Description: Cimetidine oral milk instructions by the State Drug Administration on April 16, 2002 Drug Administration Note letter [2002] No. 106 "on the publication of the fourth batch of chemical drug instructions directory notice" issued. State Drug Administration published the instructions is standardized after the revision of the proposed reference sample, the enterprise has any doubt, you can propose changes. Indications] should be consistent with the original approved content; [adverse reactions], [drug interactions] and other items, the enterprise to provide the instructions can not be less than those listed in the sample. For the sample specification of the empty or not listed in the full project, should require companies to fill in according to the actual situation, such as trade names, specifications, etc..
Drug Name
Generic Name: Cimetidine
Previous Name:
Trade Name:
English Name: Cimetidine Oral Emulsion
Chinese Pinyin: Ximitiding Koufuru
The main ingredient of this product is: Cimetidine. Its chemical name is N'methyl N''[2[[(5methyl1Himidazol-4-yl) methyl] thio] ethyl] N cyanoguanidine.
Structure:
Molecular Formula: C10H16N6S
Molecular Weight: 252.34
Properties
Pharmacology and Toxicology
It is a kind of H2-receptor antagonist, which can significantly inhibit gastric acid secretion induced by food, histamine, pentagastrin, caffeine, and insulin ***. It has preventive and protective effects on corrosive gastritis caused by chemical ***, and also has obvious curative effects on stress gastric ulcer and upper gastrointestinal bleeding. This product has anti-androgen effect, in the treatment of hirsutism has a certain value. This product can weaken the activity of immunosuppressive cells, enhance the immune response, thereby inhibiting tumor metastasis and prolonging the survival period.
Pharmacokinetics
The product is rapidly absorbed from the small intestine after oral administration, with a bioavailability of about 60-70%, and reaches the effective blood concentration (0.5 μg/ml) in half an hour, and reaches the peak concentration in 45-90 minutes, with an average Cmax of 1.44 μg/ml. The effective blood concentration can be maintained for 4 hours. The plasma protein binding rate is 15-20%, t1/2 is about 2 hours (t1/2 is significantly prolonged in patients with chronic renal insufficiency, about 4.9 hours, attention should be paid to reduce the dosage or adjust the dosage interval), the Vd is 2.1 ± 1 L/kg, and the renal clearance is 12 ± 3 ml/kg/minute. It is widely distributed in the body in systemic tissues (except brain), metabolized in the liver, and mainly excreted by the kidneys, 44-70% is excreted in the urine in its original form, 10% can be excreted in the feces, and 80-90% of the oral dose can be eliminated in 12 hours.
Indications
Clinically, it is mainly used for: ①A variety of acid-related diseases: such as duodenal ulcer, gastric ulcer, Zuo Ai syndrome, upper gastrointestinal hemorrhage, reflux esophagitis, hyperacidic gastritis and so on. ② It has been reported to be used in the treatment of herpes zoster and other herpetic infections including genital.
Dosage
Oral: ① Adults: 200-400mg each time, 800-1600mg a day, usually in the meal and bedtime once, the course of treatment is usually 4-6 weeks. Another advocate of a day's amount of two times (400mg each time) or tonic therapy (800mg at night, a one-time oral). Children: 5-10mg/kg according to body weight, 2-4 times a day, after meals, and in severe cases, 1 additional dose before bedtime. Can also refer to the method of adults, 1 day's dose divided into 2 times or a meal, the course of treatment is the same as above.
