Andrés Navarro-Ruiz

Acute Seizures Due to a Probable Interaction between Valproic Acid and Meropenem

OBJECTIVE: To report a probable interaction between meropenem and valproic acid that resulted in the development of epileptic seizures. CASE SUMMARY: A 21-year-old woman presented to our emergency department because of a new-onset, generalized tonic—clonic seizure and was admitted to the intensive care unit. Treatment with valproic acid 1000 mg as a continuous intravenous infusion over 24 hours was initiated. On day 6, the serum concentration of valproic acid was 52.5 μg/mL. On day 13, treatment with intravenous meropenem 1 g 3 times daily was started. On day 15, when the patient was afebrile, numerous myoclonic episodes occurred involving her arms and face; the serum concentration of valproic acid at that time was 42 μg/mL. The valproic acid dose was increased to 2880 mg. Two days later, a generalized tonic—clonic seizure occurred despite the increased dosage, and the plasma concentration of valproic acid fell to 7 μg/mL. The valproic acid dose was increased the following day to 3600 mg; however, the serum concentrations remained <10 μg/mL. On day 19, based on the results of a blood culture and the suspicion of an interaction between meropenem and valproic acid, meropenem therapy was suspended. The serum concentration of valproic acid was 52.4 μg/mL on day 27. Three days later, the patient was asymptomatic and was discharged. DISCUSSION: Coadministration of valproic acid and other drugs that are metabolized by the hepatic cytochrome P450 isoenzyme system can lead to clinically relevant interactions by induction or inhibition of enzymes in shared metabolic pathways. In view of studies in experimental models, the interaction between carbapenem antibiotics and valproic acid is at least possible. Use of the Naranjo probability scale indicated a probable relationship between acute seizures and a meropenem—valproic acid interaction in this patient. CONCLUSIONS: This case report provides strong evidence for an interaction between valproic acid and meropenem. Clinicians should be aware of this potential interaction that may be associated with a serious adverse effect as the result of the decrease of the valproic acid serum concentrations.

Adverse Cutaneous Reactions Induced by TNF-α Antagonist Therapy

Objective: To review adverse cutaneous drug reactions induced by tumor necrosis factor alpha (TNF-&agr;) antagonist therapy. Methods: A literature search was performed using PubMed (1996–March 2009), EMBASE, and selected MEDLINE Ovid bibliography searches. All language clinical trial data, case reports, letters, and review articles identified from the data sources were used. Results: Since the introduction of TNF-&agr; antagonist, the incidence of adverse cutaneous drug reactions has increased significantly. A wide range of different skin lesions might occur during TNF-&agr; antagonist treatment. New onset or exacerbation of psoriasis has been reported in patients treated with TNF-&agr; antagonists for a variety of rheumatologic conditions. TNF-&agr; antagonist therapy has been associated with a lupus-like syndrome; most of these case reports occurred in patients receiving either etanercept or infliximab. Serious skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely with the use of TNF-&agr; antagonists. Conclusions: As the use of TNF-&agr; antagonists continues to increase, the diagnosis and management of cutaneous side effects will become an increasingly important challenge. In patients receiving TNF-&agr; antagonist treatment, skin disease should be considered, and clinicians need to be aware of the adverse reactions of these drugs.

Optic Neuritis with Concurrent Etanercept and Isoniazid Therapy

OBJECTIVE To report a case of optic neuritis associated with concurrent etanercept and isoniazid therapy. CASE SUMMARY A 55-year-old man diagnosed as having rheumatoid arthritis had received treatment with nonsteroidal anti-inflammatory drugs, sulfasalazine, oral methotrexate, leflunomide, and deflazacort. Four months prior to admission, he had a Disease Activity Score of 6.06; treatment with etanercept was considered. Three months prior to admission, because of evidence of latent tuberculosis, isoniazid 300 mg once daily and pyridoxine 50 mg once daily were prescribed. Treatment with subcutaneous etanercept 25 mg twice weekly was started 5 days after isoniazid was initiated. Two weeks prior to admission, the patient developed blurred vision in his left eye. Ten days later, his vision worsened and he was hospitalized. The visual acuity in both eyes was 0.7, and a campimetric examination was compatible with optic neuritis. Magnetic resonance imaging of the brain revealed lesions suggesting demyelinating lesions. The clinical course was consistent with bilateral optic neuritis. Etanercept was stopped, and isoniazid was replaced with rifampin 600 mg once daily. The patient was treated with intravenous methylprednisolone hemisuccinate 1 g/day for 5 days followed by oral prednisolone, resulting in a minor subjective improvement in left eye visual acuity. He then received oral prednisone for 3 weeks, slowly tapering to discontinuation. DISCUSSION No physiologic factors could have predisposed this patient to develop optic neuritis. He was not diagnosed with a demyelinating disease or underlying systemic condition. The optic neuritis was unlikely to be an early manifestation of multiple sclerosis based on the clinical course and the negative results of the imaging tests. Furthermore, there was a close temporal correlation between the drug exposure and the onset of symptoms. After discontinuation of etanercept and isoniazid therapy, the patients general condition improved. Use of the Naranjo probability scale indicated a possible relationship between optic neuritis and combined etanercept–isoniazid therapy. CONCLUSIONS Patients initiated on etanercept and isoniazid should be closely monitored for the development of adverse neurologic signs and effects. If optic neuritis is determined, etanercept and isoniazid should be discontinued immediately.

