ticlopidine

tye-KLOE-pi-deen

Oral route(Tablet)

Can cause life-threatening hematological adverse reactions, including neutropenia/agranulocytosis, thrombotic thrombocytopenic purpura (TTP) and aplastic anemia. Hematological adverse reactions cannot be reliably predicted by any identified demographic or clinical characteristics. During the first 3 months of treatment, patients receiving ticlopidine must, therefore, be hematologically and clinically monitored for evidence of neutropenia or TTP. If any such evidence is seen, ticlopidine should be immediately discontinued .

Commonly used brand name(s)

In the U.S.

• Ticlid

Available Dosage Forms:

• Tablet

Therapeutic Class: Platelet Aggregation Inhibitor

Pharmacologic Class: ADP-Induced Aggregation Inhibitor

Uses For ticlopidine

Ticlopidine is used to lessen the chance of having a stroke. It is given to people who have already had a stroke and to people with certain medical problems that may lead to a stroke. Because ticlopidine can cause serious side effects, especially during the first 3 months of treatment, it is used mostly for people who cannot take aspirin to prevent strokes.

A stroke may occur when blood flow to the brain is interrupted by a blood clot. Ticlopidine reduces the chance that a harmful blood clot will form, by preventing certain cells in the blood from clumping together. This effect of ticlopidine may also increase the chance of serious bleeding in some people.

ticlopidine is available only with a doctor's prescription.

Before Using ticlopidine

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 ticlopidine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to ticlopidine 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

There is no specific information comparing use of ticlopidine in children with use in other age groups.

Geriatric

ticlopidine has been tested and has not been shown to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	B	Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

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 ticlopidine, 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 ticlopidine 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.

• Abciximab


• Acenocoumarol


• Alteplase, Recombinant


• Argatroban


• Aspirin


• Bivalirudin


• Bromfenac


• Celecoxib


• Cilostazol


• Citalopram


• Clopidogrel


• Dabigatran Etexilate


• Dalteparin


• Danaparoid


• Desirudin


• Desvenlafaxine


• Diclofenac


• Diflunisal


• Drotrecogin Alfa


• Duloxetine


• Enoxaparin


• Escitalopram


• Etodolac


• Fluoxetine


• Flurbiprofen


• Fluvoxamine


• Fondaparinux


• Heparin


• Ibuprofen


• Ibuprofen Lysine


• Indomethacin


• Ketoprofen


• Ketorolac


• Lepirudin


• Magnesium Salicylate


• Mefenamic Acid


• Meloxicam


• Milnacipran


• Nabumetone


• Naproxen


• Nefazodone


• Nepafenac


• Oxaprozin


• Paroxetine


• Phenindione


• Phenprocoumon


• Piroxicam


• Protein C, Human


• Rivaroxaban


• Salsalate


• Sertraline


• Sulindac


• Tinzaparin


• Tizanidine


• Tolmetin


• Venlafaxine


• Warfarin

Using ticlopidine 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.

• Aluminum Carbonate, Basic


• Aluminum Hydroxide


• Aluminum Phosphate


• Calcium


• Carbamazepine


• Dihydroxyaluminum Aminoacetate


• Dihydroxyaluminum Sodium Carbonate


• Fosphenytoin


• Magaldrate


• Magnesium Carbonate


• Magnesium Hydroxide


• Magnesium Oxide


• Magnesium Trisilicate


• Phenytoin


• Theophylline


• Warfarin

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 ticlopidine. Make sure you tell your doctor if you have any other medical problems, especially:

• Blood clotting problems, such as hemophilia and von Willebrand's disease, or


• Liver disease (severe) or


• Stomach ulcers—The chance of serious bleeding may be increased

• Blood disease—The chance of serious side effects may be increased

• Kidney disease (severe)—Ticlopidine is removed from the body more slowly when the kidneys are not working properly. This may increase the chance of side effects

Also, tell your doctor if you have ever had a problem called thrombotic thrombocytopenic purpura (TTP). This problem could reoccur if you take ticlopidine.

Proper Use of ticlopidine

Ticlopidine should be taken with food. This increases the amount of medicine that is absorbed into the body. It may also lessen the chance of stomach upset.

Take ticlopidine only as directed by your doctor. Ticlopidine will not work properly if you take less of it than directed. Taking more ticlopidine than directed may increase the chance of serious side effects without increasing the helpful effects.

Dosing

The dose of ticlopidine 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 ticlopidine. If your dose is different, do not change it unless your doctor tells you to do so.

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

• For oral dosage form (tablets):
  
  • For prevention of strokes:
    
    • Adults—1 tablet (250 mg) two times a day, with food.
    
    
    • Children—It is not likely that ticlopidine would be used to help prevent strokes in children. If a child needs ticlopidine, however, the dose would have to be determined by the doctor.
    
    
  
  
  • For prevention of strokes or heart attack following heart stent procedure:
    
    • Adults—1 tablet (250 mg) two times a day, with food together with your doctor's recommended dose of aspirin for up to 30 days following the procedure
    
    
    • Children—It is not likely that ticlopidine would be used to help prevent strokes or heart attack in children. If a child needs ticlopidine, however, the dose would have to be determined by the doctor
    
    
  
  

Missed Dose

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

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using ticlopidine

It is very important that blood tests be done before treatment is started with ticlopidine, and repeated every 2 weeks for the first 3 months of treatment with ticlopidine. The tests are needed to find out whether certain side effects are occurring. Finding these side effects early helps to prevent them from becoming serious. Your doctor will arrange for the blood tests to be done. Be sure that you do not miss any appointments for these tests. You will probably not need to have your blood tested so often after the first 3 months of treatment, because the side effects are less likely to occur after that time.

Tell all medical doctors, dentists, nurses, and pharmacists you go to that you are taking ticlopidine. Ticlopidine may increase the risk of serious bleeding during an operation or some kinds of dental work. Therefore, treatment may have to be stopped about 10 days to 2 weeks before the operation or dental work is done.

Ticlopidine may cause serious bleeding, especially after an injury. Sometimes, bleeding inside the body can occur without your knowing about it. Ask your doctor whether there are certain activities you should avoid while taking ticlopidine (for example, sports that can cause injuries). Also, check with your doctor immediately if you are injured while being treated with ticlopidine.

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

• Bruising or bleeding, especially bleeding that is hard to stop. Bleeding inside the body sometimes appears as bloody or black, tarry stools, or faintness. Also, bleeding may occur from the gums when brushing or flossing teeth.


• Any sign of infection, such as fever, chills, or sore throat.


• Sores, ulcers, or white spots in the mouth.


• Dark or bloody urine, difficulty in speaking, fever, pale color of skin, pinpoint red spots on skin, convulsions (seizures), weakness, or yellow eyes or skin.