Adverse reactions
Due to the wide distribution of this product in the body, the pharmacological effect of the complex, so the side effects and adverse reactions are more. ① Digestive system reactions: the more common are diarrhea, abdominal distension, bitter mouth, dry mouth, mild elevation of serum aminotransferases, etc. Occasionally, severe hepatitis, hepatic necrosis, hepatic steatosis, etc.. ② urinary reactions: in recent years, there are many reports of acute interstitial nephritis caused by this product, resulting in renal failure. However, this toxic reaction is reversible, and renal function can be normalized after stopping the drug. In order to avoid nephrotoxicity, attention should be paid to checking renal function during the use of the drug. Hematopoietic system reactions: the product has a certain inhibitory effect on the bone marrow, a small number of patients can occur reversible moderate leukopenia or granulocytopenia, there are thrombocytopenia and autoimmune hemolytic anemia, the incidence of which is 0.02 per thousand of the users of the drug. It has also been reported that this product can cause aplastic anemia. Attention should be paid to check the blood picture during the use of the drug. ④Central nervous system reaction: this product can pass the blood-brain barrier and has a certain degree of neurotoxicity. Dizziness, headache, fatigue and drowsiness are more common. A few patients may experience restlessness, dulled sensation, slurred speech, sweating, localized convulsions or epileptiform seizures, as well as hallucinations, delusions and other symptoms. It causes toxic symptoms and blood concentration more than 2μg/ml, and mostly occurs in the elderly, young children or patients with hepatic or renal insufficiency, so it should be used with caution. ⑤ Cardiovascular system reaction: there may be bradycardia or tachycardia, facial flushing and so on. When injected intravenously, it may cause blood pressure to drop, premature atrial contraction and cardiac arrest. ⑥Effects on endocrine and skin: due to the anti-androgenic effect, a large dose of the drug (daily dose of >1.6g) can cause male *** development, female breast milk overflow, *** Decrease, impotence, *** count reduction, etc., which can be disappeared after stopping the drug. May inhibit sebum secretion, inducing exfoliative dermatitis, dry skin, sebum-deficient dermatitis, alopecia, oral ulcers. Rashes, giant urticaria, and drug fever also occur.
Contraindications
It is contraindicated in pregnant and lactating women.
Precautions
① In order to monitor the occurrence of toxic reactions of this product on the human system organs, before and during the use of the drug should be checked regularly for liver and renal function and blood, especially in patients with pre-existing liver and kidney disease. ② sudden stopping the drug after the "rebound phenomenon": sudden stopping the drug, may cause chronic peptic ulcer perforation, is estimated to be caused by the high acidity of the rebound after stopping. Therefore, it is necessary to continue to take the drug (400mg per night) for 3 months after completion of treatment. ③The application of this product may constitute interference with the results of experimental examinations: false-positive occult blood test of gastric juice may occur within 15 minutes after oral administration; blood salicylic acid concentration, serum creatinine, prolactin, aminotransferase and other concentrations may be increased; and the concentration of parathyroid hormone may be decreased. ④ There are reports of acute pancreatitis caused by the application of this product in animal experiments and clinics, so it should not be used in patients with acute pancreatitis. ⑤ The drug concentration in the cerebrospinal fluid of patients with severe hepatic insufficiency is twice as high as that of normal people after taking the regular dose, so it is easy to be poisoned. After the appearance of neurotoxicity, usually only need to reduce the dose appropriately to disappear. The symptoms of neurotoxicity are very similar to those caused by central anticholinergics, and the symptoms can be improved by treatment with the cholagogue toxic lentil alkaloids. Therefore, concomitant use of this product with central anticholinergics should be avoided to prevent exacerbation of central neurotoxic reactions.
Medication for pregnant and lactating women
① Due to its ability to cross the placental barrier and enter breast milk, it is contraindicated in pregnant and lactating women to avoid causing liver dysfunction in the fetus and infant.
Pediatric use
Young children are prone to central nervous system toxicity, so it should be used with caution.
Elderly patients
The kidneys are an important organ in the metabolism of this product, and the clearance of this product through the kidneys decreases with age, therefore, the dose should be reduced in elderly patients to prevent the occurrence of toxic psychosis.
