PRANDIMET TAB美国近期刚上市，本品是首个和唯一速效促分泌药瑞格列奈与胰岛素敏感药盐酸二甲双胍的固定剂量制剂。
美国FDA批准诺和诺德公司（Novo Nordisk）的瑞格列奈＋盐酸二甲双胍复方片（replaglinide＋metformin HCl，PrandiMet）上市，用于治疗2型糖尿病。本品剂量规格：瑞格列奈/盐酸二甲双胍 1
mg/500mg，2mg/500 mg。
本品是首个和唯一速效促分泌药瑞格列奈与胰岛素敏感药盐酸二甲双胍的固定剂量制剂。本品已被证明可降低不能采用美格列奈（meglitinide）和（或）二甲双胍很好地控制高血糖2型糖尿病成人患者的血糖。美国FDA批准本品是基于瑞格列奈/盐酸二甲双胍 1 mg/500 mg，2 mg/500 mg与相应剂量的
瑞格列奈和盐酸二甲双胍单一药物制剂联用呈相近的生物等效性数据。
临床研究证明；
本品可安全有效地降低血红蛋白A1c浓度。本品提供了两药在1片中方便服药的制剂。瑞格列奈刺激餐后胰腺分泌胰岛素，从而降低餐后2小时血糖（PPG），二甲双胍减少由肝产生的血糖量从而降低空腹血糖(FPG)，改善人体对胰岛素的自然反应。本品不可用于治疗1型糖尿病或糖尿病酮酸中毒。
由于二甲双胍积蓄可造成乳酸酸中毒，增加了脓毒病、脱水、过量摄入酒精、肝损伤、肾损伤和充血性心力衰竭的危险。症状表现为不适、肌痛、呼吸抑制、嗜睡增加和非特异性腹部不适。实验室检查出现pH值降低和血中乳酸盐增加。若疑有酸中毒应停用本品，并立即送该患者住院治疗。
PrandiMet(metformin hydrochloride/repaglinide)
Drug SummaryNovo Nordisk
Prandimet
(metformin hydrochloride/repaglinide)
BOXED WARNING
Lactic acidosis may occur due to metformin accumulation; risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute CHF. If acidosis is suspected, d/c and hospitalize patient immediately.
THERAPEUTIC CLASS
Biguanide/meglitinide
DEA CLASS
RX
ADULT DOSAGE & INDICATIONS
Type 2 Diabetes Mellitus
In patients who are already treated w/ a meglitinide and metformin or who have inadequate glycemic control on a meglitinide alone or metformin alone
May administer bid-tid
Inadequately Controlled w/ Metformin Monotherapy:
Initial: 1mg/500mg bid w/ meals
Titrate: Gradually escalate dose based on glycemic response
Inadequately Controlled w/ Meglitinide Monotherapy:
Initial: 500mg of metformin component bid
Titrate: Gradually escalate dose based on glycemic response
Currently Using Repaglinide and Metformin Concomitantly:
Initial: Initiate at a dose similar to, but not exceeding, doses of current repaglinide and metformin therapy
Titrate: Increase as necessary to achieve targeted glycemic control
Max: (10mg/2500mg)/day or (4mg/1000mg)/meal
ADMINISTRATION
Oral route
Take dose w/in 15 min ac; timing may vary from immediately preceding meal up to 30 min before meal.
If meal is skipped, skip dose for that meal.
HOW SUPPLIED
Tab: (Repaglinide/Metformin) 1mg/500mg, 2mg/500mg
CONTRAINDICATIONS
Renal impairment (eg, SrCr ≥1.5mg/dL [males], ≥1.4mg/dL [females], or abnormal CrCl), acute or chronic metabolic acidosis, including diabetic ketoacidosis, concomitant gemfibrozil, known hypersensitivity to PrandiMet or any inactive ingredients in the product.
WARNINGS/PRECAUTIONS
Do not initiate in patients ≥80 yrs of age unless renal function is normal. Temporarily d/c at the time of or prior to intravascular contrast studies with iodinated materials, and withhold for 48 hrs subsequent to the procedure and reinstitute only if renal function is normal. Avoid with hepatic impairment. May cause hypoglycemia; risk increased in elderly, debilitated, or malnourished patients, or with adrenal or pituitary insufficiency. May decrease vitamin B12 levels; measure hematologic parameters annually. Suspend temporarily for any surgical procedure (except minor procedures not associated with restricted food and fluid intake); restart when oral intake is resumed and renal function is normal. Temporary loss of glycemic control may occur when exposed to stress; may need to withhold therapy and temporarily administer insulin. D/C promptly in hypoxic states (eg, acute CHF, shock, acute myocardial infarction). eva luate promptly for evidence of ketoacidosis or lactic acidosis if laboratory abnormalities or clinical illness develops; d/c immediately if acidosis occurs.
