Web PLR Content Directory Colorado: 2016

Thursday, 29 September 2016

Cartaretin

Cartaretin may be available in the countries listed below.

Ingredient matches for Cartaretin

Calcium Carbonate

Calcium Carbonate is reported as an ingredient of Cartaretin in the following countries:

Japan

International Drug Name Search

Sahne

Sahne may be available in the countries listed below.

Ingredient matches for Sahne

Retinol

Retinol is reported as an ingredient of Sahne in the following countries:

Japan

International Drug Name Search

Carofertin

Carofertin may be available in the countries listed below.

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Carofertin

Betacarotene

Betacarotene is reported as an ingredient of Carofertin in the following countries:

Austria

Germany

Poland

International Drug Name Search

Wednesday, 28 September 2016

Cynocort

Cynocort may be available in the countries listed below.

Ingredient matches for Cynocort

Triamcinolone

Triamcinolone 16α,17α-acetonide (a derivative of Triamcinolone) is reported as an ingredient of Cynocort in the following countries:

Bangladesh

International Drug Name Search

Carovit

Carovit may be available in the countries listed below.

Ingredient matches for Carovit

Betacarotene

Betacarotene is reported as an ingredient of Carovit in the following countries:

Turkey

International Drug Name Search

Carpilo

Carpilo may be available in the countries listed below.

Ingredient matches for Carpilo

Carteolol

Carteolol hydrochloride (a derivative of Carteolol) is reported as an ingredient of Carpilo in the following countries:

France

Pilocarpine

Pilocarpine hydrochloride (a derivative of Pilocarpine) is reported as an ingredient of Carpilo in the following countries:

France

International Drug Name Search

Viread

In the US, Viread (tenofovir systemic) is a member of the drug class nucleoside reverse transcriptase inhibitors (NRTIs) and is used to treat Hepatitis B, HIV Infection and Nonoccupational Exposure.

US matches:

Viread

UK matches:

Viread 245 mg film-coated tablets (SPC)

Ingredient matches for Viread

Tenofovir

Tenofovir is reported as an ingredient of Viread in the following countries:

Turkey

Tenofovir disoproxil fumarate (a derivative of Tenofovir) is reported as an ingredient of Viread in the following countries:

Argentina

Australia

Austria

Belgium

Canada

Chile

Cyprus

Czech Republic

Denmark

Finland

France

Germany

Greece

Hungary

Iceland

Ireland

Israel

Italy

Japan

Luxembourg

Mexico

Netherlands

New Zealand

Norway

Poland

Slovakia

South Africa

Spain

Sweden

Switzerland

United Kingdom

United States

International Drug Name Search

Glossary

SPC

Summary of Product Characteristics (UK)

Click for further information on drug naming conventions and International Nonproprietary Names.

Cloroptic

Cloroptic may be available in the countries listed below.

Ingredient matches for Cloroptic

Chloramphenicol

Chloramphenicol is reported as an ingredient of Cloroptic in the following countries:

Peru

International Drug Name Search

Calcilift - Bolus

Calcilift - Bolus may be available in the countries listed below.

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Calcilift - Bolus

Calcium Formate

Calcium Formate is reported as an ingredient of Calcilift - Bolus in the following countries:

Germany

Magnesium Chloride

Magnesium Chloride is reported as an ingredient of Calcilift - Bolus in the following countries:

Germany

Magnesium Oxide

Magnesium Oxide is reported as an ingredient of Calcilift - Bolus in the following countries:

Germany

International Drug Name Search

Cylocide

Cylocide may be available in the countries listed below.

Ingredient matches for Cylocide

Cytarabine

Cytarabine is reported as an ingredient of Cylocide in the following countries:

Japan

Taiwan

International Drug Name Search

Carnitine Chloride

Carnitine Chloride may be available in the countries listed below.

Ingredient matches for Carnitine Chloride

Carnitine

Carnitine Chloride (JAN) is also known as Carnitine (Rec.INN)

International Drug Name Search

Glossary

JAN	Japanese Accepted Name
Rec.INN	Recommended International Nonproprietary Name (World Health Organization)

Click for further information on drug naming conventions and International Nonproprietary Names.

Generic Name: prenatal multivitamins (PRE nay tal VYE ta mins)

Brand Names: Advance Care Plus, Bright Beginnings, Cavan Folate, Cavan One, Cavan-Heme OB, Cenogen Ultra, CitraNatal Rx, Co Natal FA, Complete Natal DHA, Complete-RF, CompleteNate, Concept OB, Docosavit, Dualvit OB, Duet, Edge OB, Elite OB 400, Femecal OB, Folbecal, Folcaps Care One, Folivan-OB, Foltabs, Gesticare, Icar Prenatal, Icare Prenatal Rx, Inatal Advance, Infanate DHA, Kolnatal DHA, Lactocal-F, Marnatal-F, Maternity, Maxinate, Mission Prenatal, Multi-Nate 30, Multinatal Plus, Nata 29 Prenatal, Natachew, Natafort, Natelle, Neevo, Nestabs, Nexa Select with DHA, Novanatal, NovaStart, O-Cal Prenatal, OB Complete, OB Natal One, Ob-20, Obtrex DHA, OptiNate, Paire OB Plus DHA, PNV Select, PNV-Total, PR Natal 400, Pre-H-Cal, Precare, PreferaOB, Premesis Rx, PrenaCare, PrenaFirst, PrenaPlus, Prenatabs OBN, Prenatabs Rx, Prenatal 1 Plus 1, Prenatal Elite, Prenatal Multivitamins, Prenatal Plus, Prenatal S, Prenatal-U, Prenate Advanced Formula, Prenate DHA, Prenate Elite, Prenavite FC, PreNexa, PreQue 10, Previte Rx, PrimaCare, Pruet DHA, RE OB Plus DHA, Renate, RightStep, Rovin-NV, Se-Care, Se-Natal One, Se-Plete DHA, Se-Tan DHA, Select-OB, Seton ET, Strongstart, Stuart Prenatal with Beta Carotene, Tandem OB, Taron-BC, Tri Rx, TriAdvance, TriCare, Trimesis Rx, Trinate, Triveen-PRx RNF, UltimateCare Advance, Ultra-Natal, Vemavite PRX 2, VeNatal FA, Verotin-BY, Verotin-GR, Vinacal OR, Vinatal Forte, Vinate Advanced (New Formula), Vinate AZ, Vinate Care, Vinate Good Start, Vinate II (New Formula), Vinate III, Vinate One, Vitafol-OB, VitaNatal OB plus DHA, Vitaphil, Vitaphil Aide, Vitaphil Plus DHA, Vitaspire, Viva DHA, Vol-Nate, Vol-Plus, Vol-Tab Rx, Vynatal F.A., Zatean-CH, Zatean-PN

What are Renate DHA (prenatal multivitamins)?

There are many brands and forms of prenatal vitamin available and not all brands are listed on this leaflet.

Prenatal vitamins are a combination of many different vitamins that are normally found in foods and other natural sources.

Prenatal vitamins are used to provide the additional vitamins needed during pregnancy. Minerals may also be contained in prenatal multivitamins.

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

What is the most important information I should know about prenatal vitamins?

There are many brands and forms of prenatal vitamin available and not all brands are listed on this leaflet.

Never take more than the recommended dose of a multivitamin. Avoid taking any other multivitamin product within 2 hours before or after you take your prenatal vitamins. Taking similar vitamin products together at the same time can result in a vitamin overdose or serious side effects.

Many multivitamin products also contain minerals such as calcium, iron, magnesium, potassium, and zinc. Minerals (especially taken in large doses) can cause side effects such as tooth staining, increased urination, stomach bleeding, uneven heart rate, confusion, and muscle weakness or limp feeling. Read the label of any multivitamin product you take to make sure you are aware of what it contains.

Seek emergency medical attention if you think you have used too much of this medicine. An overdose of vitamins A, D, E, or K can cause serious or life-threatening side effects and can also harm your unborn baby. Certain minerals contained in a prenatal multivitamin may also cause serious overdose symptoms or harm to the baby if you take too much.

Overdose symptoms may include stomach pain, vomiting, diarrhea, constipation, loss of appetite, hair loss, peeling skin, tingly feeling in or around your mouth, changes in menstrual periods, weight loss, severe headache, muscle or joint pain, severe back pain, blood in your urine, pale skin, and easy bruising or bleeding.

Do not take this medication with milk, other dairy products, calcium supplements, or antacids that contain calcium. Calcium may make it harder for your body to absorb certain ingredients of the multivitamin.

What should I discuss with my healthcare provider before taking prenatal vitamins?

Many vitamins can cause serious or life-threatening side effects if taken in large doses. Do not take more of this medication than directed on the label or prescribed by your doctor.

Before taking prenatal vitamins, tell your doctor about all of your medical conditions.

You may need to continue taking prenatal vitamins if you breast-feed your baby. Ask your doctor about taking this medication while breast-feeding.

How should I take prenatal vitamins?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended.

Never take more than the recommended dose of prenatal vitamins.

Take your prenatal vitamin with a full glass of water.

Swallow the regular tablet or capsule whole. Do not break, chew, crush, or open it.

The chewable tablet must be chewed or allowed to dissolve in your mouth before swallowing. You may also allow the chewable tablet to dissolve in drinking water, fruit juice, or infant formula (but not milk or other dairy products). Drink this mixture right away.

Use prenatal vitamins regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Store at room temperature away from moisture and heat. Keep prenatal vitamins in their original container. Storing vitamins in a glass container can ruin the medication.

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?

What should I avoid while taking prenatal vitamins?

Avoid taking any other multivitamin product within 2 hours before or after you take your prenatal vitamins. Taking similar vitamin products together at the same time can result in a vitamin overdose or serious side effects.

Avoid the regular use of salt substitutes in your diet if your multivitamin contains potassium. If you are on a low-salt diet, ask your doctor before taking a vitamin or mineral supplement.

Prenatal vitamins 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.

When taken as directed, prenatal vitamins are not expected to cause serious side effects. Less serious side effects may include:

upset stomach;

headache; or

unusual or unpleasant taste in your mouth.

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.

What other drugs will affect prenatal vitamins?

Vitamin and mineral supplements can interact with certain medications, or affect how medications work in your body. Before taking a prenatal vitamin, tell your doctor if you also use:

diuretics (water pills);

heart or blood pressure medications;

tretinoin (Vesanoid);

isotretinoin (Accutane, Amnesteen, Clavaris, Sotret);

trimethoprim and sulfamethoxazole (Cotrim, Bactrim, Gantanol, Gantrisin, Septra, TMP/SMX); or

an NSAID (non-steroidal anti-inflammatory drug) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Cataflam, Voltaren), indomethacin (Indocin), meloxicam (Mobic), and others.

