Omesil

Omesil may be available in the countries listed below.

Ingredient matches for Omesil

Omeprazole

Omeprazole is reported as an ingredient of Omesil in the following countries:

• Bangladesh

International Drug Name Search

Glimepirid AbZ

Glimepirid AbZ may be available in the countries listed below.

Ingredient matches for Glimepirid AbZ

Glimepiride

Glimepiride is reported as an ingredient of Glimepirid AbZ in the following countries:

• Germany

International Drug Name Search

Risperidona Davur

Risperidona Davur may be available in the countries listed below.

Ingredient matches for Risperidona Davur

Risperidone

Risperidone is reported as an ingredient of Risperidona Davur in the following countries:

• Spain

International Drug Name Search

Coumadin Intravenous

Generic Name: warfarin (Intravenous route)

WAR-far-in

Intravenous route(Powder for Solution)

Warfarin can cause major or fatal bleeding. Regular monitoring of INR should be performed on all treated patients. Drugs, dietary changes, and other factors affect INR levels achieved with warfarin sodium therapy. Instruct patients about prevention measures to minimize risk of bleeding and to report signs and symptoms of bleeding .

Commonly used brand name(s)

In the U.S.

• Coumadin

Available Dosage Forms:

• Powder for Solution

Therapeutic Class: Anticoagulant

Chemical Class: Coumarin (class)

Uses For Coumadin

Warfarin injection is an anticoagulant. It is used to decrease the clotting ability of the blood and to help prevent harmful clots from forming in the blood vessels. It is often used to prevent or treat deep venous thrombosis, a condition in which harmful blood clots form in the blood vessels of the legs. These blood clots can travel to the lungs and cause a condition called pulmonary embolism. Warfarin is also used to prevent or treat blood clots that are caused by certain heart conditions or open-heart surgery. It may be used after a heart attack to prevent blood clots from forming. Although it will not dissolve blood clots that have already formed, warfarin may keep the clots from becoming larger and causing more serious problems.

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

Before Using Coumadin

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 warfarin injection in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of warfarin injection in the elderly. However, elderly patients may require caution and an adjustment in the dose, especially those who are at risk of bleeding.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	X	Studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. This drug should not be used in women who are or may become pregnant because the risk clearly outweighs any possible benefit.

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 receiving 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.

• Tamoxifen

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


• Acenocoumarol


• Alteplase, Recombinant


• Amiodarone


• Anistreplase


• Aprepitant


• Aspirin


• Bivalirudin


• Capecitabine


• Carboplatin


• Celecoxib


• Chamomile


• Citalopram


• Clopidogrel


• Cyclophosphamide


• Dabigatran Etexilate


• Dalteparin


• Danaparoid


• Desvenlafaxine


• Dipyridamole


• Doxorubicin


• Dronedarone


• Drotrecogin Alfa


• Enoxaparin


• Eptifibatide


• Escitalopram


• Etoposide


• Etravirine


• Fenofibrate


• Fenofibric Acid


• Fish Oil


• Fluconazole


• Fluorouracil


• Fluoxetine


• Fluvoxamine


• Garlic


• Ginkgo


• Imatinib


• Infliximab


• Influenza Virus Vaccine


• Ketoprofen


• Leflunomide


• Lepirudin


• Levofloxacin


• Lycium


• Marijuana


• Mechlorethamine


• Methotrexate


• Methyl Salicylate


• Metronidazole


• Milnacipran


• Moxifloxacin


• Naproxen


• Noscapine


• Oxandrolone


• Papaya


• Paroxetine


• Phenindione


• Phenprocoumon


• Prasugrel


• Procarbazine


• Proguanil


• Reteplase, Recombinant


• Rivaroxaban


• Ropinirole


• Sertraline


• Simvastatin


• Sitaxsentan


• St John's Wort


• Streptokinase


• Sulfamethoxazole


• Sulfisoxazole


• Tan-Shen


• Tenecteplase


• Testosterone


• Ticlopidine


• Tinzaparin


• Tirofiban


• Torsemide


• Urokinase


• Valproic Acid


• Venlafaxine


• Vilazodone


• Vincristine


• Vindesine

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.