Henoch-Schönlein purpura associated with clarithromycin. Case report and review of literature clarithromycin. Case report and review of literature

OBJECTIVE: To report a case of Henoch-Schonlein purpura that appears to be related to the intake of clarithromycin for pharyngitis/tonsillitis. CASE SUMMARY: We describe a case of Henoch-Schonlein associated with clarithromycin therapy in a 48-year-old white man with no history of allergic drug reactions. Four days after starting therapy, he came to our hospital emergency room because of a non-pruritic palpable purpuric rash on the trunk and extremities and arthralgias involving elbows and knees. Administration of clarithromycin was suspended, in a few days, arthralgias and skin lesions quickly resolved. Three weeks later, the patient presented again with abdominal pain, dark-red urine and swelling of the legs. Urinalysis revealed proteinuria of 11 g/24 h and hematuria. A percutaneous renal biopsy showed a diffuse endocapillary proliferative glomerulonephritis with segmental areas of fibrinoid necrosis within glomeruli, on immunofluorescence study granular deposits of IgA and C3 were present in the mesangium and capillary walls. A diagnosis of HSP was made. We suspected that the causative agent might be clarithromycin since this was the only drug added before the cutaneous and renal condition appeared. CONCLUSIONS: Our case and the previous case suggest that HSP may represent a potential adverse effect of clarithromycin, clinicians should be alerted to this potentially severe side effect of such a widely used drug. In accordance with the data obtained and based on the Naranjo algorithm, the adverse reaction could be considered possible.

Acenocoumarol-Induced Henoch-Schönlein Purpura

OBJECTIVE To report a probable case of Henoch-Schönlein purpura associated with acenocoumarol therapy. CASE SUMMARY A 76-year-old white woman was prescribed acenocoumarol for chronic atrial fibrillation. Two months after starting therapy, the patient came to our hospitals emergency department because of abdominal pain associated with vomiting. Physical examination revealed multiple round, confluent, purpuric lesions with some vesicles and an area of residual pigmentation. Lesions were present predominantly on the legs and gluteus, and also on the abdomen and arms. Skin biopsy of the lesions was compatible with leukocytoclastic vasculitis with deposition of immunoglobulin A. An upper intestinal endoscopy was done and identified purpuric mucosal lesions in the fundus, body, and antrum of the stomach and the duodenal bulb. Renal function was not affected, although proteinuria (1.26 g/day) was found and microscopic hematuria was observed. DISCUSSION The most likely cause of the Henoch–Schönlein purpura in this case was considered to be acenocoumarol because of the close temporal relationship between exposure to the drug and onset of symptoms, as well as the rapid resolution of the symptoms and signs after acenocoumarol was discontinued. The oral anticoagulant was the only identifiable precipitant that the patient encountered before the Henoch–Schönlein purpura developed. An objective causality assessment revealed that the adverse drug event was probable. CONCLUSIONS This case report illustrates a probable association between Henoch–Schönlein purpura and acenocoumarol. As of December 2003, this reaction had not been previously reported. Clinicians should be aware of this potential adverse effect of a widely used drug.

Recombinant Factor VIIa is an Effective Therapy for Abdominal Surgery and Severe Thrombocytopenia: A Case Report

A 50-year-old woman was admitted to the emergency room. An appendectomy was done. On the sixth day the patient’s general state deteriorated and she became somnolent with jaundice due to distal obstructive choledocholithiasis. The results of laboratory tests were platelets 12 x 109/L, prothrombin time 13 seconds, international normalized ratio 1.19, activated partial thromboplastin time 31.8 seconds, and fibrinogen 8.78 g/L. There was no evidence of disseminated intravascular coagulation. In view of the patient’s clinical condition, surgery was considered to be indicated. Because it was a life-threatening situation and at the time there was no platelet concentrate available for immediate transfusion, she was treated with a single dose of recombinant factor VIIa (rFVIIa) (60 μg/kg).The dose of 60 μg/kg was selected on the basis of experience with rFVIIa in the treatment of hemophilic patients. In this case, use of rFVIIa was a valid alternative to control the bleeding in a patient with thrombocytopenia. However, despite the efficacy of the treatment, it should not be forgotten that it was used because of the unavailability of platelets and that we were dealing with a life-threatening situation. Clinical trials should be carried out to verify the safety, effectiveness, and efficiency of rFVIIa in these cases.

