Baclofen neurotoxicity in chronic hemodialysis

Charcoal hemoperfusion is an effective treatment in acute drug intoxication with small volume of distribution. For certain drugs, clearance rates are higher with hemoperfusion than hemodialysis. We describe a patient with severe valproic acid overdose who developed severe hemolysis and acute renal failure related to charcoal hemoperfusion treatment. A 50-year-old female was admitted to the hospital following valproic acid overdose. Initial valproic acid level was 73.6 mg/L, and she was treated with oral activated charcoal. Four hours later she developed mental status changes with valproic acid level at 490.9 mg/L and prolonged QT interval. Charcoal hemoperfusion was started with blood flow rate 400 ml/min. Patient developed bleeding with evidence of severe  

     

Clearance of myoglobin by high cutoff continuous veno‐venous hemodialysis in a patient with rhabdomyolysis: A case report

Continuous veno‐venous hemodialysis using high cutoff filters (HCO‐CVVHD) is a promising technique, which may be effective to decrease the extremely high level of circulating myoglobin in patients with rhabdomyolysis (RM). Here, we report a patient with RM caused by heat stroke who was successfully treated by HCO‐CVVHD. A male patient received HCO‐CVVHD with 4 L/h dialysate for 5 days and then pre‐dilution continuous veno‐venous hemofiltration (CVVH) at a dose of 4 L/h until recovery of renal function. The clearance of myoglobin and albumin at 5 minutes, and at 4, 12, and 24 hours were calculated. The serum myoglobin level decreased from a peak of 25,400 ng/mL on admission to 133 ng/mL at discharge. During HCO‐CVVHD, the mean clearances of serum myoglobin at four timepoints were 61.3 (range, 61.0–61.6), 52.3 (38.9–65.8), 47.3 (46.8–47.9), and 43.7 (39.5–48.0) mL/min, respectively, and the mean clearances of albumin were 12.4 (range, 11.8–13.1), 3.1 (2.5–3.8), 1.2 (1.0–1.4), and 0.8 (0.6–1.0) mL/min, respectively. During CVVH, the clearance rates of myoglobin at 5 minutes and 24 hours were 17.0 and 3.8 mL/min, respectively, with a negligible clearance of albumin. HCO‐CVVHD can effectively decrease serum myoglobin in patients with RM because of much higher clearance of myoglobin than CVVH. However, attention should be paid to albumin loss during HCO‐CVVHD.     

Severe carbamazepine intoxication unresponsive to albumin‐enhanced continuous venovenous hemodiafiltration with low dialysate flow

Carbamazepine (CBZ) intoxication can be associated with severe toxicity, including neurological and cardio‐respiratory abnormalities. Highly protein‐bound, CBZ is not removed efficiently through conventional hemodialysis. Charcoal hemoperfusion is the most effective extracorporeal elimination therapy for CBZ intoxication. Recent reports have indicated that continuous venovenous hemodiafiltration (CVVHDF), albumin‐enhanced continuous venovenous hemodialysis, high‐flux hemodialysis and plasma exchange can be as effective as charcoal hemoperfusion. In contrast to recent reports, which demonstrated the effectiveness of CVVHDF with high dialysate flow in CBZ intoxication, we observed that serum CBZ level was decreased minimally by albumin‐enhanced CVVHDF with low dialysate flow. Therefore, albumin‐enhanced CVVHDF with high dialysate flow should be considered in severe CBZ intoxication, if hemoperfusion is unavailable because of the lack of facilities or if it cannot be performed.     

Sustained low-efficiency dialysis with filtration (SLEDD-f) in the management of acute sodium valproate intoxication

Hemodialysis is only infrequently used in drug overdosage situations. The efficacy of hemodialysis to remove the drug depends upon the pharmacokinetics and pharmacodynamics of the drug. At normal therapeutic concentrations, valproic acid is predominantly protein bound and therefore removal by hemodialysis is limited. In an overdose situation, protein binding is rapidly saturated and therefore the substantially larger quantities of the free drug can rapidly cause toxicity. Slow low-efficient daily diafiltration (SLEDD) has not previously been utilized in a drug overdose situation. We report the effective use of SLEDD to remove high toxic concentrations of valproic acid in an overdose situation. Slow low-efficient daily diafiltration also prevented the rebound phenomenon that can occur as the excess drug is released from its protein-bound stores. Hybrid dialysis therapies deserve further evaluation in the management of other poisonings where extra-corporeal therapy is indicated.     

