【药品名称】     
通用名称：西咪替丁注射液
英文名称：Cimetidine Injection               
汉语拼音：Ximitiding Zhusheye
【成份】         
本品主要成份为西咪替丁。其化学名称为：1-甲基-2-氰基-3-[2-[[（5-甲基咪唑-4-基）甲基]硫代]乙基]胍。
化学结构式：
分子式：C10H16N6S 
分子量：252.34
辅料为稀盐酸、注射用水。
【性状】 本品为无色的澄明液体。
【适应症】用于消化道溃疡。
【规格】 2ml:0.2g
【用法用量】
静脉滴注。本品0.2g用5%葡萄糖注射液或0.9%氯化钠注射液或葡萄糖氯化钠注射液250～500ml稀释后静脉滴注，滴速为每小时1～4mg/kg，每次0.2～0.6g。
静脉注射。用上述溶液20ml稀释后缓慢静脉注射（2～3分钟），6小时1次，每次0.2g。肌内注射。一次0.2g，6小时1次。
【不良反应】
1.消化系统反应。较常见腹泻、腹胀、口干、血清氨基转移酶轻度升高，偶见严重肝炎、肝坏死、肝脂肪性变等。动物实验和临床均有应用本品导致急性胰腺炎的报道。突然停药，可能导致慢性消化性溃疡穿孔。
2.泌尿系统反应。有引起急性间质肾炎致衰竭的报道，但此种毒性反应是可逆的。
3.造血系统反应。对骨髓有一定抑制作用。少数病人发生可逆性中等程度的白细胞或粒细胞减少。
4.中枢神经系统反应。可通过血脑屏障，具有一定的神经毒性。较常见有头晕、头痛、嗜睡等。少数可出现不安，感觉迟钝，语言含糊，出汗或癫痫样发作，以及幻觉、妄想等症状，引起中毒症状的血药浓度多在2μg/ml，而且多发生于老人，幼儿或肝肾功能不全的患者。出现神经毒性后，一般只需适当减少剂量即可消失，用拟胆碱药毒扁豆碱治疗，其症状可得到改善。
5.心血管系统反应，可有心动过缓，面部潮红等。静脉注射时偶见血压骤降、房性早搏、心跳呼吸骤停 、呼吸短促或呼吸困难。
6.对内分泌和皮肤的影响，本品具有抗雄性激素作用，用药剂量较大时可引起男性乳房发育、女性溢乳、性欲减退、阳痿、精子计数减少等，停药后即可消失；可抑制皮脂分泌、诱发剥脱性皮炎、脱发、口腔溃疡等。
【禁忌】
1.孕妇及哺乳期妇女禁用。
2.对本品过敏者禁用。                                            
【注意事项】 
1、不宜用于急性胰腺炎。
2、用药期间应注意检查肾功能和血常规。
3、应避免本品与中枢抗胆碱药同时使用，以防加重中枢神经毒性反应。
4、用本品时应禁用咖啡因及含咖啡因的饮料。
5、慢性消化性溃疡突然停药可能导致穿孔，估计为停用后回跳的高酸度所致。故完成治疗后尚需继续服药（每晚400mg）3个月。
6、对诊断的干扰：胃液隐血试验可出现假阳性；血液水杨酸浓度、血清肌酐、催乳素、氨基转移酶等浓度均可能升高；甲状旁腺激素浓度则可能降低。
7、下列情况应慎用
（1）严重心脏及呼吸系统疾患；肝、肾功能不全患者慎用。
（2）慢性炎症，如系统性红斑狼疮（SLE），西咪替丁的骨髓性可能增高。
（3）器质性脑病。
【孕妇及哺乳期妇女用药】
本品能透过胎盘屏障，并能进入乳汁，引起胎儿和婴儿肝功能障碍，故禁用。
【儿童用药】 
儿童慎用。
【老年用药】
老年患者慎用。用药间隔时间可延长，剂量酌减。
【药物相互作用】
1、与制酸药伍用，对十二指肠溃疡有缓解疼痛之效，但西咪替丁的吸收可能减少，故一般不提倡。
2、本品与硫糖铝合用可能降低硫糖铝疗效（因硫糖铝需经胃酸水解后才能发挥作用）。加重镇静及其他中枢神经抑制症状，并可发展为呼吸及循环衰竭。如必须与抗酸剂合用，两者应至少相隔1小时。
3、与香豆素类抗凝药伍用时，凝血酶原时间可进一步延长，因此须密切注意病情变化，并调整抗凝药用量。
4、与其他肝内代谢药伍用均应慎用。
5、与苯妥英钠伍用时，后者血药浓度增高，毒性可能增强，注意定期复查周围血象。
6、本品可使维拉帕米的绝对生物利用度提高近一倍，应注意。
7、病人同时服用地高辛和奎尼丁时，不宜再用本品。
8、本品可减弱四环素的作用及增强阿司匹林的作用。
9、可干扰酮康唑的吸收，降低其抗真菌活性。
10、本品与卡托普利伍用有可能引起精神病症状。
