pi-o-GLIT-a-zone

Therapeutic Classification: antidiabetics

Pharmacologic Classification: thiazolidinediones

• Type 2 diabetes mellitus.

• Improves sensitivity to insulin by acting as an agonist at receptor sites involved in insulin responsiveness and subsequent glucose production and utilization.
• Requires insulin for activity.

• Decreased insulin resistance, resulting in glycemic control without hypoglycemia.

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.

(effects on blood glucose)

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)
• Women of reproductive potential
• OB: Safety not established in pregnancy
• Lactation: Safety not established in breastfeeding.

CV: edema, HF.

EENT: macular edema.

GI: ↑liver enzymes, LIVER FAILURE.

GU: BLADDER CANCER.

Hemat: anemia.

MS: fractures (arm, hand, foot) (females), RHABDOMYOLYSIS.

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.
• Concurrent use with 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 produce ↑ hypoglycemic effects.

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

(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].

• Observe patient taking concurrent insulin for signs and symptoms of hypoglycemic reactions (sweating, hunger, weakness, dizziness, tremor, tachycardia, anxiety).
• Assess for signs and symptoms of HF (edema, dyspnea, rapid weight gain, unusual tiredness) after initiation and with dose increases.

• Monitor serum glucose and A_1c periodically during therapy to evaluate effectiveness.
  • Monitor CBC with differential periodically during therapy. May cause ↓ in hemoglobin and hematocrit, usually during the first 4–12 wk of therapy; then levels stabilize.
  • Monitor serum AST, ALT, alkaline phosphatase, and total bilirubin levels before starting therapy and periodically thereafter or if jaundice or symptoms of hepatic impairment occur. Pioglitazone should not be started in patients with active liver disease or ALT levels >2.5 times the upper limit of normal (ULN). Patients with mild ALT ↑ should have more frequent monitoring. If ALT ↑ to >3 times ULN, recheck ALT promptly. Discontinue pioglitazone if ALT remains >3 times ULN.
  • May cause transient ↑ in CK levels.

• 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.

• Instruct patient to take medication 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 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 tsp of sugar, honey, or corn syrup dissolved in water and notify health care professional.
• 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 professional should be notified if significant changes occur.
• Advise patient to notify health care professional immediately if signs of hepatic dysfunction (nausea, vomiting, upper right abdominal pain, fatigue, anorexia, dark urine, jaundice), bladder cancer (hematuria, dysuria, urinary urgency), or HF (edema, shortness of breath, rapid weight gain, tiredness) occur.
• Advise patient to inform health care professional of medication regimen before treatment or surgery.
• Insulin is the preferred method of controlling blood glucose during pregnancy. May cause ovulation in anovulatory women; counsel females of reproductive potential that higher doses of oral contraceptives or a form of contraception other than oral contraceptives may be required. Advise patient to notify health care professional promptly if pregnancy is planned or suspected or if breastfeeding.
• Advise patient to carry a form of sugar (sugar packets, candy) and identification describing disease process and medication regimen at all times.
• Emphasize the importance of routine follow-up exams.

• Control of blood glucose levels.

Actos