Penicillin V Potassium

Dosage Form: tablet
Penicillin-VK

Penicillin V Potassium Tablets, USP

250 mg (400,000 Units)

500 mg (800,000 Units)

To reduce the development of drug-resistant bacteria and maintain the effectiveness of penicillin-VK and other antibacterial drugs, penicillin-VK should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Penicillin V Potassium Description

Penicillin V is the phenoxymethyl analog of penicillin G.

Penicillin V Potassium is the potassium salt of penicillin V.

Molecular Formula: C16H17O5KN2S Molecular Weight: 388.5

Penicillin -VK (Penicillin V Potassium Tablets USP), for oral administration, contain 250 mg (400,000 units) or 500 mg (800,000 units) Penicillin V Potassium. In addition, each tablet contains the following inactive ingredients: hydroxypropyl methylcellulose, magnesium stearate, polyethylene glycol, povidone, talc, and titanium dioxide.

Penicillin V Potassium - Clinical Pharmacology

Penicillin V exerts a bactericidal action against penicillin-sensitive microorganisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell-wall mucopeptide. It is not active against the penicillinase-producing bacteria, which include many strains of staphylococci. The drug exerts high in vitro activity against staphylococci (except penicillinase-producing strains), streptococci (groups A, C, G, H, L and M), and pneumococci. Other organisms sensitive in vitro to penicillin V are Corynebacterium diphtheriae, Bacillus anthracis, Clostridia, Actinomyces bovis, Streptobacillus moniliformis, Listeria monocytogenes, Leptospira, and Neisseria gonorrhoeae. Treponema pallidum is extremely sensitive.

The potassium salt of penicillin V has the distinct advantage over penicillin G in resistance to inactivation by gastric acid. It may be given with meals; however, blood levels are slightly higher when the drug is given on an empty stomach. Average blood levels are two to five times higher than the levels following the same dose of oral penicillin G and also show much less individual variation.

Once absorbed, penicillin V is about 80% bound to serum protein. Tissue levels are highest in the kidneys, with lesser amounts in the liver, skin, and intestines. Small amounts are found in all other body tissues and the cerebrospinal fluid. The drug is excreted as rapidly as it is absorbed in individuals with normal kidney function; however, recovery of the drug from the urine indicates that only about 25% of the dose given is absorbed. In neonates, young infants, and individuals with impaired kidney function, excretion is considerably delayed.

Indications and Usage for Penicillin V Potassium

Penicillin V Potassium tablets are indicated in the treatment of mild to moderately severe infections due to penicillin G-sensitive microorganisms. Therapy should be guided by bacteriological studies (including sensitivity tests) and by clinical response.

NOTE: Severe pneumonia, empyema, bacteremia, pericarditis, meningitis, and arthritis should not be treated with penicillin V during the acute stage. Indicated surgical procedures should be performed.

The following infections will usually respond to adequate dosage of penicillin V.

Streptococcal infections (without bacteremia). Mild-to-moderate infections of the upper respiratory tract, scarlet fever, and mild erysipelas.

NOTE: Streptococci in groups A, C, G, H, L, and M are very sensitive to penicillin. Other groups, including group D (enterococcus), are resistant.

Pneumococcal infections – Mild to moderately severe infections of the respiratory tract.

Staphylococcal infections – penicillin G-sensitive. Mild infections of the skin and soft tissues.

NOTE: Reports indicate an increasing number of strains of staphylococci resistant to penicillin G, emphasizing the need for culture and sensitivity studies in treating suspected staphylococcal infections.

Fusospirochetosis (Vincents gingivitis and pharyngitis) – Mild to moderately severe infections of the oropharynx usually respond to therapy with oral penicillin.

NOTE: Necessary dental care should be accomplished in infections involving the gum tissue.

Medical conditions in which oral penicillin therapy is indicated as prophylaxis: For the prevention of recurrence following rheumatic fever and/or chorea: Prophylaxis with oral penicillin on a continuing basis has proven effective in preventing recurrence of these conditions.

Although no controlled clinical efficacy studies have been conducted, penicillin V has been suggested by the American Heart Association and the American Dental Association for use as an oral regimen for prophylaxis against bacterial endocarditis in patients who have congenital heart disease or rheumatic or other acquired valvular heart disease when they undergo dental procedures and surgical procedures of the upper respiratory tract1. Oral penicillin should not be used in those patients at particularly high risk for endocarditis (e.g., those with prosthetic heart valves or surgically constructed systemicpulmonary shunts). Penicillin V should not be used as adjunctive prophylaxis for genitourinary instrumentation or surgery, lower-intestinal tract surgery, sigmoidoscopy, and childbirth. Since it may happen that alpha hemolytic streptococci relatively resistant to penicillin may be found when patients are receiving continuous oral penicillin for secondary prevention of rheumatic fever, prophylactic agents other than penicillin may be chosen for these patients and prescribed in addition to their continuous rheumatic fever prophylactic regimen.

NOTE: When selecting antibiotics for the prevention of bacterial endocarditis, the physician or dentist should read the full joint statement of the American Heart Association and the American Dental Association1.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of penicillin-VK and other antibacterial drugs, penicillin-VK should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Contraindications

A previous hypersensitivity reaction to any penicillin is a contraindication.

Warnings

SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (anaphylactic) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH Penicillin V Potassium TABLETS, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, OR OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, Penicillin V Potassium TABLETS SHOULD BE DISCONTINUED AND APPROPRIATE THERAPY INSTITUTED. SERIOUS ANALPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including penicillin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Precautions

Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma.

General

Prescribing penicillin-VK in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

The oral route of administration should not be relied upon in patients with severe illness, or with nausea, vomiting, gastric dilatation, cardiospasm, or intestinal hypermotility.

Occasional patients will not absorb therapeutic amounts of orally administered penicillin.

In streptococcal infections, therapy must be sufficient to eliminate the organism (10-day minimum); otherwise the sequelae of streptococcal disease may occur. Cultures should be taken following completion of treatment to determine whether streptococci have been eradicated.

Prolonged use of antibiotics may promote the overgrowth of nonsusceptible organisms, including fungi. Should superinfection occur, appropriate measures should be taken.

Information for Patients

Patients should be counseled that antibacterial drugs including penicillin-VK should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When penicillin-VK is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by penicillin-VK or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Adverse Reactions

Although the incidence of reactions to oral penicillins has been reported with much less frequency than following parenteral therapy, it should be remembered that all degrees of hypersensitivity, including fatal anaphylaxis, have been reported with oral penicillin.