• Acarbose


• Acemetacin


• Acetaminophen


• Allopurinol


• Aminoglutethimide


• Amitriptyline


• Amoxicillin


• Amprenavir


• Apazone


• Argatroban


• Atovaquone


• Avocado


• Azathioprine


• Azithromycin


• Bee Pollen


• Benzbromarone


• Black Tea


• Bosentan


• Bromfenac


• Butabarbital


• Butalbital


• Carbamazepine


• Cefamandole


• Cefazolin


• Chitosan


• Chloral Hydrate


• Cholestyramine


• Chondroitin


• Cimetidine


• Ciprofloxacin


• Cisapride


• Clarithromycin


• Coenzyme Q10


• Colesevelam


• Curcumin


• Cyclosporine


• Danazol


• Darunavir


• Desogestrel


• Dexamethasone


• Dexlansoprazole


• Dicloxacillin


• Dienogest


• Diflunisal


• Disopyramide


• Disulfiram


• Dong Quai


• Doxepin


• Drospirenone


• Duloxetine


• Enoxacin


• Erlotinib


• Erythromycin


• Esomeprazole


• Estradiol Cypionate


• Estradiol Valerate


• Eterobarb


• Ethinyl Estradiol


• Ethynodiol Diacetate


• Etonogestrel


• Exenatide


• Felbamate


• Fluoxymesterone


• Fluvastatin


• Gefitinib


• Gemcitabine


• Gemfibrozil


• Ginger


• Ginseng


• Glucosamine


• Glyburide


• Green Tea


• Griseofulvin


• Heparin


• Ifosfamide


• Indomethacin


• Indoprofen


• Isoniazid


• Isoxicam


• Itraconazole


• Ivermectin


• Ketoconazole


• Lactulose


• Lansoprazole


• Levamisole


• Levonorgestrel


• Lopinavir


• Lornoxicam


• Medroxyprogesterone Acetate


• Melatonin


• Meloxicam


• Menthol


• Mephobarbital


• Mercaptopurine


• Mesalamine


• Mesna


• Mestranol


• Methyltestosterone


• Miconazole


• Mitotane


• Moricizine


• Nafcillin


• Nalidixic Acid


• Nelfinavir


• Nevirapine


• Niacin


• Nilutamide


• Nimesulide


• Norelgestromin


• Norethindrone


• Norfloxacin


• Norgestimate


• Norgestrel


• Ofloxacin


• Omeprazole


• Oxyphenbutazone


• Pantoprazole


• Phenobarbital


• Phenylbutazone


• Phytonadione


• Piracetam


• Prednisone


• Primidone


• Propafenone


• Propoxyphene


• Quetiapine


• Ranitidine


• Rifabutin


• Rifampin


• Ritonavir


• Rofecoxib


• Rosuvastatin


• Roxithromycin


• Saquinavir


• Secobarbital


• Sorafenib


• Soybean


• Soy Isoflavones


• Soy Protein


• Stanozolol


• Sucralfate


• Sulfasalazine


• Sulfinpyrazone


• Sulindac


• Telithromycin


• Tenidap


• Terbinafine


• Tibolone


• Ticlopidine


• Tigecycline


• Tolterodine


• Tramadol


• Trastuzumab


• Valdecoxib


• Vancomycin


• Vemurafenib


• Vitamin A


• Vitamin E


• Vorinostat


• Zafirlukast


• Zileuton

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. 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 is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Cranberry Juice


• Pomegranate

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• High Protein Food


• Noni Juice


• Vitamin K Containing Food

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:

• Alcohol abuse, history of or


• Mental disorders (e.g., psychosis or senility)—Patients with these conditions or those who cannot cooperate should not be given warfarin.

• Blood disease or bleeding problems or


• Heart infection or


• Hypertension (high blood pressure) or


• Spinal anesthesia, recent or


• Stomach or intestinal ulcer, active or


• Stroke or


• Surgery, recent or scheduled (e.g., surgery of the eye, brain, or spine) or


• Threatened miscarriage—Should not be used in patients with any of these conditions. The risk of bleeding from warfarin may be increased.

• Catheter insertion or


• Congestive heart failure or


• Deep venous thrombosis, heparin-induced or


• Diabetes or


• Falls or blows to the body or head or


• Infection or


• Kidney disease or


• Liver disease or


• Major surgery, any type or


• Protein C deficiency (rare hereditary disease), known or suspected or


• Thrombocytopenia, heparin-induced or


• Trauma—Use with caution. This medicine may increase your risk of having serious problems.

Proper Use of Coumadin

A nurse or other trained health professional will give you this medicine. This medicine is given through a needle placed in one of your veins.

Your doctor will only give you a few doses of this medicine, and then you may be switched to an oral medicine that works the same way. If you have any concerns about this, talk to your doctor.

Carefully follow your doctor's instructions about any special diet. This medicine works best when you eat about the same amount of vitamin K in your food every day. Avoid big changes in how much vitamin K you eat. Some foods that have a high amount of vitamin K are asparagus, broccoli, brussels sprouts, cabbage, green leafy vegetables (such as collards, turnip greens, mustard greens, spinach, and salad greens), plums, rhubarb, and certain vegetable oils (such as soybean oil and canola oil).

Do not drink alcohol while you are receiving this medicine. Also avoid drinking cranberry juice or eating cranberry products.

Precautions While Using Coumadin

It is very important that your doctor check your progress at regular visits to see if the medicine is working properly. Blood tests, such as INR, are needed to check for proper dosage and unwanted side effects. Be sure to keep all appointments.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Do not stop taking any of your medicines or start any new medicines unless they have been discussed with your doctor. Keep a list of your medicines with you at all times. This includes prescription medicines, nonprescription (over-the-counter [OTC]) medicines, and herbal or vitamin supplements.

Do not take other medicines that also contain warfarin. Using too much warfarin may cause serious bleeding problems.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before having surgery or medical tests.

Check with your doctor immediately if you start to have diarrhea, fever, or any signs of infection.

This medicine may cause skin necrosis or gangrene. Call your doctor right away if you have a pain, color change, or temperature change to any area of your body. Also, call your doctor right away if you have a pain in your toes and they look purple or dark in color. These could be signs of a serious medical problem.

This medicine may increase your chance of bleeding. Check with your doctor right away if you notice any unusual bleeding or bruising; black, tarry stools; blood in the urine or stools; or pinpoint red spots on your skin. Avoid picking your nose. If you need to blow your nose, blow it gently.

Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.

Be careful not to cut yourself when you are using sharp objects, such as a safety razor or fingernail or toenail cutters. Avoid contact sports or other situations where bruising or injury could occur.

It is recommended that you carry identification that says you are using warfarin. If you have any questions about what kind of identification to carry, check with your doctor.

