Didronel PMO

1. Name Of The Medicinal Product

Didronel PMO

2. Qualitative And Quantitative Composition

A two component therapy consisting of 14 Didronel 400mg tablets and 76 Cacit 500mg effervescent tablets (equivalent to 500mg elemental calcium).

Each Didronel tablet contains 400mg of etidronate disodium, USP. Each Cacit 500mg effervescent tablet contains 1250mg of calcium carbonate, Ph.Eur., which when dispersed in water provides 500mg of elemental calcium as calcium citrate.

3. Pharmaceutical Form

Each Didronel 400mg tablet is white, capsule-shaped and marked with "NE" on one face and '406' on the other. The Cacit 500mg effervescent tablet is round, flat, white with pink speckles and has a distinctive orange flavour.

4. Clinical Particulars

4.1 Therapeutic Indications

Treatment of osteoporosis and prevention of bone loss in postmenopausal women considered at risk of developing osteoporosis. Didronel PMO is particularly indicated in patients who are unable or unwilling to take oestrogen replacement therapy.

Didronel PMO is also indicated for the prevention and treatment of corticosteroid induced osteoporosis.

4.2 Posology And Method Of Administration

Didronel PMO therapy is a long-term cyclical regimen administered in 90-day cycles. Each cycle consists of Didronel 400mg tablets for the first 14 days, followed by Cacit 500mg tablets for the remaining 76 days.

The majority of patients have been treated for 3 years, with a small number of patients treated for up to 7 years, with no clinical safety concerns. The optimum duration of treatment has not been established.

*Didronel 400mg component:

One tablet should be taken each day for 14 consecutive days on an empty stomach. It is recommended that patients take the tablet with water at the midpoint of a four hour fast (i.e. two hours before and two hours after food).

*Cacit 500mg component:

Following 14 days treatment with Didronel 400mg tablets, one Cacit tablet should be taken on a daily basis. The Cacit tablet should be dissolved in water and drunk immediately after complete dissolution.

The optimal duration of bisphosphonate treatment for osteoporosis has not been established. The need for continued treatment should be re-evaluated periodically based on the benefits and potential risks of risedronate on an individual patient basis, particularly after 5 or more years of use.

Adult and elderly:

The patient should adhere to the prescribed regimen above. Modification of the dosage for the elderly is not required.

Children:

No data exists on the use of this therapy in juvenile osteoporosis.

4.3 Contraindications

Known hypersensitivity to any of the ingredients. Treatment of patients with severe renal impairment. Patients with hypercalcaemia or hypercalciuria.

Clinically overt osteomalacia. Use in pregnancy and lactation.

4.4 Special Warnings And Precautions For Use

Clinicians should advise patients to adhere to the recommended treatment regimen, and compliance pack.

In long-term trials no clinical osteomalacia was observed in patients receiving cyclical etidronate. Following long-term therapy in excess of 4 years, analysis of bone biopsies showed an increased prevalence of peritrabecular fibrosis and histologically defined atypical and focal osteomalacia (not to be confused with the syndrome associated with "clinical osteomalacia" due to vitamin D deficiency). In addition, these laboratory findings were not associated with any clinical consequences. Osteoid, which may accumulate at high doses of continuous etidronate therapy (10-20mg/kg/day) mineralises normally after discontinuation of therapy. Continuous administration of etidronate should be avoided.

Patients with significant chronic diarrhoeal disease may experience increased frequency of bowel movements and diarrhoea. Therapy should be withheld from patients with enterocolitis because of increased frequency of bowel movements.

Etidronate disodium is not metabolized and is excreted intact via the kidney. Due to the lack of clinical experience the treatment of patients with impaired renal function should be undertaken with due caution. The use of etidronate disodium is discouraged in patients with severely impaired kidney function.

In patients with impaired renal function or a history of kidney stone formation, serum and urinary calcium should be monitored regularly.

Etidronate disodium does not adversely effect serum levels of parathyroid hormone or calcium.

Hyperphosphataemia has been observed in patients receiving etidronate disodium, usually in association with doses of 10-20mg/kg/day. No adverse effects have been traced to this, and it does not constitute grounds for discontinuing therapy. It is apparently due to a drug-related increase in renal tubular re absorption of phosphate. Serum phosphate levels generally return to normal 2-4 weeks post therapy.

Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis) has been reported in patients with cancer receiving treatment regimens including primarily intravenously administered bisphosphonates. Many of these patients were also receiving chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving bisphosphonates.

A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patient with concominant risk factors (e.g. cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene).

While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces risk of osteonecrosis of the jaw.

Clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

Patients with rare hereditary problems of fructose intolerance should not take this medicine.

Atypical fractures of the femur

Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before presenting with a completed femoral fracture. Fractures are often bilateral; therefore the contralateral femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation of bisphosphonate therapy in patients suspected to have an atypical femur fracture should be considered pending evaluation of the patient, based on an individual benefit risk assessment.

During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.