11、由于本品与氨基糖苷类相似的肌神经阻断作用，这种作用不被新斯的明对抗，只能被氯化钙对抗，因此与氨基糖苷类抗生素合用时可能导致呼吸抑制或呼吸停止。
12、与普萘洛尔、美托洛尔、甲硝唑伍用时，血药浓度可能增高。
13、与茶碱、咖啡因、氨茶碱等黄嘌呤类药伍用时，肝代谢降低，可导致清除延缓，血药浓度升高，可能发生中毒反应。
【药物过量】
常见的过量征象有呼吸短促或呼吸困难以及心动过速。处理：首先清除胃肠道内尚未吸收的药物，并给予临床监护及支持疗法，出现呼吸衰竭者，立即进行人工呼吸，心动过速者可给予β肾上腺素阻滞药。
【药理毒理】
药理作用：主要作用于壁细胞上H2受体，起竞争性抑制组胺作用，抑制基础胃酸分泌，也抑制由食物、组胺胃泌素、咖啡因及胰岛素等刺激所刺激的胃酸分泌。注射300mg，4～5小时后，抑制基础胃酸分泌可达80%，可抑制基础胃酸50%达4～5小时。
毒理研究：大鼠和犬的亚急性、慢性毒性试验证明，本品有轻度抗雄激素作用引起前列腺和精囊重量减少以及乳汁分泌，但停药后消失。无致突变、致癌、致畸胎作用，亦无依赖性和耐受性。
【药代动力学】
本品吸收后广泛分布于除脑以外的全身组织中，本品能透过通胎盘屏障，乳汁中本品浓度可高于血浆浓度。蛋白结合率为15%～20%，部分在肝脏内代谢，代谢产物为Sulphoxide和Hydroxymethylcimetiding，主要经肾排泄。24小时后注射量的约75%以原形自肾排出；10%可从粪便排出。可经血液透析清除。肾功能正常时t1/2为2小时，肌酐清除率在20～50ml/分钟者其半衰期（t1/2）为2.9小时，＜20ml/分钟者时为3.7小时，肾功能不全者为5小时。
【贮藏】密闭保存。

Cimetidine HCl, 150mg/mL, SDV, 2mL, 10 Vials/Tray
Cimetidine
Single-dose Fliptop Vial
Multiple-dose Fliptop Vial
Single-dose LifeShield® Fliptop Vial
Rx only
DESCRIPTIONCimetidine is a histamine H2 -receptor antagonist. Chemically it is N˝-cyano-N-methyl-N′-[2-[[(5-methyl-1H-imidazol-4-yl)methyl]thio]-ethyl]-guanidine.
The molecular formula for cimetidine hydrochloride is C10 H16 N6 S • HCl and the molecular weight is 288.80. The structural formula of cimetidine hydrochloride is:
Cimetidine Hydrochloride
Cimetidine contains an imidazole ring, and is chemically related to histamine.
Cimetidine hydrochloride has a bitter taste and characteristic odor.
Cimetidine hydrochloride is freely soluble in water, soluble in alcohol, very slightly soluble in chloroform and practically insoluble in ether.
Single-dose Vials for Intramuscular or Intravenous Administration:
Cimetidine Injection, USP is a sterile aqueous solution. Each mL contains cimetidine hydrochloride equivalent to 150 mg cimetidine. May contain sodium hydroxide and/or hydrochloric acid for pH adjustment. pH is 5.4 (3.8 to 6.0).
