- What is cimetidine
- Cimetidine mechanism of action
- Cimetidine vs ranitidine
- What is cimetidine used for
- Cimetidine dosage
- Usual Adult Dose for Duodenal Ulcer
- Usual Adult Dose for Duodenal Ulcer Prophylaxis
- Usual Adult Dose for Erosive Esophagitis
- Usual Adult Dose for Stress Ulcer Prophylaxis
- Usual Adult Dose for Upper GI Hemorrhage
- Usual Adult Dose for Zollinger-Ellison Syndrome
- Usual Adult Dose for Gastric Ulcer
- Usual Adult Dose for Gastroesophageal Reflux Disease (GERD)
- Usual Adult Dose for Dyspepsia
- Usual Pediatric Dose for Gastroesophageal Reflux Disease
- Usual Pediatric Dose for Dyspepsia
- Renal Dose Adjustments
- Liver Dose Adjustments
- Impaired Renal Function
- How should I take cimetidine?
- Cimetidine side effects
What is cimetidine
Cimetidine is in a class of medications called H2 blockers (histamine 2 receptor antagonist) that decreases the amount of acid made in your stomach. Cimetidine is used to treat ulcers; gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and injury of the food pipe (esophagus); and conditions where the stomach produces too much acid, such as Zollinger-Ellison syndrome. Over-the-counter cimetidine is used to prevent and treat symptoms of heartburn associated with acid indigestion and sour stomach.
Cimetidine is also used sometimes to treat stress ulcers, hives and itching, and viral warts, and to prevent aspiration pneumonia during anesthesia. Talk to your doctor about the possible risks of using this medication for your condition.
A total of 6 to 8 weeks is usually sufficient for ulcer healing. Gastroesophageal reflux disease (GERD) usually requires 8 to 12 weeks for healing. Erosive esophagitis therapy generally should not exceed 12 weeks.
Precautions: Symptomatic response to cimetidine does not rule out the possibility of gastrointestinal malignancy.
Cimetidine may be prescribed for other uses; ask your doctor or pharmacist for more information.
Cimetidine comes as a tablet and a liquid to take by mouth. It is usually taken once a day at bedtime or two to four times a day with meals and at bedtime. Over-the-counter cimetidine is usually taken once or twice a day with a glass of water. To prevent symptoms, it is taken within 30 minutes before eating or drinking foods that cause heartburn. Follow the directions on your prescription or the package label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take cimetidine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Do not take over-the-counter cimetidine for longer than 2 weeks unless your doctor tells you to. If symptoms of heartburn, acid indigestion, or sour stomach last longer than 2 weeks, stop taking cimetidine and call your doctor.
Symptomatic response to cimetidine therapy does not preclude the presence of a gastric malignancy (stomach cancer). There have been rare reports of transient healing of gastric ulcers despite subsequently documented malignancy. Reversible confusional states have been observed on occasion, predominantly, but not exclusively, in severely ill patients. Advancing age (50 or more years) and preexisting 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 3–4 days of drug withdrawal.
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 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.
Cimetidine and Pregnancy
Pregnancy Category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.
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.
Cimetidine and Breastfeeding
Cimetidine is secreted in human milk and, as a general rule, nursing should not be undertaken while a patient is on a drug.
Clinical experience in pediatric patients is limited. Therefore, cimetidine therapy cannot be recommended for pediatric patients under 16, unless, in the judgement of the physician, anticipated benefits outweigh the potential risks. In very limited experience, doses of 20–40 mg/kg per day have been used.
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.
Before taking cimetidine
- Heartburn can mimic early symptoms of a heart attack. Get emergency medical help if you have chest pain that spreads to your jaw or shoulder and you feel anxious or light-headed.
Ask a doctor or pharmacist if it is safe for you to use this medicine if you have:
- a weak immune system; or
- liver or kidney disease.
Before taking cimetidine
- tell your doctor and pharmacist if you are allergic to cimetidine or any other medications.
- tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Be sure to mention any of the following: anticoagulants (‘blood thinners’) such as warfarin (Coumadin); antidepressants (mood elevators) such as amitriptyline (Elavil), amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Adapin, Sinequan), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); chlordiazepoxide (Librium); clopidogrel (Plavix), diazepam (Valium); lidocaine (Xylocaine); metronidazole (Flagyl); nifedipine (Adalat, Procardia); phenytoin (Dilantin); propranolol (Inderal); and theophylline (Theobid, Theo-Dur). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
if you are taking antacids (Maalox, Mylanta, Tums), digoxin (Lanoxin), ketoconazole (Nizoral), or iron salts, take them 2 hours before cimetidine.
