Although cyclooxygenase 2 (COX-2) inhibitors, also called “coxibs,” can be easier on the gastrointestinal system than nonsteroidal anti-inflammatory drugs (NSAIDs are, some physicians prefer to err on the side of caution by prescribing a gastroprotective agent (GPA) as well. The coxibs were named after two recently developed anti-inflammatory drugs, canadian celecoxib (Celebrex drug, Pharmacia) and rofecoxib (Vioxx®, Merck).

Canadian researchers analyzed data from 42,267 patients who were taking COX-2 inhibitors; 8,235 patients who were taking NSAIDs, and 19,716 patients who received acetaminophen. The researchers concluded that adding a GPA to a coxib constitutes an unnecessary financial burden, particularly if the GPA prescription is unwarranted.

Physicians in the study were more likely to prescribe coxibs than NSAIDs for patients who were older or sicker or who had risk factors associated with gastropathy from NSAID use. They also tended to prescribe coxibs over acetaminophen for patients with musculo-skeletal disorders and osteoarthritis, presumably because of the anti-inflammatory analgesia associated with coxibs. (At the time of the study, rofecoxib had not yet been indicated for rheumatoid arthritis.)

As coxibs gained popularity, it was expected that prescriptions for GPAs might decline along with the decrease in NSAID prescriptions, but that was not the case. GPAs in this study, however, were prescribed 47% less often for coxib users than for NSAIDs users. Studies have indicated that coxibs—although more expensive than NSAIDs—would be cost-effective in patients at high risk for gastrointestinal events with NSAIDs, the investigators noted.

Other studies have shown that the cost-effectiveness of rofecoxib, compared with that of the nonselective NSAIDs, for patients with osteoarthritis is “sensitive to the rate of prophylactic GPA use,” according to the authors.

When the researchers re-analyzed the data, keeping only the patients who did not have any previous gastrointestinal events, cancer, or any filled prescriptions for coxibs, NSAIDs, or acetaminophen, a GPA co-prescription was 61% less frequent with coxibs than with NSAIDs. A co-prescription of a GPA with coxibs was equivalent to one with acetaminophen— a striking finding, the researchers say, considering that physicians do not perceive acetaminophen as being toxic to the gastrointestinal tract.

Etoricoxib, a highly selective COX-2 inhibitor, was evaluated in two recent trials: one for patients with rheumatoid arthritis, the other for patients with acute gouty arthritis.

In the first study, conducted for the Etoricoxib Rheumatoid Arthritis Study Group, 687 patients completed 12 weeks of treatment with placebo, etoricoxib 90 mg/day, or naproxen 500 mg BID. The study was conducted at 67 sites in 28 countries. Compared with patients on placebo, patients in both drug groups showed significant improvements in all endpoints. Similar percentages (58% and 59%) of naproxen and etoricoxib patients, respectively, responded according to American College of Rheumatology criteria: tender joint and swollen joint counts, patient and investigator assessment of disease activity. Etoricoxib treatment effects were rapid, the investigators say, occurring at the earliest time measured (week two) and were maintained over the entire study period. Both drugs were similarly well-tolerated. Only three serious clinical adverse events were judged to be drug-related: two patients on etoricoxib (duodenal ulcer and hip pain), and one on naproxen (hypertension).

In the second trial, of 150 patients in 11 countries with acute gouty arthritis, a once-daily dose of etoricoxib 120 mg worked as well for symptoms as did indometacin 50 mg three times daily for eight days. There were also controls for each drug. Both etoricoxib and indometacin groups experienced comparable pain relief, starting four hours after the initial dose. The two drugs were well-tolerated. Four patients in the indometacin group reported serious adverse events (vomiting and headache). Etoricoxib was associated with a lower incidence of drug-related adverse events (P=0.003) than indometacin.

When opioid therapy does not relieve pain or when it leaves patients with intolerable side effects, a new option might be ziconotide (SNX-111, Pfizer/Elan/ Warner-Lambert/Partner Medtronic).

In experimental studies, the fact that intrathecal ziconotide cleared rapidly suggested that it would also metabolize through the cerebrospinal fluid rapidly. One study involved 24 patients who had chronic pain from cancer, acquired immunodeficiency syndrome (AIDS), and other conditions and who experienced pain control with opioids, even when they were given intrathecally. Of those 24 patients, 19 rated their pain on the Visual Analogue Scale of Pain Intensity as 43% lower in degree and 15 patients were able to reduce their concomitant use of opioids by at least 50%. Central nervous system effects were diminished or resolved when the infusion rate was reduced or stopped.