Multiple-dose Vials for Intramuscular or Intravenous Administration:
Cimetidine Injection, USP is a sterile aqueous solution. Each mL contains cimetidine hydrochloride equivalent to 150 mg cimetidine; benzyl alcohol added as a bacteriostatic preservative, 9 mg. May contain sodium hydroxide and/or hydrochloric acid for pH adjustment. pH is 5.4 (3.8 to 6.0).
CLINICAL PHARMACOLOGYCimetidine competitively inhibits the action of histamine at the histamine H2 receptors of the parietal cells and thus is a histamine H2 -receptor antagonist.
Cimetidine is not an anticholinergic agent. Studies have shown that cimetidine inhibits both daytime and nocturnal basal gastric acid secretion. Cimetidine also inhibits gastric acid secretion stimulated by food, histamine, pentagastrin, caffeine and insulin.
Antisecretory Activity
1) Acid Secretion:Nocturnal: Cimetidine 800 mg orally at bedtime reduces mean hourly H+ activity by greater than 85% over an eight-hour period in duodenal ulcer patients, with no effect on daytime acid secretion. Cimetidine 1600 mg orally h.s. produces 100% inhibition of mean hourly H+ activity over an eight-hour period in duodenal ulcer patients, but also reduces H+ activity by 35% for an additional five hours into the following morning. Cimetidine 400 mg b.i.d. and 300 mg q.i.d. decrease nocturnal acid secretion in a dose-related manner, i.e., 47% to 83% over a six- to eight-hour period and 54% over a nine-hour period, respectively.
Food Stimulated: During the first hour after a standard experimental meal, oral cimetidine 300 mg inhibited gastric acid secretion in duodenal ulcer patients by at least 50%. During the subsequent two hours cimetidine inhibited gastric acid secretion by at least 75%.
The effect of a 300 mg breakfast dose of cimetidine continued for at least four hours and there was partial suppression of the rise in gastric acid secretion following the luncheon meal in duodenal ulcer patients. This suppression of gastric acid output was enhanced and could be maintained by another 300 mg dose of cimetidine given with lunch.
In another study, cimetidine 300 mg given with the meal increased gastric pH as compared with placebo.
Clinical TrialsDuodenal Ulcer
Cimetidine has been shown to be effective in the treatment of active duodenal ulcer and, at reduced dosage, in maintenance therapy following healing of active ulcers.
Active Duodenal Ulcer: Cimetidine accelerates the rate of duodenal ulcer healing. Healing rates reported in U.S. and foreign controlled trials with oral cimetidine are summarized below, beginning with the regimen providing the lowest nocturnal dose.
Duodenal Ulcer Healing Rates with Various Oral Cimetidine Dosage Regimens* 
A U.S., double-blind, placebo-controlled, dose-ranging study demonstrated that all once-daily at bedtime (h.s.) cimetidine regimens were superior to placebo in ulcer healing and that cimetidine 800 mg h.s. healed 75% of patients at four weeks. The healing rate with 800 mg h.s. was significantly superior to 400 mg h.s. (66%) and not significantly different from 1600 mg h.s. (81%).
In the U.S. dose-ranging trial, over 80% of patients receiving cimetidine 800 mg h.s. experienced nocturnal pain relief after one day. Relief from daytime pain was reported in approximately 70% of patients after two days. As with ulcer healing, the 800 mg h.s. dose was superior to 400 mg h.s. and not different from 1600 mg h.s.
In foreign, double-blind studies with cimetidine 800 mg h.s., 79 to 85% of patients were healed at four weeks.
While short-term treatment with cimetidine can result in complete healing of the duodenal ulcer, acute therapy will not prevent ulcer recurrence after cimetidine has been discontinued. Some follow-up studies have reported that the rate of recurrence once therapy was discontinued was slightly higher for patients healed on cimetidine than for patients healed on other forms of therapy; however, the cimetidine-treated patients generally had more severe disease.
Maintenance Therapy in Duodenal Ulcer: Treatment with a reduced dose of cimetidine has been proven effective as maintenance therapy following healing of active duodenal ulcers.