- tell your doctor if you have or have ever had human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), or kidney or liver disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking cimetidine, call your doctor.
- talk to your doctor about the risks and benefits of taking cimetidine if you are 65 years of age or older. Older adults should not usually take cimetidine because it is not as safe as other medication(s) that can be used to treat the same condition.
Cimetidine is not approved for use by anyone younger than 16 years old.
What other drugs will affect cimetidine?
If you also take ketoconazole (Nizoral), take it at least 2 hours before you take cimetidine.
Ask a doctor or pharmacist before using cimetidine with any other medications, especially:
- an antidepressant; or
- a blood thinner–warfarin, Coumadin, Jantoven.
This list is not complete and many other drugs may affect cimetidine. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.
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 concomitant administered cimetidine to maintain optimum therapeutic blood levels.
Alteration of the pH may affect the 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.
Cimetidine mechanism of action
Cimetidine 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.
1) Acid Secretion
Cimetidine 800 mg orally at bedtime reduces mean hourly H+ activity by greater than 85% over an 8-hour period in duodenal ulcer patients, with no effect on daytime acid secretion. Cimetidine 1600 mg orally at bedtime produces 100% inhibition of mean hourly H+ activity over an 8-hour period in duodenal ulcer patients, but also reduces H+ activity by 35% for an additional 5 hours into the following morning. Cimetidine 400 mg twice daily and 300 mg 4 times a day decrease nocturnal acid secretion in a dose-related manner, i.e., 47%–83% over a 6-to 8-hour period and 54% over a 9-hour period, respectively.
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 2 hours Cimetidine inhibited gastric acid secretion by at least 75%.
The effect of a 300 mg breakfast dose of Cimetidine continued for at least 4 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.
|Mean Gastric pH|
|1 hour||pH 3.5||2.6|
|2 hours||pH 3.1||1.6|
|3 hours||pH 3.8||1.9|
|4 hours||pH 6.1||2.2|
24-Hour Mean H+ Activity
Cimetidine 800 mg at bedtime, 400 mg twice daily and 300 mg 4 times a day all provide a similar, moderate (less than 60%) level of 24-hour acid suppression. However, the 800 mg bedtime regimen exerts its entire effect on nocturnal acid, and does not affect daytime gastric physiology.
Oral Cimetidine significantly inhibited gastric acid secretion stimulated by betazole (an isomer of histamine), pentagastrin, caffeine and insulin as follows:
|Stimulant||Stimulant Dose||Cimetidine||% Inhibition|
|Betazole||1.5 mg/kg (sc)||300 mg (po)||85% at 2 1/2 hours|
|Pentagastrin||6 mcg/kg/hr (iv)||100 mg/hr (iv)||60% at 1 hour|
|Caffeine||5 mg/kg/hr (iv)||300 mg (po)||100% at 1 hour|
|Insulin||0.03 units/kg/hr (iv)||100 mg/hr (iv)||82% at 1 hour|
When food and betazole were used to stimulate secretion, inhibition of hydrogen ion concentration usually ranged from 45–75% and the inhibition of volume ranged from 30–65%.
Oral Cimetidine 300 mg reduced total pepsin output as a result of the decrease in volume of gastric juice.
3) Intrinsic Factor
Intrinsic factor secretion was studied with betazole as a stimulant. Oral Cimetidine 300 mg inhibited the rise in intrinsic factor concentration produced by betazole, but some intrinsic factor was secreted at all times.
Lower Esophageal Sphincter Pressure and Gastric Emptying
Cimetidine has no effect on lower esophageal sphincter (LES) pressure or the rate of gastric emptying.
Cimetidine is rapidly absorbed after oral administration and peak levels occur in 45–90 minutes. The half-life of Cimetidine is approximately 2 hours. Both oral and parenteral (I.V. or I.M.) administration provide comparable periods of therapeutically effective blood levels; blood concentrations remain above that required to provide 80% inhibition of basal gastric acid secretion for 4–5 hours following a dose of 300 mg.
The principal route of excretion of Cimetidine is the urine. Following parenteral administration, most of the drug is excreted as the parent compound, following oral administration, the drug is more extensively metabolized, the sulfoxide being the major metabolite. Following a single oral dose, 48% of the drug is recovered from the urine after 24 hours as the parent compound. Following I.V. or I.M. administration, approximately 75% of the drug is recovered from the urine after 24 hours as the parent compound.
