Advil Allergy Sinus Caplets

Pronunciation: KLOR-fen-IR-a-meen/SOO-do-e-FED-rin/EYE-bue-PROE-fen
Generic Name: Chlorpheniramine/Pseudoephedrine/Ibuprofen
Brand Name: Advil Allergy Sinus Caplets

Advil Allergy Sinus Caplets contains a nonsteroidal anti-inflammatory drug (NSAID). It may cause an increased risk of serious and sometimes fatal heart and blood vessel problems (eg, heart attack, stroke). The risk may be greater if you already have heart problems or if you take Advil Allergy Sinus Caplets for a long time. Do not use Advil Allergy Sinus Caplets right before or after bypass heart surgery.

Advil Allergy Sinus Caplets may cause an increased risk of serious and sometimes fatal stomach ulcers and bleeding. Elderly patients may be at greater risk. This may occur without warning signs.

Advil Allergy Sinus Caplets is used for:

Relieving symptoms such as pain and sinus congestion due to colds, upper respiratory infections, and allergies. It may also used for other conditions as determined by your doctor.

Advil Allergy Sinus Caplets is an antihistamine, analgesic, and decongestant combination. The antihistamine works by blocking the action of histamine, which helps reduce symptoms such as watery eyes and sneezing. The analgesic works in the brain to help decrease pain. The decongestant works by constricting blood vessels and reducing swelling in the nasal passages, which decreases stuffiness.

Do NOT use Advil Allergy Sinus Caplets if:

• you are allergic to any ingredient in Advil Allergy Sinus Caplets


• you have had a severe allergic reaction (eg, severe rash, hives, trouble breathing, growths in the nose, dizziness) to aspirin or an NSAID (eg, ibuprofen, celecoxib)


• you have recently had or will be having bypass heart surgery


• you have severe high blood pressure, severe heart blood vessel disease, rapid heartbeat, or severe heart problems


• you are taking sodium oxybate (GHB) or if you have taken furazolidone or a monoamine oxidase inhibitor (MAOI) (eg, phenelzine) within the last 14 days


• you are in the last 3 months of pregnancy

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

Before using Advil Allergy Sinus Caplets:

Some medical conditions may interact with Advil Allergy Sinus Caplets. 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 a history of adrenal gland problems (eg, adrenal gland tumor), asthma, stomach or bowel problems (eg, bleeding, perforation, persistent or returning stomach pain or heartburn, ulcers), heart problems (eg, heart failure), high blood pressure, diabetes, blood disorders, bleeding or clotting problems, blood vessel problems, stroke, glaucoma or increased eye pressure, an enlarged prostate or other prostate problems, seizures, an overactive thyroid, kidney problems, liver problems (eg, hepatitis), or if you are at risk for any of these diseases


• if you have a history of swelling or fluid buildup, lupus, asthma, growths in the nose (nasal polyps), or mouth inflammation


• if you have fast, slow, or irregular heartbeat; or if you are dehydrated or have low fluid volume (eg, caused by diarrhea, not drinking fluids, vomiting)


• if you have poor health or low blood sodium levels, you drink alcohol, or you have a history of alcohol abuse

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

• Anticoagulants (eg, warfarin), aspirin, corticosteroids (eg, prednisone), heparin, or selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine) because the risk of stomach bleeding may be increased


• Beta-blockers (eg, propranolol), catechol-O-methyltransferase (COMT) inhibitors (eg, tolcapone), furazolidone, indomethacin, isoniazid, MAOIs (eg, phenelzine), probenecid, or tricyclic antidepressants (eg, amitriptyline) because they may increase the risk of Advil Allergy Sinus Caplets's side effects


• Bromocriptine, cyclosporine, hydantoins (eg, phenytoin), lithium, methotrexate, or quinolones (eg, ciprofloxacin) because the risk of their side effects may be increased by Advil Allergy Sinus Caplets


• Angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril) diuretics (eg, furosemide, hydrochlorothiazide), guanadrel, guanethidine, mecamylamine, methyldopa, or reserpine because their effectiveness may be decreased by Advil Allergy Sinus Caplets

This may not be a complete list of all interactions that may occur. Ask your health care provider if Advil Allergy Sinus Caplets 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 Advil Allergy Sinus Caplets:

Use Advil Allergy Sinus Caplets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Advil Allergy Sinus Caplets by mouth with or without food. It may be taken with food if it upsets your stomach. Taking it with food may not lower the risk of stomach or bowel problems (eg, bleeding, ulcers). Talk with your doctor or pharmacist if you have persistent stomach upset.


• Take Advil Allergy Sinus Caplets with a full glass of water (8 oz/240 mL) as directed by your doctor.


• If you miss a dose of Advil Allergy Sinus Caplets, 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 Advil Allergy Sinus Caplets.

Important safety information:

• Advil Allergy Sinus Caplets may cause dizziness, drowsiness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Advil Allergy Sinus Caplets with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Serious stomach ulcers or bleeding can occur with the use of Advil Allergy Sinus Caplets. Taking it in high doses or for a long time, smoking, or drinking alcohol increases the risk of these side effects. Taking Advil Allergy Sinus Caplets with food will NOT reduce the risk of these effects. Contact your doctor or emergency room at once if you develop severe stomach or back pain; black, tarry stools; vomit that looks like blood or coffee grounds; or unusual weight gain or swelling.


• Talk to your doctor before you take Advil Allergy Sinus Caplets if you drink more than 3 drinks with alcohol per day.


• Do not take diet or appetite control medicines while you are taking Advil Allergy Sinus Caplets without checking with you doctor.


• Advil Allergy Sinus Caplets has chlorpheniramine, pseudoephedrine, and ibuprofen in it. Before you start taking any new prescription or nonprescription medicine, check the label to see if it has chlorpheniramine, pseudoephedrine, or ibuprofen in it too. If it does or if you are not sure, check with your doctor or pharmacist.


• Do NOT take more than the recommended dose or take Advil Allergy Sinus Caplets for longer than prescribed without checking with your doctor.


• If your condition does not get better within 7 days or you have a fever that does not get better within 3 days, check with your doctor. If your symptoms get worse or if you have new symptoms, check with your doctor.


• Check with your doctor if you have a severe or persistent sore throat or if you have a sore throat with fever, headache, nausea, and vomiting.


