HISTAMINEH 2-RECEPTOR ANTAGONISTS (Systemic)

Some commonly used brand names are:

In the U.S.?

• Axid ³
• Axid AR ³
• Fluxid ²
• Mylanta AR Acid Reducer ²
• Pepcid ²
• Pepcid I.V. ²
• Pepcid AC Acid Controller ²
• Pepcid RPD ²
• Tagamet ¹
• Tagamet HB ¹
• Zantac ⁴
• Zantac 150 ⁴
• Zantac 300 ⁴
• Zantac 25 EFFERdose Tablets ⁴
• Zantac 150 EFFERdose Tablets ⁴

In Canada?

• Acid Control ²
• Act ²
• Apo-Cimetidine ¹
• Apo-Famotidine ²
• Apo-Nizatidine ³
• Apo-Ranitidine ⁴
• Axid ³
• Dyspep HB ²
• Gen-Cimetidine ¹
• Gen-Famotidine ²
• Gen-Ranitidine ⁴
• Maalox H2 Acid Controller ²
• Novo-Cimetine ¹
• Novo-Famotidine ²
• Novo-Ranitidine ⁴
• Nu-Cimet ¹
• Nu-Famotidine ²
• Nu-Ranit ⁴
• Pepcid ²
• Pepcid AC ²
• Pepcid I.V. ²
• Peptol ¹
• PMS-Cimetidine ¹
• Tagamet ¹
• Ulcidine ²
• Ulcidine-HB ²
• Zantac ⁴
• Zantac 75 ⁴

Category

• Histamine H ₂-receptor antagonist?Cimetidine; Famotidine; Nizatidine; Ranitidine
• Antiulcer agent?Cimetidine; Famotidine; Nizatidine; Ranitidine
• Gastric acid secretion inhibitor?Cimetidine; Famotidine; Nizatidine; Ranitidine
• Urticaria therapyadjunct?Cimetidine

Description

Histamine H ₂-receptor antagonists, also known as H ₂-blockers,are used to treat duodenal ulcers and prevent their return. They are alsoused to treat gastric ulcers and for some conditions, such as Zollinger-Ellisondisease, in which the stomach produces too much acid. In over-the-counter(OTC) strengths, these medicines are used to relieve and/or prevent heartburn,acid indigestion, and sour stomach. H ₂-blockersmay also be used for other conditions as determined by your doctor.

H ₂-blockers work by decreasing the amountof acid produced by the stomach.

They are available in the following dosage forms:

Oral
• Cimetidine
  • Oral solution (U.S. and Canada)
  • Tablets (U.S. and Canada)
• Famotidine
  • Oral suspension (U.S.)
  • Tablets (U.S. and Canada)
  • Chewable tablets (U.S. and Canada)
  • Oral disintegrating tablets (U.S.)
• Nizatidine
  • Capsules (U.S. and Canada)
  • Tablets (U.S.)
• Ranitidine
  • Syrup (U.S. and Canada)
  • Tablets (U.S. and Canada)
  • Effervescent tablets (U.S.)

Parenteral
• Cimetidine
  • Injection (U.S. and Canada)
• Famotidine
  • Injection (U.S. and Canada)
• Ranitidine
  • Injection (U.S. and Canada)

Before Using This Medicine

In deciding to use a medicine,the risks of taking the medicine must be weighed against the good it willdo. This is a decision you and your doctor will make. For H ₂-blockers, the following should be considered:

Allergies?Tell your doctor if you have ever had any unusual orallergic reaction to cimetidine, famotidine, nizatidine, or ranitidine.

Pregnancy?H ₂-blockers have notbeen studied in pregnant women. In animal studies, famotidine and ranitidinehave not been shown to cause birth defects or other problems. However, onestudy in rats suggested that cimetidine may affect male sexual development.More studies are needed to confirm this. Also, studies in rabbits with veryhigh doses have shown that nizatidine causes miscarriages and low birth weights.Make sure your doctor knows if you are pregnant or if you may become pregnantbefore taking H ₂-blockers.

Breast-feeding?Cimetidine, famotidine, nizatidine, and ranitidinepass into the breast milk and may cause unwanted effects, such as decreasedamount of stomach acid and increased excitement, in the nursing baby. It maybe necessary for you to take another medicine or to stop breast-feeding duringtreatment. Be sure you have discussed the risks and benefits of the medicinewith your doctor.

