Eperisone-Induced Anaphylaxis: Pharmacovigilance Data and Results of Allergy Testing

PURPOSE: Eperisone is an oral muscle relaxant used in musculoskeletal disorders causing muscle spasm and pain. For more effective pain control, eperisone is usually prescribed together with nonsteroidal anti-inflammatory drugs (NSAIDs). As such, eperisone may have been overlooked as the cause of anaphylaxis compared with NSAIDs. This study aimed to analyze the adverse drug reaction (ADR) reported in Korea and suggest an appropriate diagnostic approach for eperisone-induced anaphylaxis. METHODS: We reviewed eperisone-related pharmacovigilance data (Korea Institute of Drug Safety-Korea Adverse Event Reporting System [KIDS-KAERS]) reported in Korea from 2010 to 2015. ADRs with causal relationship were selected. Clinical manifestations, severity, outcomes, and re-exposure information were analyzed. For further investigation, 7-year ADR data reported in a single center were also reviewed. Oral provocation test (OPT), skin prick test (SPT) and basophil activation test (BAT) were performed in this center. RESULTS: During the study period, 207 patients had adverse reactions to eperisone. The most common ADRs were cutaneous hypersensitive reactions (30.4%) such as urticaria, itchiness or angioedema. Fifth common reported ADR was anaphylaxis. There were 35 patients with anaphylaxis, comprising 16.9% of the eperisone-related ADRs. In the single center study, there were 11 patients with eperisone-induced anaphylaxis. All the patients underwent OPT and all the provoked patients showed a positive reaction. Four of the 11 patients with anaphylaxis also underwent SPT and BAT, which were all negative. CONCLUSIONS: Incidence of eperisone-induced anaphylaxis calculated from the KIDS-KAERS database was 0.001%. Eperisone can cause hypersensitive reactions, including anaphylaxis, possibly by inducing non-immunoglobulin E-mediated immediate hypersensitivity.

Study on the effect of Eperisone in the treatment of Subacute spinal cord neurosis / 中国生化药物杂志

Objective To investigate the therapeutic effect of eperisone on patients with subacute spinal cord neuropathy with incomplete spasm.Methods Forty-eight patients with Subacute spinal cord neurosis combined degeneration of both lower extremity incomplete spasm in Department of Neurology,Zhejiang Quhua Hospital were selected and randomly divided into control group and study group.The control group were treated with folic acid and mecobalamin,the study group received more with eperisone,and 14days for one course,two groups were treated for two course.Ashworth spasm Scale,simple Fugl-Meyer score scale,improved Barthel index,bilateral H tibial nerve reflex status,clinical efficacy and complications were compared before and after the treatment.Results After treatment,levels of the flexion and extension of knee joint in 2 groups increased,and the scores of Ashworth spasticity scale decreased,scores of FMA and MBI increased,the latency of H reflex latency increased,levels of Hmax/Mmax decreased(P<0.05),compared with the control group,levels of the flexion and extension of knee joint in the study group were higher,and the scores of Ashworth spasticity scale were lower,scores of FMA and MBI were higher,the latency of H reflex latency were higher,levels of Hmax/Mmax were lower(P<0.05),the effective rate of the control group(66.67％)was lower than the study group(91.67％)(P<0.05),the non-performing rate in 2 groups had no difference(25.00％Vs 20.83％).Conclusion Eperisone has definite effect on patients with subacute spinal cord neuropathy with incomplete spasms.it can decrease muscle tension and spasticity and improve neurological function.

A case series of eperisone-induced immediate hypersensitivity

Eperisone is a widely used muscle relaxant and believed to be relatively free of adverse drug reactions. However, a rare case of fatal anaphylaxis has been reported in the literature. Poor awareness due to its rarity and combined administration with other drugs are the major hurdles in diagnosing eperisone-induced anaphylaxis. We experienced 3 cases of immediate hypersensitivity reaction occurring after eperisone administration. Case 1, a 63-year-old female, was admitted via the Emergency Department with urticaria, generalized erythroderma, sore throat, chest discomfort, and dyspnea within 1 hour after administration of common cold remedy. Case 2, a 58-year-old male, visited our allergy clinic to detect culprit drugs. He experienced itching, urticaria, hypotension for several hours after administration of the pills for back pain in the last 3 years. Case 3, a 58-year-old male developed urticaria and dyspnea after administration of medication for a headache. He also experienced urticaria and facial edema after administration of the common cold remedy. Among the medications, eperisone hydrochloride was proven as the culprit drug and others were excluded through oral provocation tests. We advised them to avoid eperisone and issued drug safety card. Clinicians should be aware that eperisone hydrochloride is a potential culprit agent of fatal anaphylaxis.

