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Lornoxicam
Lornoxicam treated with lorcainide, a new antiarrhythmic drug. Am Heart J 1984;108(6):1443–8. 15. Meinertz T, Kasper W, Kersting F, Just H, Bechtold H, Jahnchen E. Lorcainide. II. Plasma concentration-effect relationship. Clin Pharmacol Ther 1979;26(2):196–204. 16. Evers J, Buttner-Belz U. Fatal lorcainide poisoning. J Toxicol Clin Toxicol 1995;33(2):157–9.
2167
2. Kickler TS, Zinkham WH, Moser A, Shankroff J, Borel J, Moser H. Effect of erucic acid on platelets in patients with adrenoleukodystrophy. Biochem Mol Med 1996;57(2): 125–33.
Lormetazepam Lorenzo’s oil General Information Lorenzo’s oil is a 4:1 mixture of glyceryl trioleate and glyceryl trierucate. It is used in patients with adrenoleukodystrophy. The dyslipidemia in patients with adrenoleukodystrophy consists of increased blood concentrations of very-long-chain saturated fatty acids, particularly hexacosaenoic acid (C26:0). Treatment with Lorenzo’s oil has tended to normalize the abnormality in the blood while the patient deteriorates. Neurological changes are unrelated to the fatty acid changes in the blood, and, moreover, erucic acid does not seem to enter the brain. Owing to lack of controlled trials, it is not known whether it works. Registration of adverse effects with Lorenzo’s oil has been hampered by the absence of controlled trials. In 22 patients treated for at least 12 months, although Lorenzo’s oil did not seem to be beneficial, there were possible adverse effects, such as mild increases in liver enzymes (55%), thrombocytopenia (55%), gastrointestinal complaints (14%), and gingivitis (14%). Furthermore, there were falls in hemoglobin concentration and leukocyte count, and an increase in the plasma alkaline phosphatase concentration; the reduction in platelet count did not result in hemorrhage (1). Whether some of the adverse effects of Lorenzo’s oil are due to low concentrations of essential fatty acids or caused by reduced dietary fat intake is not known.
See also Benzodiazepines
General Information Lormetazepam is a short-acting benzodiazepine with effects similar to those of diazepam.
Organs and Systems Psychological, psychiatric Auditory hallucinations have been attributed to lormetazepam (1).
A 45-year-old woman with moderate depression and anxiety took lormetazepam 4 mg/day. After a few days, she noticed musical auditory hallucinations like children’s songs. There were no neurological, otological, or psychiatric causes for the hallucinations. When the dose of lormetazepam was reduced to 2 mg the auditory experience changed to ‘‘classic tinnitus.’’ The lormetazepam was eventually withdrawn, but a slight degree of tinnitus persisted.
Reference 1. Curtin F, Redmund C. Musical hallucinations during a treatment with benzodiazepine. Can J Psychiatry 2002;47(8):789–90.
Organs and Systems Hematologic Lorenzo’s oil affected blood platelet counts in 39 patients followed for 1 year (2). Blood platelet aggregation studies in those patients were normal and there were no plateletassociated immunoglobulins. It has been suggested that the thrombocytopenia might be due to platelet activation, resulting from an increase in the concentration of erucic acid in the platelet membrane (1).
References 1. van Geel BM, Assies J, Haverkort EB, Koelman JH, Verbeeten B Jr, Wanders RJ, Barth PG. Progression of abnormalities in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy despite treatment with ‘‘Lorenzo’s oil’’. J Neurol Neurosurg Psychiatry 1999;67(3):290–9. ª 2006 Elsevier B.V. All rights reserved.
Lornoxicam See also Non-steroidal anti-inflammatory drugs
General Information Data are insufficient to indicate whether the oxicam NSAID lornoxicam is safer for the gastrointestinal tract than other oxicam derivatives (SEDA-16, 113). Headache, dizziness, and gastrointestinal symptoms are the most frequent adverse effects; clinically significant gastrointestinal events include upper gastrointestinal ulceration, with or without hemorrhage or perforation (SEDA-20, 94) (SEDA-21, 107). The profile of drug interactions is similar to the profiles of other NSAIDs (SEDA-21, 108).
