pioglitazone

Absorption: Well absorbed following oral administration.

Distribution: Well distributed to tissues.

Protein Binding: >99%. Active metabolites are also highly (>99%) bound.

Metabolism/Excretion: Extensively metabolized by the liver via the CYP2C8 isoenzyme); at least two metabolites have pharmacologic activity. Primarily excreted in feces and urine as metabolites.

Half-Life: Pioglitazone: 3–7 hr; total pioglitazone (pioglitazone plus metabolites): 16–24 hr.

Time/Action Profile ⬆ ⬇

(effects on blood glucose)

ROUTE	ONSET	PEAK	DURATION
PO	30 min	2–4 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Type 1 diabetes;
Diabetic ketoacidosis;
Clinical evidence of active liver disease or ↑ ALT (>2.5 times upper limit of normal);
Active bladder cancer;
New York Heart Association (NYHA) Class III–IV HF
;
Pedi: Children.

Use Cautiously in:

Edema;
NYHA Class I–II HF
;
Hepatic impairment;
History of bladder cancer;
Women (may ↑ distal upper and lower limb fractures)
Rep: Women of reproductive potential;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema, HF

EENT: macular edema

GI: ↑liver enzymes, LIVER FAILURE

GU: BLADDER CANCER

Hemat: anemia

MS: fractures (arm, hand, foot) (women), RHABDOMYOLYSIS

Interactions ⬆ ⬇

Drug-drug:

May ↓ efficacy of hormonal contraceptives.
Strong CYP2C8 inhibitors, including gemfibrozil, may ↑ levels and risk of toxicity.
Ketoconazole may ↑ levels and risk of toxicity.
Insulin may ↑ risk of fluid retention and worsening HF.
Topiramate may ↓ levels and effectiveness.

Drug-Natural Products:

Glucosamine may worsen blood glucose control.
Chromium and coenzyme Q-10 may ↑ risk of hypoglycemia.

Route/Dosage ⬆ ⬇

PO (Adults ): No HF: 15–30 mg once daily; may ↑ in increments of 15 mg/day to 45 mg/day if needed; NYHA class I–II HF: 15 mg once daily; may ↑ in increments of 15 mg/day to 45 mg/day if needed; Concurrent use of gemfibrozil: Do not exceed 15 mg once daily.

Availability ⬆ ⬇

(Generic available)

Tablets: 15 mg; 30 mg; 45 mg
In combination with: metformin (Actoplus Met), glimepiride (Duetact), alogliptin; see Appendix [not included in this PDA edition].

Assessment ⬆ ⬇

Monitor for signs/symptoms of hypoglycemia (nausea, tachycardia, sweating, hunger, weakness, dizziness, light-headedness, confusion, tremor, anxiety).
Assess cardiac history and for signs and symptoms of HF (dyspnea, peripheral edema, rales/crackles, jugular venous distension) at initiation, during therapy, and with dose ↑.
Monitor for signs/symptoms of hepatotoxicity (fatigue, nausea, upper abdominal pain, jaundice, scleral icterus, dark urine, clay-colored stools).
Assess and monitor bone health. ↑ risk of fractures in female patients, especially in the distal upper limb (forearm, hand, wrist) or distal lower limb (foot, ankle, fibula, tibia).
Screen for history of bladder cancer prior to initiation of therapy. Prolonged use >12 mo ↑ risk of bladder cancer.

Lab Test Considerations:

Monitor serum glucose periodically and A1c every 6 mo during therapy to evaluate effectiveness.
- Monitor CBC with differential periodically during therapy. May ↓ hemoglobin and hematocrit, usually during the 1st 4–12 wk of therapy; then levels stabilize.
- Monitor serum AST, ALT, alkaline phosphatase, and total bilirubin before starting therapy and periodically thereafter or if jaundice or symptoms of hepatic impairment occur. Patients with mild ALT ↑ should have more frequent monitoring. If ALT ↑ to >3 times upper limit of normal (ULN), recheck ALT promptly. Discontinue pioglitazone if ALT remains >3 times ULN.
- May cause transient ↑ in CK levels.

Implementation ⬆ ⬇

Do not confuse Actos with Actonel.
Patients stabilized on a diabetic regimen who are exposed to stress, fever, trauma, infection, or surgery may require administration of insulin.
PO: May be administered with or without meals.

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of pioglitazone. Instruct patient to take as directed. If dose for 1 day is missed, do not double dose the next day. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
Explain need for continued medical follow-up to assess effectiveness and possible side effects of medication. Periodic lab tests may be needed.
Explain to patient that this medication controls hyperglycemia but does not cure diabetes. Therapy is long term.
Review signs of hypoglycemia and hyperglycemia with patient. If hypoglycemia occurs, advise patient to take a glass of orange juice or 2–3 teaspoons of sugar, honey, or corn syrup dissolved in water and notify health care provider.
Advise patient to carry a form of sugar (sugar packets, candy) and identification describing disease process and medication regimen at all times.
Encourage patient to follow prescribed diet, medication, and exercise regimen to prevent hypoglycemic or hyperglycemic episodes.
Instruct patient in proper testing of serum glucose and ketones. These tests should be closely monitored during periods of stress or illness, and health care provider should be notified if significant changes occur.
Advise patient to notify health care provider immediately if signs/symptoms of HF (trouble breathing, leg swelling, lung congestion, rapid weight gain) occur.
Advise patient to notify health care provider immediately if signs of hepatic impairment (fatigue, nausea, upper abdominal pain, yellowing of skin or eyes, dark urine, light-colored stools) or bladder cancer (blood in urine, urinary pain or urgency) occur.
Advise patient to inform health care provider of medication regimen before treatment or surgery.
Rep: Insulin is the preferred method of controlling blood glucose during pregnancy. May cause ovulation in anovulatory women; counsel women of reproductive potential that higher doses of oral contraceptives or a form of contraception other than oral contraceptives may be required. Advise women of reproductive potential to notify health care provider promptly if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