The FDA has approved vonoprazan (Voquezna – Phathom), a potassium-competitive acid blocker, for healing and maintenance of healing of all grades of erosive esophagitis and relief of associated heartburn in adults. Vonoprazan is also available copackaged with amoxicillin (Voquezna Dual Pak) and with amoxicillin and clarithromycin (Voquezna Triple Pak) for treatment of Helicobacter pylori infection in adults.

The FDA has approved vonoprazan, a potassium-competitive acid blocker, copackaged with amoxicillin (Voquezna Dual Pak – Phathom) and with amoxicillin and clarithromycin (Voquezna Triple Pak) for treatment of Helicobacter pylori infection in adults. Vonoprazan is the first potassium-competitive acid blocker to be approved in the US. It has been available in Japan for treatment of various acid-related disorders since 2014. Vonoprazan is not available alone in the US.

A reader commented that our recent article on Drugs for GERD and Peptic Ulcer Disease did not include enough information on dexlansoprazole (Dexilant, and generics), a proton pump inhibitor (PPI) claimed to provide "all-day and all-night relief from heartburn". Dexlansoprazole recently became available generically, but it is much more expensive than other generic PPIs.

Gastroesophageal reflux disease (GERD) is the most common GI condition encountered in the outpatient setting; it affects about 20% of people in the US.

View the Comparison Table: H2-Receptor Antagonists and PPIs

The FDA has approved a fixed-dose combination of omeprazole, amoxicillin, and rifabutin (Talicia – RedHill) for treatment of Helicobacter pylori infection in adults. Talicia is the first rifabutin-based product to be approved for this indication.

Nonopioid drugs can be used in the treatment of many nociceptive and neuropathic pain conditions. Use of opioids for pain will be reviewed in a future issue.

Gastroesophageal reflux disease (GERD) is the most frequent GI condition encountered in the outpatient setting; it affects about 20% of the US population. Heartburn and regurgitation are the classic symptoms of GERD.

View the Comparison Table: Drugs for GERD and Peptic Ulcer Disease

The FDA has approved the interleukin-6 (IL-6) receptor antagonist tocilizumab (Actemra – Genentech) for subcutaneous (SC) treatment of giant cell arteritis in adults. It is the first drug to be approved in the US for this indication. Tocilizumab is also approved for treatment of rheumatoid arthritis, polyarticular or systemic juvenile idiopathic arthritis, and cytokine release syndrome.

Proton pump inhibitors (PPIs), which are used for treatment of gastroesophageal reflux disease (GERD) and for prevention of upper gastrointestinal adverse effects caused by NSAIDs and aspirin, are one of the most commonly prescribed classes of drugs in the US. All PPIs are similarly effective and generally well tolerated, but their long-term use has been associated with a number of safety concerns. Recommendations addressing these concerns have recently been published.

About 50% of the world’s population is infected with Helicobacter pylori. These gastric bacteria can cause chronic inflammation and have been associated with development of gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Eradication of H. pylori can promote gastric healing, prevent recurrence of duodenal and gastric ulcers, and reduce the incidence of gastric cancer. Guidelines for treatment of H. pylori infection were updated recently.

The antiplatelet drug clopidogrel (Plavix, and others) reduces major cardiovascular events, but can cause bleeding. Proton pump inhibitors (PPIs) are often used with clopidogrel to prevent gastrointestinal bleeding, however, some evidence suggests that PPIs may interfere with the activation of clopidogrel and diminish its antiplatelet effect. FDA-approved labeling recommends avoiding concurrent use of the PPIs omeprazole and esomeprazole with clopidogrel.

The FDA has approved Yosprala (Aralez), a fixed-dose combination of delayed-release aspirin and immediate-release omeprazole, for secondary prevention of cardiovascular and cerebrovascular events in patients who are at risk of developing aspirin-associated gastric ulcers (≥55 years old or history of gastric ulcers). Yosprala is the first product to become available in the US that combines aspirin and a proton pump inhibitor (PPI).

