Anti-Diabetic Agents

Chapter © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Anti-Diabetic Agents 2 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Charles Ruchalski, NOTPharmD, FOR BCPS SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Introduction • Maintenance dose: © Jones &The Bartlett biguanide Learning, metformin isLLC the drug of choice as initial© Jones °&° 2000–2550Bartlett Learning,mg daily in divided LLC doses, or 2000 mg extended-release once daily NOT FORtherapy SALE for OR a newly DISTRIBUTION diagnosed patient with type 2 diabetesNOT FOR SALE OR DISTRIBUTION as an adjunct to diet and exercise. Metformin is contrain- • Renal dosage adjustment: dicated in certain patients to prevent lactic acidosis, a rare °° Not recommended in patients with renal dysfunc- but serious side effect. It is often used in combination with tion (see Contraindications below) other oral antidiabetic agents and/or insulin in patients who do not reach glycemic© Jones goals & Bartlett on those therapies.Learning, LLCAdverse Reactions: Most© JonesCommon & Bartlett Learning, LLC • Diarrhea, vomiting, dyspepsia, flatulence, metallic HbA1c reductions withNOT metformin FOR areSALE generally OR betweenDISTRIBUTION NOT FOR SALE OR DISTRIBUTION 1.5% and 2%. taste, weight loss Adverse Reactions: Rare/Severe/Important Mechanism of Action for the Drug Class • Lactic acidosis, megaloblastic anemia Improves glucose tolerance by lowering both basal and © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC postprandial plasma glucose. Decreases hepatic glucose Major Drug Interactions production,NOT FOR decreases SALE intestinal OR DISTRIBUTION absorption of glucose, NOT FOR SALE OR DISTRIBUTION Drugs Affecting Metformin and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. • Alcohol potentiates effect on lactate metabolism • Iodinated contrast media can lead to acute renal failure and metformin toxicity © Jones & Bartlett■■ Metformin Learning, LLC © Jones & Bartlett Learning, LLC Contraindications Brand Names NOT FOR SALE OR DISTRIBUTION NOT FOR• Renal SALE disease OR (males: DISTRIBUTION SrCr >1.5 mg/dl; females: SrCr Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet >1.4 mg/dl), heart failure requiring pharmacologic therapy, acute or chronic metabolic acidosis, active Generic Names liver disease Metformin, metformin extended-release © Jones & Bartlett Learning, LLCCounseling Points © Jones & Bartlett Learning, LLC Dosage Forms NOT FOR SALE OR DISTRIBUTION• Discontinue immediatelyNOT and promptlyFOR SALE notify ORhealth- DISTRIBUTION Tablets, extended-release tablets, oral solution care practitioner if unexplained myalgia, malaise, hyperventilation, or unusual somnolence because Usage these are symptoms of lactic acidosis • Type 2 diabetes mellitus*, PCOS, antipsychotic-induced ©weight Jones gain. & Bartlett Learning, LLC Key Points© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION • TemporarilyNOT FOR withhold SALE in patients OR DISTRIBUTION undergoing radio- Dosing logic procedures involving the parenteral administra- • Initial dose: tion of iodinated contrast media because it may result °° 500 mg twice daily with morning and evening in acute alteration of renal function. Do not restart meals, 850 mg once daily with a meal, or 500 mg for at least 48 hours or until renal function appears © Jones & Bartlettextended Learning, release once LLC daily with a meal © Jones adequate.& Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