After you stop taking ticlopidine, the chance of bleeding may continue for 1 or 2 weeks. During this period of time, continue to follow the same precautions that you followed while you were taking the medicine.

ticlopidine 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:

Less common or rare

• Abdominal or stomach pain (severe) or swelling


• back pain


• blistering, peeling, or loosening of the skin or lips or mucous membranes (moist lining of many body cavities, including the mouth, lips, inside of nose, anus, and vagina)


• blood in eyes


• bloody or black tarry stools


• bruising or purple areas on skin


• change in mental status


• convulsions (seizures)


• coughing up blood


• dark or bloody urine


• decreased alertness


• dizziness


• fever, chills, or sore throat


• headache (severe or continuing)


• joint pain or swelling


• nosebleeds


• pale color of skin


• paralysis or problems with coordination


• pinpoint red spots on skin


• red lesions on the skin, often with a purple center


• red, thickened, or scaly skin


• sores, ulcers, or white spots in mouth


• stammering or other difficulty in speaking


• unusually heavy bleeding or oozing from cuts or wounds


• unusual tiredness


• unusually heavy or unexpected menstrual bleeding


• vomiting of blood or material that looks like coffee grounds


• weakness


• yellow eyes or skin

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

More common

• Skin rash

Less common or rare

• General feeling of discomfort or illness


• hives or itching of skin


• ringing or buzzing in ears

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

• Abdominal or stomach pain (mild)


• diarrhea


• indigestion


• nausea

Less common

• Bloating or gas


• dizziness


• vomiting

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: ticlopidine side effects (in more detail)

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More ticlopidine resources

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

• ticlopidine Concise Consumer Information (Cerner Multum)


• Ticlopidine Prescribing Information (FDA)


• Ticlopidine MedFacts Consumer Leaflet (Wolters Kluwer)


• Ticlid Monograph (AHFS DI)


• Ticlid Prescribing Information (FDA)

Compare ticlopidine with other medications

• Cerebral Thrombosis/Embolism

Nix Complete Lice Treatment System

Generic Name: permethrin topical (per METH rin)

Brand Names: Elimite, Lice Bedding Spray, Nix Complete Lice Treatment System, Nix Cream Rinse, Nix Lice Control, RID Home Lice Control Spray for Surfaces

What is Nix Complete Lice Treatment System (permethrin topical)?

Permethrin is an anti-parasite medication.

Permethrin topical (for the skin) is used to treat head lice and scabies.

Permethrin topical may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Nix Complete Lice Treatment System (permethrin topical)?

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

Do not take this medication by mouth. It is for use only on the skin, hair, fabrics, or other surfaces. Do not apply permethrin topical to open cuts or wounds. Do not use this medication if you are allergic to permethrin or to chrysanthemums. For the most complete treatment of lice or scabies and to prevent reinfection, you must treat your environment (clothing, bedding, pillows, furniture, hats, hair brushes and accessories, etc) at the same time you treat your body.

Avoid sexual or intimate contact with others until your lice or scabies infection has cleared up. Avoid sharing hair brushes, combs, hair accessories, hats, clothing, bed linens, and other articles of personal use. Lice and scabies infections are highly contagious.

What should I discuss with my healthcare provider before using Nix Complete Lice Treatment System (permethrin topical)?

Do not use this medication if you are allergic to permethrin or to chrysanthemums. FDA pregnancy category B. Permethrin topical is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Permethrin can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Do not use this medication on an infant younger than 2 months without the advice of a doctor.

How should I use Nix Complete Lice Treatment System (permethrin topical)?

Do not take this medication by mouth. It is for use only on the skin, hair, fabrics, or other surfaces.

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

You may need to shake the medication before each use. Follow the directions on the medicine label. Do not apply permethrin topical to open cuts or wounds.

To treat scabies:

• 
  

  Make sure your skin is clean and dry. Apply a thin layer of permethrin topical to all body parts from the neck down to the soles of the feet. Rub in completely. Leave the medication on for 8 to 14 hours, then wash it off completely.

  
  


• When using permethrin topical on an infant, also apply the medication to the scalp, temples, and forehead. Avoid applying close to the eyes, nose, mouth, or genitals.


• 
  

  If your condition does not clear up within 14 days after applying permethrin topical, use another application.

  
  

To treat head lice:

• 
  

  When using the shampoo, apply it to dry hair only. Cover all hair completely and leave the shampoo in for 10 minutes. Then work into a lather using warm water and rinse out thoroughly.

  
  


• 
  

  When using the cream rinse, wash your hair using shampoo only (no conditioner or 2-in-1 shampoo). Rinse thoroughly and towel dry the hair, leaving it damp. Apply enough of the cream rinse to completely saturate all hair. Leave the cream rinse in your hair for 10 minutes.

  
  


• Use a towel or washcloth to protect your eyes while the medication is left in your hair.


• 
  

  Use a second application if lice are still seen 7 days after your first treatment.

  
  


• 
  

  You may also use a nit comb to remove lice eggs from the hair. Your hair should be slightly damp while using a nit comb. Work on only one section of hair at a time, combing through 1- to 2-inch strands from the scalp to the ends.

  
  


• 
  

  Rinse the nit comb often during use. Place removed nits into a sealed plastic bag and throw it into the trash to prevent re-infestation.

  
  


• 
  

  Check the scalp again daily to make sure all nits have been removed.

  
  

To treat pubic lice (crabs):

• 
  

  Wash and dry the treatment area. Apply permethrin topical to all pubic hair and any surrounding hairs on the thighs and around the anus.

  
  


• 
  

  Avoid getting this medication inside the rectum or vagina.

  
  


• 
  

  Leave the medication in for 10 minutes. Then work into a lather using warm water and rinse out thoroughly.

  
  


• 
  

  You may also use a nit comb to remove lice eggs from pubic hair (hair should be slightly damp).

  
  


• 
  

  All sexual partners should also be treated to prevent re-infestation of crabs.

  
  

To prevent reinfection, wash all clothing, hats, bed clothes, bed linens, and towels in hot water and dry in high heat. Dry-clean any non-washable clothing. Hair brushes, combs, and hair accessories should be soaked in hot water for at least 10 minutes.

Use permethrin surface spray to disinfect non-washable items such as:

• 
  

  furniture;

  
  


• 
  

  mattresses and pillows;

  
  


• 
  

  stuffed toys;

  
  


• 
  

  hats, gloves, and scarves;

  
  


• 
  

  headphones or headbands;

  
  


• 
  

  the inside of a bike helmet; or

  
  


• 
  

  seats and carpets inside your car.

  
  

Stuffed toys or pillows that cannot be washed should be sealed in air-tight plastic bags for 4 weeks.

Vacuum all rugs and carpets and throw away the vacuum cleaner bag.

For the most complete treatment of lice or scabies, you must treat your environment (clothing, bedding, etc) at the same time you treat your body. Store permethrin topical at room temperature away from moisture and heat.

What happens if I miss a dose?

Since permethrin topical is usually needed only once, you are not likely to be on a dosing schedule. Wait at least 7 days before using a second application.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

Symptoms of a permethrin topical overdose are unknown.

What should I avoid while using Nix Complete Lice Treatment System (permethrin topical)?

Avoid getting this medication in your mouth or eyes. If it does get into any of these areas, rinse with water.

Do not use other medicated skin products unless your doctor has told you to.

Avoid sexual or intimate contact with others until your lice or scabies infection has cleared up. Avoid sharing hair brushes, combs, hair accessories, hats, clothing, bed linens, and other articles of personal use. Lice and scabies infections are highly contagious.

Nix Complete Lice Treatment System (permethrin topical) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have severe burning, stinging, redness, or swelling after applying permethrin topical.

Less serious side effects may include:

• 
  

  itching or mild skin rash;

  
  


• 
  

  mild burning, stinging, or redness; or

  
  


• 
  

  numbness or tingling where the medication was applied.

  
  

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 Nix Complete Lice Treatment System (permethrin topical)?

