Nateglinide - Indications, Contraindications, Warnings, and Precautions

Overview

Nateglinide is a widely recommended medicine that tackles uplifted sugar levels in the blood. It comes under the category of anti-diabetic drugs, which falls under the meglitinides class. The drug regulatory body of the United States - the Food and Drug Administration - endorsed the usage of Nateglinide for patients suffering from diabetes mellitus. It is prescribed along with dietary and lifestyle modifications. Diabetes can impair the functions of diverse vital organs in the body, ranging from the eye to the heart, and hence, Nateglinide checks the progression of organ impairment by directly acting on the sugar levels. It is marketed in pill forms. It is often instructed to be taken together with other anti-diabetic drugs as a part of combination therapy.

How Does Nateglinide Work?

Nateglinide brings down the blood sugar level by enhancing the production of the hormone that regulates the sugar level. Insulin is the hormone that is responsible for keeping the sugar level within the normal range. Insufficiency in the hormone reflects an imbalance in the blood sugar level. Nateglinide counterbalances the insufficiency by enhancing insulin release by triggering the insulin-producing cells. In this way, it brings back the sugar level to the normal range.

Uses

Nateglinide is routinely prescribed for dealing with boosted sugar levels. It thereby lowers the likelihood of developing other diabetes-associated diseases.

Available Doses and Dosage Forms

• Dosage Forms: Nateglinide is available in pill form, which comes in blister packaging. It is advised to take the pill orally without breaking the pill.

• Doses: It is marketed in three distinct doses: 60 milligrams (mg), 120 mg, and 180 mg. The patient should take the dose as instructed by the doctor.

• Dosage Schedule: It is advised to take the pills thrice a day. The pill should be taken half an hour before food intake.

Warnings

• Hypoglycemia: Nateglinide carries the potential risk of hypoglycemia, where the blood sugar level abruptly falls behind the lower limit. The patient instantly elicits symptoms like shivering, unexplainable sweating, disorientation, blurry vision, weakness, loss of consciousness, and many more. A significant drop in the blood sugar level poses challenges in driving and reading, and the patient encounters trouble paying attention. Hypoglycemia is a grave condition that is capable of endangering one’s life if not treated at the right time. So, if the patient is on Nateglinide therapy, ensure that the pill is taken only after food. Any symptoms of collapsing sugar level entail immediate medical assistance.

• Diabetic Ketoacidosis: If the patient elicits signs and symptoms of diabetic ketoacidosis, it is strictly warned not to take Nateglinide pills. It is a potential complication that arises from boosted blood sugar levels, in which the patient experiences typical breaths that smell fruity, rapidly beating heart, blushing of the face, aching belly, fading of vision, weakness, and irritability. Once diabetic ketoacidosis is precipitated, the Nateglinide pill should be withdrawn, and it mandates immediate medical attention.

• Concurrent Medication: Certain medicines have an influence over the glucose level in the blood. Simultaneous intake of other drugs while on Nateglinide often demands alteration in the dosage of Nateglinide.

• Lactose Intolerance: Individuals with intolerance towards lactose should inform the concerned doctor prior to taking Nateglinide, as it contains lactose.

For Patients:

What Is Diabetes Mellitus?

Diabetes mellitus is a familiar disease condition in which the concentration of glucose in the blood elevates significantly. The optimum glucose concentration is reported to be in the range of 70 to 100 milligrams per deciliter (mg/dL) under fasting conditions. However, in diabetes mellitus, the body cannot maintain the glucose level in its optimum range. The inability of the body to maintain the optimum concentration precipitates in the form of diabetes mellitus. This elevation in the glucose concentration can be either the result of a deficiency or impaired functioning of the hormone responsible for keeping a balance on the glucose concentration. Insulin is the hormone that keeps track of the blood glucose level. Interruption in the production of insulin reflects the inadequacy of hormones to keep the glucose level under control.

At times, the glucose equilibrium imbalance may arise if the released insulin does not function properly. Likewise, the glucose equilibrium will also get disturbed if the hormone-producing cells are hampered. Considering the underlying factors, diabetes mellitus is categorized into two distinct classes - type 1 diabetes mellitus and type 2 diabetes mellitus. Type 2 diabetes mellitus is the frequently encountered form where the trouble is with insulin production and function, while in type 1 diabetes mellitus, insulin-producing cells are affected. Diabetes is a long-standing condition that, once detected, lingers over a lifetime, and increases the likelihood of other associated diseases, and eventually ends up affecting multiple organs.

When and Why Is Nateglinide Prescribed?

Nateglinide specifically works to bring down the raised sugar level in the blood. When the body’s ability to generate insulin hormones gets impaired, or when the insulin fails to act the way it is intended to, both conditions end up in diabetes mellitus. Long-term exposure to elevated sugar levels remarkably impacts the functions of various cells and organs. In such cases, anti-diabetics like Nateglinide are prescribed to restore the glucose equilibrium in the body. If diabetes mellitus is not tackled at the right time, it can bring about various complications and hamper diverse organ systems in the body.