Children?This medicine has been tested in children and, ineffective doses, has not been shown to cause different side effects or problemsthan it does in adults when used for short periods of time.

Older adults?Confusion and dizziness may be especially likelyto occur in elderly patients, who are usually more sensitive than youngeradults to the effects of H ₂-blockers.

Other medicines?Although certain medicines should not be usedtogether at all, in other cases two different medicines may be used togethereven if an interaction might occur. In these cases, your doctor may want tochange the dose, or other precautions may be necessary. When you are takingor receiving H ₂-blockers it is especially importantthat your health care professional know if you are taking any of the following:

• Aminophylline (e.g., Somophyllin) or
• Anticoagulants (blood thinners) or
• Caffeine (e.g., NoDoz) or
• Metoprolol (e.g., Lopressor) or
• Oxtriphylline (e.g., Choledyl) or
• Phenytoin (e.g., Dilantin) or
• Propranolol (e.g., Inderal) or
• Theophylline (e.g., Somophyllin-T) or
• Tricyclic antidepressants (amitriptyline [e.g., Elavil], amoxapine[e.g., Asendin], clomipramine [e.g., Anafranil], desipramine [e.g., Pertofrane],doxepin [e.g., Sinequan], imipramine [e.g., Tofranil], nortriptyline [e.g.,Aventyl], protriptyline [e.g., Vivactil], trimipramine [e.g., Surmontil])?Useof these medicines with cimetidine has been shown to increase the effectsof cimetidine. This is less of a problem with ranitidine and has not beenreported for famotidine or nizatidine. However, all of the H ₂-blockers are similar, so drug interactions may occur with any ofthem

• Itraconazole (e.g., Sporanox) or
• Ketoconazole (e.g., Nizoral)?H ₂-blockersmay decrease the effects of itraconazole or ketoconazole; H ₂-blockers should be taken at least 2 hours after these medicines

Other medical problems?The presence of other medicalproblems may affect the use of H ₂-blockers.Make sure you tell your doctor if you have any other medical problems, especially:

• Kidney disease or
• Liver disease?The H ₂-blockermay build up in the bloodstream, which may increase the risk of side effects

• Phenylketonuria (PKU)?Some H ₂-blockerscontain aspartame. Aspartame is converted to phenylalanine in the body andmust be used with caution in patients with PKU. The Pepcid AC brand of famotidinechewable tablets contains 1.4 mg of phenylalanine per 10-mg dose. The PepcidRPD brand of famotidine oral dispersible tablets contains 1.05 mg of phenylalanineper 20-mg dose. The Zantac brand of ranitidine EFFERdose tablets contain 2.81mg of phenylalanine per 25-mg dose and 16.84 mg of phenylalanine per 150-mgdose

• Porphyria (rare family disease that affects the way your body digestsfood)?May make condition worse in patients who have acute porphyria

• Weakened immune system (difficulty fighting infection)?Decreasein stomach acid caused by H ₂-blockers may increasethe possibility of a certain type of infection

Proper Use of This Medicine

For patientstaking the nonprescription strengths of thesemedicines for heartburn, acid indigestion, and sour stomach:

• Do not take the maximum daily dosage continuously for more than 2weeks, unless directed to do so by your doctor.
• If you have trouble in swallowing, or persistent abdominal pain,see your doctor promptly. These may be signs of a serious condition that mayneed different treatment.

For patients taking the prescription strengthsof these medicines for more serious problems:

• One dose a day?Take it at bedtime, unless otherwise directed.
• Two doses a day?Take one in the morning and one at bedtime.
• Several doses a day?Take them with meals and at bedtime forbest results.

It may take several days before this medicine begins to relieve stomachpain. To help relieve this pain, antacids may be taken with the H ₂-blocker, unless your doctor has told you not to use them. However,you should wait one-half to one hour between taking the antacid and the H ₂-blocker.

Take this medicine for the full time of treatment,even if you begin to feel better. Also, it is important that you keepyour appointments with your doctor for check-ups so that your doctor willbe better able to tell you when to stop taking this medicine.

For patients taking famotidine chewable tablets:

• Chew the tablets well before swallowing.

For patients taking famotidine oral disintegratingtablets:

• Make sure your hands are dry.
• Leave tablets in unopened package until the time of use, then openthe pack and remove the tablet.
• Immediately place the tablet on the tongue.
• The tablet will dissolve in seconds, and you may swallow it withyour saliva. You do not need to drink water or other liquid to swallow thetablet.

