Varenicline and proximal myopathy
Authors: Shelley E Wood and P Gerry Fegan
Published online: 1 June 2009
To the Editor: We report a case of proximal myopathy attributed to varenicline therapy to assist with smoking cessation.
A previously fit and well 27-year-old man presented to the emergency department with a 1-week history of lethargy, myalgia and limb weakness. The pain and progressive weakness incapacitated the patient to the extent of him requiring assistance to move from bed to chair.
The patient’s only medication on admission was varenicline (Champix [Pfizer]), which he had started taking about 6 weeks previously to assist with smoking cessation. He denied drinking excessive alcohol or using illicit drugs. There were no symptoms of recent infection.
On examination, a proximal myopathy with weakness of grade 2/5 for both upper and lower limbs was noted. The patient’s muscles were mildly tender, reflexes were preserved, and both cranial nerves and sensory examinations were normal. Respiratory function was not impaired and there was no evidence of fatigability.
The clinical impression was of proximal myopathy of uncertain cause. An adverse drug reaction to varenicline was considered and the medication ceased. Appropriate blood investigations and clinical neurophysiological studies were requested.
A full blood count, thyroid function tests and autoimmune screen were all normal, as were levels of electrolytes, calcium, phosphate and magnesium. The erythrocyte sedimentation rate was 15 mm/h (reference range [RR], 1–15 mm/h), the C-reactive protein level was 20 mg/L (RR, < 5 mg/L), and the creatine kinase level was 1100 U/L (RR, 30–190 U/L). Cushing disease was excluded.
Two days after cessation of varenicline, the muscle weakness had improved and the creatine kinase level had normalised. The patient declined neurophysiological studies and was discharged home. On review 1 week later, he had made a full recovery.
Varenicline is a recently marketed smoking cessation drug treatment that has been shown to be more effective than placebo and bupropion treatment.1 Varenicline acts as a partial agonist at nicotinic acetylcholine receptors in the brain.2 The agonist activity at these receptor sites reduces the symptoms of nicotine withdrawal and craving, while the antagonist activity blocks the reinforcing and rewarding properties of nicotine binding. Recognised adverse effects include nausea, headache, insomnia and abnormal dreams. Musculoskeletal effects are uncommon and limited to joint stiffness and muscle spasms.2 Potential mechanisms for myopathy include muscle cell degeneration induced by excess acetylcholine activity at the neuromuscular junction3 or possibly by varenicline’s affinity for the serotonin receptor.4
Enquiries to the Australian Adverse Drug Reactions Advisory Committee (ADRAC) and searches of the Canadian adverse drug reaction database and PubMed database failed to identify any reports of myopathy associated with varenicline. Thus we believe this to be the first reported case of proximal myopathy due to varenicline, and have reported the case to ADRAC accordingly.
References
- Cahill K, Stead L, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2008; (3): CD006103. 0_BABDCBCB
- eMIMS. Prescribing information: Champix. Sydney: CMP Medica Australia, 2006 (updated 20 Jun 2008). Subscription only. http://www.emims.net/Drugs/poisoning-and-drug-dependence/drug-and-alcohol-dependency/champix (accessed Nov 2008).
- El-Dada MD, Quik M. Involvement of nitric oxide in nicotinic receptor-mediated myopathy. J Pharmacol Exp Ther 1997; 281: 1463-1470. 0_BABCEGEA
- Mendell JR, Silverman LM, Verrill HL, et al. Imipramine-serotonin induced myopathy. Neurology 1976; 26: 968-974. 0_i1091854
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