Actos

Name: Actos

What is the dosage for Actos (pioglitazone)?

  • Actos is prescribed once daily in doses ranging from 15 to 45 mg.
  • The recommended starting dose for patients without heart failure is 15 or 30 mg and for those with heart failure it is 15 mg daily. The dose may be increased in 15 mg intervals to a maximum dose of 45 mg daily if needed.
  • Actos may be taken any time of the day, with or without meals.
  • If a dose is missed on one day, two doses should not be taken the next day to make up for the missed dose.

Introduction

Antidiabetic agent; thiazolidinedione (glitazone).1 8 9 12

Cautions for Actos

Contraindications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Initiation of therapy in patients with NYHA class III or IV heart failure.1 27 28 (See Boxed Warning.)

  • Known serious1 hypersensitivity to pioglitazone or any ingredient in the formulation.1 27 28

Warnings/Precautions

Warnings

CHF

Fluid retention associated with use of pioglitazone, alone or in combination with other antidiabetic agents, may lead to or exacerbate CHF.1 19 27 28 30 31 37 38 40 41 (See Boxed Warning.) Use in combination with insulin or in patients with NYHA class I or II heart failure may increase the risk.1

Monitor for signs and symptoms of CHF (e.g., dyspnea, rapid weight gain, edema, unexplained cough or fatigue), especially during initiation of therapy and dosage titration.1 19 27 28 37 40

If CHF develops, manage according to current standards of care.1 19 27 28 37 40 Consider dosage reduction or discontinuance of pioglitazone.1 19 27 28 37 40

Do not initiate thiazolidinedione therapy in hospitalized patients with diabetes mellitus because of delayed onset of action and potential for increased vascular volume and CHF.34

Edema

Fluid retention reported; may lead to or exacerbate CHF.1 13

Use with caution in patients with edema and in those at risk for CHF.1 27 Observe for manifestations of CHF (e.g., dyspnea, rapid weight gain, edema).1 (See CHF under Cautions.)

Weight Gain

Reported; may involve fluid retention and fat accumulation.1 (See Boxed Warning.)

Other Warnings/Precautions

Hepatic Effects

No evidence of hepatotoxicity in clinical studies to date.1 12 13 However, hepatitis, elevations in hepatic enzymes, mixed hepatocellular-cholestatic liver injury,15 and, very rarely, hepatic failure associated with fatalities reported during postmarketing experience.1

Monitor liver function tests prior to initiation of therapy, then periodically thereafter according to clinician judgment.1 12 Monitor more frequently if used in patients with mild hepatic impairment (ALT 1–2.5 times the upper limit of normal [ULN]).1 (See Hepatic Impairment under Cautions.)

Recheck liver function if ALT increases to >3 times the ULN or if manifestations suggestive of hepatic dysfunction (e.g., unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, dark urine) occur.1 Discontinue therapy if ALT remains elevated at >3 times the ULN or if jaundice develops.1

Musculoskeletal Effects

Risk of bone loss and fractures in women, and possibly in men, receiving thiazolidinedione therapy.1 29 35 36 39 47 50

Fractures reported more frequently in women receiving pioglitazone (5.1%) than in women receiving placebo (2.5%) in long-term study (mean 34.5 months follow-up).1 27 28 30 32 33 Effects noted after first year of treatment and persisted throughout treatment.1 27 28 30 32 33 Most fractures were nonvertebral, occurring in a distal limb (forearm, hand, wrist, foot, ankle, fibula, tibia).1 27 28 29

In an observational study, use of pioglitazone or rosiglitazone for approximately 12–18 months associated with twofold to threefold increase in fractures, particularly of hip and wrist.50 Overall risk of fracture similar among men and women.50

Consider risk of fracture, particularly in female patients.1 29 35 Assess and maintain bone health according to current standards of care.1 28 29 30 32 33 35

Risk of Bladder Cancer

Increased risk of bladder cancer.1 27 28 Do not use in patients with active bladder cancer; use with caution in patients with history of bladder cancer, weighing benefits of glycemic control against unknown risks of cancer recurrence.1 27 28 80

Hypoglycemia

Concomitant use of insulin or other antidiabetic drugs (e.g., insulin secretagogues) increases risk for hypoglycemia.1 27 28 May need to reduce dosage of concomitant antidiabetic agent to decrease risk of hypoglycemia.1 27 28 (See Dosage under Dosage and Administration.)