This list is not complete and other drugs may interact with prenatal vitamins. 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 Renate DHA resources

Renate DHA Side Effects (in more detail)
Renate DHA Use in Pregnancy & Breastfeeding
Renate DHA Drug Interactions
Renate DHA Support Group
0 Reviews for Renate DHA - Add your own review/rating

Renate DHA Prescribing Information (FDA)

Cal-Nate MedFacts Consumer Leaflet (Wolters Kluwer)

CareNatal DHA MedFacts Consumer Leaflet (Wolters Kluwer)

CitraNatal 90 DHA MedFacts Consumer Leaflet (Wolters Kluwer)

CitraNatal Assure Prescribing Information (FDA)

CitraNatal Harmony Prescribing Information (FDA)

Concept DHA Prescribing Information (FDA)

Docosavit Prescribing Information (FDA)

Duet DHA with Ferrazone MedFacts Consumer Leaflet (Wolters Kluwer)

Folbecal MedFacts Consumer Leaflet (Wolters Kluwer)

Folcal DHA Prescribing Information (FDA)

Folcaps Care One Prescribing Information (FDA)

Gesticare DHA Prescribing Information (FDA)

Gesticare DHA MedFacts Consumer Leaflet (Wolters Kluwer)

Inatal Advance Prescribing Information (FDA)

Inatal Ultra Prescribing Information (FDA)

Multi-Nate DHA Prescribing Information (FDA)

Multi-Nate DHA Extra Prescribing Information (FDA)

MultiNatal Plus MedFacts Consumer Leaflet (Wolters Kluwer)

Natelle One Prescribing Information (FDA)

Neevo Caplets MedFacts Consumer Leaflet (Wolters Kluwer)

Neevo DHA MedFacts Consumer Leaflet (Wolters Kluwer)

OB Complete 400 MedFacts Consumer Leaflet (Wolters Kluwer)

Paire OB Plus DHA Prescribing Information (FDA)

PreNexa MedFacts Consumer Leaflet (Wolters Kluwer)

PreNexa Prescribing Information (FDA)

PreferaOB Prescribing Information (FDA)

Prenatal Plus Prescribing Information (FDA)

Prenatal Plus Iron Prescribing Information (FDA)

Prenate Elite Prescribing Information (FDA)

Prenate Elite MedFacts Consumer Leaflet (Wolters Kluwer)

Prenate Elite tablets

Prenate Essential Prescribing Information (FDA)

PrimaCare Advantage MedFacts Consumer Leaflet (Wolters Kluwer)

PrimaCare ONE capsules

PrimaCare One MedFacts Consumer Leaflet (Wolters Kluwer)

Se-Natal 19 Chewable Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

Se-Natal 19 Prescribing Information (FDA)

Tandem DHA Prescribing Information (FDA)

Tandem OB Prescribing Information (FDA)

TriAdvance Prescribing Information (FDA)

Triveen-One MedFacts Consumer Leaflet (Wolters Kluwer)

Triveen-PRx RNF Prescribing Information (FDA)

UltimateCare ONE NF Prescribing Information (FDA)

Ultra NatalCare MedFacts Consumer Leaflet (Wolters Kluwer)

Vinate AZ Prescribing Information (FDA)

Vitafol-One MedFacts Consumer Leaflet (Wolters Kluwer)

Zatean-CH Prescribing Information (FDA)

Compare Renate DHA with other medications

Vitamin/Mineral Supplementation during Pregnancy/Lactation

Where can I get more information?

Your pharmacist can provide more information about prenatal vitamins.

See also: Renate DHA side effects (in more detail)

Tuesday, 27 September 2016

Pidezol

Pidezol may be available in the countries listed below.

Ingredient matches for Pidezol

Zolpidem

Zolpidem tartrate (a derivative of Zolpidem) is reported as an ingredient of Pidezol in the following countries:

Hungary

International Drug Name Search

Oxytetracycline Tablets BP 250mg

1. Name Of The Medicinal Product

OXYTETRACYCLINE TABLETS BP 250mg

Ashbourne's Pharmaceuticals Product Only

Oxytetramix ® 250

Oxytetracycline Tablets 250mg

2. Qualitative And Quantitative Composition

Each tablet contains 250mg Oxytetracycline Dihydrate PhEur.

3. Pharmaceutical Form

Yellow film-coated tablets.

Yellow, circular, biconvex film-coated tablets, impressed “C” on one face and the identifying letters “OT” on the reverse.

4. Clinical Particulars

4.1 Therapeutic Indications

Oxytetracycline is a bacteriostatic broad-spectrum antibiotic, active against a wide variety of Gram-positive and Gram-negative organisms.

Infections caused by oxytetracycline-sensitive organisms include:

1) Respiratory tract infections: Pneumonia, whooping cough and other lower respiratory tract infections due to susceptible strains of Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae and other organisms. Mycoplasma pneumoniae pneumonia. Treatment of chronic bronchitis (including the prophylaxis of acute exacerbations).

2) Urinary tract infections: caused by susceptible strains of the Klebsiella species. Enterobacter species, Escherichia coli, Streptococcus faecalis and other organisms.

3) Sexually transmitted diseases: Infections due to Chlamydia trachomatis including uncomplicated urethral, endocervical or rectal infections. Non-gonococcal urethritis caused by Ureaplasma urealyticum. Oxytetracycline is also indicated in chancroid, granuloma inguinale and lymphogranuloma venereum. Oxytetracycline is an alternative drug in the treatment of gonorrhoea and syphilis.

4) Skin Infections: Acne vulgaris when antibiotic therapy is considered necessary and severe rosacea.

5) Ophthalmic infections: Trachoma, although the infectious agent, as judged by immunofluorescence, is not always eliminated. Inclusion conjunctivitis may be treated with oral oxytetracycline alone or in combination with topical agents.

6) Rickettsial infections: Rocky Mountain spotted fever, typhus group, Q fever and Coxiella endocarditis and tick fevers.

7) Other infections: Stagnant loop syndrome. Psittacosis, brucellosis (in combination with streptomycin), cholera, bubonic plague, louse and tick-borne relapsing fever, tularaemia, glanders, melioidosis and acute intestinal amoebiasis (as an adjunct to amoebicides).

Oxytetracycline is an alternative drug in the treatment of leptospirosis, gas-gangrene and tetanus.

4.2 Posology And Method Of Administration

Posology

Oxytetracycline should be given one hour before or two hours after meals, since food and some dairy products interfere with absorption. Therapy should be continued for up to three days after symptoms have subsided.

All infections due to Group A beta-haemolytic streptococci should be treated for at least 10 days.

Adults (including the elderly) and children over 12 years: The minimum recommended dosage is 250mg every six hours. Therapeutic levels are attained more rapidly by the administration of 500mg initially, followed by 250mg every six hours. For severe infections, the dosage may be increased to 500mg every six hours.

Children under 12 years: Contraindicated in this age group.

Elderly: Usual adult dose. Caution should be observed as subclinical renal insufficiency may lead to drug accumulation.

Renal impairment: In general, tetracyclines are contraindicated in renal impairment and the dosing recommendations only apply if use of this class of drug is deemed absolutely essential. Total dosage should be decreased by reduction of recommended individual doses and/or by extending time intervals between doses.

Dosage Recommendations in Specific Infections:

Skin infections: 250-500mg daily in single or divided doses should be administered for at least 3 months in the treatment of acne vulgaris and severe rosacea.

Streptococcal infections: A therapeutic dose of oxytetracycline should be administered for at least 10 days.

Brucellosis: 500mg four times daily accompanied by streptomycin.

Sexually transmitted diseases: 500mg four times daily for 7 days is recommended in the following infections: uncomplicated gonococcal infections (except anorectal infections in men); uncomplicated urethra;, endocervical or rectal infection caused by Chlamydia trachomatis; non-gonoccocal urethritis caused by Ureaplasma urealyticum.

Acute epididymo-orchitis caused by Chlamydia trachomatis, or Neisseria gonorroeae: 500mg four times daily for 10 days.

Primary and Secondary syphilis: 500mg four times daily for 15 days. Syphilis of more than one year's duration, (latent syphilis of uncertain or more than one year's duration, cardiovascular or late benign syphilis) except neurosyphilis, should be treated with 500mg four times daily for 30 days. Patient compliance with this regimen may be difficult so care should be taken to encourage optimal compliance. Close follow-up including laboratory tests, is recommended.

Method of Adminstration

For oral administration.

4.3 Contraindications

Known hypersensitivity to any of the tetracyclines or any of the other ingredients in the formulation; chronic renal/hepatic dysfunction; systemic lupus erythematosus; children under 12 years; pregnancy and breastfeeding women; patients receiving vitamin A or retinoid therapy.

4.4 Special Warnings And Precautions For Use

Tetracycline drugs may cause permanent tooth discoloration (yellow-grey-brown), if administered during tooth development, in the last half of pregnancy and in infancy up to twelve years of age. Enamel hypoplasia has also been reported. This adverse reaction is more common during long-term use of the drug but has been observed following repeated short-term courses.

The anti-anabolic action of tetracyclines may cause an increase in BUN. While this is not a problem in those with normal renal function, in patients with significantly impaired renal function, higher serum levels of oxytetracycline may lead to azotaemia, hyperphosphataemia and acidosis.

When treating venereal disease, where co-existent syphilis is suspected, proper diagnostic procedures should be utilised. In all such cases, monthly serological tests should be made for at least four months.

The use of antibiotics may occasionally result in the overgrowth of nonsusceptible organisms including Candida. Constant observation of the patients is essential. If a resistant organism appears, the antibiotic should be discontinued and appropriate therapy instituted.

In long-term therapy, periodic laboratory evaluation of organ systems, including haematopoietic, renal and hepatic studies should be performed.

High doses of tetracyclines have been associated with a syndrome involving fatty liver degeneration and pancreatitis.

The use of tetracyclines in general is contraindicated in renal impairment due to excessive systemic accumulation and used with caution in patients with hepatic impairment or those receiving drugs which may have hepatotoxic effects; high doses should be avoided.

Care is advised when administering to patients with myasthenia gravis.

Photosensitivity reactions may occur in hypersensitive persons and such patients should be warned to avoid direct exposure to natural or artificial sunlight and to discontinue therapy at the first sign of skin discomfort.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Antacids containing aluminium, calcium, iron, magnesium or zinc may impair absorption of oxytetracycline. Allow two to three hours between doses of oxytetracycline and antacids.

Since oxytetracycline has been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require a downward adjustment of their anticoagulant dosage. Oxytetracycline may prolong the action of coumarin anticoagulants.

Antidiarrhoeal preparations such as kaolin-pectin and bismuth subsalicylate hinder absorption of tetracyclines.

Combination of tetracyclines with diuretics may be detrimental to renal function.

Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving oxytetracycline in conjunction with penicillin.

A few cases of pregnancy or breakthrough bleeding have been attributed to the concurrent use of oxytetracycline with oral contraceptives and alternative contraceptive advice should be sought where necessary.

There have been reports of nephrotoxicity (increased blood urea nitrogen and serum creatinine) and death in some cases when oxytetracycline therapy has been combined with methoxyflurane.

Oxytetracycline may increase the hypoglycaemic effects of insulin and sulphonylureas in patients with diabetes mellitus.

Benign intracranial hypertension has been reported following the concomitant use of tetracyclines and vitamin A or retinoids and therefore concurrent use is contraindicated.

4.6 Pregnancy And Lactation

Not to be used in pregnancy unless essential to the patient's welfare. Tetracyclines cross the placenta and may have toxic effects on foetal tissues, particularly on skeletal development, (see "Warnings" on tooth development).

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the foetus. Tetracyclines are also excreted in breast milk and are therefore contraindicated in nursing mothers.

Use in newborns, infants and children: All tetracyclines form a stable calcium complex in any bone-forming tissue.

