What medications should be held in a patient with elevated Creatine Kinase (CK) levels?

Medications to Hold When CK is Elevated

Statins should be discontinued immediately if CK levels exceed 10 times the upper limit of normal (ULN) in symptomatic patients, or if CK levels are markedly elevated (>10x ULN) even in asymptomatic patients. 1

Medication Management Algorithm for Elevated CK

Statins

1. When to discontinue statins:

   • CK >10x ULN with muscle symptoms (pain, tenderness, weakness) 1
   • CK >10x ULN even without symptoms (in asymptomatic patients) 1
   • Presence of unexplained severe muscle symptoms or fatigue even before CK results 1
   • Suspected immune-mediated necrotizing myopathy (IMNM) 2

2. When to consider temporary discontinuation or dose reduction:

   • Mild to moderate muscle symptoms with CK 3-10x ULN 1
   • Progressive elevations of CK on serial measurements with muscle discomfort 1
   • During hospitalization for major surgery 1
   • Acute conditions with high risk of developing renal failure (sepsis, shock, severe hypovolemia, major surgery, trauma, severe metabolic disorders) 2

Other Medications to Consider Holding

1. Fibrates (especially gemfibrozil):

   • Should be discontinued if used in combination with statins when CK is elevated 1
   • Particularly high risk when combined with statins

2. Niacin:

   • Consider discontinuation when used with statins and CK elevation occurs 1, 2

3. Tyrosine Kinase Inhibitors (TKIs):

   • Consider dose reduction with severe symptomatic CK elevation 3
   • Particularly brigatinib, binimetinib, cobimetinib-vemurafenib combination, aumolertinib, and sunvozertinib

4. Antipsychotics (especially second-generation):

   • Consider holding if significant CK elevation occurs 4
   • Olanzapine has been specifically associated with CK elevation

Monitoring and Follow-up

1. For patients with elevated CK:

   • Monitor CK levels weekly until resolution if values are 3-10x ULN 1
   • Evaluate for other causes of CK elevation (exercise, trauma, seizures, hypothyroidism) 1
   • Check thyroid-stimulating hormone (TSH) levels in patients with muscle symptoms 1
   • Consider checking vitamin D levels, as insufficient vitamin D (<30 ng/mL) is associated with greater CK increases in statin-treated patients 5

2. Reintroduction of medications:

   • After CK normalizes, consider restarting with a lower dose or different agent 1
   • For statins, if muscle symptoms resolve and no contraindication exists, consider a lower dose of the same statin or a different statin 1

Special Considerations and Pitfalls

• Beware of multiple contributing factors: CK elevation can be multifactorial and much more severe when multiple causes are present (e.g., drug interactions, cocaine, alcohol, infections) 6

• Avoid misdiagnosis: Not all CK elevations indicate neuroleptic malignant syndrome; intramuscular injections and physical restraints can also cause CK elevation 7

• High-risk patients requiring closer monitoring:

  • Advanced age (especially >80 years)
  • Small body frame and frailty
  • Multisystem disease (especially chronic renal insufficiency)
  • Patients on multiple medications
  • Perioperative periods 1

• Drug interactions: Pay special attention to medications that interact with statins and may increase myopathy risk, including cyclosporine, macrolide antibiotics, antifungal agents, and cytochrome P-450 inhibitors 1

By following this algorithm, you can appropriately manage medications in patients with elevated CK levels to reduce the risk of serious complications such as rhabdomyolysis and acute kidney injury.