Cimetidine vs ranitidine
Ranitidine is a class of medications called histamine-2 blockers (H2 blockers) and ranitidine works by reducing the amount of acid your stomach produces. Ranitidine is used to treat and prevent ulcers in the stomach and intestines. Ranitidine also treats conditions in which the stomach produces too much acid, such as Zollinger-Ellison syndrome. Ranitidine also treats gastroesophageal reflux disease (GERD) and other conditions in which acid backs up from the stomach into the esophagus, causing heartburn and injury of the food pipe (esophagus).
Over-the-counter ranitidine is used to prevent and treat symptoms of heartburn associated with acid indigestion and sour stomach.
Ranitidine comes as tablets, soluble (dispersible) tablets that dissolve in water to make a drink, or as a liquid that you drink.
All types of ranitidine are available on prescription. You can also buy the lowest strength 75mg tablets from pharmacies and supermarkets.
The usual dose to treat:
- indigestion or heartburn is 75mg to 300mg ranitidine a day
- stomach ulcers and inflammation of the food pipe is 300mg to 600mg ranitidine a day
- Zollinger-Ellison syndrome is 450mg to 6 grams ranitidine a day
Ranitidine liquid comes in 2 different strengths – your daily dose will depend on what your doctor prescribes. Follow your doctor’s advice about how much ranitidine to take and when.
- Doses are usually lower for children and people with kidney problems.
If a doctor prescribes ranitidine for your child, they will use your child’s weight or age to work out the right dose.
- It’s usual to take ranitidine once or twice a day.
- Some people only need to take ranitidine for a short time, when they have symptoms. Others need to take it for longer.
- You can take ranitidine with or without food.
- It’s unusual to get any side effects. However, some people may get stomach pain or constipation, or feel sick (nausea). This tends to get better as you carry on taking ranitidine.
- Ranitidine is called by the brand names Zantac, Zantac 75, Zantac EFFERdose, Zantac Syrup and Taladine
Ranitidine mechanism of action
Ranitidine is a histamine-2 antagonist or H2 blocker. Ranitidine works by reducing the amount of acid your stomach produces. Histamine is a chemical that occurs naturally in your body. Histamine encourages your stomach to produce acid which it needs to digest your food. By blocking the histamine, ranitidine reduces the amount of acid your stomach produces. Having less acid in your stomach allows ulcers and inflammation to heal. If your foodpipe (esophagus) has been damaged by stomach acid, this will also have a chance to heal.
Ranitidine reduces the amount of acid your stomach makes.
- Short-term treatment of active duodenal ulcer. Most patients heal within 4 weeks. Trials available to date have not assessed the safety of ranitidine in uncomplicated duodenal ulcer for periods of more than 8 weeks.
- Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of acute ulcers. No placebo-controlled comparative trials have been carried out for periods of longer than 1 year.
- The treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome and systemic mastocytosis).
- Short-term treatment of active, benign gastric ulcer. Most patients heal within 6 weeks and the usefulness of further treatment has not been demonstrated. Trials available to date have not assessed the safety of ranitidine in uncomplicated, benign gastric ulcer for periods of more than 6 weeks.
- Maintenance therapy for gastric ulcer patients at reduced dosage after healing of acute ulcers. Placebo-controlled trials have been carried out for 1 year.
- Treatment of gastro-esophageal reflux disease (GERD). Symptomatic relief commonly occurs within 24 hours after starting therapy with Zantac 150 mg twice daily.
- Treatment of endoscopically diagnosed erosive esophagitis. Symptomatic relief of heartburn commonly occurs within 24 hours of therapy initiation with ranitidine 150 mg 4 times daily.
- Maintenance of healing of erosive esophagitis. Placebo-controlled trials have been carried out for 48 weeks.
Concomitant antacids should be given as needed for pain relief to patients with active duodenal ulcer; active, benign gastric ulcer; hypersecretory states; GERD; and erosive esophagitis.
Ranitidine is also taken to prevent and treat stomach ulcers.
Sometimes, ranitidine is taken for a rare illness caused by a tumor in the pancreas or gut called Zollinger-Ellison syndrome.
Ranitidine isn’t suitable for some people. To make sure that it is safe for you, tell your doctor if you:
- have had an allergic reaction to ranitidine or any other medicines in the past
- have kidney problems
- have an intolerance to, or cannot absorb, some sugars such as fructose
- have been advised to eat a low calcium or low salt diet
- cannot have alcohol – ranitidine liquid contains a small amount of alcohol
- have phenylketonuria (PKU), a rare inherited illness
If you’re due to have an endoscopy to find out what’s causing your symptoms, stop taking ranitidine at least 2 weeks before your procedure. This is because ranitidine may hide some of the problems that would usually be spotted during an endoscopy.