Drug interactions
①Aluminum hydroxide, magnesium oxide, or metoclopramide (gastrofibromyalgia) taken concurrently with this product can reduce the blood concentration of this product. If it must be combined with antacids, the two should be taken at least one hour apart; if combined with metoclopramide, the dose of the product needs to be increased. ② Because aluminum thioglycollate needs to be hydrolyzed by gastric acid to play a role, this product inhibits the secretion of gastric acid, the combination of the two may make aluminum thioglycollate efficacy is reduced. ③This product can combine with cytochrome P450 through its imidazole ring, inhibit the activity of hepatic microsomal oxidase, and also reduce the blood flow into the liver. Therefore, when combined with propranolol, metoprolol, metronidazole, etc., the serum concentration of the latter will increase and the heart rate will be slowed down at rest; when combined with phenytoin sodium or other beta-lactone ureas, it may increase the blood concentration of the latter and lead to phenytoin sodium poisoning, and when it must be used in combination, the blood concentration of phenytoin sodium should be measured after 5 days so that the dosage can be adjusted. ④Combination with opioids: there are reports of respiratory depression, mental confusion, disorientation and other adverse reactions in patients with chronic renal failure. The dosage of opioids should be reduced in such patients. ⑤ This product may increase the absolute bioavailability of verapamil (isobarbital) from (26.3 ± 16.8)% to (49.3 ± 23.6)%. Care should be taken because rare but serious side effects can occur with verapamil. (vi) When combined with xanthines such as theanine and aminophylline, hepatic metabolism is decreased, which can reduce the latter's demethylated metabolic clearance by 20% to 30% and elevate its blood concentration. (vii) Combining with benzodiazepine tranquilizers (diazepam, nitrazepam, flunitrazepam, clozapine) may increase the blood concentration of diazepam, etc., aggravate sedation and other central nervous system depressant symptoms, and develop respiratory and circulatory failure, due to the inhibition of intrahepatic metabolism. (8) When patients take digoxin and quinidine at the same time, it is not advisable to use this product, because this product can inhibit the metabolism of quinidine, and the latter can displace digoxin from its binding site, which results in an increase in the blood concentration of both quinidine and digoxin. In this case, blood levels should be monitored. ⑨ This product delays the metabolism of caffeine and, when combined with it, enhances the effects of the latter and is prone to toxic reactions. Caffeine is contraindicated in patients with gastric ulcer, and caffeine and caffeinated beverages should be contraindicated when taking this product. ⑩ With warfarin anticoagulants, the rate of the latter's excretion from the body can be reduced, leading to bleeding tendency.11 Because the product increases the pH of gastric juice, when combined with tetracycline, it can reduce the rate of dissolution of tetracycline, reduce the absorption, and the effect is weakened (however, the enzyme inhibition of this product may increase the blood concentration of tetracycline); if combined with aspirin, the opposite result occurs, and it can enhance the effect of aspirin.12 Combination with ketoconazole interferes with the absorption of the latter and reduces its antifungal activity, but co-administration of some acidic beverages avoids these changes.13 Combination of this product with captopril has the potential to cause psychotic symptoms.14 Since this product has a myoneurologic blockade similar to that of the aminoglycosides, this effect is not counteracted by neostigmine but only by calcium chloride. Therefore, it may cause respiratory depression or respiratory arrest when combined with aminoglycoside antibiotics.15 Patients should take the medication on a regular basis and adhere to the regimen, which is usually most effective when taken with meals and at bedtime.
Overdose
① Clinical signs of overdose are: shortness of breath or dyspnea, tachycardia. ② treatment: first remove the gastrointestinal tract has not been absorbed drugs, and give clinical supervision and supportive therapy, respiratory failure, immediately artificial respiration, tachycardia can be given β-adrenergic blocking drugs.
Specifications
0.2g/tablet; 0.4g/tablet; 0.8g/tablet;
Expiry date
Storage
Sealed.
Approval number
Manufacturer
Company name:
Address:
Postal code:
Telephone number:
Fax number:
Website address:
Approval date:
Expiration date:
Storage
Sealed.