• Tell your doctor or dentist that you take Advil Allergy Sinus Caplets before you receive any medical or dental care, emergency care, or surgery.


• Do not take aspirin while you are using Advil Allergy Sinus Caplets unless your doctor tells you to.


• Use Advil Allergy Sinus Caplets with caution in the ELDERLY; they may be more sensitive to its effects.


• Advil Allergy Sinus Caplets should not be used in CHILDREN younger than 12 years old; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Advil Allergy Sinus Caplets while you are pregnant. Do not take Advil Allergy Sinus Caplets during the last 3 months of pregnancy. It may cause injury or death to the fetus. If you become pregnant, contact your doctor right away. Advil Allergy Sinus Caplets is found in breast milk. If you are or will be breast-feeding while you use Advil Allergy Sinus Caplets, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Advil Allergy Sinus Caplets:

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; diarrhea; dizziness; drowsiness; excitability; headache; loss of appetite; nausea; nervousness or anxiety; trouble sleeping; upset stomach; vomiting; weakness.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody or black, tarry stools; change in the amount of urine produced; chest pain; confusion; dark urine; depression; fainting; fast, slow, or irregular heartbeat; fever, chills, or persistent sore throat; hallucinations; mood or mental changes; numbness of an arm or leg; one-sided weakness; red, swollen, blistered, or peeling skin; ringing in the ears; seizures; severe dizziness, lightheadedness, or headache; severe drowsiness; severe or persistent stomach pain or nausea; severe vomiting; shortness of breath; stiff neck; sudden or unexplained weight gain; swelling of hands, legs, or feet; tremor; unusual bruising or bleeding; unusual joint or muscle pain; unusual tiredness or weakness; vision or speech changes; vomit that looks like coffee grounds; yellowing of the skin or eyes.

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

See also: Advil Allergy Sinus 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 blurred vision; confusion; hallucinations; seizures; severe dizziness, lightheadedness, or headache; severe drowsiness; severe nausea or stomach pain; slow or troubled breathing; unusual bleeding or bruising; unusually fast, slow, or irregular heartbeat; vomit that looks like coffee grounds.

Proper storage of Advil Allergy Sinus Caplets:

Store Advil Allergy Sinus Caplets at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Avoid temperatures above 104 degrees F (40 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Advil Allergy Sinus Caplets out of the reach of children and away from pets.

General information:

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


• Advil Allergy Sinus Caplets 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 Advil Allergy Sinus Caplets. 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 Advil Allergy Sinus Caplets resources

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

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Advil

Generic Name: ibuprofen (Oral route)

eye-bue-PROE-fen

Oral route(Tablet;Suspension;Capsule, Liquid Filled;Tablet, Chewable)

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. Ibuprofen is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (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.

• Addaprin


• Advil


• A-G Profen


• Bufen


• Genpril


• Haltran


• I-Prin


• Midol


• Motrin


• Nuprin


• Proprinal


• Q-Profen

In Canada

• Actiprofen


• Advil Children's


• Advil Pediatric


• Children's Motrin


• Children's Motrin Berry Flavor


• Children's Motrin Bubble Gum Flavor


• Children's Motrin Grape Flavor


• Equate Children's Ibuprofen - Berry - Dye Free


• Infants' Motrin


• Teddy's Choice Children's Ibuprofen - Berry


• Teddy's Choice Children's Ibuprofen - Bubble Gum


• Teddy's Choice Children's Ibuprofen - Grape

Available Dosage Forms:

• Suspension


• Tablet


• Capsule, Liquid Filled


• Tablet, Chewable


• Capsule

Therapeutic Class: Analgesic

Pharmacologic Class: NSAID

Chemical Class: Propionic Acid (class)

Uses For Advil

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) used to treat mild to moderate pain, and helps to relieve symptoms of arthritis (osteoarthritis, rheumatoid arthritis, or juvenile 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 .

In addition, ibuprofen can be used to treat fever, menstrual cramps, and other conditions as determined by your doctor .

This medicine is available both over-the-counter (OTC) and with your doctor's prescription .

Before Using Advil

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 ibuprofen in children below 6 months 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 ibuprofen in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require adjustment of dosage in patients receiving ibuprofen .

Pregnancy

	Pregnancy Category	Explanation
1st Trimester	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.
2nd Trimester	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.
3rd Trimester	D	Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk.

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during 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.

• Abciximab


• Ardeparin


• Argatroban


• Beta Glucan


• Bivalirudin


• Certoparin


• Cilostazol


• Citalopram


• Clopidogrel


• Clovoxamine


• Dabigatran Etexilate


• Dalteparin


• Danaparoid


• Desirudin


• Dipyridamole


• Enoxaparin


• Escitalopram


• Femoxetine


• Flesinoxan


• Fluoxetine


• Fluvoxamine


• Fondaparinux


• Ginkgo


• Heparin


• Lepirudin


• Methotrexate


• Nadroparin


• Nefazodone


• Parnaparin


• Paroxetine


• Pemetrexed


• Protein C


• Reviparin


• Rivaroxaban


• Sertraline


• Sibutramine


• Tacrolimus


• Ticlopidine


• Tinzaparin


• Tirofiban


• Vilazodone


• 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


• Amikacin


• Amiloride


• Arotinolol


• Aspirin


• 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


• Desipramine


• Desvenlafaxine


• 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


• Lithium


• Losartan


• Mepindolol


• Methyclothiazide


• Metipranolol


• Metolazone


• Metoprolol


• Milnacipran


• Moexipril


• Nadolol


• Nebivolol


• Nipradilol


• Olmesartan Medoxomil


• Oxprenolol


• Penbutolol


• Pentopril


• Perindopril


• Phenytoin


• Pindolol


• Piretanide


• Polythiazide


• Propranolol


• Quinapril


• Ramipril


• Sotalol


• Spirapril


• Spironolactone


• Tacrine


• Talinolol


• Tasosartan


• Telmisartan


• Temocapril


• Tertatolol


• Timolol


• Tolazamide


• Tolbutamide


• Torsemide


• Trandolapril


• Triamterene


• Trichlormethiazide


• Valsartan


• Venlafaxine


• Voriconazole


• 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 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—This medicine should NOT be used in patients with this condition .

• Diabetes—Use with caution. The suspension form of this medicine contains sugar .