A decrease in fibula growth rate has been observed in premature infants given oral tetracycline in doses of 25mg/kg every 6 hours. This reaction was reversed when drug was discontinued.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Very common (

Blood and lymphatic disorders:

Frequency not known: Haemolytic anaemia, thrombocytopenia, neutropenia, eosinophilia.

Endocrine disorders:

Frequency not known: brown-black microscopic discoloration of thyroid tissue in use over prolonged periods (No abnormalities of thyroid function are known to occur).

Nervous system disorders:

Frequency not known: Bulging fontanelles in infants, benign intracranial hypertension.

(Treatment should cease if evidence of raised intracranial pressure develops.)

Cardiac disorders:

Frequency not known: Pericarditis.

Gastrointestinal disorders:

Rare: oesophagitis, oesophageal ulceration

(Reported in patients receiving capsule and tablet forms of drugs in the tetracycline class. Most of these patients took medication immediately before going to bed.)

Frequency not known: Gastrointestinal irritations giving rise to nausea, abdominal discomfort, vomiting, diarrhoea, anorexia, dysphagia (If gastric irritation occurs, tablets should be taken with food.). Pseudomembranous colitis, intestinal overgrowth of resistant organisms (Candida albicans, in particular), may occur and cause glossitis, rectal and vaginal irritation and inflammatory lesions (with candidial overgrowth) in the anogenital regions. Similarly, resistant staphylococci may cause enterocolitis. Tooth discolouration, pancreatitis.

Hepatobiliary system disorders:

Frequency not known: Hepatotoxicity (hepatitis, jaundice and hepatic failure), fatty liver degeneration.

Skin and subcutaneous tissue disorders:

Uncommon: Exfoliative dermatitis

Frequency not known: Macropapular and erythematous rashes, photo-erythema (Patients exposed to direct sunlight or ultraviolet light should be advised to discontinue treatment if any skin reaction occurs). Hypersensitivity reactions: urticaria, angioneurotic oedema, anaphylaxis, anaphylactoid purpura, pericarditis, exacerbation of systemic lupus erythematosus.

Renal and urinary disorders:

Frequency not known: Renal dysfunction.

4.9 Overdose

There is no specific antidote. Gastric lavage in the first hours after ingestion along with oral administration of milk or antacids is recommended.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Oxytetracycline is a bacteriostatic antibiotic with a broad spectrum of activity against bacteria, and also some antiprotozoal properties.

5.2 Pharmacokinetic Properties

The tetracyclines are incompletely and irregularly absorbed from the gastrointestinal tract.

The degree of absorption is diminished by the soluble salts of divalent and trivalent metals, with which tetracyclines form stable complexes and to a variable degree by milk or food. Plasma concentrations will depend upon the degree of absorption. Peak plasma concentrations occur about 1 to 3 hours after ingestion.

It is recommended that tetracyclines should be given before food.

A dose of 500mg every 6 hours by mouth is reported to produce steady-state plasma concentrations of 3 to 4µg per ml.

In the circulation, tetracyclines are bound to plasma proteins in varying degrees, but reported values differ considerably: from about 20 to 40% for oxytetracycline.

They are widely distributed throughout the body tissues and fluids. Small amounts appear in saliva, and the fluids of the eye and lung.

Tetracyclines appear in the milk of nursing mothers where concentrations may be 60% or more of those in the plasma. they diffuse across the placenta and appear in the foetal circulation in concentrations of about 25 to 75% of those in the maternal blood. Tetracyclines are retained at sites of new bone formation and recent calcification and in developing teeth.

The tetracyclines are excreted in the urine and in the faeces. Renal clearance is by glomerular filtration.

The tetracyclines are excreted in the bile where concentrations 5 to 25 times those in plasma can occur. Since there is some enterohepatic reabsorption complete elimination is slow. Considerable quantities occur in the faeces after administration by mouth.

5.3 Preclinical Safety Data

Not applicable.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Also contains: magnesium stearate, maize starch, propylene glycol, colloidal silica, sodium lauryl sulphate, E104, E110, E171, E463, E464, E553

6.2 Incompatibilities

None known.

6.3 Shelf Life

Shelf-life

Three years from the date of manufacture.

Shelf-life after dilution/reconstitution

Not applicable.

Shelf-life after first opening

Not applicable.

6.4 Special Precautions For Storage

Keep container tightly closed.

Store below 25°C in a dry place.

6.5 Nature And Contents Of Container

The product containers are rigid injection moulded polypropylene or injection blow-moulded polyethylene containers and snap-on polyethylene lids; in case any supply difficulties should arise the alternative is amber glass containers with screw caps.

The product may also be supplied in blister packs in cartons:

a) Carton: Printed carton manufactured from white folding box board.

b) Blister pack: (i) 250µm white rigid PVC. (ii) Surface printed 20µm hard temper aluminium foil with 5-7g/M² PVC and PVdC compatible heat seal lacquer on the reverse side.

Pack size: 7's, 10's, 14's, 21's, 28's, 30's, 56's, 60's, 84's, 100's, 112's, 250's, 500's, 1000's

Product may also be supplied in bulk packs, for reassembly purposes only, in polybags contained in tins, skillets or polybuckets filled with suitable cushioning material. Bulk packs are included for temporary storage of the finished product before final packaging into the proposed marketing containers.

Maximum size of bulk packs: 50,000.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

Administrative Data

7. Marketing Authorisation Holder

Actavis UK Limited

(Trading style: Actavis)

Whiddon Valley

BARNSTAPLE

N Devon EX32 8NS

8. Marketing Authorisation Number(S)

PL 0142/0372

9. Date Of First Authorisation/Renewal Of The Authorisation

31.8.94

Renewed November 1999

10. Date Of Revision Of The Text

21/05/2010

Clob

Clob may be available in the countries listed below.

Ingredient matches for Clob

Clobazam

Clobazam is reported as an ingredient of Clob in the following countries:

Bangladesh

International Drug Name Search

Carpo-Miotic

Carpo-Miotic may be available in the countries listed below.

Ingredient matches for Carpo-Miotic

Pilocarpine

Pilocarpine nitrate (a derivative of Pilocarpine) is reported as an ingredient of Carpo-Miotic in the following countries:

India

International Drug Name Search

Valproate Winthrop

Valproate Winthrop may be available in the countries listed below.

Ingredient matches for Valproate Winthrop

Valproic Acid

Valproic Acid semisodium (a derivative of Valproic Acid) is reported as an ingredient of Valproate Winthrop in the following countries:

Australia

International Drug Name Search

Passagix

Passagix may be available in the countries listed below.

Ingredient matches for Passagix

Domperidone

Domperidone is reported as an ingredient of Passagix in the following countries:

Russian Federation

International Drug Name Search

ALS-Paroxetin

ALS-Paroxetin may be available in the countries listed below.

Ingredient matches for ALS-Paroxetin

Paroxetine

Paroxetine is reported as an ingredient of ALS-Paroxetin in the following countries:

Romania

International Drug Name Search

Atecilina

Atecilina may be available in the countries listed below.

Ingredient matches for Atecilina

Ampicillin

Ampicillin trihydrate (a derivative of Ampicillin) is reported as an ingredient of Atecilina in the following countries:

Argentina

International Drug Name Search

Robervital

Robervital may be available in the countries listed below.

Ingredient matches for Robervital

Oxaceprol

Oxaceprol is reported as an ingredient of Robervital in the following countries:

Spain

Tocopherol, α-

Tocopherol, α- succinate (a derivative of Tocopherol, α-) is reported as an ingredient of Robervital in the following countries:

Spain

International Drug Name Search

Chooz

In the US, Chooz (calcium carbonate systemic) is a member of the following drug classes: antacids, minerals and electrolytes and is used to treat Duodenal Ulcer, Erosive Esophagitis, GERD, Indigestion and Stomach Ulcer.

US matches:

Chooz

Ingredient matches for Chooz

Calcium Carbonate

Calcium Carbonate is reported as an ingredient of Chooz in the following countries:

United States

International Drug Name Search

Terazosina Rubio

Terazosina Rubio may be available in the countries listed below.

Ingredient matches for Terazosina Rubio

Terazosin

Terazosin hydrochloride (a derivative of Terazosin) is reported as an ingredient of Terazosina Rubio in the following countries:

Spain

International Drug Name Search

Cefuroxim Actavis

Cefuroxim Actavis may be available in the countries listed below.

Ingredient matches for Cefuroxim Actavis

Cefuroxime

Cefuroxime axetil (a derivative of Cefuroxime) is reported as an ingredient of Cefuroxim Actavis in the following countries:

Switzerland

International Drug Name Search

Cyclopentolat

Cyclopentolat may be available in the countries listed below.

Ingredient matches for Cyclopentolat

Cyclopentolate

Cyclopentolate hydrochloride (a derivative of Cyclopentolate) is reported as an ingredient of Cyclopentolat in the following countries:

Austria

International Drug Name Search

Monday, 26 September 2016

Carteol

Carteol may be available in the countries listed below.

Ingredient matches for Carteol

Carteolol

Carteolol hydrochloride (a derivative of Carteolol) is reported as an ingredient of Carteol in the following countries:

Belgium

Czech Republic

Germany

Italy

Luxembourg

Poland

Romania

Slovakia

Turkey

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Cyclobenzaprine Hydrochloride

Ingredient matches for Cyclobenzaprine Hydrochloride

Cyclobenzaprine

Cyclobenzaprine Hydrochloride (USAN) is known as Cyclobenzaprine in the US.

International Drug Name Search

Glossary

USAN

United States Adopted Name

Click for further information on drug naming conventions and International Nonproprietary Names.

Cipasid

Cipasid may be available in the countries listed below.

Ingredient matches for Cipasid

Cisapride

Cisapride is reported as an ingredient of Cipasid in the following countries:

Thailand

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Ciklosporin IVAX

Ciklosporin IVAX may be available in the countries listed below.

Ingredient matches for Ciklosporin IVAX

Ciclosporin

Ciclosporin is reported as an ingredient of Ciklosporin IVAX in the following countries:

Sweden

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Fluoro Uracil

Fluoro-Uracil may be available in the countries listed below.

Ingredient matches for Fluoro-Uracil

Fluorouracil

Fluorouracil is reported as an ingredient of Fluoro-Uracil in the following countries:

Bahrain

Brazil

Ethiopia

Hong Kong

Poland

Romania

Spain

International Drug Name Search

Cefosporen

Cefosporen may be available in the countries listed below.

Ingredient matches for Cefosporen

Cefalexin

Cefalexin is reported as an ingredient of Cefosporen in the following countries:

Argentina

International Drug Name Search

Atazid

Atazid may be available in the countries listed below.

Ingredient matches for Atazid

Candesartan

Candesartan cilexetil (a derivative of Candesartan) is reported as an ingredient of Atazid in the following countries:

Denmark

Hydrochlorothiazide

Hydrochlorothiazide is reported as an ingredient of Atazid in the following countries:

Denmark

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Madonella

Madonella may be available in the countries listed below.

Ingredient matches for Madonella

Ethinylestradiol

Ethinylestradiol is reported as an ingredient of Madonella in the following countries:

Austria

Levonorgestrel

Levonorgestrel is reported as an ingredient of Madonella in the following countries:

Austria

International Drug Name Search

NiQuitin 14 mg transdermal patches.

1. Name Of The Medicinal Product

NiQuitin 14 mg transdermal patches.

