How is tagamet supplied

For difficult to heal ulcers: see full labeling. Impaired renal or hepatic function. Pregnancy Cat. Nursing mothers: not recommended. Avoid antacids within 1 hour of dosing. In patients who complain of caffeine-related side effects caffeine dosage or intake may need to be reduced. Acetaminophen; Caffeine; Dihydrocodeine: Moderate Concomitant use of dihydrocodeine with cimetidine may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death.

If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage adjustment of dihydrocodeine until stable drug effects are achieved. Discontinuation of cimetidine could alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine.

If cimetidine is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Minor Inhibitors of CYP1A2, such as cimetidine, may inhibit the hepatic oxidative metabolism of caffeine.

Acetaminophen; Codeine: Minor Cimetidine may inhibit the conversion of codeine to morphine, codeine's active metabolite, via the CYP2D6 hepatic isoenzyme and therefore may decrease the ability for codeine to produce analgesic effect. Acetaminophen; Hydrocodone: Moderate Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of cimetidine is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough.

Hydrocodone is a CYP2D6 and CYP3A4 substrate, and coadministration with CYP2D6 and CYP3A4 inhibitors like cimetidine can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone.

If cimetidine is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. Acetaminophen; Oxycodone: Moderate Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of cimetidine is necessary.

If cimetidine is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a weak inhibitor like cimetidine can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If cimetidine is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.

When used in high doses, cimetidine has decreased the metabolism of certain opiate agonists leading to increased opiate concentrations and opiate toxicity in some patients.

The clinical significance of the interaction is not well-established. Acetohexamide: Moderate Cimetidine has been shown to affect the pharmacokinetics of some oral sulfonylureas. Patients receiving sulfonylureas should be observed for evidence of altered glycemic response when cimetidine is instituted or discontinued. The mechanism of this interaction may involve either increasing the absorption or decreasing the clearance of the sulfonylurea.

Asymptomatic hypoglycemia has been observed as a result of this interaction. It is unclear at this time if famotidine or nizatidine interact with oral sulfonylureas.

Acyclovir: Minor Cimetidine may cause a reduction in the clearance of acyclovir. The clinical significance of these pharmacokinetic interactions is unknown; however, no dosage adjustments are recommended for patients with normal renal function. Coadministration of these drugs has not been studied, but caution is warranted. Albendazole: Moderate Cimetidine administration with albendazole has been reported to increase albendazole bioavailability.

Concentrations of albendazole sulfoxide were increased in bile and cystic fluid about 2 fold in patients with hydatid cyst disease treated with cimetidine 10 mg per kg per day concomitantly with albendazole compared to administration of albendazole alone. More data are needed to elucidate the clinical consequence of this interaction. Alendronate: Moderate Although the clinical significance has not been determined, the bioavailability of oral alendronate is doubled by concomitant administration of intravenous ranitidine.

Investigations have not been undertaken to determine if other H2-antagonists have a similar effect on bioavailability. Patients should be closely monitored when H2-blockers are coadministered as they may affect the bioavailability of alendronate, possibly leading to a higher likelihood of developing adverse effects while taking alendronate. Alendronate; Cholecalciferol: Moderate Although the clinical significance has not been determined, the bioavailability of oral alendronate is doubled by concomitant administration of intravenous ranitidine.

Alfentanil: Minor Cimetidine is an inhibitor of CYP3A4 and thus, reduces the clearance of alfentanil and may prolong the duration of action of alfentanil. Smaller alfentanil doses will be needed if prolonged alfentanil administration is used. Monitor patients for adverse effects of alfentanil, such as hypotension, nausea, itching, and respiratory depression.

Alfuzosin: Moderate Alfuzosin is extensively metabolized by hepatic enzymes. Administration of of cimetidine, an inhibitor of hepatic cytochrome P, with alfuzosin may increase the serum concentration of alfuzosin. Alogliptin; Metformin: Moderate Use with caution, as cimetidine inhibits renal elimination of metformin. Consider alternatives to cimetidine. Increased metformin exposure due to use of cimetidine may lead to gastrointestinal complaints, altered glycemic control, and a potential for an increased risk for lactic acidosis.

