug name to check for interactions with ciprofloxacin.
View interaction reports for ciprofloxacin and the medicines listed below.
There are 3 alcohol/food interactions with ciprofloxacin
ciprofloxacin 500 mg drug interactions
There are 10 disease interactions with ciprofloxacin which include:
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Medical Disclaimer
Some mixtures of medications can lead to serious and even fatal consequences.
Here are 9 ways to stay safe
prednisone, amoxicillin, doxycycline, albuterol, ranitidine, metronidazole, clindamycin, cephalexin, Augmentin, azithromycin
Ciprofloxacin reviews
The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. Available for Android and iOS devices.
Subscribe to Drugs.com newsletters for the latest medication news, alerts, new drug approvals and more.
Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Data sources include IBM Watson Micromedex (updated 1 Aug 2019), Cerner Multum™ (updated 1 Aug 2019), Wolters Kluwer™ (updated 31 July 2019) and others.
Third Party Advertising
We comply with the HONcode standard for trustworthy health information – verify here
Copyright © 2000-2019 Drugs.com. All rights reserved.
Ciprofloxacin is the generic form of the brand-name antibiotic Cipro.
Doctors prescribe ciprofloxacin to treat or prevent infections caused by various bacteria that are sensitive to ciprofloxacin.
The drug works by preventing bacteria from reproducing. Ciprofloxacin belongs to a family of antibiotics called fluoroquinolones.
The Food and Drug Administration (FDA) approved ciprofloxacin in 1987 for Bayer Healthcare under the brand name Cipro.
ciprofloxacin 500 mg drug interactions
In 2004, the FDA approved generic ciprofloxacin for several drug manufacturers.
Today, companies also sell ciprofloxacin under the brand names Cipro XR Extended-Release Tablets and Proquin XR Extended-Release Tablets.
Doctors prescribe ciprofloxacin to treat infections caused by many different species of bacteria, including:
Common infections treated with ciprofloxacin include:
Ciprofloxacin won’t work against infections caused by viruses (such as colds and the flu), so your doctor will prescribe ciprofloxacin only if it’s very likely that you have a bacterial infection.
That’s because using antibiotics like ciprofloxacin against viruses or other illnesses they can’t treat increases the chance that in time they will no longer work against bacterial infections either.
Known as drug resistance, this growing worldwide threat develops because bacteria can adapt, making antibiotics less effective or not effective at all.
These multi-drug-resistant bacteria, or “superbugs,” can spread through direct contact, or indirectly in food or water.
In 2014, the Centers for Disease Control and Prevention (CDC) reported that a surge in gonorrhea rates in 17 American cities between 1991 and 2006 might have been due to ciprofloxacin resistance.
The CDC noted that roughly 820,000 gonorrhea cases develop in the United States each year and that antibiotic-resistant bacteria could affect treatment and control efforts for this sexually transmitted infection.
Ciprofloxacin may increase the risk for swelling and tearing of tendons, such as those that attach muscles to bones in the hands, shoulders, and ankles.
The likelihood of tendon damage is greater if you also take a steroid medication or if you’re older than 60. If you experience pain, swelling, or stiffness while taking ciprofloxacin, let your doctor know.
In some people, ciprofloxacin may cause changes in brain activity. This affects people with a history of seizures.
Possible symptoms of these changes include dizziness, hallucinations, tremors, seizures, confusion, depression, and suicidal thoughts.
If you have any of these symptoms while on ciprofloxacin, let your doctor know right away.
Ciprofloxacin may cause a severe reaction called anaphylaxis if you are allergic to it.
This allergic reaction, which can be life-threatening, may include hives, swelling of the throat, and difficulty breathing.
It’s important to know that once you start a course of ciprofloxacin, you should finish the whole course.
Do not stop taking ciprofloxacin, even if you feel better, until all of the medication is gone.
If you don’t take an antibiotic long enough, your infection can come back stronger. And stopping ciprofloxacin too soon can lead to bacteria becoming resistant to it.
You may not be able to take ciprofloxacin if you have a condition called myasthenia gravis. Ciprofloxacin may increase muscle weakness caused by this condition.
You should also take ciprofloxacin with caution if you have certain conditions. Tell your doctor if you have:
Before taking ciprofloxacin, women should let their doctor know if they are or may be pregnant or if they’re breastfeeding.
It’s unknown whether ciprofloxacin is safe to take during pregnancy.
Experts do know that ciprofloxacin passes through breast milk, so it is not safe to take if you are breastfeeding.
Except for children with a few specific and serious infections, no one younger than 18 should take ciprofloxacin.
The most common side effects of ciprofloxacin are nausea, diarrhea, vomiting, and rash. Let your doctor know if you have any side effects.
Less common side effects include:
Serious side effects can also occur. If you have any of these side effects, stop taking ciprofloxacin and call your doctor right away or call 911:
Some drugs may affect the way ciprofloxacin works, and ciprofloxacin may affect other drugs you are taking.
It’s very important to let your doctor know about all drugs you take, including over-the-counter (OTC) antacids, vitamins, and supplements.
Many antacids, vitamins, and supplements that contain magnesium, calcium, aluminum, iron, or zinc can interfere with ciprofloxacin.
Other OTC drugs, including such pain and fever medications as Advil, Aleve, and Motrin, may also interact with ciprofloxacin.
Ciprofloxacin may increase the effects of caffeine.
If you drink caffeinated drinks or take OTC medications that contain caffeine while taking ciprofloxacin, you may have some caffeine side effects such as nervousness, sleeplessness, or anxiety.
ciprofloxacin 500 mg drug interactions
You may not be able to take ciprofloxacin if you are also taking the drug theophylline to treat asthma and wheezing (brand names include Elixophyllin, Uniphyl, and Theo-24).
