Dosing & Uses
Dosage Forms & Strengths
tablet
- 15mg
- 30mg
- 45mg
Type 2 Diabetes Mellitus
Indicated as monotherapy or with insulin or insulin secretagogues
15-30 mg PO with meal qDay initial; may increase dose by 15 mg with careful monitoring to 45 mg qDay maximum
Monitor ALT at start of treatment, qMonth for 12 months, q3Months thereafter
Dosage Modification
Coadministration with insulin secretagogue (eg, sulfonylurea): Decrease insulin secretagogue dose
Coadministration with insulin: Decrease insulin dose by 10-25%
Coadministration with strong CYP2C8 inhibitors (eg, gemfibrozil): Limit maximum pioglitazone dose to 15 mg qDay
X-Linked Adrenoleukodystrophy (Orphan)
Hydroxypioglitazone: Orphan designation for treatment of X-linked adrenoleukodystrophy
Sponsor
- Minoryx Therapeutics S.L.; TecnoCampus Mataro-Maresme. TCM3 602, Av. Ernest Lluch, 32; Mataró, Spain
Not recommended
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Edema when used in combination with sulfonylurea or insulin (<27%)
Hypoglycemia (<27%)
Upper respiratory infection (13%)
1-10%
Headache (9%)
Heart failure (up to 8%)
Sinusitis (6%)
Fracture of bone (5%)
Pharyngitis (5%)
Myalgia (5%)
Frequency Not Defined
Aggravated diabetes
Diabetic macular edema
Hepatic failure (rare)
Increased cholesterol
Decreased serum triglycerides
Hematocrit/hemoglobin
Bladder cancer
Decreased visual acuity
Dyspnea
Increased transaminases
Pharyngitis
Sinusitis
Weight gain
Warnings
Black Box Warnings
Thiazolidinediones, including pioglitazone and rosiglitazone, cause or exacerbate congestive heart failure in some patients
After initiation of these drugs, as well as after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain; dyspnea; and/or edema); if these signs or symptoms develop, the heart failure should be managed according to the current standards of care; furthermore, discontinuation or dose reduction of these drugs must be considered.
These drugs are not recommended for patients with symptomatic heart failure; initiation of these drugs in patients with established NYHA class III or IV heart failure is contraindicated
Contraindications
Hypersensitivity to pioglitazone
Diabetic ketoacidosis
Moderate-severe hepatic impairment (ALT >2.5x ULN)
CHF (NYHA class III, IV)
Cautions
Do initiate treatment in patients with active liver disease who have ALT levels >2.5 times the upper limit of normal (ULN); if ALT >3 times the ULN, stop treatment; if ALT is 1.5-3 times the ULN, retest qWeek until normal or until it reaches 3 times the ULN and treatment must be discontinued
Not recommended for patients with symptomatic heart failure; may cause or exacerbate congestive heart failure in some patients; monitor patients carefully after initiating therapy; observe for signs and symptoms of heart failure; if signs and symptoms develop, manage heart failure according to current standards of care; consider discontinuing therapy or reducing the dose
New onset or exacerbation of existing edema and dyspnea reported
Macular edema reported; patients should be seen by an ophthalmologist if any visual symptoms arise during therapy; all diabetic patients should have regular eye exams
Delayed related weight gain reported with use; likely associated with fluid retention and fat accumulation
Thiazolidinediones, which are peroxisome proliferator-activated receptor (PPAR) gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin
Risk of hypoglycemia, in combination with insulin or other oral agents
May result in ovulation in some premenopausal, anovulatory women; ensure adequate contraception
May decrease hemoglobin/hematocrit
Increased fracture risk in females
Use with caution in premenopausal/anovulatory females (patient may resume ovulation and increase the risk of pregnancy)
Discuss potential for unintended pregnancy with premenopausal women as therapy with pioglitazone, like other thiazolidinediones, may result in ovulation in some anovulatory women
Increased risk of CHF; not recommended in symptomatic heart failure
Cancer risk
- Bladder cancer
- Pioglitazone may be linked to an increased risk of bladder cancer
- Do not prescribe for patients with active bladder cancer
- Consider benefit:risk ratio before prescribing in patients with a history of bladder cancer
- Instruct patients to contact their physician if signs of bladder cancer observed after initiating therapy (eg, blood or red colored urine, new or worsening urinary urgency, pain on urination)
- Prostate cancer
- 7/22/2015: Compared with nonuse, pioglitazone use was associated with increased risk for prostate cancer (453.3 vs. 449.3 per 100,000 person-years) [JAMA 2015 July 21;314(3):265-277]
- Pancreatic cancer
- 7/22/2015: Compared with nonuse, pioglitazone use was associated with increased risk for pancreatic cancer (81.1 vs. 48.4 per 100,000 person-years)
Pregnancy & Lactation
Pregnancy: 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; poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, still birth and delivery complications; poorly controlled diabetes increases fetal risk for major birth defects, still birth, and macrosomia related morbidity
Lactation: There is no information regarding the presence of pioglitazone in human milk, the effects on the breastfed infant, or the effects on milk production; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for pioglitazone and any potential adverse effects on the breastfed infant from pioglitazone or from the underlying maternal condition
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
Improves target-cell response to insulin; decreases hepatic gluconeogenesis; depends on the presence of insulin for activity
Absorption
Onset: Initial effect (delayed), max effect (several weeks)
Duration: 24 hr
Peak plasma time: 2-4 hr (delayed by food)
Distribution
Protein bound: >99%
Vd: 0.63 L/kg
Metabolism
Metabolized by hepatic CYP2C8 and CYP3A4 into active metabolites
Active metabolites: Metabolite II (hydroxy derivative), metabolite III (keto derivative), metabolite IV (active hydroxy derivative)
Elimination
Half-life: 3-7 hr
Excretion: Urine (15-30%)
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Patient Handout
Formulary
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