Saxagliptin - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

Overview:

Saxagliptin belongs to a class of medications that are prescribed for diabetes mellitus.

It is a dipeptidyl peptidase-4 (DPP-4) inhibitor. The Food and Drug Administration (FDA) approved Saxagliptin on July 31, 2009. Saxagliptin inhibits the dipeptidyl peptidase-4 (DPP-4) enzyme, leading to increased insulin secretion by preventing glucagon-like peptide-1 degradation, leading to decreased glucagon production.

Uses of Saxagliptin:

Saxagliptin belongs to the drug group that aims to lower the blood glucose levels in patients suffering from type 2 diabetes mellitus. Lifestyle modifications such as balanced dietary intake, regular exercise, and Saxagliptin intake can significantly lower the blood sugar levels in type 2 diabetic patients. The efficacy of Saxagliptin increases when prescribed with other anti-diabetic medications like Metformin and Sulfonylureas, researches have shown that this type of combination therapy provides excellent glycemic control. Saxagliptin is prescribed to adult diabetic patients as its efficacy in people younger than 18 years of age has not yet been established.

Dosage and Administration:

• 2.5 to 5 mg (milligrams) once daily with or without meals.

• 2.5 mg once daily is the recommended dosage for moderate to severe renal impairment patients.

• 2.5 mg once daily is the preferred dosage for patients taking cytochrome inhibitors like Ketoconazole.

• When administered in combination with other drugs like Sulfonylurea and Insulin secretagogues, the dosage of medicines prescribed in combination needs to be reduced.

Renal function tests should be advised before prescribing Saxagliptin, and periodical renal function tests should be done for patients undertaking Saxagliptin daily.

Dosage Forms and Strengths:

2.5 mg and 5 mg tablets.

Contraindications:

It is contraindicated in patients having the following conditions:

• Allergy to the drug Saxagliptin as allergic patients may show symptoms of hypersensitivity reactions like angioedema, anaphylaxis, or exfoliative skin diseases.

• Moreover, the safety of Saxagliptin in specific conditions like pregnancy has not yet been established. Hence, Saxagliptin prescription should be avoided, and alternative medications should be prescribed.

Warnings and Precautions:

1. Heart Failure: The risk of heart failure has been noted in patients who are prescribed Saxagliptin. Following are a few of the features of heart failure that should be noted in these patients:

• Shortness of breath during exercising or while doing any other physical activity, shortness of breath can also be present at rest in individuals suffering from heart failure.

• Fatigue and weakness are commonly noted, and the individual gets tired while performing basic day-to-day activities.

• Swellings in the legs, ankles and feet are an important indicator of heart failure due to electrolyte imbalance in these individuals.

• Irregular heartbeat.

• Persistent cough and wheezing with whitish or pinkish-tinged mucus are also commonly noted in these individuals.

2. Pancreatitis: Acute pancreatitis, involving fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been marked in cases managed with Saxagliptin. Constant extreme abdominal aches, periodically radiating to the back, which can or cannot be accompanied by vomiting, can be noted in individuals suffering from pancreatitis. If pancreatitis is supposed to occur, Saxagliptin should immediately be stopped, and proper treatment should be started.

3. Hypoglycemia: Clinical trials have proven the risk of hypoglycemia in patients taking Saxagliptin for diabetes mellitus management. Significant lowering of the glucose levels in the individuals shows signs and symptoms like shaking, sweating, nervousness, increased heartbeat, irritability, and dizziness. These symptoms should be periodically checked in patients who have been prescribed Saxagliptin to reduce the chances of hypoglycemic coma. Moreover, Saxagliptin, when administered in combination with other drugs like Sulfonylurea and Insulin secretagogues, the dosage of medicines prescribed in combination needs to be reduced in order to reduce the risk of hypoglycemia.

4. Hypersensitivity Reactions: Clinical trials have reported urticaria (extensively itchy rashes caused due to an allergic reaction), facial edema (swelling of the face), and exfoliative skin disease associated with individuals taking Saxagliptin for the management of type 2 diabetes mellitus. The medication should be immediately discontinued in individuals who portray symptoms of severe hypersensitivity, and emergency management protocols should be followed. Alternative drugs should be prescribed when an allergic reaction to Saxagliptin gets established to protect the individual from the life-threatening hypersensitivity reactions associated with Saxagliptin.

5. Arthralgia: Arthralgia refers to joint pain. Severe and disabling joint pain has been reported in a few individuals who have been prescribed Saxagliptin for diabetes mellitus type 2 treatments. Other causes of arthralgia should be ruled out for patients who complain about arthralgia. Once the cause of arthralgia has been established, Saxagliptin should be discontinued, and alternative medications should be prescribed under the physician's supervision.