2. Qualitative And Quantitative Composition

Each 15 cm² contains 78 mg nicotine, equivalent to 5.1 mg/cm² of nicotine and delivering 14 mg over 24 hours.

For excipients, see section 6.1.

3. Pharmaceutical Form

Transdermal patch.

Each patch is rectangular and is comprised of an outer matt pinkish tan-coloured layer, a middle silver layer and an outer clear layer which is removed prior to use.

4. Clinical Particulars

4.1 Therapeutic Indications

NiQuitin patches relieve and/or prevent craving and nicotine withdrawal symptoms associated with tobacco dependence. They are indicated to aid smokers wishing to quit or reduce prior to quitting, to assist smokers who are unwilling or unable to smoke, and as a safer alternative to smoking for smokers and those around them.

NiQuitin patches are indicated in pregnant and lactating women making a quit attempt.

If possible, when stopping smoking, NiQuitin patches should be used in conjunction with a behavioural support programme.

4.2 Posology And Method Of Administration

NiQuitin patches should be applied once a day, at the same time each day and preferably soon after waking, to a non-hairy, clean, dry skin site and worn continuously for 24 hours. The NiQuitin patch should be applied promptly on removal from its protective sachet.

Avoid applying to any skin which is broken, red or irritated. After 24 hours the used patch should be removed and a new patch applied to a fresh skin site. The patch should not be left on for longer than 24 hours. Skin sites should not be reused for at least seven days. Only one patch should be worn at a time.

Patches may be removed before going to bed if desired. However use for 24 hours is recommended to optimise the effect against morning cravings.

Concurrent behavioural support is recommended, as such programmes have been shown to be beneficial for smoking cessation.

Adults 18 years and over

Abrupt cessation of smoking:

During a quit attempt every effort should be made to stop smoking with NiQuitin patches.

NiQuitin therapy should usually begin with NiQuitin 21 mg and be reduced according to the following dosing schedule:-

Dose	Duration
Step 1 NiQuitin 21 mg	First 6 weeks
Step 2 NiQuitin 14 mg	Next 2 weeks
Step 3 NiQuitin 7 mg	Last 2 weeks

Light smokers (e.g. those who smoke less than 10 cigarettes per day) are recommended to start at Step 2 (14 mg) for 6 weeks and decrease the dose to NiQuitin 7 mg for the final 2 weeks.

Patients on NiQuitin 21 mg who experience excessive side-effects (please refer to precautions), which do not resolve within a few days, should change to NiQuitin 14mg. This strength should then be continued for the remainder of the 6 week course before stepping down to NiQuitin 7mg for two weeks. If the symptoms persist the patient should be advised to seek the advice of a healthcare professional.

For optimum results, the 10 week treatment course (8 weeks for light smokers or patients who have reduced strength as above), should be completed in full. Treatment with NiQuitin patch may be continued beyond 10 weeks if needed to stay cigarette free, however, those who have quit smoking but are having difficulty discontinuing using the patches recommended to seek additional help and advice from a healthcare professional.

Further courses may be used at a later time, for NiQuitin patch users who continue or resume smoking.

Gradual Cessation:

For smokers who are unwilling or unable to quit abruptly.

The 21 mg patch can be used daily for 2-4 weeks while the user continues to smoke as needed. At the end of the 2-4 weeks the user should quit completely and continue using Step 1 21 mg patch for 6 weeks daily without smoking. Thereafter following the Step 2 and 3 directions for abrupt cessation above. Should the patient feel able to quit completely before their designated quit date they can do so.

Reduction in smoking:

For smokers who wish to cut down with no immediate plans to quit.

A patch can be used while the user continues to smoke as needed. The user should reduce the number of cigarettes smoked as far as possible and to refrain from smoking as long as possible. Users should be encouraged to stop smoking completely as soon as possible.

If users are still feeling the need to use the patches on a regular basis 6 months after the start of treatment and have still been unable to undertake a permanent quit attempt, then it is recommended to seek additional help and advice from a healthcare professional.

Temporary Abstinence

Apply a patch to control troublesome withdrawal symptoms including craving during the period when smoking is being avoided. Users should be encouraged to stop smoking completely as soon as possible.

Adolescents and children

Adolescents (12 to 17 years) should follow the schedule of treatment for abrupt cessation of smoking as given above. Where adolescents are not ready or not able to stop smoking abruptly, advice from a healthcare professional should be sought.

Safety and effectiveness in children who smoke has not been evaluated. NiQuitin is not recommended for use in children under 12 years of age.

4.3 Contraindications

NiQuitin is contraindicated in patients with hypersensitivity to the system, the active substance, or any of the excipients.

NiQuitin patches should not be used by non-smokers, occasional smokers or children under 12 years.

4.4 Special Warnings And Precautions For Use

The risks associated with the use of NRT are substantially outweighed in virtually all circumstances by the well established dangers of continued smoking.

Patients hospitalised for MI, severe dysrhythmia or CVA who are considered to be haemodynamically unstable should be encouraged to stop smoking with non-pharmacological interventions. If this fails, NiQuitin patches may be considered, but as data on safety in this patient group are limited, initiation should only be under medical supervision. Once patients are discharged from hospital they can use NRT as normal.

Diabetes Mellitus: Patients with diabetes mellitus should be advised to monitor their blood sugar levels more closely than usual when NRT is initiated as catecholamines released by nicotine can affect carbohydrate metabolism.

Allergic reactions: Susceptibility to angioedema and urticaria.

Atopic or eczematous dermatitis (due to localised patch sensitivity): In the case of severe or persistent local reactions at the site of application (e.g. severe erythema, pruritus or oedema) or a generalised skin reaction (e.g. urticaria, hives or generalised skin rashes), users should be instructed to discontinue use of NiQuitin and contact their physician.

Contact sensitisation: Patients with contact sensitisation should be cautioned that a serious reaction could occur from exposure to other nicotine-containing products or smoking.

A risk benefit assessment should be made by an appropriate healthcare professional for patients with the following conditions:

• Renal and hepatic impairment: Use with caution in patients with moderate to severe hepatic impairment and/or severe renal impairment as the clearance of nicotine or its metabolites may be decreased with the potential for increased adverse effects.

• Phaeochromocytoma and uncontrolled hyperthyroidism: Use with caution in patients with uncontrolled hyperthyroidism or phaeochromocytoma as nicotine causes release of catecholamines.

Danger in small children: Doses of nicotine tolerated by adult and adolescent smokers can produce severe toxicity in small children that may be fatal. Products containing nicotine should not be left where they may be misused, handled or ingested by children. The patches should be folded in half with the adhesive side innermost and disposed of with care.

Stopping smoking: Polycyclic aromatic hydrocarbons in tobacco smoke induce the metabolism of drugs catalysed by CYP 1A2 (and possibly by CYP 1A1). When a smoker stops this may result in a slower metabolism and a consequent rise in blood levels of such drugs.

Transferred dependence: Transferred dependence is rare and is both less harmful and easier to break than smoking dependence.

Safety on handling: NiQuitin is potentially a dermal irritant and can cause contact sensitisation. Care should be taken during handling and in particular contact with the eyes and nose avoided. After handling, wash hands with water alone as soap may increase nicotine absorption.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No clinically relevant interactions between nicotine replacement therapy and other drugs has definitely been established, however nicotine may possibly enhance the haemodynamic effects of adenosine.

4.6 Pregnancy And Lactation

Pregnancy

Stopping smoking is the single most effective intervention for improving the health of both the pregnant smoker and her baby, and the earlier abstinence is achieved the better. However, if the mother cannot (or is considered unlikely to) quit without pharmacological support, NRT may be used as the risk to the foetus is lower than that expected with smoking tobacco. Stopping completely is by far the best option but NRT may be used in pregnancy as a safer alternative to smoking. Because of the potential for nicotine-free periods, intermittent dose forms are preferable, but patches may be necessary if there is significant nausea and/or vomiting. If patches are used they should, if possible, be removed at night when the foetus would not normally be exposed to nicotine.

Lactation

The relatively small amounts of nicotine found in breast milk during NRT use are less hazardous to the infant than second-hand smoke. Intermittent dose forms would minimize the amount of nicotine in breast milk and permit feeding when levels were at their lowest.

4.7 Effects On Ability To Drive And Use Machines

Not applicable.

4.8 Undesirable Effects

NRT may cause adverse reactions similar to those associated with nicotine administered by other means, including smoking. These may be attributable to the pharmacological effects of nicotine, some of which are dose dependent. At recommended doses, NiQuitin patches have not been found to cause any serious adverse effects. Excessive use of NiQuitin patches by those who have not been in the habit of inhaling tobacco smoke could possibly lead to nausea, faintness or headaches.

Subjects quitting smoking by any means could expect to suffer from asthenia, headache, dizziness, sleep disturbance, coughing or influenza-like illness. Certain symptoms which have been reported such as depression, irritability, nervousness, restlessness, mood lability, anxiety, drowsiness, impaired concentration and insomnia may be related to withdrawal symptoms associated with smoking cessation.

Application site reactions are the most frequent adverse reaction associated with NiQuitin. NiQuitin can cause other adverse reactions related to the pharmacological effect of nicotine or withdrawal effects related to smoking.

The following undesirable effects have been reported in clinical trials or spontaneously post-marketing.

Certain symptoms which have been reported such as depression, irritability, nervousness, restlessness, mood lability, anxiety, drowsiness, impaired concentration, insomnia and sleep disturbances may be related to withdrawal symptoms associated with smoking cessation. Subjects quitting smoking by any means could expect to suffer from asthenia, headache, dizziness, coughing or influenza-like illness.

Immune System Disorders

Uncommon>1/1000; <1/100: hypersensitivity NOS*

Very rare <1/10000: anaphylactic reactions

Psychiatric

Very common>1/10: sleep disorders including abnormal dreams and insomnia

Common>1/100; <1/10: nervousness

Nervous system disorders

Very Common>1/10: headache, dizziness

Common>1/100; <1/10: tremor

Cardiac disorders

Common>1/100; <1/10: palpitations

Uncommon>1/1000; <1/100: tachycardia NOS

Respiratory, Thoracic and Mediastinal Disorders

Common>1/100; <1/10: dyspnoea, pharyngitis, cough

Gastrointestinal Disorders

Very Common>1/10: nausea, vomiting

Common>1/100; <1/10: dyspepsia, abdominal pain upper, diarrhea NOS, dry mouth, constipation

Skin and Subcutaneous Tissue Disorders

Common>1/100; <1/10: sweating increased

Very rare> 1/100000; <1/10000: dermatitis allergic*, dermatitis contact*, photosensitivity

Musculoskeletal and Connective Tissue Disorders

Common>1/100; <1/10: arthralgia, myalgia

General Disorders and Administration Site Conditions

Very Common>1/10: application site reactions NOS*

Common>1/100; <1/10: chest pain, pain in limb, pain NOS, asthenia, fatigue

Uncommon>1/1000; <1/100 malaise, influenza-like illness

* see below

Application site reactions, including transient rash, itching, burning, tingling, numbness, swelling, pain and urticaria are the most frequent undesirable effects of NiQuitin patch. The majority of these topical reactions are minor and resolve quickly following removal of the patch. Pain or sensation of heaviness in the limb or area around which the patch is applied (e.g. chest) may be reported.