The safety and effectiveness of ranitidine have been established in the age-group of 1 month to 16 years for the treatment of duodenal and gastric ulcers, gastroesophageal reflux disease and erosive esophagitis, and the maintenance of healed duodenal and gastric ulcer. Use of ranitidine in this age-group is supported by adequate and well-controlled trials in adults, as well as additional pharmacokinetic data in pediatric patients and an analysis of the published literature.
Safety and effectiveness in pediatric patients for the treatment of pathological hypersecretory conditions or the maintenance of healing of erosive esophagitis have not been established.
Safety and effectiveness in neonates (aged younger than 1 month) have not been established.
Of the total number of subjects enrolled in US and foreign controlled clinical trials of oral formulations of ranitidine, for which there were subgroup analyses, 4,197 were aged 65 and older, while 899 were aged 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the kidney and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, caution should be exercised in dose selection, and it may be useful to monitor renal function.
Pregnancy and breastfeeding
Tell your pharmacist or doctor if you’re trying to get pregnant, are already pregnant or if you’re breastfeeding.
Usually, ranitidine is safe to take during pregnancy and while breastfeeding. Animal models have failed to reveal evidence of impaired fertility or fetal harm. It is unknown whether use of gastric-suppressing drugs are associated with childhood allergy and asthma. There are no controlled data in human pregnancy.
If you’re pregnant, it’s always better to try to treat indigestion without taking a medicine.
Your doctor or midwife will first advise you to try to ease your symptoms by eating smaller meals more often, and not eating fatty and spicy foods. They may also suggest raising the head of your bed by 10 to 20cm, so your head and chest are higher than your waist. This will help stop stomach acid travelling up towards your throat.
If these lifestyle changes don’t work, you may be recommended a medicine like ranitidine.
Pregnancy Category B. Reproduction studies have been performed in rats and rabbits at doses up to 160 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to ranitidine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Carcinogenesis, Mutagenesis, Impairment of Fertility
There was no indication of tumorigenic or carcinogenic effects in life-span studies in mice and rats at dosages up to 2,000 mg/kg/day.
Ranitidine was not mutagenic in standard bacterial tests (Salmonella, Escherichia coli) for mutagenicity at concentrations up to the maximum recommended for these assays.
In a dominant lethal assay, a single oral dose of 1,000 mg/kg to male rats was without effect on the outcome of 2 matings per week for the next 9 weeks.
Ranitidine and breastfeeding
Ranitidine is safe to take while you’re breastfeeding. It passes into breast milk, but only in small amounts which aren’t harmful to the baby.
However, if your baby is premature or has health problems check with your doctor first.
Cautions with other medicines
For safety, tell your pharmacist or doctor if you’re taking other medicines including herbal remedies, vitamins or supplements.
Some medicines can interfere with ranitidine and make you more likely to have side effects.
Tell your doctor if you’re taking these medicines before you start taking ranitidine:
- anti-fungal medicines such as itraconazole, ketoconazole or posaconazole
- any medicine used to treat cancer
- HIV medicines
Ranitidine has been reported to affect the bioavailability of other drugs through several different mechanisms such as competition for renal tubular secretion, alteration of gastric pH, and inhibition of cytochrome P450 enzymes.
Procainamide: Ranitidine, a substrate of the renal organic cation transport system, may affect the clearance of other drugs eliminated by this route. High doses of ranitidine (e.g., such as those used in the treatment of Zollinger-Ellison syndrome) have been shown to reduce the renal excretion of procainamide and N-acetylprocainamide resulting in increased plasma levels of these drugs. Although this interaction is unlikely to be clinically relevant at usual ranitidine doses, it may be prudent to monitor for procainamide toxicity when administered with oral ranitidine at a dose exceeding 300 mg per day.
Warfarin: There have been reports of altered prothrombin time among patients on concomitant warfarin and ranitidine therapy. Due to the narrow therapeutic index, close monitoring of increased or decreased prothrombin time is recommended during concurrent treatment with ranitidine.
Ranitidine may alter the absorption of drugs in which gastric pH is an important determinant of bioavailability. This can result in either an increase in absorption (e.g., triazolam, midazolam, glipizide) or a decrease in absorption (e.g., ketoconazole, atazanavir, delavirdine, gefitinib). Appropriate clinical monitoring is recommended.
Atazanavir: Atazanavir absorption may be impaired based on known interactions with other agents that increase gastric pH. Use with caution. See atazanavir label for specific recommendations.