If it is medically necessary to use cimetidine, carefully monitor. Metformin dose reduction may be needed. An interaction between metformin and oral cimetidine has been observed in normal healthy volunteers in both single- and multiple-dose drug interaction studies. Cimetidine inhibits common renal tubular transport systems involved in the renal elimination of metformin e. Alprazolam: Major Avoid coadministration of alprazolam and cimetidine due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression.

If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with cimetidine, as these benzodiazepines are not oxidatively metabolized. Altretamine: Minor Cimetidine, a known inhibitor of the cytochrome P enzyme system, can decrease the hepatic metabolism of altretamine, which could result in delayed elimination and increased blood concentrations.

Amiodarone: Moderate Cimetidine may decrease the CYP3A4 metabolism of amiodarone, potentially resulting in increased plasma concentrations of amiodarone and the active metabolite.

Amitriptyline: Moderate Cimetidine can inhibit the hepatic clearance of some tricyclic antidepressants that undergo oxidative metabolism, including amitriptyline.

Choose an alternate H2-blocker when possible; alternatively, observe patients closely for TCA-induced side effects or toxicity if the concurrent use of cimetidine is unavoidable. It has also been reported that cimetidine could potentially increase the serum concentrations of HMG-CoA reductase inhibitors via the inhibition of the hepatic isoenzymes.

Cimetidine does not alter the pharmacokinetics of atorvastatin, cerivastatin, or pravastatin. Clinical evidence of pharmacokinetic interactions with lovastatin and simvastatin is not available.

Amlodipine; Celecoxib: Minor Since celecoxib is metabolized by cytochrome P 2C9, concurrent administration with cimetidine, which can inhibit this enzyme, may result in increased levels of celecoxib. The clinical significance of this interaction has not been established. Amoxapine: Moderate Cimetidine can inhibit the systemic clearance of drugs that undergo oxidative metabolism, such as amoxapine, resulting in increased plasma levels of the antidepressant. Patients should be monitored for amoxapine-related side effects and toxicity if cimetidine is added; when possible, choose an alternative H2-blocker for treatment.

Amphetamine; Dextroamphetamine Salts: Moderate The use of H2-blockers with amphetamine therapy may change the onset of action of amphetamine or dextroamphetamine due to the increase in gastric pH. The time to maximum concentration Tmax of these amphetamines is decreased compared to when administered alone, thus increasing stimulant concentrations, which may be of particular significance with extended-release dosage forms.

Monitor clinical response and adjust if needed. Although drug interaction studies have not been conducted, the serum concentrations of cimetidine may be increased with concomitant administration of amprenavir. Theoretically, cimetidine may increase the serum concentration of amprenavir. Coadministration of anagrelide with drugs that inhibit CYP1A2, such as cimetidine, could theoretically decrease the elimination of anagrelide and increase the risk of side effects or toxicity.

Patients should be monitored for increased adverse effects if these drugs are coadministered. Alternate H2-antagonist therapy that may not interact should be considered. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Interactions with potent inhibitors of CYP3A4 such as cimetidine are possible.

However, because armodafinil is itself an inducer of the CYP3A4 isoenzyme, drug interactions due to CYP3A4 inhibition by other medications may be complex and difficult to predict. Observation of the patient for increased effects from armodafinil may be needed. Artemether; Lumefantrine: Moderate Cimetidine is an inhibitor and artemether a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased artemether concentrations.

Concomitant use warrants caution due to the potential for increased side effects. Moderate Cimetidine is an inhibitor and lumefantrine a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased lumefantrine concentrations. Concomitant use warrants caution due to the potential for increased side effects, including increased potentiation of QT prolongation. Aspirin, ASA; Butalbital; Caffeine; Codeine: Minor Cimetidine may inhibit the conversion of codeine to morphine, codeine's active metabolite, via the CYP2D6 hepatic isoenzyme and therefore may decrease the ability for codeine to produce analgesic effect.

Aspirin, ASA; Caffeine; Dihydrocodeine: Moderate Concomitant use of dihydrocodeine with cimetidine may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death.

Theoretically, CY2C19 inhibitors, such as cimetidine, could increase carisoprodol plasma levels, with potential for enhanced CNS depressant effects. Minor Cimetidine may inhibit the conversion of codeine to morphine, codeine's active metabolite, via the CYP2D6 hepatic isoenzyme and therefore may decrease the ability for codeine to produce analgesic effect. Aspirin, ASA; Oxycodone: Moderate Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of cimetidine is necessary.