• 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 ibuprofen

This section provides information on the proper use of a number of products that contain ibuprofen. It may not be specific to Advil. 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 (tablets and suspension):
  
  • For fever:
    
    • Children over 2 years of age—Use and dose must be determined by your doctor.
    
    
    • Children 6 months of age up to 2 years—Dose is based on body weight and body temperature, and must be determined by your doctor. For fever lower than 102.5 °F (39.2 °C), the dose usually is 5 milligrams (mg) per kilogram (kg) (about 2.2 mg per pound) of body weight. For higher fever, the dose usually is 10 mg per kg (about 4.5 mg per pound) of body weight. The medicine may be given every six to eight hours, as needed, up to 40 mg per kg per day.
    
    
    • Infants younger than 6 months of age—Use and dose must be determined by your doctor .
    
    
  
  
  • For menstrual cramps:
    
    • Adults—400 milligrams (mg) every four hours, as needed.
    
    
    • Children—Use and dose must be determined by your doctor .
    
    
  
  
  • For mild to moderate pain:
    
    • Adults and teenagers—400 milligrams (mg) every four to six hours, as needed.
    
    
    • Children over 6 months of age—Dose is based on body weight and must be determined by your doctor. The dose usually is 10 milligrams (mg) per kilogram (kg) of body weight every six to eight hours, as needed, up to 40 mg per kg per day.
    
    
    • Infants younger than 6 months of age—Use and dose must be determined by your doctor .
    
    
  
  
  • For osteoarthritis and rheumatoid arthritis:
    
    • Adults and teenagers—1200 milligrams (mg) up to 3200 mg per day divided into three or four equal doses.
    
    
    • Children—Dose is based on body weight and must be determined by your doctor. The dose usually is 30 milligrams (mg) to 40 mg per kilogram (kg) of body weight per day, divided into three or four doses.
    
    
    • Infants younger than 6 months of age—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 Advil

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 .

Some people who have used this medicine had symptoms of meningitis. If you have fever, headache, nausea, vomiting, and stiff neck or back while using this medicine, check with your doctor right away .

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) .

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 .

Advil 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

• Abdominal pain


• acid or sour stomach


• belching


• bloating


• cloudy urine


• decrease in amount of urine


• decrease in urine output or decrease in urine-concentrating ability


• diarrhea


• difficulty having a bowel movement (stool)


• excess air or gas in stomach or intestines


• full feeling


• heartburn


• indigestion


• itching skin


• pain or discomfort in chest, upper stomach, or throat


• pale skin


• passing gas


• nausea


• noisy, rattling breathing


• rash with flat lesions or small raised lesions on the skin


• shortness of breath


• swelling of face, fingers, hands, feet, lower legs, or ankles


• troubled breathing at rest


• troubled breathing with exertion


• unusual bleeding or bruising


• unusual tiredness or weakness


• vomiting


• weight gain

Less common

• Abdominal cramps


• stomach soreness or discomfort

Rare

• Agitation


• back, leg, or stomach pains


• bleeding gums


• blistering, peeling, loosening of skin


• blood in urine or stools


• bloody, black, or tarry stools


• blurred vision


• burning feeling in chest or stomach


• change in vision


• chest pain


• chills


• clay-colored stools


• coma


• confusion


• constipation


• cough or hoarseness


• dark urine


• decreased urine output


• depression


• difficulty breathing


• difficulty swallowing


• dilated neck veins


• dizziness


• dry mouth


• extreme fatigue


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


• fever with or without chills


• frequent urination


• general body swelling


• general feeling of tiredness or weakness


• hair loss, thinning of hair


• headache


• hives or welts


• hostility


• impaired vision


• increased blood pressure


• increased volume of pale, dilute urine


• irregular breathing


• irritability


• itching


• joint or muscle pain


• lab results that show problems with liver


• lethargy


• light-colored stools


• loss of appetite


• lower back or side pain


• muscle twitching


• nosebleeds


• painful or difficult urination


• pains in stomach, side, or abdomen, possibly radiating to the back


• pinpoint red spots on skin


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


• rash


• red skin lesions, often with a purple center


• red, irritated eyes


• redness of skin


• seizures


• severe abdominal pain, cramping, burning


• severe and continuing nausea


• sore throat


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


• stiff neck or back


• stomach upset


• stupor


• swollen or painful glands


• tenderness in stomach area


• thirst


• tightness in chest


• unpleasant breath odor


• upper right abdominal pain


• vomiting of blood


• vomiting of material that looks like coffee grounds


• wheezing


• yellow eyes and skin

Symptoms of overdose

• Bluish lips or skin


• difficulty sleeping


• disorientation


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


• drowsiness to profound coma


• hallucination


• lightheadedness or fainting


• mood or other mental changes


• muscle tremors


• not breathing


• rapid, deep breathing


• restlessness


• slow or irregular heartbeat


• stomach cramps


• sudden fainting


• sweating

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

• Continuing ringing or buzzing or other unexplained noise in ears


• hearing loss


• nervousness

Rare

• Crying


• depersonalization


• discouragement


• dry eyes


• dysphoria


• euphoria


• feeling sad or empty


• lack of appetite


• loss of interest or pleasure


• mental depression


• paranoia


• quick to react or overreact


• rapidly changing moods


• runny nose


• sleepiness or unusual drowsiness


• sleeplessness


• sneezing


• stuffy nose


• trouble concentrating


• 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: Advil 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 Advil resources

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

• Advil Consumer Overview


• Advil MedFacts Consumer Leaflet (Wolters Kluwer)


• Advil Prescribing Information (FDA)


• Ibuprofen Prescribing Information (FDA)


• Ibuprofen Professional Patient Advice (Wolters Kluwer)


• Ibuprofen Monograph (AHFS DI)


• Advil Childrens Prescribing Information (FDA)


• Advil Migraine Prescribing Information (FDA)


• Caldolor Consumer Overview


• Caldolor Injection MedFacts Consumer Leaflet (Wolters Kluwer)


• Caldolor Prescribing Information (FDA)


• IBU MedFacts Consumer Leaflet (Wolters Kluwer)


• Ibutilide Fumarate Monograph (AHFS DI)


• Motrin Consumer Overview


• Motrin Prescribing Information (FDA)


• Motrin IB Prescribing Information (FDA)


• Motrin Junior Strength Chewable Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• NeoProfen Prescribing Information (FDA)

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Advil Cold & Sinus

Generic Name: ibuprofen and pseudoephedrine (EYE bue pro fen and SOO doe ee FED rin)

Brand Names: Advil Cold & Sinus, Advil Cold and Sinus Liqui-Gel, Children's Ibuprofen Cold Relief, Dristan Sinus, Motrin Childrens Cold

What is Advil Cold & Sinus (ibuprofen and pseudoephedrine)?

