Tripride

Each 15 mg/2 mg and 30 mg/2 mg tablet contains Pioglitazone (Tripride) HCl 15 mg and 30 mg, respectively, and Glimepiride (Tripride) 2 mg.

Tripride combines 2 antihyperglycemic agents to improve glycemic control with type 2 diabetes: Pioglitazone (Tripride) hydrochloride, a member of the thiazolidinedione class, and Glimepiride (Tripride), a member of the sulfonylurea class.

Pioglitazone (Tripride) is [(±)-5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-]thiazolidinedione monohydrochloride. Its molecular formula is C₁₉H₂₀N₂O₃S·HCl.

Glimepiride (Tripride) is 1-[[p-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido)ethyl]phenyl]-sulphonyl]-3-(trans-4-methylcyclohexyl) urea. Its molecular formula is C₂₄H₃₄N₄O₅S.

Tripride is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already treated with a thiazolidinedione and sulfonylurea or who have inadequate glycemic control on a thiazolidinedione alone or a sulfonylurea alone.

Important Limitations of Use

Pioglitazone (Tripride) exerts its antihyperglycemic effect only in the presence of endogenous insulin. Tripride should not be used to treat type 1 diabetes or diabetic ketoacidosis, as it would not be effective in these settings.

Use caution in patients with liver disease.

Glimepiride (Tripride) and Pioglitazone (Tripride) is a combination of two oral diabetes medicines that help control blood sugar levels.

Glimepiride (Tripride) and Pioglitazone (Tripride) is for people with type 2 diabetes. Glimepiride (Tripride) and Pioglitazone (Tripride) is sometimes given with other diabetes medications when greater blood sugar control is needed.

This medication is not for treating type 1 diabetes.

Glimepiride (Tripride) and Pioglitazone (Tripride) may also be used for purposes not listed in this medication guide.

General: The use of antihyperglycemic therapy in the management of type 2 diabetes should be individualized on the basis of effectiveness and tolerability. Failure to follow an appropriate dosage regimen may precipitate hypoglycemia.

Recommended Dose: Selecting the starting dose of Tripride should be based on the patient's current regimen of Pioglitazone (Tripride) and/or sulfonylurea. Those patients who may be more sensitive to antihyperglycemic drugs should be monitored carefully during dose adjustment. It is recommended that a single dose of Tripride be administered once daily with the first main meal.

Patients Currently on Pioglitazone (Tripride) HCl Monotherapy: Usual Starting Dose: Glimepiride (Tripride) (1 or 2 mg once daily) and Pioglitazone (Tripride) HCl 15 or 30 mg, Tripride may be initiated at 15 mg/2 mg once daily and adjusted after assessing adequacy of therapeutic response.

Patients Currently on Glimepiride (Tripride) Monotherapy: Usual Starting Dose: Pioglitazone (Tripride) HCl (15 or 30 mg daily), Tripride may be initiated at 15 mg/2 mg once daily, and adjusted after assessing adequacy of therapeutic response.

Patients Switching from Combination Therapy of Pioglitazone (Tripride) Plus Glimepiride (Tripride) as Separate Tablets: May be initiated with 15 mg/2 mg tablet based on the dose of Pioglitazone (Tripride) HCl and Glimepiride (Tripride) already being taken. Patients who are not controlled with Pioglitazone (Tripride) HCl 15 mg in combination with Glimepiride (Tripride) should be carefully monitored when switched to Tripride.

Patients Currently on a Different Sulfonylurea Monotherapy or Switching from Combination Therapy of Pioglitazone (Tripride) Plus a Different Sulfonylurea: No exact dosage relationship exists between Glimepiride (Tripride) and the other sulfonylurea agents. Therefore, based on the maximum starting dose of Glimepiride (Tripride) 2 mg, Tripride should be limited initially to a starting dose of 15 mg/2 mg once daily, and adjusted after assessing adequacy of therapeutic response. Any change in diabetic therapy should be undertaken with care and appropriate monitoring as change in glycemic control can occur. Patients should be observed carefully for hypoglycemia (1-2 weeks) when being transferred to Tripride, especially from longer t_½ sulfonylureas due to potential overlapping of drug effect.

