Web Article Directory Curaçao: March 2012

Saturday, 31 March 2012

Soriatane

Generic Name: Acitretin
Class: Skin and Mucous Membrane Agents, Miscellaneous
VA Class: DE810
Chemical Name: all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid
Molecular Formula: C₂₁H₂₆O₃
CAS Number: 55079-83-9

Teratogenicity

Known human teratogen; very high risk of severe birth defects, generally characterized by malformations involving craniofacial, cardiovascular, skeletal, and CNS structures, if administered during pregnancy.¹ (See Fetal/Neonatal Morbidity and Mortality and also see Contraindications under Cautions.)

Contraindicated during pregnancy.¹ ²³ Acitretin must not be used in female patients who are or may become pregnant during therapy or within at least 3 years following drug discontinuance or in females who may not use reliable contraception during and for at least 3 years following cessation of therapy.¹ ⁸

Do Your PART program developed to educate females of childbearing potential and their clinicians about risks associated with acitretin and to aid in the prevention of pregnancies during and for 3 years following drug discontinuance.¹ (See Do Your PART Program under Cautions.)

Counseling about contraception and behaviors associated with increased pregnancy risk must occur monthly during and at 3-month intervals following drug discontinuance for at least 3 years.¹

If pregnancy occurs during therapy or at any time within at least 3 years following drug discontinuance, the clinician and patient should discuss the possible effects on the pregnancy.¹ (See Pregnancy under Cautions.)

Alcohol

Concomitant use of acitretin and alcohol results in formation of etretinate, a known human teratogen with a longer elimination half-life than acitretin, prolonging the duration of potential teratogenic effects of acitretin; alcohol must not be used in female patients of childbearing potential during acitretin treatment and for 2 months following drug discontinuance.¹ ² ³ ⁶ ⁸ ⁹ ¹⁰ ¹¹ ¹⁴ ¹⁸ ¹⁹ ²³ (See Specific Drugs under Interactions.)

Blood Donation

Both male and female patients receiving acitretin should not donate blood during therapy and for at least 3 years following drug discontinuance because women of childbearing potential must not receive blood from patients receiving acitretin.¹

Hepatotoxicity

Risk of developing potentially serious hepatic injury.¹ (See Hepatic Effects under Cautions.)

Monitor hepatic enzyme levels prior to initiating therapy, at weekly or biweekly intervals until stable, and thereafter at intervals based on clinician's discretion.¹ ³

If hepatotoxicity is suspected during acitretin therapy, discontinue the drug and investigate the cause of the abnormality.¹ ⁸

Introduction

Active metabolite of etretinate (no longer commercially available in US); a retinoid.¹ ⁴ ⁷ ⁸ ¹⁰ ¹¹ ¹² ¹⁷ ¹⁸ ¹⁹

Uses for Soriatane

Psoriasis

Symptomatic management of severe psoriasis.¹ ²³

Not indicated as a first-line antipsoriatic therapy in women of childbearing potential; should be used only in nonpregnant patients with severe psoriasis that is refractory to alternative therapies or in whom other therapies are contraindicated.¹ ²³ (See Teratogenicity in Boxed Warning.)

Relapse may occur when acitretin is discontinued; if clinically indicated, repeat courses of the drug may be used since clinical efficacy in relapse has been similar to that of the initial course.¹

Discoid Lupus Erythematosus

Has been used in a limited number of patients for the management of discoid lupus erythematosus†; efficacy was similar to that of hydroxychloroquine, but adverse effects were more severe and frequent with acitretin.²⁰ ²¹ Further study is needed to establish the role of acitretin in treating this condition.²⁰

Soriatane Dosage and Administration

General

Acitretin should only be prescribed by clinicians who have special competence in diagnosis and treatment of severe psoriasis, are experienced in use of systemic retinoids, and understand risk of teratogenicity.¹ (See Do Your PART Program under Cautions, and see Boxed Warning.)

Individualize dosage according to therapeutic response and the appearance of adverse effects.¹

If a patient misses a dose, the next dose should not be doubled.¹

Patients concomitantly receiving phototherapy may require dosage reduction of phototherapy.¹ (See Phototherapy under Cautions.)

Administration

Oral Administration

Administer orally once daily with the main meal.¹ ¹⁵ ¹⁶ (See Food under Pharmacokinetics.)

Dosage

Adults

Psoriasis

Oral

Initial dosage: 25–50 mg once daily.¹ ¹¹

Maintenance dosage: 25–50 mg (dependent on patient's response to initial therapy) once daily.¹ ¹¹

Relapse dosage: 25–50 mg once daily.¹ ¹¹

In clinical studies, acitretin therapy was continued for up to 18 months in some patients.¹ ²³

Prescribing Limits

Adults

Psoriasis

Oral

Dosages >50 mg daily not evaluated in controlled studies.²³

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.¹ (See Contraindications under Cautions.)

Renal Impairment

No specific dosage recommendations at this time.¹ (See Contraindications under Cautions.)

Geriatric Patients

Select dosage with caution (usually starting at the low end of the dosage range) because of possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹ (See Absorption: Special Populations, under Pharmacokinetics and also see Elimination: Special Populations, under Pharmacokinetics.)

Cautions for Soriatane

Contraindications

Females who are or may become pregnant during acitretin therapy or within at least 3 years following drug discontinuance.¹ ⁹ ¹³ (See Fetal/Neonatal Morbidity and Mortality under Cautions and also see Teratogenicity in Boxed Warning.)

Severely impaired renal or hepatic function.¹ ³ ⁹ (See Hepatic Effects under Cautions and also see Absorption: Special Populations, under Pharmacokinetics.)

Chronic, abnormally elevated blood lipids.¹ (See Effects on Lipoproteins under Cautions.)

Concomitant use with methotrexate, tetracyclines, or vitamin A and/or other oral retinoids.¹ ²³ (See Specific Drugs under Interactions.)

Known hypersensitivity to acitretin, any ingredient in the formulation, or other retinoids.¹

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Very high risk of severe birth defects if pregnancy occurs while receiving acitretin or upon drug discontinuance (birth defects reported ≥2 years after the last dose of acitretin).¹ ⁶ ⁸ ⁹ ¹⁹ Teratogenicity generally is characterized by malformations involving craniofacial, cardiovascular, skeletal, and CNS structures.¹ ⁶ ⁸ ⁹ ¹⁹ (See Do Your PART Program under Cautions, and see Teratogenicity in Boxed Warning.)

Hepatic Effects

Jaundice, acute hepatic injury, toxic hepatitis, and cirrhosis reported in limited number of patients; generally, transaminase levels returned to normal after drug discontinuance.¹ ¹¹ ¹⁹

Elevations of AST, ALT, γ-glutamyltransferase (GGT), or LDH reported in approximately one-third of patients receiving acitretin; elevations generally were mild to moderate and resolved with continued therapy, a reduction in acitretin dosage, or upon drug discontinuance.¹ ³ ⁷ ⁸ ¹¹ ¹⁷ Transient elevations of alkaline phosphatase also reported.¹ ⁸ ¹⁷ ¹⁹

Monitor hepatic enzyme levels.¹ ³ (See Hepatotoxicity in Boxed Warning.) More frequent monitoring recommended if alcoholism, diabetes mellitus, concomitant use of other hepatotoxic drugs, and/or obesity present.³

If hepatotoxicity is suspected during therapy, discontinue acitretin and investigate the cause of the abnormality.¹ ⁸

Concomitant use of acitretin and methotrexate contraindicated.¹ (See Specific Drugs under Interactions.)

Hyperostosis

Hyperostosis (including diffuse interstitial skeletal hyperostosis syndrome [DISH]) reported.¹ ³ ⁵ ⁶ ⁷ ⁸ ⁹ ¹¹ ¹⁷ ¹⁹ Changes may involve worsening of preexisting skeletal overgrowth.¹ ³ ¹⁹

Periodically monitor patients receiving long-term acitretin therapy for ossification abnormalities; radiography recommended only in the presence of symptoms or long-term acitretin use.¹ ³ ¹⁷ ¹⁹ If symptoms arise, consider the potential benefits of continued therapy compared with potential for the development of hyperostosis.¹ (See Pediatric Use under Cautions.)

Effects on Lipoproteins

In clinical trials, 66, 33, and 40% of patients experienced elevated triglycerides, elevated cholesterol, and decreased HDL-cholesterol, respectively; lipid abnormalities usually were reversible with cessation of therapy.¹ ³ ⁷ ⁸ ⁹ ¹¹ ¹⁷

Monitor fasting blood lipid concentrations prior to initiating therapy and at weekly or biweekly intervals until lipid response is established (usually within 4–8 weeks).¹ ³

Increased risk of hypertriglyceridemia in patients with diabetes mellitus, obesity, increased alcohol intake, lipid metabolism disorder, or familial history of these conditions.¹ ⁶ ⁷ ⁸ ⁹ ¹⁹ Close monitoring of serum lipid and/or glucose in these patients and in patients receiving long-term therapy recommended.¹

Use contraindicated in patients with chronic, abnormally elevated blood lipid concentrations.¹

Dietary modifications, acitretin dosage reductions, or lipid-lowering agents should be used to control clinically important triglyceride elevations;¹ ³ ⁸ ⁹ ¹⁹ consider acitretin discontinuance if hypertriglyceridemia and decreased HDL-cholesterol persist.¹

Ocular Effects

Dry eyes, irritation, and brow/lash loss reported in 23, 9, and 5%, respectively, of acitretin recipients evaluated in one study.¹ ⁸ ⁹ ¹⁵ ¹⁷ ¹⁹ Other adverse ocular effects, including decreased night vision, reported in <5% of patients.¹ ⁶ ⁸ (See Advice to Patients.)