Hypersensitivity reactions, including contact dermatitis and allergic dermatitis have also been reported. In the case of severe or persistent local reactions at the application site (e.g. severe erythema, pruritus or oedema) or a generalized skin reaction (e.g. urticaria, hives or generalised skin rashes) users should be instructed to discontinue use of NiQuitin and contact their physician.

If there is a clinically significant increase in cardiovascular or other effects attributable to nicotine, the NiQuitin dose should be reduced or discontinued.

4.9 Overdose

Symptoms: The minimum lethal dose of nicotine in a non-tolerant man has been estimated to be 40 to 60mg. Symptoms of acute nicotine poisoning include nausea, salivation, abdominal pain, diarrhoea, sweating, headache, dizziness, disturbed hearing and marked weakness. In extreme cases, these symptoms may be followed by hypotension, rapid or weak or irregular pulse, breathing difficulties, prostration, circulatory collapse and terminal convulsions.

Management of an overdose: All nicotine intake should stop immediately and the patient should be treated symptomatically. Artificial respiration with oxygen should be instituted if necessary. Activated charcoal reduces the gastro-intestinal absorption of nicotine

Overdose from topical exposure: The NiQuitin system should be removed immediately if the patient shows signs of overdosage and the patient should seek immediate medical care. The skin surface may be flushed with water and dried. No soap should be used since it may increase nicotine absorption. Nicotine will continue to be delivered into the bloodstream for several hours after removal of the system because of a depot of nicotine in the skin.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic classification: N07BA01

(Anti-smoking agents: N07BA, Nicotine 01)

Nicotine, the chief alkaloid in tobacco products and a naturally occurring autonomic drug, is an agonist at nicotine receptors in the peripheral and central nervous system and has pronounced CNS and cardiovascular effects. Withdrawal from nicotine in addicted individuals is characterised by craving, nervousness, restlessness, irritability, mood lability, anxiety, drowsiness, sleep disturbances, impaired concentration, increased appetite, minor somatic complaints (headache, myalgia, constipation, fatigue) and weight gain. Withdrawal symptoms, such as cigarette craving, may be controlled in some individuals by steady-state plasma levels lower than those for smoking.

In clinically controlled trials, NiQuitin was shown to alleviate nicotine withdrawal symptoms as well as craving. NiQuitin reduced the severity of cravings by at least 35% at all times of day during the first two weeks of abstinence, compared to placebo (p<0.05).

5.2 Pharmacokinetic Properties

Absorption

Following transdermal application, the skin rapidly absorbs nicotine released initially from the patch adhesive. The plasma concentrations of nicotine reach a plateau within 2-4 hours after initial application of NiQuitin with relatively constant plasma concentrations persisting for 24 hours or until the patch is removed. Approximately 68% of the nicotine released from the patch enters systemic circulation and the remainder of the released nicotine is lost via vaporisation from the edge of the patch.

With continuous daily application of NiQuitin (worn for 24 hours), dose-dependent steady state plasma nicotine concentrations are achieved following the second NiQuitin application and are maintained throughout the day. These steady state maximum concentrations are approximately 30% higher than those following a single application of NiQuitin.

Plasma concentrations of nicotine are proportional to dose for the three dosage forms of NiQuitin. The mean plasma steady state concentrations of nicotine are approximately 17 ng/ml for the 21 mg/day patch, 12 ng/ml for the 14 mg /day patch and 6 ng/ml for the 7 mg/day patch. For comparison, half-hourly smoking of cigarettes produces average plasma concentrations of approximately 44 ng/ml.

The pronounced early peak in nicotine blood levels seen with inhalation of cigarette smoke is not observed with NiQuitin.

Distribution

Following removal of NiQuitin, plasma nicotine concentrations decline with an apparent mean half-life of 3 hours, compared with 2 hours for IV administration due to continued absorption of nicotine from the skin depot. If NiQuitin is removed most non-smoking patients will have non-detectable nicotine concentrations in 10 to 12 hours.

A dose of radiolabelled nicotine given intravenously showed a distribution of radioactivity corresponding to the blood supply with no organ selectively taking up nicotine. The volume of distribution of nicotine is approximately 2.5 l/kg.

Metabolism

The major elimination organ is the liver and average plasma clearance is about 1.2 l/min; the kidney and the lung also metabolise nicotine. More than 20 metabolites of nicotine have been identified, all of which are believed to be pharmacologically inactive. The principal metabolites are cotinine and trans

Excretion

Both nicotine and its metabolites are excreted through the kidneys and about 10% of nicotine is excreted unchanged in the urine. As much as 30% may be excreted in the urine with maximum flow rates and extreme urine acidification (pH

There were no differences in nicotine kinetics between men and women using NiQuitin. Obese men using NiQuitin had significantly lower AUC and Cmax values compared with normal weight men. Linear regression of AUC vs total body weight showed the expected inverse relationship (AUC decreases as weight increases). Nicotine kinetics were similar for all sites of application on the upper body and upper outer arm.

5.3 Preclinical Safety Data

The general toxicity of nicotine is well known and taken into account in the recommended posology. Nicotine was not mutagenic in appropriate assays. The results of carcinogenicity assays did not provide any clear evidence of a tumorigenic effect of nicotine. In studies in pregnant animals, nicotine showed maternal toxicity, and consequential mild fetal toxicity. Additional effects included pre- and postnatal growth retardation and delays and changes in postnatal CNS development.

Effects were only noted following exposure to nicotine at levels in excess of those which will result from recommended use of NiQuitin. Effects on fertility have not been established.

Comparison of the systemic exposure necessary to elicit these adverse responses from preclinical test systems with that associated with the recommended use of NiQuitin indicate that the potential risk is low and outweighed by the demonstrable benefit of nicotine therapy in smoking cessation. However, NiQuitin should only be used by pregnant women on medical advice if other forms of treatment have failed.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Drug Reservoir:	Ethylene Vinyl Acetate Copolymer
Occlusive Backing:	Polyethylene/Aluminium/Polyethylene Terephthalate/ Ethylene vinyl acetate
Rate Controlling Membrane:	Polyethylene Film
Contact Adhesive:	Polyisobutylene B100 and B12 SFN
Protective Layer:	Siliconised Polyester Film
Printing Ink:	PMS 465 Brown Ink

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Do not store above 25°C.

6.5 Nature And Contents Of Container

7 or 14 patches in a carton. Each patch is contained in a laminate sachet.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Beecham Group PLC

980 Great West Road

Brentford

Middlesex

TW8 9GS

United Kingdom

T/A GlaxoSmithKline Consumer Healthcare

Brentford

TW8 9GS

8. Marketing Authorisation Number(S)

PL 00079/0367

9. Date Of First Authorisation/Renewal Of The Authorisation

03 April 2001

10. Date Of Revision Of The Text

11/10/2010

Carnitene sigma-tau

Carnitene sigma-tau may be available in the countries listed below.

Ingredient matches for Carnitene sigma-tau

Levocarnitine

Levocarnitine is reported as an ingredient of Carnitene sigma-tau in the following countries:

Hong Kong

Netherlands

Switzerland

International Drug Name Search

Cycléane

Cycléane may be available in the countries listed below.

Ingredient matches for Cycléane

Desogestrel

Desogestrel is reported as an ingredient of Cycléane in the following countries:

France

Ethinylestradiol

Ethinylestradiol is reported as an ingredient of Cycléane in the following countries:

France

International Drug Name Search

Cymévan

Cymévan may be available in the countries listed below.

Ingredient matches for Cymévan

Ganciclovir

Ganciclovir sodium salt (a derivative of Ganciclovir) is reported as an ingredient of Cymévan in the following countries:

France

International Drug Name Search

Friday, 23 September 2016

Asmo-Lavi

Asmo-Lavi may be available in the countries listed below.

Ingredient matches for Asmo-Lavi

Fluticasone

Fluticasone propionate (a derivative of Fluticasone) is reported as an ingredient of Asmo-Lavi in the following countries:

Portugal

International Drug Name Search

Alfa C

Alfa C may be available in the countries listed below.

Ingredient matches for Alfa C

Benzalkonium Chloride

Benzalkonium chloride (a derivative of Benzalkonium) is reported as an ingredient of Alfa C in the following countries:

Italy

International Drug Name Search

Cordarone

In the US, Cordarone (amiodarone systemic) is a member of the drug class group III antiarrhythmics and is used to treat Arrhythmia, Ventricular Fibrillation and Ventricular Tachycardia.

US matches:

Cordarone

Cordarone I.V. injection

Cordarone IV

Cordarone IV Intravenous

Cordarone injection

UK matches:

Cordarone X 100, Cordarone X 200 (SPC)
Cordarone X Intravenous (SPC)

Ingredient matches for Cordarone

Amiodarone

Amiodarone is reported as an ingredient of Cordarone in the following countries:

Estonia

Ireland

Taiwan

Tunisia

Vietnam

Amiodarone hydrochloride (a derivative of Amiodarone) is reported as an ingredient of Cordarone in the following countries:

Antigua & Barbuda

Aruba

Australia

Bahamas

Bahrain

Barbados

Belgium

Bermuda

Bosnia & Herzegowina

Bulgaria

Canada

Cayman Islands

China

Colombia

Costa Rica

Croatia (Hrvatska)

Czech Republic

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Finland

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Slovenia

South Africa

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Turkey

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United Kingdom

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Glossary

SPC

Summary of Product Characteristics (UK)

Click for further information on drug naming conventions and International Nonproprietary Names.

Topiramat-1A Pharma

Topiramat-1A Pharma may be available in the countries listed below.

Ingredient matches for Topiramat-1A Pharma

Topiramate

Topiramate is reported as an ingredient of Topiramat-1A Pharma in the following countries:

Germany

International Drug Name Search

Warfarin Sodium

Class: Coumarin Derivatives
CAS Number: 129-06-6
Brands: Coumadin

Special Alerts:

[Posted 08/16/2007] FDA approved updated labeling to include pharmacogenomics information to the CLINICAL PHARMACOLOGY, PRECAUTIONS, and DOSAGE AND ADMINISTRATION sections of the prescribing information for the widely used blood-thinning drug, warfarin (Coumadin). This new information explains that people’s genetic makeup may influence how they respond to the drug. Specifically, people with variations in two genes may need lower warfarin doses than people without these genetic variations. The two genes are called CYP2C9 and VKORC1. The CYP2C9 gene is involved in the breakdown (metabolism) of warfarin and the VKORC1 gene helps regulate the ability of warfarin to prevent blood from clotting.

The dosage and administration of warfarin must be individualized for each patient according to the particular patient’s prothrombin time (PT) / International Normalized Ratio (INR) response to the drug. The specific dose recommendations are described in the warfarin product labeling, along with the new information regarding the impact of genetic information upon the initial dose and the response to warfarin. Ongoing warfarin therapy should be guided by continued INR monitoring. For more information visit the FDA website at: .

[Posted 10/06/2006] FDA and Bristol-Myers Squibb notified pharmacists and physicians of revisions to the labeling for warfarin (Coumadin), to include a new patient Medication Guide as well as a reorganization and highlighting of the current safety information to better inform providers and patients.

The FDA regulation 21CFR 208 requires a Medication Guide to be provided with each prescription that is dispensed for products that FDA determines pose a serious and significant public health concern. Information about all currently approved Medication Guides is available at: . For more information visit the FDA website at: , and .