Coumadin 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 or nurse immediately if any of the following side effects occur:

Less common

• Abdominal or stomach pain with cramping


• bleeding gums


• blood in the urine


• bloody stools


• blurred vision


• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings


• chest pain or discomfort


• confusion


• coughing up blood


• difficulty with breathing or swallowing


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


• excessive bruising


• headache


• increased menstrual flow or vaginal bleeding


• nosebleeds


• paralysis


• peeling of the skin


• prolonged bleeding from cuts


• red or black, tarry stools


• red or dark brown urine


• shortness of breath


• sweating


• unexplained swelling


• unusual tiredness or weakness

Rare

• Arm, back, or jaw pain


• blue-green to black skin discoloration


• blue or purple toes


• change in consciousness


• chest tightness or heaviness


• chills


• clay-colored stools


• diarrhea


• dizziness


• fainting or loss of consciousness


• fast or irregular breathing


• fast or irregular heartbeat


• fever


• itching


• light-colored stools


• loss of appetite


• nausea and vomiting


• pain in the toes


• pain, redness, or sloughing of the skin


• pale skin


• skin blisters


• skin rash


• small red or purple spots on the skin


• stomach pain


• swelling of the eyes or eyelids


• tightness in the chest or wheezing


• troubled breathing with exertion


• unpleasant breath odor


• unusual bleeding or bruising


• upper right abdominal or stomach pain


• vomiting of blood


• yellow eyes and skin

Incidence not known

• Painful or prolonged erection of the penis

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:

Less common

• Joint pain


• muscle pain

Rare

• Bloated


• change in taste, or bad, unusual, or unpleasant (after) taste


• cold intolerance


• excess air or gas in the stomach or intestines


• full feeling


• general feeling of discomfort or illness


• hair loss or thinning of the hair


• hives or welts


• lack or loss of strength


• pain


• passing gas


• red, sore, or itching skin


• sores, welting, or blisters


• unusual drowsiness, dullness, or feeling of sluggishness

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: Coumadin Intravenous 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 Coumadin Intravenous resources

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

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• Antiphospholipid Syndrome
• Chronic Central Venous Catheterization
• Deep Vein Thrombosis Prophylaxis after Hip Replacement Surgery
• Deep Vein Thrombosis Prophylaxis after Knee Replacement Surgery
• Deep Vein Thrombosis, First Event
• Deep Vein Thrombosis, Recurrent Event
• Heart Attack
• Heart Failure
• Prevention of Thromboembolism in Atrial Fibrillation
• Prosthetic Heart Valves
• Prosthetic Heart Valves, Mechanical Valves
• Prosthetic Heart Valves, Tissue Valves
• Protein S Deficiency
• Pulmonary Embolism, First Event
• Pulmonary Embolism, Recurrent Event
• Thromboembolic Stroke Prophylaxis

Tussin DM

dextromethorphan hydrobromide and guaifenesin

Dosage Form: oral liquid
Drug Facts

Active ingredients

Dextromethorphan HBr, USP 10 mg

Guaifenesin, USP 100 mg

Purpose

Cough suppressant

Expectorant

Uses

temporarily relieves cough due to minor

throat and bronchial irritation as may occur with a

cold • helps loosen phlegm (mucus) and thin bronchial

secretions to make coughs more productive

Warnings

Do not use if you are now taking a prescription

monoamine oxidase inhibitor (MAOI) (certain drugs

for depression, psychiatric or emotional conditions,

or Parkinson's disease), or for 2 weeks after

stopping the MAOI drug. If you do not know if

your prescription drug contains an MAOI, ask a

doctor or pharmacist before taking this product.

Ask a doctor before use if you have

cough that occurs with too much phlegm (mucus)

• cough that lasts or is chronic such as occurs with

smoking, asthma, chronic bronchitis or emphysema

When using this product

do not use more than directed

Stop use and ask a doctor if

cough lasts more than 7 days, comes back, or is

accompanied by fever, rash, or persistent headache.

These could be signs of a serious condition.

If pregnant or breast-feeding,

ask a health

professional before use.

Keep this and all drugs out of the reach of children.

In case of accidental overdose, seek

professional assistance or contact a Poison Control

Center immediately.

Directions

do not exceed 6 doses in a 24-hour period

• this adult product is not intended for use in

children under 12 years of age

adults and children 12 years and over    2 teaspoonfuls (tsps) every 4 hours    


children under 12 years   do not use

Other information

alcohol-free • dosage cup provided

• store at controlled room temperature

Inactive ingredients

citric acid, flavor,

glucose, glycerin, high fructose corn syrup,

menthol, purified water, red 40, saccharin sodium,

sodium benzoate

Principal Display Panel

Premier Value

Tussin DM


Dextromethorphan HBr (Cough Suppressant)

Guaifenesin (Expectorant)


Controls Coughs

Loosens and Relieves  chest congestion

Alcohol Free

Cough and chest congestion formula for adults


4 fl oz (118mL)

Tussin DM  dextromethorphan hydrobromide, guaifenesin  liquid

Product Information Product Type HUMAN OTC DRUG NDC Product Code (Source) 68016-018 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Dextromethorphan Hydrobromide (Dextromethorphan) Dextromethorphan Hydrobromide 10 mg  in 5 mL GUAIFENESIN (GUAIFENESIN) GUAIFENESIN 100 mg  in 5 mL

Inactive Ingredients Ingredient Name Strength CITRIC ACID MONOHYDRATE   DEXTROSE   GLYCERIN   HIGH FRUCTOSE CORN SYRUP   MENTHOL   SACCHARIN SODIUM   SODIUM BENZOATE   FD&C RED NO. 40

Product Characteristics Color      Score      Shape Size Flavor CHERRY (Cherry) Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 68016-018-04 118 mL In 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
OTC monograph final	part341	08/21/2009

Labeler - Premier Value (101668460)

Registrant - Aaron Industries, Inc. (101896231)

Establishment
Name	Address	ID/FEI	Operations
Aaron Industries, Inc.		101896231	manufacture, analysis

Revised: 11/2009Premier Value

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• Tussin DM Side Effects (in more detail)
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• Cough
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Quinapril Cinfamed

Quinapril Cinfamed may be available in the countries listed below.

