Strong CYP2C8 inhibitor significantly increases pioglitazone exposure and half-life. Maximum pioglitazone dose limited to 15 mg daily.
Source: NLP:pioglitazone
Pioglitazone Interactions
Brand names: Pioglitazone
Peroxisome Proliferator Receptor alpha Agonist · Peroxisome Proliferator Receptor gamma Agonist · Thiazolidinedione · Peroxisome Proliferator-activated Receptor alpha Agonists · Peroxisome Proliferator-activated Receptor gamma Agonists
Route: Oral
FDA Black Box Warning
WARNING: CONGESTIVE HEART FAILURE Thiazolidinediones, including pioglitazone , cause or exacerbate congestive heart failure in some patients [see Warnings and Precautions (5.1) ] . After initiation of pioglitazone , and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema). If heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of pioglitazone must be considered. Pioglitazone is not recommended in patients with symptomatic heart failure. Initiation of pioglitazone in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated [see Contraindications (4) and Warnings and Precautions (5.1) ] . WARNING: CONGESTIVE HEART FAILURE See full prescribing information for complete boxed warning. Thiazolidinediones, including pioglitazone, cause or exacerbate congestive heart failure in some patients. (5.1) After initiation of pioglitazone, and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea, and/or edema). If heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of pioglitazone must be considered. (5.1) Pioglitazone is not recommended in patients with symptomatic heart failure. (5.1) Initiation of pioglitazone in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated. (4 , 5.1)
Contraindications
4 CONTRAINDICATIONS Initiation in patients with established NYHA Class III or IV heart failure [see Boxed Warning ]. Use in patients with known hypersensitivity to pioglitazone or any other component of pioglitazone tablets. Initiation in patients with established New York Heart Association (NYHA) Class III or IV heart failure [see Boxed Warning ] . (4) Use in patients with known hypersensitivity to pioglitazone or any other component of pioglitazone tablets. (4)
Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary Limited data with pioglitazone in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations] . In animal reproduction studies, no adverse developmental effects were observed when pioglitazone was administered to pregnant rats and rabbits during organogenesis at exposures up to 5- and 35-times the 45 mg clinical dose, respectively, based on body surface area [see Data] . The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20 to 25% in women with a HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, still birth and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity. Data Animal Data Pioglitazone administered to pregnant rats during organogenesis did not cause adverse developmental effects at a dose of 20 mg/kg (~5-times the 45 mg clinical dose), but delayed parturition and reduced embryofetal viability at 40 and 80 mg/kg, or ≥9-times the 45 mg clinical dose, by body surface area. In pregnant rabbits administered pioglitazone during organogenesis, no adverse developmental effects were observed at 80 mg/kg (~35-times the 45 mg clinical dose), but reduced embryofetal viability at 160 mg/kg, or ~69-times the 45 mg clinical dose, b
9 interactions on record
Pioglitazone + AbirateroneModerate
CYP2C8 substrate with AUC increased by 46% when co-administered with abiraterone. Monitor closely for toxicity signs.
Source: NLP:abiraterone
CYP2C8 substrate with 46% AUC increase when co-administered. Monitor closely for toxicity, especially if narrow therapeutic index.
Source: NLP:abiraterone acetate
Pioglitazone + LeflunomideModerate
Exposure to pioglitazone may be increased when coadministered with leflunomide. Monitor and adjust dose as required.
Source: NLP:leflunomide
Exposure of pioglitazone may be increased in patients taking leflunomide. Monitor and adjust dose as required.
Source: NLP:leflunomide and diclofenac sodium gel
Pioglitazone + RifampinModerate
CYP2C8 inducer may significantly decrease pioglitazone exposure. Diabetes treatment changes may be needed based on clinical response.
Source: NLP:pioglitazone
BACTRIM potentiates oral hypoglycemic effects of pioglitazone. Additional blood glucose monitoring warranted.
Source: NLP:sulfamethoxazole and trimethoprim
Pioglitazone + TeriflunomideModerate
Teriflunomide may increase exposure of pioglitazone. Monitor patients and adjust dose as required.
Source: NLP:teriflunomide
Pioglitazone + TopiramateModerate
Decrease in exposure of pioglitazone and its active metabolites; careful monitoring recommended.
Source: NLP:topiramate