Can olanzapine be given to a patient with pre-existing heart disease? Are there any known drug inte

Fråga: Can olanzapine be given to a patient with pre-existing heart disease? Are there any known drug interactions between olanzapine and any of the patient´s current medication (diltiazem, enalapril, isosorbid, lidocaine, metformin, atorvastatin, omeprazole, insulin, and valproate)?

The question concerns a 59-year-old-man with cardiac infarct, heart block, by-pass, diabetes, epilepsy and psychosis. A treatment with olanzapine is planned.

Sammanfattning: Olanzapine is not contraindicated in patients with cardiac problems; however, close surveillance is warranted in this patient due to his pre-existing cardiac disease, diabetes and epilepsy. During the early clinical evaluations of olanzapine, orthostatic hypotension, tachycardia, dizziness and prolongation of QT-intervals were observed. These reactions were however, not, considered clinically significant. There is a published case of suspected circulatory collapse and coma in connection with olanzapine. In SWEDIS there are three cases of orthostatic hypotension and one case of cardiomyopathy with possible cause relationship. No pharmacokinetic drug interaction between olanzapine and the patient´s current medication appears likely, but the possibility that olanzapine enhances the hypotensive effects of the patient´s antihypertensive drugs should be considered

Svar: During the initial evaluation phase, the safety of olanzapine was investigated in 2500 patients who were exposed to multiple doses of olanzapine in comparison to haloperidol (810 patients) or placebo (236 patients) (1,2). Patients with serious medical or neurologic illness were excluded from the studies. The duration of the studies were from six weeks up to three years. Designs of the studies included open as well as double blind clinical trials. Safety evaluations showed olanzapine to be generally well tolerated. Compared to placebo, patients treated with olanzapine experienced more often hypotension, tachycardia and dizziness. Olanzapine prolonged the QT interval on electrocardiography in eight percent of patients by a mean of 2.82 ms on average. The magnitude of these changes was however not considered clinically significant. Prolongation of the QT-interval was also observed in rats (3) and cats (4). There are no confirmed cases of torsade de pointes reported in connection with olanzapine. Weight gain was more frequent among olanzapine treated patients as compared to placebo. For the entire database (1), 41 percent of the patients treated with olanzapine gained seven percent or more of body weight compared to 12 percent of patients taking haloperidol and three percent of those taking placebo.

Olanzapine is known to cause or exacerbate diabetes by increasing body weight (5). Infrequent cardiovascular adverse events recorded during these clinical trials were cerebrovascular accident, haemorrhage, migraine, palpitation, and ventricular extrasystoles. Rare events observed included heart arrest and epilepsy. However, these events have occurred during treatment with olanzapine and they were not necessarily caused by olanzapine.

In a literature search covering the time period since olanzapine was introduced to the market, we found one case of a 43-year-old patient with schizophrenia who developed severe circulatory collapse with hypothermia and coma after 12 days of treatment with several drugs including olanzapine 20 mg per day, carbamazepine, levomepromazine and alprazolam. Olanzapine is suspected to have precipitated the reaction (6). In the Swedish side-effect register SWEDIS (7), there are four reports of circulatory reactions in connection with olanzapine. The first case concerned a 37-year-old man treated with Zyprexa (olanzepine) 5 mg daily due to psychosis. About 18 months after starting treatment with olanzapine, the patient was admitted to the hospital due to dyspnoea, swollen legs, coughing and tiredness. His weight increased from 85 kg to 130 kg during the treatment. Radiological examinations showed increased heart size. Cardiomyopathy was suspected and olanzapine was discontinued. Pulmonary X-ray taken five months later showed decreased cardiac size. Myocardial biopsy showed only fibrosis with no inflammation or deposits. His body weight decreased to 108 kg. The other three cases (two men and one woman) were at the ages of 21, 25 and 55-years-old. They were treated with olanzapine 10 mg daily. The two men fainted while taking olanzapine while the woman experienced drops in blood pressure. A cause relationship was considered possible in all three cases.

We found no reports of interactions between olanzapine and the patient´s other medications. However, it is important to consider the possibility that olanzapine enhances the hypotensive effects of the antihypertensive drugs the patient is currently using. 1 Beasley CM, Tollefson GD, Tran PV. Safety of olanzapine. J Clin Psychiatry 1997;58:13-7. 2 Olanzapine, <http://www.rxlist.com/cgi/generic/olanzapine_ad.thm> (5 Mar. 2001) 3 Leblanc G. Olanzapine. Keep an eye on this neuroleptic. Can Fam Physician 2000;46:321-36. 4 Drici MD, Wang WX, Liu XK, Woosley RL, Flockhard D. Prolongations of QT-interval in isolated feline hearts by antipsychotic drugs. J Clin Psychopharmacol 1998;18:477-81. 5 Rigalleau V, Gatta B, Bonnaud S, Masson M, Bourgeois ML, Vetgnot V, Gin H. Diabetes as a result of atypical anti-psychotic drugs - a report of three cases. Diabet Med 2000;17:484-6. 6 Joue F, Orrillard M, Marion F, Michoux I, Parisot R. Severe intoxication probably from olanzapine (Zyprexa). Beneficial effect of glucagon. Ann Fr Anesth Reanim 1999;18:686-90.