In patients with Paget's disease the excretion of hydroxyproline and serum levels for alkaline phosphatase should be regularly monitored.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Food in the stomach or upper gastrointestinal tract, particularly materials with a high calcium content such as milk, may reduce absorption of etidronate disodium. Vitamins with mineral supplements such as iron, calcium supplements, laxatives containing magnesium, or antacids containing calcium or aluminium should not be taken within two hours of dosing etidronate disodium.

The diagnostic utility of bone-imaging agents may be impaired by current or recent etidronate use.

A small number of patients in clinical trials (involving more than 600 patients) received either thiazide diuretics or intravaginal oestrogen while on this treatment. The concomitant use of either of these agents did not interfere with the positive effects of the therapy on vertebral bone mass or fracture rates.

Calcium salts may reduce the absorption of some drugs, e.g. tetracyclines. It is therefore suggested that administration of Cacit tablets be separated from these products by at least three hours.

Vitamin D causes an increase in calcium absorption and plasma calcium levels may continue to rise after stopping vitamin D therapy. Concomitant administration of Cacit tablets and vitamin D should therefore be carried out with caution.

The effects of digoxin and other cardiac glycosides may be accentuated by calcium and toxicity may be produced, especially in combination with vitamin D therapy.

There have been isolated reports of patients experiencing changes in their prothrombin times when etidronate was added to warfarin therapy. The majority ot these reports concerned variable elevations in prothrombin times without clinically significant sequelae. Although the relevance of these reports and any mechanism of coagulation alterations is unclear,patients on warfarin should have their prothrombin time monitored.

4.6 Pregnancy And Lactation

There are no adequate data from the use of Didronel in pregnant women.

Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown.

Didronel should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus.

It is not known whether this drug passes into breast milk. It should therefore not be used during lactation period.

4.7 Effects On Ability To Drive And Use Machines

Etidronate disodium does not interfere with the ability to drive or use machines.

4.8 Undesirable Effects

Gastro-intestinal

In clinical studies of 2-3 years duration, the incidence of these events were comparable to placebo. The most common effects reported in order of incidence were diarrhoea, nausea, flatulence, dyspepsia, abdominal pain, gastritis, constipation and vomiting. Reports of exacerbation of peptic ulcers with complications in a few patients.

Dermatological/hypersensitivity

Hypersensitivity reactions including angio-oedema, urticaria, rash and/or pruritus have been reported rarely. The colouring agent E110 can cause allergic-type reactions including asthma. Allergy is more common in those people who are allergic to aspirin.

Nervous System

Headache, and rarely paresthesia, peripheral neuropathy and confusion.

Haematological

There have been rare reports of leucopenia, agranulocytosis and pancytopenia.

Other

Less common effects believed to be related to therapy include arthropathies (arthralgia and arthritis), and rarely burning af the tongue, alopecia, erythema multiforme and exacerbation of asthma.

Occasional mild leg cramps have been reported in less than 5% of patients on the Didronel PMO regimen. These cramps were transient, often nocturnal and generally associated with other underlying conditions. osteonecrosis of the jaw (see section 4.4 special warnings and precautions of use) During post-marketing experience the following reactions have been reported (frequency rare):

Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction).

4.9 Overdose

Clinical experience of acute overdosage with etidronate is limited and unlikely with this compliance kit. Theoretically it would be manifested as the signs and symptoms of hypocalcaemia and possibly paresthesia of the fingers.

Treatment would consist of gastric lavage to remove unabsorbed drug along with correction of hypocalcaemia with administration of Ca2+ intravenously.

Prolonged continuous treatment (chronic overdose) has been reported to cause nephrotic syndrome and fractures.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Etidronate in an intermittent cyclical regimen, works indirectly to increase bone mass.

By timing delivery and withdrawal, the etidronate disodium component acts to modulate osteoclasts and reduce the mean resorption depth of the affected basic multicellular units (BMU).

Calcium is an essential element which has been shown to help prevent bone loss.

Epidemiological studies have suggested that there are a number of risk factors associated with postmenopausal osteoporosis, such as early menopause, a family history of osteoporosis, prolonged exposure to corticosteroid therapy, small and thin skeletal frame and excessive cigarette smoking.

5.2 Pharmacokinetic Properties

Within 24 hours, about one half of the absorbed dose of etidronate is excreted in the urine. The remainder is chemically absorbed on bone and is slowly eliminated. Unabsorbed drug is excreted in the faeces. Etidronate disodium is not metabolised. After oral doses of up to 1600mg of the disodium salt, the amount of drug absorbed is approximately 3-4%. In normal subjects, plasma half life (T½) of etidronate, based on non-compartmental pharmacokinetics is 1-6 hours.

Calcium carbonate is converted into soluble calcium salts in the stomach under the influence of hydrochloric acid. 30-80% of orally ingested calcium is absorbed both by active transport (primarily in the upper small intestine) and by passive diffusion. The distribution of calcium in the body is subject to the mechanism of physiological regulation controlled by parathyroid hormone, calcitonin, calciferol and other hormones.

When Calcium effervescent tablets are added to water, insoluble calcium carbonate is converted into calcium citrate.

