Objective To evaluate and select essential medicine for diabetes mellitus based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Six guidelines were included, three of which were evidence-based and published from 2006 to 2011. (2) Five recommended medicines were included according to recommendations and evidence of WHOEML (2011), NEML (2009), CNF (2010) and other guidelines. They were metformin, glibenclamide, glipizide, rosiglitazone and pioglitazone. Domestic evidence of the first three drugs was evaluated. (3) The first three have been marketed with the specifications and dosage forms corresponding to guidelines in China. The FBG cost-effectiveness ratios of metformin with different dosage forms as immediate release compressed tablet, enteric-coated tablet and sustained release capsule were 3.37, 3.76 and 3.50 respectively. 2-hour BG cost-effectiveness ratios of metformin were 3.74, 4.00 and 3.71 respectively. The cost-effectiveness ratio of glibenclamide and glimepiride were 11.23 and 13.81 respectively. Conclusion We offer a recommendation for: (1) Metformin (immediate release tablet/capsule for oral use, 0.25 g), contraindicated in patients with renal insufficiency. (2) Glibenclamide (tablet, 2.5 mg; capsule, 1.75 mg) and glipizide (tablet, 2.5 or 5mg; dispersible tablet, 5 mg), contraindicated in children, women during pregnancy or lactation, patients in the perioperative period of major operation, patients after total pancreatectomy, and patients allergic or adversely reacted to sulfa drug. (3) Evidence-based and standardized primary healthcare guidelines as well as clinical and pharmacoeconomic studies on diabetes mellitus (large-scale, multi-centre, randomized and double-blinded) are needed to produce high-quality local evidence.
Objective To evaluate and select essential medicine for children with fever and adult gastrointestinal flu caused by common cold using evidence-based approaches based on the burden of disease for township health centers located in eastern, central and western regions of China. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) 12 guidelines were included, 11 of which were evidence-based or based on expert consensus. We offered a recommendation for medicines used in the treatment including analgesics and antipyretics, decongestants, antihistamines, cough-relieving drug, phlegm-removing drug and drug for gastrointestinal symptoms. (2) A result of four RCTs (very low quality) indicated that in the treatment of children with cold, ibuprofen suspension had an antipyretic effect similar to paracetamol solution (for oral use) with a pooled result of 6-hour efficiency in relieving fever (RR 1.48, 95%CI 0.66 to 3.30, P=0.34). The major adverse effects of ibuprofen suspension included gastrointestinal reaction and profuse sweats (RR=1.23, 95%CI 0.72 to 2.11, P=0.45). With good applicability, ibuprofen suspension (for oral use with no need to be supervised) cost 1.93 yuan daily. (3) A result of three RCTs (low quality) indicated that after given for 30 minutes and one hour, paracetamol solution (suppository) was fairly superior to ibuprofen suspension in lowering the high temperature caused by fever (given for 30 min: MD= –0.16°C, 95%CI –0.21 to –0.11, Plt;0.01; given for one hour: MD= –0.19°C, 95%CI –0.28 to 0.10, Plt;0.01). As to adverse reaction, paracetamol solution (suppository) mainly included anal irritation, skin rashes and profuse sweats, which had a comparative result of incidence with ibuprofen suspension (RR=1.84, 95%CI 0.62 to 5.44, P=0.27). For children with fever, paracetamol solution (suppository) cost 0.90 yuan daily. With good applicability, paracetamol solution (suppository) was administered via the anus. Conclusion (1) We offer a b recommendation for ibuprofen suspension (2 g/100 mL) or acetaminophen (0.1 g/suppository) as symptomatic treatment used in children with fever, pain and discomfort caused by common cold, and for Huo Xiang Zheng Qi Jiao Nang (0.3 g/ capsule) used in adults with gastrointestinal flu. We also offer a weak recommendation for acetylcysteine (injection, 300 mg/mL, 10 mL/ampoule) used in patients with paracetamol poisoning. (2) In order to produce high-quality local evidence, we proposed that large-scale, well-designed, high-quality clinical and pharmacoeconomic studies on ibuprofen suspension and acetaminophen suppository in the treatment of children with fever, pain and discomfort caused by common cold should be further carried out. Besides, we proposed that large-scale, well-designed, high-quality clinical and pharmacoeconomic studies on Chinese patent drugs of Huo Xiang Zheng Qi used in chidren and Huo Xiang Zheng Qi Jiao Nang used in adults should further carried out. Moreover, we suggest that epidemiological investigation as well as clinical and pharmacoeconomic studies of acetylcysteine injection for paracetamol poisoning should be carried out and the instructions of acetylcysteine injection should be added in the guidelines of essential medicine in China. Finally, further studies on evidence of oxymetazoline, dextromethorphan and other Chinese patent drugs with the effect of relieving cough and treating cold should be carried out.