Delavirdine: Delavirdine absorption may be impaired based on known interactions with other agents that increase gastric pH. Chronic use of H2-receptor antagonists with delavirdine is not recommended.
Gefitinib: Gefitinib exposure was reduced by 44% with the coadministration of ranitidine and sodium bicarbonate (dosed to maintain gastric pH above 5.0). Use with caution.
Glipizide: In diabetic patients, glipizide exposure was increased by 34% following a single 150-mg dose of oral ranitidine. Use appropriate clinical monitoring when initiating or discontinuing ranitidine.
Ketoconazole: Oral ketoconazole exposure was reduced by up to 95% when oral ranitidine was coadministered in a regimen to maintain a gastric pH of 6 or above. The degree of interaction with usual dose of ranitidine (150 mg twice daily) is unknown.
Midazolam: Oral midazolam exposure in 5 healthy volunteers was increased by up to 65% when administered with oral ranitidine at a dose of 150 mg twice daily. However, in another interaction trial in 8 volunteers receiving IV midazolam, a 300-mg oral dose of ranitidine increased midazolam exposure by about 9%. Monitor patients for excessive or prolonged sedation when ranitidine is coadministered with oral midazolam.
Triazolam: Triazolam exposure in healthy volunteers was increased by approximately 30% when administered with oral ranitidine at a dose of 150 mg twice daily. Monitor patients for excessive or prolonged sedation.
These are not all the medicines that may not mix well with ranitidine. For a full list see the leaflet inside your medicines packet.
Mixing ranitidine with herbal remedies and supplements
There isn’t enough research to know if complementary medicines and herbal remedies are safe to take with ranitidine.
What is cimetidine used for
Cimetidine works by decreasing the amount of acid your stomach produces. Cimetidine is used to treat and prevent certain types of ulcer, and to treat conditions that cause the stomach to produce too much acid. Cimetidine is also used to treat gastroesophageal reflux disease (GERD), when stomach acid backs up into the esophagus and causes heartburn.
Cimetidine hydrochloride oral solution is indicated in:
- 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 6–8 weeks. 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.
- 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.
- Short-term treatment of active benign gastric ulcer. There is no information concerning usefulness of treatment periods of longer than 8 weeks.
- Erosive gastroesophageal reflux disease (GERD). Erosive esophagitis diagnosed by endoscopy. Treatment is indicated for 12 weeks for healing of lesions and control of symptoms. The use of Cimetidine beyond 12 weeks has not been established.
- The treatment of pathological hypersecretory conditions. (i.e., Zollinger-Ellison Syndrome, systemic mastocytosis, multiple endocrine adenomas).
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.
four times daily
A U.S. double blind, placebo controlled, dose ranging study demonstrated that all once daily at bedtime Cimetidine regimens were superior to placebo in ulcer healing and that Cimetidine 800 mg at bedtime healed 75% of patients at four weeks. The healing rate with 800 mg h.s. was significantly superior to 400 mg at bedtime (66%) and not significantly different from 1600 mg at bedtime (81%).
In the U.S. dose-ranging trial, over 80% of patients receiving Cimetidine 800 mg at bedtime 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, 800 mg at bedtime dose was superior to 400 mg at bedtime and not different from 1600 mg at bedtime.
In foreign, double-blind studies with Cimetidine 800 mg at bedtime, 79–85% of patients were healed at 4 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 1 year’s therapy with cimetidine 400 mg at bedtime was significantly lower (10%–45%) than in patients receiving placebo (44%–70%). Thus, from 55% to 90% of patients were maintained free of observed ulcers at the end of one year with cimetidine 400 mg at bedtime.
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 6 weeks. Patients were limited to those with ulcers ranging from 0.5 mg–2.5 cm in size. Endoscopically confirmed healing at 6 weeks was seen in significantly more cimetidine-treated patients than in patients receiving placebo, as shown below:
|week 2||14/63 (22%)||7/63 (11%)|
|total at week 6||43/65 (66%)*||30/67 (45%)|
In a similar multicenter U.S. study of the 800 mg h.s. oral regimen, the endoscopically confirmed healing rates were:
|total at week 6||63/83 (76%)*||44/80 (55%)|
Similarly in worldwide double-blind clinical studies, endoscopically evaluated benign gastric ulcer healing rates were constantly higher with cimetidine than with placebo.
