Rosuvastatin-Induced Dizziness and Pruritus: A Case Report and Summary of Statin-Associated Dizziness and Pruritus

Drug-associated adverse events can present with varying symptoms, such as dizziness and pruritus. A 48-year-old woman initiated rosuvastatin to treat her elevated triglycerides. She developed rosuvastatin-associated adverse events, which included dizziness and pruritus within two weeks after starting treatment. After stopping the medication, the dizziness immediately cleared; the pruritus diminished during the next two weeks and eventually resolved completely. Side effects associated with rosuvastatin are discussed. The possibility of a medication-related etiology should be entertained when an individual suddenly develops either dizziness or pruritus or both.


Introduction
Dizziness describes a range of sensations that can vary from feeling faint and lightheaded to weak and unsteady. In contrast, vitiligo is a false sense that a person's environment is spinning. Eliciting a comprehensive history and performing a complete physical examination can aid in determining the cause of dizziness. One possible cause of dizziness is an adverse effect of medication; therefore, the patient's drug regimen should be assessed if they present with dizziness [1].
Pruritus is an unpleasant feeling that causes the desire to scratch. Etiologies of itching include not only internal factors, such as infection, endocrine disorders, and metabolic diseases, but also external factors such as food, inhaled substances, and contact of the skin with irritants or allergens. Common causes of pruritus include contact dermatitis, eczema, and urticaria. Medications can also cause pruritus; thus, a complete history and laboratory studies may be helpful to determine the etiology of pruritus [2].
Statins are a class of drugs that inhibit the hydroxymethylglutaryl-CoA (HMG-CoA) reductase enzyme. Statins are prescribed for the prevention of cardiovascular disease because they are lipid-lowering agents; particularly, they are effective in decreasing low-density lipoprotein cholesterol in the blood. Statinassociated adverse events include hepatotoxicity, myalgias, and other muscle-related side effects such as weakness [3].
A woman with hyperlipidemia, characterized by an elevated triglyceride level and a normal cholesterol level, was evaluated by her primary care physician who decided to begin treatment with rosuvastatin. Within two weeks, she developed dizziness and pruritus. Both symptoms resolved after discontinuing the medication. Drug-related side effects of rosuvastatin are discussed, and the occurrence of statin-associated dizziness and pruritus are summarized.

Case Presentation
A 48-year-old woman was referred to a dermatologist for generalized pruritus. Her past medical history was significant for hyperlipidemia, mastodynia, obesity, and viral warts. Prior drug allergies included penicillin, morphine, and sulfamethoxazole/trimethoprim. In addition to recently beginning rosuvastatin, her chronic medications included diclofenac sodium, fluticasone, gabapentin, glucosamine chondroitin, ibuprofen, lubiprostone, and omeprazole.
Additional history revealed that she not only developed pruritus but also concurrently experienced lightheadedness and feeling faint; on several occasions, she mentioned her episodes of dizziness to her family members. Both symptoms began within two weeks after starting rosuvastatin. She independently decided to discontinue the new medication. Less than one day later, the dizziness resolved; the pruritus gradually improved by the time she was evaluated by a dermatologist.
A complete cutaneous examination was performed. There were resolving excoriations on her back and arms. There was neither evidence of burrows (which would have been suggestive of scabies) nor any lesion associated with an itch-related primary dermatosis (such as dermatitis, lichen planus, or psoriasis).
The correlation of the patient's history and clinical presentation, including the resolution of her symptoms after discontinuing the newly started medication, established a diagnosis of rosuvastatin-induced dizziness and pruritus. Since her symptoms had already improved significantly, daily topical application of an emollient cream was recommended to moisturize her skin. Subsequently, the pruritus completely resolved during the next four weeks.
The patient returned to her primary care physician. They discussed restarting rosuvastatin to confirm the occurrence of dizziness and pruritus as an adverse reaction to the drug; however, she declined this option. She began treatment with gemfibrozil without any adverse systemic or cutaneous reactions.