Ingredient matches for Quinapril Cinfamed

Quinapril

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

• Spain

International Drug Name Search

Comvax Vaccine

Dosage Form: injection, suspension
COMVAX®

[HAEMOPHILUS b CONJUGATE (MENINGOCOCCAL PROTEIN CONJUGATE) and

HEPATITIS B (RECOMBINANT) VACCINE]

Comvax Vaccine Description

COMVAX® [Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) Vaccine] is a sterile bivalent vaccine made of the antigenic components used in producing PedvaxHIB® [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)] and RECOMBIVAX HB® [Hepatitis B Vaccine (Recombinant)]. These components are the Haemophilus influenzae type b capsular polysaccharide [polyribosylribitol phosphate (PRP)] that is covalently bound to an outer membrane protein complex (OMPC) of Neisseria meningitidis and hepatitis B surface antigen (HBsAg) from recombinant yeast cultures.

Haemophilus influenzae type b and Neisseria meningitidis serogroup B are grown in complex fermentation media. The primary ingredients of the phenol-inactivated fermentation medium for Haemophilus influenzae include an extract of yeast, nicotinamide adenine dinucleotide, hemin chloride, soy peptone, dextrose, and mineral salts and for Neisseria meningitidis include an extract of yeast, amino acids and mineral salts. The PRP is purified from the culture broth by purification procedures which include ethanol fractionation, enzyme digestion, phenol extraction and diafiltration. The OMPC from Neisseria meningitidis is purified by detergent extraction, ultracentrifugation, diafiltration and sterile filtration.

The PRP-OMPC conjugate is prepared by the chemical coupling of the highly purified PRP (polyribosylribitol phosphate) of Haemophilus influenzae type b (Haemophilus b, Ross strain) to an OMPC of the B11 strain of Neisseria meningitidis serogroup B. The coupling of the PRP to the OMPC is necessary for enhanced immunogenicity of the PRP. This coupling is confirmed by analysis of the components of the conjugate following chemical treatment which yields a unique amino acid. After conjugation, the aqueous bulk is then adsorbed onto an amorphous aluminum hydroxyphosphate sulfate adjuvant (previously referred to as aluminum hydroxide).

HBsAg is produced in recombinant yeast cells. A portion of the hepatitis B virus gene, coding for HBsAg, is cloned into yeast, and the vaccine for hepatitis B is produced from cultures of this recombinant yeast strain according to methods developed in the Merck Research Laboratories. The antigen is harvested and purified from fermentation cultures of a recombinant strain of the yeast Saccharomyces cerevisiae containing the gene for the adw subtype of HBsAg. The fermentation process involves growth of Saccharomyces cerevisiae on a complex fermentation medium which consists of an extract of yeast, soy peptone, dextrose, amino acids and mineral salts.

The HBsAg protein is released from the yeast cells by mechanical cell disruption and detergent extraction, and purified by a series of physical and chemical methods, which includes ion and hydrophobic chromatography, and diafiltration. The purified protein is treated in phosphate buffer with formaldehyde and then coprecipitated with alum (potassium aluminum sulfate) to form bulk vaccine adjuvanted with amorphous aluminum hydroxyphosphate sulfate. The vaccine contains no detectable yeast DNA, and 1% or less of the protein is of yeast origin.

The individual PRP-OMPC and HBsAg adjuvanted bulks are combined to produce COMVAX. Each 0.5 mL dose of COMVAX is formulated to contain 7.5 mcg PRP conjugated to approximately 125 mcg OMPC, 5 mcg HBsAg, approximately 225 mcg aluminum as amorphous aluminum hydroxyphosphate sulfate, and 35 mcg sodium borate (decahydrate) as a pH stabilizer, in 0.9% sodium chloride. The vaccine contains not more than 0.0004% (w/v) residual formaldehyde.

The potency of the PRP-OMPC component is measured by quantitating the polysaccharide concentration by an HPLC method. The potency of the HBsAg component is measured relative to a standard by an in vitro immunoassay.

The product contains no preservative.

COMVAX is a sterile suspension for intramuscular injection.

Comvax Vaccine - Clinical Pharmacology

Haemophilus influenzae type b Disease

Prior to the introduction of Haemophilus b conjugate vaccines, Haemophilus influenzae type b (Hib) was the most frequent cause of bacterial meningitis and a leading cause of serious, systemic bacterial disease in young children worldwide.{1-4}

Hib disease occurred primarily in children under 5 years of age, and in the United States prior to the initiation of a vaccine program was estimated to account for nearly 20,000 cases of invasive infections annually, approximately 12,000 of which were meningitis. The mortality rate from Hib meningitis is about 5%. In addition, up to 35% of survivors develop neurologic sequelae including seizures, deafness, and mental retardation.{5,6} Other invasive diseases caused by this bacterium include cellulitis, epiglottitis, sepsis, pneumonia, septic arthritis, osteomyelitis, and pericarditis.