81170_CH02_PASS02.indd 15 9/10/10 3:19:51 PM Drug Class: Di-Peptidyl Peptidase-4 Inhibitor © Jones & Bartlett Learning, LLC © Jones Introduction& Bartlett Learning, LLC Generic Name NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Sitagliptin is the first di-peptidyl peptidase-4 (DPP-4) Sitagliptin inhibitor available. It inhibits the breakdown of active GLP-1 to inactive GLP-1 through the inhibition of the Dosage Forms enzyme DPP-4. Active GLP-1 is released from the α cells Tablets of the pancreas in response© Jones to food & intake. Bartlett GLP-1 Learning, plays a LLC © Jones & Bartlett Learning, LLC role in regulating blood glucose by increasing the secre- Usage tion of insulin from theNOT pancreas FOR in SALE a glucose-dependent OR DISTRIBUTION • Type 2 diabetes mellitusNOT FOR SALE OR DISTRIBUTION manner. GLP-1 also helps regulate glucagon secretion and Dosing decreases hepatic glucose production. Sitagliptin is used • 100 mg once daily with or without food as monotherapy as an adjunct to diet and exercise or in • Renal dosage adjustment: combination with other oral antidiabetic agents in patients 50 mg once daily: CrCl >30 to <50 ml/minute who do© Jonesnot reach & glycemic Bartlett goals. Learning, Average HbA1c LLC reduc- °° © Jones & Bartlett Learning, LLC 25 mg once daily: CrCl <30 ml/minute tions NOTare between FOR 0.7%SALE and OR 1%. DISTRIBUTION °° NOT FOR SALE OR DISTRIBUTION Mechanism of Action for the Drug Class Adverse Reactions: Most Common • Nasopharyngitis, nausea, diarrhea, vomiting, hypo- Inhibition of DPP-4 enhances the activity of active GLP-1, glycemia, weight loss thus increasing glucose-dependent insulin secretion and © Jones &decreasing Bartlett levels Learning, of circulating LLC glucagon and hepatic© JonesAdverse & Bartlett Reactions: Learning, Rare/Severe/Important LLC glucose production. NOT FOR SALE OR DISTRIBUTION NOT FOR• Acute SALE pancreatitis, OR DISTRIBUTION rash (Stevens–Johnson syndrome) Members of the Drug Class Major Drug Interactions In this section: Sitagliptin Other: Saxagliptin Sitagliptin’s Effect on Other Drugs • Digoxin: Increased levels © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC ■■ Sitagliptin NOT FOR SALE OR DISTRIBUTIONCounseling Points NOT FOR SALE OR DISTRIBUTION Brand Name • Discontinue immediately and promptly notify health- Januvia care practitioner if unexplained persistent nausea and vomiting occur (signs of acute pancreatitis) © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Drug Class: Insulin © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORIntroduction SALE OR DISTRIBUTION NOT MechanismFOR SALE ofOR Action DISTRIBUTION for the Drug Class The hormone insulin is endogenously released from the β Insulin lowers blood glucose by stimulating peripheral cells of the pancreas. Patients with type 1 diabetes mellitus glucose uptake, especially in skeletal muscle and fat, and have an absolute deficiency of insulin, and patients with by inhibiting hepatic glucose production. type 2 diabetes mellitus may also have a decreased production of endogenous insulin.© Jones Insulin & is Bartlett required in Learning, all type LLCUsage for the Drug Class© Jones & Bartlett Learning, LLC 1 diabetic patients as aNOT lifelong FOR treatment. SALE Insulin OR DISTRIBUTIONis com- • Type 1 diabetes mellitus*,NOT type FOR 2 diabetes SALE mellitus*, OR DISTRIBUTION monly used in type 2 diabetic patients as either adjunct hyperkalemia, DKA*/diabetic coma therapy to oral antidiabetic agents or as monotherapy as the disease progresses. Various substitutions on the insulin Dosing for the Drug Class molecule and other modifications have led to multiple • Initial dose: types© of Jones insulins. & TheseBartlett are characterizedLearning, andLLC adminis- © Jones & Bartlett Learning, LLC °° 0.5 to 1 unit/kg per day Sub-Q (high interpatient teredNOT based FORon their SALE pharmacodynamic OR DISTRIBUTION and pharmacoki- variability)NOT FOR SALE OR DISTRIBUTION netic characteristics such as onset, peak, and duration of • Maintenance dose: action. Most significantly, they are classified as rapid-acting, °° Adjust doses to achieve premeal and bedtime short-acting, intermediate-acting, or long-acting types of blood glucose levels of 80–140 mg/dl insulin. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