The most common reactions to oral penicillin are nausea, vomiting, epigastric distress, diarrhea, and black hairy tongue. The hypersensitivity reactions reported are skin eruptions (maculopapular to exfoliative dermatitis), urticaria and other serum-sicknesslike reactions, laryngeal edema, and anaphylaxis.

Fever and eosinophilia may frequently be the only reaction observed. Hemolytic anemia, leukopenia, thrombocytopenia, neuropathy, and nephropathy are infrequent reactions and usually associated with high doses of parenteral penicillin.

Penicillin V Potassium Dosage and Administration

The dosage of penicillin V should be determined according to the sensitivity of the causative microorganisms and the severity of infection, and adjusted to the clinical response of the patient.

The usual dosage recommendations for adults and children 12 years and over are as follows:

Streptococcal infections - mild to moderately severe - of the upper respiratory tract and including scarlet fever and erysipelas: 125 to 250 mg (200,000 to 400,000 units) every 6 to 8 hours for 10 days.

Pneumococcal infections - mild to moderately severe - of the respiratory tract, including otitis media: 250 to 500 mg (400,000 to 800,000 units) every 6 hours until the patient has been afebrile for at least 2 days.

Staphylococcal infections - mild infections of skin and soft tissue (culture and sensitive tests should be performed): 250 to 500 mg (400,000 to 800,000 units) every 6 to 8 hours.

Fusospirochetosis (Vincents infection) of the oropharynx. Mild to moderately severe infections: 250 to 500 mg (400,000 to 800,000 units) every 6 to 8 hours.

For the prevention of recurrence following rheumatic fever and/or chorea: 125 to 250 mg (200,000 to 400,000 units) twice daily on a continuing basis.

For prophylaxis against bacterial endocarditis1 in patients with congenital heart disease or rheumatic or other acquired valvular heart disease when undergoing dental procedures or surgical procedures of the upper respiratory tract: 2 gram of penicillin V (1 gram for children under 60 lbs.) 1 hour before the procedure, and then, 1 gram (500 mg for children under 60 lbs.) 6 hours later.

How is Penicillin V Potassium Supplied

Penicillin - VK Tablets (Penicillin V Potassium Tablets USP), 250 mg (400,000 units) are round, biconvex white tablets, debossed PVK 250 and break scored on one side and GG 949 on the reverse side.

NDC 0781-1205-01 .......bottles of 100

NDC 0781-1205-10 .......bottles of 1000

Penicillin - VK Tablets (Penicillin V Potassium Tablets USP), 500 mg (800,000 units) are oblong, biconvex white tablets, debossed PVK 500 on one side and GG 950 on the reverse side and break scored on both sides.

NDC 0781-1655-01 .......bottles of 100

NDC 0781-1655-10 .......bottles of 1000

Store at 20° - 25°C (68° - 77°F) (see USP Controlled Room Temperature).

Keep tightly closed. Dispense in a tight container, as defined in the USP.

REFERENCES

1. American Heart Association.1984. Prevention of bacterial endocarditis. Circulation 70(6):1123A –1127A.

11-2010M

46047899

Manufactured in Austria by Sandoz GmbH

for Sandoz Inc., Princeton, NJ 08540

mg Label

NDC 0781-1205-01

Penicillin-VK

Penicillin V

Potassium Tablets,

USP

250 mg

(400,000 Units)

Rx only

100 Tablets

SANDOZ

mg Label

NDC 0781-1655-01

Penicillin-VK

Penicillin V

Potassium Tablets,

USP

500 mg

(800,000 Units)

x only

100 Tablets

SANDOZ

Penicillin V Potassium  Penicillin V Potassium  tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0781-1205 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Penicillin V Potassium (PENICILLIN V) Penicillin V Potassium 250 mg

Inactive Ingredients Ingredient Name Strength HYPROMELLOSES   MAGNESIUM STEARATE   POLYETHYLENE GLYCOL   POVIDONE   TALC   TITANIUM DIOXIDE

Product Characteristics Color WHITE (slightly cream-coloured) Score 2 pieces Shape ROUND (round) Size 10mm Flavor Imprint Code GG949;PVK250 Contains

Packaging # NDC Package Description Multilevel Packaging 1 0781-1205-01 100 TABLET In 1 BOTTLE None 2 0781-1205-10 1000 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA064071	11/30/1995

Penicillin V Potassium  Penicillin V Potassium  tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0781-1655 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Penicillin V Potassium (PENICILLIN V) Penicillin V Potassium 500 mg

Inactive Ingredients Ingredient Name Strength HYPROMELLOSES   MAGNESIUM STEARATE   POLYETHYLENE GLYCOL   POVIDONE   TALC   TITANIUM DIOXIDE

Product Characteristics Color WHITE Score 2 pieces Shape OVAL (oblong) Size 17mm Flavor Imprint Code GG950;PVK500 Contains

Packaging # NDC Package Description Multilevel Packaging 1 0781-1655-01 100 TABLET In 1 BOTTLE None 2 0781-1655-10 1000 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA064071	11/30/1995

Labeler - Sandoz Inc (110342024)

Revised: 10/2011Sandoz Inc

More Penicillin V Potassium resources

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• Penicillin V Potassium Dosage
• Penicillin V Potassium Use in Pregnancy & Breastfeeding
• Drug Images
• Penicillin V Potassium Drug Interactions
• Penicillin V Potassium Support Group
• 11 Reviews for Penicillin V Potassium - Add your own review/rating

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• Actinomycosis
• Anthrax
• Anthrax Prophylaxis
• Aspiration Pneumonia
• Bacterial Infection
• Clostridial Infection
• Congenital Syphilis
• Cutaneous Bacillus anthracis
• Deep Neck Infection
• Diphtheria
• Endocarditis
• Fusospirochetosis, Trench Mouth
• Joint Infection
• Leptospirosis
• Lyme Disease, Arthritis
• Lyme Disease, Carditis
• Lyme Disease, Erythema Chronicum Migrans
• Lyme Disease, Neurologic
• Meningitis
• Meningitis, Meningococcal
• Meningitis, Pneumococcal
• Neurosyphilis
• Otitis Media
• Pneumonia
• Prevention of Perinatal Group B Streptococcal Disease
• Rat-bite Fever
• Rheumatic Fever Prophylaxis
• Skin Infection
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Estradiol Weekly Patch

Pronunciation: ES-tra-DYE-ol
Generic Name: Estradiol
Brand Name: Menostar

Estradiol Weekly Patch should not be used to prevent heart disease, heart attacks, strokes, or dementia. Estrogens have been shown to increase the risk of heart disease (including heart attack), stroke, dementia, serious blood clots (eg, in the lungs or legs), cancer of the uterus, and breast cancer in some women. Tell your doctor right away if you have unusual vaginal bleeding while you use Estradiol Weekly Patch. Talk with your doctor if you have questions about the benefits and risks of using Estradiol Weekly Patch.