Prior to the introduction of the vaccine, it was estimated that 17% of all cases of Hib disease occurred in infants less than 6 months of age. The peak incidence of Hib meningitis occurred between 6 to 11 months of age. Forty-seven percent of all cases occurred by one year of age with the remaining 53% of cases occurring over the next four years.{2,20}

Among children under 5 years of age, the risk of invasive Hib disease is increased in certain populations including the following:

• Daycare attendees{7,8,9}


• Lower socio-economic groups{10}


• Blacks{11} (especially those who lack the Km(1) immunoglobulin allotype){12}


• Caucasians who lack the G2m(23) immunoglobulin allotype{13}


• Native Americans{14-16}


• Household contacts of cases{17}


• Individuals with asplenia, sickle cell disease, or antibody deficiency syndromes.{18,19}

Prevention of Hib Disease with Vaccine

An important virulence factor of the Hib bacterium is its polysaccharide capsule (PRP). Antibody to PRP (anti-PRP) has been shown to correlate with protection against Hib disease.{3,21} While the anti-PRP level associated with protection using conjugated vaccines has not yet been determined, the level of anti-PRP associated with protection in studies using bacterial polysaccharide immune globulin or nonconjugated PRP vaccines ranged from ≥0.15 to ≥1.0 mcg/mL.{22-28}

Nonconjugated PRP vaccines are capable of stimulating B-lymphocytes to produce antibody without the help of T-lymphocytes (T-independent). The responses to many other antigens are augmented by helper T-lymphocytes (T-dependent). PedvaxHIB is a PRP-conjugate vaccine in which the PRP is covalently bound to the OMPC carrier{29} producing an antigen which is postulated to convert the T-independent antigen (PRP alone) into a T-dependent antigen resulting in both an enhanced antibody response and immunologic memory.

Clinical Trials with PedvaxHIB

The protective efficacy of the PRP-OMPC component of COMVAX was demonstrated in a randomized, double-blind, placebo-controlled study involving 3486 Native American (Navajo) infants (The Protective Efficacy Study) who completed the primary two-dose regimen for lyophilized PedvaxHIB. This population has a much higher incidence of Hib disease than the United States population as a whole and also has a lower antibody response to Haemophilus b conjugate vaccines, including PedvaxHIB.{14-16,30,31}

Each infant in this study received two doses of either placebo or lyophilized PedvaxHIB (15 mcg Haemophilus b PRP) with the first dose administered at a mean of 8 weeks of age and the second administered approximately two months later; DTP (Diphtheria and Tetanus Toxoids and whole cell Pertussis Vaccine, Adsorbed) and OPV (Poliovirus Vaccine Live Oral Trivalent) were administered concomitantly. In a subset of 416 subjects, lyophilized PedvaxHIB (15 mcg Haemophilus b PRP) induced anti-PRP levels >0.15 mcg/mL in 88% and >1.0 mcg/mL in 52% with a geometric mean titer (GMT) of 0.95 mcg/mL one to three months after the first dose; the corresponding anti-PRP levels one to three months following the second dose were 91% and 60%, respectively, with a GMT of 1.43 mcg/mL. These antibody responses were associated with a high level of protection.

Most subjects were initially followed until 15 to 18 months of age. During this time, 22 cases of invasive Hib disease occurred in the placebo group (8 cases after the first dose and 14 cases after the second dose) and only 1 case in the vaccine group (none after the first dose and 1 after the second dose). Following the primary two-dose regimen, the protective efficacy of lyophilized PedvaxHIB was calculated to be 93% with a 95% confidence interval (C.I.) of 57-98%. In the two months between the first and second doses, the difference in number of cases of disease between placebo and vaccine recipients (8 vs 0 cases, respectively) was statistically significant (p=0.008). At termination of the study, placebo recipients were offered vaccine. All original participants were then followed two years and nine months from termination of the study. During this extended follow-up, invasive Hib disease occurred in an additional 7 of the original placebo recipients prior to receiving vaccine and in 1 of the original vaccine recipients (who had received only 1 dose of vaccine). No cases of invasive Hib disease were observed in placebo recipients after they received at least one dose of vaccine. Efficacy for this follow-up period, estimated from person-days at risk, was 96.6% (95 C.I., 72.2-99.9%) in children under 18 months of age and 100% (95 C.I., 23.5-100%) in children over 18 months of age.{31} Thus, in this study, a protective efficacy of 93% was achieved with an anti-PRP level of >1.0 mcg/mL in 60% of vaccinees and a GMT of 1.43 mcg/mL one to three months after the second dose.

Hepatitis B Disease

Hepatitis B virus is an important cause of viral hepatitis. According to the Centers for Disease Control (CDC), there are an estimated 200,000-300,000 new cases of Hepatitis B infection annually in the United States.{32} There is no specific treatment for this disease. The incubation period for hepatitis B is relatively long; six weeks to six months may elapse between exposure and the onset of clinical symptoms. The prognosis following infection with hepatitis B virus is variable and dependent on at least three factors: (1) Age — infants and younger children usually experience milder initial disease than older persons but are much more likely to remain persistently infected and become at risk of developing serious chronic liver disease; (2) Dose of virus — the higher the dose, the more likely acute icteric hepatitis B will result; and, (3) Severity of associated underlying disease — underlying malignancy or pre-existing hepatic disease predisposes to increased mortality and morbidity.{34}

Hepatitis B infection fails to resolve and progresses to a chronic carrier state in 5 to 10% of older children and adults and in up to 90% of infants; chronic infection also occurs more frequently after initial anicteric hepatitis B than after initial icteric disease.{34} Consequently, carriers of HBsAg frequently give no history of having had recognized acute hepatitis. It has been estimated that more than 285 million people in the world today are persistently infected with hepatitis B virus.{35} The CDC estimates that there are approximately 1 million-1.25 million chronic carriers of hepatitis B virus in the USA.{32} Chronic carriers represent the largest human reservoir of hepatitis B virus.

