Lantus

Exelon

(rivastigmine, Novartis)

A cholinesterase inhibitor for treating mild to moderate dementia of the Alzheimer's type.

* Recommended Dosage: A dose of 3-6 mg twice a day was effective in trials. Start at 1.5 mg twice a day and slowly titrate up to a maximal dose of 12 mg/day, in two divided doses taken with breakfast and dinner.

* Special Considerations: Nearly 50% of patients on 6-12 mg/day in trials developed nausea, and 31% had at least one episode of vomiting, according to the drug's labeling. Anorexia and weight loss rates were also high. But investigator Dr. George T. Grossberg said that these rates include data from trials where forced titration was used. By starting at a low dose and gradually titrating at 2- to 4-week intervals, with the doses taken with breakfast and dinner GI side effects are lower, he said, noting that in studies where the drug was given this way, the retention rate was over 90%.

* Comment: In trials of people with mild to moderate Alzheimer's disease, mean cognitive scores among those treated with 6-12 mg/day improved over 26 weeks and were significantly different than patients on placebo, whose cognitive scores declined. Other reliable data have shown that treatment with this compound "can have as much, if not more, of an impact on behavior and activities of daily living," said Dr. Grossberg, director of geriatric psychiatry at St. Louis University.

Data on patients with moderate to severe Alzheimer's, which include peer-reviewed data presented at national meetings and data pending publication, indicate that Exelon may be even more effective in this population, he added. This maybe related to its dual mechanism of action: Exelon selectively inhibits both acetylcholinesterase, which is increased early in the disease, but drops as the disease progresses, and butyrylcholinesterase, which increases as the disease progresses, he explained. There is also laboratory evidence that butyrylcholinesterase may be needed to activate amyloid.

Aricept (donepezil) inhibits acetylcholinesterase only; Cognex (tacrine) also inhibits butyrylcholinesterase but is no longer prescribed because it causes liver toxicity said Dr. Grossberg, who has been a consultant to Novartis and served for 3 years on an international data safety monitoring board for Exelon.

Lantus

(insulin glargine injection, Aventis)

A long-acting human insulin analogue for once-daily administration for adults and children with type 1 diabetes and adults with type 2 diabetes. This is the first long acting human basal insulin analogue that is steadily absorbed over 24 hours and has no peak.

* Recommended Dosage: Individually determined dose administered subcutaneously once daily at bedtime.

* Special Considerations: As with all in-sulins, hypoglycemia is the most common adverse effect, but the risk is lower than with NPH insulin. Because of its low pH, should never be diluted or mixed with other insulins (there is no need to do this anyway since it is given alone at bedtime).

* Comment: Once injected, Lantus is slowly released from the subcutaneous tissue over 24 hours in a reproducible and predictable absorption pattern, with no peaks and a flat glycemic curve, said Dr. Robert Ratner, medical director of Med Star Clinical Research Center, Washington. This reproducibility is "critically important and is the major advantage" of Lantus over human ultralente, which is highly variable in terms of its absorption, "clearly has a peak, and causes erratic hypoglycemia," he explained.

Lantus can be used in any patients who are candidates for an overnight dose of NPH or ultralente, in combination with regular insulin or the more rapidiy acting Humalog (lispro insulin) before meals in type 1 diabetics, and with short-acting insulin or oral agents in type 2 diabetics, Dr. Ratner advised. In type 1 diabetics, Lantus as a basal bolus regimen is "as close as we can get without an insulin pump to mimicking normal physiology," he observed. Trials comparing a regimen that includes Lantus to treatment with the insulin pump are being planned.

Dr. Ratner, the principal investigator in studies of Lantus in type 1 diabetics, has received research funds from Aventis.

Lantus won't be available until later this year.

COPYRIGHT 2000 International Medical News Group
COPYRIGHT 2001 Gale Group