Ampicillin

Dosage Form: injection, powder, for solution
Ampicillin for Injection, USP

For Intravenous Injection Only

In ADD-Vantage® Drug Delivery System

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

Ampicillin Description

Ampicillin for Injection, USP ADD-Vantage®, the monosodium salt of [2S - [2α,5α,6β(S*)]] - 6 - [(aminophenylacetyl)amino] - 3,3 - dimethyl - 7 - oxo - 4 - thia - 1 - azabicyclo[3.2.0]heptane - 2 - carboxylic acid, is a synthetic penicillin. It is an antibacterial agent with a broad spectrum of bactericidal activity against both penicillin-susceptible Gram-positive organisms and many common Gram-negative pathogens.

It has the following chemical structure:

The molecular formula is C16H18N3NaO4S, and the molecular weight is 371.39. Each ADD-Vantage® vial of Ampicillin for Injection, USP contains Ampicillin sodium equivalent to 1 or 2 grams Ampicillin. Ampicillin for Injection, USP contains 2.9 milliequivalents of sodium per 1 gram of drug. Ampicillin for Injection, USP in the ADD-Vantage® vial is intended for intravenous use only.

Ampicillin - Clinical Pharmacology

Ampicillin for Injection, USP diffuses readily into most body tissues and fluids. However, penetration into the cerebrospinal fluid and brain occurs only when the meninges are inflamed. Ampicillin is excreted largely unchanged in the urine and its excretion can be delayed by concurrent administration of probenecid. The active form appears in the bile in higher concentrations than those found in serum. Ampicillin is the least serum-bound of all the penicillins, averaging about 20% compared to approximately 60 to 90% for other penicillins. Ampicillin for Injection, USP is well tolerated by most patients and has been given in doses of 2 grams daily for many weeks without adverse reactions.

Microbiology

While in vitro studies have demonstrated the susceptibility of most strains of the following organisms, clinical efficacy for infections other than those included in the INDICATIONS AND USAGE section has not been demonstrated.

The following bacteria have been shown in in vitro studies to be susceptible to Ampicillin for Injection, USP:

GRAM-POSITIVE ORGANISMS: Hemolytic and nonhemolytic streptococci, D. pneumoniae, nonpenicillinase-producing staphylococci, Clostridia spp., B. anthracis, Listeria monocytogenes, and most strains of enterococci.

GRAM-NEGATIVE ORGANISMS: H. influenzae, N. gonorrhoeae, N. meningitidis, Proteus mirabilis, and many strains of Salmonella, Shigella, and E. coli.

Ampicillin does not resist destruction by penicillinase.

Susceptibility Tests

Ampicillin Susceptibility Test Discs, 10 mcg, should be used to estimate the in vitro susceptibility of bacteria to Ampicillin for Injection, USP.

Indications and Usage for Ampicillin

Ampicillin for Injection, USP is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the following conditions:

Respiratory tract Infections caused by S. pneumoniae (formerly D. pneumoniae). Staphylococcus aureus (penicillinase and nonpenicillinase-producing), H. influenzae, and Group A beta-hemolytic Streptococci.

Bacterial Meningitis caused by E. coli, Group B Streptococci, and other Gram-negative bacteria (Listeria monocytogenes, N. meningitidis). The addition of an aminoglycoside with Ampicillin may increase its effectiveness against Gram-negative bacteria.

Septicemia and Endocarditis caused by susceptible Gram-positive organisms including Streptococcus sp., penicillin G-susceptible staphylococci, and enterococci. Gram-negative sepsis caused by E. coli, Proteus mirabilis and Salmonella sp. respond to Ampicillin. Endocarditis due to enterococcal strains usually respond to intravenous therapy. The addition of an aminoglycoside may enhance the effectiveness of Ampicillin when treating streptococcal endocarditis.

Urinary Tract Infections caused by sensitive strains of E. coli and Proteus mirabilis.

Gastrointestinal Infections caused by Salmonella typhosa (typhoid fever), other Salmonella sp., and Shigella sp. (dysentery) usually respond to oral or intravenous therapy.

Bacteriology studies to determine the causative organisms and their susceptibility to Ampicillin should be performed. Therapy may be instituted prior to obtaining results of susceptibility testing.

It is advisable to reserve the parenteral form of this drug for moderately severe and severe infections and for patients who are unable to take the oral forms. A change to oral Ampicillin may be made as soon as appropriate.

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

Indicated surgical procedures should be performed.

Contraindications

A history of a previous hypersensitivity reaction to any of the penicillins is a contraindication.

Warnings

Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more apt to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens.

There have been well-documented reports of individuals with a history of penicillin hypersensitivity reactions who have experienced severe hypersensitivity reactions when treated with a cephalosporin. Before initiating therapy with a penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, and other allergens. If an allergic reaction occurs, the drug should be discontinued and appropriate therapy instituted.

SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE, OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.

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

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

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

Precautions

General

The possibility of superinfections with mycotic organisms or bacterial pathogens should be kept in mind during therapy. In such cases, discontinue the drug and substitute appropriate treatment.

A high percentage (43 to 100 percent) of patients with infectious mononucleosis who receive Ampicillin develop a skin rash. Typically, the rash appears 7 to 10 days after the start of oral Ampicillin therapy and remains for a few days to a week after the drug is discontinued. In most cases, the rash is maculopapular, pruritic, and generalized. Therefore, the administration of Ampicillin is not recommended in patients with mononucleosis. It is not known whether these patients are truly allergic to Ampicillin.

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

Information for Patients

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

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

Laboratory Tests

As with any potent drug, periodic assessment of organ system function, including renal, hepatic, and hematopoietic, should be made during prolonged therapy.

Transient elevation of serum transaminase has been observed following administration of Ampicillin. The significance of this finding is not known.

Drug Interactions

The concurrent administration of allopurinol and Ampicillin increases substantially the incidence of skin rashes in patients receiving both drugs as compared to patients receiving Ampicillin alone. It is not known whether this potentiation of Ampicillin rashes is due to allopurinol or the hyperuricemia present in these patients.

Drug/Laboratory Test Interactions

With high urine concentrations of Ampicillin, false-positive glucose reactions may occur if Clinitest, Benedicts Solution, or Fehlings Solution are used. Therefore, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix or Tes-Tape) be used.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

No long-term animal studies have been conducted with this drug.

Pregnancy Category B

Reproduction studies have been performed in laboratory animals at doses several times the human dose and have revealed no evidence of adverse effects due to Ampicillin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Labor and Delivery

Oral Ampicillin-class antibiotics are poorly absorbed during labor. Studies in guinea pigs showed that intravenous administration of Ampicillin slightly decreased the uterine tone and frequency of contractions, but moderately increased the height and duration of contractions. However, it is not known whether use of these drugs in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary.

Nursing Mothers

Ampicillin is excreted in trace amounts in human milk. Therefore, caution should be exercised when Ampicillin-class antibiotics are administered to a nursing woman.

Pediatric Use

Guidelines for the administration of these drugs to children are presented in DOSAGE AND ADMINISTRATION.

Adverse Reactions

As with other penicillins, it may be expected that untoward reactions will be essentially limited to sensitivity phenomena. They are more likely to occur in individuals who have previously demonstrated hypersensitivity to penicillins and in those with a history of allergy, asthma, hay fever, or urticaria.