Atazanavir: Major Coadministration of H2-blockers with atazanavir reduces serum atazanavir concentrations; however, H2-blockers can be used under specific administration restrictions. Significant reductions in atazanavir serum concentrations may lead to therapeutic failure and the development of HIV resistance. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with an H2- blocker.

Atazanavir; Cobicistat: Major Coadministration of H2-blockers with atazanavir reduces serum atazanavir concentrations; however, H2-blockers can be used under specific administration restrictions. A dosage adjustment of atomoxetine may be needed in normal populations also known as extensive metabolizers when atomoxetine is administered with inhibitors of the CYP2D6 enzyme, such as cimetidine.

In vitro studies suggest that coadministration of CYP2D6 inhibitors to poor metabolizers will not further increase the plasma concentrations of atomoxetine. Theoretically, systemic exposure of nasally administered azelastine may be increased by coadministration with cimetidine, although an interaction has not been documented.

Azelastine; Fluticasone: Moderate Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures.

Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.

Beclomethasone: Moderate Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Belladonna Alkaloids; Ergotamine; Phenobarbital: Major Coadministration of ergotamine with inhibitors of CYP3A4, such as cimetidine, may potentially increase the risk of ergot toxicity.

Coadministration should be done cautiously, and avoided when possible. Belzutifan: Moderate Monitor for anemia and hypoxia if concomitant use of cimetidine with belzutifan is necessary due to increased plasma exposure of belzutifan which may increase the incidence and severity of adverse reactions. Reduce the dose of belzutifan as recommended if anemia or hypoxia occur. Bendamustine: Major Consider the use of an alternative therapy if cimetidine treatment is needed in patients receiving bendamustine.

Cimetidine may increase bendamustine exposure, which may increase the risk of adverse reactions e. Benzhydrocodone; Acetaminophen: Moderate Concurrent use of benzhydrocodone with cimetidine may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved.

Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of cimetidine in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists.

If cimetidine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Betamethasone: Moderate Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention.

Bisacodyl: Minor The concomitant use of bisacodyl tablets with H2-blockers can cause the enteric coating of the bisacody tablet to dissolve prematurely, leading to possible gastric irritation or dyspepsia. Avoid H2-blockers within 1 hour before or after the bisacodyl dosage. Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: Moderate Cimetidine is an enzyme inhibitor that can decrease the hepatic metabolism of metronidazole.

As a result, elimination can be delayed and serum metronidazole concentrations can increase. The sequelae of this interaction are unclear, although prolonged administration of metronidazole has been associated with seizures. If possible, cimetidine should not be used during metronidazole therapy. Bismuth Subsalicylate: Minor H2-blockers may increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate. Bismuth Subsalicylate; Metronidazole; Tetracycline: Moderate Cimetidine is an enzyme inhibitor that can decrease the hepatic metabolism of metronidazole.

Minor H2-blockers may increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate. Boceprevir: Moderate Close clinical monitoring is advised when administering cimetidine with boceprevir due to an increased potential for boceprevir-related adverse events.

If cimetidine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of cimetidine and boceprevir. Cimetidine is an inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may be elevated.

Bortezomib: Minor Agents that inhibit cytochrome P 3A4 may increase the exposure to bortezomib and increase the risk for toxicity; however, bortezomib is also metabolized by other CYP isoenzymes.

Therefore, the clinical significance of concurrent administration of bortezomib with cimetidine is not known. Bosutinib: Moderate Bosutinib displays pH-dependent aqueous solubility; therefore, concomitant use of bosutinib and H2-blockers may result in decreased plasma exposure of bosutinib. Separate the administration of bosutinib and H2-blockers by more than 2 hours. Brimonidine; Timolol: Moderate Monitor for an increased incidence of timolol-related adverse effects if cimetidine and timolol are used concomitantly.

Coadministration of cimetidine and timolol may result in increased plasma concentrations of timolol. Cimetidine is a CYP2D6 inhibitor. Timolol is a CYP2D6 substrate. Brompheniramine; Guaifenesin; Hydrocodone: Moderate Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of cimetidine is necessary. Brompheniramine; Hydrocodone; Pseudoephedrine: Moderate Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of cimetidine is necessary.