6. Macrovascular Outcomes: Various clinical trials have studied conditions like thrombolysis and macrovascular outcomes. No confirmed outcome has been established yet to ensure the connection between Saxagliptin intake and macrovascular complications.

Drug Interactions:

Drugs like Ketoconazole which are cytochrome inhibitors when prescribed along with Saxagliptin, result in an increased concentration of Saxagliptin. A 2.5 mg/day dosage is prescribed to compensate for the increased Saxagliptin concentration.

Adverse Reactions Associated With Saxagliptin:

Adverse reactions include unexpected or dangerous reactions associated with a particular drug. Following are a few commonly associated adverse reactions with Saxagliptin:

• Respiratory Tract Infection: Upper respiratory tract infection, like coughing and wheezing, is a very commonly noted adverse reaction associated with Saxagliptin.

• Peripheral Edema: Swelling noted in the legs, particularly associated with water retention, is a commonly associated adverse reaction with Saxagliptin.

Individuals affected by these adverse reactions are advised to discontinue the medication and take alternative medicines for diabetes mellitus treatment as suggested by their physician.

For Patients:

What Is Type 2 Diabetes?

Type 2 diabetes is a chronic metabolic disorder characterized by high sugar or glucose levels in the blood.

Diabetes mellitus is a common metabolic disorder.

Following are the types of diabetes mellitus:

• Type 1 Diabetes Mellitus: It is noted in the early stage of life.

• Type 2 Diabetes Mellitus: It is stated later in life as it develops over time.

Insulin is the hormone that is produced in the pancreas by a particular type of cell known as beta cells. Insulin is required to catabolize (break down) blood sugar in the cells. Glucose is stored in the cells and later utilized by the body for various activities. Still, in metabolic disorders like type 2 diabetes, the fat cells, liver cells, and muscle cells do not react perfectly to Insulin. Therefore, blood sugar does not get into these cells to be reserved for energy. When sugar cannot be burnt or utilized by the cells, an increased sugar level in the blood occurs. This increased sugar level is called hyperglycemia.

Hyperglycemia is the diagnostic feature of type 2 diabetes mellitus. The body is incapable of using glucose for energy in people suffering from diabetes mellitus, and type 2 diabetes mellitus typically evolves gradually over time. Most individuals with the disorder complain of weight gain, and increased fat levels make it more difficult for the body to utilize Insulin correctly. Type 2 diabetes can also be present in individuals who are not overweight.

What Is Saxagliptin Used For?

Saxagliptin belongs to the drug group that aims to lower the blood glucose levels in patients suffering from type 2 diabetes mellitus. 2.5 or 5 mg once daily with or without meals is the dosage of Saxagliptin. Lifestyle modifications such as balanced dietary intake, regular exercise, and Saxagliptin intake can significantly lower the blood sugar levels in type 2 diabetic patients. The efficacy of Saxagliptin increases when prescribed with other anti-diabetic medications like Metformin and Sulfonylureas, researches have shown that this type of combination therapy provides excellent glycemic control. Saxagliptin is prescribed to adult diabetic patients as its efficacy in people younger than 18 years of age has not yet been established.

General Consideration:

• Saxagliptin may generate serious side effects such as hypoglycemia (severe reduction in blood sugar levels), arthralgia (severe joint pain), hypersensitivity reactions, and pancreatitis (inflammation of the pancreas). In severe conditions, even heart failure can also occur. So, individuals who are under Saxagliptin should keep a check on the signs and symptoms of the side effects associated with the drug, and they should immediately report any abnormal features to their consulting doctor.

• Saxagliptin cannot be prescribed to individuals less than 18 years of age.

• Saxagliptin is also contraindicated in pregnant individuals.

How Is Saxagliptin Taken?

Saxagliptin is manufactured in the form of tablets. Dosages of 2.5 mg and 5 mg are available in the market. Physicians advise a single dose of Saxagliptin on a daily basis, with or without the meal. The doctor's advice is to follow the same time daily for taking the drug Saxagliptin. It is always advisable that the patient should carefully read the doctor's prescription before taking the medication, and in case of any confusion, they should immediately consult the doctor.

What Is to Be Done in Case of a Missed Dose and an Overdose of Saxagliptin?

Usually, the prescribed dose for Saxagliptin is 5 mg per day. Still, in many cases, like when the individual is suffering from a kidney disorder or taking another drug in combination with Saxagliptin, the prescribed dose is 2.5 mg daily.

• Missed Dose: In case the patient forgets to take the prescribed dose of the tablet, or in any case, the amount is missed, then the tablet should be taken as soon as they remember, or if it is time for the second dose, then the individual can skip the first dose and immediately take the second prescribed dose.