Clinical Experiences High‐flux hemodialysis in the treatment of severe valproic acid overdose: A case report

Introduction:  Hemoperfusion, with or without hemodialysis, has been used to treat patients suffering from severe valproic acid poisoning. We report a patient suffering from severe valproic acid intoxication who was treated effectively with high‐flux hemodialysis alone. Case:  A 20‐year‐old man with a history of bipolar disorder was admitted after having ingested unknown amounts of valproic acid (Depakote®), prednisone, and erythromycin. He was agitated and obtunded but hemodynamically stable initially. Serum valproic acid level was 1,028 μg/mL. Urine toxicology screen as well as serum levels of ethanol, acetaminophen, and acetylsalicylic acid levels were negative. A gastric lavage was followed by activated charcoal instillation. Subsequent myoclonic twitchings that progressed to continuous seizure activity were managed with intravenous lorazepam therapy and endotracheal intubation. Serum valproic acid value measured two hours after admission remained elevated at 1,046 μg/mL. Hemodialysis was performed continuously for 10.5 hours using a high‐flux, polysulfone dialyzer (Polyflux 21S, Fresenius Medical Care, Lexington, MA), a dialyzer blood flow of 200–300 mL/min, and a dialysate flow of 500 mL/min. The therapy brought about a fall in serum valproic acid level to 110 μg/mL and a complete recovery of the patient. Discussion:  Valproic acid (144 Dalton) is 90–95% protein‐bound at therapeutic serum values. However, in the face of an overdose, the unbound fraction rises because of saturation of protein‐binding sites. This unbound fraction is readily dialyzable. We suggest that high‐flux hemodialysis is effective in the treatment of severe valproic acid poisoning.     

Successful treatment of carbamazepine poisoning with hemodialysis: a case report and review of the literature

A 48-year-old man was brought to the emergency room after ingesting an unknown amount of carbamazepine. He was unconscious and not responding to the noxious stimuli. He was intubated and was placed on mechanical ventilation because of respiratory insufficiency. Primary detoxification was performed with a gastric lavage and charcoal instillation. His serum carbamazepine level was 25.6 mcg/mL at the time of admission. His computed tomography of the brain was normal. He was managed conservatively but there was no improvement in his neurological status in the next 24 hours. Serum carbamazepine level was repeated and reported to be 28.3 mcg/mL. As there was no improvement in his sensorium and the serum carbamazepine levels remained persistently high, extracorporeal removal of carbamazepine was attempted. As the facility to carry out hemoperfusion was not available immediately, the decision to initiate hemodialysis was taken. After 3 sessions of hemodialysis, his sensorium improved markedly and the carbamazepine level at this time was within the therapeutic range. He was discharged after psychiatry consultation and counseling. We review the literature regarding extra corporeal techniques for the removal of carbamazepine and discuss them in this article.     

Acute hemolysis with acute renal failure in a patient with valproic acid poisoning treated with charcoal hemoperfusion

Hemoperfusion consists of the passage of anticoagulated blood through a column containing adsorbent particles. It was introduced in 1940 and refined from 1950 to 1970, and then introduced clinically for the treatment of acute intoxications between 1970 and 1980. Life-threatening valproic acid toxicity is an indication for coated charcoal hemoperfusion usually accomplished without complications, but we report a case of acute severe intravascular hemolysis during the time of hemoperfusion with coated charcoal column.     

High sodium continuous veno‐venous hemodialysis with regional citrate anticoagulation and online dialysate generation in patients with acute liver failure and cerebral edema

Introduction: Acute liver failure is associated with a high mortality rate. Induction of plasma hypertonicity with mannitol or hypertonic saline remains the cornerstone in the management of resultant cerebral edema. Significant disadvantages of this approach include poor or unpredictable control of serum sodium concentration and volume expansion, among others. Methods: We used high sodium continuous veno‐venous hemodialysis with regional citrate anticoagulation and online dialysate generation to accurately control the serum sodium in eleven patients with acute liver failure, renal failure, and cerebral edema. We used a Fresenius 2008 K/K2 machine in hemodialysis mode to deliver a blood flow of 60 ml/minute and dialysate flow of 400 ml/minute. Our previously published protocol results in complete removal of infused citrate by the dialyzer. On‐line clearance calculations were used to model the time required to reach the target serum sodium. Findings: All patients achieved serum sodium within 2 mEq/L of target without fluctuations or rebound. Nine patients survived without requiring liver transplantation and two died despite reaching the prescribed serum sodium target. We did not encounter any citrate toxicity. Discussion: We describe a novel approach for delivering continuous osmotherapy to patients with acute liver failure, renal failure, and cerebral edema. In comparison to standard therapy, the described modality enables precise titration of serum sodium without undesirable fluctuations in extracellular fluid volume. A particular advantage is zero delivery of citrate to this vulnerable group of patients with acute liver failure.     