In numerous placebo-controlled studies conducted worldwide, the percent of patients with observed ulcers at the end of one year’s therapy with cimetidine 400 mg h.s. was significantly lower (10% to 45%) than in patients receiving placebo (44% to 70%). Thus, from 55% to 90% of patients were maintained free of observed ulcers at the end of one year with cimetidine 400 mg h.s.
Factors such as smoking, duration and severity of disease, gender, and genetic traits may contribute to variations in actual percentages.
Trials of other anti-ulcer therapy, whether placebo-controlled, positive-controlled or open, have demonstrated a range of results similar to that seen with cimetidine.
Active Benign Gastric Ulcer
Cimetidine has been shown to be effective in the short-term treatment of active benign gastric ulcer.
In a multicenter, double-blind U.S. study, patients with endoscopically confirmed benign gastric ulcer were treated with cimetidine 300 mg four times a day or with placebo for six weeks. Patients were limited to those with ulcers ranging from 0.5 to 2.5 cm in size. Endoscopically confirmed healing at six weeks was seen in significantly* more cimetidine treated patients than in patients receiving placebo, as shown below:
In a similar multicenter U.S. study of the 800 mg h.s. oral regimen, the endoscopically confirmed healing rates were:
Similarly, in worldwide double-blind clinical studies, endoscopically evaluated benign gastric ulcer healing rates were consistently higher with cimetidine than with placebo.
Prevention of Upper Gastrointestinal Bleeding in Critically Ill Patients
A double-blind, placebo-controlled randomized study of continuous infusion cimetidine was performed in 131 critically ill patients (mean APACHE II score = 15.99) to compare the incidence of upper gastrointestinal bleeding, manifested as hematemesis or bright red blood which did not clear after adjustment of the nasogastric tube and a 5 to 10 minute lavage, persistent Gastroccult (R) positive coffee grounds for 8 consecutive hours which did not clear with 100 cc lavage and/or which were accompanied by a drop in hematocrit of 5 percentage points, or melena, with an endoscopically documented upper gastrointestinal source of bleed. 14% (9/65) of patients treated with cimetidine continuous infusion developed bleeding compared to 33% (22/66) of the placebo group. Coffee grounds was the manifestation of bleeding that accounted for the difference between groups. Another randomized, double-blind placebo-controlled study confirmed these results for an end point of upper gastrointestinal bleeding with a confirmed upper gastrointestinal source noted on endoscopy, and by post hoc analyses of bleeding episodes between groups.
Pathological Hypersecretory Conditions (such as Zollinger-Ellison Syndrome)
Cimetidine significantly inhibited gastric acid secretion and reduced occurrence of diarrhea, anorexia and pain in patients with pathological hypersecretion associated with Zollinger-Ellison Syndrome, systemic mastocytosis and multiple endocrine adenomas. Use of cimetidine was also followed by healing of intractable ulcers.
INDICATIONS AND USAGECimetidine Injection, USP is indicated in:
(1) Short-term treatment of active duodenal ulcer. Most patients heal within 4 weeks and there is rarely reason to use cimetidine at full dosage for longer than 6 to 8 weeks (see DOSAGE AND ADMINISTRATION — Duodenal Ulcer). Concomitant antacids should be given as needed for relief of pain. However, simultaneous administration of oral cimetidine and antacids is not recommended, since antacids have been reported to interfere with the absorption of oral cimetidine.
(2) Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of active ulcer. Patients have been maintained on continued treatment with cimetidine 400 mg h.s. for periods of up to five years.
(3) Short-term treatment of active benign gastric ulcer. There is no information concerning usefulness of treatment periods of longer than 8 weeks.
(4) Prevention of upper gastrointestinal bleeding in critically ill patients.
(5) The treatment of pathological hypersecretory conditions (i.e., Zollinger-Ellison Syndrome, systemic mastocytosis, multiple endocrine adenomas).
CONTRAINDICATIONS
Cimetidine is contraindicated for patients known to have hypersensitivity to the product.
PRECAUTIONSGeneral: Rare instances of cardiac arrhythmias and hypotension have been reported following the rapid administration of cimetidine hydrochloride injection by intravenous bolus.