Ibuprofen is nonsteroidal anti-inflammatory drugs (NSAID) that reduces hormones that cause inflammation and pain in the body.

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

The combination of ibuprofen and pseudoephedrine is used to treat stuffy nose, sinus congestion, cough, and pain or fever caused by the common cold or flu.

Ibuprofen and pseudoephedrine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Advil Cold & Sinus (ibuprofen and pseudoephedrine)?

Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Do not use ibuprofen and pseudoephedrine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) within the past 14 days.

Ibuprofen may cause life-threatening heart or circulation problems such as heart attack or stroke, especially if you use it long term. Do not use this medication just before or after heart bypass surgery (coronary artery bypass graft, or CABG).

Get emergency medical help if you have chest pain, weakness, shortness of breath, slurred speech, or problems with vision or balance.

Ibuprofen may also cause serious effects on the stomach or intestines, including bleeding or perforation (forming of a hole). These conditions can be fatal and can occur without warning while you are taking ibuprofen, especially in older adults.

Call your doctor at once if you have symptoms of stomach bleeding such as black, bloody, or tarry stools, or coughing up blood or vomit that looks like coffee grounds. Do not take more of this medication than is recommended. An overdose of ibuprofen can cause damage to your stomach or intestines.

What should I discuss with my doctor before taking Advil Cold & Sinus (ibuprofen and pseudoephedrine)?

Do not use this medication just before or after heart bypass surgery (coronary artery bypass graft, or CABG).

Ibuprofen may cause life-threatening heart or circulation problems such as heart attack or stroke, especially if you use it long term.

Ibuprofen may also cause serious effects on the stomach or intestines, including bleeding or perforation (forming of a hole). These conditions can be fatal and can occur without warning while you are taking ibuprofen, especially in older adults.

Do not use ibuprofen and pseudoephedrine 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. You should not use this medication if you are allergic to ibuprofen or pseudoephedrine, or if you have:

• 
  

  a stomach ulcer or active bleeding in your stomach or intestines;

  
  


• 
  

  polyps in your nose; or

  
  


• 
  

  a history of allergic reaction to aspirin or other NSAIDs.

  
  

Ask a doctor or pharmacist if it is safe for you to take this medicine if you have:

• 
  

  a history of stomach ulcers or bleeding;

  
  


• 
  

  heart disease, congestive heart failure, high blood pressure;

  
  


• 
  

  systemic lupus erythematosus (SLE);

  
  


• liver or kidney disease;


• 
  

  a thyroid disorder;

  
  


• 
  

  diabetes;

  
  


• 
  

  enlarged prostate or problems with urination;

  
  


• 
  

  a bleeding or blood clotting disorder; or

  
  


• 
  

  if you smoke.

  
  

Taking ibuprofen during the last 3 months of pregnancy may result in birth defects and prolonged labor and delivery. Do not take this medication without medical advice if you are pregnant. It is not known whether ibuprofen and pseudoephedrine passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Advil Cold & Sinus (ibuprofen 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. Cold medicine is usually taken only for a short time until your symptoms clear up.

An overdose of ibuprofen can damage your stomach or intestines. Adults should not take more than 800 milligrams per dose or 3200 mg per day (4 maximum doses).

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Shake the oral suspension (liquid) well just before you measure a dose. Measure the liquid 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. Call your doctor if you have a fever lasting longer than 3 days, if you have new symptoms, or if your condition does not improve after taking this medication for 7 days.

If you need surgery, tell the surgeon ahead of time that you are using ibuprofen and pseudoephedrine. You may need to stop using the medicine for a short time.

Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Since cold medicine is usually taken only as 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.

Overdose symptoms may include nausea, vomiting, stomach pain, dizziness, feeling restless or nervous, blurred vision, sweating, breathing problems, or seizure (convulsions).

What should I avoid while taking Advil Cold & Sinus (ibuprofen and pseudoephedrine)?

Ask a doctor or pharmacist before using any other cough, cold, or pain medicine. Ibuprofen and pseudoephedrine are contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains ibuprofen or pseudoephedrine. Avoid drinking alcohol. It may increase your risk of stomach bleeding.

Advil Cold & Sinus (ibuprofen 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. Stop taking this medication and call your doctor at once if you have a serious side effect such as:

• 
  

  chest pain, weakness, shortness of breath, slurred speech, problems with vision or balance;

  
  


• 
  

  bloody, or tarry stools, coughing up blood or vomit that looks like coffee grounds;

  
  


• 
  

  fast, pounding, or uneven heartbeat;

  
  


• 
  

  severe dizziness, anxiety, restless feeling, or nervousness;

  
  


• 
  

  easy bruising or bleeding, unusual weakness, fever, chills, body aches, flu symptoms;

  
  


• 
  

  dangerously high blood pressure (severe headache, buzzing in your ears, confusion, chest pain, shortness of breath);

  
  


• 
  

  urinating less than usual or not at all;

  
  


• 
  

  skin rash, severe tingling, numbness, pain, muscle weakness; or

  
  


• 
  

  fever, headache, neck stiffness, chills, increased sensitivity to light, purple spots on the skin, and/or seizure (convulsions).

  
  

Less serious side effects may include:

• 
  

  upset stomach, nausea, heartburn, diarrhea, constipation;

  
  


• 
  

  bloating, gas, loss of appetite;

  
  


• 
  

  warmth, tingling, or redness under your skin;

  
  


• 
  

  dizziness, headache, feeling excited or restless;

  
  


• 
  

  sleep problems (insomnia); or

  
  


• 
  

  mild itching or skin rash.

  
  

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 Advil Cold & Sinus (ibuprofen and pseudoephedrine)?

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

• 
  

  a blood thinner such as warfarin (Coumadin, Jantoven);

  
  


• 
  

  steroids (prednisone and others);

  
  


• 
  

  diuretics (water pills), or medicines to treat high blood pressure;

  
  


• 
  

  a beta-blocker such as atenolol (Tenormin, Tenoretic), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Dutoprol, Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others;

  
  


• 
  

  an antidepressant such as amitriptyline (Elavil, Vanatrip, Limbitrol), doxepin (Sinequan), nortriptyline (Pamelor), and others; or

  
  


• 
  

  aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others.

