Muscular weakness, paresthesia, arthralgia and polyneuropathia due to omeprazole

Fråga: Could muscular weakness, paresthesia, arthralgia and polyneuropathia be connected to treatment with esomeprazole though the drug was discontinued nine months ago?

Sammanfattning: Paresthesia is a less common adverse effect to esomeprazole and omeprazole, arthralgia and myalgia are rare and muscular weakness very rare. There are reports in the Swedish adverse drug reaction register and the WHO database as well as a few found in the literature. Very sparse information on cases with longer duration of symptoms is found however. In the databases there are a few cases where, at the time of the report, the patient has not recovered or recovered with sequelae. Symptoms however resolve in most cases after dechallenge and if a rechallenge would be beneficial to help find the right treatment strategy there are no reasons found the literature in why it should be avoided.

Svar: Paresthesia is listed as a less common adverse effect (> 1/1 000 to <1/100) to esomeprazole according to the product specification. Arthralgia and myalgia are rare (>1/10 000 to <1/1 000) and muscular weakness very rare (<1/10 000) (1). Esomeprazole is the S-isomer of omeprazole and the same frequencies of the adverse effects above are listed for omeprazole (2).

The Swedish adverse drug reaction register contains 141 reports on esomeprazole in total, five of these are on arthralgia, one on myopathy and nine on paresthesia. For omeprazole there are 758 reports in total, 11 on arthralgia, two on muscular weakness, one on polyneuropathy and 15 on parestehesia. No reports were found on remaining symptoms several months after discontinued treatment. Few reports however describe long term follow-up of outcome in the database. In one report on numbness and paresthesiae in the lower limbs during omeprazole treatment with an assessment of possible causality, the patient had not recovered at the time of the report, a month after the first symptoms. It is not specified though when the treatment was discontinued (3).

In a study from 2006 reports to the WHO database on adverse drug reactions were reviewed to assess the material in the database on myopathies related to treatment with proton pump inhibitors (PPI). 292 reports on various myopathies were found. This excluded 868 reports on myalgia which was considered a non-specific term associated with a variety of conditions and outside the scope of the study. In 69 of the 292 reports identified dechallenge was positive and in 15 rechallenge was positive. Thirty-eight did not recover and nine recovered with sequelae. In two cases the patient died and the assessments were that the reactions may have been contributory. Onset occurred a few days up to several years after administration of PPI. A few index-cases are described as well, identified from the database or through literature review. One of these cases is a male 69 year old who had myalgia and muscle weakness after using lanzoprazole, after cessation of the drug he recovered. Subsequently he was administered esomeprasole and developed the same symptoms again. Treatment was withdrawn and the patient recovered. He was then given rabeprazole and once again the same symptoms returned. After withdrawal of rabeprazole the patient recovered without sequelae. For all three PPIs in this case the national centre assessed the causality as probable (4).

A case report describes a woman who developed slowly progressive muscular weakness two weeks after starting on omeprazole 20 mg daily. A biopsy of the quadriceps muscle showed slight atrophy of type 2 fibres. Omeprazole was discontinued and the muscular weakness slowly resolved. Upon rechallenge however muscular weakness recurred after two weeks of treatment, she also had elevated creatine phosphokinase and aldolase which was not the case at the first exposure. When treatment was withdrawn weakness and enzyme abnormalities resolved in 30 days (5).

Another case report describes a woman who developed numbness and paresthesiae in her lower limbs after three months of treatment with omeprazole 20 mg. She had other concomitant medication but omeprazole was thought to be the likely reason for the symtoms and was discontinued. The symptoms then resolved and no rechallenge is described (6).

A third report describes five cases of arthralgia associated with omeprazole 20-40 mg daily. In all cases symptoms resolved after discontinued therapy. Where it is described symptoms resolved within days to weeks. In three of the five cases symptoms developed 10 to 20 days after the treatment was started. In one case symptoms developed two days after the addition of omeprazole to other treatment. In the last case the symptoms developed three to four months after starting omeprazole, the authors however cannot exclude an underlying rheumatological disease in this case (7).

In a case-control study the relative risk of developing acute idiopathic polyarthralgia during and after exposure to omeprazole, ranitidine or cimetidine was studied. 100 patients and 361 controls were identified. No increased risk was found associated with omeprazole compared to ranitidine or cimetidine. There was no increased risk associated with current drug use compared to use in the past or distant past for the three drugs (8).

We recommend that the case is reported to the Swedish adverse drug reaction register. Nexium (esomeprazol) AstraZeneca 2013-10-28. Losec (omeprazol) AstraZeneca 2013-09-27. Swedis. Svenska biverkningsregistret. Utdrag 2014-01-21 Clark DW, Strandell J. Myopathy including polymyossitis: a likely class adverse effect of proton pump inhibitors? Eur J Clin Pharmacol 2006;62(6):473-9 Garrote FJ, Lacambra C, del Ser T, Garcia Diaz B, Obeso G, Solis J. Subacute myopathy durine omeprazole therapy. Lancet 1992;340(8820):672 Sellapah S. An unusual side effect of omeprazole: case report. Br J Gen Pract 1990;40(338):389 Beutler M, Hartmann K, Kuhn M, Gartmann J. Arthralgias and omeprazole. BMJ 1994;309(6969):1620 Meier CR, Jick H. Omeprazole, H2 blockers, and polyarthralgia: case-control study. BMJ 1997;315(7118):1283