2168 Losartan
Drug–Drug Interactions
Lornoxicam increased the mean serum concentration of racemic warfarin and correspondingly increased its anticoagulant effect (3).
effects were cough (17%), malaise and lassitude (15%), dizziness (15%), headache or migraine (11%), nausea and vomiting (6.0%), rash (5.0%), dyspnea (4.9%), edema (4.8%), dyspepsia (4.2%), and diarrhea (3.7%). These were also the most common reasons for drug withdrawal. The seemingly high incidence of cough may have been due to carry over from previous use of ACE inhibitors. In 1378 patients with mild to moderate hypertension valsartan 80 mg/day has been compared with losartan 50 mg/ day and placebo for 8 weeks (3). This study confirmed the excellent tolerance profile, not different from placebo, of both angiotensin II receptor antagonists. An extensive review of the use of losartan, with special focus on elderly patients, has included an update on the tolerability profile, mainly in clinical trials, but with no significant new information (4).
References
Organs and Systems
1. Masche UP, Rentsch KM, von Felten A, Meier PJ, Fattinger KE. Opposite effects of lornoxicam co-administration on phenprocoumon pharmacokinetics and pharmacodynamics. Eur J Clin Pharmacol 1999;54(11):857–64. 2. Masche UP, Rentsch KM, von Felten A, Meier PJ, Fattinger KE. No clinically relevant effect of lornoxicam intake on acenocoumarol pharmacokinetics and pharmacodynamics. Eur J Clin Pharmacol 1999;54(11):865–8. 3. Ravic M, Johnston A, Turner P, Ferber HP. A study of the interaction between lornoxicam and warfarin in healthy volunteers. Hum Exp Toxicol 1990;9(6):413–14.
Nervous system
Phenprocoumon Lornoxicam altered the pharmacokinetics of the more potent S-isomer of phenprocoumon and to a lesser extent R-phenprocoumon, with a reduction in factor II and VII activity (1). In contrast, at the upper limit of the recommended doses lornoxicam did not alter the pharmacokinetics of R-acenocoumarol or the anticoagulant activity of acenocoumarol (2). Warfarin
Losartan See also Angiotensin II receptor antagonists
General Information Losartan is a non-peptide, selective angiotensin type 1 (AT1) receptor antagonist. Because it has been suggested that there is a local renin–angiotensin system in the eye, losartan may be useful in treating glaucoma. In a small, well-designed, placebo-controlled, crossover study in four groups of subjects—controls, hypertensive patients with normal intraocular pressure, and patients with primary open-angle glaucoma with and without hypertension—a single oral dose of losartan 50 mg produced a drop in intraocular pressure in all subjects within 2–6 hours after drug intake, proportional to baseline eye pressure (1). Blood pressure fell only in the hypertensive subjects. Thus, the fall in intraocular pressure was independent of the systemic effect on blood pressure. Beyond the potential for using losartan as a therapy for glaucoma, ophthalmologists should take into account concomitant therapy with losartan (and possibly other angiotensin receptor antagonists) when measuring intraocular pressure. Using the method of prescription event monitoring (PEM), the incidence densities of adverse effects per 1000 patient-months of exposure have been measured in 14 522 patients (2). Most were hypertensive (63%). During treatment months 2–6, the commonest adverse ª 2006 Elsevier B.V. All rights reserved.
An isolated case of migraine occurring after a single dose of losartan was reported (5). The temporal association during challenge and rechallenge, although in unblinded conditions, argues for a possible causal relation. Sensory systems There have been reports of taste disturbance in patients taking ACE inhibitors, tentatively attributed to chelation of metal ions. However, no mechanism for taste loss due to angiotensin-II receptor blockers has been proposed. Reversible loss of taste discrimination has been reported with losartan (6). In two cases dysgeusia occurred some time after switching from an ACE inhibitor to losartan (1 week in one case and 3 months in the other). In both cases the dysgeusia disappeared after withdrawal of losartan (timing not reported in one case, 1 week after in the other) (7). The authors referred to previously reported cases, one with losartan (8) and one with valsartan (9), and to a personal communication from the manufacturer of 12 other cases within a large safety monitoring program. Hematologic Anemia in hemodialysis (10) and mainly in renal transplant patients has been reported (11–13). The suggested mechanism is by an action on erythropoietin, similar to that of ACE inhibitors, which produce the same adverse effect. However, in a small uncontrolled but prospective study, losartan given for 3 months to 15 patients on chronic hemodialysis with anemia, neither altered plasma erythropoietin concentrations nor aggravated the anemia (14). In those taking losartan there was no need for higher doses of co-administered r-Hu Epo in order to correct anemia, in contrast to controls. Liver Hepatic injury due to losartan is a recognized rare adverse effect (15).