Photo-Induced Stevens–Johnson Syndrome Due to Sulfasalazine Therapy

OBJECTIVE: To report a case of photo-induced Stevens–Johnson Syndrome (SJS) due to sulfasalazine therapy. CASE SUMMARY: Photo-induced SJS associated with sulfasalazine therapy occurred in a 34-year-old white man diagnosed as having seronegative symmetrical polyarthritis with no predisposing factors. According to his medical record, the patient had received methotrexate, levofolinate calcium, deflazacort, and diclofenac sodium as needed. Two months prior to admission, methotrexate and diclofenac sodium were suspended and treatment with sulfasalazine was started. The patient presented to our emergency department because of severe erythema confined to sun-exposed areas; annular lesions on the extremities and the mucosa were affected. Nikolskys sign was present. A skin biopsy was compatible with SJS, and the clinical diagnosis was SJS induced by sulfasalazine. Administration of sulfasalazine was suspended, which resulted in an improvement in the skin lesions and general state of health. The patient was discharged without further symptoms. DISCUSSION: The observed reaction to sulfasalazine was considered phototoxic, as lesions appeared like a burn rash reaction in sun-exposed areas when sulfasalazine treatment was started and the reaction progressed to SJS. It seems that there was a correlation between the time course of the reaction and the administration of sulfasalazine. An objective causality assessment revealed that the adverse effect was possible. CONCLUSIONS: To our knowledge, this is the first report of photo-induced SJS due to sulfasalazine therapy. Clinicians should be aware of this infrequent but severe reaction. If clinical evaluation leads to the suspicion of SJS, sulfasalazine should be discontinued immediately.

Unrecognized delayed toxic lithium peak concentration in an acute poisoning with sustained release lithium product.

A 32-year-old female with a history of bipolar disorder was admitted after taking approximately 16 g of an extended-release lithium carbonate formulation in an attempted suicide. Five hours after consumption, the lithium serum level was 3.2 mEq/L. Fourteen hours after consumption, the lithium level was 5.1 mEq/L and the patient was asymptomatic. Due to a level >4 mEq/L, the patient was transferred to a renal medicine service for hemodialysis. The lithium concentration 6 hours after the hemodialysis was 2.54 mEq/L. Thirty seven hours after the consumption (15 hours after hemodialysis), lithium levels increased up to 6.09 mEq/L. A second hemodialysis session was performed, which successfully reduced the serum lithium concentration to 1.86 mEq/L. Lithium levels 85 hours after the consumption were 0.61 mEq/L and the patient was transferred to the Psychiatry Department. Unrecognized delayed toxic peak lithium concentration may appear in an acute poisoning with a sustained release lithium product. Therefore, patients presenting with acute intoxication with extended release formulations should be managed with caution, and continued drug monitoring is suggested.

Ciprofloxacin, but not Levofloxacin, Affects Cyclosporine Blood Levels in a Patient with Pure Red Blood Cell Aplasia

A 38-year-old man diagnosed with pure red blood cell aplasia was undergoing treatment with cyclosporine 200 mg/day. On day 41, the cyclosporine dose was increased to 250 mg/day. On day 45, the patient was hospitalized with fever, and ciprofloxacin 200 mg IV tid was begun. The level of cyclosporine was 297 ng/mL, which obliged us to reduce cyclosporine to 200 mg/day. On day 59, ciprofloxacin was discontinued. On day 80, the patient was hospitalized with fever, and levofloxacin 500 mg/d IV was begun. The patient was continued on cyclosporine 250 mg/day. On day 90, levofloxacin was discontinued. The cyclosporine dose-to-blood level ratio was maintained constant in subsequent controls. In this patient, the substantial and sustained increase in cyclosporine blood levels after ciprofloxacin was added to the patients therapy and the decrease in cyclosporine blood levels after the withdrawal of ciprofloxacin suggest a potential interaction. Levofloxacin therapy could be a therapeutic alternative, although pharmacokinetic/pharmacodynamic studies should be conducted.

Extracorporeal Removal of Vancomycin by Plasmapheresis

I. FernandoNH, Hurwitz HI. Targetedtherapyof colorectalcancer: clinical experiencewith bevacizumab. OncoJogist2004;9(suppll):11-8. 2. GordonMS, Cunningham D. Managingpatientstreatedwithbevacizumab combination therapy. Oncology2005;69(suppl 3):25-33. 3. HenryTO,Annex BH,McKendallGR,etal. The VIVA trial: vascularendothelial growth factor in ischemiafor vascularangiogenesis. Circulation 2003;107:1359-65. 4. Katoh M, Egashira K, Mitsui T, et aI. Angiotensin-converting enzyme inhibitorprevents plasminogenactivator inhibitor-I expression in a rat model with cardiovascularremodelinginducedby chronic inhibitionof nitricoxidesynthesis. J Mol Cell Cardiol2000;32:73-83. 5. Hara A, WadaT, Furuichi K, et al, Blockadeof VEGF acceleratesproteinuria, via decrease in nephrin expression in rat crescentic glomerulonephritis. KidneyInt 2006;69:1986-95.