Pioglitazone (Dosing, Interaction, Side Effect, Administration, Etc..)

CLASS:
Antidiabetic
Thiazolidinedione

DOSING:

Adult Dose

:
Important Note:
Obtain liver function tests prior to initiation of therapy
Beers Criteria: Use caution or avoid use as potentially inappropriate in older adults

Type 2 diabetes mellitus:
Initial; 15 or 30 mg orally once daily; titrate in 15-mg increments; Maximum 45 mg daily

Pediatric Dose

:
Important Note:
Obtain liver function tests prior to initiation of therapy
Beers Criteria: Use caution or avoid use as potentially inappropriate in older adults

General Dosage Information:
Safety and effectiveness not established in pediatric patients; use is not recommended







MECHANISM OF ACTION:
Pioglitazone hydrochloride; a thiazolidinedione antidiabetic agent and a potent peroxisome proliferator-activated receptor-gamma (PPAR (gamma)) agonist; is dependent on the presence of insulin for its mechanism of action. It increases insulin-dependent glucose disposal and decreases hepatic glucose output by decreasing insulin resistance in the periphery and in the liver

ADVERSE EFFECT:
Common:
Cardiovascular:
Edema (4.8% to 15.3%)

Endocrine metabolic:
Weight increased

Hematologic:
Anemia (less than or equal to 2%)

Musculoskeletal:
Fracture of bone (5.1%)
Myalgia (5.4%)

Neurologic:
Headache (9.1%)

Respiratory:
Pharyngitis (5.1%)
Sinusitis (6.3%)
Upper respiratory infection (13.2%)

Serious:
Cardiovascular:
Congestive heart failure

Hepatic:
Alanine aminotransferase(ALT)/ Serum glutamic pyruvic transaminase (SGPT) level raised (0.3%)

Liver failure Ophthalmic:
Diabetic macular edema

Renal:
Bladder cancer (0.23% to 0.54%)

Respiratory:
Pneumonia

CONTRAINDICATION:
New York Heart Association Class III or IV heart failure
Hypersensitivity to

pioglitazone hydrochloride

or any other component of the product

INTERACTION:
Strong CYP2C8 Inhibitors:
An inhibitor of CYP2C8 (e.g.; gemfibrozil) significantly increases the exposure (area under the serum concentration-time curve or AUC) and half-life (t½) of

pioglitazone

. Therefore; the

maximum recommended dose of pioglitazone

is 15 mg daily if used in combination with gemfibrozil or other strong CYP2C8 inhibitors. Since the

minimum dose of pioglitazone

exceeds 15 mg; patients taking concomitant strong CYP2C8 inhibitors should switch to individual components of ; unless the prescribing health care provider determines that the benefit of clearly outweighs the risk of increased pioglitazone exposure

CYP2C8 Inducers:
An inducer of CYP2C8 (e.g.; rifampin) may significantly decrease the exposure (AUC) of pioglitazone. Therefore; if an inducer of CYP2C8 is started or stopped during treatment with pioglitazone; changes in diabetes treatment may be needed based on clinical response without exceeding the maximum recommended

daily dose of 45 mg for pioglitazone

Major:
Acarbose (theoretical)
Balofloxacin (theoretical)
Besifloxacin (theoretical)
Chlorpropamide (theoretical)
Ciprofloxacin (theoretical)
Enoxacin (theoretical)
Fleroxacin (theoretical)
Flumequine (theoretical)
Gatifloxacin (theoretical)
Gemifloxacin (theoretical)
Glimepiride (theoretical)
Glipizide (theoretical)
Glyburide (theoretical)
Ifosfamide (theoretical)
Insulin (theoretical)
Insulin Aspart; Recombinant (theoretical)
Insulin Bovine (theoretical)
Insulin Degludec (theoretical)
Insulin Detemir (theoretical)
Insulin Glargine; Recombinant (theoretical)
Insulin Glulisine (theoretical)
Insulin Lispro; Recombinant (theoretical)
Lanreotide (theoretical)
Levofloxacin (theoretical)
Lomefloxacin (theoretical)
Metformin (theoretical)
Moxifloxacin (theoretical)
Nadifloxacin (theoretical)
Nateglinide (theoretical)
Nifedipine (probable)
Norfloxacin (theoretical)
Octreotide (theoretical)
Ofloxacin (theoretical)
Pasireotide (theoretical)
Pazufloxacin (theoretical)
Pefloxacin (theoretical)
Piperaquine (theoretical)
Pixantrone (theoretical)
Prulifloxacin (theoretical)
Repaglinide (theoretical)
Rufloxacin (theoretical)
Sparfloxacin (theoretical)
Thioctic Acid (theoretical)
Tolazamide (theoretical)
Tolbutamide (theoretical)
Tolvaptan (theoretical)
Tosufloxacin (theoretical)