5.3 Preclinical Safety Data

In long-term studies in mice and rats, there was no evidence of carcinogenicity with etidronate disodium. All in vitro and in vivo assays conducted to assess the mutagenic potential of etidronate disodium have been negative.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Etidronate disodium tablets contain microcrystalline cellulose, pregelatinised starch and magnesium stearate. Cacit tablets contain citric acid, sodium saccharin, sodium cyclamate, sunset yellow (E110) and orange flavouring.

6.2 Incompatibilities

None.

6.3 Shelf Life

The expiry date for the compliance pack should not exceed 3 years from the date of its manufacture.

6.4 Special Precautions For Storage

Store in a dry place below 30°C. Since Cacit 500mg tablets are hygroscopic, the stopper should be carefully replaced after use.

6.5 Nature And Contents Of Container

14 Didronel 400mg tablets in a blister plus four polypropylene tubes, each containing 19 Cacit 500mg tablets, all packaged in a compliance kit.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Warner Chilcott UK Limited

Old Belfast Road,

Millbrook,

Larne,

County Antrim,

BT40 2SH

8. Marketing Authorisation Number(S)

PL 10947/0019

9. Date Of First Authorisation/Renewal Of The Authorisation

24/02/2009

10. Date Of Revision Of The Text

15/09/2011

Nilstat Topical Ointment Topical

Generic Name: nystatin (Topical route)

nye-STAT-in

Commonly used brand name(s)

In the U.S.

• Mycostatin


• Nystop


• Pedi-Dri

In Canada

• Mycostatin Cream


• Mycostatin Ointment


• Mycostatin Powder


• Nadostine


• Nilstat Topical Cream


• Nilstat Topical Ointment


• Nyaderm Cream


• Nyaderm Ointment

Available Dosage Forms:

• Powder


• Cream


• Ointment

Therapeutic Class: Antifungal

Chemical Class: Polyene

Uses For Nilstat Topical Ointment

Nystatin belongs to the group of medicines called antifungals. Topical nystatin is used to treat some types of fungus infections of the skin.

Nystatin is available in the U.S. only with your doctor's prescription.

Before Using Nilstat Topical Ointment

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

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Although there is no specific information comparing use of topical nystatin in children with use in other age groups, this medicine is not expected to cause different side effects or problems in children than it does in adults.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of topical nystatin in the elderly with use in other age groups.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Proper Use of nystatin

This section provides information on the proper use of a number of products that contain nystatin. It may not be specific to Nilstat Topical Ointment. Please read with care.

Topical nystatin should not be used in the eyes.

Apply enough nystatin to cover the affected area.

For patients using the powder form of this medicine on the feet:

• Sprinkle the powder between the toes, on the feet, and in socks and shoes.

The use of any kind of occlusive dressing (airtight covering, such as kitchen plastic wrap) over this medicine may increase the chance of irritation. Therefore, do not bandage, wrap, or apply any occlusive dressing over this medicine unless directed to do so by your doctor. When using this medicine on the diaper area of children, avoid tight-fitting diapers and plastic pants.

To help clear up your infection completely, keep using this medicine for the full time of treatment, even if your condition has improved. Do not miss any doses.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For topical dosage forms (cream or ointment):
  
  • For fungus infections:
    
    • Adults and children—Apply to the affected area(s) of the skin two times a day.
    
    
  
  


• For topical dosage form (powder):
  
  • For fungus infections:
    
    • Adults and children—Apply to the affected area(s) of the skin two or three times a day.
    
    
  
  

Missed Dose

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

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Nilstat Topical Ointment Side Effects

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 may need medical attention.

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

• Skin irritation not present before use of this medicine

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

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• Nilstat Topical Ointment Topical Use in Pregnancy & Breastfeeding
• Nilstat Topical Ointment Topical Support Group
• 6 Reviews for Nilstat Topical Topical - Add your own review/rating

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• Cutaneous Candidiasis
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Alzheimer's Disease Medications

Definition of Alzheimer's Disease:

A progressive, neurodegenerative disease characterised by loss of function and death of nerve cells in several areas of the brain leading to loss of cognitive function such as memory and language.

The cause of nerve cell death is unknown but the cells are recognised by the appearance of unusual helical protein filaments in the nerve cells

Drugs associated with Alzheimer's Disease

The following drugs and medications are in some way related to, or used in the treatment of Alzheimer's Disease. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Learn more about Alzheimer's Disease

Medical Encyclopedia:

• Alzheimer's disease

Harvard Health Guide:

• Symptoms and treatment for Alzheimer's Disease

Drugs.com Health Center:

• Mental Health Disorders

Drug List:

Alpha-E

Amino-Opti-E

Aqua-Gem-E

Aqua-E

Aquasol-E

Aquavite-E

Aricept

Aricept-Odt-Orally-Disintegrating-Tablets

Axona

Centrum-Singles-Vitamin-E

Cognex

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pioglitazone

pye-oh-GLI-ta-zone

Oral route(Tablet)

Pioglitazone hydrochloride may cause or worsen congestive heart failure. Monitor patients for signs and symptoms of heart failure after initiation or dose increases. Should such signs and symptoms of congestive heart failure develop, manage according to current standards of care and consider discontinuing therapy or a dose reduction. Pioglitazone hydrochloride is not recommended in patients with symptomatic heart failure and is contraindicated in patients with established NYHA Class III or IV heart failure .