It is not likely that other drugs you take orally or inject will have an effect on topically applied permethrin. But many drugs can interact with each other. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Nix Complete Lice Treatment System resources

• Nix Complete Lice Treatment System Side Effects (in more detail)
• Nix Complete Lice Treatment System Use in Pregnancy & Breastfeeding
• 0 Reviews for Nix Complete Lice Treatment - Add your own review/rating

• Acticin Cream MedFacts Consumer Leaflet (Wolters Kluwer)


• Acticin Topical Advanced Consumer (Micromedex) - Includes Dosage Information


• Elimite Prescribing Information (FDA)

Compare Nix Complete Lice Treatment System with other medications

• Head Lice
• Lice
• Scabies

Where can I get more information?

• Your pharmacist has additional information about permethrin topical written for health professionals that you may read.

See also: Nix Complete Lice Treatment side effects (in more detail)

Sodium Chloride Irrigation Hospira

0.45% SODIUM CHLORIDE IRRIGATION, USP

0.9% SODIUM CHLORIDE IRRIGATION, USP

For All General Irrigation, Washing, Rinsing and Dilution Purposes

Not For Injection By Usual Parenteral Routes

Flexible Irrigation Container

Semi-rigid Irrigation Container

Rx only

Sodium Chloride Irrigation Hospira Description

These products are sterile, nonpyrogenic solutions of electrolytes in water for injection intended only for sterile irrigation, washing, rinsing and dilution purposes.

Each 100 mL of 0.45% Sodium Chloride Irrigation, USP contains: Sodium chloride 450 mg; pH 5.6 (4.5 to 7.0). The solution is hypotonic (154 mOsmol/liter, CALC.) and has the following electrolyte content (mEq/liter): Na+ 77; Cl− 77.

Each 100 mL of 0.9% Sodium Chloride Irrigation, USP contains: Sodium chloride 900 mg; pH 5.6 (4.5 to 7.0). May contain sodium hydroxide and/or hydrochloric acid for pH adjustment. The solution is isotonic (308 mOsmol/liter, CALC.) and has the following electrolyte content (mEq/liter): Na+ 154; Cl− 154.

These irrigations contain no bacteriostat, antimicrobial agent or added buffer and are intended only for use as single-dose or short procedure irrigation. When smaller volumes are required the unused portion should be discarded.

Each of these irrigations may be classified as a sterile irrigant, wash, rinse, diluent and pharmaceutical vehicle.

Sodium Chloride, USP is chemically designated NaCl, a white crystalline powder freely soluble in water.

Water for Injection, USP is chemically designated H2O.

The flexible plastic container is fabricated from a specially formulated polyvinylchloride. Water can permeate from inside the container into the overwrap but not in amounts sufficient to affect the solution significantly.

The semi-rigid container is fabricated from a specially formulated polyolefin. It is a copolymer of ethylene and propylene. The container requires no vapor barrier to maintain the proper drug concentration.

Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the plastic container materials. Exposure to temperatures above 25°C/77°F during transport and storage will lead to minor losses in moisture content. Higher temperatures lead to greater losses. It is unlikely that these minor losses will lead to clinically significant changes within the expiration period.

Sodium Chloride Irrigation Hospira - Clinical Pharmacology

Each of these irrigation solutions exert a mechanical cleansing action for sterile irrigation of body cavities, tissues or wounds, indwelling urethral catheters and surgical drainage tubes and for washing, rinsing or soaking surgical dressings, instruments and laboratory specimens. Each also serves as a diluent or vehicle for drugs used for irrigation or other pharmaceutical preparations.

0.45% Sodium Chloride Irrigation, USP provides a hypotonic half-strength saline irrigation identical in composition with 0.45% Sodium Chloride Injection, USP.

0.9% Sodium Chloride Irrigation, USP provides an isotonic saline irrigation identical in composition with 0.9% Sodium Chloride Injection, USP (normal saline).

0.9% Sodium Chloride Irrigation, USP is considered generally compatible with living tissues and organs; 0.45% Sodium Chloride Irrigation, USP may be used alone or combined with appropriate additives when 0.9% sodium chloride is considered too irritating for wounds or other altered structures.

Sodium chloride in water dissociates to provide sodium (Na+) and chloride (Cl−) ions. Sodium (Na+) is the principal cation of the extracellular fluid and plays a large part in the therapy of fluid and electrolyte disturbances. Chloride (Cl−) has an integral role in buffering action when oxygen and carbon dioxide exchange occurs in the red blood cells. The distribution and excretion of sodium (Na+) and chloride (Cl−) are largely under the control of the kidney which maintains a balance between intake and output.

Water is an essential constituent of all body tissues and accounts for approximately 70% of total body weight. Average normal adult daily requirement ranges from two to three liters (1.0 to 1.5 liters each for insensible water loss by perspiration and urine production).

Water balance is maintained by various regulatory mechanisms. Water distribution depends primarily on the concentration of electrolytes in the body compartments and sodium (Na+) plays a major role in maintaining physiologic equilibrium.

Indications and Usage for Sodium Chloride Irrigation Hospira

Each of these solutions is indicated for all general irrigation, washing, rinsing and dilution purposes which permit use of a sterile, nonpyrogenic electrolyte solution.

Contraindications

NOT FOR INJECTION BY USUAL PARENTERAL ROUTES.

An electrolyte solution should not be used for irrigation during electrosurgical procedures.

Warnings

FOR IRRIGATION ONLY. NOT FOR INJECTION.

Entry of a hypotonic solution into the circulation may cause hemolysis.

Irrigating fluids have been demonstrated to enter the systemic circulation in relatively large volumes; thus each of these irrigations must be regarded as a systemic drug. Absorption of large amounts can cause fluid and/or solute overloading resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema.

The risk of dilutional states is inversely proportional to the electrolyte concentrations of administered parenteral solutions. The risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to the electrolyte concentrations of such solutions.

Do not heat container over 66°C (150°F).

Precautions

Do not use for irrigation that may result in absorption into the blood.

Caution should be observed when a hypotonic solution is used for continuous irrigation or allowed to “dwell” inside body cavities because of possible absorption into the blood stream and the production of intravascular hemolysis and circulatory overload.

Aseptic technique is essential with the use of sterile solutions for irrigation of body cavities, wounds and urethral catheters or for wetting dressings that come in contact with body tissues.

When used as a “pour” irrigation, no part of the contents should be allowed to contact the surface below the outer protected thread area of the semi-rigid wide mouth container. The flexible container is designed for use with nonvented irrigation sets. When used for irrigation via irrigation equipment, the administration set should be attached promptly. Unused portions should be discarded and a fresh container of appropriate size used for the start-up of each cycle or repeat procedure. For repeated irrigations of urethral catheters, a separate container should be used for each patient.

Do not administer unless solution is clear, seal is intact and container is undamaged.

Discard unused portion.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Studies with Sodium Chloride Irrigation, USP have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility.

Nursing Mothers:

Caution should be exercised when Sodium Chloride Irrigation, USP is administered to a nursing woman.

Pregnancy:

Teratogenic Effects.

Pregnancy Category C. Animal reproduction studies have not been conducted with Sodium Chloride Irrigation, USP. It is also not known whether Sodium Chloride Irrigation, USP can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Sodium Chloride Irrigation, USP should be given to a pregnant woman only if clearly needed.

