Risperidone with Simvastatin Interaction Details

Brand Names Associated with Risperidone

Brand Names Associated with Simvastatin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 10, 2023

Interaction Effect

Increased simvastatin serum concentrations with an increased risk of myopathy or rhabdomyolysis

Interaction Summary

Concomitant use of risperiDONE and simvastatin may increase the bioavailability of simvastatin. RisperiDONE and simvastation are both metabolized by cytochrome P450-3A4 (CYP3A4). Although risperiDONE is predominantly metabolized by CYP2D6, individuals having a slow metabolizer phenotype due to possession of a CYP2D6 polymorphic genotype may convert to CYP3A4 as the primary isoform for risperiDONE metabolism. As a result, risperiDONE may competitively inhibit simvastatin metabolism, thereby increasing the risk of myopathy and rhabdomyolysis. In a case report, a patient developed rhabdomyolysis complicated by acute compartment syndrome after receiving simvastatin concomitantly with risperiDONE.

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Concomitant use of risperiDONE with simvastatin is not recommended. If concurrent therapy is required, monitor patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness). Monitor creatine kinase (CK) levels and discontinue use if CK levels show a marked increase, or if myopathy or rhabdomyolysis is diagnosed or suspected.

Mechanism Of Interaction

Competitive inhibition of cytochrome P450-3A4-mediated simvastatin metabolism

Literature Reports

A) Rhabdomyolysis occurred in a 22-year-old man after simvastatin 10 milligrams (mg) daily was added to a stable treatment regimen comprising clonazepam 2 mg and risperiDONE 4 mg daily. Approximately 5 days after beginning simvastatin treatment, the patient presented with right ankle and heel pain. Over the next 24 hours, the pain advanced proximally and increased in severity, with the extremity showing signs of warmth, erythema, rash, and pronounced tenseness of the distal muscle compartments. Serum creatine kinase (CK), aspartate and alanine aminotransferase concentrations were 12, 408 units/liter (L), 296 International Units (IU)/L, and 97 IU/L, respectively. CK concentrations peaked at 25, 498 units/L. Simvastatin was withdrawn and the patient required emergent decompression fasciotomies due to acute compartment syndrome of the right lower extremity. RisperiDONE and clonazepam were continued without incident .

Risperidone Overview

• Risperidone is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions) in adults and teenagers 13 years of age and older. It is also used to treat episodes of mania (frenzied, abnormally excited, or irritated mood) or mixed episodes (symptoms of mania and depression that happen together) in adults and in teenagers and children 10 years of age and older with bipolar disorder (manic depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Risperidone is also used to treat behavior problems such as aggression, self-injury, and sudden mood changes in teenagers and children 5 to 16 years of age who have autism (a condition that causes repetitive behavior, difficulty interacting with others, and problems with communication). Risperidone is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain.

Simvastatin Overview

• Simvastatin is used together with diet, weight-loss, and exercise to reduce the risk of heart attack and stroke and to decrease the chance that heart surgery will be needed in people who have heart disease or who are at risk of developing heart disease. Simvastatin is also used to decrease the amount of fatty substances such as low-density lipoprotein (LDL) cholesterol (''bad cholesterol'') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol (''good cholesterol'') in the blood. Simvastatin may also be used to decrease the amount of cholesterol and other fatty substances in the blood in children and teenagers 10 to 17 years of age who have familial heterozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Simvastatin is in a class of medications called HMG-CoA reductase inhibitors (statins). It works by slowing the production of cholesterol in the body to decrease the amount of cholesterol that may build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.

• Accumulation of cholesterol and fats along the walls of your arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to your heart, brain, and other parts of your body. Lowering your blood level of cholesterol and fats with simvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.

Return To Our Drug Interaction Homepage

Feedback, Question Or Comment About This Information?

Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.