The comparative effects of Itopride and Levosulpiride orally used in patients suffering from Non-ulcer dyspepsia

Background: Itopride and Levosulpiride both comes under the group of Prokinetic drugs. These drugs are used for the treatment of non-ulcer dyspepsia, heart burn, nausea and vomiting. Both drugs act on dopaminergic D2 receptor as antagonist and increases the concentration of acetylcholine so that gastric peristalsis will be increase and that time pressure at lower oesophageal sphincter will be increase thus gastric motility increases and there will be good gastro-duodenal co-ordination.Method: This study has to conduct on patients with complains of non-ulcer dyspepsia attended Medical outdoor and department of pharmacology of SKMCH Muzaffarpur, Bihar, India. The total 60 patients have to include in the study, which have to randomly divide in two groups. Group A (itopride) comprising of 30 patients and Group B (Levosulpiride) comprising of 30 patients. Patients have to randomly allocate to receive one tablet of itopride hydrochloride, 50 mg three times daily before meal and one tablet Levosulpiride of 75 mg three times daily before meal. Authors have to enroll the patients at the interval of two weeks and continue it upto 3 months.Results: Study did not found any remarkable change in biochemistry profile. Only QT prolongation changes were found in two patients, but no serious cardiac toxicity was observed with patient receiving Levosulpiride. Neither QT prolongation nor serious cardiac toxicity was observed with itopride hydrochloride therapy.Conclusions: In present study, efficacy of Itopride was comparable to Levosulpiride in relieving the symptoms of non-ulcer dyspepsia. Both the drugs were clinically and biochemically well tolerated. QT prolongation changes were found in two patients, but no serious cardiac toxicity was observed with patient receiving Levosulpiride. Itopride does not show cardiac toxicity and any changes in ECG.

Prescription pattern & adverse drug reactions of prokinetics

Background & objectives: Prokinetics are extensively prescribed leading to several adverse events (AEs). The aim of this study was to assess the prescription pattern in patients receiving prokinetics, and characteristics of adverse drug reactions (ADRs) in an outpatient department set up in a tertiary care hospital in western India. Methods: Patients attending outpatient departments of a tertiary care hospital and who had received prokinetic agent for at least seven days over the last one month were enrolled. Causality assessment of AEs was done and assessed for severity, preventability, seriousness and predictability. Results: A total of 304 patients [161 males (52.96%); 143 females (47.04%)] were enrolled. Most prescriptions (299/304, 98%) included domperidone, most commonly prescribed as fixed-dose combination (FDC) with pantoprazole (274/304, 90%). Prokinetic dose was not mentioned in 251/304 (83%) prescriptions, and 18/304 (6%) did not mention frequency. Of the 378 AEs reported from 179 patients (47.35%), 306 (81%) were mild, all non-serious; 272 (72%) not preventable and 291 (77%) predictable in nature. Decreased appetite (n=31, 8.2%) and fatigue (n=27,7.14%) were most commonly reported. Causality assessment by the World Health Organization-Uppsala Monitoring Centre scale showed that 180 AEs were related to suspected drug (17 probable and 163 possible ADRs). Significant correlation was observed for AEs with increasing number of drugs per prescription (Spearman's R=+0.8, P =0.05) and with increasing therapy duration (Spearman's R=+1.00, P <0.001). Interpretation & conclusions: Our findings showed that prokinetics were often prescribed as FDCs, with incomplete prescriptions. Domperidone was found to be associated with multiple AEs. It is suggested that regular prescription monitoring should be done in hospitals to encourage rational use of drugs.

Trends in the Prevalence of Drug-Induced Parkinsonism in Korea

PURPOSE: Discontinuation of offending drugs can prevent drug-induced parkinsonism (DIP) before it occurs and reverse or cure it afterwards. The aim of this study was to investigate the prevalence of DIP and the utilization of offending drugs through an analysis of representative nationwide claims data. MATERIALS AND METHODS: We selected DIP patients of ages ranging from 40 to 100 years old with the G21.1 code from the Korean National Service Health Insurance Claims database from 2009 to 2015. The annual standardized prevalence of DIP was explored from 2009 to 2015. Trends were estimated using the compound annual growth rate (CAGR) and the Cochran-Armitage test for DIP over the course of 6 years. Additionally, the utilization of offending drugs was analyzed. RESULTS: The annual prevalence of DIP was 4.09 per 100000 people in 2009 and 7.02 in 2015 (CAGR: 9.42%, p<0.001). Levosulpiride use before and after DIP diagnosis showed a clear trend for decreasing utilization (CAGR: −5.4%, −4.3% respectively), whereas the CAGR for itopride and metoclopramide increased by 12.7% and 6.4%, respectively. In 2015, approximately 46.6% (858/1840 persons) of DIP patients were prescribed offending drugs after DIP diagnosis. The most commonly prescribed causative drug after DIP diagnosis was levosulpiride. CONCLUSION: The prevalence of DIP has increased. To prevent or decrease DIP, we suggest that physicians reduce prescriptions of benzamide derivatives that have been most commonly used, and that attempts be made to find other alternative drugs. Additionally, the need for continuing education about offending drugs should be emphasized.

Hyperprolactinemia after taking Levosulpiride and its Causality Assessment: An Adverse Event Reported by a Community Pharmacy

Levosulpiride is one of the most frequently prescribed medicines in Korea. An adverse drug reaction (ADR) after taking levosulpiride was reported at a community pharmacy in Korea. A 31-year-old woman reported the symptoms of lactation and amenorrhea after taking levosulpiride; an evaluation of whether these symptoms were caused by the medication was therefore necessary. Several tools can be used to determine if the ADR resulted from the administered drug or other factors, including the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) criteria, the Naranjo scale, and the Korean causality assessment algorithm (Ver. 2). The causality was evaluated as “possible” by the WHO-UMC and Naranjo scales, but as “probable” by the Korean causality assessment algorithm (Ver. 2). In conclusion, the information provided did not indicate definite causality and there were slight differences in the results obtained from each assessment method.