Pediatric Use:

Safety and effectiveness of Sodium Chloride irrigation solution in pediatric patients have not been established by adequate and well-controlled trials. However, the use of Sodium Chloride irrigation solution in the pediatric population is referenced in the medical literature. The Warnings, Precautions, and Adverse Reactions identified in the label should be observed in the pediatric population.

Geriatric Use:

An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients.

This drug is known to be substantially secreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Adverse Reactions

Possible adverse effects arising from the irrigation of body cavities, tissues, or indwelling catheters and tubes are usually avoidable when proper procedures are followed. Displaced catheters or drainage tubes can lead to irrigation or infiltration of unintended structures or cavities. Excessive volume or pressure during irrigation of closed cavities may cause undue distension or disruption of tissues. Accidental contamination from careless technique may transmit infection.

Should any adverse reaction occur, discontinue the irrigant, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary.

Overdosage

In the event of overhydration or solute overload, re-evaluate the patient and institute appropriate corrective measures. See WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS.

Sodium Chloride Irrigation Hospira Dosage and Administration

The dose is dependent upon the capacity or surface area of the structure to be irrigated and the nature of the procedure. When used as a diluent or vehicle for other drugs, the manufacturer’s recommendations should be followed.

Drug Interactions

Additives may be incompatible. Consult with pharmacist, if available. When introducing additives, use aseptic technique, mix thoroughly and do not store.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution container permits. See PRECAUTIONS.

How is Sodium Chloride Irrigation Hospira Supplied

0.45% Sodium Chloride Irrigation, USP:

Container Size	NDC
Single-dose 2000 mL flexible irrigation container	0409-7975-07

0.9% Sodium Chloride Irrigation, USP:

Container Size	NDC
Single-dose 500 mL semi-rigid irrigation container	0409-6138-03
Single-dose 250 mL semi-rigid irrigation container	0409-6138-22
Single-dose 1000 mL semi-rigid irrigation container	0409-7138-09
Single-dose 1500 mL semi-rigid irrigation container	0409-7138-36
Single-dose 1000 mL flexible irrigation container	0409-7972-05
Single-dose 2000 mL flexible irrigation container	0409-7972-07

Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Protect from freezing.

Revised: May, 2009

Printed in USA	EN-2130
Hospira, Inc., Lake Forest, IL 60045 USA

IM-0687

IM-1153

RL-2095

SODIUM CHLORIDE  sodium chloride  irrigant

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0409-7972 Route of Administration IRRIGATION DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength SODIUM CHLORIDE (SODIUM CATION and CHLORIDE ION) SODIUM CHLORIDE 900 mg  in 100 mL

Inactive Ingredients Ingredient Name Strength WATER

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0409-7972-05 12 BAG In 1 CASE contains a BAG 1 1000 mL In 1 BAG This package is contained within the CASE (0409-7972-05) 2 0409-7972-07 6 BAG In 1 CASE contains a BAG 2 2000 mL In 1 BAG This package is contained within the CASE (0409-7972-07)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA018314	05/17/2010

SODIUM CHLORIDE  sodium chloride  irrigant

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0409-7975 Route of Administration IRRIGATION DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength SODIUM CHLORIDE (SODIUM CATION and CHLORIDE ION) SODIUM CHLORIDE 450 mg  in 100 mL

Inactive Ingredients Ingredient Name Strength WATER

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0409-7975-07 6 BAG In 1 CASE contains a BAG 1 2000 mL In 1 BAG This package is contained within the CASE (0409-7975-07)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA018380	05/17/2010

SODIUM CHLORIDE  sodium chloride  irrigant

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0409-7138 Route of Administration IRRIGATION DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength SODIUM CHLORIDE (SODIUM CATION and CHLORIDE ION) SODIUM CHLORIDE 900 mg  in 100 mL

Inactive Ingredients Ingredient Name Strength WATER

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0409-7138-09 12 BOTTLE In 1 CASE contains a BOTTLE, PLASTIC 1 1000 mL In 1 BOTTLE, PLASTIC This package is contained within the CASE (0409-7138-09) 2 0409-7138-36 9 BOTTLE In 1 CASE contains a BOTTLE, PLASTIC 2 1500 mL In 1 BOTTLE, PLASTIC This package is contained within the CASE (0409-7138-36)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA017514	05/17/2010

SODIUM CHLORIDE  sodium chloride  irrigant

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0409-6138 Route of Administration IRRIGATION DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength SODIUM CHLORIDE (SODIUM CATION and CHLORIDE ION) SODIUM CHLORIDE 900 mg  in 100 mL

Inactive Ingredients Ingredient Name Strength WATER

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0409-6138-22 24 BOTTLE In 1 CASE contains a BOTTLE, PLASTIC 1 250 mL In 1 BOTTLE, PLASTIC This package is contained within the CASE (0409-6138-22) 2 0409-6138-03 24 BOTTLE In 1 CASE contains a BOTTLE, PLASTIC 2 500 mL In 1 BOTTLE, PLASTIC This package is contained within the CASE (0409-6138-03)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA017514	05/17/2010

Labeler - Hospira, Inc. (141588017)

Revised: 05/2011Hospira, Inc.

AMAG Pharmaceuticals, Inc

Address AMAG Pharmaceuticals, Inc, 125 CambridgePark Drive 6th Floor Cambridge, MA 02140 Contact Details Phone: (617) 498-3300 Website: http://www.amagpharma.com Careers: http://www.amagpharma.com/employment/

Talacen

Pronunciation: a-SEET-a-MIN-oh-fen/pen-TAZ-oh-seen
Generic Name: Acetaminophen/Pentazocine
Brand Name: Generic only. No brands available.

Talacen contains acetaminophen. Severe and sometimes fatal liver problems, including the need for liver transplant, have been reported with the use of acetaminophen. Most cases of these liver problems occurred in patients taking excessive doses of acetaminophen (more than 4,000 mg per day). Also, patients who developed these liver problems were often using more than 1 medicine that contained acetaminophen. Discuss any questions or concerns with your doctor.

Talacen is used for:

Relieving mild to moderate pain.

Talacen is a narcotic and analgesic combination. It works in the brain to reduce pain.

Do NOT use Talacen if:

• you are allergic to any ingredient in Talacen


• you have a dependence on opiates (eg, morphine) or you are taking sodium oxybate (GHB)

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

Before using Talacen:

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

• if you are pregnant, planning to become pregnant, or are breast-feeding


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


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


• if you have poor health, low blood oxygen levels, high blood carbon dioxide levels, stomach pain, or severe or persistent diarrhea caused by antibiotic use (pseudomembranous colitis)


• if you have a history of a recent head injury, growths in the brain (eg, tumors), increased pressure in the brain, or seizures


• if you have a history of stomach or bowel problems (eg, inflammation, stomach or bowel surgery), lung or breathing problems (eg, asthma, chronic obstructive pulmonary disease [COPD]), liver problems (eg, hepatitis), kidney problems, heart problems (eg, cor pulmonale), a recent heart attack, high blood pressure, the blood disease porphyria, thyroid problems, adrenal gland problems (eg, Addison disease), an enlarged prostate or benign prostatic hypertrophy (BPH), gallbladder problems, inflammation of the pancreas (pancreatitis), urinary blockage or trouble urinating, or curvature of the spine (scoliosis)