Therapeutics (AZCERT) has recently added the proton pump inhibitors (PPIs) omeprazole (Prilosec, and others), esomeprazole (Nexium, and others), lansoprazole (Prevacid, and others), and pantoprazole (Protonix, and generics) to its lists of Drugs with Conditional Risk of Torsades de Pointes (TdP) and Drugs to Avoid in Patients with Congenital Long QT Syndrome.1

PPIs do not directly cause prolongation of the QT interval, but they can cause hypomagnesemia, which is often accompanied by hypocalcemia and hypokalemia and can result in cardiac repolarization disturbances such as QT interval prolongation.2 Reports have described cases of QT interval prolongation and TdP associated with severe PPI-induced hypomagnesemia.3,4 TdP has also been reported in patients taking a PPI concomitantly with drugs that directly prolong the QT interval.5,6 The newer PPIs dexlansoprazole (Dexilant) and rabeprazole (Aciphex, and generics) have not been linked to QT interval prolongation or TdP to date, but they have been associated with hypomagnesemia.

Serum magnesium levels should be monitored periodically in patients taking a PPI for an extended period of time (>2 weeks). If possible, extended PPI therapy should be avoided in patients who require treatment with drugs that carry a known risk of TdP7 and in those with long QT syndrome. If extended PPI therapy must be used with a drug that prolongs the QT interval, close monitoring of magnesium levels and the QT interval is recommended.

1. AZCERT. New drugs added to CredibleMeds drugs lists. November 2, 2016. Available at: www.crediblemeds.org. Accessed November 22, 2016.
2. In brief: PPIs and hypomagnesemia. Med Lett Drugs Ther 2011; 53:25.
3. EJ Hoorn et al. A case series of proton pump inhibitor-induced hypomagnesemia. Am J Kidney Dis 2010; 56:112.
4. BA Hansen and Ø Bruserud. Hypomagnesemia as a potentially life-threatening adverse effect of omeprazole. Oxf Med Case Reports 2016; 2016:147.
5. H Asajima et al. Lansoprazole precipitated QT prolongation and torsade de pointes associated with disopyramide. Eur J Clin Pharmacol 2012; 68:331.
6. JN Bibawy et al. Pantoprazole (proton pump inhibitor) contributing to torsades de pointes storm. Circ Arrhythm Electrophysiol 2013; 6:e17.
7. RL Woosley and KA Romero. QT drugs list. Available at: www.crediblemeds. org. Accessed November 22, 2016.

Download complete U.S. English article

An article published in the New York Times on May 1, 2015 listed the 10 drugs on which Medicare Part D spent the most in 2013. The most costly ($2.53 billion) was the proton pump inhibitor (PPI) Nexium (esomeprazole magnesium), which has recently become available generically.

The FDA has approved Viekira Pak (Abbvie), a fixed-dose combination of two new direct-acting antiviral agents (ombitasvir, paritaprevir) with the pharmacologic enhancer ritonavir in one tablet, co-packaged with a third new direct-acting antiviral agent (dasabuvir) in a second tablet, for oral treatment of chronic hepatitis C virus (HCV) genotype 1 infection. Genotype 1 is responsible for 70-80% of HCV infections in the US.

Many different drugs are used for treatment of osteoarthritis pain, but none of them prevent progression of the disease. Many nonpharmacologic approaches are available as well, including weight management, exercise, physical therapy, assistive devices, and total joint arthroplasty. New guidelines for the management of osteoarthritis have recently been published.

Aminosalicylates are effective for induction and maintenance of remission in mild to moderate ulcerative colitis. They are not recommended for treatment of Crohn's disease.

FORMULATIONS — Oral mesalamine is rapidly absorbed in the small intestine and most of the drug does not reach the colon. Pentasa releases mesalamine gradually throughout the gastrointestinal tract. Delzicol, Asacol HD, Lialda, and Apriso delay the release of the drug until it reaches the distal ileum and colon. Sulfasalazine (Azulfidine, and generics), balsalazide (Colazal, and others), and olsalazine (Dipentum) are prodrugs; mesalamine is azo-bonded to a second moiety and released in the colon following bacterial cleavage of the bond. Mesalamine is also available as an enema (Rowasa, and generics) and as a rectal suppository (Canasa).

The FDA has approved the proton pump inhibitor (PPI) esomeprazole strontium for use in adults for the same indications as esomeprazole magnesium (Nexium): treatment of gastroesophageal reflux disease (GERD), prevention of NSAID-induced gastric ulcers, eradication of Helicobacter pylori, and treatment of pathological hypersecretory conditions. It was first marketed in December 2013 as a branded drug (Esomeprazole Strontium) and a month later as a generic drug.