If visual difficulties occur during therapy, discontinue the drug and perform an ophthalmologic examination.¹

Pancreatitis

Lipid elevations reported in 25–50% of acitretin recipients;¹ ⁶ ⁸ ¹⁹ elevations of triglycerides to concentrations associated with fatal fulminant pancreatitis are rare; however, cases have been reported with acitretin.¹ ³ ⁸ ¹⁹ Rare cases of pancreatitis without hypertriglyceridemia also reported.¹

Pseudotumor Cerebri

Pseudotumor cerebri (benign intracranial hypertension) has been reported with acitretin and other oral retinoids (e.g., isotretinoin); some patients with pseudotumor cerebri were receiving concomitant isotretinoin and tetracycline therapy.¹ ⁶ ⁸ ¹⁵ ¹⁹ However, also has been reported in one patient receiving acitretin without concomitant tetracycline.¹ ³

Screen patients who develop manifestations of pseudotumor cerebri (e.g., headache, nausea and vomiting, visual disturbances) for the presence of papilledema and, if present, discontinue the drug immediately and refer to a neurologist for further evaluation and care.¹ ³ ⁸

Concomitant use of acitretin and tetracyclines contraindicated.¹ (See Specific Drugs under Interactions.)

Sensitivity Reactions

Photosensitivity

Avoid exposure to natural or artificial (e.g., sun lamps) sunlight; effects of UV light enhanced by acitretin.¹ ³ (See Phototherapy under Cautions.)

General Precautions

Do Your PART Program

Do Your PART program developed to reinforce importance of pregnancy prevention by providing information on risks of fetal exposure to acitretin and to help prevent pregnancy.¹ (See Teratogenicity in Boxed Warning and also see Fetal/Neonatal Morbidity and Mortality under Cautions.)

Patient must complete and sign a Patient Agreement/Informed Consent form detailing risks of potential birth defects, contraceptive failure, and alcohol ingestion, and importance of pregnancy prevention during and after drug discontinuance.¹ ²³ A Soriatane Patient/Contraceptive Counseling Referral form also is provided, allowing for free initial contraceptive counseling session and pregnancy testing.¹ ²³ A Medication Guide for all patients and a patient survey for women of childbearing potential also are included.¹ ²³

Prior to issuing the initial prescription for acitretin, exclude pregnancy by 2 negative serum or urine tests (perform second test during the first 5 days of the menstrual period immediately prior to initiation of acitretin therapy); exclude pregnancy by monthly testing during therapy and every 3 months after therapy discontinuance.¹ ²³ Initial testing should be performed by a clinician.¹

To enhance compliance with pregnancy testing, a limited supply of acitretin should be prescribed.¹

Pregnancy must be prevented by simultaneous use of 2 forms of reliable contraception (unless patient is absolutely abstinent, has undergone a hysterectomy, or is postmenopausal) for at least 1 month prior to therapy initiation, during, and for at least 3 years following cessation of therapy.¹ ² ³ ²³ (See Advice to Patients.)

For detailed information regarding the program's requirements, consult the manufacturer's prescribing information; prescribers should contact the manufacturer to obtain information on materials available for the program.¹ ²³ To obtain further information regarding contraception options, patients should contact the Birth Control Counseling line at 800-739-6700.²³

Psychiatric Disorders

Depression and other psychiatric symptoms (e.g., aggressive feelings, self-injurious thoughts or behaviors, suicidal thoughts) reported;¹ ⁶ not known whether related to acitretin or to other factors.¹ Such events also reported with other systemic retinoids.¹

Patients who experience symptoms of depression or other psychiatric symptoms during acitretin therapy should discontinue the drug and immediately notify their prescribing clinician.¹

Phototherapy

Concomitant use of phototherapy and acitretin may result in increased risk of erythema (e.g., burning); if concomitant use cannot be avoided, substantially reduce the phototherapy dose based upon patient response.¹

Specific Populations

Pregnancy

Category X.¹ ⁸ ¹⁹ Report all pregnancies during therapy or up to 3 years following discontinuance of drug to Stiefel Laboratories at 888-500-3376 or to FDA MedWatch Program at 800-FDA-1088.¹ ²³ (See Fetal/Neonatal Morbidity and Mortality under Cautions and also see Teratogenicity in Boxed Warning.)

Lactation

Distributed into milk;¹ ¹⁸ women receiving acitretin should not breast-feed.¹ ¹⁵ ²³

Pediatric Use

Safety and efficacy not established.¹ ²³

Ossification of interosseous ligaments and tendons of the extremities, skeletal hyperostoses, decreases in bone mineral density, and premature epiphyseal closure reported in children with other systemic retinoids, including etretinate (no longer commercially available in US).¹ ⁹ A causal relationship has not been established between the use of acitretin and these effects, and it is unknown whether these occurrences are more severe or appear more frequently in children.¹ However, the manufacturer states that there is special concern because of the implications for growth potential in this population.¹

Geriatric Use

Insufficient clinical trial experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹ Other reported clinical experience has not identified differences in responses between geriatric and younger patients.¹ (See Geriatric Patients under Dosage and Administration.)

Common Adverse Effects

Cheilitis, alopecia, skin peeling, rhinitis, dry skin, nail disorder, pruritus, rigors, xerophthalmia, dry mouth, epistaxis, arthralgia, spinal hyperostosis, rash, hyperesthesia, paresthesia, paronychia, skin atrophy.¹ ³ ⁵ ⁶ ⁷ ⁸ ⁹ ¹¹ ¹⁵ ¹⁷ ¹⁹

Many reported adverse effects resemble those associated with hypervitaminosis A.¹

Laboratory abnormalities (e.g., increased or decreased electrolytes, hematocrit, hemoglobin, and glucose; increased liver transaminases, uric acid, BUN, and total and LDL-cholesterol; decreased HDL-cholesterol).¹ (See Hepatic Effects under Cautions and also see Effects on Lipoproteins under Cautions.)

Interactions for Soriatane

Specific Drugs

Acitretin is not metabolized by hepatic microsomal enzymes.²³ (See Metabolism under Pharmacokinetics.)

Drug	Interaction	Comments
Alcohol	Concomitant administration of alcohol and acitretin resulted in formation of etretinate, a known human teratogen with a longer elimination half-life than acitretin; may increase duration of teratogenic effects of acitretin¹ ³ ⁶ ⁸ ⁹ ¹⁰ ¹¹ ¹⁴ ¹⁸ ¹⁹ Concomitant use may result in hepatotoxicity³	Avoid concomitant use of alcohol from any source during and for 2 months after acitretin therapy cessation in women of childbearing potential¹ ² ³ ¹⁸ ¹⁹ ²³
Aspirin	Possible potentiation of mucosal damage with high-dose aspirin therapy⁹	Avoid concomitant therapy with high-dose aspirin⁹
Cimetidine	Pharmacokinetic interaction unlikely¹
Contraceptives (estrogen-progestin combinations)	Unknown if pharmacokinetic interaction exists between acitretin and combination hormonal contraceptives¹	See Teratogenicity in Boxed Warning
Contraceptives (progestin-only)	Acitretin interferes with contraceptive effect of low-dose oral progestin-only preparations (i.e., minipill)	Unknown if other progestational contraceptives (e.g., implants, injectables) are adequate methods of contraception during acitretin therapy¹ Concomitant use not recommended¹ ³ ¹¹ ¹⁴
Corticosteroids	Concomitant use may result in hyperlipidemia or pseudotumor cerebri³	Careful monitoring recommended if used concomitantly³
Digoxin	Pharmacokinetic interaction unlikely¹
Glibenclamide (not commercially available in US)	Potentiation of hypoglycemic effects of glibenclamide¹	Use with caution; careful monitoring of diabetic patients recommended¹
Glyburide	Pharmacokinetic interaction unlikely¹
Methotrexate	Increased risk of hepatitis¹ (see Hepatic Effects under Cautions)	Concomitant use contraindicated¹
Phenytoin	Possible pharmacokinetic interaction (reduced phenytoin protein binding)¹
Retinoids, oral	Possible additive adverse effects (e.g., hypervitaminosis A)¹ ³	Concomitant use not recommended¹ ³
St. John's wort (Hypericum perforatum)	Possible risk of hormonal contraceptive failure during concomitant use¹	Concomitant use not recommended¹
Tetracyclines (e.g., minocycline)	Possible increased risk for pseudotumor cerebri and photosensitivity¹ ³ ⁹ ¹¹ (see Pseudotumor Cerebri under Cautions)	Concomitant use contraindicated¹ ⁹
Vitamin A	Possible additive adverse effects (e.g., hypervitaminosis A)¹ ³ ¹¹	Concomitant use contraindicated¹ ³ ⁹ ²³
Warfarin	No effect observed on warfarin protein binding¹