The following adverse reactions have been reported as associated with the use of Ampicillin:

Gastrointestinal

Glossitis, stomatitis, black hairy tongue, nausea, vomiting, enterocolitis, pseudomembranous colitis, and diarrhea. (These reactions are usually associated with oral dosage forms.)

Hypersensitivity Reactions

Skin rashes and urticaria have been reported frequently. A few cases of exfoliative dermatitis and erythema multiforme have been reported. Anaphylaxis is the most serious reaction experienced and has usually been associated with the parenteral dosage form.

Note: Urticaria, other skin rashes, and serum sickness-like reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, Ampicillin should be discontinued, unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to Ampicillin therapy. Serious anaphylactic reactions require the immediate use of epinephrine, oxygen, and intravenous steroids.

Liver– A moderate rise in serum glutamic oxaloacetic transaminase (SGOT) has been noted, particularly in infants, but the significance of this finding is unknown. Mild transitory SGOT elevations have been observed in individuals receiving larger (two to four times) than usual and oft-repeated intramuscular injections. Evidence indicates that glutamic oxaloacetic transaminase (GOT) is released at the site of intramuscular injection of Ampicillin sodium and that the presence of increased amounts of this enzyme in the blood does not necessarily indicate liver involvement.

Hemic and Lymphatic Systems– Anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported during therapy with the penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.

Overdosage

In cases of overdose, discontinue medication, treat symptomatically, and institute supportive measures as required. In patients with renal function impairment, Ampicillin-class antibiotics can be removed by hemodialysis but not peritoneal dialysis.

Ampicillin Dosage and Administration

The Single Use ADD-Vantage® vials are for intravenous use only.

Infections of the respiratory tract and soft tissues.

Patients weighing 40 kg (88 lbs) or more: 250 to 500 mg every 6 hours.

Patients weighing less than 40 kg (88 lbs): 25 to 50 mg/kg/day in equally divided doses at 6- to 8- hour intervals.

Infections of the gastrointestinal and genitourinary tracts (including those caused by Neisseria gonorrhoeae in females).

Patients weighing 40 kg (88 lbs) or more: 500 mg every 6 hours.

Patients weighing less than 40 kg (88 lbs): 50 mg/kg/day in equally divided doses at 6- to 8- hour intervals.

In the treatment of chronic urinary tract and intestinal infections, frequent bacteriological and clinical appraisal is necessary. Smaller doses than those recommended above should not be used. Higher doses should be used for stubborn or severe infections. In stubborn infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy.

Urethritis in males due to N. gonorrhoeae.

Adults – Two doses of 500 mg each at an interval of 8 to 12 hours. Treatment may be repeated if necessary or extended if required.

In the treatment of complications of gonorrheal urethritis, such as prostatitis and epididymitis, prolonged and intensive therapy is recommended. Cases of gonorrhea with a suspected primary lesion of syphilis should have darkfield examinations before receiving treatment. In all other cases where concomitant syphilis is suspected, monthly serological tests should be made for a minimum of four months. The doses for the preceding infections may be given by intravenous route. A change to oral Ampicillin may be made when appropriate.

Bacterial Meningitis

Adults and children – 150 to 200 mg/kg/day in equally divided doses every 3 to 4 hours. (Treatment may be initiated with intravenous drip therapy and continued with intramuscular injections.) The doses for other infections may be given by either the intravenous or intramuscular route.

Septicemia

Adults and children – 150 to 200 mg/kg/day. Start with intravenous administration for at least three days and continue with the intramuscular route every 3 to 4 hours.

Treatment of all infections should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. A minimum of 10-days treatment is recommended for any infection caused by Group A beta-hemolytic streptococci to help prevent the occurrence of acute rheumatic fever or acute glomerulonephritis.

DIRECTIONS FOR USE

ADD-Vantage® Vial – Ampicillin for injection 1 and 2 grams.

The ADD-Vantage® vials for intravenous use only are to be used with ADD-Vantage® diluent containers: 0.9% Sodium Chloride Injection, USP, 50 mL and 100 mL, or 5% Dextrose Injection, USP, 50 mL and 100 mL.

Reconstitute ADD-Vantage® vial as directed in INSTRUCTIONS FOR USE.

Use only freshly prepared solutions. Intravenous injections should be administered immediately after reconstitution since the potency may decrease.

Summary of Utility Times for Constituted Ampicillin for Injection in the Hospira ADD-Vantage® System

Vial Size	IV Solution	Final Concentration	Utility Times
1 g Vial	5% Dextrose Injection, USP	10 mg/mL	2 Hours at 25°C
1 g Vial	0.9% Sodium Chloride Injection, USP	10 mg/mL	8 Hours at 25° C
2 g Vial	5% Dextrose Injection, USP	20 mg/mL	1 Hour at 25° C
2 g Vial	0.9% Sodium Chloride Injection, USP	40 mg/mL	6 Hours at 25° C

INSTRUCTIONS FOR USE

To Open Diluent Container:

Peel overwrap from the corner and remove container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.

To Assemble Vial and Flexible Diluent Container:

(Use Aseptic Technique)

1. Remove the protective covers from the top of the vial and the vial port on the diluent container as follows:
   
   a. To remove the breakaway vial cap, swing the pull ring over the top of the vial and pull down far enough to start the opening (SEE FIGURE 1), then pull straight up to remove the cap. (SEE FIGURE 2.)
   
   NOTE: Do not access vial with syringe.
   
   
   
   
   
   b. To remove the vial port cover, grasp the tab on the pull ring, pull up to break the three tie strings, then pull back to remove the cover. (SEE FIGURE 3.)


2. Screw the vial into the vial port until it will go no further. THE VIAL MUST BE SCREWED IN TIGHTLY TO ASSURE A SEAL. This occurs approximately 1/2 turn (180°) after the first audible click. (SEE FIGURE 4.) The clicking sound does not assure a seal; the vial must be turned as far as it will go. NOTE: Once vial is seated, do not attempt to remove. (SEE FIGURE 4.)


3. Recheck the vial to assure that it is tight by trying to turn it further in the direction of assembly.


4. Label appropriately.
   
   
   

To Prepare Admixture:

1. Squeeze the bottom of the diluent container gently to inflate the portion of the container surrounding the end of the drug vial.


2. With the other hand, push the drug vial down into the container telescoping the walls of the container. Grasp the inner cap of the vial through the walls of the container. (SEE FIGURE 5.)


3. Pull the inner cap from the drug vial. (SEE FIGURE 6.) Verify that the rubber stopper has been pulled out, allowing the drug and diluent to mix.


4. Mix container contents thoroughly and use within the specified time.
   
   
   

Preparation for Administration:

(Use Aseptic Technique)

1. Confirm the activation and admixture of vial contents.


2. Check for leaks by squeezing container firmly. If leaks are found, discard unit as sterility may be impaired.


3. Close flow control clamp of administration set.


4. Remove cover from outlet port at bottom of container.


5. Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated.
   
   NOTE: See full directions on administration set carton.


6. Lift the free end of the hanger loop on the bottom of the vial, breaking the two tie strings. Bend the loop outward to lock it in the upright position, then suspend container from hanger.


7. Squeeze and release drip chamber to establish proper fluid level in chamber.


8. Open flow control clamp and clear air from set. Close clamp.


9. Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture.


10. Regulate rate of administration with flow control clamp.

WARNING: Do not use flexible container in series connections.

How is Ampicillin Supplied

Ampicillin for Injection, USP ADD-Vantage® for intravenous injection.