Symptomatic response to cimetidine therapy does not preclude the presence of a gastric malignancy. There have been rare reports of transient healing of gastric ulcers despite subsequently documented malignancy.
Reversible confusional states (see ADVERSE REACTIONS) have been observed on occasion, predominantly, but not exclusively, in severely ill patients. Advancing age (50 or more years) and pre-existing liver and/or renal disease appear to be contributing factors. In some patients these confusional states have been mild and have not required discontinuation of cimetidine therapy. In cases where discontinuation was judged necessary, the condition usually cleared within 3 to 4 days of drug withdrawal.
Drug Interactions: Cimetidine, apparently through an effect on certain microsomal enzyme systems, has been reported to reduce the hepatic metabolism of warfarin-type anticoagulants, phenytoin, propranolol, nifedipine, chlordiazepoxide, diazepam, certain tricyclic antidepressants, lidocaine, theophylline and metronidazole, thereby delaying elimination and increasing blood levels of these drugs.
Clinically significant effects have been reported with the warfarin anticoagulants; therefore, close monitoring of prothrombin time is recommended, and adjustment of the anticoagulant dose may be necessary when cimetidine is administered concomitantly. Interaction with phenytoin, lidocaine and theophylline has also been reported to produce adverse clinical effects.
However, a crossover study in healthy subjects receiving either cimetidine 300 mg q.i.d. or 800 mg h.s. concomitantly with a 300 mg b.i.d. dosage of theophylline extended-release tablets demonstrated less alteration in steady-state theophylline peak serum levels with the 800 mg h.s. regimen, particularly in subjects aged 54 years and older. Data beyond ten days are not available. (Note: All patients receiving theophylline should be monitored appropriately, regardless of concomitant drug therapy.)
Dosage of the drugs mentioned above and other similarly metabolized drugs, particularly those of low therapeutic ratio or in patients with renal and/or hepatic impairment, may require adjustment when starting or stopping concomitantly administered cimetidine to maintain optimum therapeutic blood levels.
Alteration of pH may affect absorption of certain drugs (e.g., ketoconazole). If these products are needed, they should be given at least 2 hours before cimetidine administration.
Additional clinical experience may reveal other drugs affected by the concomitant administration of cimetidine.
Carcinogenesis, Mutagenesis, Impairment of Fertility: In a 24-month toxicity study conducted in rats, at dose levels of 150, 378 and 950 mg/kg/day (approximately 8 to 48 times the recommended human dose), there was a small increase in the incidence of benign Leydig cell tumors in each dose group; when the combined drug-treated groups and control groups were compared, this increase reached statistical significance. In a subsequent 24 month study, there were no differences between the rats receiving 150 mg/kg/day and the untreated controls. However, a statistically significant increase in benign Leydig cell tumor incidence was seen in the rats that received 378 and 950 mg/kg/day. These tumors were common in control groups as well as treated groups and the difference became apparent only in aged rats.
Cimetidine has demonstrated a weak antiandrogenic effect. In animal studies this was manifested as reduced prostate and seminal vesicle weights. However, there was no impairment of mating performance or fertility, nor any harm to the fetus in these animals at doses 8 to 48 times the full therapeutic dose of cimetidine, as compared with controls. The cases of gynecomastia seen in patients treated for one month or longer may be related to this effect.
In human studies, cimetidine has been shown to have no effect on spermatogenesis, sperm count, motility, morphology or in vitro fertilizing capacity.
Pregnancy: Teratogenic Effects.Pregnancy Category B: Reproduction studies have been performed in rats, rabbits and mice at doses up to 40 times the normal human dose and have revealed no evidence of impaired fertility or harm to the fetus due to cimetidine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing Mothers: Cimetidine is secreted in human milk and, as a general rule, nursing should not be undertaken while a patient is on a drug.
Pediatric Use: Clinical experience in pediatric patients is limited. Therefore, cimetidine therapy cannot be recommended for pediatric patients under 16, unless, in the judgment of the physician, anticipated benefits outweigh the potential risks. In very limited experience, doses of 20 to 40 mg/kg per day have been used.