• if you have a history of mental or mood problems, suicidal thoughts or actions, or drug or alcohol abuse or dependence


• if you are in alcohol withdrawal or if you smoke


• if you have taken a monoamine oxidase inhibitor (MAOI) (eg, phenelzine) within the past 14 days

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

• Anticholinergic medicines (eg, oxybutynin, scopolamine) because the risk of severe constipation or trouble urinating may be increased


• Cimetidine, certain nausea medicines (eg, ondansetron), phenothiazines (eg, chlorpromazine), sodium oxybate (GHB), or other narcotic medicines (eg, oxycodone) because they may increase the risk of Talacen's side effects


• Anticoagulants (eg, warfarin), MAOIs (eg, phenelzine), or sibutramine because the risk of their side effects may be increased by Talacen


• Naltrexone or rifamycins (eg, rifampin) because they may decrease the effectiveness of Talacen


• Methadone or other narcotic medicines (eg, oxycodone) because their effectiveness may be decreased by Talacen


• Medicines that may harm the liver (eg, methotrexate, ketoconazole, isoniazid, certain medicines for HIV infection) because the risk of liver side effects may be increased. Ask your doctor if you are unsure if any of your medicines might harm the liver

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

How to use Talacen:

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

• Talacen may be taken with or without food. If stomach upset occurs, take with food to reduce stomach irritation.


• If you miss a dose of Talacen and you are taking it regularly, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Talacen.

Important safety information:

• Talacen may cause drowsiness, dizziness, or blurred vision. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Talacen. Using Talacen alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.


• Avoid drinking alcohol while you are taking Talacen.


• Check with your doctor before you use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while taking Talacen; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.


• Do not change your dose or change how often you take Talacen without checking with your doctor.


• If you have been taking Talacen for a prolonged period of time, do not stop taking it without checking with your doctor.


• Tell your doctor or dentist that you take Talacen before you receive any medical or dental care, emergency care, or surgery.


• Talacen contains acetaminophen. Before you begin taking any new prescription or nonprescription medicine, read the ingredients to see if it also contains acetaminophen. If it does or if you are uncertain, contact your doctor or pharmacist.


• Talacen may contain sulfites, which can cause allergic reactions in certain individuals (eg, asthma patients). If you have previously had allergic reactions to sulfites, contact your doctor or pharmacist to determine if the medicine you are taking contains sulfites.


• Talacen may increase your risk of seizures, especially if you have a history of seizures. Contact your doctor right away if you have a seizure while taking Talacen.


• Talacen may cause constipation. To prevent constipation, maintain a diet adequate in fiber, drink plenty of water, and exercise. Talk to your doctor about using fiber laxatives or stool softeners to prevent or treat constipation while you take Talacen.


• Use Talacen with caution in the ELDERLY; they may be more sensitive to its effects, especially breathing problems, confusion, and hallucinations.


• Use Talacen with extreme caution in CHILDREN younger than 12 years of age. Safety and effectiveness in this age group have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant while taking Talacen, discuss with your doctor the benefits and risks of using Talacen during pregnancy. Talacen is found in breast milk. If you are or will be breast-feeding while you are using Talacen, check with your doctor or pharmacist to discuss the risks to your baby.

When used for long periods of time or at high doses, some people develop a need to continue taking Talacen. This is known as DEPENDENCE or addiction.

If you suddenly stop taking Talacen, you may experience WITHDRAWAL symptoms, including anxiety; diarrhea; fever, runny nose, or sneezing; goose bumps and abnormal skin sensations; nausea; vomiting; pain; rigid muscles; rapid heartbeat; seeing, hearing, or feeling things that are not there; shivering or tremors; sweating; and trouble sleeping.

Possible side effects of Talacen:

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

Constipation; dizziness; drowsiness; headache; light-headedness; nausea; sweating; vomiting.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, throat, or tongue); blistered, red, peeling, or swollen skin; confusion; disorientation; fainting; fast heartbeat; hallucinations; mental or mood changes (eg, depression, exaggerated sense of well-being); seizures; severe or persistent drowsiness, dizziness, light-headedness, or headache; severe stomach pain; slow or shallow breathing; tremor; trouble sleeping; trouble urinating; vision problems (eg, blurred vision); weakness.

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

See also: Talacen side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include anxiety; burning, numbness, or tingling; confusion; excessive sweating; extreme fatigue; fainting; fast heartbeat; hallucinations; loss of consciousness; nausea; seizures; slow and shallow breathing; symptoms of liver problems (eg, dark urine, loss of appetite, right-sided stomach pain, yellowing of the eyes or skin); unusual bruising or bleeding; unusual drowsiness, dizziness, headache, or light-headedness; unusual thoughts; vomiting.

Proper storage of Talacen:

Store Talacen between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Talacen out of the reach of children and away from pets.

General information:

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


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


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


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

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

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Talacen resources

• Talacen Side Effects (in more detail)
• Talacen Use in Pregnancy & Breastfeeding
• Drug Images
• Talacen Drug Interactions
• Talacen Support Group
• 1 Review for Talacen - Add your own review/rating

• Talacen Prescribing Information (FDA)


• Talacen Concise Consumer Information (Cerner Multum)


• Talacen Advanced Consumer (Micromedex) - Includes Dosage Information

Compare Talacen with other medications

• Pain

Ramipril 1.25mg Tablets

1. Name Of The Medicinal Product

Ramipril 1.25 mg Tablets

Ramipril 2.5 mg Tablets

Ramipril 5 mg Tablets

Ramipril 10 mg Tablets

2. Qualitative And Quantitative Composition

Each tablet contains ramipril 1.25 mg.

Each tablet contains ramipril 2.5 mg.

Each tablet contains ramipril 5 mg.

Each tablet contains ramipril 10 mg.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Tablet

1.25mg: White to almost white oblong tablets with score-line.

Upper stamp: 1.25 & logo (

Lower stamp: HMN & 1.25

The score-line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

2.5mg: Yellowish to yellow oblong tablets with score-line.

Upper stamp: 2.5 & logo (

Lower stamp: HMR & 2.5

The tablet can be divided into equal halves.

5mg: Pale red oblong tablets with score-line.

Upper stamp: 5 & logo (

Lower stamp: HMP & 5.

The tablet can be divided into equal halves.

10mg: White to almost white, oblong tablets with a score-line

Upper stamp: HMO/HMO

The tablet can be divided into equal halves.

4. Clinical Particulars

4.1 Therapeutic Indications

- Treatment of hypertension.

- Cardiovascular prevention: reduction of cardiovascular morbidity and mortality in patients with:

• manifest atherothrombotic cardiovascular disease (history of coronary heart disease or stroke, or peripheral vascular disease) or • diabetes with at least one cardiovascular risk factor (see section 5.1).

- Treatment of renal disease:

• Incipient glomerular diabetic nephropathy as defined by the presence of microalbuminuria, • Manifest glomerular diabetic nephropathy as defined by macroproteinuria in patients with at least one cardiovascular risk factor (see section 5.1), • Manifest glomerular non diabetic nephropathy as defined by macroproteinuria

- Treatment of symptomatic heart failure.

- Secondary prevention after acute myocardial infarction: reduction of mortality from the acute phase of myocardial infarction in patients with clinical signs of heart failure when started> 48 hours following acute myocardial infarction.