Commonly used brand name(s)

In the U.S.

• Actos

Available Dosage Forms:

• Tablet

Therapeutic Class: Antidiabetic

Chemical Class: Thiazolidinedione

Uses For pioglitazone

Pioglitazone is used to treat a type of diabetes mellitus called type 2 diabetes. It may be used alone or with other medicines such as insulin, metformin, or sulfonylurea agents. Pioglitazone is used together with a proper diet and exercise to help control blood sugar levels. It does this by helping your body use insulin better.

pioglitazone is available only with your doctor's prescription.

Before Using pioglitazone

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

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to pioglitazone or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of pioglitazone in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of pioglitazone in the elderly. However, elderly patients are more likely to have age-related heart disease, which may require an adjustment in the dose for patients receiving pioglitazone.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking pioglitazone, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using pioglitazone with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Tolvaptan

Using pioglitazone with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Atorvastatin


• Bitter Melon


• Desogestrel


• Dienogest


• Drospirenone


• Estradiol Cypionate


• Estradiol Valerate


• Ethinyl Estradiol


• Ethynodiol Diacetate


• Etonogestrel


• Fenugreek


• Gemfibrozil


• Glucomannan


• Guar Gum


• Ketoconazole


• Levonorgestrel


• Medroxyprogesterone Acetate


• Mestranol


• Norelgestromin


• Norethindrone


• Norgestimate


• Norgestrel


• Psyllium


• Rifampin


• Topiramate

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of pioglitazone. Make sure you tell your doctor if you have any other medical problems, especially:

• Bladder cancer, active or


• Diabetic ketoacidosis (ketones in the blood) or


• Heart failure, severe or


• Type I diabetes—Should not be used in patients with these conditions.

• Diabetic macular edema (swelling of the back of the eye) or


• Edema (fluid retention or swelling) or


• Heart disease or


• Liver disease—Use with caution. May make these conditions worse.

• Fever or


• Infection or


• Surgery or


• Trauma—Use with caution. These conditions may cause problems with blood sugar control.

• Fragile bones (especially in women)—Use with caution. pioglitazone may increase the risk for fractures.

Proper Use of pioglitazone

Take pioglitazone only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered.

Carefully follow the special diet your doctor gave you. This is the most important part of controlling your diabetes and will help the medicine work properly. Also, exercise regularly and test for sugar in your blood or urine as directed.

pioglitazone should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

The tablets may be taken with or without food.

Dosing

The dose of pioglitazone will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of pioglitazone. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  
  • For type 2 diabetes:
    
    • Adults—At first, 15 or 30 milligrams (mg) once a day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 45 mg once a day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of pioglitazone, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using pioglitazone

It is very important that your doctor check your progress at regular visits to make sure that pioglitazone is working properly. Blood and urine tests may be needed to check for unwanted effects.

Certain women may be at an increased risk for pregnancy while taking pioglitazone. If you had problems ovulating and had irregular periods in the past, pioglitazone may cause you to ovulate. This could increase your chance of becoming pregnant. If you are a woman of childbearing potential, you should discuss birth control options with your doctor.

Check with your doctor right away if you start having chest pain; shortness of breath; excessive swelling of the hands, wrist, ankles, or feet; or if you are rapidly gaining weight. These may be symptoms of a serious heart problem.

If you have abdominal or stomach pain; dark urine; a loss of appetite; nausea or vomiting; unusual tiredness or weakness; or yellow eyes or skin, check with your doctor right away. These may be symptoms of a serious liver problem.

Check with your doctor right away if blurred vision, decreased vision, or any other change in vision occurs while you are taking pioglitazone. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

pioglitazone may increase the risk for bone fractures in women. Ask your doctor about ways to keep your bones strong to help prevent fractures.

pioglitazone may increase your risk for bladder cancer if you take it for more than 12 months. Tell your doctor right away if you have blood in the urine; a frequent, strong, or increased urge to urinate; painful urination; or pain in the back, lower abdomen, or stomach.

It is very important to carefully follow any instructions from your doctor about:

• Alcohol—Drinking alcohol may cause severe low blood sugar. Discuss this with your doctor.


• Other medicines—Do not take other medicines unless they have been discussed with your doctor. This especially includes nonprescription medicines such as aspirin, and medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems.


• Counseling—Other family members need to learn how to prevent side effects or help with side effects if they occur. Also, diabetic patients may need special counseling about diabetes medicine dosing changes that might occur because of lifestyle changes, such as changes in exercise and diet. Counseling on contraception and pregnancy may be needed because of the problems that can occur during pregnancy in patients with diabetes.


• Travel—Keep a recent prescription and your medical history with you. Be prepared for an emergency as you would normally. Make allowances for changing time zones and keep your meal times as close as possible to your usual meal times.