Immunocompromised Patients: In immunocompromised patients, decreased gastric acidity, including that produced by acid-suppressing agents such as cimetidine, may increase the possibility of a hyperinfection of strongyloidiasis.
ADVERSE REACTIONSAdverse effects reported in patients taking cimetidine are described below by body system. Incidence figures of 1 in 100 and greater are generally derived from controlled clinical studies.
Gastrointestinal: Diarrhea (usually mild) has been reported in approximately 1 in 100 patients.
CNS: Headaches, ranging from mild to severe, have been reported in 3.5% of 924 patients taking 1600 mg/day, 2.1% of 2,225 patients taking 800 mg/day and 2.3% of 1,897 patients taking placebo. Dizziness and somnolence (usually mild) have been reported in approximately 1 in 100 patients on either 1600 mg/day or 800mg/day.
Reversible confusional states, e.g., mental confusion, agitation, psychosis, depression, anxiety, hallucinations, disorientation, have been reported predominantly, but not exclusively, in severely ill patients. They have usually developed within 2 to 3 days of initiation of cimetidine therapy and have cleared within 3 to 4 days of discontinuation of the drug.
Endocrine: Gynecomastia has been reported in patients treated for one month or longer. In patients being treated for pathological hypersecretory states, this occurred in about 4% of cases while in all others the incidence was 0.3% to 1% in various studies. No evidence of induced endocrine dysfunction was found, and the condition remained unchanged or returned toward normal with continuing cimetidine treatment.
Reversible impotence has been reported in patients with pathological hypersecretory disorders, e.g., Zollinger-Ellison Syndrome, receiving cimetidine, particularly in high doses, for at least 12 months (range 12 to 79 months, mean 38 months). However, in large-scale surveillance studies at regular dosage, the incidence has not exceeded that commonly reported in the general population.
Hematologic: Decreased white blood cell counts in cimetidine-treated patients (approximately 1 per 100,000 patients), including agranulocytosis (approximately 3 per million patients), have been reported, including a few reports of recurrence on rechallenge. Most of these reports were in patients who had serious concomitant illnesses and received drugs and/or treatment known to produce neutropenia. Thrombocytopenia (approximately 3 per million patients) and, very rarely, cases of pancytopenia or aplastic anemia have also been reported. As with some other H2 -receptor antagonists, there have been extremely rare reports of immune hemolytic anemia.
Hepatobiliary: Dose-related increases in serum transaminase have been reported. In most cases they did not progress with continued therapy and returned to normal at the end of therapy. There have been rare reports of cholestatic or mixed cholestatic hepatocellular effects. These were usually reversible. Because of the predominance of cholestatic features, severe parenchymal injury is considered highly unlikely. However, as in the occasional liver injury with other H2 -receptor antagonists, in exceedingly rare circumstances fatal outcomes have been reported.
There has been reported a single case of biopsy-proven periportal hepatic fibrosis in a patient receiving cimetidine.
Rare cases of pancreatitis, which cleared on withdrawal of the drug, have been reported.
Hypersensitivity: Rare cases of fever and allergic reactions including anaphylaxis and hypersensitivity vasculitis, which cleared on withdrawal of the drug, have been reported.
Renal: Small, possibly dose-related increases in plasma creatinine, presumably due to competition for renal tubular secretion, are not uncommon and do not signify deteriorating renal function. Rare cases of interstitial nephritis and urinary retention, which cleared on withdrawal of the drug, have been reported.
Cardiovascular: Rare cases of bradycardia, tachycardia and A-V heart block have been reported with H2 -receptor antagonists.
Musculoskeletal: There have been rare reports of reversible arthralgia and myalgia; exacerbation of joint symptoms in patients with pre-existing arthritis has also been reported. Such symptoms have usually been alleviated by a reduction in cimetidine dosage. Rare cases of polymyositis have been reported, but no causal relationship has been established.
Integumental: Mild rash and, very rarely, cases of severe generalized skin reactions including Stevens-Johnson syndrome, epidermal necrolysis, erythema multiforme, exfoliative dermatitis and generalized exfoliative erythroderma have been reported with H2 -receptor antagonists. Reversible alopecia has been reported very rarely.
Immune Function: There have been extremely rare reports of strongyloidiasis hyperinfection in immunocompromised patients.
