Glipless®
Sitagliptin F.C tablet
Introduction
Category:
inhibitor of the dipeptidyl peptidase-4
(DPP-4) enzyme.
(Drug Facts)
Chemistry:
Sitagliptin phosphate monohydrate is
described chemically as 7-[(3R)-3-amino-4-(2,4,5trifluorophenyl)butanoyl] -3-(trifluoromethyl)-
5,6,7,8-tetrahydro -1,2,4-triazolo[4,3-a]pyrazine monophosphate monohydrate. C16H15F6N5O•H3PO4•H2O=523.3
Mechanism of action:
DPP-4
inhibitor; therefore, increase and prolongs incretin hormone activity, which is
inactivated by DPP-4 enzyme
Incretins
increase insulin release and synthesis from pancreatic beta cells and reduce
glucagon secretion from pancreatic alpha cells.
(Drug Facts)
Pharmacokinetics:
|
Absorption
|
bioavailability is approximately 87%
|
|
Protein binding
|
38%
|
|
Metabolism
|
Approximately 79% is excreted unchanged in
the urine
|
|
Time to Peak Concentration
|
1-4
hours
|
|
Elimination
|
Urine :
87%
Feces :
13%
|
(Facts, Martindale)
Indications:
Sitagliptin
is indicated as an adjunct to diet and exercise to improve glycemic control in
adults with type 2 diabetes mellitus.
(PDR)
Contraindications:
Known serious hypersensitivity (e.g., anaphylaxis,
angioedema) to sitagliptin or any ingredient in formulation.
(PDR)
Warnings & Precautions:
1.Tell your doctor if you have or have had:
- a disease of the pancreas (such as
pancreatitis)
- gallstones, alcohol dependence or very high
levels of triglycerides (a form of fat) in your blood. These medical
conditions can increase your chance of getting pancreatitis
- type 1 diabetes
- diabetic ketoacidosis (a complication of diabetes
with high blood sugar, rapid weight loss, nausea or vomiting)
- any past or present kidney problems.
- an allergic reaction to Sitagliptin
2.Children and adolescents below 18 years should not use this medicine.
3.Tell your doctor or pharmacist if you are taking, have recently taken or
might take any other medicines.
-
In particular, tell your doctor
if you are taking digoxin (a medicine used to treat heart problems). The level
of digoxin in your blood may need to be checked if taking with Sitagliptin.
4.This medicine has no or negligible influence on the ability to drive and
use machines. However, dizziness and drowsiness have been reported, which may
affect your ability to drive or use machines.
5.Taking this medicine in combination with medicines called sulphonylureas
or with insulin can cause hypoglycemia, which may affect your ability to drive
and use machines or work without safe foothold.
(www.medicines.org.uk )
Pregnancy:
There are no adequate data from the use of sitagliptin in pregnant
women. Studies in animals have shown reproductive toxicity at high doses. The
potential risk for humans is unknown. Due to lack of human data, Sitagliptin
should not be used during pregnancy.
(www.medicines.org.uk )
Breast-feeding:
not
known whether distributed into human milk.
(PDR)
Drug Interactions:
Drugs Metabolized by Hepatic Microsomal Enzymes
Does
not inhibit CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4 in vitro or
induce CYP3A4. Pharmacokinetic interactions with drugs metabolized by these
isoenzymes unlikely.
Inhibitors of P-glycoprotein Transport System
Substrate
of p-glycoprotein transport system. Potential pharmacokinetic interaction
(increased absorption and renal clearance of sitagliptin) with p-glycoprotein
inhibitors
Clinically
important pharmacokinetic interactions with p-glycoprotein inhibitors unlikely.
Does not appear to inhibit p-glycoprotein transport system.
Drugs Secreted by Renal Tubular Cationic Transport
Substrate
of organic anion transport system; pharmacokinetic interaction unlikely with
substrates of organic cationic transport system.
Protein-bound Drugs
Pharmacokinetic
interaction unlikely
(Martindale/ Drug Facts)
Adverse Reactions:
Adverse effects reported with sitagliptin include upper respiratory-tract
infections, headache, and nasopharyngitis. Hypersensitivity reactions including
anaphylaxis, angioedema, urticaria, rash, and Stevens-Johnson syndrome have also
been reported.
(Martindale)
Over dosage:
During controlled clinical trials in healthy subjects, single doses
of up to 800 mg sitagliptin were administered. Minimal increases in QTc, not
considered to be clinically relevant, were observed in one study at a dose of
800 mg sitagliptin. There is no experience with doses above 800 mg in clinical
studies.
(www.medicines.org.uk)
Dosage
& Administration:
Adults
Diabetes Mellitus
Oral
Sitagliptin monotherapy: Maximum 100 mg daily. Fixed combination with metformin
hydrochloride: Maximum 100 mg of sitagliptin and 2 g of metformin hydrochloride
daily (in divided doses).
(PDR)
Storage:
Store below 30˚ C and protect from humidity and direct light.
How supplied:
Sitagliptin
is as available as 25&50&100 mg, Pink, mustard, peach. There are
blisters of 10’s in a box of 30’s.
References:
1- Drug
Facts 2015
2-
Martindale (39) 2017
3- PDR 2016
4-www.medicines.org.uk