Things to Inform the Doctor Before Taking Nateglinide:

Before initiating Nateglinide therapy, the patient should provide all the required medical information to the concerned physician. Some of the relevant information that should never be missed includes the following:

• Prior allergic responses encountered upon intake of Nateglinide or other medicine containing any of the constituents in Nateglinide should be discussed with the doctor to prevent exaggerated allergic reactions upon subsequent intake.

• The patient should share the entire details of medications that are currently undertaken, encompassing prescription medicines, supplementary medicines, non-prescription medicines, and even herbal medicines. Certain medications influence the effect of Nateglinide, while others may alter the glucose level. Therefore, prior knowledge of possible drug-to-drug associations aids in tracking undue influence from other drugs.

• If the person is suffering from other systemic diseases like liver disease, pituitary disease, adrenal insufficiency (trouble in adrenal hormone production), or has a history of certain diseases, the doctor should be made aware of all the conditions.

• If the patient is pregnant and planning to conceive, keep the physician updated regarding the matter. Pregnant patients are advised to take Nateglinide only under the doctor's confirmation.

• The safety of Nateglinide in breastfeeding women is still under discussion; hence, it should be discussed with the doctor before starting Nateglinide.

Things to Consider While Taking Nateglinide:

• Nateglinide is capable of inducing hypoglycemia; hence, patients should keep an eye on the signs of hypoglycemia like shivering, fading of vision, and many more.

• Any form of unwanted reaction upon intake of Nateglinide should be immediately reported to the concerned doctor.

• If the person conceives while on Nateglinide, it should be discussed with the doctor to look for any potential risk associated with Nateglinide.

What Are the Instructions to Be Followed While on Nateglinide?

• Patients are instructed to take the exact dose as advised by the doctor. Altering the dose without medical consultation can precipitate various health complications.

• It is advised to take Nateglinide half an hour before food to ensure prompt action of the medicine.

• It is strictly advised not to take Nateglinide if the person cannot take meals followed by medicine intake, as it carries the potential risk of hypoglycemia.

• Do not initiate Nateglinide medication without getting advice from a doctor. Self-medication often ends up in possible health concerns and undesirable side effects.

What Are the Possible Side Effects of Nateglinide?

• The most frequently reported side effect of Nateglinide is hypoglycemia. The person experiences a spectrum of symptoms like weakness, pale skin, hunger, fading vision, tremors, confusion, sweating, and many more. Disorientation, seizure, and collapse are grave symptoms associated with depleted sugar levels and demand prompt treatment.

• Gastrointestinal troubles in the form of indigestion, nausea (tendency to vomit), belly pain, constipation, and loose stools are also reported with the intake of Nateglinide.

• Blocked and runny noses are also elicited by individuals who are administered Nateglinide. In addition, certain patients elicit associated flu, cough, and sneezing.

• Joint pain and body aches are notable side effects of Nateglinide, which often troubles patients and enhances tiredness.

What Should Be Done if a Dose Is Missed?

If the person forgets to take the drug before food and recalls it only after having food, it is advised to disregard the dose. Similarly, if the person recalls the forgotten dose quite late, such that it is time for the subsequent dose, take the dose and no need to consider the previous dose. The patients are instructed to take Nateglinide only if it is followed by food intake; otherwise, it is advised not to take Nateglinide.

How Can We Treat Nateglinide Overdose?

Consuming Nateglinide in a dose higher than the prescribed dose enhances the likelihood of developing hypotension. Hence, it is advised to monitor for symptoms of hypotension. Minor symptoms are often tackled with oral glucose, but in the event of severe symptoms like collapse, immediate medical attention is demanded to safeguard the person’s life.

How to Store Nateglinide?

• Nateglinide is advised to be stored in the package it comes in till the time of consumption. It is marketed in both bottles and blister packets.

• It should be stored within the temperature range of 15 degrees Celsius to 30 degrees Celsius. Exposure to heat, as well as cold, can impact the pill constituents; hence, not advised.

• Patients are strictly warned not to consume the pill once the pills are out of date.

• Make sure that the medicine is inaccessible to small kids; otherwise, it would end up in accidental intake of pills by small children, which can be dangerous.

• Never keep the Nateglinide pills in the refrigerator or freezer.

For Doctors:

Indications

• Type 2 diabetes mellitus.

Contraindications

Nateglinide should not be taken under certain conditions. Contraindications for Nateglinide include:

• Individuals who experienced sensitivity and allergic response to the Nateglinide pill or any of the components in Nateglinide.

• Individuals suffering from type 1 diabetes mellitus.

• Known diabetic patients currently reached the stage of diabetic ketoacidosis.