Chronic fondaparinux use in a hemodialysis patient with heparin‐induced thrombocytopenia type II and extracorporeal circuit thrombosis—A case report and review of the literature

Heparin‐induced thrombocytopenia (HIT) is a potentially life‐threatening condition that can develop after exposure to unfractionated or low–molecular‐weight heparins. Treatment options appear to be limited in patients on concurrent intermittent hemodialysis. We report the case of an 88‐year‐old man newly initiated on high‐flux hemodialysis who developed HIT and extracorporeal circuit thrombosis after 3 weeks of exposure to unfractionated heparin. Our patient was successfully treated with fondaparinux 2.5 mg subcutaneously three times per week and citrate during dialysis sessions. Antifactor Xa levels were measured on several occasions while receiving fondaparinux.     

Regional Anticoagulation with Sodium Citrate in Pediatric Patients on Intermittent Hemodialysis Therapy with Bleeding Risks

Heparin‐free anticoagulation in hemodialysis (HD) is advocated for patients with clotting abnormalities and risk of bleeding. Objective: First publication on regional citrate anticoagulation (RCA) in children. RCA is free from systemic effects, guarantees excellent dialyzer life, but requires careful monitoring. Methods: We report on 3 patients treated by intermittent RCA HD (4 h each, high‐flux dialyzer F40, Fresenius): (1) 17‐year‐old boy (renal transplant failure, access via cubital Cimino fistula) after hypertensive intra‐cerebral hemorrhage (2 sessions); (2) 13‐year‐old girl (hemolytic uremic syndrome, access via jugular vein Shaldon catheter) after abdominal surgery and bleeding (8 sessions); and (3) 7‐year‐old boy (hyperoxaluria, access via PermCath^® jugular vein catheter) after renal transplant biopsy (3 sessions). Sodium citrate 30% was infused into the extra corporeal circuit (blood flow 150 mL/min) before dialyzer (initial flow 30 mL/min) and calcium gluconate 10% for antidote into venous line near of catheter or fistula (initial flow 40 mL/min). Post‐dialyzer extracorporeal serum Ca⁺⁺ (aim < 0.3 mmol/L) and pre‐dialyzer intra‐corporeal Ca⁺⁺ (aim > 0.9) were measured for every 30 min. Serum Na⁺, K⁺, base excess (BE), blood flow, blood pressure, heart rate, and blood out‐flow and in‐flow pressure were also monitored. Results: For adequate RCA (mean extracorporeal serum Ca⁺⁺ 0.24 ± 0.04 mmol/L), a mean citrate flow of 36.1 ± 5.9 mL/h and a mean calcium substitution rate of 40.8 ± 3.4 mL/h were needed. Intra‐corporeal Ca⁺⁺ was kept at 1.10 ± 0.07 mmol/L. Extracorporeal activated clotting time (ACT) was 194 ± 41 and intra‐corporeal ACT 90 ± 12 sec. Serum Na⁺, K⁺, and BE during HD were 138 ± 2, 3.5 ± 0.3, and ?0.6 ± 1.1 mmol/L, respectively. Mean arterial blood pressures of patients 1–3 were 117 ± 5, 103 ± 5, and 102 ± 6 mmHg. All patients were stable and without any bleeding during HD. The only adverse event was 1 episode of hypocalcemia (Ca⁺⁺ < 0.6 mmol/L) cured by stopping dialysis. Conclusions: Local anticoagulation with sodium citrate during intermittent HD can be applied safely in children and adolescents.     