Introduction

Anticoagulant; a coumarin derivative.²¹¹

Uses for Warfarin Sodium

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Treatment/Secondary Prevention of Venous Thrombosis and Pulmonary Embolism

Used as follow-up to initial heparin anticoagulation for treatment of proximal DVT or nonmassive acute pulmonary embolism; initiate concomitantly with full-dose IV or adjusted-dose sub-Q unfractionated heparin or a weight-based dosage of sub-Q low molecular weight (LMW) heparin.³⁶⁵ ⁴⁰⁷ ⁴²⁷ ⁴⁴⁶ May consider thrombolytic therapy in those with massive pulmonary embolism with hemodynamic instability or severe ileofemoral thrombosis.³³² ⁴²⁷

LMW heparin or sub-Q unfractionated heparin used as alternative therapy for secondary prevention of DVT and pulmonary embolism when warfarin is contraindicated or inconvenient.⁴²⁹ ⁴⁴⁶

Secondary prevention of DVT and pulmonary embolism in patients with concurrent cancer; LMW heparin preferred in such patients.⁴²⁷

Secondary prevention of venous thromboembolism or pulmonary embolism associated with reversible or time-limited risk factors (e.g., transient immobilization, trauma, surgery, pharmacologic doses of estrogen, central venous catheter).³⁶⁵ ⁴³⁷ ⁴⁴⁶

Secondary prevention of venous thromboembolism associated with thrombophilic conditions (e.g., combined factor V Leiden and prothrombin 20210 gene mutations).⁴²⁷ ⁴²⁹

Secondary prevention of venous thromboembolism in children with ongoing risk factors such as active nephrotic syndrome, ongoing asparaginase therapy, or lupus anticoagulant.⁴⁴⁶

Prophylaxis in General Surgery

American College of Chest Physicians (ACCP) prefers other drug therapies (LMW heparin or low-dose unfractionated heparin) or non-drug therapies (intermittent pneumatic compression, elastic stockings) in most moderate- to high-risk general surgery patients†.³³³ ³⁶⁶ ⁴³⁰

Prophylaxis in Hip-Replacement Surgery

Short-term prophylaxis in patients undergoing hip-replacement surgery as one of several therapeutic options (fondaparinux, LMW heparin).³⁶⁶ ⁴³⁰ ²⁰⁰ ²⁰⁸ ³³³ ³⁶⁶ ⁴³⁰

Consider extended prophylaxis (≤28–35 days) in patients undergoing hip-replacement surgery who have ongoing risk factors for venous thromboembolism (e.g., obesity, delayed mobilization, cancer, history of venous thromboembolism).⁴³⁰

Prophylaxis in Hip-fracture Surgery

Short-term prophylaxis in patients undergoing hip-fracture surgery†, as one of several therapeutic options (fondaparinux, LMW heparin).²⁰⁰ ²⁰⁸ ³³³ ³⁶⁶ ⁴³⁰

Consider extended prophylaxis (≤28–35 days) in patients undergoing hip-fracture surgery who have ongoing risk factors for venous thromboembolism (e.g., obesity, delayed mobilization, cancer, history of venous thromboembolism).⁴³⁰

Prophylaxis in Knee-replacement Surgery

Short-term prophylaxis in patients undergoing knee-replacement surgery† as one of several therapeutic options (LMW heparin, fondaparinux, intermittent pneumatic compression).²⁰⁰ ²⁰⁸ ³³³ ³⁶⁶ ⁴³⁰

Prophylaxis in Trauma

Prevention of thromboembolism in the rehabilitation phase of acute spinal cord injury†, as an alternative to continued therapy with an LMW heparin.³⁶⁶ ⁴³⁰

Prevention of thromboembolism in other types of trauma† after initial treatment with an LMW heparin in patients with an ongoing risk of venous thromboembolism requiring extended hospital stays.⁴³⁰

Continued prophylaxis with warfarin or an LMW heparin after hospital discharge suggested by ACCP in selected patients with impaired mobility.⁴³⁰

Embolism Associated with Atrial Fibrillation/Flutter

Prophylaxis of thromboembolic episodes in patients with persistent or paroxysmal atrial fibrillation who are at high risk for stroke (e.g., history of stroke, TIA, or systemic embolism; poor left ventricular systolic function and/or CHF; hypertension; diabetes mellitus; >75 years of age) or as alternative to aspirin in patients with persistent or paroxysmal atrial fibrillation and no other high-risk factors.²¹¹ ⁴³¹ ⁴³⁴ ^e

Prevention of thromboembolism in patients with atrial flutter† with or without mitral valve stenosis.^a ⁴³¹ Use alone or in combination with aspirin in patients with atrial flutter and prosthetic heart valves.⁴³¹

Patients with “lone” atrial fibrillation should be offered aspirin rather than warfarin because of their relatively low risk of stroke.²²³ ²⁷⁹ ²⁸³ ³³⁵ ³³⁹ ³⁴⁴ ³⁴⁶ ³⁶⁷ ³⁶⁸ ³⁶⁹ ⁴³¹ ACCP, ACC, and AHA state that patients who decline therapy with warfarin or who are extremely poor candidates for oral anticoagulation also should be offered aspirin, except when contraindicated.³³⁵ ³³⁹ ³⁴⁹ ³⁶⁷ ³⁶⁸ ⁴³¹

Short-term prevention of thromboembolism in patients with atrial fibrillation (>48 hours) who are at high risk for stroke after open-heart surgery.⁴³¹

Thromboprophylaxis during Cardioversion of Atrial Fibrillation/Flutter

Prevention of embolization in patients undergoing pharmacologic or electrical cardioversion of atrial fibrillation/flutter†.^a ⁴³¹

Embolism Associated with Valvular Heart Disease

Prevention of thromboembolism associated with various types of valvular heart disease†, in combination with or as alternative to low-dose aspirin; choice of antithrombotic therapy depends on risks of thromboembolism versus hemorrhagic complications from such therapy.³⁴⁰ ³⁴⁴ ³⁷¹ ^c

Many experts recommend long-term oral anticoagulation with warfarin therapy in patients with rheumatic mitral valve disease† and atrial fibrillation or a history of systemic embolism (e.g., stroke).³⁴⁰ ³⁴¹ ³⁷¹ ^c Add low-dose aspirin therapy in patients with atrial fibrillation or history of systemic embolism who have a breakthrough embolic event despite prophylactic anticoagulation; may use another oral platelet-aggregation inhibitor (e.g., dipyridamole, clopidogrel) if aspirin not tolerated.³⁷¹ ⁴³³ ^c

Consider long-term anticoagulation in patients with rheumatic mitral valve disease† and normal sinus rhythm who have a left atrial diameter >5.5 cm (high risk of atrial fibrillation).³⁴⁰ ³⁷¹ ^c

Prophylaxis with warfarin (target INR 2.5, range 2–3) recommended by ACC/AHA in selected high-risk patients with mitral valve prolapse† and atrial fibrillation (i.e., those ≥65 years of age or those with mitral valve regurgitation, hypertension, or a history of heart failure).³⁴¹ Patients <65 years of age with mitral valve prolapse and atrial fibrillation who do not have these risk factors for thromboembolism and those with mitral valve prolapse and unexplained TIAs should be considered for low-dose aspirin therapy.³⁴⁰ ³⁴¹ ³⁷¹ ^c Also consider long-term warfarin prophylaxis in patients with mitral valve prolapse who have atrial fibrillation, a history of systemic embolism (e.g., stroke), or recurrent TIAs despite aspirin therapy.³⁴⁰ ³⁴¹ ³⁷¹ ^c

Adjusted-dose warfarin also recommended by some clinicians for prevention of thromboembolic events in patients with mitral valve regurgitation and concomitant atrial fibrillation or a history of systemic embolism.³⁴¹ ³⁷¹

Long-term antithrombotic therapy generally not recommended in patients with mitral annular calcification who lack a history of thromboembolism or atrial fibrillation.³⁴⁰ ³⁷¹ ^c However, ACCP suggests that long-term warfarin therapy be given to patients with mitral annular calcification complicated by systemic embolism not documented to be calcific embolism or in those who have atrial fibrillation.³⁴⁰ ³⁷¹ ^c

Generally should not initiate anticoagulant therapy in patients with uncomplicated infective endocarditis involving a native valve because of the risk of hemorrhage and lack of documented efficacy.³⁴⁰ ³⁷¹

Oral anticoagulant therapy recommended in patients undergoing mitral valvuloplasty beginning 3 weeks prior to the procedure and continuing for 4 weeks following the procedure.^c

Generally should not initiate long-term anticoagulant therapy in patients with aortic arch valve disease unless warranted by a coexisting condition.³⁷¹ ^c However, ACCP states that patients with mobile aortic atheromas and aortic plaques >4 mm (as measured by transesophageal echocardiography) should receive long-term anticoagulation with warfarin.³⁷¹ ^c

Thromboembolism Associated with Prosthetic Heart Valves

Follow-up anticoagulation after unfractionated heparin or an LMW heparin for prevention of thromboembolic complications associated with heart valve replacement.²¹¹ ³⁴¹ ³⁴⁷ ³⁷⁰ ⁴³³ ^c

Risk of systemic embolism is higher with prosthetic mechanical than with bioprosthetic heart valves, higher with first-generation mechanical (e.g., caged ball, caged disk) valves than with newer mechanical (e.g., bileaflet, Medtronic Hall tilting disk) heart valves, higher with more than one prosthetic valve, and higher with prosthetic mitral than with aortic valves; risk also increases in the presence of atrial fibrillation.³⁴¹ ³⁴² ³⁴³ ³⁴⁷ ³⁷⁰ ⁴³¹ ⁴³³ Lifelong prophylaxis required in all patients with mechanical heart valves because of associated high risk of thromboembolism.³⁴¹ ³⁴⁷ ³⁷⁰

Combination therapy with aspirin recommended in patients with mechanical heart valves and additional risk factors (e.g., atrial fibrillation, left atrial enlargement, endocardial damage, low ejection fraction).⁴³³

Combination therapy with aspirin recommended in patients with first-generation mechanical heart valves.⁴³³

Short-term (3 months) prophylaxis in patients with a bioprosthetic valve in the mitral position; follow-up with long-term aspirin therapy in patients with no continuing risk factors who are in normal sinus rhythm.⁴³³

Short-term (3 months) prophylaxis with warfarin or aspirin in patients with a bioprosthetic valve in the aortic position; follow-up with aspirin in patients with no continuing risk factors who are in normal sinus rhythm.⁴³³

Short-term prophylaxis in patients with a bioprosthetic valve and evidence of a left atrial thrombus.⁴³³

Long-term prophylaxis in patients with a bioprosthetic valve and other risk factors (e.g., atrial fibrillation, prior thromboembolism, left ventricular dysfunction, hypercoagulable states).³⁴¹ ³⁴⁷ ³⁷⁰ ⁴³³

Generally should not initiate anticoagulant therapy in patients with uncomplicated infective endocarditis involving a bioprosthetic heart valve because of the risk of hemorrhage and lack of documented efficacy.³⁴⁰ ³⁷¹ ⁴³³ However, ACCP states that patients with mechanical prosthetic valves receiving long-term anticoagulation who develop infective endocarditis generally should remain on anticoagulant therapy unless there are specific contraindications, keeping in mind the substantial risk of intracranial hemorrhage.³⁴⁰ ³⁷¹ ^c

