Thiazolidinedione (oral antidiabetic)
Pioglitazone is an oral medicine used to treat type 2 diabetes, which helps the body use insulin better. It is taken once a day, with or without food.
Also known as: Actos
DailyMed/FDA (NIH/NLM) — approved Pioglitazone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31619517-a590-408a-ae9e-76c99f0a0a1d ; EMC-UK (MHRA) — approved Pioglitazone SmPC: https://www.medicines.org.uk/emc/product/12841/smpc — with additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Combining glimepiride with pioglitazone increases the risk of hypoglycaemia. If used together, your doctor may reduce the glimepiride dose.
Pioglitazone sensitises tissues to insulin; when combined with a sulfonylurea (secretagogue), the hypoglycaemic effect is additive. The approved pioglitazone label (DailyMed) states that, when used with insulin or secretagogues, a lower dose of these may be needed to reduce the risk of hypoglycaemia. This combination is common in type 2 diabetes combination therapy.
Combining a thiazolidinedione with an insulin secretagogue increases the risk of hypoglycaemia; the sulfonylurea dose may need to be reduced (and pioglitazone if oedema/heart failure).
Additive hypoglycaemic effect of insulin sensitisation with secretion stimulation.
Capillary glucose; signs of fluid retention/oedema (pioglitazone effect).
Hypoglycaemia; sudden oedema, shortness of breath (heart failure) — medical attention.
If the combination is needed, reduce the sulfonylurea dose and monitor blood glucose, especially in the first weeks.
DailyMed/FDA (NIH/NLM) — approved Pioglitazone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31619517-a590-408a-ae9e-76c99f0a0a1d ; EMC-UK (MHRA) — approved Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/smpc ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Combining gliclazide with pioglitazone increases the risk of hypoglycaemia. Your doctor may reduce the gliclazide dose.
Pioglitazone improves insulin sensitivity; with sulfonylureas, the effect on blood glucose is additive and the risk of hypoglycaemia increases, requiring a secretagogue dose reduction. The pioglitazone label (DailyMed) recommends a lower dose of insulin or secretagogues when combined. The combination is used in poorly controlled type 2 diabetes.
Thiazolidinedione + sulfonylurea: additive hypoglycaemic effect; a sulfonylurea dose reduction may be needed. Also watch for pioglitazone fluid retention/oedema.
Additive hypoglycaemic effect of insulin sensitisation with secretion stimulation.
Capillary glucose; oedema and signs of heart failure.
Hypoglycaemia; sudden oedema, dyspnoea.
Reduce the sulfonylurea dose when starting pioglitazone and monitor blood glucose in the first weeks.
DailyMed/FDA (NIH/NLM) — approved Pioglitazone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31619517-a590-408a-ae9e-76c99f0a0a1d ; EMC-UK (MHRA) — approved Gliclazide SmPC: https://www.medicines.org.uk/emc/product/1321/smpc ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Rifampicin can reduce the effect of pioglitazone, requiring blood glucose monitoring and a possible dose increase.
Pioglitazone is mainly metabolised by CYP2C8; rifampicin, a potent inducer of this isoenzyme, reduces pioglitazone AUC by about 54% (EMC-UK SmPC). The reduced exposure can compromise glycaemic control. This combination occurs in patients with tuberculosis and diabetes.
Rifampicin (a CYP2C8 inducer) reduces pioglitazone AUC by 54%; the pioglitazone dose may need to be increased with blood glucose monitoring.
CYP2C8 induction by rifampicin, accelerating pioglitazone metabolism.
Capillary glucose and HbA1c during concurrent treatment.
Hyperglycaemia — thirst, polyuria, fatigue.
Monitor blood glucose and consider increasing the pioglitazone dose during rifampicin; readjust at the end of the antibiotic.
EMC-UK (MHRA) — approved Pioglitazone SmPC: https://www.medicines.org.uk/emc/product/12841/smpc ; DailyMed/FDA (NIH/NLM) — approved Rifampicin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Acute alcohol intoxication is a contraindication to pioglitazone; alcohol increases the risk of metabolic acidosis and of hypoglycaemia when combined with secretagogues.
Avoid acute alcohol intoxication and excessive alcohol intake during treatment.
EMC-UK (MHRA) — approved Pioglitazone SmPC: https://www.medicines.org.uk/emc/product/12841/smpc
Pioglitazone causes fluid retention that can precipitate or worsen heart failure; it is contraindicated in NYHA III–IV heart failure and should be used with caution in NYHA I–II.
Do not start in patients with established heart failure (NYHA III–IV); in NYHA I–II, start at a low dose and watch for oedema, weight gain and dyspnoea.
DailyMed/FDA (NIH/NLM) — approved Pioglitazone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31619517-a590-408a-ae9e-76c99f0a0a1d ; EMC-UK (MHRA) — approved Pioglitazone SmPC: https://www.medicines.org.uk/emc/product/12841/smpc
Pioglitazone may increase the risk of bladder cancer; do not use in patients with active bladder cancer or a history of the disease.
Do not use in patients with active or prior bladder cancer; investigate macroscopic haematuria before starting and during treatment.
DailyMed/FDA (NIH/NLM) — approved Pioglitazone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31619517-a590-408a-ae9e-76c99f0a0a1d
Pioglitazone is contraindicated in hepatic impairment; cases of hepatic failure, sometimes fatal, have been reported.
Do not use in patients with hepatic impairment; check liver tests before starting and stop if liver injury occurs.
DailyMed/FDA (NIH/NLM) — approved Pioglitazone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31619517-a590-408a-ae9e-76c99f0a0a1d
Pioglitazone should not be used in pregnancy (inadequate human data; foetotoxicity in animals).
Do not use in any trimester; if pregnancy occurs, stop treatment.
Do not use during breastfeeding (present in milk in animals; unknown in humans).
Not recommended in women of childbearing potential without effective contraception; if pregnancy is desired, stop and switch to insulin/metformin as guided.
EMC-UK (MHRA) — approved Pioglitazone SmPC: https://www.medicines.org.uk/emc/product/12841/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Thiazolidinedione that improves glycaemic control in type 2 diabetes: it reduces insulin resistance, with decreases in plasma glucose, plasma insulin and HbA1c. In patients with dyslipidaemia it lowers serum triglycerides and increases HDL cholesterol. Additive effect when combined with sulfonylureas, metformin or insulin.
Agonist of peroxisome proliferator-activated receptor-gamma (PPAR-gamma), which modulates the transcription of insulin-responsive genes involved in glucose and lipid metabolism control. It decreases insulin resistance in the periphery and in the liver; it is not an insulin secretagogue.
Peak plasma concentrations occur within 2 hours of dosing; food delays the peak to 3 to 4 hours without changing the extent of absorption. It is extensively bound to plasma proteins (over 99%), mainly albumin; the apparent volume of distribution is 0.63 L/kg.
Extensively metabolised by hydroxylation and oxidation (with partial conjugation to glucuronides and sulfates). CYP2C8 is the main isoenzyme, with a minor contribution from CYP3A4; the active metabolites M-III and M-IV predominate in the circulation. About 15 to 30% of the dose is recovered in urine; the remainder is excreted in bile and eliminated in faeces.
The mean serum half-life of pioglitazone is 3 to 7 hours and that of the active metabolites M-III and M-IV 16 to 24 hours.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