Estradiol Weekly Patch should be used for the shortest possible time at the lowest effective dose to minimize the risk of these side effects. Talk with your doctor regularly about your need to use Estradiol Weekly Patch.

Estradiol Weekly Patch is used for:

Preventing osteoporosis in certain women who have already gone through menopause.

Estradiol Weekly Patch is an estrogen hormone used to provide the female hormone when the body no longer produces enough.

Do NOT use Estradiol Weekly Patch if:

• you are allergic to any ingredient in Estradiol Weekly Patch


• you are pregnant or suspect you may be pregnant, have recently given birth or are breast-feeding, have vaginal bleeding of abnormal or unknown cause, or have cancer of the uterus


• you have known or suspected breast cancer (unless directed by your doctor), or you have cancers that are estrogen-dependent


• you have blood clots, circulation disorders, or liver problems


• you have had a recent heart attack or stroke

Contact your doctor or health care provider right away if any of these apply to you.

Before using Estradiol Weekly Patch:

Some medical conditions may interact with Estradiol Weekly Patch. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are planning to become pregnant


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a family history of breast cancer, or you have breast lumps or disease, or an abnormal mammogram


• if you have yellowing of the whites of the eyes or skin during pregnancy or with past estrogen use, or high blood pressure during pregnancy (toxemia)


• if you have a vaginal infection or womb problems (eg, uterine fibroids/endometriosis, abnormal vaginal bleeding, other uterine problems)


• if you have abnormal calcium levels in the blood, asthma, cancer, certain blood disorder (porphyria), cholesterol or lipid problems, depression, diabetes, epilepsy, excessive weight gain, gallbladder disease, heart disease or other heart problems, high blood pressure, kidney or liver disease, low thyroid hormone levels, lupus, migraine headaches, pancreas disease, seizures, or yellowing of the skin or eyes


• if you smoke or will be having surgery

Some MEDICINES MAY INTERACT with Estradiol Weekly Patch. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Anticoagulants (eg, warfarin), corticosteroids (eg, prednisone), succinylcholine, tacrine or because their actions and the risk of their side effects may be increased by Estradiol Weekly Patch


• Anticoagulants (eg, warfarin) because their effectiveness may be decreased by Estradiol Weekly Patch


• Barbiturates (eg, phenobarbital), hydantoins (eg, phenytoin), or rifampin because they may decrease Estradiol Weekly Patch's effectiveness

This may not be a complete list of all interactions that may occur. Ask your health care provider if Estradiol Weekly Patch may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Estradiol Weekly Patch:

Use Estradiol Weekly Patch as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Estradiol Weekly Patch. Talk to your pharmacist if you have questions about this information.


• If you are switching from oral estrogen to Estradiol Weekly Patch, stop taking the oral estrogen and wait 1 week before using Estradiol Weekly Patch. However, if symptoms return, you may start using Estradiol Weekly Patch sooner.


• One patch is usually applied to the skin and worn for 1 week and then replaced. Follow the dosing schedule carefully.


• Do not open the sealed pouch containing the patch until ready to use. Open the pouch and remove the patch from the protective liner. Apply to an area of clean, dry skin on the lower stomach area below the belly button. Press the patch firmly against the skin for about 10 seconds to be sure the patch stays on. If the system lifts, press down to reapply. Wear only 1 system at any one time.


• Do not place the patch on the breast. Make sure the application site is not oily, damaged, or irritated. Avoid applying to the waistline because tight clothing may rub the patch off. Do not put the patch on areas where sitting may loosen it. Do not apply to a site that is exposed to sunlight. Contact with water while bathing, showering, or swimming will not affect the patch.


• After removing the used patch, fold it in half with the sticky sides together. Discard the patch out of the reach of children and away from pets.


• Apply a new patch to a different area to prevent skin irritation. Use a different site when replacing the patch and do not repeat the same site for at least 1 week. If the area around the patch becomes red, itchy, or irritated, try a new site. If the irritation continues or becomes worse, notify your doctor promptly.


• Grapefruit and grapefruit juice may increase the risk of Estradiol Weekly Patch's side effects. Talk to your doctor before including grapefruit or grapefruit juice in your diet while you are taking Estradiol Weekly Patch.


• If you forget to change the patch as scheduled, change it as soon as possible and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Estradiol Weekly Patch.

Important safety information:

• Estradiol Weekly Patch may cause dizziness. This effect may be worse if you take it with alcohol or certain medicines. Use Estradiol Weekly Patch with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Limit alcoholic beverages while you are using Estradiol Weekly Patch.


• Estradiol Weekly Patch may cause dark skin patches on your face (melasma). Exposure to the sun may make these patches darker and you may need to avoid prolonged sun exposure and sunlamps. Consult your doctor regarding the use of sunscreens and protective clothing.


• Estradiol Weekly Patch may increase the risk of blood clots. The risk may be greater if you smoke (especially in women older than 35 years of age).


• Contact your doctor if vaginal bleeding of unknown cause occurs. This could be a sign of a serious condition requiring immediate medical attention.


• Contact your doctor if vaginal discomfort occurs or if you suspect you have developed an infection while taking Estradiol Weekly Patch.


• Follow your doctor's instructions for examining your breasts, and report any lumps immediately.


• If you wear contact lenses and you develop problems with them, contact your doctor.


• If you will be having surgery or will be confined to a chair or bed for a long period of time (eg, a long plane flight), notify your doctor beforehand. Special precautions may need to be taken in these circumstances while you are taking Estradiol Weekly Patch.


• Nonprescription therapy to help prevent bone loss includes a weight-bearing exercise plan, as well as adequate daily calcium and vitamin D intake. Consult your doctor or pharmacist for more details.


• Estradiol Weekly Patch may increase the risk of breast and endometrial cancer.


• Diabetes patients - Estradiol Weekly Patch may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• Estradiol Weekly Patch may interfere with certain lab tests. Be sure your doctor and lab personnel know you are using Estradiol Weekly Patch.


• Lab tests, including physical exams and blood pressure, may be performed while you use Estradiol Weekly Patch. You should have breast and pelvic exams, and a Pap test at least once a year. You should also have periodic mammograms as determined by your doctor. Be sure to keep all doctor and lab appointments.