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Rofecoxib (Vioxx®, Merck) works as well as naproxen (e.g., Drug Naprosyn®, Roche) at controlling the symptoms of osteoarthritis and is also effective at a much lower dose and with less severe adverse gastrointestinal (GI) effects. The ADVANTAGE (Assessment of Differences between Vioxx And Naproxen To Ascertain Gastrointestinal tolerability and Effectiveness) Study Group compared the use of rofecoxib 25 mg/day with that of naproxen 500 mg twice daily in 5,557 older patients with osteoarthritis. This is thought to be the largest trial to compare GI symptoms that prompt patients to discontinue treatment.

Overall, a statistically significant lower number of patients stopped taking rofecoxib (5.9%) because of GI adverse drug events (ADEs) compared with the naproxen group (8.1%). A similar risk of ending treatment was noted among subgroups of patients using low-dose aspirin and among those who had previously ceased to use their arthritis medication because of GI symptoms. Improved GI tolerability was confirmed by the decreased use of gastroprotective medications and by a reduced incidence of serious GI events, such as perforations, ulcers, and bleeding. No significant differences were observed in general, cardiovascular, or hypertension-related ADEs.

The FDA has approved the daily use of the anticonvulsant drug canadian topiramate (Topamax®, Ortho-McNeil) to prevent migraine headaches.

Stopping migraines before they start is controversial. The therapy may reduce the frequency of migraines but rarely eliminates them entirely.

In two studies of 900 patients who suffered four to eight migraines a month, the patients were given daily doses of the drug or a placebo. About 50% of the patients taking Topamax® reported at least a 50% reduction in the number of monthly headaches. Most patients who responded to therapy started feeling better in the first month.

Beta blockers, tricyclic antidepressants (TCAs), calcium-channel blockers, and even botulinum (Botox®) are also prescribed to prevent migraine; however, beta blockers can make exercise difficult, TCAs are associated with potential urination problems and weight gain, calcium-channel blockers may work better than beta blockers for migraine accompanied by an aura, anticonvulsants (e.g., Topa-max®) may cause tingling and memory lapses, and Botox® is expensive.

The most common side effects of Generic Topamax are tingling and fatigue and occasional memory or concentration problems. From 5% to 12% of patients reported weight loss.

Most patients use triptans (e.g., suma-triptan succinate [Generic Imitrex®]) to relieve occasional migraines, but these do not work for 20% to 30% of patients.

Doctors hope that the attention given to the recent drug approval will prompt more patients to seek treatment for their pain. The problem is often undertreated, either because patients don’t ask for help or because doctors don’t take it seriously.

Whereas a six-month supply of Topa-max costs $655, a six-month supply of generic propranolol sells for $16.

In Canada, when the Ontario government began paying for a new generation of supposedly safer arthritis drugs, the number of hospital admissions for stomach bleeding rose.

The unexpected finding runs counter to expectations that these widely prescribed drugs, called cyclooxygenase (COX-2) inhibitors, would relieve pain and inflammation with little risk of stomach upset and irritation. This analysis, however, is based on a retrospective look at health data for elderly people rather than on a more rigorous trial.

The COX-2 inhibitors, part of a class of drugs known as NSAIDs, have become blockbusters. For many doctors, managing the risk of stomach bleeding seemed worth the price, as that is a major drawback of the older NSAIDs, such as ibuprofen and aspirin, which sell for pennies a day.

The authors of the Canadian report could not trace each bleeding case to the use of a specific NSAID. Nevertheless, the report suggested that the increased use of COX-2 inhibitors and gastrointestinal (GI) bleeding are directly related.

Researchers believe that the use of COX-2 inhibitors, including rofecoxib (Vioxx®, Merck), drug celecoxib (Celebrex generic (Pfizer), and drug meloxicam (Mobic canadian, Boehringer Ingelheim), has resulted in more stomach bleeding because more patients have been encouraged to use the newer drugs. In fact, a group of 90,000 people who had not been taking any NSAIDs started taking COX-2 drugs after the Ontario government began paying for them. Afterward, hospital admissions for GI bleeding increased by 10% out of a pool of 1.3 million elderly patients in Ontario.

Other factors, such as the increased use of over-the-counter NSAIDs, might explain the study results.

When hormone replacement therapy is not an option for patients with hot flashes, gabapentin (Medication Neurontin, Pfizer), usually prescribed for pain, might be a solution.

A patient at the University of Buffalo was experiencing severe hot flashes 20 to 30 times a day after a hysterectomy and a salpingo-oophorectomy at age 32. Her nighttime sleep was disrupted. Conjugated estrogens and selective serotonin reuptake inhibitors (SSRIs), which are used to treat depression, had no effect.

Her physician prescribed gabapentin 300 mg three times daily and removed an drug estradiol patch that she had been wearing. Within three weeks, the hot flashes were dramatically reduced, to only a few a day. A month later, they became more frequent again, and the gabapentin dosage was raised to four times daily, with positive results. The patient’s sleep improved, and she experienced no side effects.

Gabapentin, estrogen, and SSRIs may all target different cellular sources of the flushing.