For patients taking ranitidine effervescenttablets:

• Remove the foil wrapping and dissolve the dose in 6 to 8 ounces ofwater before drinking.
• Do not chew, swallow whole or dissolve on the tongue
• The amount you should give to your infant is to be measured withthe specially marked dropper or oral syringe. Ask your doctor if you are unsurehow much medicine to give your infant.

Dosing?The dose of histamine H ₂-receptor antagonists (also called H ₂-blockers)will be different for different patients. Follow yourdoctor's orders or the directions on the label. The following informationincludes only the average doses of these medicines. If your dose is different, do not change it unless your doctor tells you todo so.

The number of capsules or tablets or teaspoonfuls of solution, suspension,or syrup that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed betweendoses, and the length of time you take the medicine depend on the medicalproblem for which you are taking the H ₂-receptorantagonist.

For cimetidine
• For oral dosage forms (solution and tablets):
  • To treat duodenal or gastric ulcers:
    • Older adults, adults, and teenagers?300 milligrams (mg) fourtimes a day, with meals and at bedtime. Some people may take 400 or 600 mgtwo times a day, on waking up and at bedtime. Others may take 800 mg at bedtime.
    • Children?20 to 40 mg per kilogram (kg) (9.1 to 18.2 mg perpound) of body weight a day, divided into four doses, taken with meals andat bedtime.
  • To prevent duodenal ulcers:
    • Older adults, adults, and teenagers?300 mg two times a day,on waking up and at bedtime. Instead some people may take 400 mg at bedtime.
    • Children?Dose must be determined by your doctor.
  • To treat heartburn, acid indigestion, and sour stomach:
    • Adults and teenagers?100 to 200 mg with water when symptomsstart. The dose may be repeated once in twenty-four hours. Do not take morethan 400 mg in twenty-four hours.
    • Children?Dose must be determined by your doctor.
  • To prevent heartburn, acid indigestion, and sour stomach:
    • Adults and teenagers?100 to 200 mg with water up to one hourbefore eating food or drinking beverages you expect to cause symptoms. Donot take more than 400 mg in twenty-four hours.
    • Children?Dose must be determined by your doctor.
  • To treat conditions in which the stomach produces too much acid:
    • Adults?300 mg four times a day, with meals and at bedtime.Your doctor may change the dose if needed.
    • Children?Dose must be determined by your doctor.
  • To treat gastroesophageal reflux disease:
    • Adults?800 to 1600 mg a day, divided into smaller doses. Treatmentusually lasts for 12 weeks.
    • Children?Dose must be determined by your doctor.
• For injectable dosage form:
  • To treat duodenal ulcers, gastric ulcers or conditions in which thestomach produces too much acid:
    • Older adults, adults, and teenagers?300 mg injected into muscle,every six to eight hours. Or, 300 mg injected slowly into a vein every sixto eight hours. Instead, 900 mg may be injected slowly into a vein aroundthe clock at the rate of 37.5 mg per hour. Some people may need 150 mg atfirst, before beginning the around-the-clock treatment.
    • Children?5 to 10 mg per kg (2.3 to 4.5 mg per pound) of bodyweight injected into a vein or muscle, every six to eight hours.
  • To prevent stress-related bleeding:
    • Older adults, adults, and teenagers?50 mg per hour injectedslowly into a vein around the clock for up to 7 days.
    • Children?Dose must be determined by your doctor.

For famotidine
• For oral dosage forms (suspension, tablets,chewable tablets, and oral disintegrating tablets):
  • To treat duodenal ulcers:
    • Older adults, adults, and teenagers?40 milligrams (mg) oncea day at bedtime. Some people may take 20 mg two times day.
    • Children?Dose must be determined by your doctor.
  • To prevent duodenal ulcers:
    • Older adults, adults, and teenagers?20 mg once a day at bedtime.
    • Children?Dose must be determined by your doctor.
  • To treat gastric ulcers:
    • Older adults, adults, and teenagers?40 mg once a day at bedtime.
    • Children?Dose must be determined by your doctor.
  • To treat heartburn, acid indigestion, and sour stomach:
    • Adults and teenagers?10 mg with water when symptoms start.The dose may be repeated once in twenty-four hours. Do not take more than20 mg in twenty-four hours.
    • Children?Dose must be determined by your doctor.
  • To prevent heartburn, acid indigestion, and sour stomach:
    • Adults and teenagers?10 mg taken one hour before eating a mealyou expect to cause symptoms. The dose may be repeated once in twenty-fourhours. Do not take more than 20 mg in twenty-four hours.
    • Children?Dose must be determined by your doctor.
  • To treat conditions in which the stomach produces too much acid:
    • Older adults, adults, and children?20 mg every six hours. Yourdoctor may change the dose if needed.
    • Children?Dose must be determined by your doctor.
  • To treat gastroesophageal reflux disease:
    • Older adults, adults, and teenagers?20 mg two times a day,usually for up to 6 weeks.
    • Children weighing more than 10 kg (22 pounds)?1 to 2 mg perkilogram (kg) (0.5 to 0.9 mg per pound) of body weight a day divided intotwo doses.
    • Children weighing less than 10 kg (22 pounds)?1 to 2 mg perkg (0.5 to 0.9 mg per pound) of body weight a day, divided into three doses.
• For injectable dosage form:
  • To treat duodenal ulcers, gastric ulcers, or conditions in whichthe stomach produces too much acid:
    • Older adults, adults, and teenagers?20 mg injected into a vein,every twelve hours.
    • Children?Dose must be determined by your doctor.

