Rosiglitazone; Uses, Contra indications, Dosage, Side Effects, Drug Interaction

Rosiglitazone is an anti-diabetic drug in the thiazolidinedione class of drugs. It is marketed by the pharmaceutical company GlaxoSmithKline as a stand-alone drug (Avandia) and in combination with metformin (Avandamet) or with glimepiride (Avandaryl). Like other thiazolidinediones, the mechanism of action of rosiglitazone is by activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPARγ.

Rosiglitazone is an anti-diabetic drug from the thiazolidinedione class. Like other thiazolidinediones, its mechanism of action is by activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPAR-gamma. Rosiglitazone is a pure ligand of PPAR-gamma, and has no PPAR-alpha-binding action. Apart from its effect on insulin resistance, it appears to have an anti-inflammatory effect: nuclear factor kappa-B (NF& #954; B) levels fall and inhibitor levels increase in patients on rosiglitazone (Mohanty et al). It increases glyceroneogenesis and reduces the release of free fatty acids from adipocytes; Rosiglitazone is an anti-diabetic drug from the thiazolidinedione class. It is being marketed as Avandia by the pharmaceutical company GlaxoSmithKline, both as a standalone preparation and in combination with metformin (Avandamet). Another combination drug approved by the FDA is Avandaryl (with glimepiride); Like other thiazolidinediones, its mechanism of action is by activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPAR-gamma. Rosiglitazone is a pure ligand of PPAR-gamma, and has no PPAR-alpha binding action. Apart from its effect on insulin resistance, it appears to have an anti-inflammatory effect: nuclear factor kappa-B (NFkB) levels fall and inhibitor (IkB) levels increase in patients on rosiglitazone (Mohanty et al). It increases glyceroneogenesis and reduces the release of free fatty acids from adipocytes.

Mechanism of Action of Rosiglitazone

Rosiglitazone acts as a highly selective and potent agonist at peroxisome proliferator activated receptors (PPAR) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPAR-gamma receptors regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In this way, rosiglitazone enhances tissue sensitivity to insulin.

Rosiglitazone is a thiazolidinedione antidiabetic agent that is effective only in the presence of insulin. Its primary action is to decrease insulin resistance at peripheral sites and in the liver. This results in increased insulin-dependent glucose disposal and decreased hepatic glucose output. These effects are accomplished by selective binding at the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) which is found in adipose tissue, skeletal muscle, and the liver. Activation of these receptors modulates transcription of several insulin responsive genes that control glucose and lipid metabolism.

Rosiglitazone acts principally by increasing insulin sensitivity in target tissues, as well as decreasing hepatic gluconeogenesis. Rosiglitazoneis a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist that increases transcription of insulin-responsive genes and increases insulin sensitivity. Rosiglitazone, like other thiazolidinediones, ameliorates insulin resistance associated with type 2 diabetes mellitus without stimulating insulin release from pancreatic beta cells, thus avoiding the risk of hypoglycemia. Because rosiglitazone does not lower glucose concentrations below euglycemia, the drug is appropriately referred to as an antidiabetic agent rather than a hypoglycemic agent. Some evidence suggests that the glucoregulatory effects of thiazolidinediones are mediated in part via reduced systemic and tissue lipid availability. Circulating concentrations of insulin and C-peptide are reduced during rosiglitazone therapy.

Indications of Rosiglitazone

Type 2 Diabetes Mellitus
Nonalcoholic Fatty Liver Disease
To improve glycemic control in adult patients with type 2 diabetes mellitus as an adjunct to diet and exercise.