  
  

This list is not complete and other drugs may interact with ibuprofen 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 Advil Cold & Sinus resources

• Advil Cold & Sinus Side Effects (in more detail)
• Advil Cold & Sinus Use in Pregnancy & Breastfeeding
• Drug Images
• Advil Cold & Sinus Drug Interactions
• Advil Cold & Sinus Support Group
• 2 Reviews for Advil Cold & Sinus - Add your own review/rating

Compare Advil Cold & Sinus with other medications

• Sinus Symptoms

Where can I get more information?

• Your pharmacist can provide more information about ibuprofen and pseudoephedrine.

See also: Advil Cold & Sinus side effects (in more detail)

Advate

antihemophilic factor, human recombinant

Dosage Form: injection
FULL PRESCRIBING INFORMATION

Indications and Usage for Advate

Control and Prevention of Bleeding Episodes

Advate is an antihemophilic factor (recombinant) indicated for control and prevention of bleeding episodes in adults and children with Hemophilia A.

Perioperative Management

Advate is indicated in the perioperative management in adults and children with Hemophilia A.

Advate is not indicated for the treatment of von Willebrand's disease.

Advate Dosage and Administration

For Intravenous Use After Reconstitution only

• Treatment with Advate should be initiated under the supervision of a physician experienced in the treatment of hemophilia A.


• Each vial of Advate has the recombinant Factor VIII potency in international units stated on the label. The expected in vivo peak increase in Factor VIII level expressed as IU/dL of plasma or percent normal can be estimated by multiplying the dose administered per kg body weight (IU/kg) by 2.


• The dosage and duration depend on the severity of Factor VIII deficiency, the location and extent of the bleeding, and the patient's clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life-threatening bleeding episodes. [Control and Prevention of Bleeding Episodes (2.1) and Perioperative Management (2.2)]

The expected in vivo peak increase in Factor VIII level expressed as IU/dL (or % of normal) can be estimated using the following formulas:

IU/dL (or % of normal)=[Total Dose (IU)/body weight (kg)] × 2 [IU/dL]/[IU/kg]

OR

Dose (IU) = body weight (kg) × Desired Factor VIII Rise (IU/dL or % of normal) × 0.5 (IU/kg per IU/dL)

Examples (assuming patient's baseline Factor VIII level is < 1% of normal):

1. A dose of 1750 IU Advate administered to a 70 kg patient should be expected to result in a peak post-infusion Factor VIII increase of 1750 IU × {[2 IU/dL]/[IU/kg]}/[70 kg] = 50 IU/dL (50% of normal).


2. A peak level of 70% is required in a 40 kg child. In this situation, the appropriate dose would be 40 kg × 70 IU/dL/{[2 IU/dL]/[IU/kg]} = 1400 IU.

The dose and frequency of administration should be based on the individual clinical response. Patients may vary in their pharmacokinetic (e.g. half-life, in vivo recovery) and clinical responses to Advate. Although you can estimate the dose by the calculations above, it is highly recommended that, whenever possible, appropriate laboratory tests including serial Factor VIII activity assays be performed  [see WARNINGS and PRECAUTIONS: Monitoring Laboratory Tests (5.4) and Pharmacokinetics (12.3)].

Control and Prevention of Bleeding Episodes

A guide for dosing in the treatment of bleeding episodes is provided in Table 1. The careful control of treatment dose is especially important in cases of life-threatening episodes.

Table 1 Guide to Advate Dosing for Treatment of Bleeding Episodes in Adults and Children

* Dose (IU/kg) = Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)
Degree of Hemorrhage Or Type of Bleeding Episodes	Required Peak Post-infusion Factor VIII Activity in the Blood (as % of Normal or IU/dL)	Dosage and Frequency Necessary to Maintain the Therapeutic Plasma Level
Minor Early hemarthrosis, mild muscle bleeding, or mild oral bleeding episode.	20-40	10-20 IU/kg* Repeat infusions every 12 to 24 hours (8 to 24 hours for patients under the age of 6) for one to three days until the bleeding episode is resolved (as indicated by relief of pain) or healing is achieved.
Moderate Moderate bleeding into muscles, bleeding into the oral cavity, definite hemarthroses, and known trauma.	30-60	15-30 IU per kg* Repeat infusions every 12 to 24 hours (8 to 24 hours for patients under the age of 6) for three days or more until the bleeding episode is resolved (as indicated by relief of pain) or healing is achieved.
Major Significant gastrointestinal bleeding, intracranial, intra-abdominal or intrathoracic bleeding, central nervous system bleeding, bleeding in the retropharyngeal or retroperitoneal spaces or iliopsoas sheath, Fractures, Head trauma.	60-100	Initial dose 30-50 IU per kg: Repeat dose 30-50 IU per kg every 8 to 24 hours (6 to 12 hours for patients under the age of 6) until resolution of the bleeding episode has occurred.

Peri-operative Management

A guide for dosing in perioperative management is provided in Table 2. The careful control of dose and duration of treatment is especially important in cases of major surgery or life-threatening bleeding episodes.

Table 2 Guide to Advate Dosing for Perioperative Management in Adults and Children

Type of Surgery	Required Peak Post-infusion Factor VIII Activity in the Blood (% of Normal or IU/dL)	Frequency of Infusion
* Dose (IU/kg) = Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)
Minor Including tooth extraction	60-100	A single bolus infusion (30-50 IU/kg*) beginning within one hour of the operation. Optional additional dosing every 12 to 24 hours as needed to control bleeding. For dental procedures, adjunctive therapy may be considered.
Major Examples include intracranial, Intra-abdominal, or Intrathoracic surgery, joint replacement surgery	80-120 (pre- and post-operative)	Preoperative bolus infusion: 40-60 IU/kg*. Verify 100% activity has been achieved prior to surgery. Maintenance bolus infusion (40-60 IU/kg*) repeat infusions every 8 to 24 hours (6 to 24 hours for patients under the age of 6), depending on the desired level of Factor VIII and state of wound healing.

Instruction for Use

Advate is administered by intravenous (IV) injection after reconstitution. Patients should follow the specific reconstitution and administration procedures provided by their physicians.

