Nateglinide; Uses, Dosage, Side Effects, Interactions Nateglinide is a phenylalanine derivative of the meglitinide class of agents with hypoglycemic activity. Nateglinide, compared to repaglinide, binds with a higher affinity to the SUR1 subunit and with a faster onset of action and a shorter duration of action. This agent is metabolized by the cytochrome P450 isoenzyme CYP2C9, and, to a lesser extent, by CYP3A4. The parent drug and metabolites are mainly excreted in the urine and its half-life is about 1.5 hours. Nateglinide is an oral hypoglycemic agent and amino acid derivative that stimulates insulin secretion from the pancreas and is used in the therapy of type 2 diabetes. Nateglinide has been linked to rare instances of clinically apparent acute liver injury. Nateglinide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the meglitinide class of short-acting insulin secretagogues, which act by binding to β cells of the pancreas to stimulate insulin release. Nateglinide is an amino acid derivative that induces an early insulin response to meals decreasing postprandial blood glucose levels. It should only be taken with meals and meal-time doses should be skipped with any skipped meal. Mechanism of Action of Nateglinide Nateglinide activity is dependent on the presence of functioning β cells and glucose. In contrast to sulfonylurea insulin secretatogogues, nateglinide has no effect on insulin release in the absence of glucose. Rather, it potentiates the effect of extracellular glucose on ATP-sensitive potassium channel and has little effect on insulin levels between meals and overnight. As such, nateglinide is more effective at reducing postprandial blood glucose levels than fasting blood glucose levels and requires a longer duration of therapy (approximately one month) before decreases in fasting blood glucose are observed. The insulinotropic effects of nateglinide are highest at intermediate glucose levels (3 to 10 mmol/L) and it does not increase insulin release already stimulated by high glucose concentrations (greater than 15 mmol/L). Nateglinide appears to be selective for pancreatic β cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue. You Might Also Read Apalutamide - Uses, Dosage, Side Effects, InteractionsIndications of Nateglinide Type 2 Diabetes Mellitus Treatment of non-insulin dependent-diabetes mellitus in conjunction with diet and exercise. For the treatment of non-insulin dependent-diabetes mellitus in conjunction with diet and exercise. Combination therapy with metformin in type 2 diabetic patients inadequately controlled despite a maximally tolerated dose of metformin alone. Combination therapy with metformin in type 2 diabetic patients inadequately controlled despite a maximally tolerated dose of metformin alone Contra-Indications of Nateglinide Low blood sugar Pituitary hormone deficiency Decreased function of the adrenal gland Inadequate vitamin B12 Excess body acid Extreme loss of body water The habit of drinking too much alcohol Alcohol intoxication Heart attack Suddenly serious symptoms of heart failure Liver problems Recent operation Fever Shock Severe vomiting Severe diarrhea Serious lack of oxygen in the blood Weakened patient Injury Sepsis syndrome X-Ray Study with intravenous iodine contrast agent Kidney disease with a likely reduction in kidney function Acute inflammation of the pancreas Chronic inflammation of the pancreas Moderate to Severe kidney impairment. Dosage of Nateglinide Strengths: 60 mg; 120 mg Diabetes Type 2 Initial dose: 120 mg orally 3 times a day before meals Maintenance dose: 60 to 120 mg orally 3 times a day before meals Side Effects of Nateglinide Most common Abdominal or stomach discomfort increased urination. low blood pressure, difficult, burning, or painful urination increased potassium blood levels (hyperkalemia), low blood sugar (hypoglycemia), and diarrhea Cough runny or stuffy nose sore throat 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 a cough or hoarseness decreased appetite diarrhea fast or shallow breathing fever or chills the general feeling of discomfort lower back or side pain muscle pain or cramping painful or difficult urination You Might Also Read Procyclidine; Uses, Dosage, Side Effects, Drug InteractionsLess common 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 a runny nose sneezing stuffy nose swollen joints Drug Interactions of Nateglinide Canagliflozin may interact with following drugs, supplements & may decrease the efficacy of the drug androgens (e.g., methyltestosterone, nandrolone, testosterone) angiotensin-converting enzyme inhibitors (ACEIs; captopril, ramipril) angiotensin receptor blockers (ARBs; e.g., candesartan, irbesartan, losartan) antipsychotic medications (e.g., chlorpromazine, haloperidol, olanzapine, birth control pills bupropion atorvastatin atypical antipsychotics (e.g., aripiprazole, clozapine, olanzapine; quetiapine, risperidone) “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole) barbiturates (e.g., pentobarbital, phenobarbital) cyclosporine lanreotide levodopa 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 sulfonamide antibiotics (“sulfas”; e.g., sulfisoxazole, sulfamethoxazole) Pregnancy & Lactation of Nateglinide FDA Pregnancy Category C Pregnancy This medication should not be used during pregnancy. If you think you may be pregnant or if you become pregnant while taking this medication, contact your doctor immediately. Lactation It is not known if nateglinide passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. References DrugBank http://www.drugbank.ca/drugs/DB00731 http://www.drugbank.ca/drugs/DB00731#targets http://www.drugbank.ca/drugs/DB00731#enzymes http://www.drugbank.ca/drugs/DB00731#transporters http://www.drugbank.ca/drugs/DB00731#carriersEPA DSStox https://comptox.epa.gov/dashboard/dsstoxdb/results?search=DTXSID9040687 https://clinicaltrials.gov/ https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=NATEGLINID .fda.gov/spa/data/02e04883-ce27-4ac3-9be1-3ad80db4d496/02e04883-ce27-4ac3-9be1-3ad80db4d496.xml https://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm162549.htm https://online.epocrates.com/u/1032335/nateglinide/Contraindications+Cautions LiverTox https://livertox.nlm.nih.gov/Nateglinide.htm NCIT https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C61858 FDA/SPL Indexing Data https://www.fda.gov/ForIndustry/DataStandards/SubstanceRegistrationSystem-UniqueIngredientIdentifierUNII/ EU Community Register of Medicinal Products https://ec.europa.eu/health/documents/community-register/html/h174.htm https://ec.europa.eu/health/documents/community-register/html/h175.htm https://www.drugs.com/cdi/nateglinide.html https://www.drugs.com/starlix.html WHO ATC https://www.whocc.no/atc/ https://www.whocc.no/atc_ddd_index/ European Chemicals Agency (ECHA) https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/174974 European Chemicals Agency – ECHA https://www.echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database/-/discli/details/174974 FDA Orange Book https://www.fda.gov/Drugs/InformationOnDrugs/ucm129662.htm MassBank of North America (MoNA) http://mona.fiehnlab.ucdavis.edu/spectra/browse?inchikey=OELFLUMRDSZNSF-OFLPRAFFSA-N PubMed Health ww.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011357/ Show MoreYou Might Also Read Anti viral,Anti fungal, Anti helmintics drug.The latest classification