Generic name: Pioglitazone

Actos (pioglitazone) is a thiazolidinedione antidiabetic medication used to help control blood sugar levels in people with type 2 diabetes. It works by increasing the body’s sensitivity to insulin, which helps to lower blood sugar levels. Actos is usually taken once daily, with or without food.

Pharmacokinetics

Pioglitazone is rapidly and completely absorbed after oral administration, with peak plasma concentrations occurring within 1-2 hours. The mean bioavailability of pioglitazone is approximately 100%. Pioglitazone undergoes extensive metabolism via oxidative biotransformation, with less than 5% of the dose recovered as unchanged drug in urine. The primary metabolic pathway involves hydrolysis of the thiazolidinedione ring, followed by oxidation of the resulting sulfoxide moiety to a sulfone. Cytochrome P450 3A4 (CYP3A4) is the predominant isozyme responsible for pioglitazone metabolism.

There are no significant differences in the pharmacokinetics of pioglitazone between males and females.

Pioglitazone is extensively bound to plasma proteins (>99%), primarily albumin. The binding is non-specific and does not show saturation over the concentration range achieved with therapeutic doses.

The mean elimination half-life of pioglitazone is approximately 12 hours. Pioglitazone and its metabolites are primarily eliminated in the urine, with less than 1% of the dose recovered as unchanged drug.

Indications and usage

Actos is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Contraindications

Actos is contraindicated in patients with known hypersensitivity to pioglitazone or any of the other ingredients in the formulation.

Side Effects

Actos may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

  • bloating
  • constipation
  • diarrhoea
  • headache
  • dizziness
  • heartburn
  • gas
  • indigestion
  • mild skin rash
  • stuffy nose
  • sore throat
  • tiredness

Actos may cause other side effects.

Actos may not be right for everyone. Actos can also cause weight gain. If you experience any serious side effects from taking Actos, contact your doctor immediately.

Warnings and precautions

Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema, urticaria, and rash, have been reported with pioglitazone. If hypersensitivity reactions occur, discontinue use of pioglitazone and initiate appropriate therapy.

Fluid Retention: Edema has been reported in clinical trials with pioglitazone. Weight gain can occur with pioglitazone use; monitor body weight regularly. In patients with pre-existing heart failure, monitor signs and symptoms of worsening heart failure. If edema or weight gain occurs, evaluate the need for continuation of pioglitazone.

Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with pioglitazone or any other anti-diabetic drug.

Hepatic Impairment: Avoid use of pioglitazone in patients with active liver disease or unexplained transaminase elevations. If signs or symptoms of liver injury occur, promptly discontinue use of pioglitazone and initiate appropriate therapy.

Adverse reactions

The most common adverse reactions (≥5%) reported in clinical trials with pioglitazone are upper respiratory tract infection, sinusitis, headache, back pain, and edema.

Drug interactions

CYP3A4 Inhibitors: Avoid concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, gemfibrozil, ritonavir) and pioglitazone. If a strong CYP3A4 inhibitor must be used, monitor the patient closely for signs and symptoms of pioglitazone toxicity (e.g., edema, weight gain, hypoglycemia) and adjust the pioglitazone dose as needed.

Hepatic Impairment: Avoid use of pioglitazone in patients with active liver disease or unexplained transaminase elevations. If signs or symptoms of liver injury occur, promptly discontinue use of pioglitazone and initiate appropriate therapy.

Use in specific populations

Pregnancy: Based on results from animal studies, pioglitazone may cause fetal harm.

Nursing mothers: It is not known whether pioglitazone is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from pioglitazone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric use: The safety and efficacy of Actos in pediatric patients have not been established.

Geriatric use: No overall differences in effectiveness or safety were observed between geriatric and younger patients in clinical trials.

Females of Reproductive Potential: Based on results from animal studies, pioglitazone may cause fetal harm.

Pioglitazone is not recommended for use in pregnant women or women of childbearing potential not using effective contraception. If pioglitazone is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Dosage

Actos is usually taken once daily, with or without food.

If you miss a dose of Actos, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not take two doses of Actos at the same time.

Overdose

If you take too much Actos, call your doctor or poison control center immediately. Symptoms of an overdose may include:

  • confusion
  • dizziness
  • headache
  • light-headedness
  • nausea
  • vomiting

Storage

Store Actos at room temperature away from light and moisture. Do not store in the bathroom. Keep Actos out of the reach of children and pets.

Do not take Actos if it has expired or is damaged. Talk to your pharmacist about the proper disposal of your medication.