• In case of emergency—There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says that you have diabetes and a list of all of your medicines.


• Symptoms of fluid retention—Know what to do if you start to retain fluid. Fluid retention may worsen or lead to heart problems.

pioglitazone does not cause hypoglycemia (low blood sugar). However, low blood sugar can occur if you delay or miss a meal or snack, exercise more than usual, drink alcohol, cannot eat because of nausea or vomiting, or take pioglitazone with another type of diabetes medicine. The symptoms of low blood sugar must be treated before they lead to unconsciousness (passing out). Different people feel different symptoms of low blood sugar. It is important that you learn which symptoms of low blood sugar you usually have so that you can treat it quickly.

• Symptoms of low blood sugar include anxiety; behavior change similar to being drunk; blurred vision; cold sweats; confusion; cool, pale skin; difficulty with thinking; drowsiness; excessive hunger; fast heartbeat; headache that continues; nausea; nervousness; nightmares; restless sleep; shakiness; slurred speech; or unusual tiredness or weakness.


• If the symptoms of low blood sugar occur, eat glucose tablets or gel, corn syrup, honey, or sugar cubes; or drink fruit juice, non-diet soft drinks, or sugar dissolved in water to relieve the symptoms. Also, check your blood for low blood sugar. Glucagon is used in emergency situations when severe symptoms such as seizures (convulsions) or unconsciousness occur. Have a glucagon kit available, along with a syringe and needle, and know how to use it. Members of your family also should know how to use it.

Hyperglycemia (high blood sugar) may occur if you do not take enough or skip a dose of your medicine, overeat or do not follow your meal plan, have a fever or infection, or do not exercise as much as usual.

• Symptoms of high blood sugar include blurred vision; drowsiness; dry mouth; flushed, dry skin; fruit-like breath odor; increased urination (frequency and amount); ketones in the urine; loss of appetite; stomachache, nausea, or vomiting; tiredness; trouble with breathing (rapid and deep); unconsciousness; or unusual thirst.


• If the symptoms of high blood sugar occur, check your blood sugar level and call your doctor for instructions.

pioglitazone Side Effects

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 may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

• Chest pain


• decreased urine output


• dilated neck veins


• extreme fatigue


• irregular breathing


• irregular heartbeat


• problems with teeth


• shortness of breath


• swelling of the face, fingers, feet, or lower legs


• tightness in the chest


• trouble with breathing


• weight gain


• wheezing

Less common

• Pain or swelling in the arms or legs without an injury


• pale skin


• swelling


• trouble with breathing when active


• unusual bleeding or bruising


• unusual tiredness or weakness

Incidence not known

• Dark urine


• loss of appetite


• nausea or vomiting


• stomach pain


• unexplained, rapid weight gain


• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Blurred vision or other changes in vision


• cough


• dry mouth


• flushed, dry skin


• fruit-like breath odor


• headache


• increased hunger


• increased thirst


• increased urination


• loss of consciousness


• muscle pain or soreness


• problems with your teeth


• runny or stuffy nose


• sore throat


• stomachache


• sweating


• unexplained weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: pioglitazone side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More pioglitazone resources

• Pioglitazone Side Effects (in more detail)
• Pioglitazone Dosage
• Pioglitazone Use in Pregnancy & Breastfeeding
• Pioglitazone Drug Interactions
• Pioglitazone Support Group
• 26 Reviews for Pioglitazone - Add your own review/rating

• Pioglitazone MedFacts Consumer Leaflet (Wolters Kluwer)


• Actos Prescribing Information (FDA)


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Cimetidine

Generic Name: Cimetidine hydrochloride

Dosage Form: oral solution
Cimetidine HYDROCHLORIDE ORAL SOLUTION

0506

Rx only

Cimetidine Description

Cimetidine is a histamine H2-receptor antagonist. Chemically it is N"-cyano-N-methyl-N'-[2-[[(5-methyl-1H-imidazol-4-yl)methyl]thio]-ethyl]-guanidine. The structural formula is:

C10H16N6S•HCl M.W. 288.80

Cimetidine contains an imidazole ring, and is chemically related to histamine.

(The liquid dosage form contains Cimetidine as the hydrochloride.)

Cimetidine hydrochloride has a bitter taste and characteristic odor.

Solubility Characteristics

Cimetidine hydrochloride is freely soluble in water, soluble in alcohol, very slightly soluble in chloroform and practically insoluble in ether.

Each 5 mL (one teaspoonful), for oral administration contains, Cimetidine hydrochloride equivalent to 300 mg of Cimetidine; alcohol, 2.8%. Inactive ingredients consist of FD&C Yellow No. 6, artificial peach mint flavor, hydrochloric acid, methylparaben, poloxamer 407, propylene glycol, propylparaben, purified water, saccharin sodium, sodium chloride, dibasic sodium phosphate heptahydrate and sorbitol solution.

Cimetidine - Clinical Pharmacology

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.