OVERDOSAGEStudies in animals indicate that toxic doses are associated with respiratory failure and tachycardia which may be controlled by assisted respiration and the administration of a beta blocker.
Reported acute ingestions orally of up to 20 grams have been associated with transient adverse effects similar to those encountered in normal clinical experience. The usual measures to remove unabsorbed material from the gastrointestinal tract, clinical monitoring and supportive therapy, should be employed.
There have been reports of severe CNS symptoms, including unresponsiveness, following ingestion of between 20 and 40 grams of cimetidine, and extremely rare reports following concomitant use of multiple CNS- active medications and ingestion of cimetidine at doses less than 20 grams. An elderly, terminally ill dehydrated patient with organic brain syndrome receiving concomitant antipsychotic agents and cimetidine 4800 mg intravenously over a 24 hour period experienced mental deterioration with reversal on cimetidine discontinuation.
There have been two deaths in adults who were reported to have ingested over 40grams orally on a single occasion.
DOSAGE AND ADMINISTRATIONParenteral Administration
In hospitalized patients with pathological hypersecretory conditions or intractable ulcers, or in patients who are unable to take oral medication, cimetidine may be administered parenterally.
The doses and regimen for parenteral administration in patients with GERD have not been established.
Recommendations for Parenteral Administration:
Intramuscular Injection: 300 mg every 6 to 8 hours (no dilution necessary). Transient pain at the site of injection has been reported.
Intravenous Injection: 300 mg every 6 to 8 hours. In some patients it may be necessary to increase dosage. When this is necessary, the increases should be made by more frequent administration of a 300 mg dose, but should not exceed 2400 mg per day. Dilute Cimetidine Injection, USP, 300 mg, in Sodium Chloride Injection (0.9%) or another compatible I.V. solution (see Stability of Cimetidine Injection, USP) to a total volume of 20 mL and inject over a period of not less than 5 minutes (see PRECAUTIONS).
Intermittent Intravenous Infusion: 300 mg every 6 to 8 hours, infused over 15 to 20 minutes. In some patients it may be necessary to increase dosage. When this is necessary, the increases should be made by more frequent administration of a 300 mg dose, but should not exceed 2400 mg per day.
Dilute Cimetidine Injection, USP, 300 mg, in at least 50 mL of 5% Dextrose Injection, or another compatible I.V. solution (see Stability of Cimetidine Injection, USP).
Continuous Intravenous Infusion: 37.5 mg/hour (900 mg/day). For patients requiring a more rapid elevation of gastric pH, continuous infusion may be preceded by a 150 mg loading dose administered by I.V. infusion as described above. Dilute 900 mg Cimetidine Injection, USP in a compatible I.V. fluid (see Stability of Cimetidine Injection, USP) for constant rate infusion over a 24-hour period. Note: Cimetidine Injection, USP may be diluted in 100 to 1000 mL; however, a volumetric pump is recommended if the volume for 24-hour infusion is less than 250 mL. In one study in patients with pathological hypersecretory states, the mean infused dose of cimetidine was 160 mg/hour with a range of 40 to 600 mg/hour.
These doses maintained the intragastric acid secretory rate at 10 mEq/hour or less. The infusion rate should be adjusted to individual patient requirements.
Stability of Cimetidine Injection, USP
When added to or diluted with most commonly used intravenous solutions, e.g., Sodium Chloride Injection (0.9%), Dextrose Injection (5% or 10%), Lactated Ringer’s Injection, 5% Sodium Bicarbonate Injection, Cimetidine Injection, USP should not be used after more than 48 hours of storage at room temperature.
NOTE: The products accompanying this insert are for I.M./I.V. use only. Much of the following relates to the use of oral cimetidine and is for informational purposes only. See Parenteral Administration (above) for specific dosing recommendations.
Duodenal Ulcer
Active Duodenal Ulcer
Clinical studies have indicated that suppression of nocturnal acid is the most important factor in duodenal ulcer healing (see CLINICAL PHARMACOLOGY — Acid Secretion). This is supported by recent clinical trials (see Clinical Trials—Active Duodenal Ulcer). Therefore, there is no apparent rationale, except for familiarity with use, for treating with anything other than a once-daily at bedtime oral dosage regimen (h.s.).