• Estradiol Weekly Patch should not be used in CHILDREN; safety and effectiveness in children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: Do not use Estradiol Weekly Patch if you are pregnant. Avoid becoming pregnant while you are taking it. If you think you may be pregnant, contact your doctor right away. Estradiol Weekly Patch may be found in breast milk. If you are or will be breast-feeding while you use Estradiol Weekly Patch, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Estradiol Weekly Patch:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Breast pain or tenderness; headache; hair loss; mild nausea or vomiting; spotting or breakthrough bleeding; stomach cramps or bloating.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); back pain;breast discharge or lump in the breast; calf or leg pain or swelling; chest pain; coughing up blood; dark urine; depression; dizziness; fainting; fever; memory problems; mental or mood changes; muscle pain; one-sided weakness; painful or difficult urination; persistent or severe breast pain or tenderness; persistent or severe headache, nausea, or vomiting; severe stomach pain or swelling; slurred speech; sudden shortness of breath; sunburn-like rash; swelling of hands, legs, or feet; unusual vaginal bleeding, discharge, itching, or odor; vision changes; vomiting; weakness or numbness of an arm or leg; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include excessive vaginal bleeding; severe nausea; vomiting.

Proper storage of Estradiol Weekly Patch:

Store Estradiol Weekly Patch at room temperature, 59 to 86 degrees F (15 to 30 degrees C). Store in original packaging until just before use. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Estradiol Weekly Patch out of the reach of children and away from pets.

General information:

• If you have any questions about Estradiol Weekly Patch, please talk with your doctor, pharmacist, or other health care provider.


• Estradiol Weekly Patch is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Estradiol Weekly Patch. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

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• Estradiol Support Group
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Gyno-Pevaryl 1 Vaginal Pessary

1. Name Of The Medicinal Product

Gyno-Pevaryl 1 Vaginal Pessary.

2. Qualitative And Quantitative Composition

Each pessary contains econazole nitrate PhEur 150 mg.

3. Pharmaceutical Form

Light beige torpedo shaped pessary,

4. Clinical Particulars

4.1 Therapeutic Indications

Vaginitis due to Candida Albicans and other yeasts.

4.2 Posology And Method Of Administration

For vaginal administration.

Adults:

Insert one pessary high into the vagina at night prior to retiring.

Children:

Gyno-Pevaryl 1 pessary is not indicated for use in children under the age of 16 years.

Elderly:

No specific dosage recommendations or precautions apply.

4.3 Contraindications

Hypersensitivity to any imidazole preparation, other vaginal antifungal products or to any ingredients of Gyno-Pevaryl 1 vaginal pessary.

4.4 Special Warnings And Precautions For Use

This preparation is not for oral uses

Hypersensitivity has rarely been recorded; if it should occur administration should be discontinued.

Contact between contraceptive diaphragms or condoms and this product must be avoided since the rubber may be damaged by the preparation.

Patients using spermicidal contraceptives should consult their physician since any local vaginal treatment may inactivate the spermicidal contraceptive.

Gyno-Pevaryl 1 vaginal pessary should not be used in conjunction with other internal or external treatment of the genitalia.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Although not studied, based on the chemical similarity of econazole with other imidazole compounds, a theoretical potential for competitive interaction with compounds metabolized by CYP3A4/2C9 exists. Due to the limited systemic availability after vaginal application (see 5.2. Pharmacokinetic Properties), clinically relevant interactions are unlikely to occur. In patients on oral anticoagulants, such as warfarin and acenocoumarol, caution should be exercised and the anticoagulant effect should be monitored more frequently.

Adjustment of the oral anticoagulant dosage may be necessary during and after the treatment with econazole.

4.6 Pregnancy And Lactation

Pregnancy

In animals, econazole nitrate has shown no teratogenic effects but is foetotoxic at high doses. The significance of this to man is unknown as there is no evidence of an increased risk when taken in human pregnancy. However, because there is vaginal absorption, as with other imidazoles, econazole should be used in pregnancy only if the practitioner considers it to be necessary.

Lactation

Following oral administration of econazole nitrate to lactating rats, econazole and/or metabolites were excreted in milk and were found in nursing pups. It is not known whether econazole nitrate is excreted in human milk. Caution should be exercised when using Gyno-Pevaryl 1 vaginal pessaries if the patient is breast-feeding.

4.7 Effects On Ability To Drive And Use Machines

None known

4.8 Undesirable Effects

The most frequently reported adverse events in clinical trials were application site reactions, such as burning and stinging sensations, pruritus, and erythema.

Including the above mentioned adverse drug reactions (ADRs), the following table displays ADRs that have been reported with the use of Gynaecological Formulation from either clinical trial or postmarketing experiences. The displayed frequency categories use the following convention:

Very common (

Adverse drug reactions

System Organ Class	Adverse Drug Reactions
Frequency Category
		Not known
Skin and Subcutaneous Tissue Disorders			Angioedema Rash Urticaria Erythema Pruritus Burning sensation Hypersensitivity

4.9 Overdose

This product is intended for vaginal use. Overdose with econazole nitrate has not been reported to date. In the event of accidental ingestion, nausea, vomiting and diarrhoea may occur. If necessary treat symptomatically

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic classification: (Antiinfectives and antiseptics, excl. combinations with corticosteroids, imidazole derivatives)

ATC code: G01A F05

Econazole is an imidazole derivative. The compound acts by damaging the membranes of bacterial and fungal cells; both the cellular and subcellular membranes are affected. Econazole apparently disturbs the permeability characteristics of the membrane which allow leakage of potassium and sodium ions and other intra cellular components. Macro-molecular synthesis may also be inhibited. Econazole is active against dermatophytes, yeast, moulds and Gram positive bacteria. Gram negative bacteria are generally resistant to econazole.

5.2 Pharmacokinetic Properties

Econazole nitrate is poorly absorbed after vaginal application. Using radiolabelled techniques, it has been determined that between 2.5% and 7% of vaginally applied econazole nitrate is absorbed. However, no antimycotic activity could be detected in the serum after vaginal application of 5 g or 1% econazole nitrate cream or a suppository containing 50 mg econazole nitrate.

5.3 Preclinical Safety Data

No relevant information other than that contained elsewhere in the Summary of Product Characteristics.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Polygel

Colloidal silicon dioxide

Witepsol H19

Wecobee FS

Stearyl heptanoate

6.2 Incompatibilities

None stated.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Do not store above 30°C.

6.5 Nature And Contents Of Container

Multi-plast strip or PVC/PE moulds, containing one pessary.

