Pioglitazone

BRAND NAMES

Actoplus Met: Actoplus Met combines pioglitazone and metformin, two oral diabetes medications that help manage glucose levels and available strengths of 15/500 mg and 15/850 mg.

Actos: It contains pioglitazone hydrochloride with available strengths 15mg, 30 mg, and 45 mg. This helps to prevent major diabetes consequences, such as kidney damage and blindness.

DUETACT The oral antihyperglycemic medications pioglitazone hydrochloride and glimepiride, which come in 30 mg/2 mg and 30 mg/4 mg dosages and are used to treat type 2 diabetes, are included in DUETACT tablets.

Incresync: Incresync contains alogliptin and pioglitazone. These are available in form of film coated tablets.

MECHANISM OF ACTION

A specific agonist at peroxisome proliferator-activated receptor-gamma (PPARγ), pomegranate, liver, and skeletal muscle are among the target tissues of pioglitazone's insulin action. Insulin-responsive genes that regulate the synthesis, transport, and utilization of glucose and lipids are more transcriptionally active when PPARγ is activated. By this method, pioglitazone decreases hepatic glucose synthesis (gluconeogenesis) and increases tissue sensitivity to insulin; as a result, insulin resistance linked to type 2 diabetes mellitus is alleviated without a rise in pancreatic beta cell release of insulin.

PHARMACOKINETICS

Absorption

When pioglitazone is taken orally, peak blood concentrations are seen in 2 hours (Tmax). Food does not change the amount of absorption, but it does slightly postpone the time to peak serum concentration, bringing it up to 3–4 hours. Once daily pioglitazone dosing for seven days results in steady-state concentrations of both the parent medication and its main active metabolites. Cmax and AUC rise in direct proportion to dosages taken. Over 99 percent of it is bound to proteins.

Distribution

Pioglitazone has an apparent volume of distribution of 0.63 L/kg on average.

Metabolism

Pioglitazone is extensively degraded by hydroxylation and oxidation, with the resultant metabolites partially transformed to glucuronide or sulfate conjugates. The pharmacologically active M-IV and M-III metabolites are the primary metabolites identified in human serum, with circulating concentrations equivalent to or greater than those of the parent drug. Pioglitazone metabolism is primarily mediated by CYP2C8 and, to a lesser extent, CYP3A4. There is also some evidence suggesting a role by extrahepatic CYP1A1.

Elimination

Approximately 15-30% of orally given pioglitazone is excreted in urine. The majority of its removal is thought to occur through the excretion of unaltered medication in bile or as metabolites in feces. Its elimination half-life ranges between 3 and 7 hours.

PHARMACODYNAMICS

Pioglitazone enhances insulin sensitivity, insulin-dependent glucose clearance, and glucose homeostasis. In those with type 2 diabetes, these results lead to reduced plasma glucose, insulin, and HbA1c levels.

Pioglitazone has been linked to significant fluid retention and the development or exacerbation of congestive heart failure; hence, it should be avoided in individuals with or at risk of developing heart failure. There is some evidence that pioglitazone may raise the chance of getting bladder cancer. Pioglitazone should be avoided in individuals with current bladder cancer and taken with care in those who have a history of bladder cancer.

DRUG AND ADMINISTRATION

Pioglitazone is used orally, with or without meals. It can be taken alone, although it is most commonly used in combination with metformin/sulfonylurea or insulin treatment. When administered alone, pioglitazone can reduce hemoglobin A1C levels by between 0.5 and 1.4 percent. The amount of improvement in glycemic control depends on when used with other antidiabetics, including insulin. 
For adults, the starting dosage is 15 mg or 30 mg orally once a day. For individuals who do not respond well, dosage increases of 15 mg of the medication are recommended as needed. The maximum daily dosage is 45 mg administered orally.

CONTRAINDICATIONS

Pioglitazone has the following contraindications:

• Hypoglycemia, hence it's critical to regularly check blood sugar.
• Liver transaminase readings more than 2.5 times higher than the upper limit of normal, indicative of active liver disease
• Individuals who have a history of pioglitazone or any of its component sensitivities
• Microscopic hemorrhagia without further investigation, active (present) bladder cancer, or a history of bladder cancer
• Type 1 diabetes or diabetic ketoacidosis, as pioglitazone is only effective when insulin is present.
• Any indication of an excess of fluid
• Microscopic hemorrhagia without further investigation, active (present) bladder cancer, or a history of bladder cancer

Drug Interactions 
Pioglitazone may interact with one or more of the following:

• Diabetes drugs include acarbose, canagliflozin, glyburide, insulin, linagliptin, lixisenatide, and metformin.
• Abiraterone acetate.
•  HIV protease inhibitors include atazanavir, indinavir, ritonavir, and saquinavir.
•  Acetylsalicylic Acid 
• androgens -testosterone
•  Common diuretics include furosemide, hydrochlorothiazide, and triamterene.
• Oestrogens include conjugated oestrogen, oestradiol, and ethinyl oestradiol.
• Atypical antipsychotics include clozapine, olanzapine, quetiapine, and risperidone.

SIDE EFFECTS

The common side effects of pioglitazone include

• Sore throat
• dry mouth
• chest pain
• sweating
• decreased urine output
• stomach pain
• cough
• difficulty in breathing
• irregular heartbeat
• extreme fatigue

TOXICITY

There is no known antidote for pioglitazone overdose; the only available option is supportive care.