Anaphylaxis caused by muscle relaxant (eperisone hydrochloride)

Eperisone hydrochloride is an antispasmodic drug, decreasing spasticity of skeletal muscle and alleviating stiffness, and as a consequence, controlling pain. It is preferably prescribed with other analgesics, beneficially less decreasing alertness compared with other antispasmodics. Its fatal drug adverse reactions were rarely reported. A 70 year-old female with hives, swollen face, hoarse voice, and near fainting admitted via emergency department. She suffered from the series of the fatal symptoms after administration of the pills, prescribed for her neck pain. Two months before, she had experienced hives on similar medications. At presentation, she revealed hypoxemia and hypotension, and treated with epinephrine, glucocorticoids and antihistamines. Among the medicines she took, eperisone hydrochloride was proven as the causative medicine and others were excluded in oral provocation tests. The positive result in intradermal test with eperisone hydrochloride suggested immediate-type hypersensitivity reaction. We report a case of anaphylaxis to eperisone hydrochloride, one of the widely prescribed medicines in clinical practice, previously without awareness of drug adverse reaction.

The efficacy of proquazone combined with eperisone in treatment of tension headache / 中国基层医药

Objective To observe the clinical efficacy and adverse reactions of proquazone combined with eperisone in treating tension headache.Methods 285 tension headache patients in our hospital from 2009 to 2011were randomly divided into A,B,C three groups.Group A with 95 cases used only eperisone treatment,while B group with 95 cases used only proquazone.Group C with 95 cases received eperisone combined with proquazone treatment.The frequency of migraine attacks,the attack average time,and VAS score of patients were observed.Results The headache frequency,seizure duration and VAS score of group C was (2.01 ± 1.02) times/week,(4.28 ± 2.14) h,(3.42 ± 1.03) points,which were significantly less than those in group A and group B (t =8.682,7.879,13.396,14.140,16.408,21.481,all P ＜ 0.05).The incidence rate of adverse reaction of group C was 37.89％,that in group A was 36.84％,and group B was 34.73％.The difference among them was not statistically significant(P ＞ 0.05).But the incidence rate of drowsiness and indifferent symptom in group C was significandy higher than A and B group.The difference was statistically significant (x2 =34.381,13.821,all P ＜ 0.05).Conclusion Eperisone combined with proquazone could treat tension headaches well,because it can effectively reduce the frequency of migraine attacks in patients as well as the degree of pain.And it could also alleviate the patients' symptoms.In addition,the combination therapy did not increase the incidence rate of adverse reactions in patients.So it has better security and good cilinical promotion.But it couldn't be proscribed to the people with high-risk occupation for its suppression to CNS.

Bioequivalence of HCP1104, a New Fixed Dose Combination Drug and Co-administration of Eperisone 50 mg and Aceclofenac 100 mg: A Partial Replicated Crossover Study Design to Estimate the Pharmacokinetics of Highly Variable Drugs

BACKGROUND: This clinical study was conducted to compare pharmacokinetics of eperisone and aceclofenac of HCP1104, a new fixed dose combination drug with those in co-administration of eperisone 50 mg and aceclofenac 100 mg. The study used a partial replicated study design to characterize intra-subject variability of eperisone when co-administrated with aceclofenac. METHODS: A partial replicated crossover design was employed in 30 subjects. Each subject received a single dose of co-administration of eperisone 50 mg and aceclofenac 100 mg on two occasions and a single dose of 1 capsule of HCP1104. Blood samples were obtained for 24 hrs after dosing, and plasma was assayed for eperisone and aceclofenac by Liquid chromatography-electrospray ionization-mass spectrometry. RESULTS: Using an average bioequivalence criterion, the 90 % confidence limits for Ln-transformed Cmax and AUClast for aceclofenac fell wihin the acceptable range of 80 - 125 %. Point estimates of eperisone AUClast and Cmax were 1.0152 and 1.0490, respectively and the 90 % confidence interval for Cmax was 0.8499 - 1.3025. The within-subject coefficient of variation of Cmax for the reference was 50.198 %. Acceptance range for eperisone Cmax based on new bioequivalence guidance for highly variable drugs was extended to 0.6984 - 1.4319. CONCLUSION: The extent of exposure and rate of absorption of both eperisone and aceclofenac with a single dose of HCP1104 capsule were equivalent to those with co-administration of a marketed eperisone 50 mg tablet and a marketed aceclofenac 100 mg tablet under fasting conditions in healthy adult males.

Effect of Combination of Baclofen, Tizanidine and Eperisone on Moderate to Severe Spasticity after Spinal Cord Injury / 中国康复理论与实践

@#Objective To investigate the effect of combination of baclofen, tizanidine and eperisone on moderate or severe spasticity after spinal cord injury. Methods 18 inpatients with moderate (n=2) or severe (n=16) spasticity after spinal cord injury were treated with combination of 2 or 3 kinds of drugs for 2 months, and followed up for at least 4 months with modified Ashworth scale (MAS). Their blood pressure, blood and urine routine, liver and kidney function were observed. Results Among the 16 cases of severe spasticity (MAS≥3), MAS reduced 3 grades in 3 cases, 2 grades in 12 cases, 1 grade in 1 case, with alleviation of phantom pain. For the cases of moderate spasticity (MAS=2), the MAS reduced 1 grade with alleviation of phantom pain. Slightly drowsiness was observed in 2 cases. No hepatic or renal dysfunctions was found. Conclusion Combination of baclofen, tizanidine and eperisone is effective on moderate or severe spasticity after spinal cord injury with limited side-effects.

