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Drug details for : JANUVIA Film-Coated Tablets
| Drug class description : | DPP-4 Inhibitor |
| Generic Name : | Sitagliptin |
| Drug description : | Film-coated tablet (tablet). Round, beige film-coated tablet with “277” on one side. |
| Presentation : | Each tablet contains sitagliptin phosphate monohydrate, equivalent to 100 mg sitagliptin. |
| Indications : | JANUVIA is indicated in patients with type 2 diabetes mellitus to improve glycaemic control in combination with metformin when diet and exercise, plus metformin do not provide adequate glycaemic control. For patients with type 2 diabetes mellitus in whom use of a PPAR? agonist (i.e. a thiazolidinedione) is appropriate, JANUVIA is indicated in combination with the PPAR? agonist when diet and exercise plus the PPAR? agonist alone, do not provide adequate glycaemic control. |
| Adult Dosage : | The dose of JANUVIA is 100 mg once daily. The dosage of metformin or PPAR? agonist should be maintained, and sitagliptin administered concomitantly. If a dose is missed, it should be taken as soon as the patient remembers. A double dose should not be taken on the same day. JANUVIA can be taken with or without food. Patients with renal insufficiency For patients with mild renal insufficiency (creatinine clearance [CrCl] 50 ml/min), no dosage adjustment for JANUVIA is required. Clinical study experience with JANUVIA in patients with moderate or severe renal insufficiency is limited. Therefore, use of JANUVIA is not recommended in this patient population. Patients with hepatic insufficiency No dosage adjustment is necessary for patients with mild to moderate hepatic insufficiency. JANUVIA has not been studied in patients with severe hepatic insufficiency. |
| Child Dosage : | JANUVIA is not recommended for use in children below 18 years of age due to a lack of data on its safety and efficacy. |
| Elderly Dosage : | No dosage adjustment is necessary based on age. Limited safety data is available in patients 75 years of age and care should be exercised. |
| Contra Indications : | Hypersensitivity to the active substance or to any of the excipients. |
| Special Precautions : | General: JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Hypoglycaemia: In clinical trials of JANUVIA as monotherapy and sitagliptin as part of combination therapy with metformin or pioglitazone, rates of hypoglycaemia reported with sitagliptin were similar to rates in patients taking placebo. The use of sitagliptin in combination with medicinal products known to cause hypoglycaemia, such as sulfonylureas or insulin, has not been adequately studied. Renal insufficiency: As the experience is limited, patients with moderate to severe renal insufficiency should not be treated with JANUVIA. |
| Interactions : | Effects of other medicinal products on sitagliptin Clinical data described below suggest that the risk for clinically meaningful interactions by co-administered medicinal products is low. Metformin : Co-administration of multiple twice-daily doses of 1,000 mg metformin with 50 mg sitagliptin did not meaningfully alter the pharmacokinetics of sitagliptin in patients with type 2 diabetes. Ciclosporin : A study was conducted to assess the effect of ciclosporin, a potent inhibitor of pglycoprotein, on the pharmacokinetics of sitagliptin. Co-administration of a single 100 mg oral dose of sitagliptin and a single 600 mg oral dose of ciclosporin increased the AUC and Cmax of sitagliptin by approximately 29 % and 68 %, respectively. These changes in sitagliptin pharmacokinetics were not considered to be clinically meaningful. The renal clearance of sitagliptin was not meaningfully altered. Therefore, meaningful interactions would not be expected with other pglycoprotein inhibitors. In vitro studies indicated that the primary enzyme responsible for the limited metabolism of sitagliptin is CYP3A4, with contribution from CYP2C8. In patients with normal renal function, metabolism, including via CYP3A4, plays only a small role in the clearance of sitagliptin. Metabolism may play a more significant role in the elimination of sitagliptin in the setting of severe renal insufficiency or ESRD. For this reason, it is possible that potent CYP3A4 inhibitors (i.e. ketoconazole, itraconazole, ritonavir, clarithromycin) could alter the phamacokinetics of sitagliptin in patients with severe renal insufficiency or ESRD. The effects of potent CYP3A4 inhibitors in the setting of renal insufficiency have not been assessed in a clinical study. In vitro transport studies showed that sitagliptin is a substrate for p-glycoprotein and OAT3. OAT3 mediated transport of sitagliptin was inhibited in vitro by probenecid, although the risk of clinically meaningful interactions is considered to be low. Concomitant administration of OAT3 inhibitors has not been evaluated in vivo. Effects of sitagliptin on other medicinal products In vitro data suggest that sitagliptin does not inhibit nor induce CYP450 isoenzymes. In clinical studies, sitagliptin did not meaningfully alter the pharmacokinetics of metformin, glyburide, simvastatin, rosiglitazone, warfarin, or oral contraceptives, providing in vivo evidence of a low propensity for causing interactions