What is TRIJARDY XR and how is it used?
TRIJARDY XR is a prescription medicine that contains 3 diabetes medicines, empagliflozin (JARDIANCE), linagliptin (TRADJENTA), and metformin hydrochloride. TRIJARDY XR can be used:
- along with diet and exercise to lower blood sugar in adults with type 2 diabetes,
- in adults with type 2 diabetes who have known cardiovascular disease when empagliflozin (JARDIANCE), one of the medicines in TRIJARDY XR, is needed to reduce the risk of cardiovascular death.
- TRIJARDY XR is not for people with type 1 diabetes.
- TRIJARDY XR is not for people with diabetic ketoacidosis (increased ketones in the blood or urine).
- If you have had pancreatitis in the past, it is not known if you have a higher chance of getting pancreatitis while you take TRIJARDY XR.
- It is not known if TRIJARDY XR is safe and effective in children under 18 years of age.
What are the possible side effects of TRIJARDY XR?
TRIJARDY XR may cause serious side effects, including:
- See “What is the most important information I should know about TRIJARDY XR?”
- Dehydration. Dehydration may increase your risk of low blood pressure. TRIJARDY XR can cause some people to have dehydration (the loss of body water and salt). Dehydration may cause you to feel dizzy, faint, light-headed, or weak, especially when you stand up (orthostatic hypotension). You may be at higher risk of dehydration if you:
- have low blood pressure
- are on low sodium (salt) diet
- have kidney problems
- take medicines to lower your blood pressure, including diuretics (water pills)
- are 65 years of age or older
- Ketoacidosis (increased ketones in your blood or urine). Ketoacidosis has happened in people who have type 1 diabetes or type 2 diabetes, during treatment with empagliflozin, one of the medicines in TRIJARDY XR. Ketoacidosis has also happened in people with diabetes who were sick or who had surgery during treatment with TRIJARDY XR. Ketoacidosis is a serious condition, which needs to be treated in a hospital. Ketoacidosis may lead to death. Ketoacidosis can happen with TRIJARDY XR even if your blood sugar is less than 250 mg/dL. Stop taking TRIJARDY XR and call your doctor right away or go to the nearest hospital emergency room if you get any of the following symptoms:
- trouble breathing
- stomach-area (abdominal) pain
If you get any of these symptoms during treatment with TRIJARDY XR, if possible, check for ketones in your urine, even if your blood sugar is less than 250 mg/dL.
- Kidney problems. Sudden kidney injury has happened to people taking TRIJARDY XR. Talk to your doctor right away if you:
- reduce the amount of food or liquid you drink for example, if you are sick or cannot eat or
- start to lose liquids from your body for example, from vomiting, diarrhea or being in the sun too long
- Serious urinary tract infections. Serious urinary tract infections that may lead to hospitalization have happened in people who are taking empagliflozin, one of the medicines in TRIJARDY XR. Tell your doctor if you have any signs or symptoms of a urinary tract infection such as a burning feeling when passing urine, a need to urinate often, the need to urinate right away, pain in the lower part of your stomach (pelvis), or blood in the urine. Sometimes people also may have a fever, back pain, nausea or vomiting.
- Low blood sugar (hypoglycemia). If you take TRIJARDY XR with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin, your risk of getting low blood sugar is higher. The dose of your sulfonylurea medicine or insulin may need to be lowered while you take TRIJARDY XR. Signs and symptoms of low blood sugar may include:
- shaking or feeling
- fast heartbeat jittery
- A rare but serious bacterial infection that causes damage to the tissue under the skin (necrotizing fasciitis) in the area between and around the anus and genitals (perineum). Necrotizing fasciitis of the perineum has happened in women and men who take empagliflozin, one of the medicines in TRIJARDY XR. Necrotizing fasciitis of the perineum may lead to hospitalization, may require multiple surgeries, and may lead to death. Seek medical attention immediately if you have a fever or you are feeling very weak, tired or uncomfortable (malaise), and you develop any of the following symptoms in the area between and around your anus and genitals:
- pain or tenderness
- redness of skin (erythema)
- Vaginal yeast infection. Women who take TRIJARDY XR may get vaginal yeast infections. Symptoms of a vaginal yeast infection include vaginal odor, white or yellowish vaginal discharge (discharge may be lumpy or look like cottage cheese), or vaginal itching.
- Yeast infection of the penis (balanitis). Men who take TRIJARDY XR may get a yeast infection of the skin around the penis. Certain men who are not circumcised may have swelling of the penis that makes it difficult to pull back the skin around the tip of the penis. Other symptoms of a yeast infection of the penis include redness, itching, or swelling of the penis, rash of the penis, foul smelling discharge from the penis, or pain in the skin around the penis.
Talk to your doctor about what to do if you get symptoms of a yeast infection of the vagina or penis. Your doctor may suggest you use an over-the-counter antifungal medicine. Talk to your doctor right away if you use an over-the-counter antifungal medication and your symptoms do not go away.