Treatment of “breakthrough” thromboembolic events in patients with prosthetic heart valves receiving thromboprophylaxis.²¹¹ ³⁴¹ ⁴³³ ^c Combination therapy with aspirin recommended in patients with breakthrough embolic event despite warfarin therapy.⁴³³ ³⁴¹ ³⁷⁰ ⁴³³ ^c

Thromboembolism Following ST-Segment Elevation MI

Used as adjunctive therapy with platelet-aggregation inhibitors (e.g., aspirin, clopidogrel) after coronary artery reperfusion for the prevention of early reocclusion and death.²¹¹ ²²⁶ ²⁴² ²⁴³ ²⁴⁴ ²⁴⁵ ²⁴⁶ ²⁴⁷ ²⁴⁸ ²⁴⁹ ²⁵⁰ ²⁵¹ ²⁵² ³⁴⁸ ³⁵⁰ ³⁷² ⁴³² ⁴⁴⁰

Used short-term with an LMW heparin in the treatment of DVT or pulmonary embolism following MI in hospitalized patients.⁴³²

Used in selected patients to reduce the incidence of thromboembolic events such as stroke or systemic embolization following MI.²¹¹ ²²⁶ ²⁵⁶ ²⁶⁸ ²⁶⁹ ²⁷⁰ ²⁷¹ ²⁷² ³⁴⁸ ⁴³² ⁴⁴⁰ ACC and AHA recommend follow-up anticoagulation (3 months) at hospital discharge and adjunctive aspirin after initiation of unfractionated heparin or an LMW heparin in patients at high risk for systemic emboli.⁴³² ACCP suggests oral anticoagulation and aspirin following MI for 3 months in those at high risk for embolism.³⁴⁸ ³⁵⁰ ³⁷² ⁴³⁷

ACC and AHA recommend long-term anticoagulation alone or with aspirin at hospital discharge in patients without stent implantation who have coexisting conditions (i.e., atrial fibrillation, left ventricular thrombus, cerebral emboli, extensive wall motion abnormality) that warrant such therapy.⁴³²

Used as an alternative to clopidogrel in patients who are unable to take daily aspirin therapy and who do not have a stent implanted.⁴³²

Primary Prevention of Thromboembolic Events in CAD

Used to reduce the incidence of cardiovascular events and mortality† in patients at high risk for CAD.³⁷² ⁴³⁷

Thromboembolism Associated with Other Cardiovascular Diseases

Used in conjunction with aspirin to prevent thrombi and infarction in children with Kawasaki disease†.⁴⁴⁶

Used as primary prophylaxis for thrombotic complications in children with dilated cardiomyopathy† awaiting a cardiac transplant.⁴⁴⁶

May be used as primary prevention of thromboembolic events in children undergoing Fontan surgery for congenital univentricular heart lesions†; use with aspirin (5 mg/kg daily) as follow-up to heparin therapy.⁴⁴⁶

Cerebral Thromboembolism

Secondary prevention in patients with TIAs† or mild ischemic stroke and concurrent atrial fibrillation, provided no contraindications to therapy exist.³³⁵ ³³⁸ ³⁴⁹ ³⁵² ³⁷³ ⁴³² ⁴³⁴

Used in conjunction with aspirin for prevention of recurrent stroke in patients at high risk for recurring cerebral embolism from other cardiac sources (e.g., mechanical prosthetic heart valves, recent MI, left ventricular thrombus, dilated cardiomyopathies, marantic endocarditis, extensive wall-motion abnormalities).³³⁵ ³³⁸ ³⁴⁹ ³⁵² ⁴³² Follow-up anticoagulation after heparin or an LMW heparin in patients with recent MI and acute ischemic stroke and cardiac sources of embolism.⁴³²

Has been used as follow-up anticoagulation after heparin therapy for the prevention of embolism in paralyzed or immobile patients with progressive stroke† (when the suspected mechanism is thromboembolic) or stroke-in-evolution†.²¹² ³⁷³ However, use of heparin or an LMW heparin not recommended by ACCP in patients with a stroke-in-evolution because of lack of conclusive data on efficacy and safety.⁴³⁴

Short-term (3–6 months) follow-up anticoagulation with warfarin or an LMW heparin after heparin or an LMW heparin in children with arterial ischemic stroke from cardiac sources† or vascular dissection.⁴⁴⁶ May initiate aspirin following completion of anticoagulation.⁴⁴⁶

Long-term antithrombotic therapy generally not recommended in asymptomatic patients with a patent foramen ovale or atrial septal aneurysm unless such patients have unexplained system embolism or TIAs and demonstrable venous thrombosis or pulmonary embolism.³⁴⁰ ³⁷¹ Treatment of suspected DVT in patients with cryptogenic stroke and patent foramen ovale†.⁴³⁴ ACCP suggests use of antiplatelet agents over warfarin in patients with cryptogenic stroke and patent foramen ovale without DVT.⁴³⁴

ACCP suggests either oral anticoagulation or antiplatelet agents for secondary prophylaxis in patients with cryptogenic stroke and mobile arch thrombi†.⁴³⁴

Oral anticoagulation (3–6 months) recommended by ACCP as follow-up to unfractionated heparin or an LMW heparin in patients with acute cerebral venous sinus thrombosis†.

Thrombosis Associated with CABG

Prevention of saphenous vein or internal mammary artery graft occlusion following CABG†.³⁷⁶ ⁴⁴⁸ ACCP recommends use in combination with aspirin when other coexisting conditions (e.g., heart valve replacement) warrant such therapy.³⁷⁶ ⁴⁴⁸

Prevention of Stent Thrombosis and Restenosis Following PCI

Has been used short-term for prevention of stent thrombosis after stent placement† or long-term (1–6 months) for prevention of restenosis following PCI†.⁴⁴⁷ Since warfarin has no apparent advantages over antiplatelet therapy, not routinely recommended by ACCP after PCI if no other indications for anticoagulation exist.⁴⁴⁷

Arterial Occlusive Disease

Has been used in selected patients with peripheral arterial occlusive disease†, but ACCP currently recommends against use of anticoagulants for intermittent claudication.³⁷⁷ ⁴⁴⁹

Treatment/Secondary Prevention in Arterial Vascular Surgery

ACCP recommends long-term follow-up oral anticoagulation after initial heparin treatment in patients undergoing embolectomy†.³⁷⁷ ⁴⁴⁹

ACCP recommends long-term oral anticoagulation in postsurgical patients following pulmonary thromboendarterectomy† and in patients ineligible for such a procedure.⁴²⁷

Prevention (combined with aspirin therapy) of embolism in selected (high risk for graft thrombosis and limb loss) patients after infrainguinal femoropopliteal or distal vein bypass†.³⁷⁷ ⁴⁴⁹

Heparin-Induced Thrombocytopenia³⁸⁷ ³⁹² ³⁹³

Has been administered as follow-up treatment of heparin-induced thrombocytopenia† when substantial recovery has occurred (i.e., platelet counts ≥ 100,000–150,000/mm³ and are stable) after therapy with a direct thrombin inhibitor (e.g., lepirudin, bivalirudin, argatroban).³⁹² ⁴⁴¹ ⁴⁴² ⁴⁴³ ⁴⁴⁴ Overlap therapy for approximately 5 days until an adequate response to warfarin is obtained.³⁸⁷ ³⁹² ³⁹³

Warfarin Sodium Dosage and Administration

General

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Carefully individualize dosage based on clinical and laboratory findings (i.e., determination of INR and/or PT ratios).²¹¹ Adjust dosage in small increments and carefully monitor patient response.^a Determine optimum duration of therapy by the condition being treated and its severity.^a

Determine PT prior to and 24 hours after initiation of therapy.²¹¹ ^a ⁴²⁶ Determine PT daily until the PT/INR is in the therapeutic range.²¹¹ Intervals between subsequent PT determinations based on clinician’s judgment and patient’s response.²¹¹ Determine PT/INR generally every 1–4 weeks after a stable dosage has been determined.²¹¹ ⁴²⁶

Determine PT when different warfarin preparations (e.g., proprietary versus generic) are interchanged.²¹¹ ^a Determine PT when concomitant drug therapy is added, discontinued, or taken irregularly.²¹¹ ^a

Dosage does not vary with the route of administration.²¹¹

Administration of large loading doses (i.e., >20 mg) not recommended.²¹¹ ⁴²⁶ Possible increased risk of hemorrhage or necrosis.²¹¹ (See Hemorrhage under Cautions.)

For follow-up therapy after heparin, the manufacturer recommends that therapy with heparin and warfarin be used concurrently for at least 4–5 days or until the desired PT/INR has been achieved.²¹¹ Some clinicians recommend that unfractionated heparin or an LMW heparin be used concurrently with warfarin for about 5–7 days or until the desired INR has been achieved for 2 consecutive days.⁴²⁷

Increased risk of thrombosis or rebound thromboembolism has been suggested following abrupt discontinuance of warfarin therapy; some manufacturers recommend gradually decreasing dosage (e.g., over 3–4 weeks) when withdrawing therapy.^a

Transferring from Anticoagulation with Direct Thrombin Inhibitors

For follow-up therapy after most direct thrombin inhibitors, overlap therapy with direct thrombin inhibitors for ≥5 days until desired INR has been achieved for 2 consecutive days.⁴⁴¹ ⁴⁴³

Combined therapy with argatroban and warfarin prolongs the PT and INR beyond that produced by warfarin alone.³⁹² ⁴⁴¹ Determine PT and INR daily during concurrent argatroban and warfarin therapy.³⁹² Continue to monitor the effects of argatroban using aPTT during conversion to warfarin.³⁹²

For an argatroban infusion rate ≤2 mcg/kg per minute, discontinue argatroban therapy when INR on combined therapy >4.³⁹² Avoid overshooting target INR, as supratherapeutic INRs during concomitant therapy with direct thrombin inhibitors and warfarin have been associated with necrosis or gangrene of the skin or limbs.⁴⁴¹ ⁴⁴² ⁴⁴⁴

Determine INR 4–6 hours after discontinuance of argatroban infusion during warfarin monotherapy.³⁹² If INR is below the desired therapeutic range, resume argatroban infusion.³⁹² Repeat attempts to discontinue argatroban daily and until INR (4–6 hours after discontinuance of argatroban) on warfarin alone is in therapeutic range.³⁹²

For argatroban infusion rates >2 mcg/kg per minute, reduce infusion rate temporarily to 2 mcg/kg per minute, and reinstitute the procedure just described for conversion to oral therapy.³⁹² Repeat INR determination 4–6 hours after reduction of the argatroban infusion and reinstitute procedure just described for conversion to oral therapy.³⁹²

Administration

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Administer orally.^a Administer by IV injection when a coumarin derivative is indicated and oral therapy is not feasible.²¹¹

IM administration not recommended.²¹¹

Oral Administration

Administer orally in a single, daily dose.^a

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Reconstitution

Reconstitute powder for injection with 2.7 mL of sterile water for injection to a final concentration of 2 mg/mL.²¹¹

Rate of Administration

Inject slowly (over 1–2 minutes) into a peripheral vein.²¹¹

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as warfarin sodium; dosage expressed in terms of the salt.²¹¹ ³³⁰

Pediatric Patients

Venous Thrombosis and Pulmonary Embolism

Treatment or Secondary Prevention

Oral

Neonates with homozygous protein C deficiency and associated purpura fulminans: Maintenance of an INR of 2.5–4.5 long-term suggested.⁴⁴⁶