Antisecretory Activity

1) Acid Secretion

Nocturnal

Cimetidine 800 mg orally at bedtime reduces mean hourly H+ activity by greater than 85% over an eight-hour period in duodenal ulcer patients, with no effect on daytime acid secretion. Cimetidine 1600 mg orally h.s. produces 100% inhibition of mean hourly H+ activity over an eight-hour period in duodenal ulcer patients, but also reduces H+ activity by 35% for an additional five hours into the following morning. Cimetidine 400 mg b.i.d. and 300 mg q.i.d. decrease nocturnal acid secretion in a dose-related manner, i.e., 47% to 83% over a six- to eight-hour period and 54% over a nine-hour period, respectively.

Food Stimulated

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 two hours Cimetidine inhibited gastric acid secretion by at least 75%.

The effect of a 300 mg breakfast dose of Cimetidine continued for at least four 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

	Cimetidine	Placebo
1 hour	3.5	2.6
2 hours	3.1	1.6
3 hours	3.8	1.9
4 hours	6.1	2.2

24-Hour Mean H+ Activity

Cimetidine 800 mg h.s., 400 mg b.i.d. and 300 mg q.i.d. all provide a similar, moderate (less than 60%) level of 24-hour acid suppression. However, the 800 mg h.s. regimen exerts its entire effect on nocturnal acid, and does not affect daytime gastric physiology.

Chemically Stimulated

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 ½ 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% to 75% and the inhibition of volume ranged from 30% to 65%.

2) Pepsin

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.

Other

Lower Esophageal Sphincter Pressure and Gastric Emptying

Cimetidine has no effect on lower esophageal sphincter (LES) pressure or the rate of gastric emptying.

Pharmacokinetics

Cimetidine is rapidly absorbed after oral administration and peak levels occur in 45 to 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 to 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.

Clinical Trials

Duodenal Ulcer

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.

Duodenal Ulcer Healing Rates with Various Oral Cimetidine Dosage Regimens*

* Averages from controlled clinical trials.
Regimen	300 mg q.i.d.	400 mg b.i.d.	800 mg h.s.	1600 mg h.s.
week 4	68%	73%	80%	86%
week 6	80%	80%	89%	--
week 8	--	92%	94%	--

A U.S., double-blind, placebo-controlled, dose-ranging study demonstrated that all once-daily at bedtime (h.s.) Cimetidine regimens were superior to placebo in ulcer healing and that Cimetidine 800 mg h.s. healed 75% of patients at four weeks. The healing rate with 800 mg h.s. was significantly superior to 400 mg h.s. (66%) and not significantly different from 1600 mg h.s. (81%).

In the U.S. dose-ranging trial, over 80% of patients receiving Cimetidine 800 mg h.s. 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, the 800 mg h.s. dose was superior to 400 mg h.s. and not different from 1600 mg h.s.

In foreign, double-blind studies with Cimetidine 800 mg h.s., 79% to 85% of patients were healed at four 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 one year's therapy with Cimetidine 400 mg h.s. was significantly lower (10% to 45%) than in patients receiving placebo (44% to 70%). Thus, from 55% to 90% of patients were maintained free of observed ulcers at the end of one year with Cimetidine 400 mg h.s.

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 six weeks. Patients were limited to those with ulcers ranging from 0.5 to 2.5 cm in size. Endoscopically confirmed healing at six weeks was seen in significantly* more Cimetidine-treated patients than in patients receiving placebo, as shown below:

	Cimetidine	Placebo
week 2	14/63 (22%)	7/63 (11%)
total at week 6	43/65 (66%)*	30/67 (45%)

* p<0.05

In a similar multicenter U.S. study of the 800 mg h.s. oral regimen, the endoscopically confirmed healing rates were:

	Cimetidine	Placebo
total at week 6	63/83 (76%)*	44/80 (55%)

* p=0.005

Similarly, in worldwide double-blind clinical studies, endoscopically evaluated benign gastric ulcer healing rates were consistently 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:

Trial	Cimetidine (800 mg b.i.d.)	Cimetidine (400 mg q.i.d.)	Placebo	p-Value (800 mg b.i.d. vs. placebo)
1 Week 6	45%	52%	26%	0.02
Week 12	60%	66%	42%	0.02
2 Week 6	50%		20%	<0.01
Week 12	67%		36%	<0.01

In these trials Cimetidine was superior to placebo by most measures in improving symptoms of day- and night-time heartburn, with many of the differences statistically significant. The q.i.d. regimen was generally somewhat better than the b.i.d. 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.

Indications and Usage for Cimetidine

Cimetidine hydrochloride oral solution is indicated in:

1) 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 to 8 weeks (see DOSAGE AND ADMINISTRATION - Duodenal Ulcer). 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.

2) 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.

3) Short-term treatment of active benign gastric ulcer.

There is no information concerning usefulness of treatment periods of longer than 8 weeks.

4) 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 (see DOSAGE AND ADMINISTRATION - GERD).

5) The treatment of pathological hypersecretory conditions

(i.e., Zollinger-Ellison Syndrome, systemic mastocytosis, multiple endocrine adenomas).

Contraindications

Cimetidine is contraindicated for patients known to have hypersensitivity to the product.