1 applicator

Gyno-Pevaryl 1 Vaginal Pessary (PL 0242/0226) is also contained in:

Gyno-Pevaryl 1 C.P. PACK Vaginal Pessary and Cream

(PL 0242/0226 & PL 0242/0229)

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Janssen-Cilag Limited

50-100 Holmers Farm Way

High Wycombe

Buckinghamshire

HP12 4EG

UK

8. Marketing Authorisation Number(S)

PL 00242/0226

9. Date Of First Authorisation/Renewal Of The Authorisation

1 October 1995/June 2003

10. Date Of Revision Of The Text

23^rd March 2011

losartan

Generic Name: losartan (loe SAR tan)

Brand Names: Cozaar

What is losartan?

Losartan is in a group of drugs called angiotensin II receptor antagonists. Losartan keeps blood vessels from narrowing, which lowers blood pressure and improves blood flow.

Losartan is used to treat high blood pressure (hypertension). It is also used to lower the risk of stroke in certain people with heart disease.

Losartan is used to slow long-term kidney damage in people with type 2 diabetes who also have high blood pressure.

Losartan may also be used for purposes not listed in this medication guide.

What is the most important information I should know about losartan?

Do not use losartan if you are pregnant. It could harm the unborn baby. Stop using this medication and tell your doctor right away if you become pregnant during treatment. You should not use this medication if you are allergic to losartan. Drinking alcohol can further lower your blood pressure and may increase certain side effects of losartan. Do not use potassium supplements or salt substitutes while you are taking losartan, unless your doctor has told you to.

Your blood pressure will need to be checked often. Visit your doctor regularly.

Keep using this medication even if you feel fine. High blood pressure often has no symptoms.

In rare cases, losartan can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Call your doctor right away if you have muscle pain, tenderness, or weakness especially if you also have fever, nausea or vomiting, and dark colored urine.

What should I discuss with my healthcare provider before taking losartan?

You should not use this medication if you are allergic to losartan.

To make sure you can safely take losartan, tell your doctor if you have any of these other conditions:

• kidney disease;


• liver disease;


• 
  

  congestive heart failure;

  
  


• 
  

  an electrolyte imbalance (such as low levels of potassium in your blood); or

  
  


• 
  

  if you are dehydrated.

  
  

FDA pregnancy category D. Do not use losartan if you are pregnant. It could harm the unborn baby. Stop using this medication and tell your doctor right away if you become pregnant. Losartan can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. It is not known whether losartan passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take losartan?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

You may take losartan with or without food.

Call your doctor if you have ongoing vomiting or diarrhea, or if you are sweating more than usual. You can easily become dehydrated while taking this medication, which can lead to severely low blood pressure or a serious electrolyte imbalance.

Your blood pressure will need to be checked often. Visit your doctor regularly.

It may take 3 to 6 weeks of using this medicine before your blood pressure is under control. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve after 3 weeks of treatment.

Keep using this medication even if you feel fine. High blood pressure often has no symptoms.

Store at room temperature away from moisture, heat, and light.

See also: Losartan dosage (in more detail)

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include fast or slow heartbeat, dizziness, or feeling like you might pass out.

What should I avoid while taking losartan?

Drinking alcohol can further lower your blood pressure and may increase certain side effects of losartan. Do not use potassium supplements or salt substitutes while you are taking losartan, unless your doctor has told you to. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Losartan side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. In rare cases, losartan can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Call your doctor right away if you have muscle pain, tenderness, or weakness especially if you also have fever, nausea or vomiting, and dark colored urine. Call your doctor at once if you have a serious side effect such as:

• 
  

  feeling like you might pass out;

  
  


• 
  

  pain or burning when you urinate;

  
  


• 
  

  pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;

  
  


• 
  

  wheezing, chest pain;

  
  


• 
  

  drowsiness, confusion, mood changes, increased thirst, loss of appetite, nausea and vomiting;

  
  


• 
  

  swelling, weight gain, feeling short of breath, urinating less than usual or not at all; or

  
  


• 
  

  high potassium (slow heart rate, weak pulse, muscle weakness, tingly feeling).

  
  

Less serious side effects may include:

• 
  

  cold or flu symptoms such as stuffy nose, sneezing, sore throat, fever;

  
  


• 
  

  dry cough;

  
  


• 
  

  muscle cramps;

  
  


• 
  

  pain in your legs or back;

  
  


• 
  

  stomach pain, diarrhea;

  
  


• 
  

  headache, dizziness;

  
  


• 
  

  tired feeling; or

  
  


• 
  

  sleep problems (insomnia).

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Losartan Dosing Information

Usual Adult Dose for Diabetic Nephropathy:

Initial dose: 50 mg orally once a day.
Maintenance dose: 25 to 100 mg orally in 1 to 2 divided doses.

Usual Adult Dose for Hypertension:

Initial dose: 50 mg orally once a day.
Maintenance dose: 25 to 100 mg orally in 1 to 2 divided doses.

What other drugs will affect losartan?

Tell your doctor about all other medicines you use, especially:

• 
  

  a diuretic (water pill);

  
  


• 
  

  lithium (Eskalith, Lithobid);

  
  


• 
  

  celecoxib (Celebrex); or

  
  


• 
  

  aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen (Motrin, Advil), diclofenac (Cataflam, Voltaren), etodolac (Lodine), indomethacin (Indocin), nabumetone (Relafen), naproxen (Aleve, Naprosyn), meloxicam (Mobic), piroxicam (Feldene), and others.

  
  

This list is not complete and other drugs may interact with losartan. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More losartan resources

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

• losartan Advanced Consumer (Micromedex) - Includes Dosage Information


• Losartan MedFacts Consumer Leaflet (Wolters Kluwer)


• Losartan Prescribing Information (FDA)


• Cozaar Prescribing Information (FDA)


• Cozaar Monograph (AHFS DI)


• Cozaar Consumer Overview

Compare losartan with other medications

• Diabetic Kidney Disease
• High Blood Pressure

Where can I get more information?

• Your pharmacist can provide more information about losartan.

See also: losartan side effects (in more detail)

Paracetamol and Codeine Caplets

Paracetamol & Codeine Caplets (Boots Company plc)

Read all of this leaflet carefully because it contains important information for you.

This medicine is available without prescription to treat minor conditions. However, you still need to take it carefully to get the best results from it.

• This medicine can only be used for the short term treatment of acute moderate pain such as headache, period pain, neuralgia, toothache and rheumatic pain that is not relieved by aspirin, ibuprofen or paracetamol alone


• 
  You should only take this product for a maximum of 3 days at a time. If you need to take it for longer than 3 days you should see your doctor or pharmacist for advice


• 
  This medicine contains codeine which can cause addiction if you take it continuously for more than 3 days. This can give you withdrawal symptoms from the medicine when you stop taking it


• 
  If you take this medicine for headaches for more than 3 days it can make them worse


• Keep this leaflet, you may need to read it again


• Ask your pharmacist if you need more information or advice

What this medicine is for

This medicine contains Codeine and Paracetamol which belong to a group of medicines called analgesics to relieve pain.