For nizatidine
• For oral dosage forms (capsules and tablets):
  • To treat duodenal or gastric ulcers:
    • Older adults, adults, and teenagers?300 milligrams (mg) oncea day at bedtime. Some people may take 150 mg two times a day.
    • Children?Dose must be determined by your doctor.
  • To prevent duodenal ulcers:
    • Adults and teenagers?150 mg once a day at bedtime.
    • Children?Dose must be determined by your doctor.
  • To prevent heartburn, acid indigestion, and sour stomach:
    • Adults and teenagers?75 mg taken thirty to sixty minutes beforeeating a meal you expect to cause symptoms. The dose may be repeated oncein twenty-four hours.
    • Children?Dose must be determined by your doctor.
  • To treat gastroesophageal reflux disease:
    • Adults and teenagers?150 mg two times a day.
    • Children?Dose must be determined by your doctor.

For ranitidine
• For oral dosage forms (syrup, tablets,effervescent tablets):
  • To treat duodenal ulcers:
    • Older adults, adults, and teenagers?150 milligrams (mg) twotimes a day. Some people may take 300 mg once a day at bedtime.
    • Children?2 to 4 mg per kilogram (kg) (1 to 2 mg per pound)of body weight per day, usually given as two divided doses. However, yourtotal dose will not be more than 300 mg a day.
  • To prevent duodenal ulcers:
    • Older adults, adults, and teenagers?150 mg at bedtime.
    • Children?Dose must be determined by your doctor.
  • To treat gastric ulcers:
    • Older adults, adults, and teenagers?150 mg two times a day.
    • Children?2 to 4 mg per kilogram (1 to 2 mg per pound) of bodyweight per day, usually given as two divided doses. However, your total dosewill not be more than 300 mg a day.
  • To treat heartburn, acid indigestion, and sour stomach:
    • Adults and teenagers?150 mg with water when symptoms start.The dose may be repeated once in twenty-four hours. Do not take more than300 mg in twenty-four hours.
    • Children?Dose must be determined by your doctor.
  • To prevent heartburn, acid indigestion, and sour stomach:
    • Adults and teenagers?150 mg with water taken thirty to sixtyminutes before eating a meal or drinking beverages you expect to cause symptoms.Do not take more than 300 mg in twenty-four hours.
    • Children?Dose must be determined by your doctor.
  • To treat some conditions in which the stomach produces too much acid:
    • Older adults, adults, and teenagers?150 mg two times a day.Your doctor may change the dose if needed.
    • Children?Dose must be determined by your doctor.
  • To treat gastroesophageal reflux disease:
    • Older adults, adults, and teenagers?150 mg two times a day.Your dose may be increased if needed.
    • Children?5 to 10 mg per kg (2.3 to 4.6 mg per pound) of bodyweight a day, usually divided and given in two doses during the day. However,most children usually will not take more than 300 mg a day.
• For injectable dosage form:
  • To treat duodenal ulcers, gastric ulcers, or conditions in whichthe stomach produces too much acid:
    • Older adults, adults, and teenagers?50 mg injected into a muscleevery six to eight hours. Or, 50 mg injected slowly into a vein every sixto eight hours. Instead, you may receive 6.25 mg per hour injected slowlyinto a vein around the clock. However, most people will usually not need morethan 400 mg a day.
  • To treat duodenal or gastric ulcers:
    • Children?2 to 4 mg per kg (1 to 2 mg per pound) of body weighta day, injected slowly into a vein.