Strontium is incorporated into bone. It is not recommended for use in children or during pregnancy because of the absence of safety data in those populations. Use of esomeprazole strontium is not recommended for patients with severe renal impairment.

Esomeprazole strontium is the seventh PPI to become available as a single agent in the US. No new clinical trials were required for its approval, which was based on earlier clinical trials with esomeprazole magnesium. All of the PPIs appear to be equally effective.1

1. Drugs for peptic ulcer disease and GERD. Treat Guidel Med Lett 2014; 12:25.

Download complete U.S. English article

H2-RECEPTOR ANTAGONISTS (H2RAs) — Currently available H2RAs are listed in Table 1. These drugs inhibit the action of histamine at the H2-receptor of the gastric parietal cell, decreasing basal acid secretion and, to a lesser degree, food-stimulated acid secretion. All H2RAs are about equally effective for treatment of PUD and GERD. H2RAs are faster acting than PPIs in relieving symptoms of dyspepsia or GERD, but they are not as effective as PPIs in relieving symptoms or in healing erosive esophagitis. Repeated administration of H2RAs leads to pharmacologic tolerance and has been associated with the development of new dyspeptic symptoms. Rebound acid hypersecretion can occur after stopping H2RAs.

Pain can be acute or chronic. The two major types of chronic pain are nociceptive pain and neuropathic pain. Nociceptive pain can be treated with nonopioid analgesics or opioids. Neuropathic pain is less responsive to opioids and is often treated with adjuvant drugs such as antidepressants and antiepileptics. Combining different types of analgesics may provide an additive analgesic effect without increasing adverse effects.

The FDA has approved Duexis (Horizon), a fixed-dose combination of the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen and the H2-receptor antagonist (H2RA) famotidine, for symptomatic relief of osteoarthritis and rheumatoid arthritis and to decrease the risk of developing gastric and duodenal ulcers in patients at risk for NSAID-associated ulcers. Vimovo, a combination of the NSAID naproxen and the proton pump inhibitor (PPI) esomeprazole, is also approved by the FDA for prevention of NSAID-associated gastric ulcers.

Peptic ulcer disease (PUD) is usually caused by nonsteroidal anti-inflammatory drugs (NSAIDs) or by infection with Helicobacter pylori. Gastroesophageal reflux disease (GERD) can be caused by transient lower esophageal sphincter relaxation, reduced lower esophageal sphincter tone, hiatal hernia, delayed gastric emptying or hormonal changes due to pregnancy. Acid suppressive therapy is the cornerstone of management for both PUD and GERD.

Use of a proton pump inhibitor (PPI) to protect against gastrointestinal (GI) bleeding in patients taking the antiplatelet agent clopidogrel (Plavix) may interfere with the activation of clopidogrel and diminish its antiplatelet effect, increasing the risk of cardiovascular events.1 A randomized, placebo-controlled trial (COGENT) has found that use of the PPI omeprazole in patients taking clopidogrel in addition to aspirin decreased the incidence of GI bleeding without increasing the risk of a cardiovascular event, but the number of cardiovascular events was small and the formulation of omeprazole was atypical.2 The FDA in the same issue of the same journal cautioned against concluding from the results of COGENT that concurrent use of clopidogrel and omeprazole is safe.3

To some extent, all PPIs reduce the enzymatic activity of CYP2C19, which is thought to be mainly responsible for the bioactivation of clopidogrel. Omeprazole is a strong inhibitor of CYP2C19; pantoprazole (Protonix, and others) appears to have less effect on CYP2C19 and not to attenuate the antiplatelet effect of clopidogrel.4-6 Medical Letter consultants believe that patients at risk for upper GI bleeding who take clopidogrel should also take a PPI, but not omeprazole. Until more data become available on other PPIs, pantoprazole would be a reasonable choice.

1. PPI interactions with clopidogrel revisited. Med Lett Drugs Ther 2009; 51:13.

2. DL Bhatt et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010; 363:1909.

3. MR Southworth and R Temple. Interaction of clopidogrel and omeprazole. N Engl J Med 2010; 363:1977.

4. DJ Angiolillo et al. Differential effects of omeprazole and pantoprazole on the pharmacodynamics and pharmacokinetics of clopidogrel in healthy subjects: randomized, placebo-controlled, crossover comparison studies. Clin Pharmacol Ther 2010; Sept 15 epub.