A 52-year-old woman developed jaundice, right upper abdominal discomfort, and weakness. She had had a similar problem previously, after taking losartan
2167
2. Kickler TS, Zinkham WH, Moser A, Shankroff J, Borel J, Moser H. Effect of erucic acid on platelets in patients with adrenoleukodystrophy. Biochem Mol Med 1996;57(2): 125–33.
Lormetazepam Lorenzo’s oil General Information Lorenzo’s oil is a 4:1 mixture of glyceryl trioleate and glyceryl trierucate. It is used in patients with adrenoleukodystrophy. The dyslipidemia in patients with adrenoleukodystrophy consists of increased blood concentrations of very-long-chain saturated fatty acids, particularly hexacosaenoic acid (C26:0). Treatment with Lorenzo’s oil has tended to normalize the abnormality in the blood while the patient deteriorates. Neurological changes are unrelated to the fatty acid changes in the blood, and, moreover, erucic acid does not seem to enter the brain. Owing to lack of controlled trials, it is not known whether it works. Registration of adverse effects with Lorenzo’s oil has been hampered by the absence of controlled trials. In 22 patients treated for at least 12 months, although Lorenzo’s oil did not seem to be beneficial, there were possible adverse effects, such as mild increases in liver enzymes (55%), thrombocytopenia (55%), gastrointestinal complaints (14%), and gingivitis (14%). Furthermore, there were falls in hemoglobin concentration and leukocyte count, and an increase in the plasma alkaline phosphatase concentration; the reduction in platelet count did not result in hemorrhage (1). Whether some of the adverse effects of Lorenzo’s oil are due to low concentrations of essential fatty acids or caused by reduced dietary fat intake is not known.
See also Benzodiazepines
General Information Lormetazepam is a short-acting benzodiazepine with effects similar to those of diazepam.
Organs and Systems Psychological, psychiatric Auditory hallucinations have been attributed to lormetazepam (1).
A 45-year-old woman with moderate depression and anxiety took lormetazepam 4 mg/day. After a few days, she noticed musical auditory hallucinations like children’s songs. There were no neurological, otological, or psychiatric causes for the hallucinations. When the dose of lormetazepam was reduced to 2 mg the auditory experience changed to ‘‘classic tinnitus.’’ The lormetazepam was eventually withdrawn, but a slight degree of tinnitus persisted.
Reference 1. Curtin F, Redmund C. Musical hallucinations during a treatment with benzodiazepine. Can J Psychiatry 2002;47(8):789–90.
Organs and Systems Hematologic Lorenzo’s oil affected blood platelet counts in 39 patients followed for 1 year (2). Blood platelet aggregation studies in those patients were normal and there were no plateletassociated immunoglobulins. It has been suggested that the thrombocytopenia might be due to platelet activation, resulting from an increase in the concentration of erucic acid in the platelet membrane (1).
References 1. van Geel BM, Assies J, Haverkort EB, Koelman JH, Verbeeten B Jr, Wanders RJ, Barth PG. Progression of abnormalities in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy despite treatment with ‘‘Lorenzo’s oil’’. J Neurol Neurosurg Psychiatry 1999;67(3):290–9. ª 2006 Elsevier B.V. All rights reserved.
Lornoxicam See also Non-steroidal anti-inflammatory drugs
General Information Data are insufficient to indicate whether the oxicam NSAID lornoxicam is safer for the gastrointestinal tract than other oxicam derivatives (SEDA-16, 113). Headache, dizziness, and gastrointestinal symptoms are the most frequent adverse effects; clinically significant gastrointestinal events include upper gastrointestinal ulceration, with or without hemorrhage or perforation (SEDA-20, 94) (SEDA-21, 107). The profile of drug interactions is similar to the profiles of other NSAIDs (SEDA-21, 108).
2168 Losartan
Drug–Drug Interactions
Lornoxicam increased the mean serum concentration of racemic warfarin and correspondingly increased its anticoagulant effect (3).
effects were cough (17%), malaise and lassitude (15%), dizziness (15%), headache or migraine (11%), nausea and vomiting (6.0%), rash (5.0%), dyspnea (4.9%), edema (4.8%), dyspepsia (4.2%), and diarrhea (3.7%). These were also the most common reasons for drug withdrawal. The seemingly high incidence of cough may have been due to carry over from previous use of ACE inhibitors. In 1378 patients with mild to moderate hypertension valsartan 80 mg/day has been compared with losartan 50 mg/ day and placebo for 8 weeks (3). This study confirmed the excellent tolerance profile, not different from placebo, of both angiotensin II receptor antagonists. An extensive review of the use of losartan, with special focus on elderly patients, has included an update on the tolerability profile, mainly in clinical trials, but with no significant new information (4).
