May, 2000, Volume 1
Formulary Additions
Pioglitazone (Actos®)
Takeda Pharmaceuticals America,
Inc.
Thiazolidinediones, the newest class of
antidiabetic agents, includes pioglitazone (Actos®), rosiglitazone
(Avandia®) and the recently discontinued product troglitazone
(Rezulin®). Pioglitazone is
indicated as monotherapy or in combination with metformin, insulin, or
sulfonylureas for type 2 diabetes.
These agents act by inhibiting hepatic glucose production without
increasing insulin secretion. Currently, there are no comparative efficacy studies between the
thiazolidinediones.
Pioglitazone monotherapy should be
initiated at a dose of 15mg or 30mg once daily. The dosage can be increased in increments up to 45mg once
daily. Pioglitazone can be administered
with or without food. No dosage
adjustments are necessary inpatient with renal impairment or based on gender or
age. Daily cost of pioglitazone is
$2.35 to $3.76 (daily cost of rosiglitazone is $1.98 to $2.86).
Adverse reactions for pioglitazone
include edema, slight decreases in hemoglobin, weight gain and potential
hepatotoxicity (as seen with Rezulin®). Edema was reported as mild to moderate in nature, but should be
avoided in patients with NYHA class III or IV cardiac status. Weight gain has been noted in all clinical
trials with an unknown cause, but is dose dependent. Currently, pioglitazone has had no reported cases with a definite
link between its use and liver dysfunction.
Liver monitoring should include serum alanine transaminase (ALT) levels
and monitored as follows:
|
Monitoring of Liver Function for
Thiazolidinediones: ·
Prior to initiation of therapy ·
Do not initiate therapy if the ALT value is >2.5 upper
limits of normal ·
Every 2 months for the first year ·
Periodically thereafter or any time symptoms suggest
hepatic dysfunction *If
the ALT level exceeds three times the upper limit of normal, the test should be repeated.
*If
the levels remain greater than three times the upper limit of normal or the patient is jaundiced, pioglitazone should be
discontinued. Patients should be counseled to report
signs of liver toxicity, including nausea or vomiting, abdominal pain, fatigue,
anorexia or dark urine as soon as possible. |
Pioglitazone is contraindicated in patients
with known hypersensitivity to the product.
This medication is considered pregnancy category C and not recommended
for administration in women who are nursing.
Pioglitazone has no know drug interactions. Metabolism occurs via the cytochrome P450 isoforms, CYP2C8 and
CYP3A4, therefore caution should be used with medications metabolized by the
cytochrome P450 3A4 system. This
caution extends to the oral contraceptives.
Ketoconazole significantly inhibits the metabolism of pioglitazone, but
no assessments can be make about the need for dosage adjustments when given
concurrently. Additional precautions
include the potential for hypoglycemia when pioglitazone is used in combination
with insulin or sulfonylureas.
|
FOOD/DRUG
INTERACTION: Pioglitazone may be administered without regard to food |