Objective To evaluate and select essential antihypertensive medicine using evidence-based approaches based on the burden of disease for township health centers located in eastern, central and western regions of China. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Five clinical guidelines on hypertension were included, two of which were evidence-based. (2) Totally there were nine classes and 70 antihypertensive medicines listed in the guidelines. (3) According to WHOEML (2011), NEML (2009), CNF (2010), other guidelines, and the quantity and quality of evidence, we offered a b recommendation for nifedipine, verapamil and enalapril and a weak recommendation for hydrochlorothiazide, indapamide, spironolactone, propranolol, metoprolol and amlodipine. We made a recommendation against furosemide and timolol due to the lack of evidence from guidelines. (4) Nine recommended medicines have been marketed with the dosage forms and specifications corresponding to guidelines in China. The prices of metoprolol, amlodipine and enalapril were higher than those of other six (daily cost: metoprolol 3.80 to 7.60 yuan, amlodipine 2.16 to 4.32 yuan, and enalapril 0.86 to 6.88 yuan). As a whole, the prices of recommended antihypertensive medicine were affordable. (5) Results of domestic studies indicated that three bly-recommended medicines (including nifedipine, verapamil and enalapril) were safe, effective, economical and applicable. Conclusion (1) We offer a b recommendation for nifedipine, verapamil and enalapril as antihypertensive medicine and a weak recommendation for hydrochlorothiazide, indapamide, spironolactone, propranolol, metoprolol and amlodipine. (2) There is lack of high-quality evidence from relevant domestic studies, especially on long-term safety and pharmacoeconomic evidence. (3) We propose that more studies should be carried out on the safety, efficacy and pharmacoeconomics of six medicines for which we make a weak recommendation to produce high-quality local evidence.
Objective To investigate the disease constitution and cost of inpatients in Gaozha Central Township Health Center (GzC) in Wuzhong City of Ningxia Hui Autonomous Region from 2008 to 2010, so as to provide baseline data for further research. Methods A questionnaire combined with a special interview was carried out, and case records and cost information of GzC inpatients in 2008, 2009 and 2010 (from January to November) were collected. The diseases in discharge record were classified according to International Classification of Diseases (ICD-10) based on the first diagnose and the cost was analyzed. Data including general information of the inpatients, discharge diagnosis, hospitalization expenses, and drug cost etc. were rearranged and analyzed by Excel software. Results a) The total number of the inpatients was 1124, 642 and 747 in 2008, 2009 and 2010, respectively. The female was more than the male in both 2008 (59.34% vs. 40.66%) and 2009 (60.75% vs. 39.25%), and their disease spectrum included 17 categories, which accounted for 81% of ICD-10; b) The top six most commonly seen systematic diseases with a constituent ratio from 86.63% to 92.06% in recent three years were as follows: the respiratory system, digestive system, circulatory system, genitourinary system, injury and toxicosis, skeletal musculature and connective tissue disease. Except the injury and toxicosis, the other five systematic diseases were commonly seen in females rather than in males; c) The top 15 monopathies in recent three years were pulmonary infection, tracheitis or bronchitis, coronary heart disease, soft tissue injury, gastritis or chronic gastritis, upper respiratory infection, hypertension, urinary tract infection, prolapse of lumbar intervertebral disc, pelvic inflammation, fracture, pneumocardial diseases, superficial injury, chronic cholecystitis and arthritis; d) The main burdens of disease for inpatients focused on 35-54 age groups, then followed by the age groups above 55 in 2008 and 2009. Except the injury and toxicosis, the other diseases were commonly seen in females rather than in males. Pulmonary infection focused on the age groups above 35; the onset of hypertension increased obviously and a sharp rise of hypertension existed in the 45-54 age groups in 2008, but the hypertention focused on 35-44 age groups in 2009; e) The total inpatients with top 15 monopathies accounted for 64.06% to 71.21%, including 8-9 chronic diseases ranking higher in 2010, and 6-7 acute diseases focusing on infection and injury; and f) The average costs of chronic diseases were higher than those of acute diseases. Conclusion a) There is a big gap between GzC and Yong’an Central Township Health Center (YaC) regarding the level of the regional economic