Ocular Effects

New-onset or worsening (diabetic) macular edema with decreased visual acuity reported rarely; concurrent peripheral edema reported frequently.1 27 28 32 33 Symptoms improved in some patients following discontinuance of pioglitazone.1 27 28 32 33

Regular eye examinations by ophthalmologist advised.1 27 28 32 33 34 Promptly refer patients reporting visual symptoms to ophthalmologist, regardless of other concurrent therapy or physical findings.1 27 28 32 33

Ovulatory Effects

May cause ovulation in premenopausal anovulatory women; risk of pregnancy unless adequate contraceptive measures initiated.1

Macrovascular Outcomes

Evidence of macrovascular risk reduction with pioglitazone or any other antidiabetic agent has not been conclusively demonstrated in controlled clinical trials.1

Laboratory Abnormalities

Possible dose-related decreases in hemoglobin and hematocrit; usually evident within 4–12 weeks of therapy.1 May be related to plasma volume expansion.1 Rarely associated with clinically important hematologic manifestations.1

Isolated elevations in serum CK >10 times ULN noted rarely during clinical trials.1 Resolved in most patients without apparent sequelae despite continued therapy with the drug; any relationship to pioglitazone therapy unknown.1

Use of Fixed Combinations

When used in fixed combination with metformin hydrochloride or glimepiride, consider the cautions, precautions, and contraindications associated with the concomitant agent.27 28

Specific Populations

Pregnancy

Category C.1 Most clinicians recommend that insulin be used during pregnancy in women with diabetes mellitus.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Use not recommended.1

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age; use not recommended.1 13

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.1

Hepatic Impairment

Use with caution in patients with mild hepatic impairment (ALT 1–2.5 times the ULN).1 12 Use not recommended in patients with active hepatic disease, ALT >2.5 times the ULN, or troglitazone-associated jaundice (troglitazone no longer commercially available in US).1 12

Common Adverse Effects

Upper respiratory tract infection, headache, sinusitis, myalgia, pharyngitis, edema.1

Interactions for Actos

Metabolized principally by CYP2C8 and, to a lesser extent, by CYP3A4 and other isoenzymes (e.g., CYP1A1).1 Weak inducer of CYP3A4.1

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP2C8 inhibitors: Increased pioglitazone AUC and half-life; do not exceed maximum pioglitazone dosage of 15 mg once daily.1

CYP2C8 inducers: Decreased pioglitazone AUC.1 Initiation or discontinuance of a CYP2C8 inducer during pioglitazone therapy may necessitate changes in antidiabetic therapy; however, do not exceed maximum recommended pioglitazone dosage of 45 mg daily.1

Specific Drugs

Drug

Interaction

Comments

Antidiabetic agents

Additive effects; possible hypoglycemia1

May need to reduce dosage of other antidiabetic agents1

Atorvastatin

Decreased plasma concentrations and AUC for atorvastatin and pioglitazone1

Digoxin

Pharmacokinetic interaction unlikely1

Fexofenadine

Pharmacokinetic interaction unlikely1

Gemfibrozil

Increased pioglitazone AUC and half-life1 27

Do not exceed maximum pioglitazone dosage of 15 mg once daily

Ketoconazole

Increased serum concentrations and AUC for pioglitazone1 13 27

Midazolam

Decreased midazolam AUC and peak plasma concentrations1

Nifedipine, extended-release

Decreased peak plasma nifedipine concentrations and AUC1

Clinical importance unknown1

Oral contraceptives, hormonal (ethinyl estradiol/norethindrone)

Small decreases in peak plasma ethinyl estradiol concentrations and AUC1

Clinical importance unknown1

Ranitidine

Pharmacokinetic interaction unlikely1

Rifampin

Decreased pioglitazone AUC1 27

May require change in antidiabetic therapy if rifampin initiated or discontinued during pioglitazone therapy, but do not exceed maximum pioglitazone dosage of 45 mg daily1 27

Theophylline

Pharmacokinetic interaction unlikely1

Warfarin

Pharmacokinetic or pharmacologic interaction (e.g., effect on PT) unlikely1

Stability

Storage

Oral

Tablets

Tight containers at 25°C (may be exposed to 15–30°C).1 Protect from moisture and humidity.1

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Pioglitazone Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

15 mg (of pioglitazone)

Actos

Takeda

30 mg (of pioglitazone)

Actos

Takeda

45 mg (of pioglitazone)

Actos

Takeda

Pioglitazone Hydrochloride Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

15 mg (of pioglitazone) with Metformin Hydrochloride 500 mg

Actoplus Met

Takeda

15 mg (of pioglitazone) with Metformin Hydrochloride 850 mg

Actoplus Met

Takeda

30 mg (of pioglitazone) with Glimepiride 2 mg

Duetact

Takeda

30 mg (of pioglitazone) with Glimepiride 4 mg

Duetact

Takeda

Oral

Tablets, extended-release (metformin hydrochloride core)

15 mg (of pioglitazone) with Metformin Hydrochloride 1 g

Actoplus Met XR

Takeda

30 mg (of pioglitazone) with Metformin Hydrochloride 1 g

Actoplus Met XR

Takeda

Before Using Actos

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of pioglitazone in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of pioglitazone in the elderly. However, elderly patients are more likely to have age-related heart disease, which may require an adjustment in the dose for patients receiving pioglitazone.

