Utmos

Pioglitazone.

Utmos 15: Each tablet contains pioglitazone HCl 16.535 mg (equivalent to pioglitazone 15 mg).
Utmos 30: Each tablet contains pioglitazone HCl 33.07 mg (equivalent to pioglitazone 30 mg).

Pharmacodynamics: Mechanism of Action: Pioglitazone is a thiazolidinediones antidiabetic agent. Pioglitazone decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. Pioglitazone is a potent and highly selective agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). PPARγ receptors are found in tissues important for insulin action such as adipose tissue, skeletal muscle and liver.
Pharmacokinetics: Volume of distribution (V_d) of this drug is 0.63 L/kg. Protein binding is 99.8%. This drug metabolizes by hepatic (99%) via CYP2C8, CYP2C9, and CYP3A4 to both active and inactive metabolites. Elimination half-life for parent drug is 3-7 hours and elimination half-life for the total is 16-24 hours. Time to peak is about 2 hours. This drug is excreted by the urine (15% to 30%) and by feces as metabolites.

Treatment of non-insulin dependent diabetes mellitus (NIDDM, type 2). Pioglitazone is indicated for monotherapy and also in combination with a sulfonylurea, metformin or insulin together with control diet and exercise.

Recommended Doses: The initiated dose for monotherapy or combination with a sulfonylurea, metformin or insulin is 15 mg or 30 mg once daily. If the response is inadequate, the dose can be increased in increments up to 45 mg once daily. In case of pioglitazone in combination with a sulfonylurea or metformin, the current sulfonylurea dose can be continued upon initiation of pioglitazone therapy. If patients report hypoglycemia, the dose of sulfonylurea should be decreased. However, hypoglycemia does not occur during combination therapy with metformin.
Use in the children: Safety and effectiveness not established in children or adolescents younger than 18 years of age.
Mode of Administration: Pioglitazone should be taken once daily without regard to meals.

Overdose: Limited overdose data. The following have occurred with therapy: edema, hypoglycemia, hepatic enzyme elevations, paresthesia, and elevations of creatine phosphokinase.
Treatment: Decontamination: Activated charcoal.
Supportive treatment: Symptomatic and supportive. Management of hypoglycemia, fluid and electrolyte status, and hypotention may be necessary.
Monitoring of patient: Obtain a baseline blood glucose level and monitor frequently; especially when coadministered with other antidiabetic agents. Monitor hepatic enzymes following a significant overdose. Monitor vital signs, blood pressure and fluid and electrolyte status as indicated. Plasma volume expansion has been reported which may exacerbate heart failure.

Pioglitazone is contraindicated in patients with known hypersensitivity to this product or any of its components.

CONGESTIVE HEART FAILURE: Thiazolidinediones, including pioglitazone, cause or exacerbate congestive heart failure in some patients. After initiation of pioglitazone, and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain, dyspnea, tired, and/or edema). If these signs and symptoms develop, the heart failure should be managed according to current standards of care. Furthermore, discontinuation or dose reduction of pioglitazone must be considered.
Pioglitazone is not recommended in patients with symptomatic heart failure. Initiation of pioglitazone in patients with established NYHA Class III or IV heart failure is contraindicated.
Risk of bladder cancer: This drug may increase risk of bladder cancer.
Should not be used in patients with active bladder cancer.
Use with caution, benefits versus risks should be considered in patients with a prior history of bladder cancer or in patients at risk of bladder cancer.
Should any symptom or sign of haematuria, urinary incontinence, dysuria, back pain or abdominal pain occur, consult physician.
Based on Thai Ministry of Public Health Announcement: 1. Do not use pioglitazone in patients with severe degree of heart failure (established NYHA Class III or IV). This drug may cause congestive heart failure. If there are symptoms of dyspnea, feeling tired easily, rapid weight gain or severe edema after using this drug, consult physician immediately.
2. Concomitant use with NSAIDs, Coxib or insulin will increase risk of edema and congestive heart failure. Must use with caution.
3. This drug may increase risk of bladder cancer.
4. Should not be used in patients with active bladder cancer.
5. Use with caution, benefits versus risks should be considered in patients with a prior history of bladder cancer or in patients at risk of bladder cancer. Use of pioglitazone longer than one year may be associated with increased occurrence of bladder cancer.
6. Should any symptoms or signs of haematuria, urinary incontinence, dysuria, back pain or abdominal pain occur, consult physician.

