Cimetidine; Uses, Dosage, Side Effects, Drug Interactions Cimetidine is a histamine H(2)-receptor antagonist. Enhancing anti-tumor cell-mediated responses, cimetidine blocks histamine’s ability to stimulate suppressor T lymphocyte activity and to inhibit natural killer (NK) cell activity and interleukin-2 production. Cimetidine also may inhibit tumor growth by suppressing histamine’s growth-factor activity and blocking histamine-induced stimulation of vascular endothelial growth factor (VEGF), a pro-angiogenic growth factor. Cimetidine is a histamine H2 receptor antagonist that inhibits stomach acid production. It inhibits gastric acid secretion, as well as pepsin and gastrins output. It is available over-the-counter and is mainly used in the treatment of heartburn and peptic ulcers. The development of longer-acting H2 receptor antagonists with fewer drug interactions and adverse effects, such as ranitidine and famotidine, decreased the use of cimetidine, and though it is still used, cimetidine is no longer among the more widely used of the H2-receptor antagonists. Mechanism of Action of Cimetidine Cimetidine binds to an H2-receptor located on the basolateral membrane of the gastric parietal cell, blocking histamine effects. This competitive inhibition results in reduced gastric acid secretion and a reduction in gastric volume and acidity. H2 antagonists inhibit gastric acid secretion elicited by histamine & other H2 agonists in a dose-dependent, competitive manner; the degree of inhibition parallels the concentration of the drug in plasma over a wide range. The H2 antagonists also inhibit acid secretion elicited by gastrin &, to a lesser extent, by muscarinic agonists. Importantly, these drugs inhibit basal (fasting) & nocturnal acid secretion & that stimulated by food, sham feeding, fundic distention, & various pharmacological agents; this property reflects the vital role of histamine in mediating the effects of diverse stimuli. The H2 antagonists reduce both the volume of gastric juice secreted & its H+ concentration. The output of pepsin, which is secreted by the chief cells of gastric glands (mainly under cholinergic control), generally falls in parallel with the reduction in the volume of gastric juice. Cimetidine blocks H2-receptors, which in part are responsible for the inflammatory response, in the cutaneous blood vessels of humans. Indications of Cimetidine Gastro-esophageal Reflux Disease Heartburn Hypersecretion gastric Cutaneous mastocytosis Bronchogenic carcinoma Duodenal ulcer prophylaxis Erosive esophagitis Indigestion Stomach ulcer Upper GI Hemorrhage Zollinger-Ellison Syndrome Active Duodenal ulcer Benign gastric ulcers Maintenance therapy Duodenal ulcer Contra-Indications of Cimetidine Clostridium difficile infection Inadequate Vitamin B12 Low amount of magnesium in the blood Liver problems Interstitial Nephritis Subacute cutaneous lupus erythematosus Systemic Lupus Erythematosus Osteoporosis Broken Bone Allergies to Proton Pump Inhibitors Dosage of Cimetidine Strengths: 100 mg; 200 mg; 300 mg; 400 mg; 800 mg; 900 mg 300 mg/5 mL; Duodenal Ulcer Parenteral: 300 mg IV or IM every 6 to 8 hours. Alternatively, a continuous IV infusion may be administered at a rate of 37.5 to 50 mg/hour, or up to a maximum rate of 100 mg/hour (2.4 g/day). Oral: 800 mg to 1600 mg once a day at bedtime. Alternatively, dosage regimens of 300 mg four times per day, with meals and at bedtime, or 400 mg twice daily, in the morning and at bedtime, have shown to be effective. Erosive Esophagitis Parenteral: 300 mg IV or IM every 6 hours. Alternatively, a continuous IV infusion may be administered at a rate of 50 mg/hour initially, with 25 mg/hour incremental increases up to a maximum rate of 100 mg/hour (2.4 g/day). Oral: 800 mg twice a day, or alternatively, 400 mg four times a day. Stress Ulcer Prophylaxis Parenteral: 300 mg IV or IM every 6 hours. Alternatively, a continuous IV infusion may be administered at a rate of 50 mg/hour. Zollinger-Ellison Syndrome Parenteral: 300 mg IV or IM every 6 hours. Alternatively, a continuous IV infusion may be administered at a rate of 50 mg/hour initially. Infusion rates have ranged from 40 to 600 mg/hour, but should not exceed a daily total of 2.4 g. Oral: 300 mg 4 times a day with meals and at bedtime. Gastroesophageal Reflux Disease Parenteral: 300 mg IV or IM every 6 hours. Alternatively, a continuous IV infusion may be administered at a rate of 50 mg/hour. The maximum daily dose should not exceed 2.4 g. Oral: 800 mg twice a day, or 400 mg 4 times a day. Pediatric Gastroesophageal Reflux Disease Neonatal: 5 to 10 mg/kg/day administered IV or IM in divided doses every 8 to 12 hours. Infants: 10 to 20 mg/kg/day administered IV, IM, or oral in divided doses every 6 to 12 hours. Children: 20 to 40 mg/kg/day administered IV, IM, or oral in divided doses every 6 hours. Side Effects of Cimetidine The most common Nausea and vomiting Severe stomach ache Severe diarrhea Vaginal thrush Skin rash A headache chest pain constipation a cough diarrhea or loose stools difficulty with breathing dizziness heartburn muscle pain More common Abdominal or stomach pain, discomfort, or tenderness chills or fever difficulty with moving a headache, severe and throbbing joint or back pain muscle aching or cramping muscle pains or stiffness chest pressure or squeezing pain in the chest discomfort in arms, shoulders, neck or upper back excessive sweating feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis sudden tingling or coldness in an arm or leg sudden slow or difficult speech sudden drowsiness or need to sleep fast breathing sharp pain when taking a deep breath fast or slow heartbeat coughing up blood rust colored urine decreased amount of urine Rare Anxiety change in vision seizures abnormal or fast heart rate tremors weight loss chest pain or tightness confusion a cough Agitation arm, back, or jaw pain blurred vision chest pain or discomfort convulsions extra heartbeats fainting hallucinations a headache irritability lightheadedness mood or mental changes muscle pain or cramps muscle spasm or jerking of all extremities Drug Interactions of Cimetidine Cimetidine may interact with the following drugs, supplements, & may change the efficacy of the drug amiodarone azole antifungal medications (e.g., fluconazole, ketoconazole) caffeine calcium channel blockers (e.g., diltiazem, nifedipine, verapamil) carbamazepine carvedilol certain benzodiazepines (alprazolam, chlordiazepoxide, clonazepam, diazepam, flurazepam, midazolam, and triazolam) clopidogrel clozapine dasatinib glyburide (and other “sulfonylurea” diabetes medications) lidocaine metformin metoprolol pentoxifylline phenytoin propranolol salmeterol SSRIs (e.g., citalopram, fluoxetine, sertraline) sucralfate theophyllines (e.g., aminophylline, oxtriphylline, theophylline) tramadol tricyclic antidepressants(e.g., amitriptyline, clomipramine, desipramine, trimipramine) warfarin Pregnancy Catagory FDA Pregnancy Category C Pregnancy The safety of this medication for use during pregnancy has not been established. This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately. Lactation This medication passes into breast milk. If you are a breastfeeding mother and are taking cimetidine, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. 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