Ampicillin sodium equivalent to 1 or 2 grams Ampicillin per vial.

NDC 0781-9412-92 1 gram ADD-Vantage® Vial, packed in 10s

NDC 0781-9413-92 2 grams ADD-Vantage® Vial, packed in 10s

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

ADDVantage® is a trademark of Hospira Inc.

06-2011M

46066287

Manufactured in Austria by Sandoz GmbH

for Sandoz Inc., Princeton, NJ 08540

gram Label

NDC 0781-9412-15

Ampicillin

for Injection, USP

1 gram Rx only

For Intravenous

Use Only

04-2010M

46031861

grams Label

NDC 0781-9413-15

Ampicillin

for Injection, USP

2 grams Rx only

For Intravenous

Use Only

04-2010M

46031859

Ampicillin  Ampicillin sodium  injection, powder, for solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0781-9412 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Ampicillin SODIUM (Ampicillin) Ampicillin 1 g

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0781-9412-92 10 VIAL In 1 PACKAGE contains a VIAL, GLASS (0781-9412-15) 1 0781-9412-15 1 VIAL In 1 VIAL, GLASS This package is contained within the PACKAGE (0781-9412-92)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA062738	02/19/1987

Ampicillin  Ampicillin sodium  injection, powder, for solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0781-9413 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Ampicillin SODIUM (Ampicillin) Ampicillin 2 g

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0781-9413-92 10 VIAL In 1 PACKAGE contains a VIAL, GLASS (0781-9413-15) 1 0781-9413-15 1 VIAL In 1 VIAL, GLASS This package is contained within the PACKAGE (0781-9413-92)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA062738	02/19/1987

Labeler - Sandoz Inc (110342024)

Revised: 01/2012Sandoz Inc

Nalfon 200

Generic Name: fenoprofen (Oral route)

fen-oh-PROE-fen

Oral route(Tablet;Capsule)

NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may be increased in patients with cardiovascular disease or risk factors for cardiovascular disease. Fenoprofen is contraindicated for the treatment of perioperative pain in the setting of CABG surgery. NSAIDs can also cause an increased risk of serious gastrointestinal adverse events especially in the elderly, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal .

Commonly used brand name(s)

In the U.S.

• Nalfon


• Nalfon 200

Available Dosage Forms:

• Capsule


• Tablet

Therapeutic Class: Analgesic

Pharmacologic Class: NSAID

Chemical Class: Propionic Acid (class)

Uses For Nalfon 200

Fenoprofen is a nonsteroidal anti-inflammatory drug (NSAID) used to treat mild to moderate pain, and helps to relieve symptoms of arthritis (osteoarthritis and rheumatoid arthritis), such as inflammation, swelling, stiffness, and joint pain. This medicine does not cure arthritis and will help you only as long as you continue to take it .

This medicine is available only with your doctor's prescription .

Before Using Nalfon 200

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

Allergies

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

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of fenoprofen in children below 18 years of age. Safety and efficacy have not been established .

Geriatric

Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of fenoprofen in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require caution in patients receiving fenoprofen .

Breast Feeding

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

Interactions with Medicines

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

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Ketorolac


• Pentoxifylline

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

• Ardeparin


• Beta Glucan


• Certoparin


• Citalopram


• Clopidogrel


• Clovoxamine


• Dalteparin


• Danaparoid


• Desirudin


• Enoxaparin


• Escitalopram


• Femoxetine


• Flesinoxan


• Fluoxetine


• Fluvoxamine


• Ginkgo


• Methotrexate


• Nadroparin


• Nefazodone


• Parnaparin


• Paroxetine


• Pemetrexed


• Reviparin


• Sertraline


• Tacrolimus


• Tinzaparin


• Zimeldine

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

• Acebutolol


• Acetohexamide


• Alacepril


• Alprenolol


• Amiloride


• Arotinolol


• Atenolol


• Azilsartan Medoxomil


• Azosemide


• Befunolol


• Bemetizide


• Benazepril


• Bendroflumethiazide


• Benzthiazide


• Betaxolol


• Bevantolol


• Bisoprolol


• Bopindolol


• Bucindolol


• Bumetanide


• Bupranolol


• Buthiazide


• Candesartan Cilexetil


• Canrenoate


• Captopril


• Carteolol


• Carvedilol


• Celiprolol


• Chlorothiazide


• Chlorpropamide


• Chlorthalidone


• Cilazapril


• Clopamide


• Cyclopenthiazide


• Cyclosporine


• Delapril


• Desvenlafaxine


• Dicumarol


• Dilevalol


• Duloxetine


• Enalaprilat


• Enalapril Maleate


• Eprosartan


• Esmolol


• Ethacrynic Acid


• Fosinopril


• Furosemide


• Gliclazide


• Glimepiride


• Glipizide


• Gliquidone


• Glyburide


• Hydrochlorothiazide


• Hydroflumethiazide


• Imidapril


• Indapamide


• Irbesartan


• Labetalol


• Landiolol


• Levobetaxolol


• Levobunolol


• Lisinopril


• Losartan


• Mepindolol


• Methyclothiazide


• Metipranolol


• Metolazone


• Metoprolol


• Milnacipran


• Moexipril


• Nadolol


• Nebivolol


• Nipradilol


• Olmesartan Medoxomil


• Oxprenolol


• Penbutolol


• Pentopril


• Perindopril


• Pindolol


• Piretanide


• Polythiazide


• Propranolol


• Quinapril


• Ramipril


• Sotalol


• Spirapril


• Spironolactone


• Talinolol


• Tasosartan


• Telmisartan


• Temocapril


• Tertatolol


• Timolol


• Tolazamide


• Tolbutamide


• Torsemide


• Trandolapril


• Triamterene


• Trichlormethiazide


• Valsartan


• Venlafaxine


• Xipamide


• Zofenopril

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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

• Anemia or


• Asthma or


• Bleeding problems or


• Blood clots or


• Edema (fluid retention or body swelling) or


• Heart attack, history of or


• Heart disease (e.g., congestive heart failure) or


• High blood pressure or


• Kidney disease, history of or


• Liver disease (e.g., hepatitis) or


• Stomach or intestinal ulcers or bleeding or


• Stroke, history of—Use with caution. This medicine may make these conditions worse .

• Aspirin sensitivity, history of, or


• Kidney disease, severe—This medicine should NOT be used in patients with this condition .

• Heart surgery (e.g., coronary artery bypass graft [CABG] surgery)—This medicine should NOT be used to relieve pain right before or after the surgery .

Proper Use of fenoprofen

This section provides information on the proper use of a number of products that contain fenoprofen. It may not be specific to Nalfon 200. Please read with care.

For safe and effective use of this medicine, do not take more of it, do not take it more often, and do not take it for a longer time than ordered by your doctor. Taking too much of this medicine may increase the chance of unwanted effects, especially in elderly patients .

When used for severe or continuing arthritis, this medicine must be taken regularly as ordered by your doctor in order for it to help you. This medicine usually begins to work within one week, but in severe cases up to two weeks or even longer may pass before you begin to feel better. Also, several weeks may pass before you feel the full effects of this medicine .

To lessen stomach upset, you may take this medicine with food or milk .

Dosing

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

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

• For oral dosage form (capsules):
  
  • For mild to moderate pain:
    
    • Adults—200 milligrams (mg) every four to six hours as needed.
    