Moderate:
Acebutolol (probable)
Atenolol (probable)
Atorvastatin (probable)
Betaxolol (probable)
Bisoprolol (probable)
Bitter Melon (probable)
Carteolol (probable)
arvedilol (probable)
Celiprolol (probable)
Clopidogrel (probable)
Esmolol (probable)
Fenugreek (probable)
Glucomannan (probable)
Guar Gum (probable)
Ketoconazole (probable)
Labetalol (probable)
Levobunolol (probable)
Metipranolol (probable)
Metoprolol (probable)
Nadolol (probable)
Nebivolol (probable)
Nilotinib (probable)
Oxprenolol (probable)
Penbutolol (probable)
Pindolol (probable)
Practolol (probable)
Propranolol (probable)
Psyllium (probable)
Rifampin (established)
Sotalol (probable)
Timolol (probable)
Topiramate (probable)

PHARMACOKINETICS:
Absorption:
Time for Maximum Plasma Concentration (Tmax):
Oral: Within 2 hours

Effects of food:
Increase in Tmax to 3 to 4 hours

Distribution:
Volume of Distribution (Vd): 0.63 L/kg
Plasma Protein binding: Greater than 99%

Metabolism:
Metabolised by Hydroxylation and oxidation
Extrahepatic: Some
M-III (major): Active
M-IV (major): Active
CYP2C8 substrate

Excretion:
Renal excretion: 15% to 30%
Biliary excretion: Extensive; as changed and unchanged drug
Total body clearance: 5 to 7 L/hr

Elimination:
Oral: 3 to 7 hours
Geriatric: 10 hours
M-III and M-IV metabolites: 16 to 24 hours

PRECAUTION:
Beers Criteria:
Avoid

use in older adults

with heart failure due to risk of fluid retention and heart failure exacerbation

Cardiovascular:
New or worsening dose-related edema and fluid retention have been reported; use caution in patients with edema or at risk for congestive heart failure. Monitoring recommended

Endocrine and metabolic:
Concomitant

use with insulin

or other antidiabetic medications (especially insulin secretagogues such as sulfonylureas) may increase the risk for hypoglycemia

Hepatic:
Hepatic failure; including fatal cases; has been reported; screening and monitoring recommended. Interruption of therapy required for abnormal liver tests; do not restart therapy if serum ALT greater than 3 times the ULN and no other cause is identified

Musculoskeletal:
Increased risk of bone fracture in female patients; especially in the distal upper limb (forearm; hand; or wrist) or distal lower limb (foot; ankle; fibula; and tibia)

Ophthalmic:
Macular edema has been reported

Renal:
Use not recommended in patients with active bladder cancer. Weigh benefits versus risk in patients with a prior history of bladder cancer as use may increase risk of urinary bladder tumors

Prolonged use

(more than 12 months) and/or high

cumulative doses

; increased risk of bladder cancer

PREGNANCY CATEGORY:
Fetal Risk cannot be ruled out

BREAST FEEDING:
Infant Risk cannot be ruled out

MONITORING:
Achieving glycemic control; including meeting HbA1c goal is indicative of efficacy
HbA1c; twice yearly in patients who are meeting treatment goals; every 3 months in patients whose therapy has changed and/or who are not meeting glycemic goals; more frequently as clinically warranted
Blood glucose (self-monitoring); as needed to assist in meeting goals of therapy
Liver function tests; prior to initiating therapy and promptly in any patient who reports symptoms of liver injury (fatigue; anorexia; right upper abdominal discomfort; dark urine; or jaundice)
Signs and symptoms of congestive heart failure and fluid retention (excessive or rapid weight gain; dyspnea; or edema); following initiation and after any dose increase
Bone health; particularly in female patients; according to current standards of care during treatment

HOW TO TAKE OR ADMINISTRATION:
Oral:
Give without regard to meals

DOSAGE FORM:
Oral

Tablet

:
15mg
30mg
45mg

TREATMENTS:
MANAGEMENT OF MILD TO MODERATE TOXICITY:
Symptomatic and supportive care is the mainstay of treatment in patients who present with mild to moderate thiazolidinedione toxicity. If hypoglycemia develops, coingestion of other hypoglycemic agents should be considered. Hypoglycemia with thiazolidinediones is uncommon, but they are often prescribed with other antidiabetic agents that can produce hypoglycemia. A 4 to 6 hour observation period is reasonable.

MANAGEMENT OF SEVERE TOXICITY:
Early positive pressure ventilation/intubation should be performed if the patient presents with pulmonary edema. Consider diuresis in massive fluid overload. Adequate circulatory support with IV fluids and vasopressors (if needed) should be assured if a patient presents with circulatory collapse.

TOXICOLOGY:
TOXICITY:
The

minimum toxic dose

for thiazolidinediones is not well established.

PIOGLITAZONE:
An adult denied any clinical symptoms after taking up to 120 mg/day of pioglitazone for 4 days and then 180 mg/day for 7 days.

PATIENT COUNSELING OR CLINICAL TEACHING:
Advise patient to report symptoms of congestive heart failure
Advise patient to report symptoms of hepatoxicity
Warn premenopausal anovulatory women that ovulation and subsequent pregnancy may occur

Side effects

may include headaches; myalgia; pharyngitis; sinusitis; upper respiratory tract infections; edema; and weight increase
Advise patient to report symptoms of bladder cancer
Advise patient to report symptoms of macular edema


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For the Registered Medical Practitioner Only. We are not recommended for self medication. self medication is may harmful for health. We are only Provide information about medicine.