Methadone Ciprofloxacin

OPIOIDS CIPROFLOXACIN 1. Effects of methadone t by ciprofloxacin 2.1 levels of ciprofloxacin with opioids 1. Ciprofloxacin inhibits CYP1A2-, CYP2D6- and CYP3A4-mediated metabolism of methadone 2. Uncertain 1. Watch for t effects of methadone 2. Avoid opioid premedication when ciprofloxacin is used as surgical prophylaxis... 

A 35-year old Caucasian man with AIDS and multiple opportunistic infections, including Mycobacterium kansasii and Mycobacterium avium complex (MAC) disease developed moderate to severe primary sensorineural hearing loss after 4—5 months of therapy with oral azithromycin 500 mg/day. Other medications included ethambutol, isoniazid, rifabutin, ciprofloxacin, co-trimoxazole, fluconazole, zidovudine (later switched to stavudine), lamivudine, indinavir, methadone, mod-ified-release oral morphine, pseudoephedrine, diphenhydramine, megestrol acetate, trazodone, sorbitol, salbutamol by metered-dose inhaler and nebulizer, ipratropium, and oral morphine solution as needed. Significant improvement of the hearing impairment was documented 3 weeks after drug withdrawal. 

Ciprofloxacin, given to a patient who had been successfully treated with methadone for more than 6 years, caused profound sedation, confusion, and respiratory depression (73). This may have been due to inhibition of CYP1A2 and CYP3A4, two of the isozymes involved in the metabolism of methadone. 

Herrhn K, Segerdahl M, Gustafsson LL, Kalso E. Methadone, ciprofloxacin, and adverse drug reactions. Lancet 2000 356(9247) 2069-70. 

Clinically important, potentially hazardous interactions with alfentanil, aminophylline, amisulpride, amoxicillin, ampicillin, anticonvulsants, astemizole, atorvastatin, benzodiazepines, bromocriptine, buprenorphine, bupropion, carbamazepine, cilostazol, ciprofloxacin, cisapride, clindamycin, colchicine, cyclosporine, dasatinib, digoxin, dihydroergotamine, diltiazem, disopyramide, enoxacin, eplerenone, ergotamine, eszopiclone, everolimus, fluconazole, fluoxetine, fluvastatin, gatifloxacin, HMG-CoA reductase inhibitors, imatinib, itraconazole, ketoconazole, lomefloxacin, lorazepam, lovastatin, methadone, methylprednisolone, methysergide, midazolam, mizolastine, moxifloxacin, nitrazepam, norfloxacin, ofloxacin, paroxetine, pimozide, pravastatin, quinolones, ranolazine, repaglinide, rupatadine, sertraline, sildenafil, simvastatin, sparfloxacin, sulpiride, tacrolimus, terfenadine, triazolam, troleandomycin, vardenafil, verapamil, vinblastine, warfarin, zaleplon, zolpidem, zuclopenthixol... 

Noninterfering acetaminophen, amphotericin B, brotizolam, ceftazidime, ciprofloxacin, codeine, diclofenac, didanosine, domperidone, fluoxetine, foscarnet, gangiclovir, methadone, metoclopramide, mianserin, nystatin, pyrimethamine, ranitidine, sulfamethoxazole, temazepam, trimethoprim, zidovudine... 

An isolated case describes sedation, confusion and respiratoiy depression, which was attributed to the inhibition of methadone metabolism by ciprofloxacin. 

A woman taking methadone 140 mg daily for 6 years to manage pain due to chronic intestinal pseudo-obstruction was admitted to hospital because of a urinary tract infection and given ciprofloxacin 750 mg twice daily. Two days later she became sedated and confused. Ciprofloxacin was replaced with co-trimoxazole and the patient recovered within 48 hours. She was treated with ciprofloxacin for recurrent urinary-tract infections a further three times and on each occasion the patient bwame sedated, with her normal alertness regained on discontinuing ciprofloxacin. On the last oc-... 

This seems to be the only report of this interaction but it would appear to be of clinical importance. Care is needed if ciprofloxacin and methadone are given concurrently, especially if there are other factors such as smoking or the use of other enzyme inhibitors, which may also contribute to the interaction. Be alert for the need to change the methadone dosage. Consider also Quinolones + Opioids , p.338. 

Venlafaxine Inhibition of CYP3A4 by ciprofloxacin in a 61-year-old man taking methadone and venlafaxine was thought to have caused serotonin syndrome after 2 weeks therapy [54" ]. 

Lee J, Franz L, Goforth HW. Serotonin syndrome in a chronic-pain patient receiving concurrent methadone, ciprofloxacin, and venlafaxine. Psychosomatics 2009 50 (6) 638-9. 

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