    
    • Children—Use and dose must be determined by your doctor .
    
    
  
  
  • For osteoarthritis and rheumatoid arthritis:
    
    • Adults—At first, 300 or 600 mg three or four times a day. Your doctor may increase or decrease your dose as needed. However, the dose usually is not more than 3200 mg per day.
    
    
    • Children—Use and dose must be determined by your doctor .
    
    
  
  

Missed Dose

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

Storage

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

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Nalfon 200

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood and urine tests may be needed to check for unwanted effects .

This medicine may raise your risk of having a heart attack or stroke. This is more likely in people who already have heart disease. People who use this medicine for a long time might also have a higher risk .

This medicine may cause bleeding in your stomach or intestines. These problems can happen without warning signs. This is more likely if you have had a stomach ulcer in the past, if you smoke or drink alcohol regularly, if you are over 60 years old, if you are in poor health, or if you are using certain other medicines (a steroid or a blood thinner) .

Serious skin reactions can occur during treatment with this medicine. Check with your doctor right away if you have any of the following symptoms while taking this medicine: blistering, peeling, loosening of skin, chills, cough, diarrhea, fever, itching, joint or muscle pain, red skin lesions, sore throat, sores, ulcers, white spots in mouth or on lips, or unusual tiredness or weakness .

Possible warning signs of some serious side effects that can occur during treatment with this medicine may include swelling of the face, fingers, feet, and/or lower legs; severe stomach pain, black, tarry stools, and/or vomiting of blood or material that looks like coffee grounds; unusual weight gain; yellow skin or eyes; decreased urination; bleeding or bruising; and/or skin rash. Also, signs of serious heart problems could occur such as chest pain, tightness in chest, fast or irregular heartbeat, unusual flushing or warmth of skin, weakness, or slurring of speech. Stop taking this medicine and check with your doctor immediately if you notice any of these warning signs .

This medicine may also cause a serious type of allergic reaction called anaphylaxis. Although this is rare, it may occur often in patients who are allergic to aspirin or other nonsteroidal anti-inflammatory drugs. Anaphylaxis requires immediate medical attention. The most serious signs of this reaction are very fast or irregular breathing, gasping for breath, wheezing, or fainting. Other signs may include changes in skin color of the face; very fast but irregular heartbeat or pulse; hive-like swellings on the skin; and puffiness or swelling of the eyelids or around the eyes. If these effects occur, get emergency help at once .

Using this medicine while you are pregnant can harm your unborn baby. If you think you have become pregnant while using this medicine, tell your doctor right away .

Check with your doctor immediately if blurred vision, difficulty in reading, or any other change in vision occurs during or after your treatment. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor) .

This medicine may cause some people to become dizzy, lightheaded, drowsy, or less alert than they are normally. Even if taken at bedtime, it may cause some people to feel drowsy or less alert on arising. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are not alert .

Check with your doctor if you start having ringing in your ears or trouble hearing while you are using this medicine. Your doctor may want you to have your ears checked by an ear doctor especially when you are using this medicine for a long time .

Before having any kind of surgery or medical tests, tell your doctor that you are taking this medicine. It may be necessary for you to stop treatment for a while, or to change to a different nonsteroidal anti-inflammatory drug before your procedure .

Nalfon 200 Side Effects

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

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

More common

• Headache

Less common

• Abdominal pain


• bloating or swelling of face, arms, hands, lower legs, or feet


• blurred vision


• continuing ringing or buzzing or other unexplained noise in ears


• decreased hearing


• difficult or labored breathing


• fast, irregular, pounding, or racing heartbeat or pulse


• hearing loss


• itching skin


• rapid weight gain


• rash


• shortness of breath


• tightness in chest


• tingling of hands or feet


• unusual weight gain or loss


• wheezing

Rare

• Back, leg, or stomach pains


• black or red, tarry stools


• bleeding gums


• blood in vomit


• bloody or cloudy urine


• bloody stools


• burning feeling in chest or stomach


• chills


• clay-colored stools


• coughing up blood


• dark urine


• diarrhea


• difficult, burning, or painful urination


• difficulty in swallowing


• dizziness


• dry mouth


• fever with or without chills


• frequent urge to urinate


• general body swelling


• greatly decreased frequency or amount of urine


• hoarseness


• increased blood pressure


• increased menstrual flow or vaginal bleeding


• increased thirst


• indigestion


• large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs


• loss of appetite


• lower back or side pain


• nausea


• nosebleeds


• not able to pass urine


• pale skin


• paralysis


• pinpoint red or purple spots on skin


• prolonged bleeding from cuts


• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue


• red or dark brown urine


• redness of skin


• severe or continuing stomach pain


• sore throat


• sores, ulcers, or white spots on lips or in mouth


• stomach upset


• swelling of face, fingers, or lower legs


• swelling of hands, legs, and feet


• swollen or painful glands


• tenderness in stomach area


• troubled breathing


• unpleasant breath odor


• unusual bleeding or bruising


• unusual tiredness or weakness


• vomiting


• vomiting of blood or material that looks like coffee grounds


• yellow eyes or skin

Symptom of overdose

• Dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly


• irregular, fast or slow, or shallow breathing


• pale or blue lips, fingernails, or skin


• rapid, deep breathing


• restlessness


• shakiness and unsteady walk


• stomach cramps


• unsteadiness, trembling, or other problems with muscle control or coordination

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

More common

• Acid or sour stomach


• belching


• constipation


• heartburn


• lack or loss of strength


• sleepiness or unusual drowsiness


• stomach discomfort

Less common

• Body aches or pain


• cough


• ear congestion


• increased sweating


• loss of voice


• mood or mental changes


• muscle aches


• nasal congestion


• sneezing


• stuffy or runny nose


• tremor

Rare

• General feeling of discomfort or illness


• sleeplessness


• trouble sleeping


• unable to sleep

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

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

See also: Nalfon 200 side effects (in more detail)

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

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

More Nalfon 200 resources

• Nalfon 200 Side Effects (in more detail)
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• Drug Images
• Nalfon 200 Drug Interactions
• Nalfon 200 Support Group
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Malignant Hyperthermia Medications

Definition of Malignant Hyperthermia: Malignant hyperthermia is a group of inherited muscle problems characterized by muscle breakdown following certain stimuli -- such as anesthesia, extremes of exercise (particularly in hot conditions), fever, or use of stimulant drugs. The problems associated with this condition result from over-excitable muscles that contract uncontrollably, severe fever, abnormal heart rhythms, and kidney failure.

Drugs associated with Malignant Hyperthermia

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

Learn more about Malignant Hyperthermia

Medical Encyclopedia:

• Malignant hyperthermia

Harvard Health Guide:

• Symptoms and treatment for Malignant Hyperthermia

Drug List:

Dantrium

Dantrium-Intravenous

Colgate Total Whitening Gel

Dosage Form: gel, dentifrice
Colgate®

Total®

Whitening Gel

Drug Facts

Active ingredients	Purpose
Sodium fluoride 0.24% (0.14% w/v fluoride ion)	Anticavity
Triclosan 0.30%	Antigingivitis

Uses

aids in the prevention of:

• cavities


• plaque


• gingivitis

Warnings

Keep out of the reach of children under 6 years of age.

If more than used for brushing is accidentally swallowed, get medical help or contact a Poison Control Center right away.