Gastroesophageal reflux disease
In two multicenter, double-blind, placebo-controlled studies in patients with gastroesophageal reflux disease (GERD) and endoscopically proven erosions and/or ulcers, cimetidine was significantly more effective than placebo in healing lesions. The endoscopically confirmed healing rates were:
(800 mg twice daily)
(400 mg four times daily)
(800 mg twice daily vs. placebo)
In these trials cimetidine was superior to placebo by most measures in improving symptoms of day- and night-time heartburn, many of the differences statistically significant. The four times per day regimen was generally somewhat better than the two times per day regimen where these were compared.
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.
Applies to the following strengths cimetidine: 300 mg; 400 mg; 800 mg; 300 mg/5 mL; 900 mg-0.9%/250 mL; 480 mg/100 mL-0.9%; 900 mg-0.9%/500 mL; 1200 mg-0.9%/500 mL; 900 mg-0.9%/1000 mL; 1200 mg-0.9%/1000 mL; 150 mg/mL; 300 mg/50 mL-NaCl 0.9%; 200 mg; 100 mg; 200 mg/20 mL
Usual Adult Dose for Duodenal Ulcer
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. Clinical studies have indicated that suppression of nocturnal acid is the most important factor in duodenal ulcer healing. This is supported by recent clinical trials. Therefore, there is no apparent rationale, except for familiarity with use, for treating with anything other than a once-daily at bedtime dosage regimen.
In a U.S. oral dose-ranging study of 400 mg at bedtime, 800 mg at bedtime and 1600 mg at bedtime a continuous dose response relationship for ulcer healing was demonstrated.
However, 800 mg at bedtime is the dose of choice for most patients, as it provides a high healing rate (the difference between 800 mg at bedtime and 1600 mg at bedtime being small), maximal pain relief, a decreased potential for drug interactions and maximal patient convenience. Patients unhealed at four weeks or those with persistent symptoms, have been shown to benefit from 2 to 4 weeks of continued therapy.
It has been shown that patients who both have an endoscopically demonstrated ulcer larger than 1.0 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 at bedtime or 1600 mg is equivalent in all patients, 1600 mg at bedtime provides an appropriate alternative when it is important to ensure healing within 4 weeks for this subpopulation. Alternatively, approximately 94% of all patients will also heal in 8 weeks in Cimetidine 800 mg at bedtime
Other Cimetidine 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.
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 Cimetidine.
While healing with Cimetidine often occurs during the first week or two, treatment should be continued for 4–6 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.
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).
Usual Adult Dose for Duodenal Ulcer Prophylaxis
Oral: 400 mg once a day at bedtime.
Parenteral: 300 mg IV or IM once or twice a day.
Usual Adult Dose for Erosive Esophagitis
Oral: 800 mg twice a day, or alternatively, 400 mg four times a day.
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).
Usual Adult Dose for 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.
Usual Adult Dose for Upper GI Hemorrhage
Continuous IV infusion at a rate of 50 mg/hour preceded by an IV bolus dose of 150 mg. Maximum daily dose should not exceed 2.4 g.
Usual Adult Dose for Zollinger-Ellison Syndrome
Oral: 300 mg 4 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.
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.
Usual Adult Dose for Gastric Ulcer
Oral: 800 mg once a day at bedtime, or 300 mg 4 times a day with meals and at bedtime. Controlled clinical studies were limited to six weeks of treatment 800 mg at bedtime 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.
Parenteral: 300 mg IV or IM every 6 hours. Alternatively, a continuous IV infusion may be administered at a rate of 50 mg/hour.
Usual Adult Dose for Gastroesophageal Reflux Disease (GERD)
Oral: The recommended adult oral dosage for the treatment of erosive esophagitis that has been diagnosed by endoscopy is 1600 mg daily in divided doses (800 mg twice a day, or 400 mg 4 times a day) for 12 weeks. The use of cimetidine beyond 12 weeks has not been established.
Parenteral: 300 mg IV or IM every 6 hours. Alternatively, a continuous IV infusion may be administered at a rate of 50 mg/hour. Maximum daily dose should not exceed 2.4 g.
Usual Adult Dose for Dyspepsia
200 mg orally right before (or up to 30 minutes) eating. Maximum per 24 hours: 2 doses.
Usual Pediatric Dose for 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.
Usual Pediatric Dose for Dyspepsia
Greater than or equal to 12 years: 200 mg up to twice daily; may take 30 minutes prior to eating foods or beverages expected to cause heartburn or indigestion.
Renal Dose Adjustments
Creatinine Clearance <30 mL/min: Give 50% of the recommended dose to patients being treated for prevention of upper GI bleeding.
The initial recommended dosage for patients with severely impaired renal function is 300 mg orally or injectable, given every 12 hours, and if needed, the frequency may be increased to every 8 hours with caution.