5. T Cuisset et al. Comparison of omeprazole and pantoprazole influence on a high 150-mg clopidogrel maintenance dose: the PACA (Proton Pump Inhibitors And Clopidogrel Association) prospective randomized study. J Am Coll Cardiol 2009; 54:1149.

6. H Neubaurer et al. Pantoprazole does not influence the antiplatelet effect of clopidogrel – a whole blood aggregometry study after coronary stenting. J Cardiovasc Pharmacol 2010; 56:91.

Download U.S. English

The FDA has approved the marketing of Vimovo (AstraZeneca), a fixed-dose combination of the nonsteroidal anti-inflammatory drug (NSAID) naproxen and the proton pump inhibitor (PPI) esomeprazole, for symptomatic relief of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis and to decrease the risk of developing gastric ulcers in patients at risk for NSAID-associated ulcers.

Pain can be acute or chronic. Chronic pain has been broadly classified into two types: nociceptive and neuropathic. Nociceptive pain can be treated with nonopioid analgesics or opioids. Neuropathic pain is less responsive to opioids; adjuvant medicines such as antidepressants and anticonvulsants are often used to treat neuropathic pain. Combining different types of analgesics may provide an additive analgesic effect without increasing adverse effects.

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are common causes of peptic ulcer disease. Patients infected with Helicobacter pylori who take aspirin or another NSAID have an especially high risk. Drugs that have been tried for prevention of ulcers in patients taking NSAIDs including H₂-receptor antagonists, proton pump inhibitors (PPIs), aluminum- or magnesium-containing antacids, the prostaglandin misoprostol (Cytotec, and others), and antibiotics to eradicate H. pylori.

Click here to view the free full article.

The equivalence of generic drugs to their brand-name precursors continues to be controversial. The last Medical Letter review of this subject (2002) concluded that well-documented therapeutic inequivalence between brand-name and FDA-approved generic drugs had not been reported. Is that still true? New data have become available for some drugs.

Inflammatory bowel disease (IBD) is either Crohn's disease or ulcerative colitis. Drug selection is guided by disease type (Crohn's versus ulcerative colitis), severity and location and whether the goal is induction or maintenance of remission. Table 1 on page 66 lists the drugs used to treat IBD with their formulations and cost. Table 2 on page 68 lists the drugs of choice and their doses for different indications. Table 3 on page 71 lists the drugs' adverse effects and recommendations for monitoring. More detailed guidelines are available from the American College of Gastroenterology.

Apriso (Salix) is a new formulation of mesalamine (5-aminosalicylic acid; 5-ASA) approved by the FDA for maintenance of remission in mild to moderate ulcerative colitis (UC). Mesalamine is a locally acting antiinflammatory agent that is widely used both to maintain and induce remission in inflammatory bowel disease. Various mesalamine formulations have been developed to target drug delivery to areas of the small intestine and colon. Most of these agents require frequent dosing and have a high pill burden. The newest products - Lialda, introduced in 2007,1 and now Apriso - can be dosed once daily.

Disease-modifying anti-rheumatic drugs (DMARDs) are now used early in the treatment of rheumatoid arthritis (RA) to prevent irreversible damage to joints and minimize toxicities associated with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids.

The FDA has approved the proton-pump inhibitor (PPI) dexlansoprazole (Kapidex - Takeda), a delayed release formulation of the R-enantiomer of lansoprazole (Prevacid - Takeda), for treating and maintaining healing of erosive esophagitis and for treatment of heartburn associated with non-erosive gastroesophageal reflux disease (GERD).

The majority of patients with insomnia do not have a predisposing psychiatric disease. Rather, untreated insomnia may be a risk factor for development of psychiatric problems such as depression or anxiety.

Current guidelines recommend use of a proton pump inhibitor (PPI) to decrease the risk of gastrointestinal bleeding in patients taking clopidogrel (Plavix) with aspirin. A recent issue of The Medical Letter considered whether omeprazole (Prilosec, and others) or other PPIs could interfere with the antiplatelet effect of clopidogrel. The conclusion was that patients taking both drugs should probably continue to do so until more data became available. Several new publications require reconsideration of that recommendation.