A serious complication of acute hepatitis B virus infection is massive hepatic necrosis while sequelae of chronic hepatitis B include cirrhosis of the liver, chronic active hepatitis, and hepatocellular carcinoma. Chronic carriers of HBsAg appear to be at increased risk of developing hepatocellular carcinoma. Although a number of etiologic factors are associated with development of hepatocellular carcinoma, the single most important etiologic factor appears to be chronic infection with hepatitis B virus.{36} According to the CDC, hepatitis B vaccine is recognized as the first anti-cancer vaccine because it can prevent primary liver cancer.{67}

The vehicles for transmission of the virus are most often blood and blood products but the viral antigen has also been found in tears, saliva, breast milk, urine, semen, and vaginal secretions. Hepatitis B virus is capable of surviving for days on environmental surfaces exposed to body fluids containing hepatitis B virus. Infection may occur when hepatitis B virus, transmitted by infected body fluids, is implanted via mucous surfaces or percutaneously introduced through accidental or deliberate breaks in the skin. Transmission of hepatitis B virus infection is often associated with close interpersonal contact with an infected individual and with crowded living conditions.{37}

Prevention of Hepatitis B Disease with Vaccine

Hepatitis B infection and disease can be prevented through immunization with vaccines that contain viral surface antigen (HBsAg) and induce formation of protective antibody (anti-HBs).{38-39}

Multiple clinical studies have defined a protective level of anti-HBs as 1) 10 or more sample ratio units (SRU or S/N) as determined by radioimmunoassay or 2) a positive result as determined by enzyme immunoassay.{40-46} Note: 10 SRU is comparable to 10 mIU/mL of antibody.{36} The ACIP and an international group of hepatitis B experts consider an anti-HBs titer ≥10 mIU/mL an adequate response to a complete course of hepatitis B vaccine and protective against clinically significant infection (antigenemia with or without clinical disease).{36,46}

Clinical Trials with RECOMBIVAX HB

In clinical studies, 100% of 92 infants under 1 year of age born of non-carrier mothers developed a protective level of antibody (anti-HBs ≥10 mIU/mL) after receiving three 5-mcg doses of RECOMBIVAX HB at intervals of 0, 1, and 6 months.{31}

In one clinical study of RECOMBIVAX HB (2.5 mcg), which examined a different regimen of RECOMBIVAX HB, protective levels of antibody were achieved in 98% of 52 healthy infants vaccinated at 2, 4, and 12 months of age. Protective anti-HBs levels were achieved in 100% of 50 infants vaccinated at 2, 4, and 15 months of age.{47}

The protective efficacy of three 5-mcg doses of RECOMBIVAX HB, given at birth (with Hepatitis B Immune Globulin), 1, and 6 months of age, has been demonstrated in neonates born of mothers positive for both HBsAg and HBeAg (a core-associated antigenic complex which correlates with high infectivity). In this trial, after nine months of follow-up, chronic infection had not occurred in 96% of 130 infants.{48} The estimated efficacy in prevention of chronic hepatitis B infection was 95% as compared to the infection rate in untreated historical controls.{49}

Immunogenicity of COMVAX

The immunogenicity of COMVAX (7.5 mcg Haemophilus b PRP, 5 mcg HBsAg) was assessed in 1602 infants and children 6 weeks to 15 months of age in 5 clinical studies. In 2 controlled clinical trials (n=684), the immune response of COMVAX was compared with that obtained using the monovalent vaccines, PedvaxHIB (7.5 mcg Haemophilus b PRP) and RECOMBIVAX HB (5 mcg HBsAg) given at separate sites, either concurrently or one month apart. The immunogenicity of COMVAX was further assessed in 2 uncontrolled studies (n=852). In the first, a complete three-dose series of COMVAX was administered concurrently with other routine pediatric vaccines. In the second, COMVAX was administered as the third dose of Haemophilus b PRP and HBsAg concurrently with routine pediatric vaccines. COMVAX was also administered as the control arm in the evaluation of an investigational vaccine (n=66).

These studies demonstrate COMVAX to be highly immunogenic. The antibody responses are summarized below.

Antibody Responses to COMVAX in Infants Not Previously Vaccinated with Hib or Hepatitis B Vaccine

In the pivotal, controlled, multicenter, randomized, open-label study, 882 infants approximately 2 months of age, who had not previously received any Hib or hepatitis B vaccine, were assigned to receive a three-dose regimen of either COMVAX or PedvaxHIB plus RECOMBIVAX HB at approximately 2, 4, and 12-15 months of age. The proportions of evaluable vaccinees developing clinically important levels of anti-PRP (percent with >1.0 mcg/mL after the second dose, n=762) and anti-HBs (percent with ≥10 mIU/mL after the third dose, n=750) were similar in children given COMVAX or concurrent PedvaxHIB and RECOMBIVAX HB (Table 1).