Soriatane Pharmacokinetics

Absorption

Bioavailability

Absorption from GI tract is linear with dose-proportional increases at doses of 25–100 mg.¹ ²

Following administration of a single 50-mg oral acitretin dose to healthy individuals, approximately 60–72% (range: 36–109%) of dose was absorbed.¹ ² ¹⁷

High interindividual and intraindividual variation in peak plasma concentrations;² ¹⁷ mean peak plasma concentration in healthy individuals was achieved in an average of 2.7 hours (range: 2–5 hours).¹ ¹⁷ Following multiple doses in healthy individuals, steady state achieved within approximately 1–3 weeks.¹ ² ¹⁵

In patients with psoriasis, mean steady-state trough concentrations demonstrated dose-dependent increases with daily dosages of 10–50 mg.¹ Plasma concentrations were nonmeasurable 3–4 weeks after cessation of therapy.¹ ¹⁵ ¹⁷

Onset

Improvement seen within first 8 weeks of treatment in clinical trials; full efficacy usually evident within 2–3 months.¹ ²³

Food

Food enhances absorption and reduces the interindividual variability in absorption.¹ ² ³ ⁶ ⁸ ⁹ ¹⁵ ¹⁶ ¹⁷ ¹⁹

Special Populations

In healthy geriatric individuals receiving multiple doses of acitretin, plasma concentrations increased twofold compared with those in younger individuals.¹ (See Elimination: Special Populations, under Pharmacokinetics.)

In patients with end-stage renal failure receiving a single 50-mg oral acitretin dose, lower plasma concentrations (by 50–59%) were seen compared with healthy individuals; acitretin not removed by hemodialysis.¹ ¹⁷

Distribution

Extent

Distributes into skin with highest concentrations in stratum corneum.² ¹⁰ ¹⁴ Penetrates adipose tissue but does not accumulate in tissues.¹⁰ ¹³ ¹⁴ ¹⁶

Distributes into milk; crosses placenta.¹ ² ¹⁸

Small amounts of acitretin are distributed into semen; appear to pose little, if any, risk to an unborn child while a male patient is receiving the drug.¹

Plasma Protein Binding

>99.9% (mainly albumin).¹ ⁹ ¹³ ¹⁵ ¹⁶ ¹⁷

Elimination

Metabolism

Extensively metabolized by simple isomerization in liver by interconversion to 13-cis-acitretin with subsequent oxidation into chain-shortened breakdown products and conjugation to glucuronides.¹ ² ⁹ ¹¹ ¹³ ¹⁴ ¹⁶ ¹⁷ ¹⁸ Metabolized to etretinate if alcohol used concomitantly (see Specific Drugs under Interactions).¹ ⁹ Not metabolized by hepatic microsomal enzymes.²³

Elimination Route

Excreted in urine (16–53%) and feces (34–54%) as metabolites.¹ ⁷ ⁹ ¹¹

Half-life

Acitretin, following multiple doses: Estimated at about 49 hours but has been reported to range from 24–96 hours.¹ ³ ⁴ ⁶ ⁷ ⁸ ¹¹ ¹² ¹³ ¹⁴ ¹⁵ ¹⁶ ¹⁷ ¹⁸

13-cis-Acitretin, following multiple doses: About 63 hours (range: 28–157 hours).¹ ¹³ ¹⁴ ¹⁵ ¹⁷ ¹⁸

Special Populations

In healthy geriatric individuals, elimination half-life was similar to that in younger individuals.¹

Stability

Storage

Oral

Capsules

15–25°C in tight, light-resistant containers.¹ Avoid exposing opened product to high temperatures and humidity.¹

Actions

Exact mechanism of action in the treatment of psoriasis is not fully understood, but may involve inhibiting the conversion of retinol to retinoic acid, stimulating the metabolism and buffering of retinoic acid by increasing levels of cellular retinoic acid binding protein-2 (CRABP 2), and/or altering the metabolism of endogenous retinoids at the level of degradation.¹ ⁴

Modulates epidermal proliferation and cellular differentiation; demonstrates antiproliferative effect on epidermal keratinocytes in a hyperproliferative system, resulting in decreased scaling, erythema, and thickness of plaques and stratum corneum; promotes cellular proliferation in normoproliferative systems.⁵ ⁶ ⁸ ⁹ ¹³ ¹⁷ ¹⁹

Activates retinoid X receptors (RXR) and the α, β, and γ subtypes of retinoic acid receptors (RAR); potentiates epidermal growth factor-induced cell growth; increases activity of cyclic adenosine monophosphate (cAMP)-dependent protein kinases, RI (involved in cell proliferation), and RII (involved in cell differentiation and growth inhibition) in deficient areas of psoriatic fibroblasts; inhibits chemotactic responses; decreases polymorphonuclear leukocyte migration/accumulation; and increases the number of Langerhans cells in normal and psoriatic skin.⁴ ⁶ ⁸ ⁹ ¹⁷ ¹⁹

Exhibits antineoplastic activity in vitro.¹⁷

Has teratogenic effects.¹ (See Boxed Warning.)

Advice to Patients

Provide all patients with a copy of the medication guide upon initial and subsequent dispensing of drug.¹

Describe risk of birth defects.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions and also see Teratogenicity in Boxed Warning.)

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹ Necessity of advising women of childbearing potential to avoid pregnancy by using 2 methods of contraception simultaneously for ≥1 month prior to, throughout, and for ≥3 years after acitretin therapy.¹ ² At least one method of contraception must be a primary form (e.g., tubal sterilization; vasectomized partner; intrauterine device; oral, injectable, inserted, transdermal, or implanted hormonal contraceptive) unless patient practices abstinence, has undergone a hysterectomy, or is postmenopausal.¹ ²³ (See Do Your PART Program under Cautions.)

Importance of discontinuing therapy and immediately notifying clinician if pregnancy, unprotected intercourse, or a missed menstrual cycle occurs during or within 3 years after drug discontinuance.¹ (See Pregnancy under Cautions.)

Importance of warning both male and female patients not to share acitretin with anyone else and not to donate blood while receiving acitretin and for at least 3 years after cessation of therapy.¹

Importance of women avoiding alcohol from any source (e.g., OTC preparations, foods) during therapy and for 2 months following drug discontinuance.¹ ² ²³ (See Alcohol in Boxed Warning and Specific Drugs under Interactions.)

Importance of discontinuing acitretin therapy and promptly reporting symptoms of depression or other psychiatric symptoms (e.g., aggression, self-injurious behaviors, suicidal thoughts) to clinician.¹

Importance of informing clinicians if acute abdominal pain or emesis occurs; may be early indicators of pancreatitis.³

Risk of decreased night vision; importance of being cautious when driving or operating any vehicle at night.¹

Importance of advising patients who wear contact lenses that they may experience decreased tolerance to the lenses during or after therapy with the drug; lubricating ophthalmic ointments or artificial tears may be needed.¹ ⁹ ¹⁵

Importance of informing clinicians if concomitant phototherapy is being received.¹ (See Phototherapy under Cautions.)

Importance of advising patients to avoid excessive exposure to natural or artificial sunlight (e.g., sun lamps).¹ ³ (See Photosensitivity under Cautions.)

Importance of informing patients that a transient worsening of psoriasis may occur initially and that full clinical benefit may not be evident for 2–3 months.¹ ⁶ ²³

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription or OTC drugs and herbal supplements, as well as any concomitant illnesses.¹ Importance of avoiding vitamin A supplements in excess of the minimum recommended daily allowance.¹ ³ (See Contraindications under Cautions and also see Specific Drugs under Interactions.)

Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

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

Acitretin
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	10 mg	Soriatane	Stiefel
		17 mg	Soriatane	Stiefel
		22.5 mg	Soriatane	Stiefel
		25 mg	Soriatane	Stiefel

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Soriatane 25MG Capsules (GLAXO SMITH KLINE): 30/$892.97 or 60/$1,749.96

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions August 11, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Stiefel Laboratories, Inc. Soriatane (acitretin) capsules prescribing information. Coral Gables, FL; 2009 Jul.

2. Wiegand UW, Chou RC. Pharmacokinetics of acitretin and etretinate. J Am Acad of Dermatol. 1998; 39:S25-33.

3. Katz HI, Waalen J, Leach EE. Acitretin in psoriasis: An overview of adverse effects. J Am Acad Dermatol. 1999; 41:S7-12. [PubMed 10459140]

4. Saurat JH. Retinoids and psoriasis: Novel issues in retinoid pharmacology and implications for psoriasis treatment. J Am Acad Dermatol. 1999; 41:S2-6. [PubMed 10459139]

5. Janjua A, Chalmers RJG, Zheng A et al. Oral retinoids for psoriasis (protocol). Cochrane Database Syst Rev. 2007; 3:CD006139.