with substrates of CYP3A4, CYP2C8, CYP2C9, and organic cationic transporter (OCT). Sitagliptin had a small effect on plasma digoxin concentrations, and may be a mild inhibitor of p-glycoprotein in vivo. Digoxin: Sitagliptin had a small effect on plasma digoxin concentrations. Following administration of 0.25 mg digoxin concomitantly with 100 mg of JANUVIA daily for 10 days, the plasma AUC of digoxin was increased on average by 11 %, and the plasma Cmax on average by 18 %. No dosage adjustment of digoxin is recommended. However, patients at risk of digoxin toxicity should be monitored for this when sitagliptin and digoxin are administered concomitantly. Pregnancy: There are no adequate data from the use of JANUVIA 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, JANUVIA should not be used during pregnancy. Lactation: It is unknown whether sitagliptin is excreted in human breast milk. Animal studies have shown excretion of sitagliptin in breast milk. JANUVIA should not be used during breast-feeding. |
| Adverse Reactions : | In 9 large clinical trials of up to 2 years in duration, over 2,700 patients have received treatment with JANUVIA 100 mg per day alone or in combination with metformin, a sulfonylurea (with or without metformin) or a PPAR? agent. In these trials, the rate of discontinuation due to adverse experiences considered drug-related was 0.8 % with 100 mg per day and 1.5 % with other treatments. No adverse reactions considered as drug-related were reported in patients treated with sitagliptin occurring in excess > 0.2 % and difference> 1 patient) of that in patients treated with control. COMBINATION WITH METFORMIN In a 24-week study of sitagliptin 100 mg in combination with metformin, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin/metformin compared to treatment with placebo/metformin was 9.3 % and 10.1 %, respectively. Adverse reactions considered as drug-related reported in patients treated with sitagliptin occurring in excess (> 0.2 % and difference> 1 patient) of that in patients treated with placebo are as follows: Frequencies are defined as: very common ( 1/10); common ( 1/100, < 1/10); uncommon ( 1/1,000, < 1/100); rare ( 1/10,000, < 1/1,000); and very rare ( < 1/10,000). Nervous system disorders: Uncommon: somnolence. Gastro-intestinal disorders: Common: nausea, Uncommon: upper abdominal pain, diarrhoea. Investigations: Uncommon: blood glucose decreased. In a 1-year study of sitagliptin 100 mg in combination with metformin, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin/metformin compared to sulfonylurea/metformin was 14.5 % and 30.3 %, respectively. In pooled studies of up to 1 year in duration comparing sitagliptin/metformin to a sulfonylurea agent/metformin, adverse reactions considered as drug-related reported in patients treated with sitagliptin 100 mg occurring in excess > 0.2 % and difference> 1 patient) of that in patients receiving the sulfonylurea agent are as follows: Metabolism and nutrition disorders: Uncommon: anorexia. Investigations: Uncommon: weight decreased COMBINATION WITH A PPAR ? AGENT (pioglitazone) In a 24-week study of the combination of sitagliptin 100 mg and pioglitazone, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin/pioglitazone compared to patients treated with placebo/pioglitazone was 9.1 % and 9.0 %, respectively. Adverse reactions considered as drug-related reported in patients treated with JANUVIA occurring in excess > 0.2 % and difference> 1 patient) of that in patients receiving placebo are as follows: Metabolism and nutrition disorders: Common: hypoglycaemia Gastrointestinal disorders: Common: flatulence General disorders: Common: peripheral oedema In addition, in monotherapy studies of up to 24 weeks in duration of sitagliptin 100 mg alone compared to placebo, adverse reactions considered as drug-related reported in patients treated with sitagliptin in excess > 0.2 % and difference> 1 patient) of that in patients receiving placebo are headache, hypoglycaemia, constipation, and dizziness. In addition to the drug-related adverse experiences described above, adverse experiences reported regardless of causal relationship to medication and occurring in at least 5 % and more commonly in patients treated with JANUVIA included upper respiratory tract infection and nasopharyngitis. Additional adverse experiences reported regardless of causal relationship to medication that occurred more frequently in patients treated with JANUVIA (not reaching the 5% level, but occurring with an incidence of> 0.5% higher with JANUVIA than that in the control group) included osteoarthritis and pain in extremity. Across clinical studies, a small increase in white blood cell count (approximately 200 cells/microl difference in WBC vs placebo; mean baseline WBC approximately 6600 cells/microl) was observed due to an increase in neutrophils. This observation was seen in most but not all studies. This change in laboratory parameters is not considered to be clinically relevant. No clinically meaningful changes in vital signs or in ECG (including in QTc interval) were observed with JANUVIA treatment. |
| Manufacturer : | Merck Sharp & Dohme |
| Drug Availability : | (POM) |
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