16 Frequently Prescribed Medications: Drugs You Need to Know

81170_CH02_PASS02.indd 16 9/10/10 3:19:52 PM • Renal dosage adjustment: Drugs Affecting Insulin (Increased Hypoglycemic °° CrCl 10–50 ml/minute: Administer 75% of normal Effect) © Jones & Bartlettdose Learning, LLC © Jones• Alcohol& Bartlett Learning, LLC CrCl <10 ml/minute: Administer 25–50% of normal NOT FOR SALE°° OR DISTRIBUTION NOT FOR• Fluoxetine SALE OR DISTRIBUTION dose; monitor closely • Anabolic steroids Adverse Reactions for the Drug Class: Most • Lithium β• -Blockers of In s ul i n of Ty p e s Common • Sulfonamides • Hypoglycemia (anxiety,© Jones blurred & Bartlettvision, palpitations, Learning, LLC• Clonidine © Jones & Bartlett Learning, LLC shakiness, slurred speech, sweating), weight gain NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Adverse Reactions for the Drug Class: Rare/ Contraindications for the Drug Class Severe/Important • Use during severe hypoglycemia • Allergy or sensitivity to any ingredient of the product • Severe hypoglycemia (seizure/coma), edema, lipoat- rophy or lipohypertrophy at injection site © Jones & Bartlett Learning, LLC Counseling© Jones Points &for Bartlett the Drug Learning, Class LLC MajorNOT Drug FOR Interactions SALE OR for DISTRIBUTION the Drug Class • FollowNOT a prescribed FOR SALE diet and OR exercise DISTRIBUTION regularly Drugs Affecting Insulin (Decreased Hypoglycemic • Rotate injection sites to prevent lipodystrophy Effect) • Insulin requirements may change during times of illness, vomiting, fever, and emotional stress • Acetazolamide • Wear diabetic identification • Diuretics • Insulin stored at room temperature will be less painful © Jones & Bartlett• Oral contraceptives Learning, LLC © Jones & Bartlett Learning, LLC to inject compared to refrigerator-stored insulin NOT FOR SALE• Albuterol OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION • Mild episodes of hypoglycemia may be treated with • Epinephrine oral glucose or carbohydrates • Phenothiazines • Asparaginase • Estrogens Members of the Drug Class • Terbutaline © Jones & Bartlett Learning, LLCIn this section: Insulin glulisine,© Jones insulin & Bartlett lispro, insulin Learning, LLC • Corticosteroids NOT FOR SALE OR DISTRIBUTIONNPH, Insulin (R), insulin glargine,NOT insulinFOR SALEdetemir, ORinsulin DISTRIBUTION • HIV antivirals aspart; various mixtures are also available • Thyroid hormones • Diltiazem • Lithium © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Types of Insulin © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE■■ Insulin OR DISTRIBUTIONGlulisine NOT GenericFOR SALE Name OR DISTRIBUTION Brand Name Insulin lispro (rapid-acting insulin) Apidra Dosage Forms Generic Name Injection 100 units/ml (10-ml vial and 3-ml cartridge for Insulin glulisine (rapid-acting© Jones insulin) & Bartlett Learning, LLCpen use) © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Dosage Forms Dosing Injection 100 units/ml (10-ml vial and 3-ml cartridge for • Administer Sub-Q 15 minutes before or immediately pen use) after starting a meal © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Dosing ■■ Insulin NPH • NOTAdminister FOR Sub-Q SALE 15 ORminutes DISTRIBUTION before or immediately NOT FOR SALE OR DISTRIBUTION after starting a meal Brand Names Humulin N, Novolin N ■■ Insulin Lispro Brand Name Generic Name © Jones &Humalog Bartlett Learning, LLC © JonesInsulin & NPHBartlett (intermediate-acting Learning, LLC insulin) NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Chapter 2 anti-Diabetic Agents 17