6. Van De Kerkhof PCM. Update on retinoid therapy of psoriasis in: an update on the use of retinoids in dermatology. Dermatologic Therapy. 2006; 19:252-63. [PubMed 17014480]

7. Anon. Acitretin, a new retinoid. Drug Ther Bull. 1993; 31:75-6.

8. Yamauchi PS, Rizk D, Lowe NJ. Retinoid therapy for psoriasis. Dermatol Clin. 2004; 22:467-76. [PubMed 15450342]

9. Orfanos CE, Zouboulis CC, Almond-Roesler B et al. Current use and future potential role of retinoids in dermatology. Drugs. 1997; 53:358-88. [PubMed 9074840]

10. Lambert WE, Meyer E, De Leenheer AP et al. Pharmacokinetics of acitretin. Acta Derm Venerol. 1994; 186(Suppl):122-3.

11. Anon. Two new retinoids for psoriasis. Med Lett Drugs Ther. 1997; 39:105-6.

12. Lowe NJ, Lazarus V, Matt L. Systemic retinoid therapy for psoriasis. J Am Acad Dermatol. 1988; 19:186-91. [PubMed 2970476]

13. Bouvy ML, Sturkenboom MCJM, Cornel MC et al. Acitretin (Neotigason): a review of pharmacokinetics and teratogenicity and hypothesis on metabolic pathways. Pharm Weekbl Sci. 1992; 14:33-7. [PubMed 1388261]

14. Geiger JM, Baudin M, Saurat JH. Teratogenic risk with etretinate and acitretin treatment. Dermatology. 1994; 189:109-116. [PubMed 8075435]

15. Larsen FG, Nielsen-Kudsk F, Jakobsen P et al. Pharmacokinetics and therapeutic efficacy of retinoids in skin diseases. Clin Pharmacokinet. 1992; 23:42-61. [PubMed 1617858]

Friday, 30 March 2012

Sulfatol Cleanser Emulsion

Pronunciation: sul-fa-SEE-ta-mide/yoor-EE-a
Generic Name: Sulfacetamide/Urea
Brand Name: Examples include Rosula Cleanser and Sulfatol Cleanser

Sulfatol Cleanser Emulsion is used for:

Treating certain skin conditions (eg, seborrheic dermatitis), dandruff, and certain bacterial infections of the skin. It may also be used for other conditions as determined by your doctor.

Sulfatol Cleanser Emulsion is a sulfonamide antibiotic. It works by killing bacteria, helping to shed scaly skin, and softening the skin.

Do NOT use Sulfatol Cleanser Emulsion if:

you are allergic to any ingredient in Sulfatol Cleanser Emulsion

you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to any other sulfonamide medicine, such as acetazolamide, celecoxib, certain diuretics (eg, hydrochlorothiazide), glyburide, probenecid, sulfamethoxazole, valdecoxib, or zonisamide

you are taking methenamine

Contact your doctor or health care provider right away if any of these apply to you.

Before using Sulfatol Cleanser Emulsion:

Some medical conditions may interact with Sulfatol Cleanser Emulsion. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have a history of lupus

Some MEDICINES MAY INTERACT with Sulfatol Cleanser Emulsion. Tell your health care provider if you are taking any other medicines, especially any of the following:

Silver-containing products (eg, silver sulfadiazine) because they may decrease Sulfatol Cleanser Emulsion's effectiveness

Methenamine because it may increase the risk of Sulfatol Cleanser Emulsion's side effects

This may not be a complete list of all interactions that may occur. Ask your health care provider if Sulfatol Cleanser Emulsion may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Sulfatol Cleanser Emulsion:

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

Sulfatol Cleanser Emulsion is for use on the skin only. Wash your hands before and immediately after using Sulfatol Cleanser Emulsion. Clean the affected area before applying Sulfatol Cleanser Emulsion. Wet skin and apply plenty of Sulfatol Cleanser Emulsion. Rub gently into the skin for 10 to 20 seconds to form a full lather, rinse completely, and pat dry.

To clear up your infection completely, use Sulfatol Cleanser Emulsion for the full course of treatment. Keep using it even if you feel better in a few days.

Sulfatol Cleanser Emulsion works best if it is used at the same time each day.

Continue to use Sulfatol Cleanser Emulsion even if you feel well. Do not miss any doses.

If you miss a dose of Sulfatol Cleanser Emulsion, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Sulfatol Cleanser Emulsion.

Important safety information:

It may take several days for Sulfatol Cleanser Emulsion to work fully.

Avoid getting Sulfatol Cleanser Emulsion in your eyes, nose, or mouth.

Talk with your doctor before you use any other medicines or cleansers on your skin.

Contact your doctor right away if stomach pain or cramps, severe diarrhea, or bloody stools occur. Do not treat diarrhea without first checking with your doctor.

Sulfatol Cleanser Emulsion only works against bacteria; it does not treat viral infections.

Be sure to use Sulfatol Cleanser Emulsion for the full course of treatment. If you do not, the medicine may not clear up your infection completely. The bacteria could also become less sensitive to this or other medicines. This could make the infection harder to treat in the future.

Long-term or repeated use of Sulfatol Cleanser Emulsion may cause a second infection. Tell your doctor if signs of a second infection occur. Your medicine may need to be changed to treat this.

Sulfatol Cleanser Emulsion should be used with extreme caution in CHILDREN younger than 12 years old; safety and effectiveness in these children have not been confirmed.

PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Sulfatol Cleanser Emulsion while you are pregnant. It is not known if Sulfatol Cleanser Emulsion is found in breast milk after topical use. If you are or will be breast-feeding while you use Sulfatol Cleanser Emulsion, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Sulfatol Cleanser Emulsion:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Irritation, stinging, or burning of the skin.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody diarrhea; fever; joint pain; red, swollen, or blistered skin; severe diarrhea; sores in the mouth; stomach cramps/pain.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Sulfatol Cleanser Emulsion may be harmful if swallowed. Symptoms of ingestion may include change in the amount of urine; nausea; vomiting.

Proper storage of Sulfatol Cleanser Emulsion:

Store Sulfatol Cleanser Emulsion at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Do not freeze. Keep Sulfatol Cleanser Emulsion out of the reach of children and away from pets.

General information:

If you have any questions about Sulfatol Cleanser Emulsion, please talk with your doctor, pharmacist, or other health care provider.

Sulfatol Cleanser Emulsion is to be used only by the patient for whom it is prescribed. Do not share it with other people.

If your symptoms do not improve or if they become worse, check with your doctor.

Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Sulfatol Cleanser Emulsion. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Sulfatol Cleanser resources

Sulfatol Cleanser Use in Pregnancy & Breastfeeding
Sulfatol Cleanser Support Group
0 Reviews for Sulfatol - Add your own review/rating

Compare Sulfatol Cleanser with other medications

Dandruff
Seborrheic Dermatitis
Secondary Cutaneous Bacterial Infections

Tuesday, 27 March 2012

Radiographic Exam Medications

Drugs associated with Radiographic Exam

The following drugs and medications are in some way related to, or used in the treatment of Radiographic Exam. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Drug List:

Reglan

Monday, 26 March 2012

Betadine Antiseptic Paint (Molnlycke Health Care )

1. Name Of The Medicinal Product

Betadine Antiseptic Paint.

2. Qualitative And Quantitative Composition

Povidone Iodine USP 10% w/v.

3. Pharmaceutical Form

Cutaneous solution.

4. Clinical Particulars

4.1 Therapeutic Indications

As a general antiseptic paint in the prevention and treatment of infections.

4.2 Posology And Method Of Administration

For topical administration. Adults, children and the elderly: Apply Betadine Antiseptic Paint undiluted as necessary to the affected area and allow to dry. Rinse the brush thoroughly after use.

4.3 Contraindications

Hypersensitivity to iodine. History of abnormal thyroid function or goitre.

4.4 Special Warnings And Precautions For Use

If local irritation and hypersensitivity develop, then discontinue treatment.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

None stated.

4.6 Pregnancy And Lactation

Use in pregnancy and lactation should be limited to minor lesions only. Although no adverse effects have been reported from limited use, caution should be recommended and therapeutic benefit must be balanced against possible effects of the absorption of iodine on foetal thyroid function and development.

4.7 Effects On Ability To Drive And Use Machines

None stated.

4.8 Undesirable Effects

Rarely, local irritation may occur.

4.9 Overdose

In the case of deliberate or accidental ingestion of large quantities, symptomatic and supportive treatment should be provided with special attention to electrolyte balance and thyroid function.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Povidone iodine is a complex of iodine which shows all the broad-spectrum germicidal activity of elemental iodine. The germicidal activity is maintained in the presence of blood, pus, serum and necrotic tissue. It is effective in the treatment of infections caused by bacteria, fungi, yeasts and viruses (e.g. Herpes Virus Types I and II).

