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Interactions with Loperamide (oral)

If you are currently being treated with any of the following medications, you should not use Loperamide (oral) without reading these interactions.

Ritonavir

Coadministration with ritonavir may increase the plasma concentrations of loperamide. The probable mechanism is ritonavir inhibition of CYP450-mediated metabolism of loperamide. In 12 healthy volunteers, ritonavir (600 mg single dose) increased the median peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of loperamide (16 mg single dose) by 17% and 223%, respectively, compared to placebo. The oral clearance of loperamide decreased by 70% with ritonavir, and formation of its major metabolite was delayed. No serious adverse events occurred as a result of the interaction, and there were no changes in pharmacodynamic effects of loperamide as measured by pupil diameter, pain threshold, pain tolerance, and respiration. The absence of central opioid effects in the study suggests that ritonavir has little effect on P-glycoprotein-mediated transport in the blood brain barrier and does not facilitate loperamide entry into the central nervous system. Based on these observations, it appears that loperamide may be safely used with ritonavir and that a lower dosage of loperamide may be effective during treatment with ritonavir. However, data on chronic administration are lacking.

Saquinavir

GENERALLY AVOID: Coadministration with loperamide may decrease the plasma concentrations of saquinavir. The mechanism of interaction is unknown but may be mediated by the effects of loperamide on gastrointestinal motility and fluids. In 12 healthy volunteers, administration of a single 600 mg dose of saquinavir (administered as three 200 mg soft gelatin capsules) with a 16 mg dose of loperamide resulted in a 46% reduction in saquinavir peak plasma concentration (Cmax) and a 54% reduction in saquinavir systemic exposure (AUC) compared to administration with placebo. The renal clearance and elimination half-life of saquinavir were not affected. In contrast, loperamide AUC increased 41% with saquinavir versus placebo, presumably due to saquinavir inhibition of loperamide N-demethylation via CYP450 3A4. This change is unlikely to be of clinical significance.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, prolonged use of loperamide should preferably be avoided in patients treated with saquinavir, particularly if saquinavir is the sole protease inhibitor in their antiretroviral regimen. The effect of loperamide on the pharmacokinetics of other protease inhibitors or on ritonavir-boosted saquinavir is unknown.

Tacrine, Donepezil (oral), Rivastigmine, Galantamine

GENERALLY AVOID: Due to opposing effects, agents that possess anticholinergic activity (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; class IA antiarrhythmics especially disopyramide; carbamazepine; cimetidine; ranitidine) may negate the already small pharmacologic benefits of acetylcholinesterase inhibitors in the treatment of dementia. These agents may also adversely affect elderly patients in general. Clinically significant mental status changes associated with anticholinergic agents can range from mild cognitive impairment to delirium, and patients with Alzheimer's disease and other dementia are especially sensitive.

MANAGEMENT: Drugs that possess anticholinergic activity should generally be avoided in patients with Alzheimer's disease or other cognitive impairment, regardless of whether they are receiving an acetylcholinesterase inhibitor. For patients requiring treatment for adverse effects of acetylcholinesterase inhibitor therapy (e.g., gastrointestinal intolerance, urinary problems), an agent without anticholinergic properties should be used whenever possible. Otherwise, a dosage reduction, slower titration, or even discontinuation of the acetylcholinesterase inhibitor should be considered. In patients who are already receiving an acetylcholinesterase inhibitor with anticholinergic agents, every attempt should be made to discontinue the latter or substitute them with less anticholinergic alternatives. Caution is required, however, since anticholinergic withdrawal may occur. Seizures have been reported following abrupt discontinuation of anticholinergics during acetylcholinesterase inhibitor therapy.

Pramlintide

GENERALLY AVOID: The use of pramlintide in combination with drugs that alter gastrointestinal motility (e.g., loperamide; anticholinergic agents) or drugs that slow the intestinal absorption of nutrients (e.g., alpha-glucosidase inhibitors) has not been studied. Because pramlintide slows gastric emptying, the potential for a pharmacodynamic interaction is possible.

