Can olanzapine (Zyprexa) or lorazepam (Ativan) cause rhabdomyolysis?

Olanzapine and Lorazepam as Potential Causes of Rhabdomyolysis

Yes, both olanzapine and lorazepam can cause rhabdomyolysis, with olanzapine having more documented cases of this serious adverse effect.

Olanzapine and Rhabdomyolysis

Olanzapine has been clearly documented to cause rhabdomyolysis, even after long-term stable use:

• Olanzapine can cause severe rhabdomyolysis with creatine kinase (CK) levels reported as high as 345,125 U/L 1
• Cases of delayed-onset rhabdomyolysis have been reported even after 8+ years of stable olanzapine use 1
• Rhabdomyolysis with olanzapine can occur in the absence of neuroleptic malignant syndrome (NMS) 1, 2
• Pediatric and adolescent patients are also at risk, with olanzapine being reported more frequently for rhabdomyolysis in this population compared to other antipsychotics 3

Warning Signs and Risk Factors for Olanzapine-Induced Rhabdomyolysis

• Early warning signs include:

  • Muscle pain and weakness
  • Abdominal pain
  • General weakness
  • Dark urine 3

• Risk factors and triggers include:

  • Recent dose increases
  • Addition of new medications
  • Switching between antipsychotics
  • Known risk factors for rhabdomyolysis 3

Lorazepam and Rhabdomyolysis

While direct evidence linking lorazepam to rhabdomyolysis is less robust than for olanzapine, lorazepam carries specific risks:

• Parenteral formulations of lorazepam contain propylene glycol as a diluent, which can cause toxicity manifesting as metabolic acidosis and acute kidney injury 4
• Propylene glycol toxicity can occur at total daily IV doses as low as 1 mg/kg 4
• An osmol gap greater than 10-12 mOsm/L may help identify patients with significant propylene glycol accumulation 4

Clinical Implications and Monitoring

For Olanzapine:

• Monitor for muscle pain, unexplained fatigue, or weakness in patients taking olanzapine
• Obtain prompt CK measurement if these symptoms occur
• Increased vigilance during the first 2 months of treatment, dose adjustments, or when adding/switching medications 3
• Consider alternative medications in patients with risk factors for rhabdomyolysis

For Lorazepam:

• Monitor for signs of propylene glycol toxicity, especially with IV administration
• Consider measuring serum osmol gap in patients receiving higher doses
• Use with caution in patients with renal dysfunction as elimination half-life and clinical effects may be prolonged 4
• Be aware that lorazepam clearance is reduced in patients with hepatic dysfunction, elderly patients, and when administered with medications that inhibit cytochrome P450 enzyme systems 4

Management Considerations

If rhabdomyolysis is suspected:

• Immediately discontinue the suspected causative agent
• Initiate high-volume alkaline diuresis to prevent acute renal failure
• Monitor CK levels, renal function, and electrolytes
• Consider switching to alternative medications with lower risk profiles

In cases where antipsychotic therapy must be continued despite previous rhabdomyolysis, cautious switching to a different atypical antipsychotic may be considered, though close monitoring is essential 5.

Important Caveats

• Rhabdomyolysis is considered a rare adverse effect (<1%) of olanzapine 2
• The risk appears higher during medication changes, dose adjustments, or in the presence of other risk factors
• Seemingly mild symptoms like muscle pain or weakness should not be dismissed in patients taking these medications

Healthcare providers should maintain a high index of suspicion for rhabdomyolysis when patients on olanzapine or lorazepam present with muscle pain, weakness, or dark urine, especially during periods of medication adjustment or in the presence of other risk factors.