ADVERSE REACTIONS
Lactic acidosis, GI system disorder, symptomatic hypoglycemia, headache, diarrhea, nausea, upper respiratory tract infection.
DRUG INTERACTIONS
See Contraindications. May increase Cmax of fenofibrate. Metformin: Alcohol potentiates effect of metformin on lactate metabolism. Caution with drugs that may affect renal function or result in significant hemodynamic change or may interfere with the disposition of metformin, such as cationic drugs eliminated by renal tubular secretion (eg, amiloride, digoxin, morphine). Cimetidine, furosemide, nifedipine, and ibuprofen may increase levels. Propranolol may decrease levels. May decrease levels of furosemide. Repaglinide: Not for use in combination with NPH-insulin. Risk of hypoglycemia increased with alcohol. Hypoglycemia may be difficult to recognize with β-adrenergic blocking drugs. CYP2C8 inhibitors, CYP3A4 inhibitors, or CYP2C8/3A4 inducers may alter pharmacokinetics and pharmacodynamics. Clarithromycin, deferasirox, fenofibrate, gemfibrozil, itraconazole, ketoconazole, simvastatin, trimethoprim, and OATP1B1 inhibitors (eg, cyclosporine) may increase levels. Levonorgestrel/ethinyl estradiol combination may decrease area under the curve and increase Cmax. Nifedipine and rifampin may decrease levels. May increase levels of ethinyl estradiol.
PREGNANCY AND LACTATION
Pregnancy: Category C.
Lactation: Not for use in nursing.
MECHANISM OF ACTION
Metformin: Biguanide; decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Repaglinide: Meglitinide; lowers blood glucose levels by stimulating the release of insulin from the pancreas.
PHARMACOKINETICS
Absorption: Administration of variable doses resulted in different pharmacokinetic parameters. Metformin: Absolute bioavailability (50-60%) (fasted). Repaglinide: Absolute bioavailability (56%); Tmax=1 hr. Distribution: Metformin: Vd=654L. Repaglinide: (IV) Vd=31L; plasma protein binding (>98%). Metabolism: Repaglinide: Complete. CYP2C8, 3A4; oxidation, and direct conjugation with glucuronic acid; oxidized dicarboxylic acid (M2), aromatic amine (M1), acyl glucuronide (M7) (major metabolites). Elimination: Metformin: Urine (90%); T1/2=6.2 hrs (plasma), 17.6 hrs (blood). Repaglinide: Feces (90%, <2% unchanged), urine (8%, 0.1% unchanged); T1/2=1 hr.
ASSESSMENT
Assess for metabolic acidosis, diabetic ketoacidosis, type of DM, renal/hepatic function, risk factors for lactic acidosis, susceptibility to hypoglycemia, drug hypersensitivity, pregnancy/nursing status, and possible drug interactions. Assess if patient is planning to undergo any surgical procedure or is under any form of stress. Obtain baseline FPG and HbA1c.
MONITORING
Monitor for lactic acidosis, clinical illness, hypoxic states, and other adverse reactions. Monitor renal function, especially in elderly patients, at least annually. Monitor vitamin B12 levels in patients predisposed to develop subnormal vitamin B12 levels. Monitor FPG, HbA1c, and hematologic parameters periodically.
PATIENT COUNSELING
Inform of potential risks/advantages of therapy, alternative modes of therapy, the importance of adherence to dietary instructions, regular exercise program, and regular testing of blood glucose, HbA1c, renal function, and hematologic parameters. Inform about risks of hypoglycemia and lactic acidosis, their symptoms and treatment, and predisposing conditions. Instruct to seek medical advice during periods of stress as medication needs may change. Advise to d/c drug immediately and notify physician if unexplained hyperventilation, myalgia, malaise, unusual somnolence, or other nonspecific symptoms occur. Instruct to take drug with meals; if a meal is skipped, instruct to skip the dose for that meal. Counsel against excessive alcohol intake.
STORAGE
≤25°C (77°F). Protect from moisture. |