For instructions, patients should follow the recommendations in the FDA-approved patient labeling.

Reconstitution, product administration, and handling of the administration set and needles must be done with caution. Percutaneous puncture with a needle contaminated with blood can transmit infectious viruses including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs. Place needles in a sharps container after single use. Discard all equipment, including any reconstituted Advate in an appropriate container.

Preparation and Reconstitution:

The procedures below are provided as general guidelines for the reconstitution and administration of Advate. Always work on a clean surface and wash your hands before performing the following procedures.

1. Bring the Advate (dry factor concentrate) and Sterile Water for Injection, USP (diluent) to room temperature.


2. Remove caps from the factor concentrate and diluent vials.


3. Cleanse stoppers with germicidal solution, and allow to dry prior to use. Place the vials on a flat surface.


4. Open the BAXJECT II device package by peeling away the lid, without touching the inside (Figure A). Do not remove the device from the package.


5. Turn the package over. Press straight down to fully insert the clear plastic spike through the diluent vial stopper (Figure B).


6. Grip the BAXJECT II package at its edge and pull the package off the device (Figure C). Do not remove the blue cap from the BAXJECT II device. Do not touch the exposed white plastic spike.


7. Turn the system over, so that the diluent vial is on top. Quickly insert the white plastic spike fully into the Advate vial stopper by pushing straight down (Figure D). The vacuum will draw the diluent into the Advate vial.


8. Swirl gently until Advate is completely dissolved.

Do not refrigerate after reconstitution.

Administration

Advate is intended for intravenous use after reconstitution only.

• Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be clear and colorless in appearance. If not, do not use the solution and notify Baxter immediately.


• Administer Advate at room temperature not more than 3 hours after reconstitution.


• Plastic syringes must be used with this product, since proteins such as Advate tend to stick to the surface of glass syringes.

1. Use aseptic technique.


2. Remove the blue cap from the BAXJECT II device. Connect the syringe to the BAXJECT II device (Figure E). DO NOT INJECT AIR.


3. Turn the system upside down (factor concentrate vial now on top). Draw the factor concentrate into the syringe by pulling the plunger back slowly (Figure F).


4. Disconnect the syringe; attach a suitable needle and inject intravenously as instructed under Administration by Bolus Infusion.


5. If a patient is to receive more than one vial of Advate, the contents of multiple vials may be drawn into the same syringe. Please note that the BAXJECT II device is intended for use with a single vial of Advate and Sterile Water for Injection only, therefore reconstituting and withdrawing a second vial into the syringe requires a second BAXJECT II device.

Administration by bolus infusion

Administer a dose of Advate over a period of ≤ 5 minutes (maximum infusion rate, 10 mL/min). Determine the pulse rate before and during administration of Advate. Should a significant increase in pulse rate occur, reducing the rate of administration or temporarily halting the injection usually allows the symptoms to disappear promptly.

Figure A	Figure B	Figure C
Figure D	Figure E	Figure F

Dosage Forms and Strengths

Advate is available as a lyophilized powder in single use glass vials containing nominally 250, 500, 1000, 1500, 2000 or 3000 International Units (IU).

Each vial of Advate is labeled with the recombinant antihemophilic factor (rAHF) activity expressed in IU per vial. This potency assignment employs a Factor VIII concentrate standard that is referenced to a WHO International Standard for Factor VIII concentrates, and is evaluated by appropriate methodology to ensure accuracy of the results.

Contraindications

Known anaphylaxis to mouse or hamster protein or other constituents of the product.

Warnings and Precautions

General

The clinical response to Advate may vary. If bleeding is not controlled with the recommended dose, the plasma level of Factor VIII should be determined and a sufficient dose of Advate should be administered to achieve a satisfactory clinical response. If the patient's plasma Factor VIII level fails to increase as expected or if bleeding is not controlled after the expected dose, the presence of an inhibitor (neutralizing antibodies) should be suspected and appropriate testing performed.

Anaphylaxis and Hypersensitivity Reactions

Allergic-type hypersensitivity reactions, including anaphylaxis are possible and have been reported with Advate. Symptoms have manifested as dizziness, paresthesias, rash, flushing, face swelling, urticaria, dyspnea, and pruritis.[see PATIENT COUNSELING INFORMATION (17)]

Advate contains trace amounts of mouse immunoglobulin G (MuIgG; maximum of 0.1 ng.IU Advate) and hamster proteins (maximum of 1.5 ng/IU Advate.. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.

Discontinue Advate if hypersensitivity symptoms occur and administer appropriate emergency treatment.

Neutralizing Antibodies

Patients treated with AHF products should be carefully for the development of Factor VIII inhibitors by appropriate clinical observations and laboratory tests. Inhibitors have been reported following administration of Advate predominantly in previously untreated patients (PUPs) and previously minimally treated patients (MTPs). If expected plasma Factor VIII activity levels are not attained, or if bleeding is not controlled with an expected dose, an assay that measures Factor VIII inhibitor concentration should be performed [see Monitoring Laboratory Tests (5.4)].

Monitoring Laboratory Tests

• Monitor plasma Factor VIII activity levels by the one-stage clotting assay to confirm the adequate Factor VIII levels have been achieved and maintained, when clinically indicated [see DOSAGE AND ADMINISTRATION (2)].


• Monitor for development of Factor VIII inhibitors. Perform the Bethesda assay to determine if Factor VIII inhibitor is present. If expected Factor VIII activity plasma levels are not attained, or if bleeding is not controlled with the expected dose of Advate. Use Bethesda Units (BU) to titer inhibitors.
  
  • If the inhibitor is less than 10 BU per mL, the administration of additional Antihemophilic Factor concentrate may neutralize the inhibitor, and may permit an appropriate hemostatic response.
  
  
  • Adequate hemostasis may not be achieved if inhibitor titers are above 10 BU per mL. The inhibitor titer may rise following Advate infusion as a result of an anamnestic response to Factor VIII. The treatment or prevention of bleeding in such patients requires the use of alternative therapeutic approaches and agents.
  
  

Adverse Reactions

The most serious adverse drug reactions (ADRs) seen with Advate are hypersensitivity reactions and the development of high-titer inhibitors necessitating alternative treatments of Factor VIII..

The most common ADRs observed in clinical trials (frequency > 2% of subjects) were: Factor VIII inhibitor formation (observed predominantly in PUPs) and headache.(6.1)

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinical practice.