Pregnancy

Pregnancy Category Explanation
All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

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

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Acebutolol
  • Atenolol
  • Atorvastatin
  • Betaxolol
  • Bisoprolol
  • Bitter Melon
  • Carteolol
  • Carvedilol
  • Celiprolol
  • Esmolol
  • Fenugreek
  • Glucomannan
  • Guar Gum
  • Ketoconazole
  • Labetalol
  • Levobunolol
  • Metipranolol
  • Metoprolol
  • Nadolol
  • Nebivolol
  • Nilotinib
  • Oxprenolol
  • Penbutolol
  • Pindolol
  • Practolol
  • Propranolol
  • Psyllium
  • Rifampin
  • Sotalol
  • Timolol
  • Topiramate

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Bladder cancer, active or
  • Diabetic ketoacidosis (high ketones and acid in the blood) or
  • Heart failure, severe or
  • Type I diabetes—Should not be used in patients with these conditions.
  • Diabetic macular edema (swelling of the back of the eye) or
  • Edema (fluid retention or swelling) or
  • Heart disease or
  • Liver disease—Use with caution. May make these conditions worse.
  • Fever or
  • Infection or
  • Surgery or
  • Trauma—Use with caution. These conditions may cause problems with blood sugar control.

How is this medicine (Actos) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take with or without food.
  • To gain the most benefit, do not miss doses.
  • Keep taking this medicine (Actos) as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

  • Skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

What are some other side effects of Actos?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Signs of a common cold.
  • Headache.
  • Sinus pain.
  • Sore throat.
  • Muscle pain.
  • Gas.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

How do I store and/or throw out Actos?

  • Store in the original container at room temperature.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Contraindications

• Initiation in patients with established NYHA Class III or IV heart failure [see Boxed Warning]. • Use in patients with known hypersensitivity to pioglitazone or any other component of Actos.

Actos Description

Actos tablets are a thiazolidinedione and an agonist for peroxisome proliferator-activated receptor (PPAR) gamma that contains an oral antidiabetic medication: pioglitazone.

Pioglitazone [(±)-5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]-2,4-] thiazolidinedione monohydrochloride contains one asymmetric carbon, and the compound is synthesized and used as the racemic mixture. The two enantiomers of pioglitazone interconvert in vivo. No differences were found in the pharmacologic activity between the two enantiomers. The structural formula is as shown:

Pioglitazone hydrochloride is an odorless white crystalline powder that has a molecular formula of C19H20N2O3S•HCl and a molecular weight of 392.90 daltons. It is soluble in N,N-dimethylformamide, slightly soluble in anhydrous ethanol, very slightly soluble in acetone and acetonitrile, practically insoluble in water, and insoluble in ether.

Actos is available as a tablet for oral administration containing 15 mg, 30 mg, or 45 mg of pioglitazone (as the base) formulated with the following excipients: lActose monohydrate NF, hydroxypropylcellulose NF, carboxymethylcellulose calcium NF, and magnesium stearate NF.

How supplied

Dosage Forms And Strengths

Round tablet contains pioglitazone as follows:

  • 15 mg: White to off-white, debossed with “ACTOS” on one side and “15” on the other
  • 30 mg: White to off-white, debossed with “ACTOS” on one side and “30” on the other
  • 45 mg: White to off-white, debossed with “ACTOS” on one side and “45” on the other

Storage And Handling

ACTOS is available in 15 mg, 30 mg, and 45 mg tablets as follows:

15 mg tablet: White to off-white, round, convex, nonscored tablet with “ACTOS” on one side, and “15” on the other, available in:

NDC 64764-151-04 Bottles of 30
NDC 64764-151-05 Bottles of 90
NDC 64764-151-06 Bottles of 500

30 mg tablet: White to off-white, round, flat, nonscored tablet with “ACTOS” on one side, and “30” on the other, available in:

NDC 64764-301-14 Bottles of 30
NDC 64764-301-15 Bottles of 90
NDC 64764-301-16 Bottles of 500

45 mg tablet: White to off-white, round, flat, nonscored tablet with “ACTOS” on one side, and “45” on the other, available in:

NDC 64764-451-24 Bottles of 30
NDC 64764-451-25 Bottles of 90
NDC 64764-451-26 Bottles of 500

Storage

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Keep container tightly closed, and protect from light, moisture and humidity.

Distributed by: Takeda Pharmaceuticals America, Inc., Deerfield, IL 60015. Revised: Dec 2016

Manufacturer

  • Takeda Pharmaceuticals America, Inc.

Actos Usage

  • Take Actos tablets exactly as your doctor tells you to take it.
  • Your doctor may change your dose of Actos. Do not change your Actos dose unless your doctor tells you to.
  • Actos may be prescribed alone or with other diabetes medicines. This will depend on how well your blood sugar is controlled.
  • Take Actos one time each day, with or without food.
  • If you miss a dose of Actos, take your next dose as prescribed unless your doctor tells you differently. Do not take two doses at one time the next day.
  • If you take too much Actos, call your doctor or go to the nearest hospital emergency room right away.
  • If your body is under stress such as from a fever, infection, accident or surgery the dose of your diabetes medicines may need to be changed. Call your doctor right away.
  • Stay on your diet and exercise programs and test your blood sugar regularly while taking Actos.
  • Your doctor should do certain blood tests before you start and while you take Actos.
  • Your doctor should also do hemoglobin A1C testing to check how well your blood sugar is controlled with Actos.
  • Your doctor should check your eyes regularly while you take Actos.
  • It may take 2 to 3 months to see the full effect of Actos on your blood sugar level.

What happens if i miss a dose (actos)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

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