|
|
Nadeen Hosein, M.D. and Brian Pinto, Pharm.D.
11-24-2010
- The thiazolidinediones (TZDs) are PPAR (peroxisome proliferator activated receptor) gamma agonists.
- They increase insulin-dependent glucose disposal and decrease hepatic glucose output by decreasing insulin resistance in the liver and in the periphery.
- They also affect fatty acid metabolism.
- Prior to starting a TZD, check liver enzyme levels. Do not use if active liver disease is present, or if ALT (a.k.a. SGPT) is elevated by more than 2.5 times the upper limit of normal.
- Pioglitazone: 15-30 mg by mouth once a day. Maximum dose is 45 mg once daily.
- Rosiglitazone: 2-4 mg by mouth once or twice per day. Maximum total daily dose is 8 mg daily.
brand
name
| generic
| Mfg
| brand
forms
| cost*
|
| Actos | pioglitazone hydrochloride | Takeda, PD-Rx Pharmaceuticals | oral
tablet
15 mg | $149 for 30 brand name tabs |
|
|
|
| oral
tablet
30 mg | $213 for 30 brand name tabs |
|
|
|
| oral
tablet
45 mg | $233 for 30 brand name tabs |
| Avandia | rosiglitazone maleate | GlaxoSmithKline | oral
tablet
2 mg | $82 for 30 brand name tabs |
|
|
|
| oral
tablet
4 mg | $129 for 30 brand name tabs |
|
|
|
| oral
tablet
8 mg | $239 for 30 brand name tabs |
*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP).
AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's
information, and the McKesson database.
^Dosage is indicated in mg unless otherwise noted.
- No dosage adjustment necessary
- Not recommended in patients with active liver disease or with ALT (a.k.a. SGPT) elevation more than 2.5 times the upper limit of normal
- Thomson Lactation Ratings: infant risk cannot be ruled out
- Pioglitazone - BLACK BOX WARNING for CONGESTIVE HEART FAILURE: "may cause or worsen congestive heart failure. Monitor patients for signs and symptoms of heart failure; if they develop, consider discontinuing drug. Contraindicated in NYHA Class III or IV heart failure."
- Rosiglitazone - BLACK BOX WARNING for CONGESTIVE HEART FAILURE AND MYOCARDIAL ISCHEMIA: "may cause or worsen congestive heart failure. Monitor patients for signs and symptoms of heart failure; if they develop, consider discontinuing drug. Contraindicated in NYHA Class III or IV heart failure. A meta-analysis of 42 clinical studies showed rosiglitazone to be associated with an increased risk of myocardial ischemic events such as angina or myocardial infarction. Three other studies have not confirmed or excluded this risk. In their entirety, the available data on the risk of myocardial ischemia are inconclusive."
- Not to be used as antihyperglycemic therapy for type 1 diabetes mellitus or in patients with diabetic ketoacidosis.
- Monitor liver enzymes in all patients, as hepatitis and liver failure have been reported (though rare).
- Weight gain due to both fluid retention and to increased adipose tissue (evidence that the increased fat is peripheral, not central)
- Edema due to fluid retention
- Ovulation in previously anovulatory women with PCOS
- Increased risk of fracture, especially in women
- Fulminant hepatitis leading to liver failure
- Macular edema
- Pulmonary edema or pleural effusions
-
Bile acid sequestrants may decrease the absorption of TZDs. Separate the dosing of these agents by at least 2 hours.
- Nitrates may enhance the adverse/toxic effect of rosiglitazone. Specifically, a greater risk of myocardial ischemia was reported for users of this combination in a meta-analysis of 42 rosiglitazone clinical trials. Though not contraindicated in the rosiglitazone prescribing information, the combination of rosiglitazone and a nitrate is not recommended.
- Overall HbA1c reduction with the TZDs is about 1-1.5%.
- Weight gain is common and often disturbing to patients.
- Fluid retention also common. Risk for heart failure increased by approximately two-fold.
- Pioglitazone has a beneficial effect on lipids (decreased TG and increased HDL) compared to rosiglitazone.
- Controversy exists about possible increased risk for myocardial ischemia for rosiglitazone, reported in a meta-analysis (Nissen) which found an increased risk for myocardial infarction with rosiglitazone. A subsequent prospective study, (RECORD) (Home) and another meta-analysis (Selvin) have not confirmed this finding, but the FDA has a black box warning for rosiglitazone, but not pioglitazone, for myocardial ischemia (see above).
- In September 2010, the FDA announced a decision to severely reduce access to rosiglitazone after an updated meta-analysis of 52 studies demonstrated ~ 28% increased risk of myocardial ischemia with rosiglitazone (Nissen). Patients will be required to document that they understand risks of continuing on this medication once the legislation is implemented and/or that no other medication for diabetes are effective for them.
- In women, increased risk of bone fractures, especially in the distal upper limb and distal lower limb (forearm, hand, wrist, foot, ankle, tibia, fibula). Early evidence of decreased bone formation activity. (Home, Dormuth)
- No hypoglycemia unless used in conjunction with insulin or insulin secretagogues.
- Generic tablets are not available in U.S., so cost may be an issue.
- TZDs may offer particular benefits in patients with HIV-associated dyslipidemia/lipodystrophy and diabetes.
- Nissen SE, Wolski K;
Rosiglitazone Revisited: An Updated Meta-analysis of Risk for Myocardial Infarction and Cardiovascular Mortality.;
Arch Intern Med;
2010; Vol.
ISSN:
1538-3679;
PUBMED: 20656674
Rating:
Basis for recommendation
Comments:This updated meta-analysis of 52 trials found that rosiglitazone was associated with significant 28% increased risk of myocardial ischemia and prompted new FDA restrictions limiting use of the drug in September 2010.
|
|