References
Organs and Systems
1. Masche UP, Rentsch KM, von Felten A, Meier PJ, Fattinger KE. Opposite effects of lornoxicam co-administration on phenprocoumon pharmacokinetics and pharmacodynamics. Eur J Clin Pharmacol 1999;54(11):857–64. 2. Masche UP, Rentsch KM, von Felten A, Meier PJ, Fattinger KE. No clinically relevant effect of lornoxicam intake on acenocoumarol pharmacokinetics and pharmacodynamics. Eur J Clin Pharmacol 1999;54(11):865–8. 3. Ravic M, Johnston A, Turner P, Ferber HP. A study of the interaction between lornoxicam and warfarin in healthy volunteers. Hum Exp Toxicol 1990;9(6):413–14.
Nervous system
Phenprocoumon Lornoxicam altered the pharmacokinetics of the more potent S-isomer of phenprocoumon and to a lesser extent R-phenprocoumon, with a reduction in factor II and VII activity (1). In contrast, at the upper limit of the recommended doses lornoxicam did not alter the pharmacokinetics of R-acenocoumarol or the anticoagulant activity of acenocoumarol (2). Warfarin
Losartan See also Angiotensin II receptor antagonists
General Information Losartan is a non-peptide, selective angiotensin type 1 (AT1) receptor antagonist. Because it has been suggested that there is a local renin–angiotensin system in the eye, losartan may be useful in treating glaucoma. In a small, well-designed, placebo-controlled, crossover study in four groups of subjects—controls, hypertensive patients with normal intraocular pressure, and patients with primary open-angle glaucoma with and without hypertension—a single oral dose of losartan 50 mg produced a drop in intraocular pressure in all subjects within 2–6 hours after drug intake, proportional to baseline eye pressure (1). Blood pressure fell only in the hypertensive subjects. Thus, the fall in intraocular pressure was independent of the systemic effect on blood pressure. Beyond the potential for using losartan as a therapy for glaucoma, ophthalmologists should take into account concomitant therapy with losartan (and possibly other angiotensin receptor antagonists) when measuring intraocular pressure. Using the method of prescription event monitoring (PEM), the incidence densities of adverse effects per 1000 patient-months of exposure have been measured in 14 522 patients (2). Most were hypertensive (63%). During treatment months 2–6, the commonest adverse ª 2006 Elsevier B.V. All rights reserved.
An isolated case of migraine occurring after a single dose of losartan was reported (5). The temporal association during challenge and rechallenge, although in unblinded conditions, argues for a possible causal relation. Sensory systems There have been reports of taste disturbance in patients taking ACE inhibitors, tentatively attributed to chelation of metal ions. However, no mechanism for taste loss due to angiotensin-II receptor blockers has been proposed. Reversible loss of taste discrimination has been reported with losartan (6). In two cases dysgeusia occurred some time after switching from an ACE inhibitor to losartan (1 week in one case and 3 months in the other). In both cases the dysgeusia disappeared after withdrawal of losartan (timing not reported in one case, 1 week after in the other) (7). The authors referred to previously reported cases, one with losartan (8) and one with valsartan (9), and to a personal communication from the manufacturer of 12 other cases within a large safety monitoring program. Hematologic Anemia in hemodialysis (10) and mainly in renal transplant patients has been reported (11–13). The suggested mechanism is by an action on erythropoietin, similar to that of ACE inhibitors, which produce the same adverse effect. However, in a small uncontrolled but prospective study, losartan given for 3 months to 15 patients on chronic hemodialysis with anemia, neither altered plasma erythropoietin concentrations nor aggravated the anemia (14). In those taking losartan there was no need for higher doses of co-administered r-Hu Epo in order to correct anemia, in contrast to controls. Liver Hepatic injury due to losartan is a recognized rare adverse effect (15).
A 52-year-old woman developed jaundice, right upper abdominal discomfort, and weakness. She had had a similar problem previously, after taking losartan