5.2 Pharmacokinetic Properties

None stated.

5.3 Preclinical Safety Data

None stated.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Glycerol; nonoxynol 9; disodium hydrogen phosphate (anhydrous); citric acid monohydrate; industrial methylated spirit; sodium hydroxide (5% solution); purified water.

6.2 Incompatibilities

None stated.

6.3 Shelf Life

36 months unopened.

6.4 Special Precautions For Storage

Store below 25^oC.

6.5 Nature And Contents Of Container

Glass bottle with a white polypropylene cap and applicator brush containing 8ml of product.

6.6 Special Precautions For Disposal And Other Handling

None stated.

7. Marketing Authorisation Holder

Seton Healthcare Group plc, Tubiton House, Oldham, OL1 3HS.

8. Marketing Authorisation Number(S)

PL 0223/0011.

9. Date Of First Authorisation/Renewal Of The Authorisation

28^th April 1993 / 8^th November 2003.

10. Date Of Revision Of The Text

November 2003.

Sunday, 25 March 2012

analgesic combination, acetaminophen/salicylate Oral

Class Name: analgesic combination, acetaminophen/salicylate (Oral route)

Commonly used brand name(s)

In the U.S.

Backprin

Be-Flex Plus

By-Ache

Cafgesic Forte

Combiflex

Combiflex ES

Durabac

Durabac Forte

Genaced

Goody's Fast Pain Relief

Levacet

Pain-Off

Available Dosage Forms:

Tablet

Capsule, Liquid Filled

Packet

Capsule

Uses For This Medicine

Acetaminophen and salicylate combination medicines relieve pain and reduce fever. They may be used to relieve occasional pain caused by mild inflammation or arthritis (rheumatism). The acetaminophen, aspirin, and caffeine combination also may be used to relieve pain associated with migraine headaches.

Neither acetaminophen nor salicylamide is as effective as aspirin for treating chronic or severe pain, or other symptoms, caused by inflammation or arthritis. Some of these combination medicines do not contain any aspirin. Even those that do contain aspirin may not contain enough to be effective in treating these conditions.

A few reports have suggested that acetaminophen and salicylates used together may cause kidney damage or cancer of the kidney or urinary bladder. This may occur if large amounts of both medicines are taken together for a very long time. However, taking usual amounts of these combination medicines for a short time has not been shown to cause these unwanted effects. Also, these effects are not likely to occur with either acetaminophen or a salicylate used alone, even if large amounts have been taken for a long time. Therefore, for long-term use, it may be best to use either acetaminophen or a salicylate, but not both, unless you are under a doctor's care.

Before giving any of these combination medicines to a child, check the package label very carefully. Some of these medicines are too strong for use in children. If you are not certain whether a specific product can be given to a child, or if you have any questions about the amount to give, check with your health care professional.

These medicines are available without a prescription. However, your doctor may have special instructions on the proper dose of these medicines for your medical condition.

Before Using This Medicine

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group 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

For acetaminophen: Acetaminophen has been tested in children and, in effective doses, has not been shown to cause different side effects or problems than it does in adults.

For aspirin and for salicylamide: Do not give a medicine containing aspirin or salicylamide to a child with symptoms of a virus infection, especially flu or chickenpox, without first discussing its use with your child's doctor. This is very important because aspirin may cause a serious illness called Reye's syndrome in children with fever caused by a virus infection, especially flu or chickenpox. Children who do not have a virus infection may also be more sensitive to the effects of aspirin, especially if they have a fever or have lost large amounts of body fluid because of vomiting, diarrhea, or sweating. This may increase the chance of side effects during treatment.

For caffeine: There is no specific information comparing use of caffeine in children younger than 12 years of age with use in other age groups. However, caffeine is not expected to cause different side effects or problems in children than it does in adults.

Geriatric

Elderly people may be more likely than younger adults to develop serious kidney problems if they take large amounts of these combination medicines for a long time. Therefore, it is best that elderly people not take this medicine for more than 5 days in a row unless they are under a doctor's care.

For acetaminophen: Acetaminophen has been tested and, in effective doses, has not been shown to cause different side effects or problems in older people than it does in younger adults.

For aspirin: People 60 years of age and older are especially sensitive to the effects of aspirin. This may increase the chance of side effects during treatment.

For caffeine: Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of caffeine in the elderly with use in other age groups.

Pregnancy

For acetaminophen: Studies on birth defects have not been done in humans. However, acetaminophen has not been reported to cause birth defects or other problems.

For aspirin: Studies in humans have not shown that aspirin causes birth defects. However, aspirin has been shown to cause birth defects in animals. Do not take aspirin during the last 3 months of pregnancy unless it has been ordered by your doctor. Some reports have suggested that too much use of aspirin late in pregnancy may cause a decrease in the newborn's weight and possible death of the fetus or newborn infant. However, the mothers in these reports had been taking much larger amounts of aspirin than are usually recommended. Studies of mothers taking aspirin in the doses that are usually recommended did not show these unwanted effects. However, there is a chance that regular use of aspirin late in pregnancy may cause unwanted effects on the heart or blood flow in the fetus or newborn infant. Use of aspirin during the last 2 weeks of pregnancy may cause bleeding problems in the fetus before or during delivery, or in the newborn infant. Also, too much use of aspirin during the last 3 months of pregnancy may increase the length of pregnancy, prolong labor, cause other problems during delivery, or cause severe bleeding in the mother before, during, or after delivery.

For salicylamide: Studies on birth defects have not been done in humans.

For caffeine: Studies in humans have not shown that caffeine causes birth defects. However, use of large amounts of caffeine by the mother during pregnancy may cause problems with the heart rhythm of the fetus and may affect the growth of the fetus. Studies in animals have shown that caffeine causes birth defects when given in very large doses (amounts equal to the amount of caffeine in 12 to 24 cups of coffee a day).

Breast Feeding

For acetaminophen and for aspirin: Acetaminophen and aspirin pass into breast milk; however, they have not been reported to cause problems in nursing babies.

For caffeine: Caffeine (contained in some of these combination medicines) passes into breast milk in small amounts. Taking caffeine in the amounts present in these medicines has not been reported to cause problems in nursing babies. However, studies have shown that babies may appear jittery and have trouble in sleeping when their mothers drink large amounts of caffeine-containing beverages. Therefore, breast-feeding mothers who use these medicines probably should limit the amount of caffeine they take in from other medicines or from beverages

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 any of these medicines, 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 medicines in this class with any of the following medicines is not recommended. Your doctor may decide not to treat you with a medication in this class or change some of the other medicines you take.

Influenza Virus Vaccine, Live

Ketorolac

Using medicines in this class 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.

Abciximab

Acenocoumarol

Alteplase, Recombinant

Anisindione

Argatroban

Beta Glucan

Bivalirudin

Cilostazol

Citalopram

Clovoxamine

Dabigatran Etexilate

Desirudin

Desvenlafaxine

Dicumarol

Dipyridamole

Duloxetine

Eptifibatide

Escitalopram

Femoxetine

Flesinoxan

Fluoxetine

Fluvoxamine

Fondaparinux

Ginkgo

Heparin

Ketoprofen

Lepirudin

Methotrexate

Milnacipran

Mycophenolate Mofetil

Mycophenolic Acid

Naproxen

Nefazodone

Paroxetine

Phenindione

Phenprocoumon

Protein C

Quinine

Reteplase, Recombinant

Rilpivirine

Rivaroxaban

Sertraline

Sibutramine

Ticlopidine

Tirofiban

Varicella Virus Vaccine

Venlafaxine

Vilazodone

Warfarin

Zimeldine

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.

Using medicines in this class with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use your medicine, or give you special instructions about the use of food, alcohol, or tobacco.

Ethanol

Proper Use of This Medicine

Take this medicine with food or a full glass (8 ounces) of water to lessen the chance of stomach upset.

Unless otherwise directed by your doctor:

Do not take more of this medicine than directed on the package label. Taking too much acetaminophen may cause liver damage or lead to other medical problems because of an overdose. Also, taking too much aspirin can cause stomach problems or lead to other medical problems because of an overdose.

Children up to 12 years of age should not take this medicine more often than five times a day

Check with your doctor before taking one of these combination medicines to treat severe or chronic inflammation or arthritis (rheumatism). These combination medicines may not relieve the severe pain, redness, swelling, or stiffness caused by these conditions unless very large amounts are taken for a long time. It is best not to take acetaminophen and salicylate combination medicines in large amounts for a long time unless you are under a doctor's care.

If a combination medicine containing aspirin has a strong vinegar-like odor, do not use it. This odor means the medicine is breaking down. If you have any questions about this, check with your pharmacist.