MANAGEMENT: Due to its effect on gastric emptying, pramlintide therapy should not be considered for patients taking drugs that alter gastrointestinal motility or drugs that slow the intestinal absorption of nutrients.

Apraclonidine ophthalmic, Duloxetine, Eszopiclone, Ziconotide, Pregabalin, Rotigotine (transdermal), Paliperidone

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Risperidone (oral), Olanzapine, Flavoxate, Carbinoxamine, Quetiapine, Tolterodine, Ziprasidone, Aripiprazole, Trospium, Solifenacin, Darifenacin

MONITOR: Coadministration with drugs that possess significant anticholinergic activity may potentiate the antimotility effect of loperamide. An isolated case report describes an incident of fatal gastroenteritis during concomitant treatment with clozapine and loperamide. A 36-year-old man who had been treated with clozapine 500 mg/day and was previously in good health died after taking a total of 6 mg of loperamide during an outbreak of intestinal disease in a Finnish hospital. The patient received no other medications. The authors theorized that the anticholinergic effect of clozapine in combination with the antimotility effect of loperamide may have led to toxic megacolon. However, causality has not been determined.

MANAGEMENT: Until further information is available, loperamide should be used with caution in combination with drugs that possess significant anticholinergic activity (e.g., antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; class IA antiarrhythmics especially disopyramide). Ambulatory patients should also be made aware of the possibility of additive CNS effects (e.g., drowsiness, dizziness, lightheadedness, confusion) and counseled to avoid activities requiring mental alertness until they know how these agents affect them.

Lapatinib

MONITOR: Coadministration with lapatinib may increase the plasma concentrations of drugs that are substrates of the CYP450 2C8 isoenzyme, CYP450 3A4 isoenzyme, and/or P-glycoprotein efflux transporter. The mechanism is decreased clearance via these routes due to inhibition by lapatinib.

MANAGEMENT: Caution is advised if lapatinib must be used concurrently with medications that are substrates of the CYP450 2C8 isoenzyme, CYP450 3A4 isoenzyme, and/or P-glycoprotein efflux transporter, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever lapatinib is added to or withdrawn from therapy.

Tipranavir

MONITOR: Coadministration with tipranavir in combination with low-dose ritonavir may decrease the plasma concentrations of loperamide. The mechanism probably involves reduced absorption and increased first-pass clearance of loperamide due to induction of the intestinal P-glycoprotein drug efflux pump by tipranavir. In 24 study subjects, tipranavir/ritonavir (750 mg/200 mg twice a day for 10 days) decreased the mean peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of loperamide (16 mg single dose) by 61% and 51%, respectively, compared to administration of loperamide without tipranavir/ritonavir. Tipranavir/ritonavir also reduced the Cmax and AUC of the metabolite N-demethyl-loperamide by 79% and 77%, respectively. Tipranavir trough plasma concentration (Cmin) was reduced 26%.

MANAGEMENT: Clinicians and patients should be aware that pharmacologic effects of loperamide may be reduced during coadministration with tipranavir/ritonavir.

Cetirizine

MONITOR: Concurrent use of cetirizine or levocetirizine with alcohol or other central nervous system (CNS) depressants may result in additive impairment of mental alertness and performance. Several studies have shown no effect of racemic cetirizine on cognitive function, motor performance, or sleep latency as indicated by objective measurements. However, there have been reports of somnolence, fatigue, and asthenia in some patients treated with cetirizine or levocetirizine in clinical trials.

MANAGEMENT: Concomitant use of cetirizine or levocetirizine with alcohol or other CNS depressants should generally be avoided if possible. In the event that they are used together, patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Tizanidine

MONITOR: Sedation is a major side effect of tizanidine and may be potentiated by coadministration with other substances that have central nervous system-depressant effects or that may commonly cause drowsiness.

MANAGEMENT: Use of tizanidine with other substances that commonly cause sedation should be approached with caution, particularly in elderly or debilitated patients. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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