Clopidogrel (Plavix), which prevents arterial thrombosis by inhibiting platelet activation, is commonly prescribed (usually with aspirin) for months after acute coronary syndromes and stent implantation. It may also, however, increase the risk of bleeding. Therefore, a proton pump inhibitor (PPI) such as omeprazole (Prilosec, and others) is often given concurrently to decrease the risk of gastrointestinal (GI) bleeding. Some reports have suggested that omeprazole may interfere with the antiplatelet effect of clopidogrel.

Peptic ulcers caused by treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) are mainly gastric ulcers. Most duodenal and other gastric ulcers are caused by the gram-negative bacillus Helicobacter pylori. Gastroesophageal reflux disease (GERD) is caused by gastric acid reflux into the esophagus. Drugs that suppress gastric acid production are the primary treatment for GERD and peptic ulcers.

The drugs of choice for treatment of some fungal infections are listed in the tables. Some of the indications and dosages recommended here have not been approved by the FDA. Other guidelines are available from the Infectious Diseases Society of America (www.idsociety.org).

A recent advertisement for the proton pump inhibitor (PPI) lansoprazole (Prevacid - TAP) suggests that children who cough at night, complain of abdominal pain, refuse to eat, or have a bad taste in their mouths may all have gastroesophageal reflux disease (GERD). A Bunny's Tummy Trouble, a children's book about GERD published by TAP, is now available as a patient handout in pediatricians' waiting rooms. The use of acid-suppressive drugs in infants and children has increased markedly in recent years and many of these drugs are now available in child-friendly formulations. A table in the article lists some of the drugs used to treat GERD in children.

To prevent irreversible damage to joints and minimize toxicities associated with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, disease modifying anti-rheumatic drugs (DMARDs) are now used early in the treatment of rheumatoid arthritis (RA). The DMARDs listed in the table on page 84 have no immediate analgesic effects, but can control symptoms and have been shown to delay and possibly stop progression of the disease. The NSAIDs listed in the table on page 88 have analgesic and anti-inflammatory effects, but may not affect the disease process. Oral corticosteroids can rapidly relieve joint symptoms and control systemic manifestations, but their chronic use is associated with many complications.

Ramelteon (Rozerem - Takeda), a melatonin receptor agonist, has been approved by the FDA for treatment of insomnia characterized by difficulty falling asleep. Unlike all other prescription hypnotics, which are classified as schedule IV drugs, ramelteon is not a controlled substance.

The FDA recently cleared the AmpliChip CYP450 Test (Roche), which analyzes blood-derived DNA to detect genetic variations in the activity of cytochrome P450 (CYP) enzymes CYP2D6 and CYP2C19 and determines the metabolizer status of the patient. The test is intended to help guide clinicians in prescribing individualized drug therapy. About 25% of all drugs, including many antidepressants and antipsychotics, are substrates of either CYP2D6 or CYP2C19. The test is being promoted initially to psychiatrists.

The FDA has reported that 5106 elderly patients with dementia treated with atypical (second generation) antipsychotics in 17 randomized controlled trials had a higher mortality rate (4.5% vs. 2.6%) than those receiving placebo. Most of the deaths were due to cardiovascular and infectious causes (such as pneumonia). The drugs used in the trials were aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal). As the increase in mortality was considered a class effect, the FDA advisory also included ziprasidone (Geodon), clozapine (Clozaril) and the olanzapine/fluoxetine combination (Symbyax). The manufacturers of all of these drugs will be required to add a "black box" warning to their labeling.

The FDA has approved marketing of Zegerid powder for oral suspension (Santarus), an immediate-release formulation of the proton-pump inhibitor (PPI) omeprazole (Prilosec, and others). All other oral PPIs are delayed-release, enteric-coated formulations designed to prevent degradation of the drug by gastric acid. Each 20- or 40-mg packet of Zegerid contains 1680 mg of sodium bicarbonate, which protects the drug from gastric acid degradation. A dose of Zegerid contains 460 mg of sodium, which may be excessive for some patients. Zegerid is the first oral PPI to be approved by the FDA for reduction of risk of upper GI bleeding in critically ill patients. The drug may be useful for patients who are unable to swallow and have nasogastric (NG) tubes in place. Zegerid costs $70.00 for 14 days' treatment, compared to less than $10 for 14 tablets of Prilosec OTC.