Dosing

The dose medicines in this class will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of these medicines. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral (capsules or tablets [including caplets]) dosage forms:
- For pain, fever, or mild arthritis symptoms:
  - Adults and teenagers—The usual dose is 1 or 2 capsules or tablets every three, four, or six hours, depending on the strength of the product. Do not take any of these combination medicines for more than ten days, unless otherwise directed by your doctor
  - Children—Use and dose must be determined by your doctor.
- For migraine headaches:
  - Adults and teenagers—The usual dose is 2 tablets (250 mg acetaminophen, and 250 mg of aspirin, and 65 mg of caffeine in combination) every six hours as necessary for relief from migraine headaches. Do not take for relief of migraine headache for more than two days, unless otherwise directed by your doctor
  - Children—Use and dose must be determined by your doctor.

For oral (powder) dosage form:
- For pain, fever, or mild arthritis symptom:
  - Adults and teenagers—This medicine is very strong. Each packet of powder contains 260 mg of acetaminophen and 520 mg of aspirin (a total of 780 mg of both medicines). The usual dose is one packet of powder every four to six hours. Do not take this medicine for more than ten days, unless otherwise directed by your doctor.
  - Children—The oral powder dosage form is too strong to use in children 12 years of age or younger.

Storage

Keep out of the reach of children.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using This Medicine

If you will be taking this medicine for a long time, or in high doses, your doctor should check your progress at regular visits. This is especially important for elderly people, who may be more likely than younger adults to develop serious kidney problems if they take large amounts of this medicine for a long time.

Check with your doctor:

If you are taking this medicine to relieve pain and the pain lasts for more than 10 days (5 days for children), if the pain gets worse, if new symptoms occur, or if the painful area is red or swollen. These could be signs of a serious condition that needs treatment.

If you are taking this medicine to bring down a fever, and the fever lasts for more than 3 days or returns, if your fever gets worse, if new symptoms occur, or if redness or swelling is present. These could be signs of a serious condition that needs treatment.

If you are taking this medicine for a sore throat, and the sore throat is very painful, lasts for more than 2 days, or occurs together with or is followed by fever, headache, skin rash, nausea, or vomiting.

Do not take any of the combination medicines containing aspirin for 5 days before any surgery, including dental surgery, unless otherwise directed by your medical doctor or dentist. Taking aspirin during this time may cause bleeding problems.

Check the label of all over-the-counter (OTC), nonprescription, and prescription medicines you now take. If any of them contain acetaminophen, aspirin, other salicylates such as bismuth subsalicylate (e.g., Pepto Bismol) or magnesium salicylate (e.g., Nuprin Backache Caplets), or salicylic acid (present in some shampoos and skin products), check with your health care professional. Using any of them together with this medicine may cause an overdose.

Stomach problems may be more likely to occur if you drink three or more alcoholic beverages while you are taking aspirin. Also, liver damage may be more likely to occur if you drink three or more alcoholic beverages while you are taking acetaminophen.

Taking certain other medicines together with acetaminophen and salicylates may increase the chance of unwanted effects. The risk will depend on how much of each medicine you take every day, and on how long you take the medicines together. If your medical doctor or dentist directs you to take these medicines together on a regular basis, follow his or her directions carefully. However, do not take any of the following medicines together with any of these combination medicines for more than a few days unless your doctor has directed you to do so and is following your progress:

Diclofenac (e.g., Voltaren)

Diflunisal (e.g., Dolobid)

Etodolac (e.g., Lodine)

Fenoprofen (e.g., Nalfon)

Floctafenine (e.g., Idarac)

Flurbiprofen, oral (e.g., Ansaid)

Ibuprofen (e.g., Motrin)

Indomethacin (e.g., Indocin)

Ketoprofen (e.g., Orudis)

Ketorolac (e.g., Toradol)

Meclofenamate (e.g., Meclomen)

Mefenamic acid (e.g., Ponstel)

Nabumetone (e.g., Relafen)

Naproxen (e.g., Naprosyn)

Oxaprozin (e.g., Daypro)

Phenylbutazone (e.g., Butazolidin)

Piroxicam (e.g., Feldene)

Sulindac (e.g., Clinoril)

Tenoxicam (e.g., Mobiflex)

Tiaprofenic acid (e.g., Surgam)

Tolmetin (e.g., Tolectin)

The antacid present in buffered forms of these combination medicines can keep other medicines from working properly. If you need to take a buffered form of this medicine, and you are also taking one of the following medicines, be sure to take the buffered acetaminophen and salicylate combination medicine:

At least 6 hours before or 2 hours after taking ciprofloxacin (e.g., Cipro) or lomefloxacin (e.g., Maxaquin).

At least 8 hours before or 2 hours after taking enoxacin (e.g., Penetrex).

At least 2 hours after taking itraconazole (e.g., Sporanox).

At least 3 hours before or after taking ketoconazole (e.g., Nizoral).

At least 2 hours before or after taking norfloxacin (e.g., Noroxin) or ofloxacin (e.g., Floxin).

At least 3 or 4 hours before or after taking a tetracycline antibiotic by mouth.

At least 1 or 2 hours before or after taking any other medicine by mouth.

If you are taking a laxative containing cellulose, do not take it within 2 hours of taking this medicine. Taking the laxative and this medicine close together may make this medicine less effective by preventing the salicylate in it from being absorbed by your body.

Acetaminophen and salicylate combinations may interfere with the results of some medical tests. Before you have any medical tests, tell the person in charge if you have taken any of these combination medicines within the past 3 or 4 days. If possible, it is best to call the laboratory where the test will be done about 4 days ahead of time to find out whether the medicine may be taken during the 3 or 4 days before the test.

For patients with diabetes:

Acetaminophen and salicylate combinations may cause false results with some blood and urine glucose (sugar) tests. If you notice any change in your test results, or if you have any questions about this possible problem, check with your health care professional. This is especially important if your diabetes is not well-controlled.

For patients taking one of the products that contain caffeine:

Caffeine may interfere with the results of a test that uses adenosine (e.g., Adenocard) or dipyridamole (e.g., Persantine) to help find out how well your blood is flowing through certain blood vessels. Therefore, you should not have any caffeine for 8 to 12 hours before the test.

If you think that you or anyone else may have taken an overdose of this medicine, get emergency help at once. Taking an overdose of a salicylate may cause unconsciousness or death. The first symptom of an aspirin overdose may be ringing or buzzing in the ears. Other signs include convulsions (seizures), hearing loss, confusion, severe drowsiness or tiredness, severe excitement or nervousness, and unusually fast or deep breathing. Signs of severe acetaminophen overdose may not appear until 2 to 4 days after the overdose is taken, but treatment to prevent liver damage or death must be started within 24 hours or less after the overdose is taken.

Side Effects of This Medicine

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Less common or rare

Coughing

difficulty in swallowing

dizziness, lightheadedness, or feeling faint (severe)

flushing, redness, or other change in skin color

shortness of breath, troubled breathing, tightness in chest, or wheezing

sudden decrease in amount of urine

swelling of eyelids, face, or lips

Get emergency help immediately if any of the following symptoms of overdose occur:

Signs and symptoms of overdose

Agitation, anxiety, excitement, irritability, nervousness, or restlessness

any loss of hearing

bloody urine

confusion or delirium

convulsions (seizures)

diarrhea (severe or continuing)

dizziness or lightheadedness

drowsiness (severe)

fast or deep breathing

fast or irregular heartbeat (for medicines containing caffeine

frequent urination (for medicines containing caffeine)

hallucinations (seeing, hearing, or feeling things that are not there)

increased sensitivity to touch or pain (for medicines containing caffeine)

increased sweating

loss of appetite

muscle trembling or twitching (for medicines containing caffeine)

nausea or vomiting (continuing, sometimes with blood)

ringing or buzzing in ears (continuing)

seeing flashes of lights (for medicines containing caffeine)

stomach cramps or pain (severe or continuing)

swelling, pain, or tenderness in the upper abdomen or stomach area

trouble in sleeping (for medicines containing caffeine)

uncontrollable flapping movements of the hands, especially in elderly patients

unexplained fever

unexplained fever

Signs of overdose in children

Changes in behavior

drowsiness or tiredness

fast or deep breathing

Check with your doctor as soon as possible if any of the following side effects occur:

Less common or rare

Bloody or black, tarry stools

bloody or cloudy urine

fever with or without chills (not present before treatment and not caused by the condition being treated)

pain in lower back and/or side (severe and/or sharp)

pinpoint red spots on skin

skin rash, hives, or itching

sores, ulcers, or white spots on lips or in mouth

sore throat (not present before treatment and not caused by the condition being treated)

stuffy nose

swelling of face, fingers, feet, or lower legs

unusual bleeding or bruising

unusual tiredness or weakness

vomiting of blood or material that looks like coffee grounds

weight gain

yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Heartburn or indigestion (for medicines containing aspirin)

nausea, vomiting, or stomach pain (for medicines containing aspirin)

Less common

Drowsiness (for medicines containing salicylamide)

trouble in sleeping, nervousness, or jitters (for medicines containing caffeine)

After you stop using this medicine, it may still produce some side effects that need attention. During this period of time, check with your doctor immediately if you notice the following side effects:

Rare

Bloody or cloudy urine

decreased urination

swelling of face, fingers, feet, or lower legs

weight gain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The information contained in the Thomson Healthcare (Micromedex) products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Healthcare does not assume any responsibility or risk for your use of the Thomson Healthcare products.