Serious reactions, including heart attack, decreased ability to breathe, and seizures, have happened when people took these medications together.
Other medications that interact with ciprofloxacin include:
Ciprofloxacin can cause drowsiness and confusion. Don’t drive or participate in any dangerous activities until you know how ciprofloxacin affects you.
Ciprofloxacin can make your skin more sensitive to sun exposure.
Don’t use a tanning bed, and avoid long exposure to sunlight while taking it. Protect your skin in the sun with clothing or sunscreen.
You can take ciprofloxacin with or without food.
Don’t take ciprofloxacin with only dairy products or with only calcium-fortified juice because calcium can interfere with absorption of ciprofloxacin.
You can, however, take ciprofloxacin with a meal that includes dairy or calcium-fortified juice.
Your dose of ciprofloxacin will depend on the type of bacterial infection you have.
Ciprofloxacin comes in regular and extended-release tablets and as a liquid.
Take regular tablets or the liquid twice a day (morning and evening) at about the same time each day, and take extended-release tablets once a day.
Swallow all tablets whole. Don’t crush, split, or chew them.
Regular tablets come in 250, 500, and 750 milligrams (mg).
Some typical doses for common infections using regular tablets include:
A large overdose of ciprofloxacin could cause kidney damage.
In animal studies, very large doses of ciprofloxacin have caused reduced breathing, vomiting, and seizures.
If an overdose occurs, call a poison control center at 1-800-222-1222.
If you or someone else has any severe symptoms after an overdose, call 9-1-1.
Take ciprofloxacin exactly as directed by your doctor.
Don’t stop taking ciprofloxacin on your own. Skipping doses or stopping too soon can result in a more severe infection that is harder to treat.
If you miss a dose of ciprofloxacin, take the missed dose as soon as you remember.
If it’s almost time for your next regular dose, however, skip the missed dose.
Don’t double your dose to make up for the missed one.
By Chris Iliades, MD | Medically Reviewed by Farrokh Sohrabi, MD
Latest Update: 2014-07-30 Copyright © 2014 Everyday Health Media, LLC
Drugs A-Z provides drug information from Everyday Health and our partners, as well as ratings from our members, all in one place. Cerner Multum™ provides the data within some of the Basics, Side Effects, Interactions, and Dosage tabs. The information within the Reviews and FAQ tabs is proprietary to Everyday Health.
You can browse Drugs A-Z for a specific prescription or over-the-counter drug or look up drugs based on your specific condition. This information is for educational purposes only, and not meant to provide medical advice, treatment, or diagnosis. Remember to always consult your physician or health care provider before starting, stopping, or altering a treatment or health care regimen.
Every effort has been made to ensure that the information provided by on this page is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. The information on this page has been compiled for use by healthcare practitioners and consumers in the United States and therefore neither Everyday Health or its licensor warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Neither Everyday Health nor its licensors endorse drugs, diagnose patients or recommend therapy. The drug information above is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. Neither Everyday Health nor its licensor assume any responsibility for any aspect of healthcare administered with the aid of the information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have any questions about the drugs you are taking, check with your doctor, nurse or pharmacist.
1Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, MC 0603, La Jolla, CA 92093-0603, USA
2California Department of State Hospitals (DSH), Psychopharmacology Resource Network, 3102 East Highland Avenue, Patton, CA 92369, USA
2California Department of State Hospitals (DSH), Psychopharmacology Resource Network, 3102 East Highland Avenue, Patton, CA 92369, USA
2California Department of State Hospitals (DSH), Psychopharmacology Resource Network, 3102 East Highland Avenue, Patton, CA 92369, USA
3California Department of State Hospitals (DSH), Clinical Operations Advisory Council, Bateson Building, 1600 9th Street, Room 400, Sacramento, CA 95814, USA
ciprofloxacin 500 mg drug interactions
1Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, MC 0603, La Jolla, CA 92093-0603, USA
4California Department of State Hospitals (DSH), Director of Psychopharmacology Services, Bateson Building, 1600 9th Street, Room 400, Sacramento, CA 95814, USA
Objective. Clozapine provides a 50%–60% response rate in refractory schizophrenia but has a narrow therapeutic index and is susceptible to pharmacokinetic interactions, particularly with strong inhibitors or inducers of cytochrome P450 (CYP) 1A2. Case Report. We report the case of a 28-year-old nonsmoking female with intellectual disability who was maintained for 3 years on clozapine 100 mg orally twice daily. The patient was treated for presumptive urinary tract infection with ciprofloxacin 500 mg orally twice daily and two days later collapsed and died despite resuscitation efforts. The postmortem femoral clozapine plasma level was dramatically elevated at 2900 ng/mL, and the cause of death was listed as acute clozapine toxicity. Conclusion. Given the potentially fatal pharmacokinetic interaction between clozapine and ciprofloxacin, clinicians are advised to monitor baseline clozapine levels prior to adding strong CYP450 1A2 inhibitors, reduce the clozapine dose by at least two-thirds if adding a 1A2 inhibitor such as ciprofloxacin, check subsequent steady state clozapine levels, and adjust the clozapine dose to maintain levels close to those obtained at baseline.
Clozapine remains the antipsychotic of choice for patients with treatment refractory schizophrenia and for schizophrenia patients with a history of suicidality, but it does require an attentive clinician to oversee treatment due to certain common side effects (e.g., constipation, sialorrhea, orthostasis, metabolic adverse effects, and sedation) and a small number of rare but serious issues (neutropenia, seizures, myocarditis, and cardiomyopathy) [1]. Despite the burden of adverse effects and administrative issues related to ongoing hematological monitoring, no other antipsychotic approaches clozapine’s 50%–60% response rate in refractory schizophrenia using the standard definition elaborated by Kane and colleagues [1]. For typical antipsychotics, the response rate in Kane-defined refractory schizophrenia is 0%, and for olanzapine 0%–9% [2–4]. Among patients who fail olanzapine treatment, the clozapine response rate is at least 41% [5].