Thrombotic events and markers of oxidation and inflammation in hemodialysis

The goal of this study was to determine whether antioxidant therapy with vitamin E would alter the rate of vascular access complications or other macrovascular complications in hemodialysis (HD) patients. A secondary goal of the study was to explore the relationship between baseline pretreatment markers of oxidative stress (the advanced glycation end product pentosidine and basal levels of vitamin Eα and γ) and the subsequent development of access failure. Thirty‐five stable patients treated by HD were recruited for the study. Patients were provided with vitamin E (800 IU) or placebo capsules to be taken daily. Clinical variables, vascular access function (flow meter access flow measurements), and circulating blood markers were obtained initially and every 3 months throughout the study. Vitamin Eα levels rose in treated patients from 12.7 ± 4.4 to 25.1 ± 15.1 µg/mL at 3 months and 28.6 ± 14.8 µg/mL at 6 months. Vitamin Eγ levels fell in treated patients from 3.9 ± 1.7 to 2.3 ± 1.5 µg/mL at 3 months and 1.7 µg/mL at 6 months. Patients who subsequently developed repeated thrombotic vascular access events were characterized by higher baseline pentosidine content of circulating proteins. Patients who developed a myocardial infarction had higher pentosidine, lower vitamin Eα, and much lower vitamin Eγ than patients who did not develop thrombotic events. These findings lead to the speculation that the anti‐inflammatory effects of vitamin Eγ may play a more important role in thrombotic vascular events than the antioxidant effects of vitamin Eα. Additional studies of these interactions are in progress.     

Metformin intoxication requiring dialysis

Metformin (MTF) is one of the most common oral agents used to treat diabetes mellitus. Intoxication is associated with lactic acidosis and has significant clinical consequences. We report 12 cases requiring dialytic intervention. Twelve patients were analyzed from 2005 to 2010; 10 of these patients were treated with dialysis. Conventional hemodialysis (HD) and continuous veno-venous hemodialysis treatments with bicarbonate dialysis were used, and the results were presented as mean and standard deviation. The results are as follows: 33% of the patients were male, hospital stay was 9.3 (± 12) days, average MTF dose 1.7 g/day, mortality was 25%. Baseline glomerular filtration rate for these patients was 51.5?mL/min, with an average age of 64 (± 11) years. On presentation, all had acute kidney injury with blood urea nitrogen/creatinine 75 (± 30)/8.1 (± 3.7) mg/dL, lactic acid 12.4 (± 8.1) mmol/L, pH?7.04 (± 0.19), bicarbonate 7.2 (± 4.5) mmol/L. Metformin level was 25 (± 17) μg/mL; anion gap was 28 (± 9), and serum potassium was 5.4 (± 1.3) mEq/L. Seventy percent of patients were treated with conventional HD. Patients required 4 (± 5) dialysis treatments at blood flow QB 330 (± 53), dialysis flow QD 571 (± 111) for 305 (± 122) minutes. Postdialysis, the acidosis parameters improved: bicarbonate 19.2 (± 4.1) mmol/L, lactic acid 6 (± 4) mmol/L and MTF levels decreased 8.9 (± 5.7) μg/mL. Metformin percentage removal was calculated to be 60% (± 24). No difference was found between HD and continous veno-venous hemodialysis. The only difference between survivors was the age 53 (± 7) vs. 78 (± 10) (P?相似文献   

Hemodialysis for treatment of levofloxacin‐induced neurotoxicity

Levofloxacin, a third‐generation fluoroquinolone antibiotic, is rarely associated with neurotoxicity. Patients with advanced kidney disease are particularly vulnerable to this adverse effect. We present two elderly patients with kidney failure who developed levofloxacin‐induced neurotoxicity, which was successfully treated with frequent hemodialysis, resulting in the full resolution of their symptoms. Neurotoxicity is a well‐known side effect of fluoroquinolone antibiotics. Postulated mechanisms include inhibition of the gamma‐aminobutyric acid A receptors and activation of the excitatory N‐methyl‐D‐aspartate receptors. Risk factors include older age, kidney disease, pre‐existing neurological disorders, and drug–drug interactions. While management of levofloxacin‐induced neurotoxicity includes discontinuation of the drug and supportive care, hemodialysis is not recommended, despite available pharmacokinetic data in support of its dialyzability. The successful use of hemodialysis for the treatment of levofloxacin‐induced neurotoxicity observed in our two patients with kidney failure should be further considered for rapid resolution of this rare fluoroquinolone‐related adverse effect in patients with impaired kidney function.     

Case of Mycobacterium mucogenicum in a home hemodialysis patient

We present a case of a patient on home hemodialysis who developed Mycobacterium mucogenicum bacteremia. While infections with this particular organism are rare, disseminated infections have been reported and have been associated with significant morbidity and mortality. Diagnosis required appropriate cultures, understanding of natural habitat of organism and complete environmental analysis including blood, dialysis sample port, reverse osmosis and incoming water supply cultures. The patient was treated successfully with systemic antibiotics, removal of central venous catheter, patient education and complete exchange of the hemodialysis circuit.     