Advate has been evaluated in five completed studies in previously treated patents (PTPs) and one ongoing study in PUPs with severe to moderately severe Hemophilia A (Factor VIII ≤ 2% of normal). A total of 234 subjects have been treated with Advate as of March 2006. Total exposure to Advate was 44,926 infusions. The median duration of participation per subject was 370.5 (range: 1 to 1,256) days and the median exposure to Advate per subject was 128.0 (range: 1 to 598) days.

There were 2,507 adverse events (AEs) reported in 215 subjects. None of the subjects withdrew from the studies due to adverse events. There were no deaths. Nineteen treated subjects reported no AEs during their participation. The most common AEs (product-related and unrelated, according to the investigator's opinion) occurring in at least 5% if subjects who received at least 1 Advate study infusion as shown in Table 3.

 

Table 3. Adverse Events Reported by > 5% Treated of Study Subject*

* Includes data from 234, treated subjects from 5 completed studies in PTPs, and 1 ongoing study in PUPs as of 27 March 2006. † MedDRA version 8.1 was used. ‡ This percent is calculated relative to 234, the total number of treated subjects.
MedDRA† System Organ Class	MedDRA Preferred Term	Number of Events	Number of Subjects	Percent‡ of Subjects
Ear and labyrinth disorders	Ear pain	17	14	6.0
Gastrointestinal disorders	Constipation	16	12	5.1
	Diarrhoea	48	34	14.5
	Nausea	25	19	8.1
	Vomiting	53	38	16.2
General disorders and administration site conditions	Influenza like illness	17	13	5.6
	Pain	21	18	7.7
	Pyrexia	173	76	32.5
Infections and infestations	Ear infections	40	25	10.7
	Influenza	22	18	7.7
	Nasopharyngitis	121	62	26.5
	Otitis media	12	12	5.1
	Sinusitis	21	14	6.0
	Upper respiratory tract infection	49	31	13.2
Injury, poisoning and procedural complications	Accident	41	20	8.5
	Fall	22	17	7.3
	Joint sprain	16	14	6.0
	Limb injury	141	44	18.8
	Procedural pain	16	12	5.1
Musculoskeletal and connective tissue disorders	Arthralgia	79	40	17.1
	Joint swelling	15	13	5.6
	Pain in extremity	22	15	6.4
Nervous system disorders	Headache	205	64	27.4
Respiratory, thoracic and mediastinal disorders	Cough	150	68	29.1
	Nasal congestion	64	33	14.1
	Pharyngolaryngeal pain	50	32	13.7
	Rhinorrhoea	40	25	10.7
Skin and subcutaneous tissue disorders	Rash	23	19	8.1

The majority of the events in Table 3 appear to have been related to trauma, intercurrent mild respiratory or gastrointestinal disease or well-described complications of hemophilia.

Fifty-six ADRs were reported in 27 subjects. Nearly all (53/56) were isolated events or occurred once in one subject with numerous subsequent infusions without reoccurrence. The most common ADRs with a frequency greater than or equal to 2% are shown in Table 4. Of all ADRs, none were reported in neonates, 16 were reported in infants, 7 were reported in children, 8 were reported in adolescents, and 25 were reported in adults.

Table 4. Summary of Most Common Adverse Drug Reactions (ADRs)* with a frequency ≥ 2%

* ADR = Adverse Drug Reaction = adverse events considered by the investigator to be at least possibly related to administration of the product. † The Advate clinical program included 234, treated subjects from 5 completed studies in PTPs, and 1 ongoing study in PUPs as of 27 March 2006. ‡ All 5 ADRs occurred in (PUPs) from an ongoing clinical study, and all were for the development of Factor VIII inhibitors with a titer ≥ 0.6 BU that were to be reported as a serious AE.
MedDRA System Organ Class	MedDRA Preferred Term	Number of Patients	ADR Rate (% Patients)†
Investigations	Anti-Factor VIII antibody positive	5‡	2.14%
Nervous System Disorders	Headache	5	2.14%

Immunogenicity

The development of Factor VIII inhibitors with the use of Advate was evaluated in clinical studies with pediatric PTPs (<6 years of age with >50 Factor VIII exposures) and PTPs (>10 years of age with >150 Factor VIII exposures). Of 198 subjects who were treated for at least 10 exposure days or on study for a minimum of 120 days, 1 adult developed a low-titer inhibitor (2.0 [BU] in the Bethesda assay) after 26 exposure days. Eight weeks later, the inhibitor was no longer detectable, and in vivo recovery was normal at 1 and 3 hours after infusion of another marketed recombinant Factor VIII concentrate. This single event results in a Factor VIII inhibitor frequency in PTPs of 0.51% (95% CI of 0.03 and 2.91% for the risk of any Factor VIII inhibitor development). No factor VIII inhibitors were detected in the 53 treated pediatric PTPs.

In clinical studies that enrolled previously untreated subjects (defined as having had up to 3 exposures to a Factor VIII product at the time of enrollment, 5 (20%) of 25 subjects who received Advate developed inhibitors to Factor VIII. Four patients developed high titer ( > 5 BU) and one patient developed low-titer inhibitors. Inhibitors were detected at a median of 11 exposure days (range 7 to 13 exposure days) to investigational product.

Immunogenicity was also evaluated by measuring the development of antibodies to heterologous proteins. 182 treated subjects were assessed for anti-chinese hamster ovary cell protein antibodies. Of these patients, 3 showed an upward trend in antibody titer over time and 4 showed repeated but transient elevations of antibodies. 182 treated subjects were assessed for muIgGl protein antibodies. Of these 10 showed an upward trend in anti-mu IgG antibody titer over time and 2 showed repeated but transient elevations of antibodies. Four subjects who demonstrated antibody elevations reported isolated events of urticaria, pruritus, rash, and slightly elevated eosinophil counts. All of these subjects had numerous repeat exposures to the study product without recurrence of the events and a causal relationship between the antibody findings and these clinical events has not been established.

Of the 181 subjects who were treated and assessed for the presence of anti-human von Willebrand Factor (VWF) antibodies, none displayed laboratory evidence indicative of a positive serologic response.

Post Marketing Experience

The following adverse reactions have been identified during post approval use of Advate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Among patients treated with Advate, cases of serious allergic/hypersensitivity reactions including anaphylaxis have been reported and Factor VIII inhibitor formation (observed predominantly in PUPs).