One contributing factor to tolerability issues is clozapine’s narrow therapeutic index and its susceptibility to kinetic interactions with medications [6] or environmental exposures such as smoking [7]. To improve the likelihood of response and to avoid unnecessary toxicity, clozapine plasma level monitoring is commonly performed. General consensus recommendations indicate that the response threshold is approximately 350 ng/mL, with few patients tolerating plasma levels above 1000 ng/mL [8]. An audit of 104,127 samples collected over 7 years from 26,796 patients noted that 42.5% of specimens had levels < 350 ng/mL, 49.2% were 350–999 ng/mL, and only 8.4% were 1000 ng/mL or greater [9]. Clozapine's phase 1 metabolism occurs via multiple cytochrome P450 (CYP) enzymes including CYP 1A2, CYP 2D6, and to a lesser extent CYP 2C9 and CYP 3A4. As CYP 1A2 remains the primary pathway in most patients, a significant body of literature has accrued on the interaction with strong 1A2 inhibitor fluvoxamine starting in 1998 [10, 11]. It should be noted that fluvoxamine is also a strong inhibitor of 2C19 and a weak inhibitor of 2C8, 2C9, and 3A4, and this combination of activities is reported to increase clozapine levels 3- to 10-fold [12, 13]. Although ciprofloxacin is also a strong 1A2 inhibitor and has been in routine use for over 25 years [14], there is a paucity of information about the potential seriousness of its interaction with clozapine. Presented here is a case report in which use of ciprofloxacin in a patient on stable clozapine doses was associated with a fatal outcome.
Ms. X was an obese 28-year-old community dwelling nonsmoking white female (weight 81.8 kg, BMI 39 kg/m2) with severe intellectual disability and a history of behavioral disturbances consistent with schizophrenia. After failed prior trials of other antipsychotics, she had been maintained for 3 years (2009–2012) on the combination of clozapine dissolving tablets 100 mg BID, bupropion XL 150 mg qam, escitalopram 10 mg qam, N-acetylcysteine 1200 mg BID, and memantine 10 mg BID. She was also treated with L-thyroxine for hypothyroidism, famotidine for gastroesophageal reflux, fish oil and aspirin for dyslipidemia, and fluticasone and levocetirizine for seasonal allergies. Three days before her death, she was seen in the emergency room after experiencing two episodes within the same day of feeling faint without obvious precipitants. These symptoms were noted by the house staff who initially thought the patient may have been hypoglycemic due to missing breakfast, but who subsequently brought the patient to the hospital after the 2nd event. As the patient had limited verbal abilities, the staff reported that there had been no changes in her administered medications or other habits. The vital signs showed the patient to be afebrile and normotensive, with heart rate 124/min, respiratory rate 18/min, and normal oxygen saturation. The physical examination was remarkable only for tachycardia and tachypnea without evidence of respiratory distress or use of accessory muscles. The patient was not cooperative with laboratory or radiographic evaluation and was discharged home with a recommendation of lorazepam 1 mg orally every 6 hours as needed for anxiety.
The following noon the patient appeared to be at baseline and cooperated with the trip to an outpatient laboratory which found the following abnormalities: elevated total white blood cell count of 14.7 with 84.1% neutrophils, nonfasting glucose 179 mg/dL, creatinine of 1.5 mg/dL, and CO2 of 16 mmol/L. Other electrolytes, serum calcium, liver function tests, and serum osmolality were normal. Urinalysis revealed trace bacteria with 3-4 WBC per high power field. A presumptive diagnosis of urinary tract infection was made, and the patient’s primary care provider started her on ciprofloxacin 500 mg BID that evening. Two days later the patient collapsed at approximately 10:00 pm. Emergency services were called, cardiopulmonary resuscitation started immediately, and resuscitation efforts continued during the ambulance trip and in the emergency room until the patient was pronounced dead at 11:00 pm. A postmortem examination conducted the following morning at 9:14 a.m. found no evidence of major organ pathology with normal weight and appearance for heart, liver, kidneys, and lungs. A clozapine level obtained femorally was 2900 ng/mL (reported as 2.9 mcg/mL) and that obtained hepatically was 24,300 ng/mL (reported as 24.3 mcg/mL). The cause of death was listed as acute drug (clozapine) toxicity.
