COMPOSITION :

Each f/c caplet of Janutab 50mg/500mg contains: Sitagliptin (as phosphate monohydrate) 50 mg
Metformin hydrochloride 500mg.

Each f/c caplet of Janutab 50mg/850mg contains: Sitagliptin (as phosphate monohydrate) 50 mg
Metformin hydrochloride 850mg.

Each f/c caplet of Janutab plus 50mg/1000mg contains: Sitagliptin (as phosphate monohydrate) 50 mg
Metformin hydrochloride 1000mg.

DESCRIPTION :

Janutab is a combination of two antihyperglycemic agents(sitagliptin and metformin) with complementary
mechanism to improve blood sugar control in type 2 diabetics. Sitagliptin increases insulin secretion and
decreases glucagon secretion through selective inhibition of the enzyme (DPP-4) dipeptidyl peptidase 4, and
this enzyme in turn inhibits the hormones (GLP-1) glucagon like peptide-1 and (GIP) glucose dependent
insulinotropic polypeptide that are released from the intestine which are responsible for regulating the levels
of glucose in the blood by increasing the production and secretion of insulin from the pancreas when blood
glucose levels are high, as the hormone (GLP-1) reduces the secretion of glucagon from the pancreatic alpha
cells, and thus the production of glucose from the liver decreases. While metformin, is a member of the
biguanide class, lowering basal and postprandial plasma glucose. It acts by reduction of hepatic glucose
production ,increasing insulin sensitivity in muscles and delay intestinal glucose absorption.

INDICATION
Janutab is indicated to glycemic control in adult patients with type 2 diabetes mellitus as an adjunct to
proper diet and exercise.

DOSAGE & ADMINISTRATION :

- The recommended initial dose is 50mg sitagliptin/500 mg Metformin HCL twice daily with meal. Patient
with inadequate glycemic control on this dose can be titrated up to 50 sitagliptin /1000 metformin HCl twice
daily with meal , with gradual dose escalation, to reduce gastrointestinal side effect due to metformin.

- Dosage adjustment for patient with mild, moderate, severe and end stage renal disease or Patients receiving
insulin and/or insulin secretagogues (e.g. sulfonylureas) .

- Dosage adjustment is recommended in patients with renal diseases as described in schedule.

GFR ml/min Metformin Sitagliptin

Maximum daily dose is 2000 mg. No dose adjustment (Maximum

45 - 59 ; i
The starting dose is at most half of daily dose is 100 mg.)
the maximum dose.
Maximum daily dose is 1000 mg. . ; .
30 - 44 The starting dose is at most halfof Maximum daily dose is 50 mg.
the maximum dose.
<30 Metformin is contraindicated. Maximum daily dose is 25 mg.

Not to exceed the maximum recommended daily dose of 100 mg sitagliptin and 2000 mg metformin.

In patients at increased risk of further progression of renal impairment or 30-40 GFR ml/min and in the
elderly, renal function should be assess every 3-6 months.

children: The safety and efficacy of Janutab in children and adolescents under 18 years of age have not been
established.

RESTRICTIONS ON USE :

Contraindications

- Hypersensitivity to sitagliptin or metformin.

- Acute or chronic metabolic acidosis (as: lactic acidosis, ketoacidosis).

- Conditions with potential to alter renal function such as: dehydration, sever infection, shock, IV
administration of iodine contrast for X-ray examination.

- Cardiac or respiratory failure , recent myocardial infarction.

- Patients with hepatic discasc.

- Severe renal impairment: (creatinine clearance rate below 30 mL/min) .

- patients with typel diabetes, diabetic precoma.

Precautions

- The treatment of Janutab should be stopped immediately and consult the doctor ,if lactic acidosis
symptoms appear which include vomiting, abdominal pain with muscle cramps ,fatigue and difficulty in
breathing, this case occurs due to Metformin accumulation especially in patients with renal impairment.

- If pancreatitis or Bullous Pemphigoid are suspected, promptly discontinue Janutab.

- Janutab should be temporarity suspended for any surgical procedure and should not be restarted until the
patient becomes able to eat and confirm the renal function is normal.

- The caution should be taken in case of impairment of renal or hepatic function, hypoglycemia, Vitamin
B12 deficiency, erosions and blisters or patients who use insulin secretagogue medicines (sulfonylurea)or
have history of pancreas disease or eldery patients.

Effects on the ability to drive vehicles or use machines.

There is no information to suggest that Janutab affects the ability to drive or use machines.

Use in pregnancy and lactation

Janutab should not be used during pregnancy and lactation.

DRUG INTERACTIONS :

- Co-administration of Janutab with digoxin should be monitored.

- Co-administration of Janutab with insulin secretagogue drug (e.g., sulfonylurea) or insulin increase the
risk of hypoglycemia.

- Co-administration of Janutab with Carbonic anhydrase inhibitors increase risk of lactic acidosis .

- Thiazide and other diuretics,corticosteroids,phenothiazines ,thyroid products, estrogens,oral contracep-
tives,phenytoin,nicotinic acid, calcium channel blockers and isoniazid leads to loss of glycemic control
when use with janutab.

- Caution should be taken when use Janutab with furosemide or nifedipine, NSAIDs, Drugs that reduce
metformin clearance such as ranolazine, vandctanib, dolutegravir, and cimetidine

ADVERSE EFFECTS :

Common adverse effects: stuffy or runny nose and sore throat,diarrhea,nausea and vomiting, gas, stomach
discomfort, indigestion, weakness, headache, Allergic reaction ,upper respiratory infections, hypoglycemia.
Take Janutab with meals can help reduce the common stomach side effects of metformin

OVERDOSAGE:

In case of overdosage, gastric lavage and monitor ECG should be done and institute suppporting therapy.
Hemodialysis may be useful for removal of overdosage of metformine. Sitgliptin may be removed by
prolonged hemodialysis.

STORAGE INSTRUCTIONS :
Store below 30°C, in a dry place.

PRESENTATIONS :

Janutab plus 1000/50 caplets : Pack of 30 caplets and hospital packs of different sizes.
Janutab 850/50 caplets : Pack of 30 caplets and hospital packs of different sizes.
Janutab 500/50 caplets : Pack of 30 caplets and hospital packs of different sizes.