The anti-PRP response after the second dose among infants given COMVAX in this study was 72.4% (C.I. 68.7, 76.0) >1.0 mcg/mL with a GMT=2.5 mcg/mL (C.I. 2.2, 2.8) and was comparable to that of infants given the PedvaxHIB and RECOMBIVAX HB controls which was 76.3% (C.I. 70.2, 82.5) with a GMT=2.8 mcg/mL (C.I. 2.2, 3.5). These responses exceed the response of Native American (Navajo) infants in a previous study of lyophilized PedvaxHIB (60% >1.0 mcg/mL; GMT=1.43 mcg/mL) that was associated with a 93% reduction in the incidence of invasive Hib disease. The efficacy of COMVAX in the prevention of invasive Hib disease is expected to be similar to that obtained with monovalent lyophilized PedvaxHIB in the Protective Efficacy Trial (see CLINICAL PHARMACOLOGY, Clinical Trials with PedvaxHIB).

The anti-HBs response after the third dose among infants given COMVAX in this study was 98.4% ≥10 mIU/mL (C.I. 97.0, 99.3) with a GMT of 4467.5 (C.I. 3786.3, 5271.3) compared to 100.0% (C.I. 97.9, 100.0) with a GMT of 6943.9 (C.I. 5555.9, 8678.7) among infants given COMVAX or concurrent PedvaxHIB and RECOMBIVAX HB.

Although the difference in anti-HBs GMT is statistically significant (p=0.011), both values are much greater than the level of 10 mIU/mL previously established as marking a protective response to hepatitis B.{42,44-46,51,52} These GMTs are higher than those observed in young infants who received the currently licensed regimen of RECOMBIVAX HB consisting of 5-mcg doses administered on the standard 0, 1, and 6-month schedule (GMT ~ 1359.9 mIU/mL).{53-55} In addition, two studies have shown that infants given 2.5-mcg doses of RECOMBIVAX HB according to the schedule used for COMVAX (2, 4, and 12-15 months of age) developed GMTs of 1245-3424 mIU/mL.{47,64} While a difference in GMT may result in differential retention of ≥10 mIU/mL of anti-HBs after a number of years, this is of no apparent clinical significance because of immunologic memory.{56,57}

Because the HBsAg component of COMVAX induces a comparable anti-HBs response to that obtained with RECOMBIVAX HB, the efficacy of COMVAX is expected to be similar (Table 1).

Table 1: Antibody Responses to COMVAX, PedvaxHIB, and RECOMBIVAX HB in Infants Not Previously Vaccinated with Hib or Hepatitis B Vaccine

Vaccine	Age (months)	Time	n	Anti-PRP % Subjects with >0.15 mcg/mL >1.0 mcg/mL		Anti-PRP GMT (mcg/mL)	n	Anti-HBs % Subjects ≥10 mIU/mL	Anti-HBs GMT (mIU/mL)
* Postvaccination responses were determined approximately two months after doses 1 and 2. † C.I.’s of comparisons: Dose 2 Anti-PRP: 95% C.I. on difference in % >1.0 mcg/mL (-11.2, 3.1); 95% C.I. on ratio of GMT (0.69, 1.17) Dose 3 Anti-HBs: 95% C.I. on difference in % ≥10 mIU/mL (-2.9, -0.6); 95% C.I. on ratio of GMT (0.49, 0.91) ‡ Postvaccination responses were determined approximately one month after administration of dose 3. More than three-quarters of the infants in the study received DTP and OPV concomitantly with the first two doses of COMVAX or PedvaxHIB plus RECOMBIVAX HB, and approximately one-third received M-M-R® II (Measles, Mumps, and Rubella Virus Vaccine Live) with the third dose of these vaccines at 12 or 15 months of age.
COMVAX		Prevaccination	633	34.4	4.7	0.1	603	10.6	0.6
(7.5 mcg PRP,	2	Dose 1*	620	88.9	51.5	1.0	595	34.3	4.2
5 mcg HBsAg)	4	Dose 2*	576	94.8	72.4†	2.5†	571	92.1	113.9
[N=661]	12/15	Dose 3‡	570	99.3	92.6	9.5	571	98.4	4467.5†
PedvaxHIB		Prevaccination	208	33.7	5.8	0.1	196	7.1	0.5
(7.5 mcg PRP)	2	Dose 1*	202	90.1	53.5	1.1	198	41.9	5.3
+	4	Dose 2*	186	95.2	76.3†	2.8†	185	98.4†	255.7
RECOMBIVAX HB (5 mcg HBsAg) [N=221]	12/15	Dose 3‡	181	98.9	92.3	10.2	179	100.0†	6943.9†

Antibody Responses to COMVAX in Infants Previously Vaccinated with Hepatitis B Vaccine at Birth

Two clinical studies assessed antibody responses to a three-dose series of COMVAX in 128 evaluable infants who were previously given a birth dose of hepatitis B vaccine. Table 2 summarizes the anti-PRP and anti-HBs responses of these infants. The antibody responses were clinically comparable to those observed in the pivotal trial of COMVAX (Table 1).