Precautions

General

Symptomatic response to Cimetidine therapy does not preclude the presence of a gastric malignancy. There have been rare reports of transient healing of gastric ulcers despite subsequently documented malignancy.

Reversible confusional states (see ADVERSE REACTIONS) 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 to 4 days of drug withdrawal.

Drug Interactions

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 concomitantly administered Cimetidine to maintain optimum therapeutic blood levels.

Alteration of pH may affect 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.

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 as well as treated 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.

Pregnancy

Teratogenic Effects.

Pregnancy Category B

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.

Nursing Mothers

Cimetidine is secreted in human milk and, as a general rule, nursing should not be undertaken while a patient is on a drug.

Pediatric Use

Clinical experience in pediatric patients is limited. Therefore, Cimetidine therapy cannot be recommended for pediatric patients under 16, unless, in the judgment of the physician, anticipated benefits outweigh the potential risks. In very limited experience, doses of 20 to 40 mg/kg per day have been used.

Immunocompromised Patients

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.

Adverse Reactions

Adverse effects reported in patients taking Cimetidine are described below by body system. Incidence figures of 1 in 100 and greater are generally derived from controlled clinical studies.

Gastrointestinal

Diarrhea (usually mild) has been reported in approximately 1 in 100 patients.

CNS

Headaches, ranging from mild to severe, have been reported in 3.5% of 924 patients taking 1600 mg/day, 2.1% of 2,225 patients taking 800 mg/day and 2.3% of 1,897 patients taking placebo. Dizziness and somnolence (usually mild) have been reported in approximately 1 in 100 patients on either 1600 mg/day or 800 mg/day.

Reversible confusional states, e.g., mental confusion, agitation, psychosis, depression, anxiety, hallucinations, disorientation, have been reported predominantly, but not exclusively, in severely ill patients. They have usually developed within 2 to 3 days of initiation of Cimetidine therapy and have cleared within 3 to 4 days of discontinuation of the drug.

Endocrine

Gynecomastia has been reported in patients treated for one month or longer. In patients being treated for pathological hypersecretory states, this occurred in about 4% of cases while in all others the incidence was 0.3% to 1% in various studies. No evidence of induced endocrine dysfunction was found, and the condition remained unchanged or returned toward normal with continuing Cimetidine treatment.

Reversible impotence has been reported in patients with pathological hypersecretory disorders, e.g., Zollinger-Ellison Syndrome, receiving Cimetidine, particularly in high doses, for at least 12 months (range 12 to 79 months, mean 38 months). However, in large-scale surveillance studies at regular dosage, the incidence has not exceeded that commonly reported in the general population.

Hematologic

Decreased white blood cell counts in Cimetidine-treated patients (approximately 1 per 100,000 patients), including agranulocytosis (approximately 3 per million patients), have been reported, including a few reports of recurrence on rechallenge. Most of these reports were in patients who had serious concomitant illnesses and received drugs and/or treatment known to produce neutropenia. Thrombocytopenia (approximately 3 per million patients) and, very rarely, cases of pancytopenia or aplastic anemia have also been reported. As with some other H2-receptor antagonists, there have been extremely rare reports of immune hemolytic anemia.

Hepatobiliary

Dose-related increases in serum transaminase have been reported. In most cases they did not progress with continued therapy and returned to normal at the end of therapy. There have been rare reports of cholestatic or mixed cholestatic-hepatocellular effects. These were usually reversible. Because of the predominance of cholestatic features, severe parenchymal injury is considered highly unlikely. However, as in the occasional liver injury with other H2-receptor antagonists, in exceedingly rare circumstances fatal outcomes have been reported.

There has been reported a single case of biopsy-proven periportal hepatic fibrosis in a patient receiving Cimetidine.

Rare cases of pancreatitis, which cleared on withdrawal of the drug, have been reported.

Hypersensitivity

Rare cases of fever and allergic reactions including anaphylaxis and hypersensitivity vasculitis, which cleared on withdrawal of the drug, have been reported.

Renal

Small, possibly dose-related increases in plasma creatinine, presumably due to competition for renal tubular secretion, are not uncommon and do not signify deteriorating renal function. Rare cases of interstitial nephritis and urinary retention, which cleared on withdrawal of the drug, have been reported.

Cardiovascular

Rare cases of bradycardia, tachycardia and A-V heart block have been reported with H2-receptor antagonists.

Musculoskeletal

There have been rare reports of reversible arthralgia and myalgia; exacerbation of joint symptoms in patients with preexisting arthritis has also been reported. Such symptoms have usually been alleviated by a reduction in Cimetidine dosage. Rare cases of polymyositis have been reported, but no causal relationship has been established.

Integumental

Mild rash and, very rarely, cases of severe generalized skin reactions including Stevens-Johnson syndrome, epidermal necrolysis, erythema multiforme, exfoliative dermatitis and generalized exfoliative erythroderma have been reported with H2-receptor antagonists. Reversible alopecia has been reported very rarely.

Immune Function

There have been extremely rare reports of strongyloidiasis hyperinfection in immunocompromised patients.