Liver Dose Adjustments
Dosage adjustments should be considered for patients with severe liver disease.
Dosage adjustments are based on patient’s individual needs. In adults with normal renal and liver function, the maximum oral or injectable dosage in a 24 hour period should not exceed 2.4 g.
Dosage adjustments may be necessary to maintain an intragastric acid secretory rate at 10 mEq/hr or less.
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.
Slightly dialyzable (5% to 20%). Schedule the dose to begin at the end of the hemodialysis session.
How should I take cimetidine?
Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.
Cimetidine is usually taken with meals or at bedtime.
Take cimetidine with a full glass of water.
Measure liquid medicine carefully. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).
It may take up to 8 weeks for an ulcer to heal. Use this medicine for the full prescribed length of time, even if your symptoms quickly improve.
Your ulcer may take longer to heal if you smoke cigarettes.
Call your doctor if your symptoms do not improve, or if they get worse.
Store at room temperature away from moisture, heat, and light.
What happens if I miss a dose?
Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.
Cimetidine side effects
Cimetidine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- breast enlargement
Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them, stop using cimetidine and call your doctor immediately:
- seeing things or hearing voices that do not exist (hallucinating)
- changes in mood, anxiety, agitation
- breast swelling or tenderness
- easy bruising or bleeding, unusual weakness
- jaundice (yellowing of the skin or eyes).
Cimetidine may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
Get emergency medical help if you have signs of an allergic reaction:
- difficult breathing,
- swelling in your face or throat
- a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (https://www.fda.gov/Safety/MedWatch/default.htm)
Nervous system side effects have included headache (up to 3.5%), dizziness (1%), and somnolence (1%). Severe mental status changes, including depression, agitation, disorientation, confusion, delirium, unsteadiness, slurred speech, lethargy, hallucinations, and coma, while uncommon, have been reported frequently in the literature. Other nervous system effects reported are extrapyramidal symptoms, cerebellar syndrome with encephalopathy, and paresthesias. Critical illness, advanced age, renal, and/or liver disease appear to be associated with an increased risk for central nervous system toxicity.
The mechanism by which cimetidine induces mental status changes is not well established but appears to involve increased serum concentrations of cimetidine and, possibly, cimetidine sulfoxide. Advanced age has been implicated in many case reports of mental status changes, however, the pharmacokinetics of cimetidine correlate more closely with renal function, making renal dysfunction associated with advanced age a more likely risk factor than age itself. In addition, enhanced cimetidine penetration of the blood brain barrier has been demonstrated in patients with liver disease. Onset of symptoms have usually developed within 2 to 3 days of start of therapy, but may be delayed. Following discontinuation of cimetidine, mental status usually normalizes over several days.
Psychiatric side effects may accompany other signs and symptoms of neurologic toxicity such as unsteadiness, slurred speech, and lethargy. Age, renal dysfunction, and/or liver disease may be predisposing factors in these cases.
Psychiatric side effects in the form of severe depression, suicidal ideation, paranoia, and frank psychosis have also been reported in otherwise healthy patients.
Psychiatric side effects have included depression, paranoia, agitation, mania, hallucinations, psychosis, and loss of libido. These side effects may be accompanied by other signs and symptoms of neurologic toxicity. Critical illness, advanced age, renal, and/or liver disease appear to be associated with an increased risk for central nervous system toxicity, including psychiatric disturbances.
Endocrine side effects have included gynecomastia, occurring in 0.3% to 1% of patients treated for nonhypersecretory conditions for 1 month or longer. In patients treated for pathologic hypersecretory conditions, this occurred in about 4% of cases. In the majority of cases, however, hormone levels remain in the normal range. In addition, galactorrhea, impotence, and transient alopecia as well as a case of possible cimetidine-induced hypoparathyroidism have been reported.
A large population-based cohort study involving 81,535 men evaluated the risk of gynecomastia associated with cimetidine, ranitidine, misoprostol, and omeprazole. Overall, 37,202 men received cimetidine. Gynecomastia developed in 86 men treated with cimetidine. The relative risk of gynecomastia during cimetidine treatment compared to a control population not treated with cimetidine was 7.2. Use of daily doses of 1000 mg or more was associated with a relative risk of 43.5.
Luteinizing hormone (LH), follicle-stimulating hormone (FSH), serum prolactin, testosterone, and estradiol levels are usually within the normal range in patients who develop gynecomastia or breast tenderness while on cimetidine. However, decreases in serum testosterone and increases in LH and estradiol as well as increases in serum prolactin have been reported on occasion.
