Drug Interaction

Urgency / Type of response

Background / Requestor info

Determine question(s)

Classify question

• Drug-drug interaction

• patient has gone home without med while pharmacist clarifies prescription
• simvastatin is not an urgent med
• within 24 hours, so pharmacist can contact MD if needed
• call pharmacist back / fax evidence if found

• community pharmacist filling a prescription for simvastatin
• interaction appeared in dispensing software
• does not have enough information about interaction to act

Is there any evidence to support a drug interaction between risperidone and simvastatin? If yes, what is the severity and how should it be managed?

Is there a drug interaction between risperidone and simvastatin?

Martindale's

CPS

AHFS DI

Hansten & Horn

Drug Interactions: Analysis and Management

Risperdal monograph

• no mention of simvastatin

Zocor monograph

• no mention of risperidone

No interactions listed

Risperidone

• no interaction listed

Simvastatin

• no interaction listed

Stockley's Drug Interactions 8th ed

Lexi Interact in Lexi-Comp Online

Drug Interaction Facts

by Facts & Comparisons

No interactions listed

No interactions identified

No interaction listed

PubMed search

Micromedex

Warning:

Concurrent use of RISPERIDONE and SIMVASTATIN may result in increased simvastatin serum concentrations with an increased risk of myopathy or rhabdomyolysis.

Clinical Management:

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.

Probable Mechanism: competitive inhibition of cytochrome P450-3A4-mediated simvastatin metabolism

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 (Webber et al, 2004).

Literature:

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 (Webber et al, 2004).

Reference(s):

Webber MA, Mahmud W, Lightfoot JD et al: Rhabdomyolysis and compartment syndrome with coadministration of risperidone and simvastatin. J Psychopharmacol September, 2004; 18(3):432-434.

simvastatin AND risperidone AND drug interaction Limits: English

J Psychopharmacol. 2004 Sep;18(3):432-4.

Rhabdomyolysis and compartment syndrome with coadministration of risperidone and simvastatin. Webber MA, Mahmud W, Lightfoot JD, Shekhar A.

We report a case of rhabdomyolysis and acute compartment syndrome of the lower extremity in a schizophrenic patient taking risperidone following the addition of simvastatin to treat hyperlipidemia. We suspect that disrupted drug metabolism, resulting from interactions with cytochrome P450 enzymes, rapidly elevated drug plasma levels, which then led to muscle toxicity. Clinicians who pharmacologically treat medical comorbidities in patients receiving atypical antipsychotics must be proactive in anticipating potential drug-drug interactions.

PMID: 15358990