4.2 Posology And Method Of Administration

Oral use

It is recommended that RAMIPRIL is taken each day at the same time of the day.

RAMIPRIL can be taken before, with or after meals, because food intake does not modify its bioavailability (see section 5.2). RAMIPRIL has to be swallowed with liquid. It must not be chewed or crushed.

Adults

Diuretic-Treated patients

Hypotension may occur following initiation of therapy with RAMIPRIL; this is more likely in patients who are being treated concurrently with diuretics. Caution is therefore recommended since these patients may be volume and/or salt depleted.

If possible, the diuretic should be discontinued 2 to 3 days before beginning therapy with RAMIPRIL (see section 4.4).

In hypertensive patients in whom the diuretic is not discontinued, therapy with RAMIPRIL should be initiated with a 1.25 mg dose. Renal function and serum potassium should be monitored. The subsequent dosage of RAMIPRIL should be adjusted according to blood pressure target.

Hypertension

The dose should be individualised according to the patient profile (see section 4.4) and blood pressure control.

RAMIPRIL may be used in monotherapy or in combination with other classes of antihypertensive medicinal products.

Starting dose

RAMIPRIL should be started gradually with an initial recommended dose of 2.5 mg daily.

Patients with a strongly activated renin-angiotensin-aldosterone system may experience an excessive drop in blood pressure following the initial dose. A starting dose of 1.25 mg is recommended in such patients and the initiation of treatment should take place under medical supervision (see section 4.4).

Titration and maintenance dose

The dose can be doubled at interval of two to four weeks to progressively achieve target blood pressure; the maximum permitted dose of RAMIPRIL is 10 mg daily. Usually the dose is administered once daily.

Cardiovascular prevention

Starting dose

The recommended initial dose is 2.5 mg of RAMIPRIL once daily.

Titration and maintenance dose

Depending on the patient's tolerability to the active substance, the dose should be gradually increased. It is recommended to double the dose after one or two weeks of treatment and - after another two to three weeks - to increase it up to the target maintenance dose of 10 mg RAMIPRIL once daily.

See also posology on diuretic treated patients above.

Treatment of renal disease

In patients with diabetes and microalbuminuria:

Starting dose:

The recommended initial dose is 1.25 mg of RAMIPRIL once daily.

Titration and maintenance dose

Depending on the patient's tolerability to the active substance, the dose is subsequently increased. Doubling the once daily dose to 2.5 mg after two weeks and then to 5 mg after a further two weeks is recommended.

In patients with diabetes and at least one cardiovascular risk

Starting dose:

The recommended initial dose is 2.5 mg of RAMIPRIL once daily.

Titration and maintenance dose

Depending on the patient's tolerability to the active substance, the dose is subsequently increased. Doubling the daily dose to 5 mg RAMIPRIL after one or two weeks and then to 10 mg RAMIPRIL after a further two or three weeks is recommended. The target daily dose is 10 mg.

In patients with non- diabetic nephropathy as defined by macroproteinuria

Starting dose:

The recommended initial dose is 1.25 mg of RAMIPRIL once daily.

Titration and maintenance dose

Depending on the patient's tolerability to the active substance, the dose is subsequently increased. Doubling the once daily dose to 2.5 mg after two weeks and then to 5 mg after a further two weeks is recommended.

Symptomatic heart failure

Starting dose

In patients stabilized on diuretic therapy, the recommended initial dose is 1.25 mg daily.

Titration and maintenance dose

RAMIPRIL should be titrated by doubling the dose every one to two weeks up to a maximum daily dose of 10 mg. Two administrations per day are preferable.

Secondary prevention after acute myocardial infarction and with heart failure

Starting dose

After 48 hours, following myocardial infarction in a clinically and haemodynamically stable patient, the starting dose is 2.5 mg twice daily for three days. If the initial 2.5 mg dose is not tolerated a dose of 1.25 mg twice a day should be given for two days before increasing to 2.5 mg and 5 mg twice a day. If the dose cannot be increased to 2.5 mg twice a day the treatment should be withdrawn.

See also posology on diuretic treated patients above.

Titration and maintenance dose

The daily dose is subsequently increased by doubling the dose at intervals of one to three days up to the target maintenance dose of 5 mg twice daily.

The maintenance dose is divided in 2 administrations per day where possible.

If the dose cannot be increased to 2.5 mg twice a day treatment should be withdrawn. Sufficient experience is still lacking in the treatment of patients with severe (NYHA IV) heart failure immediately after myocardial infarction. Should the decision be taken to treat these patients, it is recommended that therapy be started at 1.25 mg once daily and that particular caution be exercised in any dose increase.

Special populations

Patients with renal impairment

Daily dose in patients with renal impairment should be based on creatinine clearance (see section 5.2):

- if creatinine clearance is

- if creatinine clearance is between 30-60 ml/min, it is not necessary to adjust the initial dose (2.5 mg/day); the maximal daily dose is 5 mg;

- if creatinine clearance is between 10-30 ml/min, the initial dose is 1.25 mg/day and the maximal daily dose is 5 mg;

- in haemodialysed hypertensive patients: ramipril is slightly dialysable; the initial dose is 1.25 mg/day and the maximal daily dose is 5 mg; the medicinal product should be administered few hours after haemodialysis is performed.

Patients with hepatic impairment (see section 5.2)

In patients with hepatic impairment, treatment with RAMIPRIL must be initiated only under close medical supervision and the maximum daily dose is 2.5 mg RAMIPRIL.

Elderly

Initial doses should be lower and subsequent dose titration should be more gradual because of greater chance of undesirable effects especially in very old and frail patients. A reduced initial dose of 1.25 mg ramipril should be considered.

Paediatric population

RAMIPRIL is not recommended for use in children and adolescents below 18 years of age due to insufficient data on safety and efficacy.

4.3 Contraindications

- Hypersensitivity to the active substance, to any of the excipients or any other ACE (Angiotensin Converting Enzyme) inhibitors (see section 6.1)

- History of angioedema (hereditary, idiopathic or due to previous angioedema with ACE inhibitors or AIIRAs)

- Extracorporeal treatments leading to contact of blood with negatively charged surfaces (see section 4.5)

- Significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney

- 2nd and 3rd trimester of pregnancy (see sections 4.4 and 4.6)

- Ramipril must not be used in patients with hypotensive or haemodynamically unstable states.

4.4 Special Warnings And Precautions For Use

Special populations

- Pregnancy: ACE inhibitors such as ramipril, or Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued ACE inhibitor/ AIIRAs therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors/ AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).

- Patients at particular risk of hypotension

- Patients with strongly activated renin-angiotensin-aldosterone system

Patients with strongly activated renin-angiotensin-aldosterone system are at risk of an acute pronounced fall in blood pressure and deterioration of renal function due to ACE inhibition, especially when an ACE inhibitor or a concomitant diuretic is given for the first time or at first dose increase.

Significant activation of renin-angiotensin-aldosterone system is to be anticipated and medical supervision including blood pressure monitoring is necessary, for example in:

- patients with severe hypertension

- patients with decompensated congestive heart failure

- patients with haemodynamically relevant left ventricular inflow or outflow impediment (e.g. stenosis of the aortic or mitral valve)

- patients with unilateral renal artery stenosis with a second functional kidney

- patients in whom fluid or salt depletion exists or may develop (including patients with diuretics)

- patients with liver cirrhosis and/or ascites

- patients undergoing major surgery or during anaesthesia with agents that produce hypotension.

