Clinically Important Dug Interactions in Hyperlipidemia

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Antihyperlipidemic drugs significantly interact with drugs such as CYP3A4 Inhibitors (Azole Antifungals (Fluconazole, etc), Macrolide Antibiotics (Clarithromycin, etc), Grape Fruit Juice (GFJ), etc.

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Clinically Important Drug Interactions in Hyperlipidemia:

Clinically Important Drug Interactions in Hyperlipidemia Dr. P.Naina Mohamed PhD Pharmacologist

Introduction:

Introduction An adverse drug interaction is defined as an interaction between one or more coadministered medications which leads to decreased therapeutic efficacy or elevated risk of toxicity of any of the coadministered medications. Drug interactions can be caused by Prescription and Over-the-counter (OTC) medications, herbal products or vitamins, foods, diseases, and genetics (family history). It is estimated that people over 65 take an average of seven drugs at any one time to treat a variety of illnesses including higher cholesterol, diabetes, hypertension, etc. With this amount of medicine use, the probability that a person will take two prescribed drugs that may interact with one another is very high.

Hyperlipidemia:

Hyperlipidemia Abnormally elevated levels of lipids (Cholesterol ( Hypercholesterolemia ) or Triglycerides ( Hypertryglyceridemia )) is termed as Hyperlipidemia . Types of Hyperlipidemia : Primary (Familial) Hyperlipidemia Hypolipoproteinemia type I Hyperlipoproteinemia type II Hypolipoproteinemia Type Iia Hypolipoproteinemia Type Iib Hyperlipoproteinemia type III Hyperlipoproteinemia type IV Hyperlipoproteinemia type V Secondary (Acquired) Hyperlipidemia – Associated with Fatty foods, Physical inactivity, Obesity and Diabetes.

Antihyperlipidemics:

Antihyperlipidemics Statins (HMG CoA Reductase Inhibitors ) Simvastain , Lovastatin, Atorvastatin, Rosuvastatin , Pravastatin, etc. Fibrates Gemfibrozil, Clofibrate , Fenofibrate , etc. Bile acid Sequestrants Cholestyramine, Colestipol and Colesevelam Niacin Ezetimibe Lomitapide

Contraindicated Combinations:

Contraindicated Combinations Simvastatin or Lovastatin + CYP3A4 Inhibitors (Azole Antifungals ( Fluconazole, etc ), Macrolide Antibiotics (Clarithromycin, etc ), Protease Inhibitors – Antivirals (Ritonavir, etc ) etc ) Simvastatin + Gemfibrozil Gemfibrozil + Repaglinide Gemfibrozil + Dasabuvir Fibrates + Ciprofibrate Lomitapide + CYP3A4 Inhibitors (Azole antifungals – Ketoconazole , Macrolide antibiotics – Clarithromycin , etc )

Combinations elevating the risk of Rhabdomyolysis :

Combinations elevating the risk of Rhabdomyolysis Simvastatin or Lovastatin + CYP3A4 Inhibitors (Azole Antifungals ( Fluconazole, etc ), Macrolide Antibiotics (Clarithromycin, etc ), Protease Inhibitors – Antivirals (Ritonavir, etc ) etc ) Simvastatin + Gemfibrozil Fibrates + Ciprofibrate Statins + Warfarin Statins + Colchicine Statins + Daptomycin Statins + Grapefruit Juice Statins + Niacin Simvastatin + Ciprofloxacin Simvastatin + Amlodipine Simvastatin + Tadalafil Simvastatin+ Cranberry Juice

Statins & CYP3A4 Inhibitors :

Statins & CYP3A4 Inhibitors Concomitant use of Statins like Simvastatin or Lovastatin and CYP3A4 Inhibitors is Contraindicated . Monitor the patients for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness) and creatine kinase (CK) levels, if other statins such as Atorvastatin, Fluvastatin or Cerivastatin used along with CYP3A4 Inhbitors . http://onlinelibrary.wiley.com/doi/10.1002/pds.3199/full

Statins & Fibrates:

Statins & Fibrates Use of Simvastatin with Gemfibrozil is Contraindicated . Concomitant use of other Statins and fibrates must be undertaken cautiously. Monitor liver function and creatine kinase regularly. To minimise peak dose interactions, fibrates should be prescribed in the morning and statins at night. http :// www.ncbi.nlm.nih.gov/pubmed/14682608

Gemfibrozil & Repaglinide :

Gemfibrozil & Repaglinide If the combination of Gemfibrozil and Repaglinide is considered clinically necessary, the dose of Repaglinide should be reduced and blood glucose concentrations carefully monitored. http ://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2010.03772.x/abstract;jsessionid=48F9DF92C02827B672F706A516086D2B.f03t03

Gemfibrozil & Dasabuvir :

Gemfibrozil & Dasabuvir Concomitant use of D asabuvir and Gemfibrozil is contraindicated due to a 10-fold increase in D asabuvir concentrations and an increased risk of QT prolongation. http ://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm175927.htm

Fibrates & Ciprofibrate:

Fibrates & Ciprofibrate The combined use of Fibrates and Ciprofibrate is contraindicated due to an increased risk of rhabdomyolysis and myoglobulinuria . https://www.medicines.org.uk/emc/medicine/22264

Lomitapide & CYP3A4 Inhibitors :

Lomitapide & CYP3A4 Inhibitors The concomitant use of L omitapide and a CYP3A4 inhibitor is contraindicated . If treatment with a CYP3A4 inhibitor is unavoidable, discontinue lomitapide during the course of treatment.