Saturday, 24 March 2012

Actos

Generic Name: Pioglitazone Hydrochloride
Class: Thiazolidinediones
ATC Class: A10BG03
VA Class: HS502
Chemical Name: (±)-5-[p-[2-(5-Ethyl-2-pyridyl)ethoxy]benzyl]-2,4-thiazolidinedione monohydrochloride
Molecular Formula: C₁₉H₂₀N₂O₃S•ClH
CAS Number: 112529-15-4

Special Alerts:

[Posted 09/17/2010] ISSUE: FDA notified healthcare professionals and patients that the Agency is reviewing data from an ongoing, ten-year epidemiological study designed to evaluate whether pioglitazone (Actos) is associated with an increased risk of bladder cancer. Findings from studies in animals and humans suggest this is a potential safety risk that needs further study. At this time, FDA has not concluded that pioglitazone increases the risk of bladder cancer. Its review is ongoing, and the Agency will update the public when it has additional information.

BACKGROUND: The drug manufacturer, Takeda, conducted a planned analysis of the study data at the five-year mark, and submitted their results to FDA. Overall, there was no statistically significant association between pioglitazone exposure and bladder cancer risk. However, further analyses were also performed looking at how long patients were on pioglitazone and the total amount of the drug they received during that time. An increased risk of bladder cancer was observed among patients with the longest exposure to pioglitazone, as well as in those exposed to the highest cumulative dose of pioglitazone.

RECOMMENDATIONS: Healthcare professionals should continue to follow the recommendations in the drug label when prescribing pioglitazone. Patients should continue taking pioglitazone unless told otherwise by their healthcare professional. Patients who are concerned about the possible risks associated with using pioglitazone should talk to their healthcare professional.

Additional Information for Patients, Information for Healthcare Professionals, and a Data Summary are provided in the Drug Safety Communication. For more information visit the FDA website at: and .

[Posted 08/14/2007] After a review of postmarketing adverse event reports, FDA determined that an updated label with a boxed warning on the risks of heart failure was needed for the entire thiazolidinedione class of antidiabetic drugs. These drugs are used in conjunction with diet and exercise to improve blood sugar control in adults with type 2 (non-insulin-dependent) diabetes. Manufacturers of certain drugs have agreed to the upgraded warning.

The strengthened warning advises healthcare professionals to observe patients carefully for the signs and symptoms of heart failure, including excessive, rapid weight gain, shortness of breath, and edema after starting drug therapy. Patients with these symptoms who then develop heart failure should receive appropriate management of the heart failure and use of the drug should be reconsidered. People who have questions should contact their healthcare providers to discuss alternative treatments. For more information visit the FDA website at: , , and .

[Posted 03/09/2007] Takeda and FDA notified healthcare professionals of recent safety data concerning pioglitazone-containing products. The results of an analysis of the manufacturer’s clinical trial database of pioglitazone showed more reports of fractures in female patients taking pioglitazone than those taking a comparator (either placebo or active). The majority of fractures observed in female patients were in the distal upper limb (forearm, hand and wrist) or distal lower limb (foot, ankle, fibula and tibia). There were more than 8100 patients in the pioglitazone-treated groups and over 7400 patients in the comparator-treated groups. The duration of pioglitazone treatment was up to 3.5 years. Healthcare professionals should consider the risk of fracture when initiating or treating female patients with type 2 diabetes mellitus with pioglitazone-containing products. For more information visit the FDA website at: and .

REMS:

FDA approved a REMS for pioglitazone to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of pioglitazone and consists of the following: medication guide. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

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

Uses for Actos

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.

Diabetes Mellitus

Used alone or in combination with a sulfonylurea, metformin, or insulin as an adjunct to diet and exercise for the management of type 2 (noninsulin-dependent) diabetes mellitus (NIDDM).¹ ² Should be added to, not substituted for, other antidiabetic agents in patients whose NIDDM is not adequately controlled by these agents.¹³

May be added to glyburide/metformin fixed combination therapy if hyperglycemia is not adequately controlled with the fixed combination.¹⁴ May be used in combination with repaglinide if hyperglycemia is not adequately controlled with diet, exercise, and monotherapy with another oral antidiabetic agent.¹⁷

Not effective as sole therapy for type 1 diabetes mellitus or diabetic ketoacidosis; insulin is necessary.¹

Actos Dosage and Administration

Administration

Oral Administration

Administer orally once daily without regard to meals.¹

Dosage

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.

Available as pioglitazone hydrochloride; dosage expressed in terms of pioglitazone.¹

Adults

Diabetes Mellitus

Monotherapy

Oral

Initially, 15 or 30 mg once daily.¹ If response is inadequate, increase dosage in increments, up to a maximum dosage of 45 mg daily.¹ If response is inadequate with monotherapy, consider combination therapy.¹

Combination with Other Antidiabetic Agents

Oral

May continue current dosage of the sulfonylurea, metformin, or insulin upon initiation of pioglitazone.¹

Combination therapy with a sulfonylurea: Initially, 15 or 30 mg once daily.¹ If hypoglycemia occurs, reduce sulfonylurea dosage.¹

Combination therapy with metformin: Initially, 15 or 30 mg once daily.¹ Adjustment of metformin dosage unlikely.¹

Combination therapy with insulin: Initially, 15 or 30 mg once daily.¹ If hypoglycemia occurs or if fasting plasma glucose (FPG) concentrations decrease to <100 mg/dL, decrease insulin dosage by 10–25%.¹ Further adjustments should be individualized based on therapeutic response.¹

Prescribing Limits

Adults

Maximum 45 mg daily (as monotherapy or in combination with a sulfonylurea, metformin, or insulin).¹

Special Populations

Renal Impairment

No dosage adjustment necessary.¹

Geriatric Patients

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.

No dosage adjustment necessary.¹

CHF

Should be initiated at the lowest approved dosage in patients with type 2 diabetes and systolic CHF (NYHA class II).¹ If subsequent dosage escalation is necessary, increase dosage gradually only after several months of treatment.¹ Monitor carefully for weight gain, edema, or other manifestations of CHF exacerbation.¹ Use not recommended in patients with more severe CHF (NYHA class III or IV).¹

Cautions for Actos

Contraindications

Known hypersensitivity to pioglitazone or any ingredient in the formulation.¹

Warnings/Precautions

Warnings

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.

Effects on Fluid Balance

Risk of fluid retention; may cause or exacerbate heart failure.¹ ¹³ Weight gain reported, possibly associated with fluid retention and fat accumulation.¹

Use with caution in patients with edema.¹ Observe for manifestations of heart failure (e.g., dyspnea, rapid weight gain, edema) and discontinue therapy if any deterioration in cardiac status occurs.¹ Use not recommended in patients with New York Heart Association (NYHA) class III or IV heart failure.¹

General Precautions

Ovulatory Effects

Possible ovulation in premenopausal anovulatory women; risk of pregnancy unless contraceptive measures initiated.¹

Hematologic Effects

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

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

Specific Populations

Pregnancy

Category C.¹ Most clinicians recommend that insulin be used during pregnancy.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.¹ ¹²

Common Adverse Effects

Upper respiratory tract infection, headache, sinusitis, myalgia, tooth disorder, aggravation of diabetes mellitus, 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

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
Ketoconazole	Increased serum concentrations and AUC for pioglitazone¹³
Midazolam	Decreased midazolam concentrations¹
Nifedipine, extended-release	Decreased peak nifedipine concentrations and AUC¹	Clinical importance unknown¹
Oral contraceptives, hormonal (ethinyl estradiol and norethindrone)	Decreased ethinyl estradiol concentrations¹	Clinical importance unknown¹
Ranitidine	Pharmacokinetic interaction unlikely¹
Theophylline	Pharmacokinetic interaction unlikely¹
Warfarin	Pharmacokinetic or pharmacologic interaction (e.g., effect on PT) unlikely¹

Actos Pharmacokinetics

Absorption

Bioavailability

Peak serum concentrations attained within 2 hours.¹

Absolute bioavailability is 83%.^a

Food

Food delays time to peak serum concentration to 3–4 hours but does not affect extent of absorption.¹

Special Populations

In patients with hepatic impairment (Child-Pugh class B or C), peak pioglitazone concentration is decreased by 45%.¹

In geriatric patients, AUC of pioglitazone is increased; not clinically relevant.¹

In females, peak serum concentration and AUC are increased by 20–60%.¹

Distribution

Extent

Distributed into milk in rats.¹ Not known whether the drug distributes into human milk.¹

Plasma Protein Binding

>99% (mainly albumin).¹

Elimination

Metabolism

Extensively metabolized, principally by CYP2C8 and, to a lesser extent, by CYP3A4 and other isoenzymes (e.g., CYP1A1).¹

Elimination Route

Excreted in urine (15–30%) and in feces, primarily as metabolites.¹

Half-life

3–7 hours (for pioglitazone) or 16–24 hours (for pioglitazone and metabolites).¹

Special Populations

In geriatric patients, terminal half-life is prolonged; not clinically relevant.¹

Stability

Storage

Oral

Tablets

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

Actions

Structurally and pharmacologically related to rosiglitazone and troglitazone (no longer commercially available in the US);¹ ⁸ ⁹ ¹ ¹² unrelated to other antidiabetic agents (e.g., sulfonylureas, biguanides, α-glucosidase inhibitors).¹ ¹²

A peroxisome proliferator-activated receptor_γ (PPAR_γ) agonist; increases transcription of insulin-responsive genes.¹

Increases insulin sensitivity in target tissues and decreases hepatic gluconeogenesis.¹ Ameliorates insulin resistance associated with type 2 diabetes mellitus without increasing insulin secretion from pancreatic β cells.¹ Does not lower glucose concentrations below euglycemia.¹

Ineffective in absence of insulin.¹

Advice to Patients

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.