Maximum Recommended Dose: The maximum recommended daily dose for Pioglitazone (Tripride) is 15 mg plus Glimepiride (Tripride) 2 mg or a Pioglitazone (Tripride) 30 mg plus Glimepiride (Tripride) 4 mg formulation for oral administration.

Maximum Recommended Daily Dose: Pioglitazone (Tripride) is 45 mg and Glimepiride (Tripride) is 8 mg. Tripride should therefore not be given more than once daily at any of the tablet strengths.

Elderly, Debilitated or Malnourished Patients, or in Patients with Renal or Hepatic Impairment: Initial dosing, dose increments, and maintenance dosage of Tripride should be conservative to avoid hypoglycemic reactions. These patients should be started at Glimepiride (Tripride) 1 mg prior to prescribing Tripride. During initiation of Tripride therapy and any subsequent dose adjustment, patients should be observed carefully for hypoglycemia. Therapy with Tripride should not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels (ALT >2.5 x ULN) at start of therapy. The lowest approved dose of Tripride therapy should be prescribed to patients with type 2 diabetes and systolic dysfunction only after titration from Pioglitazone (Tripride) HCl 15-30 mg has been safely tolerated. If subsequent dose adjustment is necessary, patients should be carefully monitored for weight gain, edema or signs and symptoms of congestive heart failure exacerbation.

See also:
What is the most important information I should know about Tripride?

Hypersensitivity to Pioglitazone (Tripride) HCl, Glimepiride (Tripride) or any of component of Tripride.

Patients with diabetic ketoacidosis, with or without coma. This condition should be treated with insulin. Those with antihypertensive effect in the presence of insulin; therefore, Tripride should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

Patients with moderate to severe heart failure or liver problems.

Use in pregnancy & lactation. Children.

Tripride is not recommended in patients with symptomatic heart failure.

Initiation of Tripride in patients with established NYHA Class III or IV heart failure is contraindicated.

Use Tripride as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Tripride comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Tripride refilled.
• Take Tripride by mouth with breakfast or the first main meal of the day unless instructed otherwise by your doctor.
• Continue to take Tripride even if you feel well. Do not miss any doses.
• Taking Tripride at the same time each day will help you remember to take it.
• If you miss a dose of Tripride, skip the missed dose and go back to your regular dosing schedule, unless your doctor directs you otherwise. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Tripride.

Use: Labeled Indications

Diabetes mellitus, type 2: Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM) as an adjunct to diet and exercise in adult patients already treated with a thiazolidinedione and a sulfonylurea or who have inadequate control on either agent alone

See also:
What other drugs will affect Tripride?

Strong CYP2C8 Inhibitors

Pioglitazone (Tripride)

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 (Tripride). Therefore, the maximum recommended dose of Pioglitazone (Tripride) is 15 mg daily if used in combination with gemfibrozil or other strong CYP2C8 inhibitors. Since the minimum dose of Pioglitazone (Tripride) in Tripride exceeds 15 mg, patients taking concomitant strong CYP2C8 inhibitors should switch to individual components of Tripride, unless the prescribing health care provider determines that the benefit of Tripride clearly outweighs the risk of increased Pioglitazone (Tripride) exposure.

CYP2C8 Inducers

Pioglitazone (Tripride)

An inducer of CYP2C8 (e.g., rifampin) may significantly decrease the exposure (AUC) of Pioglitazone (Tripride). Therefore, if an inducer of CYP2C8 is started or stopped during treatment with Pioglitazone (Tripride), changes in diabetes treatment may be needed based on clinical response without exceeding the maximum recommended daily dose of 45 mg for Pioglitazone (Tripride).

Drugs Affecting Glucose Metabolism

Glimepiride (Tripride)

A number of medications affect glucose metabolism and may require Tripride dose adjustment and particularly close monitoring for hypoglycemia or worsening glycemic control.

The following are examples of medications that may increase the glucose-lowering effect of sulfonylureas including Glimepiride (Tripride), a component of Tripride, increasing the susceptibility to and/or intensity of hypoglycemia: oral anti-diabetic medications, pramlintide acetate, insulin, angiotensin converting enzyme (ACE) inhibitors, H2 receptor antagonists, fibrates, propoxyphene, pentoxifylline, somatostatin analogs, anabolic steroids and androgens, cyclophosphamide, phenyramidol, guanethidine, fluconazole, sulfinpyrazone, tetracyclines, clarithromycin, disopyramide, quinolones, and those drugs that are highly protein-bound, such as fluoxetine, nonsteroidal antiinflammatory drugs, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid and monoamine oxidase inhibitors. When these medications are administered to a patient receiving Tripride, monitor the patient closely for hypoglycemia. When these medications are withdrawn from a patient receiving Tripride, monitor the patient closely for worsening glycemic control.