81170_CH02_PASS02.indd 17 9/10/10 3:19:52 PM Dosage Forms Dosage Forms Injection, suspension, 100 units/ml (10-ml vial and 3-ml Injection 100 units/ml (10-ml vial and 3-ml cartridge for © Jones cartridge& Bartlett for penLearning, use) LLC © Jonespen use) & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FORDosing SALE OR DISTRIBUTION ■■ Insulin Glargine • NPH should only be mixed with regular insulin Brand Name • Draw regular insulin into the syringe first; then add Lantus the NPH insulin to the syringe © Jones & Bartlett Learning, LLCGeneric Name © Jones & Bartlett Learning, LLC ■■ Insulin RegularNOT FOR SALE OR DISTRIBUTIONInsulin glargine (long-actingNOT insulin) FOR SALE OR DISTRIBUTION Brand Names Dosage Forms Humulin R, Novolin R Injection 100 units/ml (10-ml vial and 3-ml cartridge for Generic Name pen use) Insulin© regularJones (short-acting & Bartlett insulin) Learning, LLC Dosing © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Dosage Forms • When changing to insulin glargine from once-daily Injection 100 units/ml (10-ml vial and 3-ml cartridge for NPH, the initial dose of insulin glargine should be pen use) the same. When changing to insulin glargine from twice-daily NPH, the initial dose of insulin glargine should be reduced by 20% and adjusted according to © Jones &Dosing Bartlett Learning, LLC © Jones & Bartlett Learning, LLC • Administer Sub-Q 30 minutes before a meal patient response. NOT FOR SALE• Caution: OR A DISTRIBUTION concentrated 20-ml vial containing 500 units/NOT FOR• Administer SALE OR once DISTRIBUTION daily ml is available • Starting dose in a type 2 diabetic patient is 10 units at bedtime and titrate according to patient response ■■ 70% NPH and 30% Regular Insulin Detemir Insulin Mixture ■■ © Jones & Bartlett Learning, LLCBrand Name © Jones & Bartlett Learning, LLC Brand Names NOT FOR SALE OR DISTRIBUTIONLevemir NOT FOR SALE OR DISTRIBUTION Humulin 70/30, Novolin 70/30 Generic Name Generic Name Insulin detemir (long-acting insulin) 70% NPH and 30% regular insulin mixture © Jones & Bartlett Learning, LLC Dosage Forms© Jones & Bartlett Learning, LLC Dosage Forms NOT FOR SALE OR DISTRIBUTION • InjectionNOT 100 FOR units/ml SALE (10-ml OR vial DISTRIBUTION and 3-ml cartridge Injection, suspension, 100 units/ml (10-ml vial and 3-ml for pen use) cartridge for pen use) Dosing ■■ 50% NPH and 50% Regular • Indicated for once-daily or twice-daily dosing Insulin Mixture © Jones & Bartlett Learning, LLC © Jones• Once& Bartlett daily is dosedLearning, Sub-Q withLLC the evening meal or at bedtime NOT FORBrand SALE Name OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Humulin 50/50 • Twice daily is dosed every 12 hours Generic Name ■■ Insulin Aspart 50% NPH and 50% regular insulin mixture Brand Name NovoLog Dosage Forms © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Injection, suspension, NOT100 units/ml FOR SALE(10-ml vialOR and DISTRIBUTION 3-ml Generic Name NOT FOR SALE OR DISTRIBUTION cartridge for pen use) Insulin aspart (rapid-acting insulin) ■■ 75% Intermediate-Acting Lispro Dosage Forms Suspension and 25% Rapidacting Injection 100 units/ml (10-ml vial and 3-ml cartridge for ©L isproJones Solution & Bartlett Learning, LLC pen use) © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Brand Name Dosing Humalog Mix 75/25 • Administer Sub-Q 15 minutes before or immediately Generic Name after starting a meal 75% intermediate-acting lispro suspension and 25% rapid- © Jones &acting Bartlett lispro solutionLearning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

18 Frequently Prescribed Medications: Drugs You Need to Know

81170_CH02_PASS02.indd 18 9/10/10 3:19:53 PM Table 2-1 © Jones &Comparison Bartlett Learning, of Insulin LLCProducts © Jones & Bartlett Learning, LLC NOT FOR SALEProduct OR DISTRIBUTION Onset, hoursNOT FORPeak, SALE hours OR DISTRIBUTIONDuration, hours Appearance