Severe hypocalcemia was reported in an elderly woman treated with cimetidine postoperatively. There was some evidence in this case to support a possible cimetidine-induced reduction in parathyroid hormone with subsequent hypocalcemia. More study is needed to confirm this.
In a study involving medical ICU patients requiring invasive blood pressure monitoring for circulatory instability or with a need for repeated arterial blood gas draws, an average decrease of 14 mmHg in systolic and 9 mmHg in diastolic pressure was noted in 74% (50/68) of patients following administration of cimetidine 200 mg IV over 3 minutes. In 13% of patients, systolic pressure decreased by more than 30 mmHg.
Most cardiovascular side effects are noted following rapid intravenous administration. While administration by slow infusion appears to reduce the incidence of such effects, serious cardiovascular events, including sinus arrest, have been reported with continuous intravenous infusions as well as oral administration.
Cardiovascular side effects have been rarely reported. These are usually associated with rapid intravenous administration. Tachycardia, bradycardia, hypotension, QT interval prolongation, premature ventricular contractions, junctional rhythm, AV block, and sinus arrest have been reported with H2 receptor antagonist.
Hematologic side effects have rarely included leukopenia, eosinophilia, neutropenia, thrombocytopenia, agranulocytosis, and aplastic anemia. The manufacturer also reports extremely rare cases of autoimmune hemolytic anemia.
Rare cases of irreversible or fatal blood dyscrasias have been reported in the literature. While rare, hematologic abnormalities should be considered in patients treated with cimetidine who develop fever, chills, sore throat, easy bruising, and other signs or symptoms suggestive of a blood dyscrasia.
Hepatic side effects have included elevations in liver function tests and hepatitis of both cholestatic and mixed cholestatic-hepatocellular types. Some presentations of cimetidine-induced hepatitis have features suggestive of a hypersensitivity response.
Overall, serious hepatotoxicity due to cimetidine is rare. Bridging hepatic necrosis, centrilobular hepatic necrosis, and intrahepatic cholestasis have been noted on biopsy in cases of cimetidine-induced hepatitis. In some cases, liver toxicity has been associated with fever, rash, and eosinophilia, suggesting a hypersensitivity etiology.
Cimetidine-induced hepatitis in a patient with a history of famotidine-induced hepatitis has been reported in at least one case. Extreme caution is recommended when initiating cimetidine therapy in a patient with a history of other H2-antagonist-induced hepatotoxicity.
Liver injury, with fatal outcome, has been reported with the use of other H2 receptor antagonists.
Renal side effects have included elevations in serum creatinine. However, such elevations are generally due to competitive inhibition of tubular secretion of creatinine rather than a result of impaired glomerular filtration or renal toxicity. Rare cases of acute renal failure and interstitial nephritis have been reported.
Elevations in serum creatinine by as much as 20% are reported during cimetidine therapy. Cimetidine is thought to competitively inhibit the secretion of creatinine by the renal proximal tubules resulting in a reduction in creatinine clearance. Creatinine does not appear to affect cimetidine transport, except at very high concentrations.
Overt renal toxicity, such as renal failure and interstitial nephritis, is rare. In some cases, cimetidine-induced renal toxicity has been attributed to a delayed-type hypersensitivity.
Gastrointestinal side effects have been reported rarely. These have included diarrhea (1%) which is generally mild although severe cases have been reported, nausea/vomiting (0.6%), constipation (0.2%), dry mouth, and taste changes. In addition, cases of parotitis, phytobezoars, and pancreatitis have been reported.
Dermatologic side effects have included mild rash as well as severe dry skin (xerosis), seborrheic dermatitis, erythema annular centrifugum, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, and toxic epidermal necrolysis. Reversible alopecia has also been reported rarely.
Antiandrogen and sebum-inhibitory effects are proposed mechanisms by which cimetidine causes severe xerosis and asteatotic dermatitis.
Musculoskeletal side effects have rarely included arthralgias, inflammatory arthritis, gout-like arthritis, and myalgias. The manufacturer reports rare cases of polymyositis although causality is unknown.
Immunologic side effects have included a case of exacerbation of cutaneous systemic lupus erythematosus and cimetidine-induced cutaneous vasculitis. Strongyloidiasis hyperinfection has been reported rarely in immunocompromised patients.
Hypersensitivity side effects have included urticaria, pruritus, fever, angioedema, and anaphylaxis. In addition, a case of drug fever in association with leukocytosis and abdominal pain has also been reported. Vasculitis has been reported. It resolved on discontinuation of cimetidine.