The following are examples of medications that may reduce the glucose-lowering effect of sulfonylureas including Glimepiride (Tripride), leading to worsening glycemic control: danazol, glucagon, somatropin, protease inhibitors, atypical antipsychotic medications (e.g., olanzapine and clozapine), barbiturates, diazoxide, laxatives, rifampin, thiazides and other diuretics, corticosteroids, phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics (e.g., epinephrine, albuterol, terbutaline), and isoniazid. When these medications are administered to a patient receiving Tripride, monitor the patient closely for worsening glycemic control. When these medications are withdrawn from a patient receiving Tripride, monitor the patient closely for hypoglycemia.

Beta-blockers, clonidine, and reserpine may lead to either potentiation or weakening of Tripride's glucose-lowering effect.

Both acute and chronic alcohol intake may potentiate or weaken the glucose-lowering action of Tripride in an unpredictable fashion.

The signs of hypoglycemia may be reduced or absent in patients taking sympatholytic drugs such as beta-blockers, clonidine, guanethidine, and reserpine.

Miconazole

Glimepiride (Tripride)

A potential interaction between oral miconazole and sulfonylureas leading to severe hypoglycemia has been reported. Whether this interaction also occurs with other dosage forms of miconazole is not known.

CYP2C9 Interactions

Glimepiride (Tripride)

There may be an interaction between Glimepiride (Tripride) and inhibitors (e.g., fluconazole) and inducers (e.g., rifampin) of CYP2C9. Fluconazole may inhibit the metabolism of Glimepiride (Tripride), causing increased plasma concentrations of Glimepiride (Tripride) which may lead to hypoglycemia. Rifampin may induce the metabolism of Glimepiride (Tripride), causing decreased plasma concentrations of Glimepiride (Tripride) which may lead to worsening glycemic control.

Concomitant Administration Of Colesevelam

Glimepiride (Tripride)

Colesevelam can reduce the maximum plasma concentrations and total exposure of Glimepiride (Tripride) when the two are coadministered. However, absorption is not reduced when Glimepiride (Tripride) is administered four hours prior to colesevelam. Therefore, Tripride should be administered at least four hours prior to colesevelam.

See also:
What are the possible side effects of Tripride?

Applies to Glimepiride (Tripride) / Pioglitazone (Tripride): oral tablet

In addition to its needed effects, some unwanted effects may be caused by Glimepiride (Tripride) / Pioglitazone (Tripride). In the event that any of these side effects do occur, they may require medical attention.

Major Side Effects

You should check with your doctor immediately if any of these side effects occur when taking Glimepiride (Tripride) / Pioglitazone (Tripride):

More common:

• Anxiety
• bladder pain
• bloody or cloudy urine
• blurred vision
• chills
• cold sweats
• coma
• confusion
• cool, pale skin
• depression
• difficult, burning, or painful urination
• fast heartbeat
• frequent urge to urinate
• headache
• increased hunger
• increased weight
• lower back or side pain
• nausea
• nightmares
• seizures
• shakiness
• slurred speech
• swelling of the feet or lower legs
• unusual tiredness or weakness

• Accidental injury
• loss of appetite
• pain or swelling in the arms or legs without any injury
• pale skin
• stomach pain
• troubled breathing with exertion
• unusual bleeding or bruising
• vomiting
• weight loss
• yellow eyes or skin

Minor Side Effects

Some of the side effects that can occur with Glimepiride (Tripride) / Pioglitazone (Tripride) may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common:

• Body aches or pain
• cough
• diarrhea
• difficulty with moving
• dryness or soreness of the throat
• ear congestion
• fever
• hoarseness
• joint pain
• loss of voice
• muscle aching or cramping
• muscle pains or stiffness
• runny nose
• sneezing
• stuffy nose
• swollen joints
• tender, swollen glands in the neck
• tooth disorder
• trouble swallowing
• voice changes

• Dizziness
• itching skin
• lack or loss of strength
• skin rash