Ask a dentist before use if you have

• bleeding or redness lasting more than 2 weeks


• pain, swelling, pus, loose teeth, or more spacing between teeth

These may be signs of periodontitis, a serious form of gum disease.

Directions

supervise children as necessary until capable of using without supervision.

adults and children 6 years of age and older	brush teeth thoroughly, preferably after each meal or at least twice a day, or as directed by a dentist or a physician
children under 12 years	instruct in good brushing and rinsing habits (to minimize swallowing)
children under 6 years	do not use unless directed by a dentist or a physician

Antiplaque and antigingivitis use not proven in children.

Inactive ingredients

water, hydrated silica, glycerin, sorbitol, PVM/MA copolymer, sodium lauryl sulfate, cellulose gum, flavor, sodium hydroxide, propylene glycol, carrageenan, sodium saccharin, mica, titanium dioxide, FD&C blue no.1

Questions or comments?

Call toll-free 1-800-468-6502

Dist. by:

COLGATE-PALMOLIVE COMPANY

New York, NY 10022

www.colgatetotal.com

PRINCIPAL DISPLAY PANEL - 221 g Tube Carton

Helps Prevent Cavities • Gingivitis • Plaque

Colgate®

Anticavity Fluoride and Antigingivitis Toothpaste

Total®

Whitening

Gel

ADA

Accepted

American

Dental

Association ®

NET WT 7.8 OZ (221 g)

Fights Tartar Buildup • Whitens Teeth

COLGATE  TOTAL WHITENING sodium fluoride and triclosan  gel, dentifrice

Product Information Product Type HUMAN OTC DRUG NDC Product Code (Source) 65954-002 Route of Administration DENTAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Sodium Fluoride (Fluoride Ion) Sodium Fluoride 2.4 mg  in 1 g Triclosan (Triclosan) Triclosan 3 mg  in 1 g

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color WHITE, BLUE Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 65954-002-78 1 TUBE In 1 CARTON contains a TUBE 1 221 g In 1 TUBE This package is contained within the CARTON (65954-002-78)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA020231	10/01/2009

Labeler - Mission Hills, S.A. de C.V. (812312122)

Revised: 09/2010Mission Hills, S.A. de C.V.

More Colgate Total Whitening Gel resources

• Colgate Total Whitening Gel Use in Pregnancy & Breastfeeding
• Colgate Total Whitening Gel Support Group
• 3 Reviews for Colgate Total Whitening - Add your own review/rating

Compare Colgate Total Whitening Gel with other medications

• Prevention of Dental Caries

Warfarin Tablets 1mg

1. Name Of The Medicinal Product

Warfarin Tablets 1mg

2. Qualitative And Quantitative Composition

Each tablet contains 1 mg warfarin sodium (as clathrate).

3. Pharmaceutical Form

Round brown uncoated tablet, scored and marked 'W1' on one side with company logo on reverse.

4. Clinical Particulars

4.1 Therapeutic Indications

For prophylaxis against venous thrombosis and pulmonary embolism, and for use in the treatment of these conditions to prevent their extension. For the prophylaxis of systemic embolisation in patients with rheumatic heart disease and atrial fibrillation.

4.2 Posology And Method Of Administration

Warfarin tablets are for oral administration.

An initial daily dose of 10mg on the first two days. Subsequent daily doses should be adjusted according to the results of the prothrombin time or other appropriate coagulation tests. The single daily maintenance requirement is usually between 5mg and 12mg, but can vary between 2mg and 30mg.

The maintenance dose is omitted if the prothrombin time is excessively prolonged.

Use in elderly patients: The elderly are generally more sensitive to the effects of warfarin and often require a smaller dose on a weight for weight basis than younger patients.

Target INR

By referring to the target INR (see below), the dosage of warfarin can be adjusted depending on the deviation of the patient's INR from the target value. An INR within 0.5 INR units of the target is considered to be generally satisfactory.

The following target INR values are based on guidelines from The British Society for Haematology:

Indication	Target INR
Pulmonary embolus	2.5
Proximal deep vein thrombosis	2.5
Calf vein thrombosis in non-surgical patients with no persistent risk factors	2.5
Post-operative calf vein thrombosis without persistent risk factors	2.5
Recurrence of venous thromboembolism when no longer on warfarin therapy	2.5
Recurrence of venous thromboembolism whilst on warfarin therapy	3.5
Symptomatic inherited thrombophilia	2.5
Antiphospholipid syndrome	3.5
Non-rheumatic atrial fibrillation	2.5
Atrial fibrillation due to rheumatic heart disease, congenital heart disease, thyrotoxicosis	2.5
Cardioversion	2.5
Mural thrombus	2.5
Cardiomyopathy	2.5
Mechanical prosthetic heart valve	3.5

4.3 Contraindications

• Known hypersensitivity to warfarin or to any of the excipients

• Haemorrhagic stroke (see section 4.4 for further details)

• Clinically significant bleeding

• Within 72 hours of major surgery with risk of severe bleeding (for information on other surgery, see section 4.4)

• Within 48 hours postpartum

• Pregnancy (first and third trimesters, see section 4.6)

• Drugs where interactions may lead to a significantly increased risk of bleeding (see section 4.5)

4.4 Special Warnings And Precautions For Use

Most adverse events reported with warfarin are a result of over anticoagulation therefore it is important that the need for therapy is reviewed on a regular basis and therapy discontinued when no longer required.

Patients should be given a patient-held information booklet ('warfarin card') and informed of symptoms for which they should seek medical attention.

Commencement of therapy

Monitoring

When warfarin is started using a standard dosing regimen the INR should be determined daily or on alternate days in the early days of treatment. Once the INR has stabilised in the target range the INR can be determined at longer intervals.

INR should be monitored more frequently in patients at an increased risk of over coagulation e.g. patients with severe hypertension, liver or renal disease.

Patients for whom adherence may be difficult should be monitored more frequently.

Thrombophilia

Patients with protein C deficiency are at risk of developing skin necrosis when starting warfarin treatment. In patients with protein C deficiency, therapy should be introduced without a loading dose of warfarin even if heparin is given. Patients with protein S deficiency may also be at risk and it is advisable to introduce warfarin therapy slowly in these circumstances.

Risk of haemorrhage

The most frequently reported adverse effect of all oral anticoagulants is haemorrhage. Warfarin should be given with caution to patients where there is a risk of serious haemorrhage (e.g. concomitant NSAID use, recent ischaemic stroke, bacterial endocarditis, previous gastrointestinal bleeding).

Risk factors for bleeding include high intensity of anticoagulation (INR>4.0), age

Checking the INR and reducing or omitting doses depending on INR level is essential, following consultation with anticoagulation services if necessary. If the INR is found to be too high, reduce dose or stop warfarin treatment; sometimes it will be necessary to reverse anticoagulation. INR should be checked within 2–3 days to ensure that it is falling.

Any concomitant anti-platelet drugs should be used with caution due to an increased risk of bleeding.

Haemorrhage

Haemorrhage can indicate an overdose of warfarin has been taken. For advice on treatment of haemorrhage see section 4.9.

Unexpected bleeding at therapeutic levels should always be investigated and INR monitored.

Ischaemic stroke

Anticoagulation following an ischaemic stroke increases the risk of secondary haemorrhage into the infarcted brain. In patients with atrial fibrillation long term treatment with warfarin is beneficial, but the risk of early recurrent embolism is low and therefore a break in treatment after ischaemic stroke is justified. Warfarin treatment should be re-started 2–14 days following ischaemic stroke, depending on the size of the infarct and blood pressure. In patients with large embolic strokes, or uncontrolled hypertension, warfarin treatment should be stopped for 14 days.