Budesonide: Moderate Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Moderate Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Likewise, the dissolution of the coating of extended-release budesonide tablets Uceris is pH dependent.

Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. Budesonide; Formoterol: Moderate Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention.

Budesonide; Glycopyrrolate; Formoterol: Moderate Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Bupivacaine; Lidocaine: Moderate Concomitant use of systemic lidocaine and cimetidine may increase lidocaine plasma concentrations. Monitor for lidocaine toxicity if used together. Buprenorphine: Minor Since the metabolism of buprenorphine is mediated by the CYP3A4 isozyme, co-administration of drugs that inhibit CYP3A4, such as cimetidine, may cause decreased clearance of buprenorphine.

Thus, there is a potential for excessive buprenorphine-related side effects. Buprenorphine; Naloxone: Minor Since the metabolism of buprenorphine is mediated by the CYP3A4 isozyme, co-administration of drugs that inhibit CYP3A4, such as cimetidine, may cause decreased clearance of buprenorphine. Bupropion: Moderate Cimetidine has resulted in increased plasma concentrations of the active metabolites, threohydrobupropion and erythrobupropion, but the clinical significance is not known.

Bupropion; Naltrexone: Moderate Cimetidine has resulted in increased plasma concentrations of the active metabolites, threohydrobupropion and erythrobupropion, but the clinical significance is not known.

Buspirone: Moderate CYP3A4 inhibitors, such as cimetidine, may decrease systemic clearance of buspirone leading to increased or prolonged effects. If buspirone is to be administered concurrently with significant CYP3A4 inhibitors, a low dose of buspirone is recommended initially. Butalbital; Acetaminophen; Caffeine; Codeine: Minor Cimetidine may inhibit the conversion of codeine to morphine, codeine's active metabolite, via the CYP2D6 hepatic isoenzyme and therefore may decrease the ability for codeine to produce analgesic effect.

Cabotegravir; Rilpivirine: Moderate Coadministration with cimetidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of H2 receptor antagonist for at least 12 hours before and at least 4 hours after administering rilpivirine. Calcium Carbonate; Risedronate: Major Use of H2-blockers with delayed-release risedronate tablets Atelvia is not recommended.

Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. Canagliflozin; Metformin: Moderate Use with caution, as cimetidine inhibits renal elimination of metformin.

Drugs known to inhibit CYP3A4, such as cimetidine, may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations. Serum carbamazepine concentrations should be monitored closely during coadministration; reduce carbamazepine doses may be necessary.

Carbinoxamine; Hydrocodone; Phenylephrine: Moderate Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of cimetidine is necessary. Carbinoxamine; Hydrocodone; Pseudoephedrine: Moderate Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of cimetidine is necessary.

Consider using an alternative agent in place of cimetidine. Carvedilol: Moderate Monitor for an increased incidence of carvedilol-related adverse effects if cimetidine and carvedilol are used concomitantly. Maximum serum concentrations of carvedilol are not increased. The clinical significance of this pharmacokinetic interaction is unclear. Cefditoren: Moderate Cefditoren pivoxil absorption may be decreased by H2-blockers.

Coadministration is not recommended. The clinical significance of this interaction is not known. Cefpodoxime: Moderate H2-blockers should be avoided during treatment with cefpodoxime. Coadministration could result in antibiotic failure. H2-blockers increase gastric pH. Cefpodoxime proxetil requires low gastric pH for dissolution. Ceftibuten: Minor H2-blockers can affect the pharmacokinetics of some orally-administered cephalosporins.

The oral bioavailability of ceftibuten was reported to be increased by the administration of mg of ranitidine PO every 12 hours for 3 days, but this interaction is of unknown clinical relevance. Cefuroxime: Major Avoid the concomitant use of H2-blockers and cefuroxime.

Drugs that reduce gastric acidity, such as H2-blockers, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.

Celecoxib: Minor Since celecoxib is metabolized by cytochrome P 2C9, concurrent administration with cimetidine, which can inhibit this enzyme, may result in increased levels of celecoxib. Cetrorelix: Minor Drugs that cause hyperprolactinemia, such as cimetidine, should not be administered concomitantly with gonadotropin releasing hormone analogs since hyperprolactinemia down-regulates the number of pituitary GnRH receptors.