Missed dose?If you miss a dose of this medicine, take it assoon as possible. However, if it is almost time for your next dose, skip themissed dose and go back to your regular dosing schedule. Do not double doses.

Storage?To store this medicine:

• Keep out of the reach of children.
• Store away from heat and direct light.
• Do not store the capsule or tablet form of this medicine in the bathroom,near the kitchen sink, or in other damp places. Heat or moisture may causethe medicine to break down.
• Keep the liquid form of this medicine from freezing.
• Do not keep outdated medicine or medicine no longer needed. Be surethat any discarded medicine is out of the reach of children.

Precautions While Using This Medicine

Sometests may be affected by this medicine. Tell the doctor in charge that youare taking this medicine before:

• You have any skin tests for allergies.
• You have any tests to determine how much acid your stomach produces.

Remember that certain medicines, such as aspirin, and certain foods anddrinks (e.g., citrus products, carbonated drinks, etc.) irritate the stomachand may make your problem worse.

Cigarette smoking tends to decrease the effect of H ₂-blockers by increasing the amount of acid produced by the stomach.This is more likely to affect the stomach's nighttime production of acid.While taking H ₂-blockers, stop smoking completely,or at least do not smoke after taking the last dose of the day.

Drinking alcoholic beverages while taking an H ₂-receptor antagonist has been reported to increase the blood levelsof alcohol. You should consult your health care professional for guidance.

Check with your doctor if your ulcer pain continues or gets worse.

Side Effects of This Medicine

Along with its needed effects, a medicine may cause some unwanted effects.Although not all of these side effects may occur, if they do occur they mayneed medical attention.

Check with your doctor as soon as possible if any of the following sideeffects occur:

Rare

Abdominal pain; back, leg, or stomachpain; bleeding or crusting sores on lips; blistering, burning, redness, scaling, or tenderness of skin ; blisters on palms of hands and soles of feet; changes in vision or blurred vision; confusion; coughing or difficulty in swallowing; dark-colored urine; dizziness; fainting; fast, pounding, or irregularheartbeat; fever and/or chills; flu-like symptoms; general feeling of discomfortor illness; hives; inflammationof blood vessels; joint pain; light-colored stools; mood or mental changes, includinganxiety, agitation, confusion, hallucinations (seeing, hearing, or feelingthings that are not there), mental depression, nervousness, or severe mentalillness; muscle cramps or aches; nausea, vomiting, or loss of appetite; pain; peeling or sloughing of skin; red orirritated eyes; shortness of breath; skin rash or itching; slow heartbeat; sore throat; sores, ulcers,or white spots on lips, in mouth, or on genitals; sudden difficult breathing; swelling of face, lips,mouth, tongue, or eyelids; swelling of hands or feet; swollen or painful glands; tightness in chest; troubled breathing; unusual bleeding or bruising; unusualtiredness or weakness; unusually slow or irregularbreathing; wheezing; yelloweyes or skin

Other side effects may occur that usually do not need medicalattention. These side effects may go away during treatment as your body adjuststo the medicine. However, check with your doctor if any of the following sideeffects continue or are bothersome:

Less common or rare

Constipation; decreased sexual ability(especially in patients with Zollinger-Ellison disease who have received highdoses of cimetidine for at least 1 year); decreasein sexual desire; diarrhea; difficult urination; dizziness; drowsiness; dryness of mouth or skin; headache; increased or decreased urination; increased sweating; lossof hair ; ringing or buzzing in ears; runny nose; swelling of breasts or breastsoreness in females and males; trouble in sleeping

Not all of the side effects listed abovehave been reported for each of these medicines, but they have been reportedfor at least one of them. All of the H ₂-blockersare similar, so any of the above side effects may occur with any of thesemedicines.

Other side effects not listed above may also occur insome patients. If you notice any other effects, check with your doctor.

Additional Information

Once a medicine has been approvedfor marketing for a certain use, experience may show that it is also usefulfor other medical problems. Although these uses are not included in productlabeling, H ₂-blockers are used in certain patientswith the following medical conditions:

• Damage to the stomach and/or intestines due to stress or trauma
• Hives
• Pancreatic problems
• Stomach or intestinal ulcers (sores) resulting from damage causedby medication used to treat rheumatoid arthritis

Other than the above information, there is no additional information relatingto proper use, precautions, or side effects for these uses.