Statins & CYP3A4 Inducers:

Statins & CYP3A4 Inducers Adjust the dose of statins, if statins and CYP3A4 inducers are used concomitantly. http://onlinelibrary.wiley.com/doi/10.1016/j.clpt.2006.09.003/abstract

Statins + Warfarin:

Statins + Warfarin Other statins like Fluvastatin , Rosuvastatin and Lovastatin interact with Warfarin and elevate the bleeding risk moderately. The INR (International normalized ratio should be closely monitored in patients taking statins and warfarin. Monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness) and creatine kinase (CK) levels. http :// onlinelibrary.wiley.com/doi/10.1592/phco.24.2.285.33137/abstract

Statins & Colchicine :

Statins & Colchicine Monitor patients for signs and symptoms of myopathy or rhabdomyolysis, if concomitant use of these drugs is necessary, especially during initial therapy . http://onlinelibrary.wiley.com/doi/10.1002/psb.200617117/pdf

Statins & Daptomycin :

Statins & Daptomycin Monitor patients for CPK levels and symptoms of myopathy including muscle pain or weakness. http://aop.sagepub.com/content/48/3/320.long

Statins & Grapefruit Juice:

Statins & Grapefruit Juice The concomitant use of Statins (Simvastatin, Lovastatin and Atorvastatin) with grapefruit juice should be avoided. http :// www.nature.com/ejcn/journal/v58/n1/full/1601736a.html

Simvastatin & Ciprofloxacin:

Simvastatin & Ciprofloxacin Monitor the patients for signs and symptoms of myopathy or rhabdomyolysis, if Simvastatin and Ciprofloxacin (Weak CYP3A4 inhibitor) are used concomitantly. http://www.ncbi.nlm.nih.gov/pubmed/19151423

Simvastatin & Amlodipine:

Simvastatin & Amlodipine The dose of simvastatin should not exceed 20 mg/day when both these drugs used together. Monitor the patients for signs and symptoms of myopathy or rhabdomyolysis. http:// www.nature.com/hr/journal/v28/n3/full/hr200529a.html

Simvastatin & Tadalafil:

Simvastatin & Tadalafil Avoid using Simvastatin and Tadalafil concomitantly. Monitor patients for symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness), if concurrent therapy is required . http ://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728614 /

Simvastatin & Cranberry Juice:

Simvastatin & Cranberry Juice Patients should report the healthcare professional regarding unexplained muscle pain or symptoms of hepatitis, such as yellow skin or eyes, dark-colored urine, or pale stools, while taking Simvastatin and Cranberry juice tigether . http :// www.consultant360.com/articles/interaction-between-simvastatin-and-cranberry-juice-elder

Niacin & Statins:

Niacin & Statins If coadministration of Niacin and Statins is required, monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (Muscle pain, Tenderness , or weakness ). Periodic creatine kinase (CK) determinations may be advisable . http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110829 /

Fibrates & Sulfonylureas:

Fibrates & Sulfonylureas Closely monitor for hypoglycemia, if concomitant use is required. http://onlinelibrary.wiley.com/doi/10.1002/cpt.297/abstract

Bile acid sequestrants & Ezetimibe or Bezafibrate:

Bile acid sequestrants & Ezetimibe or Bezafibrate Ezetimibe or Bezafibrate should be administered at least two hours before or four hours after taking a bile acid sequestrant . http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110829/

Ezetimibe & Fibrates:

Ezetimibe & Fibrates Coadministration of Ezetimibe and a Fibrate except fenofibrate , is not recommended. https:// www.merck.com/product/usa/pi_circulars/z/zetia/zetia_pi.pdf

Ezetimibe & Warfarin:

Ezetimibe & Warfarin Frequent monitoring of PT/INR is recommended, if ezetimibe and warfarin are used concomitantly. Warfarin dosage should be adjusted accordingly. http:// link.springer.com/article/10.1007/s00380-016-0832-z

Niacin & Warfarin:

Niacin & Warfarin More frequent monitoring of INR and/or prothrombin time is recommended, if concomitant therapy is required. http:// aop.sagepub.com/content/45/11/e58.long

Lomitapide & Warfarin:

Lomitapide & Warfarin The INR of the patients receiving concurrent lomitapide and warfarin therapy, should be monitored regularly and adjust warfarin dose accordingly. http :// www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM323841.pdf

Lomitapide & Simvastatin or Lovastatin :

Lomitapide & Simvastatin or Lovastatin Concomitant use of Lomitapide and Simvastatin or Lovastatin, warrants the monitoring of patients for the symptoms of myopathy. http :// link.springer.com/chapter/10.1007%2F978-3-319-20433-8_8

Lomitapide + Grape Fruit Juice :

Lomitapide + Grape Fruit Juice Patients receiving lomitapide should avoid the ingestion of Grapefruit juice. http:// www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM428212.pdf

Lomitapide & Alcohol :

Lomitapide & Alcohol The patients taking lomitapide should be instructed about the elevated risk of liver injury associated to Alcohol. http:// circ.ahajournals.org/content/129/9/1022

Conclusion:

Conclusion The occurrence of significant morbidity and mortality can be reduced by minimizing the risk for drug interactions. The hyperlipidemic patients should bring a list of all the drugs they are taking including prescription drugs, over-the-counter drugs, and any supplements, herbal or otherwise, during their visit to the D octor or P harmacist . The risk of adverse effects could be reduced and the quality of life for patients improved by healthcare professionals through the screening, education, and follow up on suspected drug interactions. If possible, the hyperlipidemic patients are recommended to fill all their prescriptions at one pharmacy.

References:

References Stockley’s Drug Interactions, 9e Karen Baxter Hurst's The Heart, 13e Valentin Fuster , Richard A. Walsh, Robert A. Harrington Basic & Clinical Pharmacology, 12e Bertram G. Katzung , Susan B. Masters, Anthony J. Trevor http://www.micromedexsolutions.com

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