Children >2 months of age with first episode idiopathic thromboembolic event: Follow-up anticoagulation after heparin or an LMW heparin with dosage adjusted to maintain a target INR of 2.5 (range 2–3) for at least 6 months.⁴⁴⁶

Children >2 months of age with first episode thromboembolic event secondary to precipitating factors: Maintenance of a target INR of 2.5 (range 2–3) is suggested for 3 months or until resolution of such factors.⁴⁴⁶ Such factors include cancer, trauma/surgery, congenital heart disease, or systemic lupus erythematosus.⁴⁴⁶

Children >2 months of age with recurrent thromboembolic events secondary to precipitating factors after previous 3 months of oral anticoagulation: Continued maintenance of a target INR of 2.5 (range 2–3) is suggested for another 3 months or until resolution of such factors.⁴⁴⁶

Children with recurrent idiopathic thromboembolic events: Indefinite oral anticoagulation at low (INR of 1.3–1.8) to moderate intensity (INR of 2–3) suggested.⁴²⁶ ⁴⁴⁶

Children >2 months of age with central venous catheter-associated venous thromboembolic events: Adjust dosage to maintain target INR of 2.5 (range 2–3) for 3 months.⁴⁴⁶

Children >2 months of age with first DVT associated with a central venous catheter after previous 3 months of oral anticoagulation for catheter-related thrombosis: Continue anticoagulation at a lower intensity (INR 1.5–1.8) until the central venous catheter is removed.⁴⁴⁶

Children >2 months of age with recurrent thrombosis associated with a central venous catheter after previous 3 months of oral anticoagulation: Continue anticoagulation at a lower intensity (INR 1.5–1.8) until the central venous catheter is removed.⁴⁴⁶

Children >2 months of age with breakthrough thrombosis associated with central venous catheters despite low-intensity oral anticoagulation: Increase of the anticoagulation to an INR of 2–3 until the catheter is removed or for a minimum of 3 months.⁴⁴⁶

Children >2 months of age receiving long-term total parenteral nutrition via a central venous catheter: Continuous dosage at INR 2–2.5 suggested or alternatively, for the first 3 months after each central venous catheter is inserted.⁴⁴⁶

Cardiovascular Conditions†

Oral

Giant coronary aneurysms following Kawasaki disease†: Adjustment of dosage to maintain an INR of 2–3 with aspirin (3–5 mg/kg daily) is suggested to reduce subsequent thrombosis and infarction.⁴⁴⁶

Neonates and children with dilated cardiomyopathy†: Primary prophylaxis at INR of 2–3 suggested while the child is awaiting a cardiac transplant.⁴⁴⁶

Fontan surgery for congenital univentricular heart lesions†: Maintenance of an INR of 2–3 following full-dose heparin suggested for primary prevention of thromboembolic events; the optimal duration of therapy unknown.⁴⁴⁶

Cerebral Thromboembolism

Acute Cerebral Venous Sinus Thrombosis†

Oral

Secondary prevention†: Follow-up oral anticoagulation at a target INR of 2.5 (range 2–3) for 3–6 months after therapy with unfractionated heparin or an LMW heparin.⁴⁴⁶

Adults

Venous Thrombosis and Pulmonary Embolism

Treatment or Secondary Prevention

Oral

As follow-up to therapy with heparin or an LMW heparin, initial dose is 5–10 mg daily.²¹¹ ³³² ³³⁴ ³⁶⁵ ⁴⁰⁷ ⁴²⁶ Adjust subsequent daily dosage to achieve and maintain a target INR of 2.5 (range 2–3) for ≥3 months.²¹¹ ³³² ³³⁴ ³⁶⁵ ⁴⁰⁷

Individualize length of treatment of DVT or pulmonary embolism based on age, comorbid conditions, and the likelihood of recurrence.³⁶⁵ ⁴²⁷

DVT or pulmonary embolism with reversible or time-limited risk factors for venous thromboembolism: Adjust dosage to maintain a target INR of 2.5 (range 2–3) for at least 3 months.³⁶⁵ ⁴²⁷

First episode of idiopathic DVT: Adjust dosage to maintain a target INR of 2.5 (range 2–3) for at least 6–12 months.³³² ³⁶⁵ ⁴²⁷ ⁴⁴⁶

First episode of DVT or pulmonary embolism and continuing risk factors: Adjust dosage to maintain a target INR of 2.5 (range 2–3) for at least 6–12 months.³⁶⁵ ⁴²⁷ Such factors include cancer, antithrombin III or protein C or S deficiencies, antiphospholipid antibody syndrome, factor V Leiden or prothrombin 20210A gene mutations, homocysteinemia, and high levels of factor VII.³⁶⁵ ⁴²⁷

First episode of DVT or pulmonary embolism with antiphospholipid antibodies or ≥2 thrombophilic conditions: Adjust dosage to maintain a target INR of 2.5 (range 2–3) for 12 months.⁴²⁷ Indefinite anticoagulation suggested in these patients.⁴²⁷

Consider long-term therapy in patients with risk factors for recurrent thromboembolism, including venous insufficiency, idiopathic venous thromboembolism, and history of thrombotic events (≥2 episodes).²¹¹ ⁴²⁷ ⁴⁴⁶

Prophylaxis in Hip-replacement Surgery

Oral

Initially, 5–10 mg daily with dosage adjusted to achieve a target INR of 2.5 (range 2–3) for ≥10 days.³³³ ³⁶⁶ ⁴³⁰

Initiate prophylaxis for venous thromboembolism perioperatively (the evening before or after surgery).²⁰³ ²⁰⁸ ³³³ ³⁶⁶ ⁴³⁰

Extended prophylaxis for ≤28–35 days with warfarin, fondaparinux, or LMW heparin recommended.⁴³⁰

Prophylaxis in Hip-fracture Surgery

Oral

Initially, 5–10 mg daily with dosage adjusted to achieve a target INR of 2.5 (range 2–3) for ≥10 days.³³³ ³⁶⁶ ⁴³⁰

Initiate prophylaxis for venous thromboembolism preoperatively with heparin or a LMW heparin if surgery is delayed or after surgery once hemostasis has been demonstrated.⁴³⁰ Continue prophylactic anticoagulant therapy with warfarin, a LMW heparin, or fondaparinux following surgery for 28–35 days.⁴³⁰

Prophylaxis in Knee-replacement Surgery

Oral

Initially, 5–10 mg daily with dosage adjusted to achieve a target INR of 2.5 (range 2–3) for 10 days.³³³ ³⁶⁶ ⁴³⁰

Initiate prophylaxis for venous thromboembolism perioperatively (the evening before or after surgery).²⁰³ ²⁰⁸ ³³³ ³⁶⁶ ⁴³⁰

Prophylaxis in Trauma

Oral

Acute spinal cord injury: Following initial therapy with an LMW heparin, adjust warfarin sodium dosage to a target INR of 2.5 (range 2–3) in the rehabilitation phase.³⁶⁶ ⁴³⁰ Continue prophylactic anticoagulant therapy following trauma for a minimum of 3 months or until completion of the inpatient phase of rehabilitation.⁴³⁰

Trauma patients with impaired mobility: Adjust dosage to a target INR of 2.5 (range 2–3) after hospital discharge.⁴³⁰

Embolism Associated with Atrial Fibrillation/Flutter

Oral

Adjust dosage for long-term oral anticoagulation to a target INR of 2.5 (range 2–3) in patients who are at high risk for stroke.³³⁵ ³³⁹ ³⁴⁴ ³⁴⁵ ³⁴⁹ ³⁶⁸ ⁴³¹ ⁴³⁴

For atrial fibrillation persisting for >48 hours after open-heart surgery: Maintain a target INR of 2.5 (range 2–3) in patients at high risk for stroke for several weeks following reversion to normal sinus rhythm.⁴³¹

Atrial flutter and mitral stenosis: Adjust dosage to maintain a target INR of 2.5 (range 2–3).⁴³¹

Thromboprophylaxis during Cardioversion of Atrial Fibrillation/Flutter

Oral

Initiate at least 3–4 weeks prior to cardioversion (target INR of 2.5, range 2–3) and continue after the procedure until normal sinus rhythm has been maintained for 3–4 weeks.³³⁴ ³³⁵ ³³⁶ ³³⁹ ³⁶⁷ ³⁶⁸ ⁴³¹ For emergency cardioversion, administer for ≥4 weeks as follow-up anticoagulation after initiating periprocedural IV heparin.³³⁵ ³³⁶ ³³⁹ ³⁴¹ ³⁶⁷ ³⁶⁸ ⁴³¹

Embolism Associated with Valvular Heart Disease

Oral

Mitral valve disease associated with rheumatic fever or mitral valve regurgitation: Adjust dosage to prolong the INR to a target of 2.5 (range 2–3) in patients who have either concurrent paroxysmal or chronic persistent atrial fibrillation or a history of systemic embolism (e.g., stroke).³⁴⁰ ³⁷¹ ⁴³³ Add aspirin (75–100 mg daily) to therapy in patients who have a breakthrough embolic event.³⁷¹ ⁴³³

Rheumatic mitral valve disease with left atrial hypertrophy (left atrial diameter exceeding 5.5 cm) and normal sinus rhythm: Long-term anticoagulation at a target INR of 2.5 (range 2–3).³⁴⁰ ³⁷¹ ⁴³³

Mitral valve prolapse and a history of systemic embolism (e.g., stroke), or recurrent TIAs despite aspirin therapy: Maintain a target INR of 2.5 (range 2–3).³⁴⁰ ³⁴¹ ³⁷¹ ⁴³³

Mitral annular calcification complicated by systemic embolism (noncalcific systemic embolism): Long-term prophylaxis at a target INR of 2.5 (range 2–3) suggested.³⁴⁰ ³⁷¹ ⁴³³

Patients undergoing percutaneous mitral valvuloplasty: Maintain a target INR of 2.5 (range 2–3) for 3 weeks prior to the procedure and for 4 weeks after the procedure.⁴³³

Thromboembolism Associated with Prosthetic Heart Valves

Prophylaxis

Oral

Bioprosthetic valve in the aortic position: Adjust dosage to maintain a target INR of 2.5 (range 2–3) during the first 3 months.⁴³³

Bioprosthetic valve in the mitral position: Adjust dosage to maintain a target INR of 2.5 (range 2–3) for the first 3 months.⁴³³

Mitral bioprosthetic heart valve and additional risk factors (atrial fibrillation, left ventricular dysfunction, prior thromboembolism, hypercoagulable states³⁴¹ ): Maintenance of a target INR of 3 (range 2.5–3.5) for ≥3 months recommended by ACC and AHA.³⁴¹

Bioprosthetic valves with evidence of a left atrial thrombus at valve replacement surgery: Adjust dosage to maintain a target INR of 2.5 (range 2–3) for the first 3 months.⁴³³

Patients with bioprosthetic valves who have a history of systemic embolism: Maintenance of a target INR of 2.5 (range 2–3) for 3–12 months recommended by ACCP.⁴³³

Patients with newer (e.g., bileaflet, Medtronic disk) mechanical heart valves in the aortic position with no additional risk factors: Adjust dosage to a target INR of 2.5 (range 2–3) long-term.³⁴¹ ³⁴⁷ ³⁷⁰ ⁴³³

Tilting disk valves and bileaflet mechanical heart valves i