Comparison of urea clearance in low‐efficiency low‐flux vs. high‐efficiency high‐flux dialyzer membrane with reduced blood and dialysate flow: An in vitro analysis

Rapid removal of small molecules during hemodialysis places an acutely ill patient with kidney failure at an increased risk of hemodynamic instability and for dialysis disequilibrium syndrome. The use of high‐flux, high‐efficiency (HEF) dialyzers may increase this risk despite reductions in blood and dialysate flow. We performed in vitro experiments to compare urea clearance at low dialysate flow and various blood flows using a low‐efficiency low‐flux (LEF) and a HEF membrane. Compared to LEF, there was a significant increase in the clearance of urea at all blood flows with the HEF (all P values < 0.005). HEF dialyzer (F180NR) had higher urea clearance at a blood flow of 150 mL/min than LEF dialyzer (F5) at blood flow of 300 mL/min (144.1 ± 0.99 vs. 130.1 ± 0.001 mL/min for F180 vs. F5, respectively, P < 0.002). Our data suggest that use of HEF dialyzer are not as safe as LEF in high‐risk acute dialysis patients since these are associated with more rapid removal of urea despite reduction in blood and dialysate flow as compared to LEF.     

The CLOCK trial,a double‐blinded randomized controlled trial: Trisodium citrate 30% and minocycline 3 mg/mL plus EDTA 30 mg/mL are effective and safe for catheter patency maintenance among CKD 5D patients on hemodialysis

Introduction: Poor blood flow rate (PF) is highly prevalent among CKD 5D patients with long‐term central venous catheters. Heparin catheter lock solutions are commonly used to maintain catheter patency, however the incidence of PF remains high. The purpose of the CLOCK Trial was to evaluate two catheter lock solutions on reduction of PF incidence. Methods: Seventy‐five CKD 5D patients on high‐efficiency hemodialysis at the Integrated Centre of Nephrology (Guarulhos, Brazil) were randomized 1:1:1 to receive a lock solution combining minocycline 3 mg/mL with the anticoagulant/chelation agent EDTA 30 mg/mL (M‐EDTA) or heparin 1000 IU/mL (H) or trisodium citrate 30% (TSC) vs. Hfor 15 weeks. A total of 68 patients completed the trial in which both investigators and patients were blinded to treatment allocation. The primary end‐point was the occurrence of hydraulic resistance and secondary safety end‐point was adverse drug reactions related to the lock solutions. Findings: At the beginning of the trial, 7 patients were excluded from this trial due to their poor catheter care. The incidence of hydraulic resistance was significantly higher among patients on H (18/23) compared to TSC (4/22) and M‐EDTA (2/23) lock solutions, (P < 0.001). Discussion: The CLOCK Trial suggests TSC and M‐EDTA may preserve catheter patency better than H. TSC may be a better option due the lack of association with long‐term antimicrobial resistance.     

Remove or not,that is the question: A case report on carotid artery cannulation during indwelling venous hemodialysis catheter

A 58‐year‐old woman visited the emergency department for acute occlusion of arteriovenous fistula. One session of hemodialysis was scheduled via temporary venous hemodialysis catheter before thrombectomy. Unfortunately, neck arterial cannulation was discovered after complete placement of catheter. The catheter was removed immediately but bleeding could not be stopped. Pseudoaneurysm over the right carotid artery was proved by angiography and repaired by graft stent. Arterial cannulation during venous hemodialysis catheter insertion is a rare but serious complication and there is no standard response recommended. Immediate removal of the misplaced hemodialysis catheter might not be the best choice. We suggest to leave the misplaced catheter in artery until further intervention in consideration of complications and repair access. Every hemodialysis center should standardize responses to arterial cannulation during venous hemodialysis catheter indwelling, especially carotid puncture happens, according to the medical facility.     

