Dapagliflozin

BRAND NAME:

Farxiga: The main ingredient in Farxiga medication is Dapagliflozin 5 and 10 mg, which is available in the form of film coated tablets. It may be given to specific persons with diabetes, heart diseases, or kidney diseases to enhance their results.

Qtern: Qtern is a combination tablet of saxagliptin (5 mg) and dapagliflozin (10mg) is used to treat type 2 diabetes mellitus. It aids in the management of the elevated blood sugar levels associated with diabetes. This minimizes the risk of major diabetes complications while also helping to prevent heart disease.

Xigduo: It is the combinational drug containing dapagliflozin 5mg and metformin hydrochloride 850mg or 1000mg which is available in the form film coated tablets.

Qtermet XR: Qtermet XR tablets are available in the market with the composition of dapagliflozin/saxagliptin/metformin HCl extended-release (2.5mg/2.5mg/1000mg, 5mg/2.5mg/1000mg, 5mg/5mg/1000mg, 10mg/5mg/1000mg).

MECHANISM OF ACTION:

The sodium-glucose co-transporter 2 is mainly found in the proximal tubule of the nephron, and dapagliflozin inhibits it. Because SGLT2 supports 90% of the reabsorption of glucose in the kidneys, its blockage permits the excretion of glucose in the urine. Patients with type-2 diabetes mellitus may benefit from improved glycemic control and possible weight loss due to this excretion.

PHARMACOKINETICS:

Absorption: The absolute oral bioavailability of dapagliflozin after administering a 10 mg dosage is 78%. Dapagliflozin administered with a high-fat meal reduces Cmax by up to 50% and extends Tmax by about 1 hour, but does not affect AUC when compared to the fasting condition. 

After patients had been fasting for one hour, oral dapagliflozin reached its maximal concentration. Following oral administration of dapagliflozin, the maximal plasma concentration usually reaches within 2 hours of fasting. Cmax and AUC values rise proportionally with dapagliflozin dose in the therapeutic dose range.

Distribution: The distribution volume was estimated as 118L.

Metabolism: Dapagliflozin is metabolised by cytochrome p-4501A1, CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP3A4, uridine diphosphate glucuronyltransferase 1A9, UGT2B4, and UGT2B7. UGT1A9 is responsible for the conversion of glucose to the main metabolite. 

Dapagliflozin is primarily glucuronidated, yielding inactive 3-O-glucuronidated metabolites, a de-ethylated metabolite, and a hydroxylated metabolite. 

Excretion: Dapagliflozin and its associated metabolites are largely removed through the renal route. Following a single 50 mg dose of dapagliflozin, 75% and 21% of total radioactivity are eliminated in the urine and feces, respectively. Less than 2% of the dosage is eliminated in urine as the parent medication. The parent medication is eliminated in feces at a rate of about 15%.

PHARMACODYNAMICS:

After taking dapagliflozin, both healthy people and those with type 2 diabetes mellitus saw an increase in the amount of glucose released in their urine. Dapagliflozin dosages of 10 mg per day for weeks in patients with type 2 diabetes mellitus resulted in approximately 70 grams of glucose excreted in urine per day by week 12. At a daily dose of 20 mg dapagliflozin, glucose excretion was found to be near maximum. Urine glucose excretion and urinary volume both rise when using dapagliflozin. After discontinuing dapagliflozin, the increase in urine glucose excretion usually returns to baseline within 3 days for the 10 mg dose. Dapagliflozin lowers sodium reabsorption and increases sodium delivery to the distal tubule. This may influence a variety of psychological activities, including, but not limited to, lowering both pre- and post-loading of the heart, down-regulating sympathetic activity, and decreasing intraglomerular pressure, which is thought to be mediated by increased tubuloglomerular feedback. Single dosages of up to 500mg of dapagliflozin had no clinically significant effect on the QTC interval in healthy persons. 

ADMINISTRATION:

• The starting dose is 5 mg once a day, which is increased to 10 mg once day to attain the desired glycemic goal.
• Dapagliflozin is given in the morning, with or without food, as prescribed by a doctor.

DOSAGE AND STRENGTH:

• Take dapagliflozin as prescribed by your doctor. Don't chew or break the medication. Based on factors including age, body weight, and disease state, the doctor will determine the appropriate dosage and length of time. Only stop taking the medication if your doctor recommends you to do so. 
• Dapagliflozin is available in two strengths: 5 mg and 10 mg. 

CONTRAINDICATIONS:

• History of severe hypersensitive reaction 
• Severe kidney dysfunction, ESRD dialysis

DRUG INTERACTIONS:

• Some medications may enhance the effects of dapagliflozin.
• Dapagliflozin interacts with several medications, including Furosemide, a diuretic, can raise the risk of dehydration while lowering blood pressure.
• Tamsulosin - to treat an enlarged prostate.
• Levodopa - for Parkinson's disease.
• Gatifloxacin- Antibiotics
• Baclofen, a muscle relaxant.
• Amlodipine and bisoprolol are heart-related medications.
• Glipizide and glimepiride are antidiabetic medications. 
• Consult your doctor before using dapagliflozin with pain relievers such as ibuprofen or aspirin, as these medications can often induce low blood sugar levels. 

FOOD INTERACTIONS:

Avoid excessive or prolonged alcohol consumption. Drinking alcohol frequently may result in ketoacidosis. 

SIDE EFFECTS:

The side effects of dapagliflozin include

• Confusion
• Dizziness
• Chills
• Anxiety
• Depression
• Difficult, burning, or painful urination
• Cool, pale skin
• Fast heartbeat
• Headache
• Increased hunger
• Increased thirst
• Loss of appetite
• Nausea
• Seizures
• Vomiting
• Weight gain
• Swelling of the face or lower legs

OVERDOSE:

Dapagliflozin overdose can result in dehydration, nausea, vomiting, and fever. Low blood sugar can induce several symptoms such as tremors, impaired speech, and fainting. 

TOXICITY:

On the other hand, maternal toxicity and renal pelvic dilatation were linked to late-stage exposure at far greater concentrations than the maximum allowable human dose. Pregnancy-related animal experiments demonstrated no harm to the fetus in the first trimester. These results suggest that dapagliflozin should not be used in the second or third trimester of pregnancy. Age, gender, race, and body weight did not influence the amount of dapagliflozin that was needed. When dapagliflozin is used in children younger than two, it can lead to abnormal kidney development. Patients with a creatinine clearance of less than 45 mL/min are not advised to take dapagliflozin, and those with a clearance of less than 30 mL/min should not take it. 

STORAGE CONDITIONS:

Store at temperature conditions (20-25°C, 68-77°F).