It can be used for the short term treatment of acute moderate pain such as headache, period pain, neuralgia, toothache and rheumatic pain that is not relieved by aspirin, ibuprofen or paracetamol alone.

Before you take this medicine

• 
  This medicine contains codeine which can cause addiction if you take it continuously for more than 3 days. This can give you withdrawal symptoms from the medicine when you stop taking it


• 
  If you take a painkiller for headaches for more than 3 days it can make them worse This medicine can be taken by adults and children aged 6 years and over. However, some people should not take this medicine or should seek the advice of their pharmacist or doctor first.

Do not take:

• 
  If you are allergic to any of the ingredients


• 
  If you have severe liver disease
  


• 
  If you are pregnant
  

Talk to your pharmacist or doctor:

• If you have kidney problems


• If you have other liver problems (including a disease caused by drinking alcohol)


• If you are breastfeeding

Other important information

Information about some of the ingredients in this medicine: Sodium metabisulphite (E223) may rarely cause severe allergic reactions, tightness of the chest or difficulty in breathing.

If you take other medicines

This medicine contains paracetamol. Do not take with any other paracetamol containing products.

Before you take these caplets, make sure that you tell your pharmacist about ANY other medicines you might be using at the same time, particularly the following:

• Domperidone or metoclopramide, for nausea and vomiting (may increase the pain relief effect of paracetamol or the codeine in this medicine may reduce the effect of these medicines on the stomach)


• Colestyramine, for lowering blood lipid levels (may reduce the pain relief effect of paracetamol)


• Warfarin or other coumarins (for thinning the blood) – if you take warfarin you can take occasional doses of this medicine, but talk to your doctor first before you take it on a regular basis


• Mexiletine (for heart rhythm problems) – codeine may reduce the effects of this medicine


• Sleeping tablets, sedatives, tricylic antidepressants or phenothiazine tranquillisers (you may feel more sleepy if you take these medicines)

If you are unsure about interactions with any other medicines, talk to your pharmacist. This includes medicines prescribed by your doctor and medicine you have bought for yourself, including herbal and homeopathic remedies.

How to take this medicine

Check the foil is not broken before first use. If it is, do not take that caplet.

Adults and children of 12 years and over

Take one or two caplets

Every 4 to 6 hours if you need to.

Don't take more than 8 caplets in any 24 hours.

Children of 6 to 11 years

Take half to one caplet

Every 4 to 6 hours if you need to.

Don't take more than 4 caplets in any 24 hours.

Swallow each caplet whole with water.

Do not take for more than 3 days. If you need to use this medicine for more than 3 days you must speak to your doctor or pharmacist.

Do not give to children under 6 years.

Do not take more than the amount recommended above.

If symptoms persist consult your doctor.

If you take too many caplets: Immediate medical advice should be sought in the event of an overdose, even if you feel well, because of the risk of delayed, serious liver damage. Go to your nearest hospital casualty department. Take your medicine and this leaflet with you.

Possible withdrawal effects when stopping treatment

This medicine contains codeine and can cause addiction if you take it continuously for more than 3 days. When you stop taking it you may get withdrawal symptoms. You should talk to your doctor or pharmacist if you think you are suffering from withdrawal symptoms.

Possible side effects

Most people will not have problems, but some people may have side effects when taking this medicine. If you have any unwanted side effects you should seek advice from your doctor, pharmacist or other healthcare professional.

Also you can help to make sure that medicines remain as safe as possible by reporting any unwanted side effects via the internet at www.yellowcard.gov.uk; alternatively you can call Freephone 0808 100 3352 (available between 10 am – 2 pm Monday-Friday) or fill in a paper form available from your local pharmacy.

If you get any of these serious side effects, stop taking the caplets. See a doctor at once:

• Difficulty in breathing, swelling of the face, neck, tongue or throat (severe allergic reactions)

These other effects are less serious. If they bother you talk to a pharmacist:

• Other allergic reactions (e.g. skin rash)


• Feeling sick, being sick


• Constipation, dry mouth, sweating


• Unusual bruising, or infections such as sore throats – this may be a sign of very rare changes in the blood

If any side effect becomes severe, or you notice any side effect not listed here, please tell your pharmacist or doctor.

How do I know if I am addicted?

If you take the medicine according to the instructions on the pack it is unlikely that you will become addicted to the medicine. However, if the following apply to you it is important that you talk to your doctor:

• You need to take the medicine for longer periods of time


• You need to take more than the recommended amount


• When you stop taking the medicine you feel very unwell but you feel better if you start taking the medicine again

How to store this medicine

Keep this medicine in a safe place out of the sight and reach of children, preferably in a locked cupboard.

Use by the date on the end flap of the carton.

What is in this medicine

Each tablet contains Codeine Phosphate Hemihydrate 8 mg, Paracetamol 500 mg, which are the active ingredients.

As well as the active ingredients, the tablets also contain maize starch, microcrystalline cellulose, magnesium stearate, sodium metabisulphite (E223)

This pack contains 32 white capsule shaped tablets.

Who makes this medicine

Manufactured for the Marketing Authorisation holder

The Boots Company PLC

Nottingham

NG2 3AA

by

Hamol Limited Nottingham

NG90 2DB

Leaflet prepared December 2009

P

If you would like any further information about this medicine, please contact

The Boots Company PLC

Nottingham

NG2 3AA

Other formats

To request a copy of this leaflet in Braille, large print or audio please call, free of charge:

0800 198 5000 (UK only)

Please be ready to give the following information:

Product name: Boots Paracetamol & Codeine Caplets

Reference number: 00014/0251

This is a service provided by the Royal National Institute of Blind People.

BTC51565 vF 18/01/10

Bedranol 160mg SR Capsules

1. Name Of The Medicinal Product

Bedranol* (Propranolol Hydrochloride) SR Capsules 160mg[1].

2. Qualitative And Quantitative Composition

Each capsule contains propranolol hydrochloride BP 160mg.

3. Pharmaceutical Form

Sustained release capsule.

4. Clinical Particulars

4.1 Therapeutic Indications

a) Control of hypertension.

b) Management of angina.

c) Prophylaxis of migraine.

d) Management of essential tremor.

e) Management of anxiety.

f) Adjunctive management of thyrotoxicosis.

g) Prophylaxis of upper gastro-intestinal bleeding in patients with portal hypertension and oesophageal varices.