Ciprofloxacin is a fluoroquinolone antibiotic whose broad spectrum of activity was noted in the early 1980s [22]. By 1987, kinetic interactions between ciprofloxacin and other medications, particularly theophylline, were well documented and presumed to be based on inhibition of metabolism by the responsible cytochrome P450 enzyme [23], later characterized in 1992 as CYP 1A2 [14]. For most of the 1990s, the primary CYP pathways for clozapine’s phase 1 metabolism were unclear, and the CLOZARIL® package insert (PI) for 1997 states that systematic kinetic interaction studies were lacking (Table 1). Language in the 1997 PI focuses on protein binding, CYP 2D6 polymorphisms and interactions; no other isoenzymes are named. The August 2001 PI reflects advancing knowledge in this area and not only mentions CYP 1A2, 2D6, and 3A4 but also discusses a 14-day interaction study with fluvoxamine in which plasma concentrations of clozapine + metabolites increased 3-fold. During this same time frame, the first reports of interactions between clozapine and ciprofloxacin were published by Markowitz et al. in 1997 [15], Raaska and Neuvonen in 2000 [16], and Gex-Fabry et al. in 2001 [17] (Table 3). While the first two publications involved low doses of either clozapine or ciprofloxacin, the case description by Gex-Fabry et al. revealed the potential for a serious kinetic interaction, with clozapine levels increasing by a factor of 3.4 to 1218 ng/mL and a significant shift in the clozapine to N-desmethylclozapine (DMC) ratio from 1.82 to 3.33 [17]. This potential interaction with ciprofloxacin was formally acknowledged by the US Food and Drug Administration (FDA) in 2005 and is reflected in a change in PI wording for CLOZARIL in December 2005 (Table 1). This interaction was also acknowledged more broadly in the medical literature, with reviews in 2006 and 2007 commenting on the fact that ciprofloxacin ranked among the most potent CYP 1A2 inhibitors, thus placing clozapine treated patients at risk for adverse effects when combined with ciprofloxacin [6, 24]. Given the limited number of publications involving comedication with ciprofloxacin, none of these reviews raised the risk of fatality nor offered any new data beyond that in the 3 earlier case reports. Three subsequent case reports by Sambhi et al. in 2007 [18], Brownlowe and Sola in 2008 [19], and Brouwers et al. in 2009 [20] documented that a kinetic interaction between these two medications could lead to levels that potentially might be fatal, although no fatalities occurred. Starting in July 2013, the United States entered the era of structured PIs with FDA mandated language regarding the strength of inhibitors and inducers (Table 4). The revised clozapine PI (Table 1) now contained specific language on dosage modifications when adding or removing strong 1A2 inhibitors, thus incorporating knowledge about fluvoxamine and ciprofloxacin that had been in the literature for over 10 years.
Sequential changes in CLOZARIL package insert warnings about pharmacokinetic interactions with ciprofloxacin.
Source: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ ApprovalHistory#apphist
accessed 07/01/2016.
Published reports of ciprofloxacin-clozapine interaction.
DMC: N-desmethylclozapine; CK: creatine kinase; UTI: urinary tract infection.
US FDA classification of in vivo cytochrome P450 inhibitors by impact on area under the curve (AUC) and clearance [21].
While the peripheral and central postmortem clozapine levels in this case were extraordinarily high and consistent with a fatal outcome, there are two factors that must be considered: (a) this patient had a complex clinical picture and was receiving many medications; (b) postmortem redistribution effects must be accounted for to assess the true nature of ciprofloxacin’s effect. Although methods for measuring clozapine and its metabolite N-desmethylclozapine (DMC) in whole blood and tissue were available by 1993 [25], the extent of postmortem redistribution of newer lipophilic antipsychotics was not recognized until 1998 with the publication of an olanzapine case report showing significantly higher cardiac and biliary levels than those from the gastric specimen [26]. The first report discussing postmortem redistribution of clozapine occurred in 2003, and the authors cast doubt on the validity of the intracardiac clozapine blood level 4500 ng/mL in a patient on a stable clozapine dose of 350 mg/d who had refused her clozapine for 24 hours before death [27]. Flanagan et al.’s paper later that year using porcine data [28] and subsequent publications from human cases outlined considerations in interpreting postmortem levels in clozapine-related deaths [29, 30] (see the following list of Flanagan’s criteria). While central postmortem clozapine levels are unreliable and differ by 10-fold or more from peripheral values, even under ideal circumstances, samples obtained from femoral veins may rise as much as 1.5-fold after death [31].
Flanagan’s List of Issue to Address When Investigating Clozapine-Related Death [30]
Is there circumstantial or pathological evidence of self-poisoning?
Is there evidence of prior recent exposure to clozapine (i.e., is the patient likely to have been tolerant of the hypotensive effects of the drug?)
Was blood collected postmortem by venipuncture from a peripheral vein before opening the body?
Was the patient prescribed any other drugs and were other drugs looked for on toxicological analysis?
What was the clozapine dose and dosage regimen?
Were tablets or suspension dispensed?
Did smoking habit or clozapine dosage change recently?
Was there a history of substance abuse?
Was the blood norclozapine level measured?
Are antemortem plasma or whole blood clozapine/norclozapine results available?
Was histology performed, especially heart and liver?
Was there evidence of pneumonia?
Was there clinical or postmortem evidence of vomiting, aspiration of vomit, or other GI tract problem?
As the death in this case occurred in hospital and the autopsy was performed within 10 hours, the extent of postmortem redistribution is greatly minimized using the criteria set forth by Flanagan (see the prior list of Flanagan’s criteria). Nonetheless, the fact that hepatic clozapine levels were 8-fold higher than femoral levels reflects how quickly this process can occur. Using the worst case estimate that the femoral levels may have increased up to 50% since the time of death [31], we arrive at an antemortem plasma clozapine level of 1933 ng/mL at the minimum. Since this patient did not control her own medication supply, had no history of medication hoarding, and was adherent with medications, the high plasma level is certainly the product of the interaction between clozapine and the strong CYP1A2 inhibitor ciprofloxacin started two days previously.