Rapid-Acting r e as Sulfonylu Cl ass : D r u g insulin Aspart (NovoLog) 0.25 1-2 3–5 Clear insulin Glulisine (Apidra) 0.25 1 3–4 Clear insulin Lispro (Humalog) 0.25 0.5–1.5 3–4 Clear Short-Acting © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC regular Insulin (HNOTumulin FOR R, Novolin SALE R) OR DISTRIBUTION 0.5–1 2–3 3–6NOT FOR SALEClear OR DISTRIBUTION Intermediate-Acting nph Insulin (Humulin N, Novolin N) 2–4 6–10 10–16 Cloudy Long-Acting insulin Detemir (Levemir) 4 N/A 12–24 Clear i©nsulin Jones Glargine & Bartlett(Lantus) Learning, LLC 4 N/A© Jones & Bartlett24 Learning,Clear LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ■■ 70% Intermediate-Acting Insulin Dosage Forms Aspart Suspension and 30% • Injection 100 units/ml (10-ml vial and 3-ml cartridge Rapid-Acting Aspart Solution for pen use) © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Brand Name ■■ Comparison of Insulin Products NOT FORNovoLog SALE MixOR 70/30DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Refer to Table 2-1. Generic Name 70% intermediate-acting insulin aspart suspension and 30% rapid-acting aspart solution © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning,Drug LLC Class: Sulfonylureas© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Introduction Adverse Reactions for the Drug Class: Rare/ The sulfonylureas are used as adjuncts to diet and exer- Severe/Important cise in patients with type 2 diabetes mellitus. Although • SIADH (most commonly with chlorpropamide); periodically used as monotherapy, sulfonylureas are more disulfiram-like reactions © Jones &commonly Bartlett used Learning, in combination LLC with other oral antidia-© Jones & Bartlett Learning, LLC NOT FORbetic SALE agents OR in DISTRIBUTIONpatients who do not reach glycemic goals,NOT MajorFOR SALE Drug InteractionsOR DISTRIBUTION for the Drug Class sometimes in the same formulation. General dosing Drugs Affecting Sulfonylureas guidelines are to start with a low dose and titrate upward • Anticoagulants, azole antifungals, gemfibrozil- according to patient response while monitoring for signs enhanced hypoglycemic effects and symptoms of hypoglycemia, which is a common • β-Blockers: Decreased hypoglycemic effects; also may adverse effect. Use caution© Jones in patients& Bartlett with Learning, renal or LLC mask signs and symptoms© Jones of hypoglycemia & Bartlett Learning, LLC hepatic impairment. HbA1cNOT FORreductions SALE are ORbetween DISTRIBUTION 1% NOT FOR SALE OR DISTRIBUTION and 2%. Sulfonylurea Effects on Other Drugs • Digoxin: Increased levels Mechanism of Action for the Drug Class Lowers blood glucose by stimulating insulin release from Contraindications for the Drug Class the β© cells Jones of the & pancreatic Bartlett islets. Learning, LLC • Diabetes© Jones complicated & Bartlett by ketoacidosis, Learning, withLLC or NOT FOR SALE OR DISTRIBUTION withoutNOT coma FOR SALE OR DISTRIBUTION Usage for the Drug Class • Type 1 diabetes mellitus • Type 2 diabetes mellitus* • Diabetes complicated by pregnancy Adverse Reactions for the Drug Class: Most Counseling Points for the Drug Class Common © Jones & Bartlett Learning, LLC © Jones• Monitor& Bartlett glucose Learning, as directed LLCand be aware of the signs • Hypoglycemia, GI distress, dizziness and symptoms of hypoglycemia NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Chapter 2 anti-Diabetic Agents 19

