Calabrese et al the cytochrome P450 systems potentiating other drugs. The drugs most cited are benzodiazepines, theophylline, and the calcium-channel blockers, but their effects seem to be slight (Raiha et al 1991) (Table 2). The most signiﬁcant interaction is suggested to be between PPIs and warfarin. Also in this case it has been shown that 16% of patients on warfarin, taking an acid suppressive drug, presented ﬂuctuations in international normalized ratio (INR) but only in those in intermittent PPIs (Raiha et al 1992). Pantoprazole has shown to have fewer drug interactions than older PPIs because of a lower afﬁnity for cytocrome P450 (Stupnicki et al 2004). Moreover a pharmacokinetics evaluation of pantoprazole shows that it may be a good choice for the treatment of the older patient with GERD because it is also independent of the patient’s age (Pilotto et al 2005). Dosage adjustments for PPIs are not necessary in elderly patients experiencing renal failure and mild hepatic impairment. Pantoprazole should be used with caution in patients with severe hepatic impairment (Raiha et al 2005). There is concern regarding the use of nonsteroidal anti- inﬂammatory drugs (NSAIDs) that elderly widely use to provide effective pain relief in chronic arthritic, inﬂammatory conditions, and prophylaxis against cardiovascular events. However, despite the great beneﬁts associated with NSAIDs use, up to 25% of patients taking NSAIDs experience chronic upper gastrointestinal adverse effects (Singh and Triadaphilopoulos 1999). Among adverse effects, severe complications of the gastro-intestinal tract are included, and it has been estimated a 4% of major accidents in the older subject (Armstrong and Blower 1997). PPIs such as pantoprazole are emerging as effective agents that protect the stomach and the duodenum during NSAID administration (Cheer et al 2003). Table 2 Effects of pantoprazole when co-administered with other drugs Drug Pantoprazole Carbamazepine (Tegretol) None Clarithromycin (Biaxin) Unknown Diazepam (Valium) None Digoxin > Absorpition Ketoconazole (Nizoral) Unknown Methotrexate Unknown Nifedipine (Procardia) > Absorption Oral contraceptives None Phenytoin (Dilantin) None Warfarin (Coumadin) None Theophylline None A study in healthy volunteers has shown that even a low dose of aspirin causes signiﬁcant injury to the stomach whereas coadministration with pantoprazole offers protection against such damage (Muller and Simon 1998). This gastroprotective effect of pantoprazole translates into clinical beneﬁts by reducing the damage in long-term users. Pantoprazole has also been shown to be superior to placebo in the prevention of NSAIDs-associated peptic ulcers (Bianchi Porro et al 2000). In this study pantoprazole 40 mg once daily or placebo was administered for 12 weeks to patients requiring long-term NSAIDs. At baseline about half of patients had endoscopically detected gastroduodenal lesions while the other half had normal or hyperaemic mucosa at baseline. After 12 weeks the probability of remaining free of gastric or duodenal ulcers was 72% in the pantoprazole group compared with 59% in the placebo group. An other study focused on the prevention of NSAIDs- associated lesions and it concluded that for patients taking NSAIDs continually, pantoprazole 20 mg once daily or omeprazole 20 mg once daily provided effective and well- tolerated prophylaxis against gastrointestinal lesions (Regula and Butruk 2006). Regarding the use of misoprostol in the prevention of gastrointestinal lesions, a interesting study shows that pantoprazole 20 mg once daily is superior to misoprostol 200 μg twice daily in the prevention of lesions and symptoms in patients on continuous long-term treatment with NSAID and at risk to develop such lesions or symptoms (Stupnicki et al 2003). Conclusions This review shows that PPIs are highly effective drugs that have revolutionized the management of GERD. Pantoprazole is sig- niﬁcantly efﬁcacious both for acute esophageal healing both for long-term treatment with excellent control of relapse of esophagitis and symptoms. This report also conﬁrms that panto- prazole is a well tolerated treatment even for long-term therapy with optimal tolerability. It is perfectly suited for use in patients taking concomitant therapies and in particular in the elderly. There is a limited body of evidence advocating the optimal dosage for long-term treatment. Clinical practice suggests that at least a low dose maintenance should be carefully taken in consideration especially in the elderly as they are more exposed to severe complications. References Ahnfeldt-Mollerup I, Fly GF, Knudsen MH. 1997. Dyspepsia in general practice. A study among users of anti-ulcer agents. Ugeskr Laeger, 159:3772–6. 90 Clinical Interventions in Aging 2007:2(1)