The one unknown is to what extent ciprofloxacin increased this patient’s plasma clozapine levels. There is no record of outpatient clozapine levels obtained in the year prior to this incident, so one must infer from the clinical information an estimated level based on the dose, age, gender, weight, and status as a nonsmoker, with the added interaction from the CYP 2D6 inhibitor bupropion. The clozapine plasma level equation derived by Rostami-Hodjegan and colleagues from 4963 specimens permit calculation of an estimated plasma clozapine level with only one assumption: that this nonsmoking patient is a CYP 1A2 extensive metabolizer [32]. Using their equation, the estimated clozapine level without the bupropion interaction is 262 ng/mL. While CYP 2D6 is a minor phase 1 metabolic pathway for clozapine, strong 2D6 inhibitors increase plasma clozapine levels 40%–70% [13], with one case report of paroxetine increasing clozapine levels 100% in a patient whose baseline clozapine level was in the range of 666 ng/mL–684 ng/mL [33]. When that patient’s clozapine dose was halved, paroxetine increased clozapine levels approximately 30% [33]. As this patient’s estimated plasma clozapine level is <300 ng/mL, a 100% increase from bupropion is unlikely, but if we use the high value of 70% obtained from case reports with strong 2D6 inhibitors, the estimated baseline clozapine level for this patient prior to ciprofloxacin exposure was 445 ng/mL. The exposure to ciprofloxacin is thus estimated to have increased this patient's clozapine levels 4.5-fold at the minimum, resulting in the patient's demise; moreover, the extent of this interaction is consistent with that reported for fluvoxamine. Unfortunately, the absence of antemortem levels necessitates speculation, but the prior use of bupropion combined with the later exposure to ciprofloxacin both emerge as important factors to consider in this outcome.
Although the possibility of an interaction between clozapine and ciprofloxacin has been documented in the literature since 1997 and language in the clozapine PI has existed since 2005, the potential for a fatal outcome has not been previously reported. Clinicians prescribing medications with narrow therapeutic indices must be mindful of potentially important kinetic interactions and have a reliable resource to identify kinetic data when adding agents to high-risk medications. Should newer medications be developed that are strong CYP 1A2 inhibitors, the message from this case should be heeded: (a) baseline plasma clozapine levels must be obtained prior to adding the strong CYP 1A2 inhibitor; (b) the clozapine dose reduced by at least two-thirds (and further if the patient complains of adverse effects); (c) clozapine plasma levels must be rechecked after steady state is reached with the new medication and the clozapine dose adjusted accordingly. In patients with cognitive dysfunction or more severe intellectual disabilities, avoidance of this interaction completely appears prudent, as the patient may not be able to express their physical discomfort, potentially resulting in a serious or fatal outcome.
US July 2013 CLOZARIL package insert table on dose adjustment in patients taking concomitant strong CYP 1A2 inhibitors.
Drs. Cummings, Dardashti, and Proctor have nothing to disclose. Dr. Meyer reports having received speaking or advising fees from Acadia, Alkermes, Forum, Merck, Otsuka-USA, and Sunovion. Dr. Stahl reports having received advising fees, consulting fees, speaking fees, and/or research grants from Acadia, Alkermes, Biomarin, Clintara, Eli-Lilly, EnVivo, Forest, Forum, GenoMind, JayMac, Jazz, Lundbeck, Merck, Novartis, Orexigen, Otsuka-USA, PamLabs, Pfizer, RCT Logic, Servier, Shire, Sprout, Sunovion, Sunovion-UK, Taisho, Takeda, Teva, Tonix, and Trius.
The authors declare that there are no competing interests regarding the publication of this paper.
ciprofloxacin 500 mg drug interactions
National Center for
Biotechnology Information,
U.S. National Library of Medicine
8600 Rockville Pike, Bethesda
MD, 20894
USA
The cytochrome P450 (CYP450) system comprises more than 40 individual enzymes that have been identified in humans. Six major CYP450 isoenzymes are responsible for more than 90% of oxidation of drugs in humans: 1A2, 3A4, 2C9, 2C19, 2D6, and 2E1.1 Methadone is metabolized by several CYP450 isoenzymes (1A2, 3A4, 2B6, 2C8, 2C9, 2C19, and 2D6) to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), an inactive metabolite.2–4 CYP3A4 is considered the primary isoenzyme responsible for metabolism, followed by CYP2D6.2
Various drugs may inhibit the CYP450 system. Among the quinolone antibiotics, ciprofloxacin has been demonstrated in vitro to be one of the more potent of these inhibitors,5 affecting in particular CYP1A2 and CYP3A4.5,6 However, the clinical response is sometimes difficult to predict, and the significance of the interaction differs among patients.
This report describes a patient who was receiving a stable dose of methadone for treatment of heroin addiction and in whom severe respiratory depression developed after initiation of ciprofloxacin for aspiration pneumonia.
A man in his mid-50s* presented to hospital with fracture of the left ankle after the bicycle he was riding was struck by a car. His blood pressure was 170/90 mm Hg, heart rate 75/min, and respiratory rate 18/min. The patient had a history of hepatitis A, and both alkaline phosphatase (134 U/L; normal range 45–125 U/L) and γ-glutamyl transferase (594 U/L; normal range 10–50 U/L) were elevated. He was a smoker (3–4 packs/day) and had previously been an injection drug user (heroin and cocaine), for which methadone 50 mg PO once daily had been prescribed for at least 6 months before the current admission. He denied use of any other medication.
After undergoing open reduction and internal fixation of the left ankle on the day of admission, the patient was admitted to the orthopedic unit and continued to receive methadone 50 mg PO once daily. His other medications included dalteparin 5000 units SC daily, thiamine 100 mg PO daily, folic acid 5 mg PO daily, and methotrimeprazine 10–15 mg PO at bedtime as needed (of which 4 doses had been received before the event described below). For pain, he was receiving morphine 5–10 mg PO or SC q3h as needed (of which 9 doses PO and 2 doses SC had been received before the event), morphine 2 mg IV q1h prn (of which 4 doses had been received before the event), and acetaminophen 325 mg with codeine 30 mg 1 or 2 tablets q4h PO prn (of which 3 doses of 2 tablets each had been received before the event).
ciprofloxacin 500 mg drug interactions
Three days after the surgery, the patient reported shortness of breath. Cefuroxime 750 mg IV q8h was started for presumed pneumonia, along with aggressive bronchodilation with nebulized salbutamol and ipratropium. The patient was transferred to the intensive care unit for close observation of hypoxic respiratory failure. At the time, oxygen saturation was 88% on 95% oxygen, and the respiratory rate was 16/min. The patient’s fever spiked to 39.1°C, and he had symptoms of yellow sputum and crackles. The white blood cell count was normal, at 6.4 × 109/L (normal range 4 × 109/L to 11 × 109/L). Chest radiography showed atelectasis, consolidation in the lower left lobe, and bilateral pleural effusion. Aspiration pneumonia was diagnosed, and the patient was transferred back to the orthopedic unit later the same day.
