Rabeprazole interactions

Rabeprazole (AcipHex) [Antiulcer Agent/Proton Pump Inhibitor] Uses PUD, GERD, ZE H. pylori Action Proton pump inhibitor Dose 20 mg/d may T to 60 mg/d H. pylori 20 mg PO bid X 7 d (w/ amoxicillin and clarithromycin) do not crush/chew tabs Caution [B, /—] Disp Tabs SE HA, fatigue, GI upset Interactions t Effects OF cyclosporine, digoxin -1- effects OF ketoconazole EMS None OD May cause N, tach, dry mouth, and drowsiness symptomatic and supportive... 

Omeprazole (Prilosec) was the original PPI this drug is now joined by esomeprazole (Nexium), lansoprazole (Prevacid), pantoprazole (Protonix), and rabeprazole (AcipHex) (see Table 27-2). All of these drugs are similar, with selection often depending on cost, availability, and the drug interaction potential of each agent.15 Likewise, nonprescription forms of certain PPIs are now available, and these forms offer a convenient,... 

Omeprazole carries a higher risk for interactions as it has a high affinity for CYP2C19 and a somewhat lower affinity for CYP3A4. Pantoprazole (which is further metabolized by non-saturable phase II reactions after initial metabolism by CYP isoenzymes) has a lower potential for interaction associated with CYP450 inhibition, It is also likely that, despite the limited information, esomeprazole, lansoprazole and rabeprazole also have weaker potential for interaction compared with omeprazole. Pantoprazole has been reported to be used without dose adjustments in critical care patients with organ dysfunction. 

Figure 2. Relative potency of the various cytochrome P450 enzymes in the metabolism of commonly prescribed proton pump inhibitors (PPi) is noted. Patients with genetic polymorphisms of the CYP2C19 pathway (poor metaboUzers) utilize the CYP3A4 pathway (dotted line) for PPi metabolism. Calcineurin inhibitors (CNI) also use the CYP3A4 pathway for their metabolism. As a result, the "poor metaboUzers" are at risk to develop elevated CNI levels when concurrently receiving a PPI. In contrast, rabeprazole is safe as it has a "non-enzymatic"pathway for its metabolism, avoiding an interaction with the CNI.

Clinically important, potentially hazardous interactions with alprazolam, amiodarone, amphotericin B, arbutamine, bendroflumethiazide, benzthiazide, bisacodyl, bumetanide, carbimazole, chlorothiazide, chlorthalidone, cholestyramine, clarithromycin, conivaptan, cyclosporine, cyclothiazide, dan-shen, demeclocycline, devil s claw, dexmedetomidine, doxycycline, erythromycin, esomeprazole, ethacrynic acid, flunisolide, furosemide, ginseng, glycopyrrolate, glycopyrronium, hawthorn (fruit, leaf, flower extract), horsetail, hydrochlorothiazide, hydroflumethiazide, indapamide, licorice, lopinavir, mepenzolate, methyclothiazide, metolazone, minocycline, mistletoe, oxprenolol, oxytetracycline, paroxetine, phenylbutazone, polythiazide, propafenone, propantheline, quinethazone, quinidine, rabeprazole, rifampin, roxithromycin, sarsaparilla, senna, Siberian ginseng, squill, St John s wort, telithromycin, teriparatide, tetracycline, thiazide diuretics, tolvaptan, trichlormethiazide, verapamil... 

Clinically important, potentially hazardous interactions with amiodarone, atazanavir, azithromycin, bosentan, ciprofibrate, clarithromycin, clopidogrel, cyclosporine, darunavir, delavirdine, diltiazem, erythromycin, fosamprenavir, fusidic acid, gemfibrozil, grapefruit juice, imatinib, itraconazole, lopinavir, rabeprazole, ranolazine, red rice yeast, ritonavir, roxithromycin, selenium, St John s wort, tacrolimus, telithromycin, tipranavir, verapamil, warfarin... 

Drug interactions with omeprazole are of particular concern in patients who are considered slow metabolizers, as found in approximately 3% of the Caucasian population. Unfortunately, it is unclear which patients have the polymorphic gene variation that makes them slow metabolizers. Like omeprazole, the metabolism of esomeprazole may also be altered in patients with this polymorphic gene variation. Rabeprazole increases digoxin trough concentrations by approximately 20%. Patients on potentially interacting drugs should be monitored closely for potential problems. 

