Empagliflozin and linagliptin

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Empagliflozin/linagliptin falls into category ­C. There are no well-controlled studies that have been done in pregnant women. Empagliflozin/linagliptin should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

In the U.S.

• Glyxambi

Available Dosage Forms:

• Tablet

Pharmacologic Class: Sodium Glucose Co-Transporter 2 Inhibitor

• Tell all of your health care providers that you take empagliflozin and linagliptin. This includes your doctors, nurses, pharmacists, and dentists.
• Low blood sugar can happen. The chance of low blood sugar may be raised when this medicine is used with other drugs for high blood sugar (diabetes). Signs may be dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating. Call your doctor right away if you have any of these signs. Follow what you have been told to do if you get low blood sugar. This may include taking glucose tablets, liquid glucose, or some fruit juices.
• Do not drive if your blood sugar has been low. There is a greater chance of you having a crash.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• If you are dehydrated, talk with your doctor.
• If loose stools (diarrhea) happen or you are throwing up, call your doctor. You will need to drink more fluids to keep from losing too much fluid.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take empagliflozin and linagliptin.
• It may be harder to control your blood sugar during times of stress like when you have a fever, an infection, an injury, or surgery. A change in level of physical activity or exercise and a change in diet may also affect your blood sugar. Talk with your doctor.
• Talk with your doctor before you drink alcohol.
• Very bad and sometimes deadly pancreas problems (pancreatitis) have happened with this medicine. This could happen at any time during care. Signs of pancreatitis include very bad stomach pain, very bad back pain, or very upset stomach or throwing up. Call your doctor right away if you have any of these signs.
• Too much acid in the blood or urine (ketoacidosis) and very bad urinary tract infections (UTIs) have happened with empagliflozin and linagliptin. Ketoacidosis can be deadly. Both of these health problems may need to be treated in a hospital. Talk with the doctor.
• Kidney problems have happened with this medicine. Sometimes, kidney problems may need to be treated in the hospital. Dialysis may also be needed. Talk with your doctor.
• Heart failure has happened in people taking drugs like this one. Tell your doctor if you have ever had heart failure or kidney problems. Call your doctor right away if you feel very tired or you have shortness of breath, a big weight gain, or swelling in the arms or legs.
• If you are 65 or older, use empagliflozin and linagliptin with care. You could have more side effects.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking this medicine, call your doctor right away.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• Antidiabetic Agent, Dipeptidyl Peptidase 4 (DPP-4) Inhibitor
• Antidiabetic Agent, Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor
• Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor

Empagliflozin: By inhibiting sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubules, empagliflozin reduces reabsorption of filtered glucose from the tubular lumen and lowers the renal threshold for glucose (RTG). SGLT2 is the main site of filtered glucose reabsorption; reduction of filtered glucose reabsorption and lowering of RTG result in increased urinary excretion of glucose, thereby reducing plasma glucose concentrations.

Linagliptin: Inhibits dipeptidyl peptidase IV (DPP-IV) enzyme resulting in prolonged active incretin levels. Incretin hormones (eg, glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic beta cells and decreasing glucagon secretion from pancreatic alpha cells. Decreased glucagon secretion results in decreased hepatic glucose production. Under normal physiologic circumstances, incretin hormones are released by the intestine throughout the day and levels are increased in response to a meal; incretin hormones are rapidly inactivated by the DPP-IV enzyme.

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

According to the manufacturer, use is not recommended during the second and third trimesters. Refer to individual monographs.

Commonly reported side effects of empagliflozin/linagliptin include: urinary tract infection. Other side effects include: increased ldl cholesterol. See below for a comprehensive list of adverse effects.

Initial dose: Empagliflozin 10 mg-linagliptin 5 mg orally once a day in the morning
-May increase to empagliflozin 25 mg-linagliptin 5 mg orally once a day for patients tolerating the lower dose
Maximum dose: Empagliflozin 25 mg-linagliptin 5 mg per day

Comments:
-Empagliflozin has been shown to reduce the risk of cardiovascular (CV) death in adults with type 2 diabetes mellitus and established CV; however, the effectiveness of this combination drug on reducing the risk of CV death in patients with type 2 diabetes mellitus and CV disease has not been established.
-When used in combination with insulin or insulin secretagogues, a lower dose of the insulin secretagogues or insulin may be necessary to reduce the risk of hypoglycemia.

Use: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both empagliflozin and linagliptin is appropriate.

Administration advice:
-Take once daily in the morning with or without food.
-If a dose is missed, take it as soon as you remember; do not double the next dose.

General:
-Not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
-This drug has not been studied in patients with a history of pancreatitis.
-Correct any volume depletion prior to initiating therapy.

Monitoring:
-Monitor for signs and symptoms of hypotension; increase monitoring where volume contraction is expected.
-Monitor volume status and electrolytes during treatment, especially in those with conditions that may lead to fluid loss
-Monitor renal function prior to initiating therapy, at least yearly after initiation, and prior to initiation of any concomitant medicinal product that may have a negative impact on renal function.
-Monitor for signs and symptoms of pancreatitis
-Monitor glycemic control
-Evaluate for the presence ketoacidosis in symptomatic patients, regardless of presenting blood glucose levels.

Patient advice:
-Patients should be instructed to maintain adequate fluid intake to avoid adverse reactions related to volume depletion.
-This drug will cause the urine to test positive for glucose.
-Inform patient that genital mycotic infections, urinary tract infections, and hypersensitivity reactions may occur; patients should be instructed to contact their healthcare provider if these occur.
-Patients experiencing symptoms of ketoacidosis such as difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue, or sleepiness should be instructed to seek immediate medical attention.
-Instruct patients to contact their health care provider if they develop severe and persistent joint pain or blisters or erosions of the skin.

Studies in rats have shown adverse renal changes when empagliflozin was administered during a period of renal development. Doses of approximately 13-times the maximum clinical dose caused renal pelvic and tubule dilations. Administration of both components during the period of organogenesis was not teratogenic in rats in doses up to 253 and 353 times the expected clinical exposure for empagliflozin and linagliptin, respectively. There are no adequate well-controlled studies in pregnant women with this combination drug or with its components. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

Use is not recommended during the second and third trimesters of pregnancy US FDA pregnancy category: Not Assigned Risk Summary: Animal data has shown adverse renal effects with empagliflozin administration during the renal development period which corresponds to the late second and third trimesters of human pregnancy. Adverse developmental effects were not observed when this combination drug was administered to pregnant rats during organogenesis. Comment: Poorly controlled diabetes during pregnancy increases maternal and fetal risks for adverse outcomes.