development, the situation of disease burden and cost of inpatients. The former is demonstrated as general Central Township Health Center, while the latter as affluent Central Township Health Center in western China; b) In recent three years, the main systematic diseases are in respiratory, circulatory and digestive system; the inpatients suffer from more chronic diseases rather than acute diseases in their young age; the acute diseases mainly include infection and injury, and the pulmonary infection has ranked as the first during the past three years; c) The inpatients in 2008 and 2009 are mainly in ages of 35 to 54, and then are over 55 years old. Except the injury and toxicosis, the other diseases were commonly seen in females rather than in males; d) The patients’ average costs of chronic diseases for hospitalization and drug in 2010 were lower than those of YaC. Consideration on reasonable constitution of the cost for hospitalization should be paid attention to; and e) It is urgent to strengthen the construction of infrastructure and informatization in GzC.
Objective To provide baseline datum for further evidence-based selecting essential health technology or essential medicine by comparing the top 15 inpatient diseases in the three pilot township clinics in western China from 2008 to 2010. Methods With the key words as disease spectrum, constitution of disease, inpatient disease category, inpatient diseases and so on, such databases as CBM, CNKI, VIP, WanFang and official websites of Ministry of Health were searched on computer, and the manual search was also conducted in combination to extract the related datum of provinces where the pilot township health centers were situated. The Excel software was used for data classification and analyses. Results (1) Among the 16 included literatures including 15 journal papers and 1 master thesis, 4 scored from zero to 3.5, 9 scored from 3.5 to 6.75, and the left 3 scored 7 or more than 7; (2) The common inpatient diseases in the township health centers in eastern, central and western regions in China were different. The upper respiratory tract infection, acute/chronic bronchitis, acute/chronic gastritis and appendicitis were the common inpatient diseases in the township health centers throughout China. The pneumonia, emphysema, cholelithiasis, cholecystitis, and acute/chronic gastroenteritis were the common inpatient diseases in the township health centers in southwest and northwest regions. The top 15 inpatient diseases in the three pilot township clinics in this study covered all the common inpatient diseases in the township health centers in southwest and northwest regions in China; (3) The total number of the top 15 inpatient diseases of the three pilot township health centers in western China between 2008 and 2010 was 35, including 20 chronic and 15 acute diseases. The chronic diseases were chronic bronchitis, chronic gastritis, hypertension, lumbar/cervical disease, cholelithiasis or cholecystitis, coronary heart disease, chronic pulmonary heart disease, urinary calculi, pelvic inflammation, vertebrobasilar insufficiency, arthritis, acute exacerbation of chronic bronchitis, Meniere’s disease, chronic obstructive emphysema, myocardial ischemia, prostatitis, etc.. The acute diseases were upper respiratory tract infection, pulmonary infection, fracture, superficial injury, acute appendicitis, acute bronchitis, urinary tract infection, acute gastritis, acute gastroenteritis, delivery amp; cesarean section, soft tissue injury, acute urticaria, etc.; and (4) While the common inpatient disease categories were relatively centralized and stable, but some of them were different in regions, inpatients’ age and sex structure. Conclusion (1) There are some differences in the common inpatient diseases in the township health centers among eastern, central and western regions in China, thus it is necessary to select essential health technology and essential medicine according to local conditions; (2) As a good representation, the common inpatients diseases in the three pilot township health centers in western China can provide the baseline evidence for selecting essential health technology and essential medicine for the township health centers in western China; (3) There are lack of national/regional statistics, survey data and evidence-based research on disease spectrum of the township health centers currently. While the investigation methods or statistics measurements/quality of these included studies are variable without standard regulation; and (4) It suggests that the state and every provinces should implement and improve the statistic analysis of disease spectrum of the township health centers, train staffs and fulfill the construction of information system.