Two days later, there was little improvement, and a consultant respirologist recommended that antibiotic coverage be broadened. Cefuroxime was discontinued, and ciprofloxacin 400 mg IV q12h and clindamycin 600 mg IV q8h were initiated. After 2 doses of each drug, the patient became extremely drowsy, pinpoint pupils were observed, and respiratory depression occurred (respiratory rate 8/min). He was given 2 IV bolus doses of naloxone 0.4 mg, with no significant improvement; the respiratory rate remained at 6–10/min. Methadone, ciprofloxacin, and clindamycin were discontinued, and a 24-h naloxone infusion (0.4 mg/h) was initiated. One hour after the infusion was started, the patient’s respiratory rate normalized to 18/min. Twenty-four hours later, the respiratory rate had increased to 20/min. The patient continued to receive morphine as needed for pain (with 3 doses being received during naloxone infusion), with no further adverse reaction. The antibiotic therapy was switched to ticarcillin–clavulanate 3.1 g IV q6h. Methadone was restarted 4 days later at 25 mg PO daily (half the original dose). Methotrimeprazine was withheld for 3 nights while the methadone was being held because of the patient’s decreased level of consciousness, but it was resumed on the night before re-initiation of methadone and was continued nightly until discharge 5 days later. The patient was discharged on oral amoxicillin–clavulanate 500/125 mg q8h and methadone 25 mg PO daily.
Many drug interactions can be traced to the CYPP450 system. However, clinically significant adverse reactions generally occur with drugs having a low therapeutic index (for which there is little difference between effective and toxic concentrations) or drugs with severe adverse effects.7
In the case reported here, it was suspected that the patient was experiencing methadone toxicity due to an interaction with ciprofloxacin, whereby the metabolism of methadone by the CYP3A4 and CYP1A2 isoenzymes was inhibited. This interaction resulted in a life-threatening adverse event. It is difficult to predict the potential for drug interactions with methadone because of its wide interpatient pharmacokinetic variability. The elimination half-life ranges between 15 and 60 h, depending largely upon genetically determined variability in the activity of the CYP450 isoenzymes.2,4 As well, because of its basic and lipophilic properties, methadone is widely distributed into the tissues; its slow release from tissue-binding sites may prolong its presence in the serum, allowing cumulative effects to occur. After repeated dosing of methadone, the elimination half-life can increase to as long as 120 h.2
The clinical significance of a patient’s response to a drug interaction with the CYP450 isoenzyme system depends on genetic variability, concomitant therapy, concurrent medical conditions, alcohol consumption, smoking, obesity, and liver function.1 CYP3A4 is the most abundant CYP450 isoenzyme in the body, accounting for the majority of drug interactions. This isoenzyme can vary 30-fold between individuals in terms of its concentration and activity in the liver.4 Thus, interindividual variability can be significant even in the absence of interacting substances. Furthermore, methadone’s low affinity for CYP3A4 suggests that this metabolic pathway is easily inhibited. Inhibitors of this isoenzyme (e.g., ketoconazole, diazepam) can inhibit the formation of EDDP by up to 80%.2 This patient’s history of liver disease, as suggested by the history of hepatitis A and elevation of liver enzymes, may have further aggravated the toxic effects of methadone resulting from inhibition of CYP3A4 by ciprofloxacin, as other pathways for its elimination may have been diminished.
In addition, cessation of smoking during the hospital stay may have diminished the activity of CYP1A2, which would otherwise be induced by smoking.4 As such, inhibition of CYP1A2 by ciprofloxacin might have had a greater impact in this patient than would have been the case for a nonsmoker.8
CYP2D6 has a secondary role in methadone metabolism and can significantly lower methadone clearance, especially in patients with poor CYP2D6 metabolism.2 CYP2D6 can also be deficient in a small fraction of the population, which would increase sensitivity to the effects of methadone.4 The patient described here was receiving a low dose of methotrimeprazine, a strong inhibitor of CYP2D6.9 However, it was not until after ciprofloxacin was added to the patient’s drug regimen that the respiratory depressant effects of the methadone became apparent. Although the low dose of methotrimeprazine was unlikely to have caused the severe respiratory depression, this drug in combination with ciprofloxacin may have further inhibited the metabolism of methadone. After the ciprofloxacin was discontinued and the methadone was resumed, 5 doses of methotrimeprazine were given with no untoward effects.
Other factors that may have contributed to the respiratory depression include the other opioid narcotics that the patient received postoperatively and his underlying aspiration pneumonia. Clindamycin, the antibiotic that was used in conjunction with ciprofloxacin to treat the pneumonia, may have also contributed to the respiratory depression through inhibition of neuromuscular transmission or direct inhibition of contractility.10 Case reports have shown that clindamycin-induced neuromuscular blockade and potentiation of local anesthetic effect can ultimately lead to respiratory depression.10,11 However, the patient’s response to naloxone in the current case suggests an adverse effect of an opioid, rather than neuromuscular blockade, as the cause of respiratory depression.