4.2 Posology And Method Of Administration

Adults:

(i) Hypertension

The initial dose is usually 160mg daily taken orally in the morning or evening. An adequate response is seen by most patients at this dosage. If necessary the dose can be increased to 320mg. A further reduction in blood pressure may be achieved by combining Bedranol* SR with other anti-hypertensive agents.

(ii) Angina, essential tremor, thyrotoxicosis, and the prophylaxis of migraine

The usual dose is 80mg daily, taken orally in the morning or evening. The dose may be increased to 160mg, and then if necessary further increased to 240mg per day.

(iii) Situational and generalised anxiety

A daily dose of one Bedranol* SR 80 mg Capsule should be sufficient to provide short-term relief of acute situational anxiety. Generalised anxiety, requiring longer term therapy, usually responds adequately at the same dosage. In some case the dosage may be increased to 160 mg. Patients should be reviewed after 6 – 12 months of treatment.

(iv) Portal hypertension

Dosage should be aimed to achieve approximately 25% reduction in resting heart rate. Dosing should initiated at 80 mg increasing to 160 mg depending on heart rate response. Further 80 mg increments may be added up to a maximum dose of 320 mg once daily.

Elderly patients:

The evidence concerning the relationship between blood level and age is conflicting. For patients already established on 160mg propranolol daily, one capsule of Bedranol* SR may be given. It is suggested that elderly patients being started off on propranolol treatment may need smaller initial doses and in these circumstances an alternative preparation should be used.

Children:

Bedranol* SR is not suitable for use in children.

Method of administration: Oral.

4.3 Contraindications

Bedranol* SR must not be used if any of the following conditions are present:

• hypersensitivity to propranolol or any of the other ingredients

• a history of bronchospasm or asthma

• bradycardia

• second or third degree heart block

• sick sinus syndrome

• cardiogenic shock

• uncontrolled heart failure

• hypotension

• severe peripheral arterial disease

• Prinzmetal's angina

• untreated phaeochromocytoma

• prolonged fasting, or prone to hypoglycaemia

• metabolic acidosis.

4.4 Special Warnings And Precautions For Use

Patients with a history of wheezing or asthma should not take propranolol unless it is considered essential. The label will carry the following warning: “Do not take this medicine if you have a history of wheezing or asthma.”. The patient information leaflet will state “Do not take this medicine if you have a history of wheezing or asthma. Consult your doctor or pharmacist first.”.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Intolerance to propranolol, shown as bradycardia and hypotension may occur, in which case propranolol should be withdrawn. If necessary, treatment for overdose should be started.

Beta-blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions, they also may make patients less responsive to doses of adrenaline used to treat the allergic reactions.

Withdrawal of the drug for any reason should be gradual.

In patients with ischaemic heart disease treatment must not be discontinued abruptly. Either the equivalent dose of another beta-blocker may be substituted, or the withdrawal of Bedranol* SR should be gradual. This can be carried out by substituting the equivalent dose in propranolol 40mg tablets and then reducing the dose.

Bedranol* SR should be used with caution in patients whose cardiac reserve is poor.

Bedranol* SR may aggravate peripheral arterial circulatory disturbances.

As propranolol has a negative effect on conduction time, care must be taken when giving it to patients with first degree heart block.

Care must be taken in patients with renal or hepatic dysfunction when beginning treatment and choosing the initial dose.

Bedranol* SR should be used with care in patients with decompensated cirrhosis.

In patients with portal hypertension, liver function may deteriorate. There have been reports that treatment with propranolol may increase the risk of developing hepatic encephalopathy.

Propranolol, as with other beta-blocking drugs may block the symptoms of hypoglycaemia (especially tachycardia). It may even cause hypoglycaemia in non-diabetic patients e.g. neonates, infants, children, elderly patients, patients on haemodialysis or patients suffering from chronic liver disease and patients suffering from overdose. It has rarely caused seizures and/or coma in isolated patients. Caution should be exercised in the concurrent use of propranolol therapy in diabetic patients as it may prolong the hypoglycaemic response to insulin.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Care should be taken when prescribing beta-adrenoceptor blocking drugs with Class 1 antidysrhythmic agents there is an increased risk of myocardial depression and bradycardia, there is also an increased risk of lidocane toxicity. The antidysrhythmic propafenone increases plasma concentration of propranolol.

Beta-adrenoceptor blocking drugs should be used with caution in combination with calcium channel blockers such as verapamil or diltiazem in patients with impaired ventricular function. These should not be given to patients with conduction abnormalities. Beta-blockers or calcium channel blockers should not be given intravenously within 48 hours of discontinuing either one or the other.

Use with nifedipine or other dihydropyridines may cause an increased risk of hypotension, and heart failure may occur in patients with undiscovered cardiac insufficiency.

Propranolol modifies the tachycardia of hypoglycaemia and care should be taken when treating diabetic patients with Bedranol* SR whether or not they are also taking hypoglycaemic agents. Propranolol may prolong the hypoglycaemic response to insulin.

Use of adrenaline or other sympathomimetics with propranolol may counteract the effect of propranolol. Care should be taken in giving parenteral administration of adrenaline to patients taking beta-blocking drugs as, rarely, vasoconstriction, hypertension and bradycardia may result.

Rebound hypertension which can follow after withdrawal of clonidine may be exacerbated by beta-blockers. Therefore, if the patient is transferring from clonidine to propranolol, the latter treatment should be started several days after clonidine has been stopped. If Bedranol* SR and clonidine are given together, clonidine should be discontinued several days after stopping treatment with Bedranol* SR.

Digitoxin or digoxin taken at the same time as beta-blockers can increase atrioventricular conduction time.

Ergotamine, dihydroergotamine or related compounds given with propranolol have resulted in reports of vasospastic reactions in some patients.

The hypotensive effects of propranolol may be decreased if the patient also takes prostaglandin synthetase inhibitors, e.g. ibuprofen or indometacin.

If propranolol is taken with chlorpromazine, plasma levels of both agents may be increased, leading to enhanced antipsychotic and elevated antihypertensive effects.

Concomitant administration of rifampicin with propranolol may result in reduced plasma concentrations of propranolol. Thyroxine taken at the same time as propranolol also has this effect.

Cimetidine taken at the same time as propranolol will increase propranolol plasma levels. Fluvoxamine taken with propranolol also has this effect.

Alcohol enhances hypotensive effect.

It may be necessary to withdraw Bedranol* SR before surgery (24 hours should be allowed to elapse between the last dose and anaesthesia). If Bedranol* SR is continued throughout surgery the anaesthetist should be told and care should be taken in selecting and using suitable anaesthetic agents (note bupivacaine toxicity with propranolol)). An anaesthetic agent with as little myocardial depression as possible should be used. Beta-blockers used with anaesthesic agents may result in attenuation of reflex tachycardia and the risk of hypotension may increase.