Importance of adhering to diet and exercise regimen.¹ Importance of regular monitoring (preferably self-monitoring) of blood glucose and HbA_1c.¹

Importance of immediately informing clinician if potential manifestations of heart failure (e.g., rapid weight gain, edema, shortness of breath) occur.¹

Importance of informing patients that liver function tests will be performed prior to initiation of therapy and periodically thereafter.¹ (See Hepatic Effects under Cautions.) Advise patients to inform clinician if potential manifestations of hepatic dysfunction (e.g., unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, dark urine) occur.¹

Risk of hypoglycemia in patients receiving concomitant antidiabetic agent therapy.¹ Provide instructions regarding management of hypoglycemia, including recognition of symptoms, predisposing conditions, and treatment.¹

Risk of pregnancy in premenopausal anovulatory women.¹ Advise patients to utilize effective contraception during therapy.¹

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.¹

Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

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

Pioglitazone Hydrochloride
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	15 mg	Actos	Takeda
		30 mg	Actos	Takeda
		45 mg	Actos	Takeda

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Actoplus Met 15-500MG Tablets (TAKEDA PHARMACEUTICALS): 30/$135.99 or 90/$385.98

Actoplus Met 15-850MG Tablets (TAKEDA PHARMACEUTICALS): 30/$135.99 or 90/$385.98

Actoplus met XR 15-1000MG 24-hr Tablets (TAKEDA PHARMACEUTICALS): 30/$145.45 or 90/$415.57

Actoplus met XR 30-1000MG 24-hr Tablets (TAKEDA PHARMACEUTICALS): 30/$280.99 or 90/$800.00

Actos 15MG Tablets (TAKEDA PHARMACEUTICALS): 30/$179.98 or 90/$515.96

Actos 30MG Tablets (TAKEDA PHARMACEUTICALS): 30/$273.98 or 90/$799.99

Actos 45MG Tablets (TAKEDA PHARMACEUTICALS): 30/$289.99 or 90/$849.97

Duetact 30-2MG Tablets (TAKEDA PHARMACEUTICALS): 30/$274.29 or 90/$796.86

Duetact 30-4MG Tablets (TAKEDA PHARMACEUTICALS): 30/$255.58 or 90/$712.75

Disclaimer

References

1. Takeda Pharmaceuticals America. Actos (pioglitazone hydrochloride) tablets prescribing information. Lincolnshire, IL; 2004 July.

2. Kawamori R, Matsuhisa M, Kinoshita J et al. Pioglitazone enhances splanchnic glucose uptake as well as peripheral glucose uptake in non-insulin-dependent diabetes mellitus. AD-4833 Clamp-OGL Study Group. Diabetes Res Clin Pract 1998 Jul;41(1):35-43.

3. Berger J, Bailey P, Biswas C et al. Thiazolidinediones produce a conformational change in peroxisomal proliferator-activated receptor-γ: binding and activation correlate with antidiabetic actions in db/db mice. Endocrinology. 1996; 137:4189-95. [PubMed 8828476]

4. Parke-Davis. Rezulin (troglitazone) tablets prescribing information. Morris Plains, NJ; 1998 Jul.

5. Parke-Davis. Rezulin (troglitazone) tablets prescribing information. Morris Plains, NJ; 1999 Jun.

6. Sigmund WR II. Dear health professional letter regarding important prescribing information for Rezulin. Morris Plains: Parke-Davis. (undated)

7. Anon. New labeling and use changes for Rezulin. FDA Talk Paper. Rackville, MD: Food and Drug Administration; 1999 Jun 16.

8. Young PW, Buckle DR, Cantello BC et al. Identification of high-affinity binding sites for the insulin sensitizer rosiglitazone (BRL-49653) in rodent and human adipocytes using a radioiodinated ligand for peroxisonal proliferator-activated receptor gamma. J Pharmacol Exp Ther. 1998; 284:751-9. [PubMed 9454824]

9. Arakawa K, Inamasu M, Matsumoto M et al. Novel benzoxazol 2,4-thiazolidinediones as potent hypoglycemic agents. Chem Pharm Bull. 1997; 45:1984-93. [PubMed 9433768]

10. Matsuhisa M, Shiz Q, Wan C et al. The effect of pioglitazone on hepatic glucose uptake measured with indirect and direct methods in alloxan-induced diabetic dogs. Diabetes. 1997; 46:224-31. [PubMed 9000698]

11. Tanis SP, Parker TT, Colca JR et al. Synthesis and biological activity of metabolites of the antidiabetic, antihyperglycemic agent pioglitazone. J Med Chem. 1996; 39:5053-63. [PubMed 8978836]

12. Anon. Rosiglitazone for type 2 diabetes mellitus. Med Lett Drugs Ther. 1999; 41:71-3. [PubMed 10603986]

13. Takeda Pharmaceuticals North America, Indianapolis, IN: Personal communication.

14. Bristol-Myers-Squibb Company. Glucovance(glyburide and metformin hydrochloride) tablets prescribing information. Princeton, NJ; 2001 Mar.

15. May LD, Lefkowitch JH, Kram MT et al. Mixed hepatocellular-cholestatic liver injury after pioglitazone therapy. Ann Intern Med. 2002; 136:449-52. [IDIS 480334] [PubMed 11900497]

16. American Diabetes Association. Type 2 diabetes in children and adolescents. Pediatrics. 2000; 105:671-80. [IDIS 443594] [PubMed 10699131]

17. Novo Nordisk. Prandin(repaglinide) tablets prescribing information. Princeton, NJ; 2002 Oct.

18. Kipnes MS, Krosnick A, Rendell MS et al. Pioglitazone hydrochloride in combination with sulfonylurea therapy improves glycemic control in patients with type 2 diabetes mellitus: a randomized, placebo-controlled study. Am J Med. 2001; 111:10-7. [IDIS 467740] [PubMed 11448655]

19. Nesto RW, Bell D, Bonow RO et al for the American Heart Association and American Diabetes Association. AHA/ADA consensus statement: thiazolidinedione use, fluid retention, and congestive heart failure. Circulation. 2003; 108:2941-48. [IDIS 511519] [PubMed 14662691]

20. Kidd RS, Straughn AB, Meyer MC et al. Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. Pharmacogenetics. 1999; 9:71-80. [IDIS 424517] [PubMed 10208645]

21. Bottorf M, Hansen P. Long-term safety of hepatic hydroxymethyl glutaryl coenzyme A reductase inhibitors: the role of metabolism. Arch Intern Med. 2000; 160:2273-80. [IDIS 453535] [PubMed 10927723]

22. Nowak SN, Edwards DJ, Clarke A et al. Pioglitazone: effect on CYP3A4 activity. J Clin Pharmacol. 2002; 42:1299-1302. [IDIS 492542] [PubMed 12463723]

23. Yeates RA< Scharpf F, Laufen H et al. Screening for cytochrome P450 3a in man: studies with midazolam and nifedipine. J Pharm Pharmacol. 1996; 48:933-4. [IDIS 376297] [PubMed 8910856]

24. Ma JD, Nafziger AN, Kashuba ADM et al. Limited sampling strategy of S-warfarin concentrations, but not warfarin S/R rations accurately predicts S-warfarin AUC during basline and inhibition in CYP2C9 extensive metabolizers. J Clin Pharmacol. 2004; 44:570-6. [IDIS 516320] [PubMed 15145963]

25. Martinez C, Albet C, Agundez JAG et al. Comparative in vitor and in vivo inhibition of cytochrome P450 CYP1A2, CYP2Dg, and CYP3A4 by H₂-receptor antagonists. Clin Pharmacol Ther. 1999; 65:369-76. [PubMed 10223772]

26. Bachmann K, White D, Jauregui L et al. An evaluation of the dose-dependent inhibition of CYP1A2 by rofecoxib using theophylline as a CYP1A2 probe. J Clin Pharmacol. 2003; 43:1082-90. [IDIS 505406] [PubMed 14517190]

a. Hanefeld M. Pharmcokinetics and clinical efficacy of pioglitazone. Int J Clin Pract Suppl. 2001; 121:19-25. [PubMed 11594240]

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Actos Prescribing Information (FDA)

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