Drug Interaction:
Rifampicin, Sulfonylurea, insulin
Indication:
Tradienta (linagliptin) tablets
Initial U.S. Approval: 2011
RECENT MAJOR CHANGES
Indications and Usage Important Limitations of Use (1.2) 8/2012
Dosage and Administration Concomitant Use with an Insulin Secretagogue
(e.g., Sulfonylurea) or with Insulin (2.2) 8/2012
Warnings and Precautions Use with Medications Known to Cause
Hypoglycemia (5.1) 8/2012
Drug Name- Tradjenta
Active Ingredient - Linagliptin
As an adjunct to diet and excercise to improve glycemic control in adults
with type 2 diabetes mellitus
Indication-
As an adjunct to diet and excercise to improve glycemic control in adults
with type 2 diabetes mellitus
Approved by FDA on 02-5-2011 (Ref- FDA approved List- 2011)
Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
Linagliptin film coated 23-01-2012
tablets 5mg
As a adjunct to diet and excercise to improve glycemic control in adults
with type 2 diabetes mellitus. Important limitations of use-
i.Should not be used in patients with type 1 diabetes or for the treatment
of Diabetes Ketoacidosis
ii. Has not been studied in combination with Insulin
FIXED DOSE COMBINATIONS APPROVED BY DCG(I)
FROM JANUARY 1961 TILL NOVEMBER 2014
Name of Drug Indication Date of Approval
Linagliptin 2.5mg/2.5mg/2.5mg + 26-07-2013
Metformin 500mg/850mg/1000mg
Film coated tablets
As an adjunct to diet and excercise to improve glycemia
control in adults with Type II Diabetes Mellitus when
treatment of with Linagliptin and Metformin is appropiate
Adverse Reaction:
Adverse reactions reported in (5%) of patients treated with TRADJENTA and more
commonly than in patients treated with placebo included nasopharyngitis
Hypoglycemia was more commonly reported in patients treated with the combination
of TRADJENTA and sulfonylurea compared with those treated with the combination of
placebo and sulfonylurea
Pancreatitis was reported more often in patients treated with linagliptin
(15.2 per 10,000 patient years versus 3.7 per 10,000 patient years for comparator)
Contra-Indications:
CONTRAINDICATIONS
History of hypersensitivity reaction to linagliptin, such as urticaria, angioedema,
or bronchial hyperreactivity
WARNINGS AND PRECAUTIONS
When used with an insulin secretagogue (e.g., sulfonylurea) or insulin, consider
lowering the dose of the insulin secretagogue or insulin to reduce the risk
of hypoglycemia
There have been no clinical studies establishing conclusive evidence of macrovascular
risk reduction with TRADJENTA or any other antidiabetic drug
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
TRADJENTA is 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
Important limitations of use:
Should not be used in patients with type 1 diabetes or for the treatment of
diabetic ketoacidosis
DOSAGE AND ADMINISTRATION
„h The recommended dose of TRADJENTA is 5 mg once daily.
TRADJENTA can be taken with or without food.
DOSAGE FORMS AND STRENGTHS
Tablets: 5 mg
Patient Information:
PATIENT COUNSELING INFORMATION
Instructions
1. Inform patients of the potential risks and benefits of TRADJENTA and of alternative
modes of therapy. Also inform patients about the importance of adherence to
dietary instructions, regular physical activity, periodic blood glucose monitoring
and A1C testing, recognition and management of hypoglycemia and hyperglycemia,
and assessment for diabetes complications.
2. Advise patients to seek medical advice promptly during periods of stress such as fever,
trauma, infection, or surgery, as medication requirements may change.
3.Instruct patients to take TRADJENTA only as prescribed. If a dose is missed,
advise patients not to double their next dose.
4.Instruct patients to read the Patient Information before starting TRADJENTA therapy
and to reread it each time the prescription is renewed.
5.Instruct patients to inform their doctor or pharmacist if they develop any unusua
symptom, or if any known symptom persists or worsens.
6. Laboratory Tests
Inform patients that response to all diabetic therapies should be monitored by
periodic measurements of blood glucose and A1C levels, with a goal of decreasing these
levels toward the normal range. A1C monitoring is especially useful for evaluating
long-term glycemic control.
Pharmacology/ Pharmacokinetics:
1. Mechanism of Action
Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones
glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide
(GIP). Thus, linagliptin increases the concentrations of active incretin hormones,
stimulating the release of insulin in a glucose-dependent manner and decreasing
the levels of glucagon in the circulation.
2 Pharmacokinetics
The pharmacokinetics of linagliptin has been characterized in healthy subjects
and patients with type 2 diabetes. After oral administration of a single 5-mg dose
to healthy subjects, peak plasma concentrations of linagliptin occurred at
approximately 1.5 hours post dose (Tmax); the mean plasma area under
the curve (AUC) was 139 nmol*h/L and maximum concentration (Cmax) was 8.9 nmol/L.
Plasma concentrations of linagliptin decline in at least a biphasic manner with
a long terminal half-life (>100 hours), related to the saturable binding of
linagliptin to DPP-4.
The prolonged elimination phase does not contribute to the accumulation of the drug
of linagliptin, as determined from oral administration of multiple doses
of linagliptin 5 mg, is approximately 12 hours. After once-daily dosing,
steady-state plasma concentrations of linagliptin 5 mg are reached by
the third dose, and Cmax and AUC increased by a factor of 1.3 at steady
state compared with the first dose. The intra-subject and inter-subject coefficients
of variation for linagliptin AUC were small (12.6% and 28.5%, respectively).
Plasma AUC of linagliptin increased in a less than dose-proportional manner
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category B
Reproduction studies have been performed in rats and rabbits. There are, however,
no adequate and well-controlled studies in pregnant women. Because animal
reproduction studies are not always predictive of human response, this drug should
be used during pregnancy only if clearly needed.
2. Nursing Mothers
Available animal data have shown excretion of linagliptin in milk at a milk-to-plasma
ratio of 4:1. It is not known whether this drug is excreted in human milk.
Because many drugs are excreted in human milk, caution should be exercised
when TRADJENTA is administered to a nursing woman.
3. Pediatric Use
Safety and effectiveness of TRADJENTA in pediatric patients have not been established.
4. Geriatric Use
No overall differences in safety or effectiveness were observed between patients
65 years and over and younger patients. Therefore, no dose adjustment is
recommended in the elderly population. While clinical studies of linagliptin
have not identified differences in response between the elderly and younger
patients, greater sensitivity of some older individuals cannot be ruled out.
Manufacturer Details