Phosphorus Clearance Using Two Hemodialyzers Placed in Parallel

Control of hyperphosphatemia is a major goal in patients with end‐stage renal disease. However, removal of retained inorganic phosphorus during hemodialysis remains a major problem. We compared clearances and total phosphate removal in large patients treated with two F‐80 dialyzers (Fresenius Medical Care of North America, Lexington, MA, U.S.A.) placed in parallel, and small patients dialyzed with a single F‐80 dialyzer (SD). Clearances were obtained using total dialysate collections. Eight dialysate collections (5 patients) using double parallel dialyzers (DD group) were compared with 5 dialysate collections (4 patients) using single dialyzers (SD group). Blood and dialysate flow rates and time of dialysis treatment were identical between the groups. The DD group's Kt/V _urea was 1.46 ± 0.13; SD group's Kt/V _urea was 1.35 ± 0.09 (p = 0.2). Absolute phosphorus removal was 1594 ± 300 mg for the DD group, compared to 1108 ± 285 mg in the SD group (p = 0.03). Urea clearance in the DD group was 285 ± 25 mL/minute and 251 ± 27 mL/ min in the SD group (p = 0.082). Phosphorus clearance was 178 ± 32 mL/min in the DD group and 149 ± 38 mL/min in the SD group (p = 0.039). There was no correlation between phosphorus clearance and dialyzer reuse. The bulk of phosphorus removal was achieved during the first 2 hours of hemodialysis. This finding is consistent with the hypothesis that there are at least two pools of body phosphorus. Using hemodialyzers placed in parallel led to higher phosphate clearance and total phosphorus removal. This higher phosphate removal may be related in part to increasing the concentration gradient for transfer out of a second compartment.     

Citrate anticoagulant hemodialysate in renal failure patients at high risk of bleeding

Objective: The aim of this study was to observe the anticoagulant effect of the new type of citrate anticoagulant hemodialysate in renal failure patients at high risk of bleeding. Methods: 57 patients at high risk of bleeding were given hemodialysis for 4 hours and were divided into 3 groups according to hemodialysis procedures: Group 1 was saline‐flush hemodialysed with bicarbonate hemodialysate. Group 2 was hemodialysed with citrate hemodialysate and with no anticoagulant. Group 3 was hemodialysed with bicarbonate hemodialysate and with nadroparin calcium (a low molecular weight heparin, LMWH) as anticoagulant. Bleeding complication, coagulation of extracorporeal circuit, venous blood pressure, heart rate, QT_C, activated coagulation time (ACT), ionized‐calcium (iCa⁺⁺), total calcium and pH, , Na⁺, K⁺, Cl^?, BUN, Cr, GPT, GST, TBIL, DBIL, as well as the blood cell counts were monitored during hemodialysis, and a scanning electron microscopic (SEM) analysis was used to investigate the morphology of thrombus formation and cellular aggregation on the interior surface of hemodialysis membranes. Results: During the hemodialysis in Group 1, venous blood pressure increased continuously, resulting in the failure of hemodialysis for 4 out of 19 patients. Hemodialysis for 4 hours in Group 2 were all successfully fulfilled. No bleeding episodes occurred. No severe clotting of dialyzers and blood accesses was observed. ACT was extended and iCa⁺⁺ decreased obviously in the venous line, but ACT and iCa⁺⁺ in vivo were normal. pH, tended to increase but not to metabolic alkalosis levels. Na⁺, K⁺, Cl^?, GPT, GST, TBIL, DBIL, as well as the counts of blood cells were all within the normal range. There was no severe thrombus observed by SEM in the hollow fibers. In Group 3, severe bleeding complication happened to 3 out of 19 patients, and one of them died. ACT was extended obviously at the arterial end. Conclusions: The citrate anticoagulant hemodialysate was proved to be practical, safe and effective. So it is indicated for patients with an active or recently active bleeding focus.     

Development of fixed dose combination tablets of aripiprazole plus divalproex sodium and their simultaneous determination using HPLC-UV

A vast majority of psychiatric patients are effectively treated with combination of drugs to improve efficacy and adherence, but due to limited research and development in fixed dose combination (FDC) in psychiatry, these products are not commonly available. The aim of this study is to prepare cost effective FDC tablets containing aripiprazole and divalproex sodium. Two batches of fixed dose combination tablets, FDC1 and FDC2, were successfully prepared using wet granulation technique. Furthermore, aripiprazole tablets A1 and A2 and divalproex tablets D1 were also formulated as reference to compare the in vitro availability profile. An accurate and simple isocratic HPLC method was established and validated for the simultaneous quantification of aripiprazole and valproic acid in the FDC tablets. A reversed-phase C18 (250?×?4.6?mm) column in isocratic mode was used. The mobile phase consisted of acetonitrile and 0.32% KH₂PO₄ (60:40, v/v), flow rate was set at 1.0?mL/min and the detection was performed at 210?nm. Average percent recoveries of aripiprazole and valproic acid were 96.0 and 95.5%, respectively, meeting the official requirements. The newly developed FDC product may be used for the better therapeutic outcomes of combined use of aripiprazole and valproic acid, which may improve patient adherence.