81170_CH02_PASS02.indd 19 9/10/10 3:19:53 PM Members of the Drug Class Dosing In this section: Glimepiride, glipizide, glyburide • Initial dose: © Jones & Others:Bartlett Acetohexamide, Learning, LLC chlorpropamide, tolazamide,© Jones °&° Glucotrol:Bartlett 2.5–5Learning, mg once LLC daily 30 minutes before NOT FORtolbutamide SALE OR DISTRIBUTION NOT FOR SALEbreakfast OR DISTRIBUTION °° Glucotrol XL: 5 mg extended release once daily ■■ Glimepiride with breakfast • Maintenance dose: Brand Name °° Glucotrol: 10–40 mg daily (>15 mg/day should be Amaryl © Jones & Bartlett Learning, LLC divided) © Jones & Bartlett Learning, LLC °° Glucotrol XL: 5–20 mg extended-release once daily Generic Name NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Glimepiride ■■ Glyburide Brand Names Dosage Forms DiaBeta, Micronase, Glynase PresTab Tablets© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Generic Name NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Dosing Glyburide • Initial dose: Dosage Forms °° 1–2 mg once daily at breakfast • Maintenance dose: Tablets © Jones & Bartlett°° 1–8 mg Learning, once daily LLC © JonesDosing & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ■■ Glipizide DiaBeta and Micronase • Initial dose: Brand Names °° 1.25–5 mg once daily with breakfast Glucotrol, Glucotrol XL • Maintenance dose: °° 1.25–20 mg once daily; may give as single or divided Generic Names © Jones & Bartlett Learning, LLC doses © Jones & Bartlett Learning, LLC Glipizide, glipizide extended-releaseNOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Glynase PresTab Dosage Forms • Initial dose: °° 1.5–3 mg once daily with breakfast Tablets, extended-release tablets • Maintenance dose: © Jones & Bartlett Learning, LLC °° 1.5–12© Jones mg once & daily; Bartlett may give Learning, as single or LLCdivided NOT FOR SALE OR DISTRIBUTION dosesNOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Drug Class: ThiazolidinedionesNOT FOR SALE OR DISTRIBUTION Introduction recommended to avoid use in patients with hepatic dys- The thiazolidinediones, pioglitazone and rosiglitazone, function. HbA1c reductions are between 1% and 1.5%. decrease insulin resistance© Jones by enhancing & Bartlett insulin-receptor Learning, LLCMechanism of Action for© Jonesthe Drug & BartlettClass Learning, LLC sensitivity. They are used as adjuncts to diet and exercise Increase insulin sensitivity by affecting the peroxisome in patients with type 2NOT diabetes FOR mellitus. SALE Although OR DISTRIBUTION peri- NOT FOR SALE OR DISTRIBUTION proliferator-activated receptor γ (PPAR γ). Acting as an odically used as monotherapy, thiazolidinediones are more agonist to these receptors, they decrease insulin resistance frequently used in combination with other oral antidia- in adipose tissue, skeletal muscle, and the liver. betic agents and/or insulin in patients who do not reach glycemic goals. Recent clinical data suggest that patients © Jones & Bartlett Learning, LLC Usage for© theJones Drug & ClassBartlett Learning, LLC taking thiazolidinediones may be at an increased risk of • Type 2 diabetes mellitus* myocardialNOT FOR infarction SALE and OR death, DISTRIBUTION and so they should be NOT FOR SALE OR DISTRIBUTION used with caution in patients with a history of previous Adverse Reactions for the Drug Class: Most cardiac disease. They are not recommended in patients Common with NYHA class III and IV heart failure. A structurally • Weight gain, edema, hypoglycemia (when used with similar thiazolidinedione, troglitazone, was removed from insulin or other oral antidiabetic drugs that may © Jones &the Bartlett market due Learning, to cases of LLC liver failure and death. It is© Jones cause& Bartlett hypoglycemia) Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

20 Frequently Prescribed Medications: Drugs You Need to Know

81170_CH02_PASS02.indd 20 9/10/10 3:19:54 PM Adverse Reactions for the Drug Class: Rare/ Generic Name Severe/Important Pioglitazone © Jones & • BartlettHepatic Learning, failure, heart LLC failure, anemia, ovulation in© Jones & Bartlett Learning, LLC Dosage Forms NOT FOR SALEanovulatory OR DISTRIBUTION premenopausal women, bone loss NOT FOR SALE OR DISTRIBUTION Tablets Major Drug Interactions for the Drug Class Drug Affecting Thiazolidinediones Dosing • Gemfibrozil: Increased levels • Initial dose: • Rifampin: Decreased© Jones levels & Bartlett Learning, LLC °° 15–30 mg once daily© without Jones regard & Bartlett to meals Learning, LLC • Maintenance dose: NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Thiazolidinedione Effects on Other Drugs °° 15–45 mg once daily • Oral contraceptives: Decreased efficacy ■■ Rosiglitazone Contraindications for the Drug Class • Patients with NYHA class III and IV heart failure Brand Name • ©Active Jones liver &disease Bartlett (alanine Learning, aminotransferase LLC [ALT] Avandia © Jones & Bartlett Learning, LLC NOT>2.5 times FOR the SALE upper limitOR ofDISTRIBUTION normal) NOT FOR SALE OR DISTRIBUTION • Concurrent insulin or nitrate use with rosiglitazone Generic Name Rosiglitazone Counseling Points for the Drug Class • Report signs and symptoms of liver dysfunction and/ Dosage Forms © Jones & Bartlettor shortness Learning, of breath LLCimmediately © JonesTablets & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Members of the Drug Class Dosing In this section: Pioglitazone, rosiglitazone • Initial dose: °° 4 mg once daily as a single or divided dose ■■ Pioglitazone • Maintenance dose: © Jones & Bartlett Learning, LLC °° 4–8 mg once daily © Jones & Bartlett Learning, LLC Brand Name Actos NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