Objective To evaluate and select essential medicine for bone fracture using evidence-based methods based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) 17 guidelines were included, six of which were evidence-based or based on expert consensus. We found that for fracture, global guidelines recommended surgical treatment and analgesics, while domestic guidelines recommended Chinese patent drugs. (2) A result of one RCT (low quality) indicated that Shang Ke Jie Gu Pian (name of a Chinese patent drug) shortened the clinical recovery time of fracture (MD=–4.2, 95%CI –5.25 to –3.14). A result of one RCT indicated that Shang Ke Jiu Ji Pian had a higher total clinical efficiency compared with San Qi Pian (name of a Chinese patent drug) (RR=1.28, 95%CI 1.11 to 1.47). A result of one RCT (low quality) indicated that Shang Ke Jiu Ji Pian (name of a Chinese patent drug) had a better effect than Shenyang Hong Yao Pian (name of a Chinese patent drug) in promoting the growth of osteotylus (RR=1.48, 95%CI 1.27 to 1.73) and also it had a higher clinical recovery rate (RR=1.62, 95%CI 1.37 to 1.9) compared to Shenyang Hong Yao Pian. A result of one RCT (moderate quality) indicated that Shang Ke Jiu Ji Pian was slightly better than Die Da Wan (name of Chinese patent drug) in regard to the recovery score of fracture (MD=0.25, 95%CI 0.026 to 0.47). A result of one RCT (low quality) indicated that compared to fracture reduction alone Shang Ke Jiu Ji Pian efficiently relieved pain (MD=–25.9, 95% –32.6 to –19.19) and shortened pain time (MD=–38.6, 95% –41.44 to –35.77). A result of one quasi-RCT (low quality) indicated that Shang Ke Jiu Ji Pian had a higher efficiency in relieving pain than benorylate (RR=1.13, 95%CI 1.04 to 1.23). A result of one RCT (low quality) indicated that Shang Ke Jiu Ji Pian had a higher efficiency than Shenyang Hong Yao Pian in relieving pain and swelling (RR=2.4, 95%CI 1.88 to 3.02). A result of one RCT (moderate quality) indicated that Shang Ke Jiu Ji Pian was superior to Die Da Wan in relieving pain and swelling (MD=–0.4, 95%CI –0.60 to –0.2). A result of two RCT (n=198) indicated that Shang Ke Jie Gu Pian caused no adverse reaction. With good applicability, Shang Ke Jie Gu Pian (taken with warm water or rice wine) cost 7.47 yuan daily. Conclusion (1) We offer a b recommendation for Shang Ke Jie Gu Pian and Jie Gu Qi Li Pian used in the treatment of adult fracture. (2) We should carry out more large-sample and controlled trials and improve outcome indicator in order to produce high-quality local evidence.
