قرص آوانو 25/5 میلی گرم

Avano®
Blood glucose lowering agent, with the brand name Avano® (generic name: Empagliflozin-Linagliptin)

Description
Empagliflozin-Linagliptin is a fixed combination medicine with the brand name Avano®, manufactured by Arvand Pharmed company. This medicine is prescribed for people with type 2 diabetes to control blood glucose.

Product Information
Avano® is a combination of empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Empagliflozin is indicated to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease. 

Product Review
What is Empagliflozin-Linagliptin’s mechanism of action?
Avano® combines 2 antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes: empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, and linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor. 
Empagliflozin: By inhibiting sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubules, empagliflozin reduces reabsorption of filtered glucose from the nephron. SGLT2 is the main site of filtered glucose reabsorption; reduction of filtered glucose reabsorption results in increased urinary excretion of glucose, thereby reducing plasma glucose concentrations.
Linagliptin: Inhibits dipeptidyl peptidase 4 (DPP-4) enzyme resulting in increased 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-4 enzyme.

What are the indications of Avano®?
Treatment of Diabetes mellitus, type 2: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Empagliflozin is indicated for risk reduction of cardiovascular mortality in adults with type 2 diabetes mellitus and established cardiovascular disease. 

What are the dosage forms of Avano®?
Oral Tablets: 10 mg empagliflozin/5 mg linagliptin - 25 mg empagliflozin/5 mg linagliptin

How is the administration of Avano®?
Avano® should be taken in the morning, with or without food.
Due to the lack of additive glycemic benefit, avoid the use of linagliptin in combination with glucagon-like peptide-1 receptor agonists. 

Does Avano® need to adjust the dose in renal failure?
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <30 mL/minute/1.73 m2: Use is not recommended.
Dialysis: Use is contraindicated.

Does Avano® need to adjust the dose for liver failure?
No dosage adjustment is necessary.

Who should not use Avano®? 
History of hypersensitivity (e.g., anaphylaxis, angioedema, exfoliative skin conditions, urticaria, bronchial hyperreactivity) to empagliflozin, linagliptin, or any component of the formulation; patients on dialysis.

Is it safe to use Avano® during pregnancy or breastfeeding?
Avano® use is not recommended during the second and third trimesters.
Due to the potential for serious adverse reactions in the breastfed infant, use during breastfeeding is not recommended.

What drugs does Avano® interact with?
The following drugs can be mentioned among the interactions of category D of Avano.
Sulfonylureas: Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors -Dipeptidyl Peptidase-4 Inhibitors may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a sodium-glucose cotransporter 2 (SGLT2) inhibitor-dipeptidyl peptidase-4 inhibitor and monitor patients for hypoglycemia. 
Insulins: Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors -Dipeptidyl Peptidase-4 inhibitors may enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor- Dipeptidyl Peptidase-4 Inhibitor and monitor patients for hypoglycemia. 
P-glycoprotein/ABCB1 Inducers (e.g., rifampin) or CYP3A4 Inducers (Strong)(e.g., carbamazepine): May decrease the serum concentration of linagliptin. Management: Strongly consider using an alternative to any P-glycoprotein inducer/ strong CYP3A4 inducer in patients treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. 

What precautions and warnings does Avano® have when using it?
• Arthralgia: arthralgia has been reported with linagliptin use; onset may occur within 1 day to years after treatment initiation and may resolve with discontinuation of therapy. Some patients may experience a recurrence of symptoms if linagliptin or other DPP-4 inhibitor therapy is resumed.
• Genital mycotic infections: Empagliflozin may increase the risk of genital mycotic infections (e.g., vulvovaginal mycotic infection, vulvovaginal candidiasis, vulvovaginitis). Patients with a history of these infections or uncircumcised males are at greater risk.
• Hypotension: Empagliflozin may cause symptomatic hypotension due to intravascular volume depletion; the risk may be increased in patients with renal impairment (i.e., eGFR <60 mL/minute/1.73 m2) who are >75 years of age, who are taking other antihypertensives (e.g., diuretics(, or with low systolic blood pressure.
• Ketoacidosis: Cases of ketoacidosis have been reported in patients with type 1 and type 2 diabetes mellitus receiving SGLT2 inhibitors; Before initiating treatment, consider risk factors that may predispose to ketoacidosis (e.g. surgery, or any other extreme stress event). Consider temporary discontinuation of therapy at least 3 days prior to surgery or any event that may precipitate ketoacidosis; ensure risk factors are resolved prior to reinitiating therapy. Patients presenting with nausea/vomiting, abdominal pain, generalized malaise, and/or shortness of breath should be assessed immediately for ketoacidosis.
• Pancreatitis: Cases of acute pancreatitis, have been reported with linagliptin. Use with caution in patients with a history of pancreatitis because it is not known if this population is at greater risk; Discontinue use and institute appropriate therapy if pancreatitis is suspected.
• Renal effects: Acute kidney injury has been reported with empagliflozin. Prior to initiation, consider risk factors for acute kidney injury (e.g., hypovolemia, chronic renal insufficiency, heart failure, use of concomitant medications [e.g., diuretics, ACE inhibitors, ARBs, or nonsteroidal anti-inflammatory drugs]). Additional abnormalities in renal function (decreased eGFR, increased serum creatinine) and adverse effects related to renal function may occur. 
• Urinary tract infection: urinary infections, including urosepsis and pyelonephritis, requiring hospitalization, have been reported with empagliflozin; treatment with empagliflozin increases the risk for urinary tract infections.

Frequently Asked Questions (FAQs)
1- What happens if you miss a dose of Avano®?
Take the medicine as soon as possible, but if it is almost time for the next dose, skip the missed dose. Do not take two doses at the same time.
2- What is the advantage of using Avano® compared to using empagliflozin and linagliptin drugs alone?
Taking two drugs in combination reduces the pill number taken daily and the frequency of drug use and increases treatment adherence. More adherence to treatment in the long term leads to better control of diabetes and reduction of its complications in the patient.
3- Can people with type 1 diabetes use this medicine? No, this medicine is used for people with type 2 diabetes.