In a U.S. oral dose-ranging study of 400 mg h.s., 800 mg h.s. and 1600 mg h.s., a continuous dose response relationship for ulcer healing was demonstrated.
However, 800mg h.s. is the dose of choice for most patients, as it provides a high healing rate (the difference between 800 mg h.s. and 1600 mg h.s. being small), maximal pain relief, a decreased potential for drug interactions (see PRECAUTIONS — Drug Interactions) and maximal patient convenience. Patients unhealed at four weeks, or those with persistent symptoms, have been shown to benefit from two to four weeks of continued therapy.
It has been shown that patients who both have an endoscopically demonstrated ulcer larger than 1 cm and are also heavy smokers (i.e., smoke one pack of cigarettes or more per day) are more difficult to heal. There is some evidence which suggests that more rapid healing can be achieved in this subpopulation with cimetidine 1600 mg at bedtime. While early pain relief with either 800 mg h.s. or 1600 mg h.s. is equivalent in all patients, 1600 mg h.s. provides an appropriate alternative when it is important to ensure healing within four weeks for this subpopulation. Alternatively, approximately 94% of all patients will also heal in eight weeks with cimetidine 800mg h.s.
Other cimetidine oral regimens in the U.S. which have been shown to be effective are: 300 mg four times daily, with meals and at bedtime, the original regimen with which U.S. physicians have the most experience, and 400 mg twice daily, in the morning and at bedtime (see Clinical Trials —Active Duodenal Ulcer).
Concomitant antacids should be given as needed for relief of pain. However, simultaneous administration of oral cimetidine and antacids is not recommended, since antacids have been reported to interfere with the absorption of oral cimetidine.
While healing with cimetidine often occurs during the first week or two, treatment should be continued for 4 to 6 weeks unless healing has been demonstrated by endoscopic examination.
Maintenance Therapy for Duodenal Ulcer
In those patients requiring maintenance therapy, the recommended adult oral dose is 400 mg at bedtime.
Active Benign Gastric Ulcer
The recommended adult oral dosage for short-term treatment of active benign gastric ulcer is 800 mg h.s., or 300 mg four times a day with meals and at bedtime. Controlled clinical studies were limited to six weeks of treatment (see Clinical Trials). 800 mg h.s. is the preferred regimen for most patients based upon convenience and reduced potential for drug interactions. Symptomatic response to cimetidine does not preclude the presence of a gastric malignancy. It is important to follow gastric ulcer patients to assure rapid progress to complete healing.
Prevention of Upper Gastrointestinal Bleeding
The recommended adult dosing regimen is continuous I.V. infusion of 50 mg/hour. Patients with creatinine clearance less than 30 cc/min. should receive half the recommended dose. Treatment beyond 7 days has not been studied.
Pathological Hypersecretory Conditions (such as Zollinger-Ellison Syndrome)
Recommended adult dosage: 300 mg four times a day with meals and at bedtime. In some patients it may be necessary to administer higher doses more frequently. Doses should be adjusted to individual patient needs, but should not usually exceed 2400 mg per day and should continue as long as clinically indicated.
Dosage Adjustment for Patients with Impaired Renal Function
Patients with severely impaired renal function have been treated with cimetidine. However, such usage has been very limited. On the basis of this experience the recommended dosage is 300 mg every 12 hours orally or by intravenous injection. Should the patient’s condition require, the frequency of dosing may be increased to every 8 hours or even further with caution. In severe renal failure, accumulation may occur and the lowest frequency of dosing compatible with an adequate patient response should be used. When liver impairment is also present, further reductions in dosage may be necessary. Hemodialysis reduces the level of circulating cimetidine. Ideally, the dosage schedule should be adjusted so that the timing of a scheduled dose coincides with the end of hemodialysis.
Patients with creatinine clearance less than 30 cc/min. who are being treated for prevention of upper gastrointestinal bleeding should receive half the recommended dose.
Do not administer product unless solution is clear and container is undamaged. Discard unused portion. All parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
HOW SUPPLIEDCimetidine Injection, USP 300 mg/2 mL cimetidine is supplied as follows:
Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Do not refrigerate.