Propranolol may affect lignocaine infusion by increasing the plasma concentration of lignocaine by approximately a third and therefore this should be avoided.

ACE inhibitors and Angiotensin-II Antagonists taken at the same time as propranolol may result in enhanced hypotensive effects. Aldesleukin and Alprostadil also has this effect.

Concomitant administration of corticosteroid may result in antagonism of hypotensive effect.

Propranolol may increase plasma concentration of rizatriptan when taken concomitantly.

Beta blockers including propranolol when taken with moxisylyte may result in severe postural hypotension

Concomitant administration of muscle relaxants may result in enhanced hypotensive effect.

Oestrogen and progestrogens, as used in the contraceptive pill, when taken with propranolol may antagonise the hypotensive effect.

The manufacturer of tropisetron advises caution for the co-administration with propranolol.

The concomitant administration of xamoterol with propranolol may result in a reduction in the beta-blockade.

Parasympathomimetics when used with propranolol increase the possibility of arrhythmias.

Interference with laboratory tests: Propranolol has been reported to interfere with the estimation of serum bilirubin by the diazo method and with the determination of catecholamines by methods using fluorescence.

4.6 Pregnancy And Lactation

Although there is no evidence that propranolol is teratogenic Bedranol* SR should not be used in pregnancy unless absolutely necessary. Beta-blockers reduce placental perfusion which may result in intra-uterine foetal death, immature or premature deliveries. Bradycardia may occur in the foetus and there may be an increased risk of cardiac and pulmonary problems in the post-natal period. Hypoglycaemia or bradycardia may occur in the neonate.

Breast-feeding is not recommended as beta-blockers taken by the mother will pass into the breast-milk.

4.7 Effects On Ability To Drive And Use Machines

Bedranol* SR should not impair ability to drive and use machines. However, sometimes dizziness or tiredness may occur. If so, the patient should not drive or operate machines.

4.8 Undesirable Effects

The following undesirable effects may occur.

Cardiovascular: deterioration of heart failure, bradycardia, postural hypotension with or without syncope may occur. Heart block, intermittent claudication or Raynaud's phenomenon may be precipitated or exacerbated. Cold extremities may occur.

Central nervous system: dizziness, confusion, mood changes, depression or psychosis and hallucinations, sleep disturbances or nightmares may occur.

Special senses: reports of visual disturbances, conjunctivitis or dry eyes have been made.

Peripheral nervous system: peripheral neuropathy or myopathies or paraesthesia may occur.

Gastrointestinal: GI disturbance including nausea, vomiting, diarrhoea, constipation or abdominal cramps have been reported.

Haematological: thrombocytopenia, purpura and rarely agranulocytosis. Eosinophilia may occur which passes quickly.

Hepatic: propranolol treatment may increase the risk of developing hepatic encephalopathy.

Respiratory: bronchospasm may occur in patients with bronchial asthma or a history of asthma. Fatalities have been reported.

Skin and hair: exacerbation of psoriasis, psoriasiform skin reactions, skin rashes, pruritus, or alopecia may occur.

Endocrine: hypoglycaemia in neonates, infants, children, elderly patients, patients on haemodialysis, patients on concomitant anti-diabetic therapy, patients with prolonged fasting and patients with chronic liver disease has been reported (see section 4.3, 4.4, 4.5).

Miscellaneous: headache, sexual dysfunction,fatigue (commonly), lassitude (often passing quickly), and an increase in antinuclear antibodies have been observed. There have been isolated reports of a myasthenia gravis-like syndrome or aggravation of myasthenia gravis.

Intolerance to propranolol, shown as bradycardia and hypotension may occur, in which case propranolol should be withdrawn. If necessary, treatment for overdose should be started.

Propranolol should be discontinued gradually if the patient's well-being is adversely affected by any undesirable effects.

4.9 Overdose

Symptoms of overdose: bradycardia, hypotension, bronchospasm and acute cardiac insufficiency.

General supportive measures should be employed such as gastric lavage, activated charcoal and a laxative to stop any remaining drug being absorbed. Shock treatment, if required should be given. Excessive bradycardia may be countered with 1-2mg IV atropine, followed if necessary by glucagon 10mg IV. This may be repeated, or followed by an intravenous infusion of glucagon 1-10mg/hour according to response. Alternatively, a beta-receptor stimulant such as isoprenaline 25mcg IV, orciprenaline 500mcg (0.5mg) IV or dobutamine 2.5-10mcg/kg/minute IV may be given.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Propranolol is a competitive blocker of beta-adrenergic receptor sites.

5.2 Pharmacokinetic Properties

Following oral administration Bedranol* SR peak plasma levels occur approximately 7 to 8.5 hours after an oral dose. Individual plasma concentrations vary. The plasma half-life of propranolol is about 3 to 6 hours. Propranolol binds well to plasma proteins. It has high lipid solubility, and crosses the blood-brain barrier, placenta and enters breast milk.

Propranolol is absorbed almost completely from the gastrointestinal tract, but binds to hepatic tissue where it is subject to first-pass metabolism.

Propranolol is metabolised in the liver, and excreted in the urine as metabolites and unchanged drug.

5.3 Preclinical Safety Data

There are no preclinical safety data of relevance to the prescriber.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Capsule contents:

Sucrose

Corn starch

Shellac

Talc

Capsule shell:

Gelatin

Titanium dioxide (E171)

Erythrosine (E127)

Printing ink:

Shellac

Black iron oxide (E172)

Propylene glycol

6.2 Incompatibilities

Not known.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

Store in a cool dry place and protect from light.

6.5 Nature And Contents Of Container

Polypropylene securitainers with polyethylene closures. Pack sizes[2]: 28, 30, 56, 60 and 100.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Sandoz Ltd

Frimley Business Park,

Frimley,

Camberley,

Surrey,

GU16 7SR.

United Kingdom

8. Marketing Authorisation Number(S)

PL 4416/0068

9. Date Of First Authorisation/Renewal Of The Authorisation

7 July 1988/7 July 1993

10. Date Of Revision Of The Text

11/2010

[1] NB This product is also known as Propanix 160-SR (for own label supply by Ashbourne Pharmaceuticals Ltd), Lopranol LA (for own label supply by Opus Pharmaceuticals only), Probeta LA (for own label supply by Trinity Pharmaceuticals Ltd only) and Rapranol (Propranolol Hydrochloride) SR 160mg Capsules (supplied by Ranbaxy (UK) Ltd. Only the relevant product name will be used throughout.

[2] Only marketed pack sizes will be shown.

* trade mark