Rosiglitazone + Metformin


Concise Prescribing Info
Indications/Uses
Type 2 DM.
Dosage/Direction for Use
Adult : PO Patients inadequately controlled on diet and exercise: Initial: 2 mg/500 mg 1-2 times/day. Patients inadequately controlled on metformin monotherapy: Initial: Rosiglitazone 4 mg/day plus the current dose of metformin. Patients inadequately controlled on rosiglitazone monotherapy: Initial: Metformin 1,000 mg/day plus the current dose of rosiglitazone. Max: Rosiglitazone 8 mg and metformin 2,000 mg/day.
Dosage Details
Oral
Type 2 diabetes mellitus
Adult: Each tab contains rosiglitazone (mg)/metformin (mg): 2/500, 4/500, 2/1,000, 4/1,000: Patients inadequately controlled on diet and exercise: Initially, 2 mg/500 mg 1-2 times daily. Patients w/ HbA1c >11% or fasting plasma glucose (FPG) >270 mg/dL: 2 mg/500 mg bid. Adjust daily dose in increments of 2 mg/500 mg in divided doses if not adequately controlled after 4 wk. Patients inadequately controlled on metformin monotherapy: Initially, rosiglitazone 4 mg daily plus the current dose of metformin. Patients inadequately controlled on rosiglitazone monotherapy: Initially, metformin 1,000 mg daily plus the current dose of rosiglitazone. Adjust daily dose in increments of rosiglitazone 4 mg if not adequately controlled after 8-12 wk and/or metformin 500 mg if not adequately controlled after 1-2 wk. Max: Rosiglitazone 8 mg and metformin 2,000 mg daily.
Renal Impairment
CrCl (mL/min) Dosage
<60 Contraindicated.
Hepatic Impairment
Severe: Contraindicated.
Administration
Should be taken with food.
Contraindications
Patient w/ established New York Heart Association (NHYA) class I to IV heart failure; acute or chronic metabolic acidosis, including diabetic ketoacidosis; type 1 DM. Conditions that may increase the risk of lactic acidosis (e.g. CV disease, acute coronary syndrome, conditions associated w/ tissue hypoxia, pulmonary embolism, pancreatitis). Excessive alcohol use. Renal (CrCl <60 mL/min) or severe hepatic impairment. Concomitant use w/ insulin and admin of IV iodinated contrast materials.
Special Precautions
Patient w/ oedema, fracture risk factors, anaemia or depressed leukocyte counts. Mild to moderate hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Oedema, wt gain, anaemia, bone fracture, nausea and vomiting, diarrhoea, headache, dyspepsia, macular oedema, decreased Hb and haematocrit, decreased vit B12 serum levels, ovulation (in premenopausal anovulatory women).
Potentially Fatal: Lactic acidosis, CHF, MI.
MonitoringParameters
Monitor for signs/symptoms of oedema or heart failure; renal function, BP, liver enzymes, fasting blood glucose and HbA1c. Regular ophth examination.
Overdosage
Symptoms: Lactic acidosis may occur from metformin overdose. Management: Supportive treatment.
Drug Interactions
Increased plasma levels w/ CYP2C8 inhibitors (e.g. gemfibrozil). Decreased plasma levels w/ CYP2C8 inducers (e.g. rifampicin).
Potentially Fatal: Increased risk of CHF w/ insulin. Alteration of renal function w/ iodinated contrast materials.
Food Interaction
Alcohol may increase the risk of lactic acidosis, avoid use.
Action
Description: Rosiglitazone lowers blood glucose by improving target cell response to insulin in adipose tissue, skeletal muscle and liver, w/o increasing pancreatic insulin secretion. Metformin improves glucose tolerance in patients w/ type 2 DM, lowering both basal and post-prandial blood glucose. It decreases hepatic gluconeogenesis, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilisation.
Pharmacokinetics:
Absorption: Rosiglitazone: Well absorbed from the GI tract. Bioavailability: 99%. Time to peak plasma concentration: Approx 1 hr. Metformin: Slowly and incompletely absorbed from the GI tract. Bioavailability: Approx 50-60%.
Distribution: Rosiglitazone: Crosses the placenta and found in foetal tissue. Plasma protein binding: Approx 99.8%. Metformin: Crosses the placenta and enters breast milk (small amounts).
Metabolism: Rosiglitazone: Extensively metabolised, mainly by CYP2C8 isoenzyme. Metformin: Not metabolised in the liver.
Excretion: Rosiglitazone: Via urine and faeces. Half-life: 3-4 hr. Metformin: Via urine (as unchanged drug). Elimination half-life: Approx 2-6 hr.
Chemical Structure

Chemical Structure Image
Rosiglitazone

Source: National Center for Biotechnology Information. PubChem Database. Rosiglitazone, CID=77999, https://pubchem.ncbi.nlm.nih.gov/compound/Rosiglitazone (accessed on Jan. 23, 2020)


Chemical Structure Image
Metformin

Source: National Center for Biotechnology Information. PubChem Database. Metformin, CID=4091, https://pubchem.ncbi.nlm.nih.gov/compound/Metformin (accessed on Jan. 20, 2020)

Storage
Store at 25°C. Protect from light.
MIMS Class
ATC Classification
A10BD03 - metformin and rosiglitazone ; Belongs to the class of combinations of oral blood glucose lowering drugs. Used in the treatment of diabetes.
References
Anon. Rosiglitazone and Metformin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 19/10/2015.

Avandamet Tablet, Film Coated (GlaxoSmithKline LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 19/10/2015.

Buckingham R (ed). Metformin Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/10/2015.

Buckingham R (ed). Rosiglitazone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/10/2015.

Disclaimer: This information is independently developed by MIMS based on Rosiglitazone + Metformin from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in