Generally, it is recommended to correct dehydration, hypovolaemia or salt depletion before initiating treatment (in patients with heart failure, however, such corrective action must be carefully weighed out against the risk of volume overload).

- Transient or persistent heart failure post MI

- Patients at risk of cardiac or cerebral ischemia in case of acute hypotension

The initial phase of treatment requires special medical supervision.

- Elderly patients

See section 4.2.

- Surgery

It is recommended that treatment with angiotensin converting enzyme inhibitors such as ramipril should be discontinued where possible one day before surgery.

- Monitoring of renal function

Renal function should be assessed before and during treatment and dosage adjusted especially in the initial weeks of treatment. Particularly careful monitoring is required in patients with renal impairment (see section 4.2). There is a risk of impairment of renal function, particularly in patients with congestive heart failure or after a renal transplant.

- Angioedema

Angioedema has been reported in patients treated with ACE inhibitors including ramipril (see section 4.8).

In case of angioedema, RAMIPRIL must be discontinued.

Emergency therapy should be instituted promptly. Patient should be kept under observation for at least 12 to 24 hours and discharged after complete resolution of the symptoms.

Intestinal angioedema has been reported in patients treated with ACE inhibitors including RAMIPRIL (see section 4.8). These patients presented with abdominal pain (with or without nausea or vomiting).

- Anaphylactic reactions during desensitization

The likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom and other allergens are increased under ACE inhibition. A temporary discontinuation of RAMIPRIL should be considered prior to desensitization.

- Hyperkalaemia

Hyperkalaemia has been observed in some patients treated with ACE inhibitors including RAMIPRIL. Patients at risk for development of hyperkalaemia include those with renal insufficiency, age (> 70 years), uncontrolled diabetes mellitus, or those using potassium salts, potassium retaining diuretics and other plasma potassium increasing active substances, or conditions such as dehydration, acute cardiac decompensation, metabolic acidosis. If concomitant use of the above mentioned agents is deemed appropriate, regular monitoring of serum potassium is recommended (see section 4.5).

Neutropenia/agranulocytosis

Neutropenia/agranulocytosis, as well as thrombocytopenia and anaemia, have been rarely seen and bone marrow depression has also been reported. It is recommended to monitor the white blood cell count to permit detection of a possible leucopoenia. More frequent monitoring is advised in the initial phase of treatment and in patients with impaired renal function, those with concomitant collagen disease (e.g. lupus erythematosus or scleroderma), and all those treated with other medicinal products that can cause changes in the blood picture (see sections 4.5 and 4.8).

Ethnic differences

ACE inhibitors cause higher rate of angioedema in black patients than in non black patients.

As with other ACE inhibitors, ramipril may be less effective in lowering blood pressure in black people than in non black patients, possibly because of a higher prevalence of hypertension with low renin level in the black hypertensive population.

Cough

Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is nonproductive, persistent and resolves after discontinuation of therapy. ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Contra-indicated combinations

Extracorporeal treatments leading to contact of blood with negatively charged surfaces such as dialysis or haemofiltration with certain high-flux membranes (e.g. polyacrylonitril membranes) and low density lipoprotein apheresis with dextran sulphate due to increased risk of severe anaphylactoid reactions (see section 4.3). If such treatment is required, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent.

Precautions for use

Potassium salts, heparin, potassium-retaining diuretics and other plasma potassium increasing active substances (including Angiotensin II antagonists, trimethoprim, tacrolimus, ciclosporin): Hyperkalaemia may occur, therefore close monitoring of serum potassium is required.

Antihypertensive agents (e.g. diuretics) and other substances that may decrease blood pressure (e.g.nitrates, tricyclic antidepressants, anaesthetics, acute alcohol intake, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin): Potentiation of the risk of hypotension is to be anticipated (see section 4.2 for diuretics)

Vasopressor sympathomimetics and other substances (e.g. isoproterenol, dobutamine, dopamine, epinephrine) that may reduce the antihypertensive effect of RAMIPRIL: Blood pressure monitoring is recommended.

Allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics and other substances that may change the blood cell count: Increased likelihood of haematological reactions (see section 4.4).

Lithium salts: Excretion of lithium may be reduced by ACE inhibitors and therefore lithium toxicity may be increased. Lithium level must be monitored.

Antidiabetic agents including insulin: Hypoglycaemic reactions may occur. Blood glucose monitoring is recommended.

Non-steroidal anti-inflammatory drugs and acetylsalicylic acid: Reduction of the antihypertensive effect of RAMIPRIL is to be anticipated. Furthermore, concomitant treatment of ACE inhibitors and NSAIDs may lead to an increased risk of worsening of renal function and to an increase in kalaemia.

4.6 Pregnancy And Lactation

RAMIPRIL is not recommended during the first trimester of pregnancy (see section 4.4) and contraindicated during the second and third trimesters of pregnancy (see section 4.3).

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started. ACE inhibitor/ Angiotensin II Receptor Antagonist (AIIRA) therapy exposure during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). (See also 5.3 'Preclinical safety data'). Should exposure to ACE inhibitor have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Newborns whose mothers have taken ACE inhibitors should be closely observed for hypotension, oliguria and hyperkalaemia (see also sections 4.3 and 4.4).

Because insufficient information is available regarding the use of ramipril during breastfeeding (see section 5.2), ramipril is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

4.7 Effects On Ability To Drive And Use Machines

Some adverse effects (e.g. symptoms of a reduction in blood pressure such as dizziness) may impair the patient's ability to concentrate and react and, therefore, constitute a risk in situations where these abilities are of particular importance (e.g. operating a vehicle or machinery).

This can happen especially at the start of treatment, or when changing over from other preparations. After the first dose or subsequent increases in dose it is not advisable to drive or operate machinery for several hours.

4.8 Undesirable Effects

The safety profile of ramipril includes persistent dry cough and reactions due to hypotension. Serious adverse reactions include angioedema, hyperkalaemia, renal or hepatic impairment, pancreatitis, severe skin reactions and neutropenia/agranulocytosis.

Adverse reactions frequency is defined using the following convention:

