Juxtapid Capsules and Simvastatin orally disintegrating tablet

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Talk to your doctor before using simvastatin together with lomitapide. Combining these medications may significantly increase the blood levels of simvastatin. This can increase the risk of side effects such as liver damage and a rare but serious condition called rhabdomyolysis that involves the breakdown of skeletal muscle tissue. In some cases, rhabdomyolysis can cause kidney damage and even death. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications, or your doctor may prescribe alternative medications that do not interact. Let your doctor know immediately if you have unexplained muscle pain, tenderness, or weakness during treatment with simvastatin or similar medications, especially if these symptoms are accompanied by fever or dark colored urine. You should also seek immediate medical attention if you develop fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

ADJUST DOSE: Coadministration with lomitapide may increase the plasma concentrations of simvastatin and lovastatin as well as their pharmacologically active acid metabolites. The proposed mechanism is lomitapide inhibition of CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of simvastatin and lovastatin and their metabolites. When a single 40 mg dose of simvastatin was coadministered with lomitapide 60 mg once daily for 7 days, simvastatin peak plasma concentration (Cmax) increased by 102% and systemic exposure (AUC) increased by 99%, while simvastatin acid Cmax and AUC increased by 57% and 71%, respectively. When a single 20 mg dose of simvastatin was coadministered with lomitapide 10 mg once daily for 7 days, the Cmax and AUC of simvastatin increased by 65% and 62%, respectively, while that of simvastatin acid increased by 35% and 39%, respectively. Although not studied, the interaction is also expected to occur with lovastatin due to its similar metabolic profile to simvastatin. Clinically, high levels of statin or HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

MANAGEMENT: Simvastatin dosage should be reduced by 50% when initiating therapy with lomitapide. While taking lomitapide, the dosage of simvastatin should be limited to 20 mg daily, or 40 mg daily for patients who have previously tolerated simvastatin 80 mg daily for at least one year without evidence of muscle toxicity. The same precaution with respect to dosage reduction may be applicable to lovastatin or red yeast rice (which contains lovastatin), although clinical data are lacking. Alternatively, fluvastatin, pitavastatin, pravastatin, or rosuvastatin may be given without dosage adjustment in patients receiving lomitapide, since they are not metabolized by CYP450 3A4. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.

MONITOR CLOSELY: Coadministration of lomitapide with other agents known to induce hepatotoxicity such as statins may potentiate the risk of liver injury. In a premarketing clinical trial, 34% (10/29) of patients treated with lomitapide had at least one elevation in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 3 times the upper limit of normal (ULN) or greater, and 14% (4/29) had at least one elevation in ALT or AST 5 times ULN or greater. There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR), or alkaline phosphatase. Lomitapide also increases hepatic fat, with or without concomitant increases in transaminases. In the same study, the median absolute increase in hepatic fat was 6% after both 26 and 78 weeks of treatment, from 1% at baseline, measured by magnetic resonance spectroscopy. Hepatic steatosis associated with lomitapide may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis. Clinical data suggest that hepatic fat accumulation is reversible after stopping treatment with lomitapide, although the long-term consequences are unknown.

MANAGEMENT: Caution is advised if lomitapide must be used in patients who are currently receiving or have recently received treatment with other hepatotoxic agents, and vice versa. Patients treated with lomitapide should have serum ALT, AST, alkaline phosphatase, and total bilirubin monitored prior to initiation of treatment and regularly during treatment in accordance with the product labeling, and the dosing adjusted or interrupted as necessary. Since alcohol may increase levels of hepatic fat and induce or exacerbate liver injury, the manufacturer recommends that patients taking lomitapide not consume more than one alcoholic drink per day. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice.

Juxtapid Capsules

Generic Name: lomitapide

Brand name: Juxtapid

Synonyms: Lomitapide

What is Juxtapid Capsules?

Simvastatin orally disintegrating tablet

Generic Name: simvastatin

Brand name: Zocor, Flolipid

Synonyms: Simvastatin

What is Simvastatin orally disintegrating tablet?