Ovulation: Therapy with thiazolidinediones may result in ovulation in some premenopausal anovulatory women. Thus, adequate contraception in premenopausal women should be recommended.
Hypoglycemia: Patients receiving pioglitazone in combination with insulin or oral hypoglycemic agents may be at risk for hypoglycemia, also it may be necessary to reduce the dose of the concomitant agent.
Cardiovascular: Pioglitazone can cause fluid retention when used alone or in combination with other antidiabetic agents, including insulin. If necessary, the patients may be treated with diuretic drugs. Weight gain possibly associated with fluid retention has been observed during therapy with pioglitazone alone or in combination with other antidiabetic agents. In case of patients with previously known heart disease, pioglitazone in combination with insulin may increase risk of congestive heart failure. Patients should be observed for signs and symptoms of heart failure (e.g. dyspnea, weight gain, and edema).
Pioglitazone should be discontinued if any deterioration in cardiac status occurs.
Pioglitazone is not recommended in patients with New York Heart Association (NYHA) class III and IV.
Edema: Pioglitazone can cause edema when used alone or in combination with other antidiabetic agents, including insulin, also pioglitazone should be used with caution in patients with edema.
Hepatic effects: Reports of hepatitis and hepatic enzyme elevations to 3 or more times the upper limit of normal have been received. Therefore, serum ALT (alanine transaminase) levels should be evaluated prior to the initiation of therapy with pioglitazone in all patients, and periodically thereafter per the clinical judgement of the health care professional. If ALT levels remain > 3 times the upper limit of normal, pioglitazone therapy should be discontinued.
Hematologic: Pioglitazone may cause decreases in hemoglobin and hematocrit. These changes primarily occurred within the first 4 to 12 weeks of therapy and remained relatively constant thereafter. These changes may be related to increased plasma volume and have rarely been associated with any significant hematologic clinical effects.
Anemia: Use with caution in patients with anemia. Anemia occurred in 1% of patients treated with pioglitazone compared to 0% of patients treated with placebo.
Weight gain: In clinical trials with pioglitazone there was evidence of dose related weight gain which may be due to fat accumulation and in some cases associated with fluid retention.
Bone fracture: Female patients with type 2 diabetes mellitus receiving pioglitazone had a higher incidence of bone fractures, with a majority of distal upper limb (forearm, hand, and wrist), or distal lower limb (foot, ankle, fibula, and tibia) than those receiving a comparator.
Macular retinal edema: Reports of new onset or worsening of diabetic macular edema with decreased visual acuity have occurred during postmarketing use of pioglitazone hydrochloride or other thiazolidinedione. Presenting symptoms have been blurred vision or decreased visual acuity. However, for some patients the macular edema was asymptomatic and detected on routine eye exam. Regular eye exams by an ophthalmologist are recommended.
Use of pioglitazone is not recommended for patients with NYHA class III and IV heart failure, as these patients were not studied during clinical trials.
This drug is not recommended in patients with hepatic disorders or patients with abnormal liver function.
Patients should be observed for signs and symptoms of heart failure (e.g. rapid weight gain, edema, dyspnea, or signs and symptoms of heart disease) and the drug should be discontinued and reported to the doctor immediately if any deterioration in cardiac status occurs.

Not recommended.

Adverse drug reactions of pioglitazone occurring in 5% or more of patients include upper respiratory tract infection, headache, sinusitis, myalgia, tooth disorder, aggravation of diabetes mellitus and pharyngitis. Adverse effects generally were similar with pioglitazone monotherapy versus combined therapy with sulfonylureas, metformin, or insulin; however, edema was more common during pioglitazone therapy than placebo.
Anemia was reported in ≤ 2% of patients treated with pioglitazone plus sulfonylurea, metformin or insulin. This symptom was mild to moderate and usually did not require drug discontinuance.
Dyspnea and either weight gain or edema have occurred during combination therapy of pioglitazone and insulin; in some cases, diuretic therapy was required to treat symptoms.
Sporadic, elevations in creatine phosphokinase levels were observed.
In clinical trials, hypoglycemia occurred in 2% of patients receiving pioglitazone in combination with a sulfonylurea and in 8 or 15% of those receiving pioglitazone 15 mg or 30 mg, respectively, in combination with insulin.

Drugs Affecting Hepatic Microsomal Enzymes: Inhibitors or inducers of cytochrome P-450 (CYP) isoenzyme 3A4; potential pharmacokinetic interaction.
Potential pharmacokinetic interaction (increased peak plasma concentrations and area under the concentration-time curve [AUC] of pioglitazone) with inhibitors of CYP3A4 (e.g. ketoconazole). Pharmacokinetic interaction unlikely with ranitidine, a relatively weak CYP3A4 inhibitor.
Pioglitazone is a weak inducer of CYP3A4. Potential pharmacokinetic interaction (reduction in peak plasma concentration and AUC) with CYP3A4 substrates (e.g. atorvastatin, midazolam, ethinyl estradiol, nifedipine ER).
Potential pharmacokinetic interaction with estrogen-progestin combination contraceptives (small decrease in peak plasma estrogen concentration and AUC): clinical importance unknown.
Pharmacokinetic interaction unlikely with CYP2C9 substrates (e.g. warfarin).
Pharmacokinetic interaction unlikely with theophylline, a CYP1A2 substrate.
Antidiabetic Agents: Pharmacokinetic interaction with metformin or glipizide unlikely.
Digoxin: Pharmacokinetic interaction unlikely.
Fexofenadine Hydrochloride: Pharmacokinetic interaction unlikely.

Store below 30 degree Celsius.

Antidiabetic Agents

A10BG03 - pioglitazone ; Belongs to the class of thiazolidinediones. Used in the treatment of diabetes.

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