The drugs of choice for treatment of some fungal infections are listed in the table that begins on page 8. Some of the indications and dosages recommended here have not been approved by the FDA.

With the removal of Vioxx from the market and concerns about cardiovascular toxicity with other selective COX-2 inhibitors, patients are looking for safe alternatives, and manufacturers of other drugs are looking for additional market share. The COX-2 inhibitors first became popular because they have less upper GI toxicity than older less selective NSAIDs, at least in the short term, in patients not taking aspirin.

Three types of analgesic drugs are available: non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; opioids; and adjuvant drugs that are not usually thought of as analgesics, such as antidepressants, which can act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. Combining two different types of analgesics may provide an additive analgesic effect without necessarily increasing adverse effects.

Antimicrobial prophylaxis can decrease the incidence of infection, particularly surgical site infection, after certain operations, but this benefit must be weighed against the risks of toxic and allergic reactions, emergence of resistant bacteria, adverse drug interactions, superinfection and cost. Medical Letter consultants generally recommend antimicrobial prophylaxis only for procedures with high infection rates, those involving implantation of prosthetic material, and those in which the consequences of infection are likely to be especially serious.

Management of intermittent claudication, the most common symptom of peripheral arterial disease (PAD), involves both risk factor modification and symptomatic treatment (WR Hiatt, N Engl J Med 2001; 344:1608; RM Schainfeld, J Am Board Fam Pract 2001; 14:443).

Most peptic ulcers not caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with infection of the gastric mucosa by the gram-negative bacilli Helicobacter pylori. The majority of NSAID-related ulcers are gastric. H. pylori infection causes both duodenal and gastric ulcers. Eradication of H. pylori promotes healing and markedly decreases recurrence of both duodenal and gastric ulcers (A Shiotamni and DY Graham, Med Clin North Am 2002; 86:1447; FKL Chan and WK Leung, Lancet 2002; 360:933). The first step in the management of peptic ulcers is the diagnosis and treatment of H. pylori.

Laparoscopic surgery has become increasingly popular for the treatment of gastroesophageal reflux disease (GERD). The usual surgical procedure, a Nissen fundoplication, prevents reflux into the esophagus. The review compares medical treatment with a proton pump inhibitor vs. surgical therapy as well as open vs. the new laparoscopic technique. Morbidity and mortality with the procedures are discussed.

The FDA recently approved the proton pump inhibitor omeprazole magnesium (Prilosec OTC) for over-the-counter use for treatment of frequent heartburn. It will be marketed in late September or early October. Five proton pump inhibitors, including omeprazole, are available by prescription in the US (Medical Letter 2001; 43:36).

Recently pharmaceutical manufacturers have marketed a stereoisomer of a successful drug nearing patent expiration as a new drug. Examples, such as esomeprazole (Nexium) , levalbuterol (Xopenex), escitalopram (Lexapro) and dexmethylphenidate

Changes caused by one drug in the absorption, distribution, metabolism or excretion of another may lead to a pharmacokinetic adverse drug interaction (DN Juurlink et al, JAMA 2003; 289:1652). Additive drug interactions, such as vasodilation caused by both sildenafil (Viagra) and nitrates, can also have adverse effects.

Many different drugs are now used to treat rheumatoid arthritis. Nonsteroidal anti-inflammatory drugs (NSAIDs), listed in the table on page 26, have analgesic and anti-inflammatory effects, but may not affect the disease process. Corticosteroids can provide rapid relief of joint symptoms and control of systemic manifestations, but chronic use is associated with many complications. The "disease-modifying" anti-rheumatic drugs (DMARDs), listed on page 29, have no immediate analgesic effects, but can control symptoms and may delay progression of the disease (American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines, Arthritis Rheum 2002; 46:328). Interactions of anti-rheumatic drugs with other drugs are listed in The Medical Letter Handbook of Adverse Drug Interactions, 2003.

Esomeprazole magnesium (Nexium - AstraZeneca), the S-isomer of omeprazole (Prilosec), is the fifth benzimidazole proton pump inhibitor to become available in the United States. Omeprazole, which was the first, is going off patent this year.