1. Which oral antidiabetic drug works primarily in the 4. Which antidiabetic mediation has the potential to © Jones & Bartlettpancreas Learning, to increase theLLC secretion of insulin? © Jones &cause Bartlett the rare Learning, but serious LLC side effect of lactic NOT FOR SALEA. AvandiaOR DISTRIBUTION NOT FORacidosis? SALE OR DISTRIBUTION B. Glucophage A. Metformin C. Micronase B. Rosiglitazone D. Actos C. Glyburide D. Sitagliptin 2. What is the correct dose of sitagliptin in a patient with type 2 diabetes© Jones and moderate & Bartlett renal dysfunction Learning, LLC5. Which of the following© isJones a contraindication & Bartlett to Learning,the LLC (CrCl ~40 ml/minute)NOT FOR SALE OR DISTRIBUTIONuse of Glucophage? NOT FOR SALE OR DISTRIBUTION A. 100 mg once daily A. Osteoporosis B. 50 mg once daily B. Obesity C. 25 mg once daily C. Hyperkalemia D. Not recommended in patients with moderate D. Renal disease © Jonesrenal dysfunction & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 6. Which diabetes medication is contraindicated in 3. NOTWhich FOR of the SALE following OR insulins DISTRIBUTION should be adminis- patientsNOT with FOR NYHA SALE III or ORIV heart DISTRIBUTION failure? tered 15 minutes prior to a meal? A. Sitagliptin A. Insulin NPH B. Rosiglitazone B. Insulin glargine C. Glimepiride C. Insulin detemir D. Insulin lispro © Jones & BartlettD. Insulin Learning, aspart LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Chapter 2 anti-Diabetic Agents 21

81170_CH02_PASS02.indd 21 9/10/10 3:19:54 PM 7. Which class of drugs is indicated for both type 1 12. Which antidiabetic medication has the potential to and type 2 diabetes mellitus? cause acute pancreatitis? © Jones & BartlettA. Biguanide Learning, LLC © Jones &A. Bartlett Glucophage Learning, LLC B. Sulfonylurea NOT FORB. SALE Januvia OR DISTRIBUTION NOT FOR SALEC. InsulinOR DISTRIBUTION C. Levemir D. Thiazolidinedione D. Amaryl 8. What is the maximum daily dose of Actos? 13. Which medication is available by the brand names A. 8 mg once daily DiaBeta, Glynase, and Micronase? B. 12 mg daily © Jones & Bartlett Learning, LLC A. Glimepiride © Jones & Bartlett Learning, LLC C. 45 mg once dailyNOT FOR SALE OR DISTRIBUTIONB. Glipizide NOT FOR SALE OR DISTRIBUTION D. 2550 mg daily C. Glyburide D. Metformin 9. What is the average HbA1c reduction expected with sitagliptin? 14. Which of the following is used to treat diabetic ©A. Jones 0.7–1% & Bartlett Learning, LLC ketoacidosis?© Jones & Bartlett Learning, LLC B. 1–1.5% A. Metformin NOTC. 1–2% FOR SALE OR DISTRIBUTION B. InsulinNOT FOR SALE OR DISTRIBUTION D. 1.5–2% C. Glipizide D. Rosiglitazone 10. What is the only insulin suspension (cloudy) that is on the market? 15. Which medication works to increase insulin sensi- © Jones & BartlettA. Insulin Learning, glulisine LLC © Jones &tivity Bartlett by affecting Learning, the peroxisome LLC proliferator-acti- NOT FOR SALEB. InsulinOR DISTRIBUTION regular NOT FORvated SALE receptor OR DISTRIBUTIONγ (PPAR γ)? C. Insulin NPH A. Insulin lispro D. Insulin glargine B. Metformin C. Pioglitazone 11. Which oral antidiabetic medication should you tem- D. Sitagliptin porarily withhold© in Jones patients & undergoing Bartlett radiologicLearning, LLC © Jones & Bartlett Learning, LLC procedures involving the parenteral administration of iodinated contrastNOT media? FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION A. Pioglitazone B. Glyburide C. Sitagliptin D. Metformin © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

22 Frequently Prescribed Medications: Drugs You Need to Know

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