Ertugliflozin-Sitagliptin

Ertugliflozin-Sitagliptin is a combination medication indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes when treatment with both ertugliflozin and sitagliptin is appropriate.

• Ertugliflozin-Sitagliptin is available under the following different brand names: Steglujan

Common side effects of Ertugliflozin-Sitagliptin include:

• genital yeast infections
• upper respiratory tract infection
• runny or stuffy nose
• headache
• urinary tract infections (UTIs)
• vaginal itching
• increased urination
• back pain
• weight loss
• thirst

Serious side effects of Ertugliflozin-Sitagliptin include:

• hives
• difficulty breathing
• swelling of the face, lips, tongue, or throat
• burning, painful, or frequent urination
• pink or bloody urine
• changes in the amount of urine
• swelling of the legs and feet
• joint pain
• unusual skin blisters
• shortness of breath
• unusual tiredness
• sudden weight gain
• nausea
• vomiting
• loss of appetite
• severe stomach pain
• back pain
• unusual vaginal discharge, burning, itching, or odor
• redness, itching, discharge, or swelling of the penis
• pain, redness, or swelling in or around the genital or anal area
• fever
• feeling unwell
• pain, tenderness, sores, or ulcers on the legs or feet
• sudden sweating
• shaking
• fast heartbeat
• hunger
• blurred vision
• dizziness
• tingling of the hands or feet
• increased thirst or urination
• urinating less than usual
• unusual dry mouth
• increased thirst
• fast heartbeat
• fainting
• lightheadedness
• severe dizziness
• rash

Rare side effects of Ertugliflozin-Sitagliptin include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 5 mg/100 mg
• 15 mg/100 mg

Type 2 diabetes

Adult dosage

• 5 mg/100 mg orally once a day in the morning initially; if additional glycemic control is needed and the starting dose is tolerated, may increase to a maximum dose of 15 mg/100 mg
• Patients on ertugliflozin: Maintain ertugliflozin dose when switched to a combination

Dosage Considerations – Should be Given as Follows:

• See "Dosages"

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Ertugliflozin-Sitagliptin has severe interactions with no other drugs
• Ertugliflozin-Sitagliptin has serious interactions with the following drugs:
  • erdafitinib
  • ethanol
  • lasmiditan
  • sotorasib
  • tepotinib
• Ertugliflozin-Sitagliptin has moderate interactions with at least 86 other drugs
• Ertugliflozin-Sitagliptin has moderate interactions with at least 75 other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Hypersensitivity to drugs or excipients; reactions such as angioedema or anaphylaxis have occurred
• Severe renal impairment (less than 30 mL/min/1.73 m2), end-stage renal disease, or dialysis

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Ertugliflozin-Sitagliptin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Ertugliflozin-Sitagliptin?”