The interaction between ketoconazole and rabeprazole is also established, but the reduction in the bioavailability is only moderate (30%) and it may be possible to accommodate this by raising tiie antifungal dosage. 

Humphries TJ, Nardi RV, Spera AC, Lazar JD, Laurent AL, Spanyers SA. Coadministration of rabeprazole sodium (E3810) and ketoconazole results in a predictable interaction with ketoconazole. Gastroenterology (1996) 110 (Suppl), A138. 

A study in epileptic patients found that omeprazole 20 mg daily did not affect the serum levels of phenytoin, whereas earlier studies in healthy subjects su ested that phenytoin levels might be modestly raised by omeprazole 40 mg daily. A study with esome-prazole also suggests it may cause a minor rise in phenytoin levels. Lansoprazole does not normally affect phenytoin levels, but an isolated case report of toxicity is tentatively attributed to an interaction. Pantoprazole and rabeprazole appear not to interact. 

Information is very limited but it seems that omeprazole 20 mg daily does not affect serum phenytoin levels, whereas 40 mg daily may possibly cause a slight increase. No special precautions would normally seem necessary if lansoprazole or omeprazole is given with phenytoin, but until more is known it would be prudent to be aware of this possible interaction if concurrent use is necessary. Similarly, the manufacturers of esomepra-zole suggest concurrent use should be monitored, although the elevation in levels seen in the study would not usually be expected to be clinically significant. More study is needed. No special precautions would seem to be necessary if rabeprazole or pantoprazole and phenytoin are given concurrently. 

Humphries TJ,NardiRV, Lazar JD, Spanyers SA. Drug-drug interaction evaluation of rabeprazole sodium a clean/e qDected slate Gut (1996) 39 (Siq)pl 3), A47. 

Gait disturbances (attributed to benzodiazepine toxicity) occurred in two patients given triazoiam and lorazepam or flu-razepam with omeprazoie, and another patient taking diazepam and omeprazole became wobbly and sedated. Lansoprazole, pan-toprazole, or rabeprazole appear not to interact to a clinically relevant extent with diazepam. Diazepam serum levels are increased by esomeprazole but the clinical relevance of this is unknown. 

Maalox does not appear to alter the pharmacokinetics of omeprazole, pantoprazole or rabeprazole. Antacids may cause a slight reduction in the bioavailability of lansoprazole. This is probably not clinically relevant but can be accommodated by separating their administration by one hour. There is no interaction between sodium alginate and omeprazole. 

Lansoprazole may increase tacrolimus levels in patients with low levels of the cytochrome P4S0 isoenzyme CYP2C19. Pantoprazole and omeprazole are predicted to interact similarly. Rabeprazole appears not to interact with tacrolimus. 

The incidence of the interaction between tacrolimus and lansoprazole is unknown. It would seem to most frequently occur in those with decreased CYP2C19 activity, and therefore it is not easy to predict which patients would be affected. The manufacturers of tacrolimus say that this interaction may also occur with omeprazole, which is metabolised in the same way as lansoprazole. It would seem prudent to monitor tacrolimus levels if either of these proton pump inhibitors is started or stopped. Although no interaction was noted in the study with pantoprazole the authors do note that it may interact like lansoprazole in patients with CYP2C19 deficiency. Rabeprazole may be a suitable alternative proton pump inhibitor as limited evidence suggests that it does not interact, and nor would it be expected to do so. 

Omeprazole may cause a small increase in theophylline clearance, and lansoprazole may canse a small decrease in theophylline levels, neither of which are likely to be clinically relevant Pantopra-zole and rabeprazole do not appear to interact with theophylline. 

In a separate study in 39 healthy volunteers the interaction of the CYP2C19 genotype and the effect of three proton pump inhibitors (omeprazole 20mg/day, lansoprazole 30 mg/day, and rabeprazole 20 mg/ day for 7 days) on the antiplatelet effect of clopidogrel 75 mg were studied [63 ]. The three proton pump inhibitors affected the efficacy of clopidogrel to different... 

Information on rabeprazole is still limited. Similar to the other PPIs, its potential to interact with other drugs and its ability to induce CYP lA isoenzymes seem to be low [65, 70]. 

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