Pioglitazone

Pioglitazone is a prescription drug indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings.

• Pioglitazone exerts its antihyperglycemic effect only in the presence of endogenous insulin. Pioglitazone should not be used to treat type 1 diabetes or diabetic ketoacidosis, as it would not be effective in these settings.
• Pioglitazone is available under the following different brand names: Actos.

Dosages of Pioglitazone:

Tablet

• 15 mg
• 30 mg
• 45 mg

Dosage Considerations – Should be Given as Follows:

Type 2 Diabetes Mellitus

• Indicated as monotherapy or with insulin or insulin secretagogues
• 15-30 mg orally with a meal every daily initially; may increase the dose by 15 mg with careful monitoring to 45 mg each day
• Monitor ALT at start of treatment, each month for 12 months, then every 3 months thereafter

Dosage Modification

• Coadministration with an insulin secretagogue (sulfonylurea): Decrease insulin secretagogue dose
• Coadministration with insulin: Decrease insulin dose by 10-25%
• Coadministration with strong CYP2C8 inhibitors (gemfibrozil): Limit maximum pioglitazone dose to 15 mg daily

Not recommended for pediatric use

Side effects of pioglitazone include:

• swelling (edema), when used in combination with sulfonylurea or insulin
• low blood sugar (hypoglycemia)
• upper respiratory infection
• headache
• heart failure
• sinus infection
• fracture of bone
• sore throat (pharyngitis)
• muscle pain
• aggravated diabetes
• diabetic swelling in the eye (macular edema)
• increased cholesterol
• decreased serum triglycerides
• decreased hematocrit/hemoglobin
• bladder cancer
• decreased visual acuity/blurred vision
• shortness of breath
• increased transaminases (amino acids)
• weight gain
• blood in urine
• abdominal pain
• feeling unwell (malaise)
• itching
• loss of appetite
• dark urine
• clay-colored stools
• yellowing of skin or eyes (jaundice)
• cold symptoms (stuffy nose, sneezing, cough)
• back pain
• tooth problems

Rare side effects of pioglitazone include:

• liver failure

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Pioglitazone has no known severe interactions with other drugs.
• Serious interactions of pioglitazone include:
  • eluxadoline
  • ethanol
• Pioglitazone has moderate interactions with at least 78 different drugs.
• Pioglitazone has minor interactions with at least 135 different drugs.

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns, or for more information about this medicine.

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 for signs and symptoms of heart failure (including excessive, rapid weight gain; shortness of breath; and/or swelling [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
• The 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
• This medication contains pioglitazone. Do not take Actos if you are allergic to pioglitazone or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Hypersensitivity to pioglitazone
• Diabetic ketoacidosis
• Moderate-severe hepatic impairment (alanine aminotransferase [ALT] over 2.5x urate-lowering therapy [ULN])
• Chronic heart failure (NYHA class III, IV)

Effects of Drug Abuse

• No information available

Short-Term Effects

• See "What Are Side Effects Associated with Using Pioglitazone?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Pioglitazone?"

Cautions

• To initiate treatment in patients with active liver disease who have alanine aminotransferase levels (ALT) greater than 2.5 times the upper limit of normal (urate-lowering therapy [ULN]); if ALT is greater than 3 times the ULN, stop treatment; if ALT is 1.5-3 times the ULN, retest weekly 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 swelling (edema) and shortness of breath (dyspnea) were reported.
• Swelling near the retina 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 low blood sugar (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 the 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 chronic heart failure; 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 are observed after initiating therapy (blood or red-colored urine, new or worsening urinary urgency, pain on urination).

Pregnancy and Lactation

• 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 the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.
• 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 the underlying maternal condition.