• Overdose: In case of overdose, the individual may have symptoms like nausea, vomiting, dizziness, or may suffer from pain in the stomach. If this happens, the patient should be immediately taken to the hospital, and a thorough checkup should be done. In severe toxicity, gastric lavage is given, and the patient is kept under medical supervision.

How Long Can a Patient Be On Saxagliptin Medication for Type 2 Diabetes Mellitus Treatment?

The role of Saxagliptin is to control blood sugar levels to prevent diabetes-associated health conditions. Individuals who respond well to the medication and the blood sugar level gets controlled without any side effects or adverse reactions then in such individuals the medication can be continued for a long span, and in particular, patients life long continuity of the medication has also been noted. Even if the blood glucose level is maintained, the patient should visit the doctor regularly to check the drug's effectiveness.

Suppose even after taking Saxagliptin regularly, the glucose level is not maintained. In that case, another group of drugs or combination therapy with other medications are prescribed for controlling the glucose levels in these individuals suffering from type 2 diabetes mellitus.

What Are the Things to Inform the Doctor Before Starting the Treatment With Saxagliptin?

Whenever an individual visits a doctor for the management of type 2 diabetes mellitus, the following pieces of information should be given to the doctor:

• Family History: The patient should inform the doctor if any family members, like their parents, are suffering from diabetes mellitus or not. They should also disclose if their siblings or spouse has any history of diabetes mellitus or not. This information helps the doctors know the disorder's hereditary pattern and the common signs and symptoms that run in the individual's family. Family history of the disorder guides the doctor in planning a better management and treatment protocol.

• Personal History: Personal history includes altered symptoms that an individual faces, like excessive weight gain or weight loss, lethargy, swollen legs, increased heart rate, increased thirst, increased urge to eat food and increased urination. This personal history regarding the individual's altered symptoms serves as a guide for the clinical diagnosis of type 2 diabetes mellitus.

• Other Systemic Disorders: The patient should always inform the doctors if they are suffering from other underlying diseases like kidney disorders or liver dysfunction. Doctors prescribe medications keeping in consideration the other underlying systemic conditions.

• Pregnancy: Pregnancy history should always be given to the doctor as many drugs like Saxagliptin are contraindicated in pregnancy as there are insufficient research papers that can confirm the safety of Saxagliptin in pregnancy.

For Doctors:

Pharmacology:

The GLP-1 receptor, a membrane-bound cell-surface receptor connected to adenylyl cyclase with the G-protein, in beta cells of the pancreas. After Saxagliptin prescription, the level of the GLP-1 receptors increases up to two to three folds. It is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor, and hence the side effects of Saxagliptin are significantly less. The development of Saxagliptin levels lasts for a 24-hour duration. Therefore, it also increases the insulin level and reduces the glucagon levels secreted from the beta cells of the pancreas.

Mechanism of Action:

Incretins are the hormones associated with glucose level management in the body, and DPP-4 inhibitors act on incretins. Incretins play an essential role in blood sugar level management by increasing the breakdown of glucose and increased consumption of glucose. Incretins also stimulate insulin production from the pancreas, thus reducing gluconeogenesis or glucose production in the liver. DPP-4 is an enzyme that is associated with membranes of various tissues, lymphocytes, and plasma.

Pharmacokinetics:

Absorption:

The bioavailability of the drug Saxagliptin for the dose of 2.5 to 5 mg is equivalent to 67 %. For a 5 mg once daily dose, the median time to maximum concentration is noted to be two hours for Saxagliptin. The protein binding of the drug in human serum is indicated to be less than ten percent which is almost negligible.

Metabolism:

Cytochrome P450 is associated with the metabolism of Saxagliptin. After absorption, fifty percent of the drug undergoes hepatic metabolism. Saxagliptin and its active metabolite 5-hydroxy Saxagliptin play an essential role in maintaining glucose levels.

Route of Elimination:

Renal and hepatic pathways are the route for eliminating the drug Saxagliptin. Renal clearance of a single 50 mg dose is 14L/hour.

Specific Populations:

• Elderly - Age had no impact on the pharmacokinetics of Saxagliptin, depending on a pharmacokinetic study.

• Race and Ethnicity - Race and ethnicity did not impact the pharmacokinetics of Saxagliptin based on the effects of people's pharmacokinetic examinations.

• Body Weight - Body weight particularly impacts the pharmacokinetics of Saxagliptin depending on the results of population pharmacokinetic examinations. The disclosure of Saxagliptin reduces with an addition in baseline body weight.

Lists of Drug Interaction:

• Abacavir.

• Abametapir.

• Abatacept.

• Acarbose.

• Acemetacin.

• Acetaminophen.

• Acetazolamide.