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Does Crestor (rosuvastatin) affect sleep?

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At a glance

  • Drug / rosuvastatin (Crestor), HMG-CoA reductase inhibitor, prescription only
  • Sleep-stage measurements in the label / none reported
  • Dosing time / any time of day, with or without food [1]
  • Morning vs evening / no AUC difference [1]
  • Peak level / 3 to 5 hours after a dose [1]
  • Half-life / about 19 hours [1]
  • Label trial reactions / headache 5.5% vs 5.0% placebo; myalgia 2.8% vs 1.3% [1]

What has been measured

Sleep architecture is what polysomnography records: how long it takes to fall asleep, time in REM and slow-wave sleep, and how often sleep breaks. The Crestor label's trial data contain no such results. What the label documents is dosing flexibility and the reactions reported in its placebo-controlled trials.

One documented difference between statins is chemistry. Rosuvastatin and pravastatin are relatively hydrophilic; simvastatin, lovastatin, atorvastatin, fluvastatin and pitavastatin are lipophilic [2]. Hydrophilic statins enter liver cells by active carrier-mediated transport rather than passive diffusion [2]. That review does not link this difference to sleep.

Does the time of day matter?

The Crestor label says the tablet can be taken at any time of day, with or without food, and states that AUC does not differ between evening and morning dosing [1]. Peak plasma concentration arrives 3 to 5 hours after a dose, and the half-life is about 19 hours [1].

What the trials recorded

In placebo-controlled studies of up to 12 weeks (placebo N=382; Crestor 5 to 40 mg N=744), reported reactions were headache 5.0% on placebo vs 5.5% on Crestor, nausea 3.1% vs 3.4%, myalgia 1.3% vs 2.8%, asthenia 2.6% vs 2.7%, and constipation 2.4% vs 2.4% [1]. These five are not a complete list of every reaction reported with rosuvastatin, so they do not settle whether sleep disturbance occurs.

Groups with higher exposure

SLCO1B1 encodes OATP1B1, and genetic variation in SLCO1B1 can alter rosuvastatin exposure [4]. The Crestor label reports higher concentrations in very small groups (3 to 5 people) with two reduced-function 521C alleles, but says the clinical impact has not been established [1][4]. Exposure is also higher in Asian patients (about 2-fold; the label says to start at 5 mg) [1][5], in severe renal impairment (about 3-fold; the label says not to exceed 10 mg daily) [1], and with cyclosporine (AUC 7.1-fold in a 10-patient heart transplant study; the label says not to exceed 5 mg daily) [1][6]. These studies measured drug concentrations, not sleep.

Frequently asked questions

Does rosuvastatin affect sleep architecture?
The Crestor label's trial data report no sleep-stage measurements, so an effect on REM or deep sleep is not documented. The label documents timing: any time of day, with or without food [1].
Is morning or evening dosing better for sleep?
The Crestor label states that AUC does not differ between evening and morning dosing [1]. Peak concentration occurs 3 to 5 hours after a dose and the half-life is about 19 hours [1]. The label does not rank one time of day above the other for sleep.
Can rosuvastatin cause insomnia?
The label's placebo-controlled trial data list five reactions: headache (5.0% placebo vs 5.5%), nausea (3.1% vs 3.4%), myalgia (1.3% vs 2.8%), asthenia (2.6% vs 2.7%) and constipation (2.4% vs 2.4%) [1]. These are not a complete list of every reported reaction, so they do not settle whether insomnia can occur.
Is rosuvastatin better for sleep than simvastatin?
No sleep comparison between the two is documented here. The documented difference is chemistry: rosuvastatin is relatively hydrophilic, while simvastatin, lovastatin and atorvastatin are lipophilic [2].

References

  1. DailyMed - CRESTOR- rosuvastatin tablet, film coated. DailyMed - CRESTOR- rosuvastatin tablet, film coated
  2. Schachter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol. 2005;19(1):117-25. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update
  3. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-207. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein
  4. Cooper-DeHoff RM, Niemi M, Ramsey LB, Luzum JA, Tarkiainen EK, Straka RJ, et al. The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clin Pharmacol Ther. 2022;111(5):1007-1021. The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms
  5. Lee E, Ryan S, Birmingham B, Zalikowski J, March R, Ambrose H, et al. Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment. Clin Pharmacol Ther. 2005;78(4):330-41. Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment
  6. Simonson SG, Raza A, Martin PD, Mitchell PD, Jarcho JA, Brown CD, et al. Rosuvastatin pharmacokinetics in heart transplant recipients administered an antirejection regimen including cyclosporine. Clin Pharmacol Ther. 2004;76(2):167-77. Rosuvastatin pharmacokinetics in heart transplant recipients administered an antirejection regimen including cyclosporine
Evidence overview for Does Crestor (rosuvastatin) affect sleep?