- Allergic (hypersensitivity) reactions. Serious allergic reactions have happened in people who are taking
- TRIJARDY XR. Symptoms may include:
- swelling of your face, lips, throat, and other areas on your skin
- difficulty with swallowing or breathing
- raised, red areas on your skin (hives)
- skin rash, itching, flaking, or peeling
If you have any of these symptoms, stop taking TRIJARDY XR and call your doctor right away or go to the nearest hospital emergency room.
- Low vitamin B12 (vitamin B12 deficiency). Using metformin for long periods of time may cause a decrease in the amount of vitamin B12 in your blood, especially if you have had low vitamin B12 blood levels before. Your doctor may do blood tests to check your vitamin B12 levels.
- Joint pain. Some people who take medicines called DPP-4 inhibitors, one of the medicines in TRIJARDY XR, may develop joint pain that can be severe. Call your doctor if you have severe joint pain.
- Skin reaction. Some people who take medicines called DPP-4 inhibitors, one of the medicines in TRIJARDY XR, may develop a skin reaction called bullous pemphigoid that can require treatment in a hospital. Tell your doctor right away if you develop blisters or the breakdown of the outer layer of your skin (erosion). Your doctor may tell you to stop taking TRIJARDY XR.
The most common side effects of TRIJARDY XR include:
- upper respiratory tract infection
- urinary tract infection
- stuffy or runny nose and sore throat
- inflammation of the stomach and intestine (gastroenteritis)
Tell your doctor if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of TRIJARDY XR. For more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL [see WARNINGS AND PRECAUTIONS].
Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing information [see DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS, and Use In Specific Populations].
If metformin-associated lactic acidosis is suspected, immediately discontinue TRIJARDY XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see WARNINGS AND PRECAUTIONS].
TRIJARDY XR tablets contain: empagliflozin, linagliptin, and metformin hydrochloride.
Empagliflozin is an orally-active inhibitor of the sodium-glucose co-transporter (SGLT2).
The chemical name of empagliflozin is D-Glucitol,1,5-anhydro-1-C-[4-chloro-3-[[4-[[(3S)-tetrahydro-3furanyl]oxy]phenyl]methyl]phenyl]-, (1S).
The molecular formula is C23H27ClO7 and the molecular weight is 450.91. The structural formula is:
Empagliflozin is a white to yellowish, non-hygroscopic powder. It is very slightly soluble in water, sparingly soluble in methanol, slightly soluble in ethanol and acetonitrile; soluble in 50% acetonitrile/water; and practically insoluble in toluene.
Linagliptin is an orally-active inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme.
The chemical name of linagliptin is 1H-Purine-2,6-dione, 8-[(3R)-3-amino-1-piperidinyl]-7-(2-butyn-1-yl)-3,7dihydro-3-methyl-1-[(4-methyl-2-quinazolinyl)methyl]
The molecular formula is C25H28N8O2 and the molecular weight is 472.54. The structural formula is:
Linagliptin is a white to yellowish, not or only slightly hygroscopic solid substance. It is very slightly soluble in water. Linagliptin is soluble in methanol, sparingly soluble in ethanol, very slightly soluble in isopropanol, and very slightly soluble in acetone.
Metformin hydrochloride (N,N-dimethylimidodicarbonimidic diamide hydrochloride) is a biguanide. Metformin hydrochloride is a white to off-white crystalline compound with a molecular formula of C4H11N5•HCl and a molecular weight of 165.63. Metformin hydrochloride is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pKa of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. The structural formula is:
Each film coated tablet of TRIJARDY XR consists of an extended-release metformin hydrochloride core tablet that is coated with the immediate-release drug substances: empagliflozin and linagliptin.
TRIJARDY XR tablets for oral administration are available in four strengths containing:
- 5 mg empagliflozin/2.5 mg linagliptin/1000 mg metformin hydrochloride extended-release
- 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin hydrochloride extended-release
- 12.5 mg empagliflozin/2.5 mg linagliptin/1000 mg metformin hydrochloride extended-release
- 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin hydrochloride extended-release
Each film-coated tablet of TRIJARDY XR contains the following inactive ingredients: Tablet Core: polyethylene oxide, hypromellose, and magnesium stearate. Film Coatings and Printing Ink: hydroxypropyl cellulose, hypromellose, talc, titanium dioxide, arginine, polyethylene glycol, carnauba wax, purified water, shellac glaze, n-butyl alcohol, propylene glycol, ammonium hydroxide, isopropyl alcohol, ferrosoferric oxide and ferric oxide yellow (5 mg/2.5 mg/1000 mg and 25 mg/5 mg/1000 mg), ferric oxide yellow and ferric oxide red (10 mg/5 mg/1000 mg), and ferrosoferric oxide and ferric oxide red (12.5 mg/2.5 mg /1000 mg).