Surgery

For surgery where there is no risk of severe bleeding, surgery can be performed with an INR of <2.5.

For surgery where there is a risk of severe bleeding, warfarin should be stopped 3 days prior to surgery.

Where it is necessary to continue anticoagulation e.g. risk of life-threatening thromboembolism, the INR should be reduced to <2.5 and heparin therapy should be started.

If surgery is required and warfarin cannot be stopped 3 days beforehand, anticoagulation should be reversed with low-dose vitamin K.

The timing for re-instating warfarin therapy depends on the risk of post-operative haemorrhage. In most instances warfarin treatment can be re-started as soon as the patient has an oral intake.

Dental Surgery

Warfarin need not be stopped before routine dental surgery, eg, tooth extraction.

Active peptic ulceration

Due to a high risk of bleeding, patients with active peptic ulcers should be treated with caution. Such patients should be reviewed regularly and informed of how to recognise bleeding and what to do in the event of bleeding occurring.

Interactions

Many drugs and foods interact with warfarin and affect the prothrombin time (see section 4.5). Any change to medication, including self-medication with OTC products, warrants increased monitoring of the INR. Patients should be instructed to inform their doctor before they start to take any additional medications including over the counter medicines, herbal remedies or vitamin preparations.

Thyroid disorders

The rate of warfarin metabolism depends on thyroid status. Therefore patients with hyper- or hypo-thyroidism should be closely monitored on starting warfarin therapy.

Additional circumstances where changes in dose may be required

The following also may exaggerate the effect of warfarin tablets, and necessitate a reduction of dosage:

• Loss of weight

• Acute illness

• Cessation of smoking

The following may reduce the effect of warfarin tablets, and require the dosage to be increased:

• Weight gain

• Diarrhoea

• Vomiting

Other warnings

Acquired or inherited warfarin resistance should be suspected if larger than usual daily doses of warfarin are required to achieve the desired anticoagulant effect.

Genetic information

Genetic variability particularly in relation to CYP2C9 and VKORC1 can significantly affect dose requirements for warfarin. If a family association with these polymorphisms is known extra care is warranted.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Warfarin has a narrow therapeutic range and care is required with all concomitant therapy. The individual product information for any new concomitant therapy should be consulted for specific guidance on warfarin dose adjustment and therapeutic monitoring. If no information is provided the possibility of an interaction should be considered. Increased monitoring should be considered when commencing any new therapy if there is any doubt as to the extent of interaction.

Pharmacodynamic interactions

Drugs which are contraindicated

Concomitant use of drugs used in the treatment or prophylaxis of thrombosis, or other drugs with adverse effects on haemostasis may increase the pharmacological effect of warfarin, increasing the risk of bleeding.

Fibrinolytic drugs such as streptokinase and alteplase are contraindicated in patients receiving warfarin.

Drugs which should be avoided if possible

The following examples should be avoided, or administered with caution with increased clinical and laboratory monitoring:

• Clopidogrel

• NSAIDs (including aspirin and cox-2 specific NSAIDS)

• Sulfinpyrazone

• Thrombin inhibitors such as bivalirudin, dabigatran

• Dipyridamole

• Unfractionated heparins and heparin derivatives, low molecular weight heparins

• Fondaparinux, rivaroxaban

• Glycoprotein IIb/IIIa receptor antagonists such as eptifibatide, tirofiban and abciximab

• Prostacyclin

• SSRI and SNRI antidepressants

• Other drugs which inhibit haemostasis, clotting or platelet action

Low-dose aspirin with warfarin may have a role in some patients but the risk of gastrointestinal bleeding is increased. Warfarin may initially be given with a heparin in the initial treatment of thrombosis, until the INR is in the correct range.

Metabolic interactions

Warfarin is a mixture of enantiomers which are metabolised by different CYPP450 cytochromes. R-warfarin is metabolised primarily by CYP1A2 and CYP3A4. S-warfarin is metabolised primarily by CYP2C9. The efficacy of warfarin is affected primarily when the metabolism of S-warfarin is altered.

Drugs that compete as substrates for these cytochromes or inhibit their activity may increase warfarin plasma concentrations and INR, potentially increasing the risk of bleeding. When these drugs are co-administered, warfarin dosage may need to be reduced and the level of monitoring increased.

Conversely, drugs which induce these metabolic pathways may decrease warfarin plasma concentrations and INR, potentially leading to reduced efficacy. When these drugs are co-administered, warfarin dosage may need to be increased and the level of monitoring increased.

There are a small subsets of drugs for which interactions are known; however their clinical effect on the INR is variable. In these cases increased monitoring on starting and stopping therapy is advised.

Care should also be taken when stopping or reducing the dose of a metabolic inhibitor or inducer, once patients are stable on this combination (offset effect).

Listed below are drugs which are known to interact with warfarin in a clinically significant way.

Examples of drugs which potentiate the effect of warfarin

allopurinol, capecitabine, erlotinib, disulfiram, azole antifungals (ketoconazole, fluconazole etc) omeprazole, paracetamol (prolonged regular use), propafenone, amiodarone, tamoxifen, methylphenidate zafirlukast, fibrates, statins (not pravastatin; predominantly associated with fluvastatin) erythromycin, sulfamethoxazole, metronidazole

Examples of drugs which antagonise the effect of warfarin

Barbiturates, primidone, carbamazepine, griseofulvin, oral contraceptives, rifampicin, azathioprine, phenytoin

Examples of drugs with variable effect

Corticosteroids, nevirapine, ritonavir

Other drug interactions

Broad spectrum antibiotics may potentiate the effect of warfarin by reducing the gut flora which produce vitamin K. Similarly, orlistat may reduce absorption of vitamin K. Cholestyramine and sucralfate potentially decrease absorption of warfarin.

Increased INR has been reported in patients taking glucosamine and warfarin. This combination is not recommended.

Interactions with herbal products

Herbal preparations containing St John's Wort (Hypericum perforatum) must not be used whilst taking warfarin due to a proven risk of decreased plasma concentrations and reduced clinical effects of warfarin.

Many other herbal products have a theoretical effect on warfarin; however most of these interactions are not proven. Patients should generally avoid taking any herbal medicines or food supplements whilst taking warfarin, and should be told to advise their doctor if they are taking any, as more frequent monitoring is advisable.

Alcohol

Acute ingestion of a large amount of alcohol may inhibit the metabolism of warfarin and increase INR. Conversely, chronic heavy alcohol intake may induce the metabolism of warfarin. Moderate alcohol intake can be permitted.

Interactions with food and food supplements

Individual case reports suggest a possible interaction between warfarin and cranberry juice, in most cases leading to an increase in INR or bleeding event. Patients should be advised to avoid cranberry products. Increased supervision and INR monitoring should be considered for any patient taking warfarin and regular cranberry juice.

Limited evidence suggests that grapefruit juice may cause a modest rise in INR in some patients taking warfarin.

Certain foods such as liver, broccoli, Brussels sprouts and green leafy vegetables contain large amounts of vitamin K. Sudden changes in diet can potentially affect control of anticoagulation. Patients should be informed of the need to seek medical advice before undertaking any major changes in diet.