Table 5 represents the most frequently reported post-marketing adverse reactions as MedDRA Preferred Terms.

Table 5. Post-Marketing Experience

* These reactions and have been manifested by dizziness, paresthesias, rash, flushing, face swelling, urticaria, and/or pruritus.
Organ System [MedDRA Primary SOC]	Preferred Term
Immune System Disorders:	Anaphylactic reaction* Hypersensitivity*
Blood And Lymphatic System Disorders:	Factor VIII inhibition
General disorders and administration site conditions	Injection site reaction Chills Fatigue Malaise

Drug Interactions

There are no known drug interactions reported with Advate. Drug interaction studies have not been performed.

USE IN SPECIFIC POPULATIONS

Pregnancy

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

Labor and Delivery

There are no adequate and well-controlled human studies that have investigated the effects of Advate during labor and delivery. Advate should be used only if clinically needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Advate is administered to a nursing woman. Advate should be given to nursing mothers only if clinically needed.

Pediatric Use

In comparison to adults, children present with higher Factor VIII clearance values and thus lower half-life and recovery of Factor VIII. This may be explained by differences in body composition and should be taken into account when dosing or following Factor VIII levels in the pediatric population. Larger or more frequent doses should be considered to account for the observed differences in adjusted recovery and terminal half-life Dose adjustment may be needed. [see Pharmacokinetics (12.3)].

Geriatric Use

Clinical studies of Advate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently compared to younger subjects. Dose selection for a geriatric patient should be individualized.

Overdosage

No symptoms of overdose with Advate have been reported.

Advate Description

Advate [Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method] is a purified glycoprotein consisting of 2,332 amino acids that is synthesized by a genetically engineered Chinese hamster ovary (CHO) cell line. In culture, the CHO cell line expresses recombinant antihemophilic factor (rAHF) into the cell culture medium. The rAHF is purified from the culture medium using a series of chromatography columns. The purification process includes an immunoaffinity chromatography step in which a monoclonal antibody directed against Factor VIII is employed to selectively isolate the rAHF from the medium. The cell culture and purification processes used in the manufacture of Advate employ no additives of human or animal origin. The production process includes a dedicated, viral inactivation solvent-detergent treatment step. The rAHF synthesized by the CHO cells has the same biological effects on clotting as Antihemophilic Factor (Human) [AHF (Human)]. Structurally the recombinant protein has a similar combination of heterogeneous heavy and light chains as found in AHF (Human).

Advate is formulated as a sterile, non-pyrogenic, white to off white powder for intravenous injection. Advate is available in single-dose vials that contain nominally 250, 500, 1000, 1500, 2000 and 3000 International Units (IU) per vial. When reconstituted with the appropriate volume of diluent, the product contains the following stabilizers in maximal amounts: 38 mg/mL mannitol, 10 mg/mL trehalose, 108 mEq/L sodium, 12 mM histidine, 12 mM Tris, 1.9 mM calcium, 0.15 mg/mL polysorbate-80, and 0.10 mg/mL glutathione. Von Willebrand Factor (vWF) is co-expressed with Factor VIII, and helps to stabilize it in culture. The final product contains no more than 2 ng vWF/IU rAHF, which will not have any clinically relevant effect in patients with von Willebrand's disease. The product contains no preservative.

Each vial of Advate is labeled with the rAHF activity expressed in IU per vial. Biological potency is determined by an in vitro assay, which employs a Factor VIII concentrate standard that is referenced to a World Health Organization (WHO) International Standard for Factor VIII concentrates. One IU, as defined by the World Health Organization standard for blood coagulation FVIII, human, is approximately equal to the level of FVIII activity found in 1 mL of fresh pooled human plasma. The specific activity of Advate is 4000 to 10000 IU per milligram of protein.

Advate - Clinical Pharmacology

Mechanism of Action

Advate temporarily replaces the missing clotting Factor VIII that is needed for effective hemostasis.

Pharmacodynamics

The activated partial thromboplastin time (aPTT) is prolonged in patients with hemophilia. Determination of (aPTT) is a conventional in vitro assay for biological activity of Factor VIII. Treatment with Advate normalizes the aPTT over the effective dosing period.

Pharmacokinetics

A randomized, crossover pharmacokinetic study of Advate produced at Orth, Austria (test) and RECOMBINATE [Antihemophilic Factor (Recombinant)] (reference) was conducted in 56 non-bleeding subjects. The subjects received either of the products as an IV infusion (50 ± 5 IU/kg body weight) and there was a washout period of 72 hours to 4 weeks between the two infusions. The pharmacokinetic parameters were calculated from Factor VIII activity measurements in blood samples obtained up to 48 hours following each infusion. Pharmacokinetic parameters for adults for each study preparation in the per-protocol analysis are presented in Table 6.

Table 6. Pharmacokinetic Parameters for Advate and RECOMBINATE (Per-Protocol Analysis, Adult Subjects age > 16 years)

* 56 subjects were enrolled in the clinical study. The per protocol analysis included 30 patients (20 adults and 10 children). The PK parameters in the table are calculated for adult subjects only. † Area under the plasma Factor VIII concentration x time curve from 0 to 48 hours post-infusion ‡ Calculated as (Cmax – baseline Factor VIII) divided by the dose in IU/kg, where Cmax is the maximal post-infusion Factor VIII measurement
Parameter	RECOMBINATE		Advate
	N	Mean ± SD	N*	Mean ± SD
AUC0-48h (IU•h/dL)†	20	1638 ± 357	20	1644 ± 338
In vivo recovery (IU/dL/IU/kg)‡	20	2.74 ± 0.56	20	2.57 ± 0.53
Half-life (h)	20	11.16± 2.50	20	12.03 ± 4.15
Cmax (IU/dL)	20	136 ± 29	20	128 ± 28
MRT (h)	20	14.68 ± 3.82	20	15.81 ± 5.91
Vss (dL/kg)	20	0.43 ± 0.10	20	0.44 ± 0.10
CL (dL/kg/h)	20	0.03 ± 0.01	20	0.03 ± 0.01

The 90% confidence intervals for the ratios of the mean AUC(0-48h) and in vivo recovery values for the test and control products were within the pre-established limits of 0.80 and 1.25. In addition, in vivo recoveries at the onset of treatment and after 75 exposure days were