Cautions

• Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, in patients taking sitagliptin reported; promptly discontinue if pancreatitis suspected
• Necrotizing fasciitis of the perineum (Fournier gangrene) reported with sodium-glucose cotransporter-2 (SGLT2) inhibitors; signs and symptoms include tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum and a fever above 100.4 °F or a general feeling of being unwell; if suspected, discontinue SGLT2 inhibitor and start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary
• Causes intravascular volume contraction; symptomatic hypotension may occur after initiating, particularly in patients with renal impairment and low systolic blood pressure, on diuretics, or who are elderly; before initiating treatment in patients with one or more of risk factors, assess volume status and renal function
• Renal impairment may occur owing to intravascular volume contraction; before initiating, consider factors that may predispose patients to acute kidney injury, including hypovolemia, chronic renal insufficiency, congestive heart failure, and concomitant medications (eg, diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs); consider temporarily discontinuing ertugliflozin in any setting of reduced oral intake or fluid loss; monitor for signs and symptoms of acute kidney injury, and, if evident, discontinue drug promptly and institute treatment
• Serious UTIs, including urosepsis and pyelonephritis, requiring hospitalization reported in patients receiving SGLT2 inhibitors
• Heart failure has been observed in cardiovascular outcomes trials for two other dipeptidyl peptidase 4 (DPP-4) inhibitors; consider the risks and benefits before initiating treatment in patients at a risk for heart failure (eg, those with a prior history of heart failure, a history of renal impairment), and observe these patients for signs and symptoms of heart failure during therapy
• Genital mycotic infections may occur; patients with a history of genital mycotic infections and uncircumcised males are more susceptible
• Serious hypersensitivity reported with sitagliptin, including anaphylaxis, angioedema, and exfoliative skin conditions, including Stevens–Johnson syndrome
• Dose-related increases in low-density lipoprotein cholesterol reported
• Severe and disabling arthralgia reported in patients taking DDP-4 inhibitors; may occur at any time; symptoms relieved upon discontinuation
• Bullous pemphigoid requiring hospitalization reported with DPP-4 inhibitors; patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of the DPP-4 inhibitor
• No conclusive evidence of macrovascular risk reduction with empagliflozin or any other antidiabetic agent
• Lower limb amputation
  • An increased risk for lower limb amputation (primarily of the toe) has been observed in clinical studies with another SGLT2 inhibitor; before initiating treatment, consider factors that may predispose the patient to an increased risk for amputations (eg, history of prior amputation, peripheral vascular disease, neuropathy, diabetic foot ulcers)
  • Counsel patients about the importance of routine preventative foot care; monitor patients receiving drugs for signs and symptoms of infection (including osteomyelitis), new pain or tenderness, and sores or ulcers involving the lower limbs, and discontinue therapy if these complications occur
• Ketoacidosis
  • Not indicated for patients with type 1 diabetes (T1D); in placebo-controlled trials, the risk for ketoacidosis was increased in patients with T1D who received SGLT2 inhibitors
  • The risk for ketoacidosis may be greater with higher doses
• Before initiating therapy, consider factors in the patient's history that may predispose to ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse
• Consider temporarily discontinuing therapy for at least 4 days for patients who undergo scheduled surgery
• Consider monitoring for ketoacidosis and temporarily discontinuing therapy in other clinical situations known to predispose to ketoacidosis (eg, prolonged fasting due to acute illness or post-surgery); ensure risk factors for ketoacidosis are resolved before restarting therapy
• Type 2 diabetes and pancreatic disorders (eg, history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes using SGLT2 inhibitors
• Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse
• Ketoacidosis and glucosuria may persist longer than typically expected; urinary glucose excretion persists for 3 days after discontinuing therapy; however, there have been postmarketing reports of ketoacidosis and/or glucosuria lasting more than 6 days and some up to 2 weeks after discontinuation of SGLT2 inhibitors
• Consider ketone monitoring in patients at a risk for ketoacidosis if indicated by the clinical situation; assess for ketoacidosis regardless of presenting blood glucose levels in patients who present with signs and symptoms consistent with severe metabolic acidosis; if ketoacidosis is suspected, discontinue therapy; promptly evaluate and treat ketoacidosis, if confirmed; monitor patients for resolution of ketoacidosis before restarting the therapy
• Educate all patients on signs and symptoms of ketoacidosis and instruct patients to discontinue therapy and seek medical attention immediately if signs and symptoms occur
• Drug interaction overview
  • Hypoglycemia risk increased with insulin and insulin secretagogues (eg, sulfonylureas); a lower dose of insulin or insulin secretagogue may be required
  • Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors, as SGLT2 inhibitors increase urinary glucose excretion and lead to positive urine glucose tests; use alternative methods to monitor glycemic control
  • Monitoring glycemic control with 1,5-AG assay is not recommended, as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors; use alternative methods to monitor glycemic control
  • Coadministration with sitagliptin has shown a slight increase in digoxin AUC (11%) and mean peak drug concentration (18%); no dosage adjustment of digoxin is required, but monitor appropriately

Pregnancy and Lactation

• Ertugliflozin
  • Based on animal data showing adverse renal effects, not recommended during the second and third trimesters of pregnancy
  • Data are limited in pregnant women and are not sufficient to determine a drug-associated risk of adverse developmental outcomes; there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy
• Sitagliptin
  • There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to sitagliptin during pregnancy
  • Healthcare providers are encouraged to report any prenatal exposure by calling the Pregnancy Registry at 1-800-986-8999
• Lactation
  • Not recommended while breastfeeding
  • Unknown if distributed in human breast milk
  • Because human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be a risk to the developing human kidney
  • Because of the potential for serious adverse reactions in a breastfed infant, advise women that Ertugliflozin-Sitagliptin is not recommended while breastfeeding