Two published case reports have described an interaction between methadone and ciprofloxacin.8,12 The first report described a patient similar to ours in whom the addition of ciprofloxacin to methadone therapy resulted in respiratory depression.8 In that case, a 42-year-old woman who had been receiving methadone 140 mg PO daily for more than 6 years was admitted to hospital for urosepsis. Ciprofloxacin 750 mg PO twice a day was initiated. Two days later, the patient became sedated and confused. Ciprofloxacin was discontinued, co-trimoxazole was initiated, and the patient recovered 48 h later. On 3 different occasions, during 3 separate hospital admissions, the patient underwent unintentional rechallenge with ciprofloxacin for recurrent urosepsis. On all 3 occasions, the patient became sedated and recovered after discontinuation of ciprofloxacin. During the last of these episodes, the patient experienced heavy sedation and respiratory depression, both of which were reversed with naloxone 0.4 mg intramuscularly. The more severe reaction during the last episode was thought to have been caused by an additional drug interaction. The patient had previously been taking venlafaxine, but it had been replaced with fluoxetine, a stronger CYP2D6 inhibitor that may have contributed to increased methadone toxicity.
The second, more recent case report described an interaction between methadone and ciprofloxacin resulting in torsades de pointes.12 A 56-year-old man who was receiving maintenance therapy with methadone 120 mg PO daily experienced torsades de pointes (QTc interval 450 ms) after self-medicating with his wife’s ciprofloxacin, which had been prescribed at a dosage of 400 mg PO bid for an upper respiratory tract infection. Both methadone and fluroquinolones have been associated with QT prolongation and torsades.12 This case further suggests that ciprofloxacin should be used with extreme caution, if at all, for methadone-dependent patients.
In our case and and the similar case reported by Herrlin and others,8 the addition of ciprofloxacin to methadone therapy led to adverse outcomes occurring within 24 to 48 h. If concomitant therapy with these 2 drugs is deemed necessary, mental status and respiratory rate should be monitored closely for several days, especially if other inhibitors of methadone metabolism are present. Patients should also be advised to report any cardiac abnormalities such as palpitations.12
We have reported a suspected drug interaction between methadone and ciprofloxacin that caused severe respiratory depression. The extent of an interaction between these drugs is unpredictable, but may be greater in patients with poor metabolism of methadone or an underlying history of liver disease, those who have stopped smoking suddenly, and those with prescriptions for other medications that inhibit the metabolic pathways of methadone. Ciprofloxacin is a commonly prescribed antibiotic, and clinicians should be vigilant for an interaction between methadone and ciprofloxacin, especially in patients who are at high risk. Alternative antibiotics should be considered.
*The patient’s consent was not obtained for publication of this case report. To protect the privacy of the individual described here and his family, all unique identifying information not pertinent to the case has been omitted from this report.
National Center for
Biotechnology Information,
U.S. National Library of Medicine
8600 Rockville Pike, Bethesda
MD, 20894
USA
(ciprofloxacin)
Ciprofloxacin is an antibiotic that belongs to the family of medications known as quinolones. It is used to treat infections caused by certain bacteria. It is most commonly used to treat infections of the skin, sinuses, bone, lung, abdomen, kidney, prostate, and bladder.
It can also be used to treat some sexually transmitted infections (STIs), some forms of infectious diarrhea, and typhoid fever.
The extended release form of ciprofloxacin is used to treat bladder and kidney infections.
This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.
ciprofloxacin 500 mg drug interactions
Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.
Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.
You may be at higher risk than you think from bacteria that can lead to pneumonia, bacteremia, and meningitis.
Sponsored
Tablets
250 mg
Each round tablet, white-to-yellowish, engraved with “CIP” and “250” with a score line between on one side and the Bayer Cross on the other, contains ciprofloxacin hydrochloride equivalent to 250 mg ciprofloxacin. Nonmedicinal ingredients: microcrystalline cellulose, maize starch, colloidal silicon dioxide, purified water, crospovidone, magnesium stearate, titanium dioxide, methylhydroxypropyl cellulose 2910-15, and polyethylene glycol.
500 mg
Each oblong tablet, white-to-yellowish, engraved with “CIP” and “500” with a score line between on one side and Bayer on the other, contains ciprofloxacin hydrochloride equivalent to 500 mg ciprofloxacin. Nonmedicinal ingredients: microcrystalline cellulose, maize starch, colloidal silicon dioxide, purified water, crospovidone, magnesium stearate, titanium dioxide, methylhydroxypropyl cellulose 2910-15, and polyethylene glycol.
750 mg
Each oblong tablet, white-to-yellowish, engraved with “CIP” and “750” with a score line between on one side and Bayer on the other, contains ciprofloxacin HCl equivalent to ciprofloxacin 750 mg. Nonmedicinal ingredients: colloidal silicon dioxide, crospovidone, methylhydroxypropyl cellulose 2910-15, magnesium stearate, maize starch, microcrystalline cellulose, polyethylene glycol, purified water, and titanium dioxide. Lactose- and tartrazine-free.
Oral suspension
Each 10 mL of ciprofloxacin oral suspension contains 1 g of ciprofloxacin. Nonmedicinal ingredients: poly (ethyl acrylate methyl methacrylate)-dispersion 30%, magnesium stearate, methyl-hydroxypropylcellulose, polysorbate 20, polyvidone 25; diluent: strawberry flavour 52312, strawberry flavour 54267, lecithin , medium chain triglycerides, sucrose micronized, and purified water.
There are important differences between the two pneumococcal vaccines for adults available in Canada.