Dosage and Administration

• Dose: Patients whose glucose value ranges close to the upper limit are advised to start with 60 mg Nateglinide pill thrice daily as an inceptive dose. For patients who are suffering from established type 2 diabetes mellitus with significantly raised blood glucose, 120 mg Nateglinide pills are advised thrice a day. The doctor prescribes the necessary dose considering the glycemic goal of the patient.

• Dosage Forms: Nateglinide is marketed only in tablet form.

• Route of Administration: Nateglinide should be consumed orally with a glass of water prior to food, ideally within half an hour. If the patient is unable to take food, then it is advised not to take the pill, as it can induce hypoglycemia.

Pharmacology

Mechanism of Action:

Nateglinide enhances the insulin release from its source organ, the pancreas, by a sequence of reactions. Within the pancreas, insulin production is carried out by the pancreatic islet cells, specifically the beta cells. These beta cells have certain potassium channels that are sensitive to ATP (adenosine triphosphate). Nateglinide exerts its effect through these channels. The association of Nateglinide with the ATP-sensitive potassium channel results in beta-cell depolarisation. Depolarisation triggers the calcium channel to open up, which is immediately succeeded by an inflow of calcium ions into the beta cells. Calcium ion inflow results in insulin release. In this way, Nateglinide works to enhance insulin release. However, Nateglinide works only if the pancreatic beta cells are functional. That is why, it is not advised for type 1 diabetes mellitus.

Pharmacodynamics:

Once Nateglinide is administered into the body, insulin release occurs in less than 20 minutes. In one hour following the administration of Nateglinide, the insulin achieves the supreme concentration in the blood. The concentration returns to the normal level in four hours.

Pharmacokinetics:

Absorption: After oral intake, just before food, the medicine attains its utmost concentration in one hour, irrespective of dose. However, the makeup of meals (fat, carbohydrates, proteins) does not influence absorption. When Nateglinide is consumed before liquid food, the utmost concentration of Nateglinide is much lower than that of solid food.

Distribution: Nateglinide is distributed with the help of plasma proteins. Albumin is the chief plasma protein concerned with Nateglinide distribution.

Metabolism: Nateglinide undergoes metabolism by the liver enzyme cytochrome P450 2C9. In addition, cytochrome 3A4 also assists in metabolism. During metabolism, Nateglinide first undergoes hydroxylation, which is then succeeded by glucuronidation.

Elimination: The Nateglinide is then removed from the body through feces and urine. Almost 83 percent of the drug is disposed of through urine, while ten percent is through feces. In the urine, nearly 16 percent of Nateglinide is detected as such without undergoing metabolic changes.

Drug Interactions

Nateglinide interacts with a range of drugs when simultaneously administered. Some of the flagged drug interactions of Nateglinide include the following:

• Concurrent intake of Nateglinide with Acetazolamide or Acetyl sulfisoxazole remarkably enhances the efficacy of Nateglinide.

• Simultaneous intake of both Nateglinide and Aspirin enhances the likelihood of developing hypoglycemia.

• When Nateglinide is combined with other anti-diabetic medicines like Sitagliptin, necessary alterations in the dose should be made.

• Nateglinide and Aceclofenac, when taken together, result in collapsed removal of Nateglinide from the body.

• If Furosemide is administered along with Nateglinide, it demands an alteration in the dose of Nateglinide. Furosemide gets in the way of Nateglinide and impairs its effectiveness.

• Medicines that fall under the category of beta blockers, like Metoprolol, enhance the intensity and likelihood of hypoglycemia, when taken with Nateglinide. Furthermore, it conceals some of the pronounced signs that flag hypoglycemia, like shivering, and a speedy heartbeat. As a result, the hypoglycemic episode develops unidentified.

• In addition to beta-blockers, Semaglutide also potentiates hypoglycemia when simultaneously administered with Nateglinide.

• Drugs like somatotropins, corticosteroids, somatostatins, thiazides, and thyroid products, when taken along with Nateglinide, diminish the effectiveness by interrupting the blood glucose.

Warnings and Precautions Before Prescribing Nategliptine

• Hypoglycemia: It is a grave complication that arises from the intake of Nateglinide, where the person elicits an abrupt collapse in the blood sugar level. As soon as the person encounters the symptoms, it is advised to take sugar-containing liquids, like juice, to tackle the hypoglycemia. If the condition advances to the severe stage marked by disorientation and collapse, immediate medical attention is needed to save the person’s life.

• Not to Skip Meals: It is strictly instructed that Nateglinide intake should be followed by food intake. Skipping food after taking Nateglinide carries the potential risk of developing hypoglycemia.

• Diabetic Ketoacidosis: Nateglinide should not be taken if the patient flags symptoms of diabetic ketoacidosis, a known complication of long-standing hyperglycemia.

• Lactose Intolerance: Patients who elicit lactose intolerance are likely to develop gastrointestinal issues following Nateglinide, as lactose is one of its components.