You Might Also Read Angina Pectoris; Causes, Symptoms, Diagnosis, Treatment

Therapeutic Uses

Type 2 Diabetes Mellitus
Antidiabetic agent
Rosiglitazone is indicated as monotherapy and as adjunctive therapy to diet and exercise in the management of patients with type 2 diabetes mellitus (previously referred to as non-insulin-dependent diabetes mellitus). Rosiglitazone is also indicated for use in combination with a sulfonylurea, metformin, or insulin when diet, exercise, and either rosiglitazone alone, a sulfonylurea alone, metforminalone or insulin alone do not result in adequate glycemic control in patients with type 2 diabetes. Rosiglitazone is also indicated for use in combination with a sulfonylurea plus metformin when diet, exercise, and both agents do not result in adequate glycemic control.
1-Methyl-4-phenylpyridinium ion (MPP(+)), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin because it elicits a severe Parkinson’s disease-like syndrome with elevation of intracellular reactive oxygen species (ROS) level and apoptotic death. Rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, has been known to show various non-hypoglycemic effects, including anti-inflammatory, anti-atherogenic, and anti-apoptotic.
In the present study, /the authors/ investigated the protective effects of rosiglitazone on MPP(+) induced cytotoxicity in human neuroblastoma SH-SY5Y cells, as well as underlying mechanism. /Their/ results suggested that the protective effects of rosiglitazone on MPP(+) induced apoptosis may be ascribed to its anti-oxidative properties, anti-apoptotic activity via inducing expression of SOD and catalase and regulating the expression of Bcl-2 and Bax. These data indicated that rosiglitazone might provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative disease such as Parkinson’s disease.

Contra Indication of Rosiglitazone

Low blood sugar
Severe Heart Failure
Liver problems
Decreased Calcification or Density of Bone
Visible Water Retention
Weight gain
Abnormal liver function tests
Broken Bone
Macular Edema

Dosages of Rosiglitazone

Strengths:2 mg; 4 mg; 8 mg

You Might Also Read Anticholinergic Drugs; Types, Indications/Uses, Side Effects, Drug Interactions

Diabetes Type 2

Initial dose: 4 mg orally once a day
Maintenance dose: If inadequate response is not achieved after 8 to 12 weeks, increase to 8 mg once a day
Maximum dose: 8 mg per day

Side Effects of Rosiglitazone

Most common

Chest pain
decreased urine output
dilated neck veins
extreme fatigue
abdominal pain,
physical weakness (asthenia)
diarrhea
gas (flatulence)
symptoms of weakness, muscle pain (myalgia)
upper respiratory tract infection
low blood sugar (hypoglycemia)
abdominal pain (GI complaints), lactic acidosis (rare)
low blood levels of vitamin B-12
nausea,vomiting
chest discomfort
chills, dizziness
bloating/abdominal distention
constipation
heartburn

More common

Abdominal or stomach discomfort
cough or hoarseness
decreased appetite
diarrhea
fast or shallow breathing
fever or chills
general feeling of discomfort
lower back or side pain
muscle pain or cramping
painful or difficult urination

Less common

Anxiety
confusion
dark urine
depression
Abnormal stools
bad, unusual, or unpleasant (after) taste
change in taste
difficulty with moving
discoloration of the fingernails or toenails
flu-like symptoms
joint pain
rash
runny nose
sneezing
stuffy nose
swollen joints

Drug Interactions of Rosiglitazone

Rosiglitazone may interact with following drugs ,suppliments & may decrease the efficacy of drug

angiotensin converting enzyme inhibitors (ACEIs; captopril, enarapril,ramipril)
alcohol
antipsychotic medications (e.g., chlorpromazine, haloperidol, olanzapine,
atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine, risperidone)
“azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
barbiturates (e.g., pentobarbital, phenobarbital)
cyclosporine
diabetes medications (e.g., chlorpropamide, glipizide, glyburide, insulin, metformin,nateglinide, pioglitazone)
diuretics (water pills; e.g., furosemide, hydrochlorothiazide, triamterene)
phenytoin
pregabalin
irbesartan
lapatinib
losartan
mifepristone
corticosteroids (e.g., dexamethasone, prednisone)
diabetic drugs (e.g., glyburide, insulin, repaglinide, sitagliptin)
diuretics (e.g., furosemide, hydrochlorothiazide)
HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir, saquinavir)
phenytoin
quinolone antibiotics (e.g., levofloxacin, moxifloxacin)
selective serotonin reuptake inhibitors (SSRIs; citalopram, fluoxetine, sertraline paroxetine,
trimethoprim
vancomycin
verapamil
warfarin

You Might Also Read Neratinib Maleate; Dosage, Side Effect, Drug Interactions

Pregnancy & Lactation of Rosiglitazone

FDA Pregnancy Category : C

Pregnancy

This medication should not be used during pregnancy. Usually insulin is used to control high blood sugars during pregnancy. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding

It is not known if rosiglitazone passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.