Objective To understand current situation of medical service and management in Yong’an Central Township Health Center (YaC) through on-the-spot investigation, in order to provide references for personal employment and essential medicines list implement in township health centers. Methods Questionnaire and focus interview were carried out, which included the general information, human resources, medical service and management, and the practice of essential medicines list. Results The hardware equipments of YaC were fine, and the target population had fairly good health and economy status. The ratio of General Practitioner (GP)/ nurse and GP/ pharmacist were all above the national average level. The members with college degree and above accounted for 61.6%, and about 88% staffs were with or below primary profession titles. There was a balance between personnel flow out and in. The drug income accounted for 53.6% of the whole in 2009 and the medical expenses increased compared to 2008. Essential medicines list was put into practice in April 1st of 2010 with no relevant technical documents as correspondence. Conclusion YaC, as a good representative of fairly well-off rural Township Health Center in western China, needs to cope with challenges of irrational personnel structure, low educational background and professional title of the staff and human resources flow, and requires developing policy and adopting measures step by step. The management of YaC may be influenced by zero-profit price of the essential medicine, and appropriate subsidy and policy support are necessary to maintain current service quality.
Objective To evaluate and select essential medicine for abortion using evidence-based approaches based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Four guidelines on medicine for abortion were included, two of which are based on evidence. (2) Included guidelines referred to eight essential medicines used in drug abortion and four antibiotics used after abortion surgery. (3) According to WHOEML (2011), NEML (2009), CNF (2010), other guideline and the quantity and quality of evidence, we offered a b recommendation for misoprostol, mifepristone, oxytocin except prostaglandins used in abortion. (4) Published literature on oxytocin, misoprostol and mifepristone were found. Oxytocin with the dosage form and specification corresponding to guidelines has been marketed in China. Oxytocin (in vial, 10 U∶1 mL) cost 1.5 yuan/injection. Mifepristone (tablet, 25 mg×1) cost 13.0 to 27.5 yuan/tablet. Misoprostol (0.2 mg×3) cost 2.8 to 3.7 yuan/ tablet. (5) Results of domestic studies indicated that mifepristone combined with misoprostol and oxytocin was safe, efficient, convenient and applicable to the treatment of abortion. Conclusion For abortion: (1) We make a recommendation for mifepristone plus misoprostol. Mifepristone (25 to 50 mg/tablet) is orally taken twice a day, continually for 2 to 3 days, the total dose of 150 mg for three days. Misoprostol (0.2 mg/ tablet) 0.6 mg is orally given on an empty stomach within 36 to 48 hours after the intake of mifepristone. (2) Oxytocin (5 to 10 U in vial) injected after delivering the placenta can reduce the volume and time of vaginal bleeding. In future, clinical study should be standardized in order to improve design and implementation quality.
Objective To systematically review the diseases constitution of children in Chinese medical institutions from 2010 to 2016, and to provide evidence for establishing essential medicine list for children (EMLc) of China. Methods We searched PubMed, EMbase, The Cochrane Library, CBM, CNKI, VIP and WanFang Data from January 2010 to February 2016 to collect studies about diseases constitution of Chinese children. Two reviewers independently screened literature, extracted data, and assessed the risk bias of included studies, then data was descriptively analyzed. Results A total of 33 studies of diseases constitution were included, involving 1 797 696 children among 0 to 18 years from 17 provinces of China. Neonatal hyperbilirubinemia, neonatal pneumonia and premature were the main diseases of inpatient newborns. The main diseases of children hospitalized were pneumonia, upper respiratory tract infection and tumor. Upper respiratory tract infection, bronchopneumonia, bronchitis and diarrhea were the main diseases of outpatients. Hyperspasmia, upper respiratory tract infection and pneumonia were the main diseases of emergency patients. Diseases constitution of different medical institution: the main diseases were pathological jaundice, neonatal asphyxia and neonatal pneumonia in both tertiary and secondary medical institution in the newborn group. In the children group, the main diseases were pneumonia, upper respiratory tract infection and bronchitis in both tertiary and secondary medical institution. Besides these diseases, indigestion and fever of unknown origin were also the main diseases of primary medical institution. Disease constitution of different areas: in the newborn group, pathological jaundice, neonatal pneumonia and neonatal hyperbilirubinemia were the main diseases in coastal areas. Neonatal pneumonia, neonatal hyperbilirubinemia and premature were the main diseases in inland areas. Neonatal hyperbilirubinemia, neonatal pneumonia and neonatal hypoxic-ischemic encephalopathy were the main diseases in remote areas. In children group, pneumonia, bronchitis and premature were the main diseases in coastal areas. Pneumonia, bronchitis and hand-foot-and-mouth disease were the main diseases in inland areas. Upper respiratory tract infection, bronchopneumonia and bronchitis were the main diseases in remote areas. Conclusion Diseases constitutions of children vary in different medical institution, and because of extreme lack of date from primary medical institution, we suggest to carry out investigation in primary medical institution to provide evidence for EMLc. Diseases constitutions of children vary in different area, additions should be made according to local conditions when essential drugs of children selected. Newborn, as a special group of children, should be considered separately when EMLc of China established.