Very common (

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

	Common	Uncommon	Rare	Very rare	Not known
Cardiac disorders		Myocardial ischaemia including angina pectoris or myocardial infarction, tachycardia, arrhythmia, palpitations, oedema peripheral
Blood and lymphatic system disorders		Eosinophilia	White blood cell count decreased (including neutropenia or agranulocytosis), red blood cell count decreased, haemoglobin decreased, platelet count decreased		Bone marrow failure, pancytopenia, haemolytic anaemia
Nervous system disorders	Headache, dizziness	Vertigo, paraesthesia, ageusia, dysgeusia,	Tremor, balance disorder		Cerebral ischaemia including ischaemic stroke and transient ischaemic attack, psychomotor skills impaired, burning sensation, parosmia
Eye disorders		Visual disturbance including blurred vision	Conjunctivitis
Ear and labyrinth disorders			Hearing impaired, tinnitus
Respiratory, thoracic and mediastinal disorders	Non-productive tickling cough, bronchitis, sinusitis, dyspnoea	Bronchospasm including asthma aggravated, nasal congestion
Gastrointestinal disorders	Gastrointestinal inflammation, digestive disturbances, abdominal discomfort, dyspepsia, diarrhoea, nausea, vomiting	Pancreatitis (cases of fatal outcome have been very exceptionally reported with ACE inhibitors), pancreatic enzymes increased, small bowel angioedema, abdominal pain upper including gastritis, constipation, dry mouth	Glossitis		Aphtous stomatitis
Renal and urinary disorders		Renal impairment including renal failure acute, urine output increased, worsening of a pre-existing proteinuria, blood urea increased, blood creatinine increased
Skin and subcutaneous tissue disorders	Rash in particular maculo-papular	Angioedema; very exceptionally, the airway obstruction resulting from angioedema may have a fatal outcome; pruritus, hyperhidrosis	Exfoliative dermatitis, urticaria, onycholysis,	Photosensitivity reaction	Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, psoriasis aggravated, dermatitis psoriasiform, pemphigoid or lichenoid exanthema or enanthema, alopecia
Musculoskeletal and connective tissue disorders	Muscle spasms, myalgia	Arthralgia
Metabolism and nutrition disorders	Blood potassium increased	Anorexia, decreased appetite,			Blood sodium decreased
Vascular disorders	Hypotension, orthostatic blood pressure decreased, syncope	Flushing	Vascular stenosis, hypoperfusion, vasculitis		Raynaud's phenomenon
General disorders and administration site conditions	Chest pain, fatigue	Pyrexia	Asthenia
Immune system disorders					Anaphylactic or anaphylactoid reactions, antinuclear antibody increased
Hepatobiliary disorders		Hepatic enzymes and/or bilirubin conjugated increased,	Jaundice cholestatic, hepatocellular damage		Acute hepatic failure, cholestatic or cytolytic hepatitis (fatal outcome has been very exceptional).
Reproductive system and breast disorders		Transient erectile impotence, libido decreased			Gynaecomastia
Psychiatric disorders		Depressed mood, anxiety, nervousness, restlessness, sleep disorder including somnolence	Confusional state		Disturbance in attention

4.9 Overdose

Symptoms associated with overdosage of ACE inhibitors may include excessive peripheral vasodilatation (with marked hypotension, shock), bradycardia, electrolyte disturbances, and renal failure. The patient should be closely monitored and the treatment should be symptomatic and supportive. Suggested measures include primary detoxification (gastric lavage, administration of adsorbents) and measures to restore haemodynamic stability, including, administration of alpha 1 adrenergic agonists or angiotensin II (angiotensinamide) administration. Ramiprilat, the active metabolite of ramipril is poorly removed from the general circulation by haemodialysis.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: ACE Inhibitors, plain, ATC code C09AA05.

Mechanism of action

Ramiprilat, the active metabolite of the prodrug ramipril, inhibits the enzyme dipeptidylcarboxypeptidase I (synonyms: angiotensin-converting enzyme; kininase II). In plasma and tissue this enzyme catalyses the conversion of angiotensin I to the active vasoconstrictor substance angiotensin II, as well as the breakdown of the active vasodilator bradykinin. Reduced angiotensin II formation and inhibition of bradykinin breakdown lead to vasodilatation.

Since angiotensin II also stimulates the release of aldosterone, ramiprilat causes a reduction in aldosterone secretion. The average response to ACE inhibitor monotherapy was lower in black (Afro-Caribbean) hypertensive patients (usually a low-renin hypertensive population) than in non-black patients.

Pharmacodynamic effects

Antihypertensive properties:

Administration of ramipril causes a marked reduction in peripheral arterial resistance. Generally, there are no major changes in renal plasma flow and glomerular filtration rate. Administration of ramipril to patients with hypertension leads to a reduction in supine and standing blood pressure without a compensatory rise in heart rate.

In most patients the onset of the antihypertensive effect of a single dose becomes apparent 1 to 2 hours after oral administration. The peak effect of a single dose is usually reached 3 to 6 hours after oral administration. The antihypertensive effect of a single dose usually lasts for 24 hours.

The maximum antihypertensive effect of continued treatment with ramipril is generally apparent after 3 to 4 weeks. It has been shown that the antihypertensive effect is sustained under long term therapy lasting 2 years.

Abrupt discontinuation of ramipril does not produce a rapid and excessive rebound increase in blood pressure.

Heart failure:

In addition to conventional therapy with diuretics and optional cardiac glycosides, ramipril has been shown to be effective in patients with functional classes II-IV of the New-York Heart Association. The drug had beneficial effects on cardiac haemodynamics (decreased left and right ventricular filling pressures, reduced total peripheral vascular resistance, increased cardiac output and improved cardiac index). It also reduced neuroendocrine activation.

Clinical efficacy and safety

Cardiovascular prevention/Nephroprotection;

A preventive placebo-controlled study (the HOPE-study), was carried out in which ramipril was added to standard therapy in more than 9,200 patients. Patients with increased risk of cardiovascular disease following either atherothrombotic cardiovascular disease (history of coronary heart disease, stroke or peripheral vascular disease) or diabetes mellitus with at least one additional risk factor (documented microalbuminuria, hypertension, elevated total cholesterol level, low high-density lipoprotein cholesterol level or cigarette smoking) were included in the study.

The study showed that ramipril statistically significantly decreases the incidence of myocardial infarction, death from cardiovascular causes and stroke, alone and combined (primary combined events).

The HOPE Study: Main Results;

	Ramipril	Placebo	relative risk (95% confidence interval)	p-value
	%	%
All patients	n=4,645	N=4,652
Primary combined events	14.0	17.8	0.78 (0.70-0.86)	<0.001
Myocardial infarction	9.9	12.3	0.80 (0.70-0.90)	<0.001
Death from cardiovascular causes	6.1	8.1	0.74 (0.64-0.87)	<0.001
Stroke	3.4	4.9	0.68 (0.56-0.84)	<0.001
Secondary endpoints
Death from any cause	10.4	12.2	0.84 (0.75-0.95)	0.005
Need for Revascularisation	16.0	18.3	0.85 (0.77-0.94)	0.002
Hospitalisation for unstable angina	12.1	12.3	0.98 (0.87-1.10)	NS
Hospitalisation for heart failure	3.2	3.5	0.88 (0.70-1.10)	0.25
Complications related to diabetes	6.4	7.6	0.84 (0.72-0.98)	0.03

The MICRO-HOPE study, a predefined substudy from HOPE, investigated the effect of the addition of ramipril 10 mg to the current medical regimen versus placebo in 3,577 patients at least

The primary analysis showed that 117 (6.5 %) participants on ramipril and 149 (8.4 %) on placebo developed overt nephropathy, which corresponds to a RRR 24 %; 95 % CI [3-40], p = 0.027.

The REIN study, a multicenter randomized, double-blind parallel group, placebo-controlled study aimed at assessing the effect of treatment with ramipril on the rate of decline of glomerular function rate (GFR) in 352 normotensive or hypertensive patients (18-70 years old) suffering from mild (i.e. mean urinary protein excretion> 1 and < 3 g/24 h) or severe proteinuria (

The main analysis of patients with the most severe proteinuria (stratum prematurely disrupted due to benefit in ramipril group) showed that the mean rate of GFR decline per month was lower with ramipril than with placebo; -0.54 (0.66) vs. -0.88 (1.03) ml/min/month, p = 0.038. The intergroup difference was thus 0.34 [0.03-0.65] per month, and around 4 ml/min/year; 23.1 % of the patients in the ramipril