Many other food supplements have a theoretical effect on warfarin; however most of these interactions are not proven. Patients should generally avoid taking any food supplements whilst taking warfarin, and should be told to advise their doctor if they are taking any, as more frequent monitoring is advisable.

Laboratory tests

Heparins and danaparoid may prolong the prothrombin time, therefore a sufficient time interval should be allowed after administration before performing the test.

4.6 Pregnancy And Lactation

Pregnancy:

Based on human experience warfarin causes congenital malformations and foetal death when administered during pregnancy.

Warfarin is contraindicated in pregnancy in the first and third trimester.

Women of child-bearing age who are taking Warfarin Tablets should use effective contraception during treatment.

Lactation:

Warfarin is excreted in breast milk in small amounts. However, at therapeutic does of warfarin no effects on the breast-feeding child are anticipated. Warfarin can be used during breast-feeding.

4.7 Effects On Ability To Drive And Use Machines

Nil.

4.8 Undesirable Effects

MedDRA system organ class	Adverse Reaction
Infections and infestations	Fever
Immune system disorders	Hypersensitivity
Nervous system disorders	Cerebral haemorrhage; Cerebral subdural haematoma
Vascular disorders	Haemorrhage
Respiratory, thoracic and mediastinal disorders	Haemothorax, epistaxis
Gastrointestinal disorders	Gastroinestinal haemorrhage, rectal haemorrhage, haematemesis; pancreatitis; diarrhoea; nausea; vomiting; melaena
Hepatobiliary disorders	Jaundice; hepatic dysfunction
Skin and subcutaneous disorders	Rash; alopecia; purpura; 'purple toes' syndrome; erythematous swollen skin patches leading to ecchymosis, infarction and skin necrosis
Renal and Urinary disorders	Haematuria
Investigations	Unexplained drop in haematocrit; haemoglobin decreased

4.9 Overdose

The benefit of gastric decontamination is uncertain. If the patient presents within 1 hour of ingestion of more than 0.25 mg/kg or more than the patient's therapeutic dose, consider activated charcoal (50 g for adults; 1 g/kg for children)

In cases of life-threatening haemorrhage

Stop warfarin treatment, give prothrombin complex concentrate (factors II, VII, IX, and X) 30–50 units/kg or (if no concentrate available) fresh frozen plasma 15 mL/kg. Discuss with local haematologist or National Poisons Information Service, or both.

Non-life threatening haemorrhage

Where anticoagulation can be suspended, give slow intravenous injection of phytomenadione (vitamin K₁) 10–20 mg for adults (250 micrograms/kg for a child)

Where rapid re-anticoagulation is desirable (eg, valve replacements) give prothrombin complex concentrate (factors II, VII, IX, and X) 30–50 units/kg or (if no concentrate available) fresh frozen plasma 15 mL/kg.

Monitor INR to determine when to restart normal therapy. Monitor INR for at least 48 hours post overdose.

For patients on long-term warfarin therapy without major haemorrhage

• INR> 8·0, no bleeding or minor bleeding—stop warfarin, and give phytomenadione (vitamin K₁) 0·5–1 mg for adults, 0·015–0·030 mg/kg (15–30 micrograms/kg) for children by slow intravenous injection or 5 mg by mouth (for partial reversal of anticoagulation give smaller oral doses of phytomenadione eg, 0·5–2·5 mg using the intravenous preparation orally); repeat dose of phytomenadione if INR still too high after 24 hours. Large doses of phytomenadione may completely reverse the effects of warfarin and make re-establishment of anticoagulation difficult.

• INR 6·0–8·0, no bleeding or minor bleeding—stop warfarin, restart when INR <5·0

• INR < 6·0 but more than 0·5 units above target value—reduce dose or stop warfarin, restart when INR <5·0

For patients NOT on long-term anticoagulants without major haemorrhage

Measure the INR (prothrombin time) at presentation and sequentially every 24–48 hours after ingestion depending on the initial dose and initial INR.

• If the INR remains normal for 24–48 hours and there is no evidence of bleeding, there should be no further monitoring necessary.

• Give vitamin K₁ (phytomenadione) if:

a) there is no active bleeding and the patient has ingested more than 0·25 mg/kg;

OR

b) the prothrombin time is already significantly prolonged (INR>4·0).

The adult dose of vitamin K₁ is 10–20 mg orally (250 micrograms/kg body weight for a child). Delay oral vitamin K₁ at least 4 hours after any activated charcoal has been given. Repeat INR at 24 hours and consider further vitamin K₁.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Warfarin is a coumarin anticoagulant which depresses the hepatic vitamin K-dependent synthesis of coagulation factors II (Prothrombin), VII, IX and X. It acts indirectly, with no effect on existing clots.

5.2 Pharmacokinetic Properties

Warfarin Sodium is readily absorbed from the gastro-intestinal tract; it can also be absorbed through the skin. It is extensively bound to plasma proteins and its plasma half-life is about 37 hours. It crosses the placenta but does not occur in significant quantities in breast milk. Warfarin is administered as a racemic mixture. The s-isomer is reported to be more potent; the R and S isomers are both metabolised in the liver, though at different rates; the stereo-isomers may also be affected differently by other drugs. The inactive metabolites are excreted in the urine following reabsorption from the bile.

5.3 Preclinical Safety Data

No further relevant information other than that which is included in other sections of the Summary of Product Characteristics.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose, Maize Starch, Sodium Starch Glycollate, Magnesium Stearate, Alumina, Tartrazine Lake ( E102 ), Amaranth Lake ( E123 ), Indigo Carmine Lake ( E132 ).

6.2 Incompatibilities

None known

6.3 Shelf Life

Securitainers: 5 years

HDPE containers: 5 years

Blister packs: 3 years

6.4 Special Precautions For Storage

Store below 25°C.

Protect from light and moisture.

6.5 Nature And Contents Of Container

Antigen International Ltd.: Polypropylene securitainers with tamper evident lid.

APS Ltd.: HDPE containers with LDPE lids or child resistant caps.

Pack size : 100 tablets, 500 tablets.

Blister strips of 14 tablets.

Pack size: 28 tablets, 56 tablets,

6.6 Special Precautions For Disposal And Other Handling

Use as directed by the physician.

7. Marketing Authorisation Holder

Antigen International Ltd.,

Roscea,

Co. Tipperary,

Ireland.

8. Marketing Authorisation Number(S)

PL 02848/0185

9. Date Of First Authorisation/Renewal Of The Authorisation

22 November 1995.

10. Date Of Revision Of The Text

16/04/2010

Theraflu (pseudoephedrine) Daytime Severe Cold

Generic Name: acetaminophen, dextromethorphan, and pseudoephedrine (a SEET a MIN oh fen, DEX troe me THOR fan, SOO doe ee FED rin)

Brand Names: Alka-Seltzer Plus Flu Liquigels, Comtrex Non-Drowsy, DayQuil, Dayquil Liquicaps, Daytime Cold, Non-Drowsy Daytime, Robitussin Honey Flu Non-Drowsy, Theraflu (pseudoephedrine) Daytime Severe Cold, Theraflu Severe Cold & Congestion Non-Drowsy, Triaminic Cough & Sore Throat (pseudoephedrine), Triaminic Softchew Throat Pain and Cough, Triaminic Softchews Cough & Sore Throat (pseudoephedrine)

What is Theraflu (pseudoephedrine) Daytime Severe Cold (acetaminophen, dextromethorphan, and pseudoephedrine)?