Objective To evaluate and select essential medicine for acute and chronic gastritis using evidence-based approaches based on the burden of disease for township health centers located in eastern, central and western regions of China. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) Five guidelines for acute gastritis and seven guidelines for chronic gastritis were included. The recommended included omeprazole, ranitidine and domperidone. (2) A result of three CCTs (n=315, low quality) indicated that omeprazole was superior to famotidine and ranitidine in alleviating symptoms of chronic gastritis such as pain or discomfort in the upper abdomen, regurgitation, a burning sensation in the heart, distention and fullness in the upper abdomen (71.2% vs. 47.3%, 94.4% vs. 84.3%, Plt;0.05). A result of one RCT (n=100, low quality) and two CCTs (n=213, low quality) indicated that in HP eradication rates, omeprazole triple therapy and the control intervention had no significant difference (OR=1.09, 95%CI 0.44 to 2.70, Pgt;0.05). A result of one RCT (n=100, low quality) indicated that omeprazole caused no adverse reaction. A result of five CCTs (n=528, low quality) indicated that adverse reaction of omeprazole included poor appetite (two cases), nausea and vomiting (four cases), headache or vertigo (one case) and increased transaminase (one case). Omeprazole cost eight yuan (tablet) or four yuan (capsule) daily. (3) HP eradication rates of ranitidine bismuth citrate was higher than the control group (OR=2.05, 95%CI 1.29 to 3.25, P=0.002). A result of 15 RCTs (n=3 638, high quality) indicated adverse reaction of ranitidine bismuth citrate mainly included symptoms in the digestive system. A result of one RCT (n=100, low quality) indicated ranitidine bismuth citrate and omeprazole triple therapy had no significant difference (Pgt;0.05) and ranitidine bismuth citrate caused no adverse reaction. Ranitidine cost 0.36 yuan (tablet), 0.40 yuan (capsule) or 2.7 to 5.4 yuan (injection) daily. (4) A result of two CCTs (n=133, low quality) indicated that compared with the control intervention, domperidone was more efficient without adverse reaction in improving indigestion, promoting gastric emptying effect, and alleviating pain and distention in the upper abdomen, belching and regurgitation. Domperidone cost 1 to 1.3 yuan daily. (5) All kinds of recommended medicines are listed and legalized in China Pharmacopoeia (2010) and CNF (2010). (6) In clinical setting, above-recommended medicines should be applied strictly according to the CNF (2010) and the National Clinical Prescription Guidelines for Essential Medicine. Conclusion For acute and chronic gastritis, indigestion and HP eradication: (1) We offer a b recommendation for omeprazole (immediate release tablet/capsule for oral use, 10 mg/tablet) which should be cautiously used in children, elderly people, and women during pregnancy or lactation. (2) We offer a b recommendation for ranitidine (immediate release tablet/capsule for oral use, 150 mg/tablet) which should be cautiously used in patients with severe insufficiency in the liver or kidney, women in the pregnancy or lactation, and children under eight years of age.