Pharmacokinetics of levosulpiride after single and multiple intramuscular administrations in healthy Chinese volunteers

The main purpose of this study was to evaluate the pharmacokinetics of levosulpiride in humans after single and multiple intramuscular injections. Six males and six females received single dose of either 25 mg or 50 mg levosulpiride, or multiple doses of 25 mg every 12 h for 5 consecutive days. In the single 25 mg study, the mean peak plasma concentration (C max) was 441 ng/mL, the mean area under the concentration-time curve from 0 to 36 h (AUC0-36) was 1724 ng h/mL, and the mean elimination half-life (t 1/2) was 7.0 h. In the single 50 mg study, the mean C max was 823 ng/mL, the mean AUC0-36 was 3748 ng·h/mL, and the mean t 1/2 was 6.8 h. After multiple doses of 25 mg levosulpiride, the average plasma concentration (C av) was 136 ng/mL, the fluctuation index (DF) was 3.60, and the accumulation ratio (R) was 1.2. Levosulpiride injections appeared to be well tolerated by the subjects, and can be used for successive administration.

The Effects of Pyridostigmine and Levosulpiride on the Contraction of Rabbit Urinary Bladders / 대한비뇨기과학회지

PURPOSE: This study was performed to identify the effects of bethanechol, pyridostigmine and levosulpiride, on the contraction of rabbit bladder strip tissue in a single agent administration, and to investigate the synergistic effects in a mixed administration. MATERIALS AND METHODS: Smooth muscle strips of bladder were prepared using female, New Zealand white, rabbits. After an equilibration period, dose response curves to each agent, with cumulative administration, were performed in the basal tension state of the strips. Each strip was then pretreated with the agent at the maximal concentration that would not induce a bladder contraction, and second dose-response curves for the other agents were obtained. Following this, the maximal stimulation with bethanechol was performed, and during the tonic response, pyridostigmine or levosulpiride was administrated to observe any synergistic effects of the agents. Similar experiments were repeated for the pyridostigmine and levosulpiride. RESULTS: Each agent elicited a dose-dependent contractile response, in the order; bethanechol (0-4.49g/100mg tissue), pyridostigmine (0-1.58g/100mg tissue) and levosulpiride (0-0.44g/100mg tissue). In the presence of pyridostigmine (3x10(-6)M) or levosulpiride (10(-4)M), no additive effects were noted after the cumulative stimulation with bethanechol (10(-10)-10(-4)M). During the tonic response of bethanechol (10(-4)M) or pyridostigmine (10(-2)M), the addition of levosulpiride (10(-2)M) induced a significant increase in the bladder strip contractions, but the addition of pyridostigmine (10(-2)M) or bethanechol (10(-4)M) decreased the maximal response (p<0.05). CONCLUSIONS: These results imply that pyridostigmine may be useful for impaired detrusor contractility management. Synergistic effects can also be expected when administrating levosulpiride, in addition to bethanechol, in improving bladder contractility.

Levosulpiride-induced Parkinsonim

The present report discusses four cases of chronic renal failure, which developed symptoms of parkinsonism in response to levosulpiride. The temporal relationship between levosulpiride discontinuation and the disappearance of parkinsonism suggests a causal link. In addition, decreased striatal dopamine transporter bindings assessed by [I-123] IPT SPECT were observed in two patients suggesting that a dopamine blocking agent causes the dysfunction of nigrostriatal dopaminergic neurons and that such injury may be involved in the pathogenesis of drug-induced parkinsonism.

Effects of Levosulpiride in Patients with Nonspecific Esophageal Motility Disorder / 대한소화관운동학회지

BACKGROUND/AIMS: Levosulpiride is the levo-enantiomer of sulpiride, a well-known antiemetic, antidyspeptic and antipsychotic drug. This study was undertaken to investigate the effects of levosulpiride on esophageal symptoms, esophageal peristalsis, and lower esophageal sphincter pressure (LESP), as well as evaluate the side effects in patients with nonspecific esophageal motility disorder (NEMD). METHODS: Thirty patients with NEMD (12 males and 18 females, with a mean age 48.6 +/- 13.0 years old) were administered 25 mg of levosulpiride t.i.d. for 2 weeks. Symptom assessment, esophageal manometry, blood biochemistry and serum prolactin concentrations were evaluated before and after treatment. For the evaluation of serum prolactin concentrations according to the dose of levosulpiride, 10 healthy volunteers were administered 25 mg or 12.5 mg of levosulpiride t.i.d., and serum prolactin concentrations were examined before and after treatment weekly. RESULTS: After treatment with levosulpiride, the symptom score was improved significantly (6.5 +/- 3.0 vs. 3.9 +/- 2.7, p < 0.05), but esophageal manometric findings were not improved. Two patients developed breast engorgement and the serum prolactin concentration was significantly elevated after treatment with levosulpiride. However, the increased serum prolactin level returned to a normal level within one week, and there was no difference in regards to the dose of levosulpiride. CONCLUSIONS: Levosulpiride did not improve the esophageal motor abnormality, but was effective for esophageal symptoms, which might be the result of the antidopaminergic effect on the central nervous system. Hyperprolactinemia developed in all patients, but it was normalized within a week, and symptoms for hyperprolactinemia were seen in only a few cases.