Efficacy of three antispasmodics on limb spasticity in patients after stroke: A comparative analysis / 中国脑血管病杂志

Objective: To compare and evaluate the efficacy and adverse reactions of tizanidine, baclofen and eperisone for treatment of limb spasticity in patients after stroke. Method: One hundred and three patients with stroke were enrolled in this prospective, randomized, controlled study. They were randomly divided into 4 groups: Tizanidine (n = 30), baclofen (n = 25), eperisone (n = 22) and control (n = 26) groups. The muscular tone, motor function and daily live activities (ADL) were evaluated with the modified Ashworth scale (MAS), Fugl-Meyer ssessment (FMA) and modified Bathel index (BI) respectively 4 and 12 weeks before and after the medication. Results: Circled digit oneTwelve weeks after the medication, the MAS scores of the upper and lower limbs of the patients were decreased in the 3 treatment groups as compared to the control group (P 0.05). Circled digit twoThe FMA scores of the upper limbs in patients of the 4 groups showed that there were no significant differences before and after the treatment (P > 0.05 all); the FMA scores of the lower limbs in patients of the 4 groups after the 12-week treatment were significantly higher than those before treatment. The average increased scores were 5 ± 3, 6 ± 5, 5 ± 4, and 4 ± 4, respectively (P 0.05). Circled digit threeCompare to the scores before the treatment, the MBI showed that there were significant differences in the average scores in the 4 groups 12 weeks after the treatment (P 0.05). Circled digit fourBlood, urine, liver and renal function tests of all patients were in the normal range before and after treatment. 10% and 8% of patients in the tizanidine and baclofen groups experienced drowsiness; 6.7%, 8%, and 4.5%. of patients in the tizanidine, baclofen, and eperisone groups had gastrointestinal discomfort; 6.7% and 8% of patients in the tizanidine and baclofen groups had blood pressure drop; and 22.7% of patients in the eperisone group had generalized weakness. The symptoms were relieved in all patients after reduce or stop the medication. Conclusion: Tizanidine, baclofen and eperisone have obviously effects for reducing muscular tone and relieving spasticity. Their therapeutic effects has no differences, but the three medicines did not show significant effect on functional recovery.

Relative bioavalability of hydrochloride eperisone granule in healthy volunteers / 中国临床药理学与治疗学

Aim The relative bioavalability of hydrochloride eperisone granule in 10 healthy volunteers was studied. Methods The time-plasma concentrations of hydrochloride eperisone granule, as test drug, and myonal, as reference drug, were determined by GC-MS, with tolperisone senuing as internal standard.The pharmacokinetic parameters of both reference and test drug were calculated and analyzed with two-one side test and confidential interval test. Results The results showed that the AUC0-8, AUC0-∞, Cmax, Tpeak, t1/2(?) and t1/2(?) were (17.9?1.3)ng?h?ml-1 and(18.6?1.6)ng?h?ml-1, (19.1?1.2)ng?h?ml-1 and (20.2?1.6)ng?h?ml-1, (5.2?0.5)ng?ml-1 and (5.4?0.5) ng?ml-1, (1.05?0.18)h and (1.08?0.23)h, (0.78? 0.13)h and ( 0.82?0.14)h,( 1.8?0.3)h and (1.8?0.3)h, respectively. The relative bioavalability of test drug was (105? 5)%. Conclusion It can be concluded that the test and reference are bioequivalented between individuals, preparations and periods.

The Clinical Evaluation Of Eperisone Hydrochloride (Mulex) / 대한류마티스학회지

Conservative treatment is the main therapy for cervicobrachial syndrome, scapulohumeral periarthritis, and lumbago as diseases with both pain and myotonia. The-conservative treatment mainly consists of medication, physiotherapy, and kinesiotherapy. In the recent years, attempts have been made to give relief to myotonia through combination therapy with antiinflammatory analgesics and muscle relaxants. The muscle relaxants using in general are tolperisone hydrochloride, chlormezanone, and diazepam. Eperizone hydrochloride(Mulex tablet) is a beta-propriophenone derivatives and a central acting muscle relaxant, And it benefited subjective symptoms such as muscular pain (lumbago, neck pain) and a stiff muscle sensation (shoulder tension, tension feeling of lower limb). Among 22 patients, there were 14 lumbagos, two cephalobrachial syndromes, one scapulohumeral periarthritis, and five combined patients were chosen and duration of symptom was 5 years (3months-15years) in average. Mulex tablet was administered in a dose of 3 tablets (150rag) per day in 22 patients for 6 weeks prospectively. We analysed general improvement rating (GIR), general usefulness rating(GUR), and overall safety rating. The general improvement rate was 78% and the aggravation rate was 4%. The complication after, madication was infrequently gastrointestinal trouble. Incidence of side effect was 22%, but all these complications were insignificant. Hematology, blood chemistry, and urinalysis after medication were normal.