Discussion
Rosuvastatin is a lipid-lowering drug that belongs to the statin class of medications. It is used to treat patients with increased cholesterol and triglycerides. Dosing of rosuvastatin is based on a patient's baseline lipid profile; daily doses range from 5 to 40 milligrams. Adverse effects of rosuvastatin include elevated creatinine kinase levels, elevated liver enzymes, myopathy, renal failure, and rhabdomyolysis [4].
Rosuvastatin-induced dizziness has previously been observed ( Table 1) [3,[5][6][7][8][9][10]. In a study of 12 patients who were started on rosuvastatin, two patients developed dizziness [5]. In another study of 172 patients, two individuals experienced dizziness [6]. Furthermore, in a study of 36 participants that was investigating the effects of coadministration of rosuvastatin and olmesartan, dizziness occurred in one participant who received only rosuvastatin in addition to four participants who received both rosuvastatin and olmesartan, further suggesting that rosuvastatin can elicit dizziness [7]. In another study in which 36 patients received either fimasartan and/or rosuvastatin, one individual experienced dizziness [8]. In a research study of 375 patients, two individuals experienced dizziness: one who received rosuvastatin and one who received rosuvastatin and ezetimibe [9]. The investigators of a final study, which included 42 patients who received rosuvastatin, observed one individual with dizziness [10].  f Dizziness occurred in one patient receiving 20 milligrams rosuvastatin daily and one patient receiving both 20 milligrams rosuvastatin and 10 milligrams ezetimibe daily.
g Dizziness was observed in one patient receiving 20 milligrams rosuvastatin daily. Dizziness was also observed in three patients receiving 80 milligrams telmisartan and one patient receiving placebo (no drug).
An estimate of the occurrence of rosuvastatin-induced dizziness, by combining the data from the studies in Table 1 that included patients from Southeast Asian countries, shows an incidence of 1.9 percent (13 of 673 patients) [3,[5][6][7][8][9][10]. The reported patient developed dizziness within two weeks of starting rosuvastatin. Her dizziness resolved almost immediately after discontinuation of the medication.
Rosuvastatin-induced pruritus has also been noted in patients treated with the drug. A 30-year-old-man with a history of hyperlipidemia and myocardial infarction developed an anaphylactic reaction, which included pruritus, to both atorvastatin and simvastatin independently. Upon the initiation of desensitization with rosuvastatin, the man also developed pruritus [11]. Similarly, a 29-year-old woman with familial hypercholesterolemia developed an allergic reaction to atorvastatin and simvastatin. After starting rosuvastatin for desensitization, she experienced pruritus and flushing [12]. Subsequently, although both patients initially experienced rosuvastatin-associated pruritus, they were able to undergo successful desensitization to the drug [11,12].
The reported patient was offered to restart rosuvastatin to establish unequivocally that her symptoms were drug-associated, but she declined to take the medication. She started a new drug for her hyperlipidemia, gemfibrozil, and did not experience any reactions to the drug. According to the Naranjo scale of adverse drug reaction probability, both symptoms received a score of eight, which implies that the dizziness and pruritus she experienced were probable reactions to rosuvastatin (  Abbreviations: +, add; -, subtract a There are published reports of either dizziness or pruritus secondary to rosuvastatin [5][6][7][8][9][10] b After rosuvastatin was discontinued, the patient received a non-statin triglyceride-lowering drug: gemfibrozil. Since the new medication was anticipated to have a therapeutic effect, it is not a true placebo; however, therapy with the new fibrate agent (gemfibrozil) may be considered a placebo-like treatment in comparison to the statin class of drug (rosuvastatin) that she was previously receiving.
c The patient informed her family about the episodes of lightheadedness and feeling faint that she was experiencing. Resolving excoriations, and evidence of her pruritus were observed during her cutaneous examination. d Naranjo scale scores are as follows: a score of greater than or equal to nine means that there is a "definite" probability that the adverse event was related to the drug, a score of five to eight means that it was a "probable" reaction, a score of one to four means that it was a "possible" reaction, and a score of zero or below means that the reaction was defined as "doubtful." Our patient's score of eight means that her dizziness and pruritus was a "probable" reaction to rosuvastatin. The reaction followed a reasonable temporal sequence after the administration of rosuvastatin, had a recognized response to rosuvastatin, was confirmed by withdrawal-but not repeat exposure to-rosuvastatin, and could not be reasonably explained by the known characteristics of the patient's clinical state [20].
There are no previous case reports of concurrent dizziness and pruritus associated with rosuvastatin. However, it is important for clinicians to recognize that new symptoms can be a result of an adverse effect of a medication. The initial treatment of medication-associated dizziness and pruritus is the discontinuation of the drug. Usually, both symptoms will spontaneously resolve once the causative agent has been stopped.

Conclusions
Rosuvastatin has been associated with several adverse events. Albeit less common, dizziness and pruritus can occur following initiation of treatment with rosuvastatin. A 48-year-old woman developed not only dizziness but also pruritus within two weeks of starting rosuvastatin. After the medication was discontinued, her dizziness resolved immediately and her pruritus significantly improved within two weeks. To the best of our knowledge, concurrent rosuvastatin-induced dizziness and pruritus have only been described in the reported woman. In addition to rosuvastatin, dizziness and pruritus have occurred in patients treated with other statins. Therefore, clinicians should consider the possibility of medication-associated etiology when a patient presents with a new onset of dizziness of generalized pruritus, or both.