Acetaminophen is a pain reliever and fever reducer.

Dextromethorphan is a cough suppressant. It affects the signals in the brain that trigger cough reflex.

Pseudoephedrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

The combination of acetaminophen, dextromethorphan, and pseudoephedrine is used to treat headache, fever, body aches, cough, stuffy nose, and sinus congestion caused by allergies, the common cold, or the flu.

This medicine will not treat a cough that is caused by smoking, asthma, or emphysema.

Acetaminophen, dextromethorphan, and pseudoephedrine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Theraflu (pseudoephedrine) Daytime Severe Cold (acetaminophen, dextromethorphan, and pseudoephedrine)?

Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death. Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. Do not use this medicine if you have untreated or uncontrolled diseases such as glaucoma, asthma or COPD, high blood pressure, heart disease, coronary artery disease, or overactive thyroid. Avoid drinking alcohol. It may increase your risk of liver damage while you are taking acetaminophen. Do not use this medicine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects. Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP.

What should I discuss with my healthcare provider before taking Theraflu (pseudoephedrine) Daytime Severe Cold (acetaminophen, dextromethorphan, and pseudoephedrine)?

Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take medicine that contains acetaminophen. Do not use this medicine if you have untreated or uncontrolled diseases such as glaucoma, asthma or COPD, high blood pressure, heart disease, coronary artery disease, or overactive thyroid. Do not use this medicine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

Ask a doctor or pharmacist if it is safe for you to take acetaminophen, dextromethorphan, and pseudoephedrine if you have:

• 
  

  liver disease, cirrhosis, or a history of alcoholism;

  
  


• 
  

  diabetes;

  
  


• 
  

  glaucoma;

  
  


• 
  

  diabetes;

  
  


• 
  

  epilepsy or other seizure disorder;

  
  


• 
  

  enlarged prostate or urination problems;

  
  


• 
  

  pheochromocytoma (an adrenal gland tumor); or

  
  


• 
  

  cough with mucus, or cough caused by emphysema or chronic bronchitis.

  
  

It is not known whether acetaminophen, dextromethorphan, and pseudoephedrine will harm an unborn baby. Do not use this medicine without a doctor's advice if you are pregnant. Acetaminophen, dextromethorphan, and pseudoephedrine may pass into breast milk and may harm a nursing baby. Decongestants may also slow breast milk production. Do not use this medicine without a doctor's advice if you are breast-feeding a baby.

Artificially sweetened cold medicine may contain phenylalanine. If you have phenylketonuria (PKU), check the medication label to see if the product contains phenylalanine.

How should I take Theraflu (pseudoephedrine) Daytime Severe Cold (acetaminophen, dextromethorphan, and pseudoephedrine)?

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. This medicine is usually taken only for a short time until your symptoms clear up.

Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death. Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving cough or cold medicine to a child. Death can occur from the misuse of cough or cold medicine in very young children.

Measure liquid medicine with a special dose measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose measuring device, ask your pharmacist for one.

The chewable tablet must be chewed thoroughly before you swallow it.

Dissolve one packet of the powder in at least 4 ounces of water. Stir this mixture and drink all of it right away.

Do not take for longer than 7 days in a row. Stop taking the medicine and call your doctor if you still have a fever after 3 days of use, you still have pain after 7 days (or 5 days if treating a child), if your symptoms get worse, or if you have a skin rash, ongoing headache, or any redness or swelling.

If you need surgery or medical tests, tell the surgeon or doctor ahead of time if you have taken this medicine within the past few days. Store at room temperature away from moisture and heat. Do not allow liquid medicine to freeze.

What happens if I miss a dose?

Since this medicine is taken when needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of acetaminophen can be fatal.

The first signs of an acetaminophen overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

Overdose symptoms may also include severe forms of some of the side effects listed in this medication guide.

What should I avoid while taking Theraflu (pseudoephedrine) Daytime Severe Cold (acetaminophen, dextromethorphan, and pseudoephedrine)?

Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP. This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Avoid drinking alcohol. It may increase your risk of liver damage while you are taking acetaminophen.

Theraflu (pseudoephedrine) Daytime Severe Cold (acetaminophen, dextromethorphan, and pseudoephedrine) 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. chest pain, fast, slow, or uneven heart rate; Stop using this medication and call your doctor at once if you have any of these serious side effects:

• 
  

  chest pain, fast, slow, or uneven heart rate;

  
  


• 
  

  severe dizziness, feeling like you might pass out;

  
  


• 
  

  mood changes, confusion, hallucinations;

  
  


• 
  

  tremor, seizure (convulsions);

  
  


• 
  

  fever;

  
  


• 
  

  urinating less than usual or not at all;

  
  


• 
  

  nausea, pain in your upper stomach, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of your skin or eyes); or

  
  


• 
  

  nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

  
  


• 
  

  dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, chest pain, uneven heartbeats, seizure).

  
  

Less serious side effects may include:

• 
  

  dizziness, weakness;

  
  


• 
  

  mild headache;

  
  


• 
  

  mild nausea, diarrhea, upset stomach;

  
  


• 
  

  dry mouth, nose, or throat;

  
  


• 
  

  feeling nervous, restless, irritable, or anxious; or

  
  


• 
  

  sleep problems (insomnia).

  
  

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

What other drugs will affect Theraflu (pseudoephedrine) Daytime Severe Cold (acetaminophen, dextromethorphan, and pseudoephedrine)?

Ask a doctor or pharmacist if it is safe for you to take this medicine if you are also using any of the following drugs:

• 
  

  leflunomide (Arava);

  
  


• 
  

  tapentadol (Nucynta);

  
  


• 
  

  an antibiotic, antifungal medicine, sulfa drug, or tuberculosis medicine;

  
  


• 
  

  an antidepressant;

  
  


• 
  

  birth control pills or hormone replacement therapy;

  
  


• 
  

  blood pressure medication;

  
  


• 
  

  cancer medicine;

  
  


• 
  

  cholesterol-lowering medications such as Lipitor, Niaspan, Zocor, Vytorin, and others;

  
  


• 
  

  gout or arthritis medications (including gold injections);

  
  


• 
  

  HIV/AIDS medication;

  
  


• 
  

  medicines to treat psychiatric disorders;

  
  


• 
  

  migraine headache medicine;

  
  


• 
  

  an NSAID such as Advil, Aleve, Arthrotec, Cataflam, Celebrex, Indocin, Motrin, Naprosyn, Treximet, Voltaren, others; or

  
  


• 
  

  seizure medication.

  
  

This list is not complete and other drugs may interact with acetaminophen, dextromethorphan, and pseudoephedrine. 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 Theraflu (pseudoephedrine) Daytime Severe Cold resources

• Theraflu (pseudoephedrine) Daytime Severe Cold Side Effects (in more detail)
• Theraflu (pseudoephedrine) Daytime Severe Cold Use in Pregnancy & Breastfeeding
• Theraflu (pseudoephedrine) Daytime Severe Cold Drug Interactions
• 0 Reviews for Theraflu (pseudoephedrine) Daytime Severe Cold - Add your own review/rating

• DayQuil Liquid MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Theraflu (pseudoephedrine) Daytime Severe Cold with other medications

• Cold Symptoms

Where can I get more information?

• Your pharmacist can provide more information about acetaminophen, dextromethorphan, and pseudoephedrine.

See also: Theraflu (pseudoephedrine) Daytime Severe Cold side effects (in more detail)