Juvisync Disease Interactions

The use of most HMG-CoA reductase inhibitors is contraindicated in patients with active liver disease, decompensated cirrhosis, or unexplained persistent elevations of serum transaminases. HMG-CoA reductase inhibitors are extensively metabolized by the liver. Decreased drug metabolism may lead to accumulation and increased risk of toxicity, including biochemical abnormalities of liver function and, rarely, jaundice, hepatitis, cirrhosis, fatty change in the liver, and fulminant hepatic necrosis. Therapy with HMG-CoA reductase inhibitors should be administered cautiously in patients with a history of liver disease and/or heavy alcohol use. A lower initial dosage may be appropriate, and clinical monitoring of liver transaminase levels according to the individual manufacturer product information is recommended. Patients who develop elevated ALT or AST levels during therapy should be monitored until abnormalities resolve. If an increase above 3 times the upper limit of normal persists, consideration should be given to a reduction in dosage or withdrawal of therapy.

Although simvastatin itself is not eliminated by the kidney, the plasma concentrations of total HMG-CoA reductase inhibitors after a single dose of simvastatin may be increased in patients with significant renal impairment, presumably due to the accumulation of active metabolites. Increased HMG-CoA reductase inhibitory activity may be associated with a greater risk of adverse effects, including hepatic and musculoskeletal toxicities. Therapy with simvastatin should be administered cautiously at a reduced dosage in patients with severe renal impairment. Close clinical monitoring is recommended.

It is recommended to assess renal function prior to initiating treatment with DPP-4 inhibitors and periodically thereafter. Patients with moderate to severe renal insufficiency and end stage renal dysfunction will require a dose adjustment. Linagliptin will not require a dose adjustment per manufacturer's information. Additionally, there have been postmarketing reports of worsening renal function in some patients with renal insufficiency taking sitagliptin at inappropriate doses.

There have been postmarketing reports of acute pancreatitis in patients taking DPP-4 inhibitors. These drugs should be used with caution in patients with a history of pancreatitis or pancreatic disease, although it is unknown if they are at increased risk. Patients should be observed for signs and symptoms of pancreatitis during treatment. If pancreatitis is suspected, treatment should be discontinued immediately and appropriate management should be initiated.

Cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) have been observed in patients receiving statins. The reports are usually not serious, and reversible upon statin discontinuation. Caution is recommended when using these agents in patients with cognitive impairment.

Increases in hemoglobin A1c and fasting serum glucose levels have been reported with the use of certain HMG-CoA reductase inhibitors. Caution should be exercised when using these agents in diabetic patients and close monitoring is recommended.

Some HMG-CoA reductase inhibitors (e.g., fluvastatin) have not been studied in patients with severe renal dysfunction or end-stage renal disease. Some others (e.g., pitavastatin, simvastatin) require a dose reduction when used in this group of patients. Caution and close monitoring are advised when using these drugs in patients with renal dysfunction.

HMG-CoA reductase inhibitors may cause myopathy and rhabdomyolysis; acute renal failure secondary to myoglobinuria and rare fatalities have occurred due to rhabdomyolysis in patients treated with statins. The myopathy may be dose-related and is characterized by unexplained muscle weakness, pain, or tenderness accompanied by increases in creatine phosphokinase (CPK) values exceeding 10 times the upper limit of normal. Therapy with HMG-CoA reductase inhibitors should be administered cautiously in patients with preexisting myopathy, in those with predisposing factors for myopathy, or with a history of myoneural disorder, since it may delay the recognition or confound the diagnosis of a drug-induced musculoskeletal effect. Patients should be advised to report promptly any unusual muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Periodic CPK determinations may be considered in some patients, although the value of such monitoring is uncertain. HMG-CoA reductase inhibitor therapy should be withdrawn if markedly elevated CPK levels occur or if drug-related myopathy is diagnosed or suspected.

Consider the risks and benefits of sitagliptin prior to initiating treatment in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment. Observe these patients for signs and symptoms of heart failure during therapy.

Sitagliptin has not been studied in patients with severe liver dysfunction