Older patients are especially susceptible to drug-induced cognitive impairment. They are more likely to be taking multiple drugs, to have higher blood levels of those drugs because of renal or hepatic dysfunction, and to have pre-existing cognitive problems that make it difficult to detect the role of drugs causing new symptoms or making old ones worse.

Pantoprazole, the fourth benzimidazole proton pump inhibitor to become available in the United States, has been marketed for short-term oral treatment of erosive gastroesophageal reflux disease (GERD).

Many different drugs are now used to treat rheumatoid arthritis. Nonsteroidal anti-inflammatory drugs (NSAIDs) have analgesic and anti-inflammatory effects, but may not affect the disease process. The "disease-modifying anti-rheumatic"drugs (DMARDs) have no immediate analgesic effects, but can control symptoms and may delay progression of the disease.

Rabeprazole, a benzimidazole proton pump inhibitor similar to omeprazole and lansoprazole, has been approved by the FDA for treatment of duodenal ulcers, healing and maintenance treatment of erosive or ulcerative gastroesophageal reflux disease, and for long-term treatment of chronic hypersecretory conditions, including Zollinger-Ellison syndrome

Reports of adverse interactions between drugs continue to accumulate. Recently, the FDA has expanded the recommendations on drug interactions found in the package inserts of new drugs.

Cilostazol, a phosphodiesterase III inhibitor that has been used in Japan since 1988, has been approved by the FDA for treatment on intermittent claudication due to occlusive peripheral arterial disease.

Citalopram hydrobromide (Celexa - Forest/Parke-Davis), a selective serotonin reuptake inhibitor (SSRI) available in Europe since 1989, has now been approved by the US Food and Drug Administration (FDA) for treatment of depression. It is being advertised as having a 'favorable side-effect profile.'

The drugs of choice for treatment of deep fungal infections are listed in the table below. Some of the indications and dosages recommended here have not been approved by the FDA.

Most peptic ulcers not caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are now thought to be associated with infection of the gastric mucosa by the gram-negative bacilli Helicobacter pylori. The majority of NSAID-related ulcers are gastric. H. pylori have been associated with both duodenal and gastric ulcers. Eradication of H. pylori promotes healing and markedly decreases recurrence of both duodenal and gastric ulcers (AH Soll, JAMA, 275:622, 1996).

The US Food and Drug Administration (FDA) recently approved the marketing of clarithromycin (Biaxin - Abbott), a macrolide antibiotic, and omeprazole (Prilosec - Astra Merck), a proton pump inhibitor, for concurrent use in treatment of duodenal ulcers associated with Helicobacter pylori.

The drugs of choice for treatment of deep fungal infections are listed in the table on page 101. Some of the indications and dosages recommended here have not been approved by the US Food and Drug Administration. More detailed guidelines are available from the Infectious Diseases Society of America (J Sobel et al, Clin Infect Dis, volume 30, April 2000).

Lansoprazole (Prevacid -TAP), a proton pump inhibitor similar to omeprazole (Prilosec - Medical Letter, 32:19, 1990), has been approved by the US Food and Drug Administration for short-term treatment of active duodenal ulcer and erosive reflux esophagitis and for long-term treatment of chronic hypersecretory conditions, including the Zollinger-Ellison syndrome.

Most peptic ulcers not caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are now thought to be associated with infection of the gastric mucosa by the gram-negative bacilli Helicobacter pylori (NIH Consensus Development Panel, JAMA, 272:65, July 6, 1994). NSAID-related ulcers are usually gastric. H. pylori have been associated with both duodenal and gastric ulcers.

Fluvastatin (Lescol - Sandoz), an HMG-CoA reductase inhibitor, was recently marketed in the USA for treatment of hypercholesterolemia. A synthetic mevalonolactone derivative, it is chemically distinct from previously available drugs in this class.

Drugs that accelerate healing and prevent relapse or reurrence of peptic ulcers act either by decreasing gastric acidity or by enhancing mucosal defense mechanisms. Risk factors that may cause breakdown of mucosal defenses include the use of aspirinor other nonsteroidal anti-inflammatory drugs (NSAIDs) and the presence of Helicobacter pylori bacterial in the gastric antrum (AH Soll, Engl J Med, 322:909, 1990; WL Peterson, N Engl J Med, 324:1043, 1991).