Can Pravachol (pravastatin) cause alveolitis or interstitial lung disease?/nBackground: The questio

Fråga: Can Pravachol (pravastatin) cause alveolitis or interstitial lung disease?

Background: The question concerns a 56-year-old male patient with a history of hypertension, chronic atrial fibrillation and hyperlipidemia. The patient started treatment with Pravachol 20 mg x1 during the summer of 1996, accidentally received 40 mg x1 during March and April 1997, after which the daily dose was reduced again to 20 mg x1. During the summer of 1997, he gradually developed muscle pain and muscle weakness, fever and weight loss. He also showed a restrictive lung function and decreased diffusing capacity of the lungs and X-rays revealed bilateral alveolar infiltrates. Based on the clinical picture, laboratory investigations and muscle biopsies, the patient has now been diagnosed to suffer from pravastatin-induced myopathy (there is no conclusive evidence for myositis) and his symptoms have improved after starting treatment with prednisolone. Could pravastatin also have caused the pulmonary symptoms?

Sammanfattning: Documentation concerning pulmonary side effects caused by HMG-CoA reductase inhibitors is scarse. Interstitial lung disease has been reported as a possible side effect of simvastatin in two cases.

Svar: The interstitial lung diseases (ILDs) are a heterogenous group of conditions that involve the alveolar walls and perialveolar tissue (1). ILD is reported to occur in 5 to 10 per cent of patients with polymyositis and dermatomyositis, but it is more common in the subgroup of patients with anti-Jo-1 antibody directed againts tRNA synthetase (which is the case for the present patient)(1).

In this patient, the clinical picture indicates a myositis but this could not be conclusively confirmed by the laboratory investigations and the muscle biopsy. Therefore, it may be difficult to distinguish whether the ILD is a secondary consequence of a (drug-induced) myositis, or more a direct effect of the drug on the lungs. We found two recent case reports of interstitial lung disease caused by simvastatin, one with and one without involvement of the muscles (2,3).

The first case report (2) concerned a 76-year-old woman treated with simvastatin 10 mg x1 for 18 months, who developed dermatomyositis with lung involvement resulting in a rapidly fatal outcome. The authors speculated that reduced levels of mevalonic acid caused by HMG-CoA reductase inhibition may cause muscle damage, although the mechanism of the drug-induced muscle toxicity remains unclear. It was suggested that simvastatin may have triggered an autoimmune dermatomyositis by producing muscle injury and releasing autoantigens, or by acting as a hapten (2).

The second case report (3) concerned a 61-year-old man who developed interstitial lung disease with pleural effusion. He had taken simvastatin 10 mg x1 for 6 months during which he developed the lung disease. The patient also had severely elevated liver enzyme values, especially transaminases and LDH, but no signs of muscle involvement or autoimmune disease. It was considered likely that he had a simvastatin-induced interstitial lung disease, based on the high number of eosinophils in the broncho-alveolar lavage. This normalized after simvastatin was discontinued and his symptoms further improved after starting prednisone therapy.

The Swedish Adverse Drug Reactions Advisory Committee (SADRAC) has so far received one report of pulmonary adverse effects possibly related to simvastatin. It concerns urticaria and deterioration of asthma in a 51-year-old male patient, which developed a few days after starting treatment with Zocord (simvastatin) 10 mg x1. The symptoms disappeared upon discontinuation of the drug.

It is recommended to report this case to SADRAC. 1 Harrison´s Principles of Internal Medicine, 1994; 13th ed, 1206-1209 2 Hill C, Zeitz C, Kirkham B: Dermatomyositis with lung involvment in a patient treated with simvastatin. Aust N Z J Med 1995; 25: 745-746 (enclosed) 3 De Groot RE, Willems LNA, Dijkman JH: Interstitiel lung disease with pleural effusion caused by simvastin. J Int Med 1996; 239: 361-363 (enclosed)