Chlordiazepoxide: Moderate Cimetidine can inhibit the hepatic clearance of some benzodiazepines that undergo oxidative metabolism, including chlordiazepoxide. Chlordiazepoxide; Amitriptyline: Moderate Cimetidine can inhibit the hepatic clearance of some benzodiazepines that undergo oxidative metabolism, including chlordiazepoxide. Moderate Cimetidine can inhibit the hepatic clearance of some tricyclic antidepressants that undergo oxidative metabolism, including amitriptyline.

Chlordiazepoxide; Clidinium: Moderate Cimetidine can inhibit the hepatic clearance of some benzodiazepines that undergo oxidative metabolism, including chlordiazepoxide. Chloroquine: Major Avoid concomitant use of chloroquine and cimetidine as cimetidine may inhibit the metabolism of chloroquine, increasing its plasma concentration.

Chlorpheniramine; Codeine: Minor Cimetidine may inhibit the conversion of codeine to morphine, codeine's active metabolite, via the CYP2D6 hepatic isoenzyme and therefore may decrease the ability for codeine to produce analgesic effect. Chlorpheniramine; Dihydrocodeine; Phenylephrine: Moderate Concomitant use of dihydrocodeine with cimetidine may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death.

Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: Moderate Concomitant use of dihydrocodeine with cimetidine may alter dihydrocodeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: Moderate Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of cimetidine is necessary.

Chlorpheniramine; Hydrocodone: Moderate Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of cimetidine is necessary. Recognizing and celebrating excellence in chemistry and celebrate your achievements.

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Commemorative Booklet PDF. As late as the s, a peptic ulcer could be a life-threatening condition. Sufferers often endured periods of intense pain over many years, especially at mealtimes and at night, with social and economic repercussions for themselves and their families. Left untreated, an ulcer could result in severe bleeding and death. A major cause of ulcers is the release of excess stomach acid, which leads to breaches in the lining of the intestinal tract.

Continuing acid secretion prevents healing. The main treatment used to be the administration of alkalis, which provided only temporary relief. Patients were told to rest and follow a bland diet. Surgery to remove part of the stomach was a last resort. The research program leading to cimetidine also represented a revolution in the way pharmaceuticals are developed.

Traditionally, the development of a new drug would often depend on the fortuitous discovery of a plant or microbial extract that showed some of the required biological activity.

Using that first extract as a lead, many similar compounds would be made and tested for pharmacological effectiveness. In many cases, the researchers did not know how the drug worked, so finding an optimal compound was difficult.

The development of cimetidine was radically different: It was one of the first drugs to be designed logically from first principles. They confirmed that a molecule found in the body called histamine triggers the release of acid when it binds to a specific receptor now called the H 2 -receptor in the stomach lining.

Their aim was to find a molecule that successfully competed with histamine in combining with the receptor, but then blocked, rather than stimulated, acid release. Such a molecule was called a histamine H 2 -receptor antagonist and represented a new class of drugs. Using a step by step analysis of structural and physical properties, the team made a series of histamine-based molecules, which were then tested for antagonist activity using carefully designed pharmacological assays.

Today, this approach of rational drug design underpins the discovery programs of many major pharmaceutical companies. The discovery of histamine H 2 -antagonists is a story of single-minded commitment by a group of creative scientists working in close collaboration in the United Kingdom.

The process of research and development for economical production of the resulting drug, cimetidine, was the work of equally creative scientists working in the United States. He soon recruited two colleagues: James Black as head of pharmacology and William Duncan as head of biochemistry. Black had been instrumental in developing beta-blocker drugs for the treatment of heart disease.

They were based on his notion of blocking the stimulating action of a molecule agonist at a receptor site implicated in the disease with a similar but inactive chemical antagonist. He was keen to start a new research program looking at histamine receptors and antagonists. Stacy Wiegman, PharmD. The over-the-counter heartburn drug Tagamet HB cimetidine is supplied as milligram mg tablets.

You may take two tablets within 24 hours. If this dosage is not controlling your symptoms or if they get worse, call your doctor.