Overdosage

Studies in animals indicate that toxic doses are associated with respiratory failure and tachycardia that may be controlled by assisted respiration and the administration of a beta-blocker.

Reported acute ingestions orally of up to 20 grams have been associated with transient adverse effects similar to those encountered in normal clinical experience. The usual measures to remove unabsorbed material from the gastrointestinal tract, clinical monitoring, and supportive therapy should be employed.

There have been reports of severe CNS symptoms, including unresponsiveness, following ingestion of between 20 and 40 grams of Cimetidine, and extremely rare reports following concomitant use of multiple CNS-active medications and ingestion of Cimetidine at doses less than 20 grams. An elderly, terminally ill dehydrated patient with organic brain syndrome receiving concomitant antipsychotic agents and Cimetidine 4800 mg intravenously over a 24 hour period experienced mental deterioration with reversal on Cimetidine discontinuation.

There have been two deaths in adults who were reported to have ingested over 40 grams orally on a single occasion.

Cimetidine Dosage and Administration

Duodenal Ulcer

Active Duodenal Ulcer

Clinical studies have indicated that suppression of nocturnal acid is the most important factor in duodenal ulcer healing (see CLINICAL PHARMACOLOGY - Antisecretory Activity - Acid Secretion). This is supported by recent clinical trials (see CLINICAL PHARMACOLOGY - Clinical Trials -Duodenal Ulcer - Active Duodenal Ulcer). Therefore, there is no apparent rationale, except for familiarity with use, for treating with anything other than a once-daily at bedtime oral dosage regimen (h.s.).

In a U.S. oral dose-ranging study of 400 mg h.s., 800 mg h.s. and 1600 mg h.s., a continuous dose response relationship for ulcer healing was demonstrated.

However, 800 mg h.s. is the dose of choice for most patients, as it provides a high healing rate (the difference between 800 mg h.s. and 1600 mg h.s. being small), maximal pain relief, a decreased potential for drug interactions (see PRECAUTIONS - Drug Interactions) and maximal patient convenience. Patients unhealed at four weeks, or those with persistent symptoms, have been shown to benefit from two to four weeks of continued therapy.

It has been shown that patients who both have an endoscopically demonstrated ulcer larger than 1 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 h.s. or 1600 mg h.s. is equivalent in all patients, 1600 mg h.s. provides an appropriate alternative when it is important to ensure healing within four weeks for this subpopulation. Alternatively, approximately 94% of all patients will also heal in eight weeks with Cimetidine 800 mg h.s.

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 (see CLINICAL PHARMACOLOGY - Clinical Trials - Duodenal Ulcer - Active Duodenal Ulcer).

Concomitant antacids should be given as needed for relief of pain. However, simultaneous administration of 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 to 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.

Active Benign Gastric Ulcer

The recommended adult oral dosage for short-term treatment of active benign gastric ulcer is 800 mg h.s., or 300 mg four times a day with meals and at bedtime. Controlled clinical studies were limited to six weeks of treatment (see CLINICAL PHARMACOLOGY - Clinical Trials). 800 mg h.s. 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.

Erosive Gastroesophageal Reflux Disease (GERD)

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 b.i.d. or 400 mg q.i.d.) for 12 weeks. The use of Cimetidine beyond 12 weeks has not been established.

Pathological Hypersecretory Conditions (such as Zollinger-Ellison Syndrome)

Recommended adult oral dosage - 300 mg four 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.

Dosage Adjustment for Patients with 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.

How is Cimetidine Supplied

Cimetidine hydrochloride oral solution 300 mg/5 mL is a clear, light orange, peach-mint flavored liquid available in 8 fl. oz. amber bottles.

Store at controlled room temperature, between 20° and 25°C (68° and 77°F) (see USP).

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

Manufactured By:

TEVA PHARMACEUTICALS USA

Sellersville, PA 18960

Rev. E 7/2003

PRINCIPAL DISPLAY PANEL

300 mg/5 mL Label Text

NDC 0093-0506-87 6505-01-199-0616

Cimetidine

HYDROCHLORIDE

ORAL SOLUTION

300 mg/5 mL*

Rx only

8 fl oz (237 mL)

TEVA

Cimetidine HYDROCHLORIDE  Cimetidine hydrochloride  solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0093-0506 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Cimetidine HYDROCHLORIDE (Cimetidine) Cimetidine 300 mg  in 5 mL

Inactive Ingredients Ingredient Name Strength FD&C YELLOW NO. 6   HYDROCHLORIC ACID   METHYLPARABEN   POLOXAMER 407   PROPYLENE GLYCOL   PROPYLPARABEN   WATER   SACCHARIN SODIUM   SODIUM CHLORIDE   SODIUM PHOSPHATE, DIBASIC, HEPTAHYDRATE   SORBITOL

Product Characteristics Color      Score      Shape Size Flavor PEACH (Peach Mint Flavor) Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0093-0506-87 237 mL In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA074610	01/21/2011

Labeler - TEVA Pharmaceuticals USA Inc (118234421)

Revised: 01/2011TEVA Pharmaceuticals USA Inc

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