The recommended adult dose of ciprofloxacin tablets ranges from 250 mg to 750 mg twice daily. Depending on the type of infection being treated, you may need to take ciprofloxacin for 3 to 14 days. For bone infections it may be necessary to take ciprofloxacin for as long as 3 months. For STIs, the dose is given once as a single dose.
Ciprofloxacin tablets may be taken with food or on an empty stomach. Drink plenty of fluids while taking ciprofloxacin and avoid dairy products. Although ciprofloxacin can be taken with meals that include milk, you should not take ciprofloxacin with dairy products alone or with calcium-fortified products. Do not take antacids; supplements with calcium, magnesium, aluminum, or iron; or multivitamins 6 hours before or 2 hours after taking ciprofloxacin.
If you are taking the suspension form of this medication, use a medication syringe to measure each dose as it gives a more accurate measurement than household teaspoons. Shake the bottle well before measuring.
Many things can affect the dose of a medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are using the medication without consulting your doctor.
It is important that this medication be taken exactly as prescribed by your doctor. Even if you start to feel better after the start of treatment, it’s important to finish the entire amount that was prescribed. This helps to prevent the infection from returning and being harder to treat. If you miss a dose, take it as soon as possible and continue with your regular schedule. If it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not administer a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.
Store the tablets at room temperature and keep them out of the reach of children. Store the oral suspension at room temperature or in the refrigerator in an upright position, protect it from freezing, and keep it out of the reach of children. After 14 days, safely discard any remaining medication.
Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.
Do not use ciprofloxacin if you:
Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.
The side effects listed below are not experienced by everyone who uses this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.
The following side effects have been reported by at least 1% of people using this medication. Many of these side effects can be managed, and some may go away on their own over time.
Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.
Although most of the side effects listed below don’t happen very often, they could lead to serious problems if you do not seek medical attention.
Check with your doctor as soon as possible if any of the following side effects occur:
Stop using the medication and seek immediate medical attention if any of the following occur:
Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.
Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.
Health Canada has issued new restrictions concerning the use of ciprofloxacin. To read the full Health Canada Advisory, visit Health Canada’s web site at www.hc-sc.gc.ca.
Allergic reactions: In rare cases, some people may develop an allergic reaction to this medication. Signs of an allergic reaction include a severe rash, swollen face, or difficulty breathing. If these occur, get immediate medical attention.
Antibiotic-related diarrhea: This medication, like other antibiotics, can cause a potentially dangerous, severe form of diarrhea called antibiotic-associated colitis or pseudomembranous colitis. Symptoms include severe, watery diarrhea that may be bloody. If you notice these symptoms, stop taking ciprofloxacin and contact your doctor as soon as possible.
Behaviour and movement changes: Rarely, this medication can cause behaviour and movement changes such as agitation, anxiety, confusion, depression, tremors, hallucinations, and other mood changes. If you experience any of the above, contact your doctor immediately.
Driving and operating heavy machinery: Ciprofloxacin may impair your ability to drive or operate machinery, especially when combined with alcohol. Do not drive or operate machinery until you know how this medication affects you.
Kidney function: Kidney disease or reduced kidney function may cause this medication to build up in the body, causing side effects, since ciprofloxacin is removed from the body primarily by the kidneys. If you have reduced kidney function or kidney disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.
Liver function: Ciprofloxacin may reduce liver function and can cause liver failure. If you have liver problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.
ciprofloxacin 500 mg drug interactions
If you experience symptoms of liver problems such as fatigue, feeling unwell, loss of appetite, nausea, yellowing of the skin or whites of the eyes, dark urine, pale stools, abdominal pain or swelling, and itchy skin, contact your doctor immediately.
Neuromuscular disorders: Ciprofloxacin may cause increased muscle weakness for people with myasthenia gravis (an autoimmune disorder that causes muscle weakness). If you have myasthenia gravis, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.
Other infections: Use of ciprofloxacin for a long time may lead to yeast infections.
QT prolongation: This medication can lengthen heartbeat as shown on an electrocardiogram test, also known as QT prolongation. Very rare cases of abnormal heartbeat have been reported in people while on ciprofloxacin, but these reports generally involved people who had conditions that predisposed them to abnormal heartbeat, or who have been taking other medications that can increase the risk of developing an abnormal heartbeat. If you have heart disease and abnormal heart rhythms, or are taking certain medications (e.g., verapamil, atazanavir), discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. If you develop heart palpitations (fast or irregular heartbeat) or experience fainting spells, stop taking ciprofloxacin and contact your doctor immediately.
Seizures: Rarely, seizures have been reported with this medication. If you have a history of epilepsy or medical conditions that increase the risk of seizures, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. If you have a seizure while taking this medication, stop taking it and get immediate medical attention.
Sucrose intolerance: The oral suspension form of this medication contains sucrose. People who have a hereditary condition that makes them intolerant to some sugars should not take the oral suspension.
Sun sensitivity: People who take ciprofloxacin are more likely to experience sunburn. Avoid exposure to excessive sunlight, including sunlamps and tanning beds. If you must spend time in the sun use sunblock with minimum SPF 15. Talk to your doctor if severe sun sensitivity occurs.
Tendinitis: Ciprofloxacin may increase the chance of tendon injury, which occurs more commonly for seniors who are also taking corticosteroid medications. If there is any new pain in the tendons, stop taking ciprofloxacin, avoid physical exercise, and consult your doctor.
Pregnancy: This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, stop taking it immediately and call your doctor.
Breast-feeding: This medication passes into breast milk. If you are a breast-feeding mother and are taking ciprofloxacin, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.
Children: The safety and effectiveness of this medication have not been established for children less than 18 years of age.
There may be an interaction between ciprofloxacin and any of the following:
If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:
An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.
Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.
All material copyright MediResource Inc. 1996 – 2019. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/Cipro
Sponsored
