Rx Update: May 2000
Mary Ross, R.Ph., M.B.A.
Peer Review Status: Internally Reviewed
Pioglitazone exerts its antiglycemic effect only in the presence of insulin and should not be used in type 1 diabetic patients or for treatment of diabetic ketoacidosis. This drug should be used with caution in patients with edema due to its effect of expansion of plasma volume. Pioglitazone may result in the resumption of ovulation in premenopausal, anovulatory women with insulin resistance; adequate contraception should be used to avoid the risk of pregnancy.
Adverse reactions commonly reported during clinical trials were upper respiratory tract infection, headache, sinusitis, myalgia, edema, pharyngitis, and anemia. Because other members of this drug class have been associated with hepatotoxicity, pioglitazone should be avoided in patients with evidence of acute liver disease, patients who exhibited hepatic dysfunction with troglitazone or rosiglitazone, and patients who have elevated liver enzymes (i.e., ALT 2.5xULN). Liver enzyme testing should be performed before initiation of pioglitazone therapy, every two months during the first year of therapy, and periodically thereafter.
Although the coadministration of oral contraceptives (ethinyl estradiol and norethindrone) and pioglitazone has not been evaluated, another thiazolidinedione reduces the plasma levels of both hormones, so additional contraceptive precautions should be used in patients on oral contraceptives and pioglitazone. The CYP3A4 substrate is partially responsible for the metabolism of pioglitazone. Ketoconazole appears to significantly inhibit the metabolism of pioglitazone; more frequent evaluation of glycemic control may be required. No drug interactions have been noted when pioglitazone was coadministered with glipizide, digoxin, warfarin, or metformin.
Pioglitazone is taken once a day without regard to meals; therapy is initiated at 15 to 30 mg. If a patient does not respond, the dose should slowly be increased to the maximum recommended dose of 45 mg a day. When used in combination with other antidiabetic agents, the dose of pioglitazone is 15 to 30 mg per day; doses of the concomitant drugs may require adjustment. Pioglitazone is available as 15 mg, 30 mg, and 45 mg tablets.
The most frequent adverse reaction to alosetron is constipation. Constipation can occur in up to 30% of patients. Alosetron should not be used in IBS patients who are currently constipated or whose predominant bowel symptom is constipation. In clinical trials, 9% of patients required interruption of therapy because of constipation and 10% required discontinuation of therapy. Other adverse effects that have been reported with alosetron therapy are nausea, GI/abdominal discomfort and pain, flatulence, dyspeptic syndrome, abdominal distention, hypertension, and acute ischemic colitis.
The recommended dose of alosetron in women with IBS is 1 mg twice daily, given without regard to food. It is available in 1 mg tablets. At UIHC, initial orders and prescriptions must be signed by an attending staff physician from the Adult Gastroenterology Service.