Table 2: Antibody Responses to COMVAX in Infants Previously Vaccinated with Hepatitis B Vaccine at Birth

Study	Age (months) at Vaccination	Time	n	Anti-PRP % Subjects with >0.15 mcg/mL >1.0 mcg/mL		Anti-PRP GMT (mcg/mL)	n	Anti-HBs % Subjects ≥10 mIU/mL	Anti-HBs GMT (mIU/mL)
* Postvaccination responses were determined approximately 2 months after dose 2 and 1 month after dose 3. † Postvaccination responses were determined approximately 2 months after doses 1, 2, and 3. Infants in these studies received DTP and OPV or eIPV (enhanced inactivated poliovirus vaccine) concomitantly with the first two doses of COMVAX, while the third dose of COMVAX was given concomitantly with DTaP (diphtheria and tetanus and acellular pertussis), OPV, and M-M-R® II at 14-15 months of age (Study 1) or with just M-M-R® II at 15 months of age (Study 2).
		Prevaccination	119	24.4	5.9	0.1	71	25.4	2.9
Study 1	2	Dose 1	---------------------------------------Not Measured------------------------------------------------
[N=126]	4	Dose 2*	111	94.6	81.1	3.3	111	98.2	417.2
	14/15	Dose 3*	88	100	93.2	11.0	87	98.9	3500.7
		Prevaccination	17	58.8	0	0.2	15	6.7	0.7
Study 2	2	Dose 1†	17	88.2	47.1	0.9	16	81.3	35.2
[N=19]	4	Dose 2†	17	100	76.5	2.8	16	100	281.8
	15	Dose 3†	15	100	100	8.5	16	100	3913.4

Interchangeability of COMVAX and Licensed Haemophilus b Conjugate Vaccines or Recombinant Hepatitis B Vaccines

Among 58 children previously given a primary course of PedvaxHIB, 90% (95% C.I. 78.8%, 96.1%) developed an anti-PRP response >1 mcg/mL with a GMT of 9.6 mcg/mL (95% C.I. 6.6, 14.1) in response to a dose of COMVAX at 12-15 months of age. Among 683 children previously given a primary course of another HIB or HIB-containing vaccine, 99% (95% C.I. 97.9%, 99.6%) developed an anti-PRP response >1 mcg/mL with a GMT of 14.9 mcg/mL (95% C.I. 13.7, 16.3) in response to a dose of COMVAX at 12-15 months of age.

In another study, COMVAX was administered either concomitantly or six weeks after vaccination with M-M-R® II and VARIVAX® (Varicella Virus Vaccine Live, Oka/Merck). Among 149 children who previously received 2 doses of monovalent Hepatitis B vaccine, 100% (95% C.I. 97.6%, 100.0%) developed an anti-HBs response ≥10 mIU/mL with a GMT of 2194.6 mIU/mL (95% C.I. 1667.8, 2887.8) in response to a dose of COMVAX at 12-15 months of age.

Antibody Responses to COMVAX and Concurrently Administered Vaccines

Immunogenicity results from open-labeled studies indicate that COMVAX can be administered concomitantly with DTP, DTaP, OPV, IPV (inactivated poliomyelitis vaccine), M-M-R II, and VARIVAX using separate sites and syringes for injectable vaccines.

DTP and DTaP

After a primary series of DTP (2, 4, 6 months of age) given concomitantly with COMVAX (2 and 4 months of age), 98.2% of 57 infants developed a 4-fold rise in antibody to diphtheria, 100% of 57 infants developed a 4-fold rise in antibody to tetanus, and 89.5% to 96.5% of 57 infants developed a 4-fold rise in antibody to pertussis antigens, depending on the assay used and adjusted for maternal antibody. In this trial, after 2 doses of COMVAX, 79.0% of 62 infants developed anti-PRP >1.0 mcg/mL and after 3 doses (2, 4, and 15 months of age), 100% of 59 infants developed ≥10 mIU/mL of anti-HBs.

After a primary series of DTaP and COMVAX given concomitantly at 2, 4, and 6 months of age, 100% of 18 infants had ≥0.01 antitoxin units/mL to diphtheria and tetanus and 94.4% to 100% of 18 infants developed a ≥4-fold rise in antibody to pertussis antigens, depending on the assay used and adjusted for maternal antibody. In this trial, after 2 doses of COMVAX, 85.7% of 63 infants developed anti-PRP >1.0 mcg/mL and after 3 doses administered on the compressed schedule of 2, 4, and 6 months of age, 92.9% of 56 infants developed ≥10 mIU/mL of anti-HBs.

OPV and IPV

After a primary series of OPV (2, 4, 6 months of age) given concomitantly with COMVAX (2 and 4 months of age), 98.3% of 60 infants had neutralizing antibody ≥1:4 to poliovirus type 1, 100% of 57 infants had neutralizing antibody ≥1:4 to poliovirus type 2 and 98.1% of 53 infants had neutralizing antibody ≥1:4 to poliovirus type 3. In this trial, after 2 doses of COMVAX, 79.0% of 62 infants developed anti-PRP >1.0 mcg/mL and after 3 doses, 100% of 59 infants developed ≥10 mIU/mL of anti-HBs.

After a primary series of IPV and COMVAX given concomitantly at 2, 4, and 6 months of age, 100% of 38 infants had neutralizing antibody ≥1:4 to poliovirus types 1, 2, and 3. In this trial, after 2 doses of COMVAX, 85.7% of 63 infants developed anti-PRP >1.0 mcg/mL and after 3 doses administered on the compressed schedule of 2, 4, and 6 months of age, 92.9% of 56 infants developed ≥10 mIU/mL of anti-HBs.

M-M-R II and VARIVAX

After concomitant vaccination of M-M-R II and VARIVAX with COMVAX (12 to 15 months of age), 99.4% of 313 children developed antibody to measles, 99.2% of 354 children developed antibody to mumps, 100% of 358 children developed antibody to rubella and 100% of 276 children developed antibody to varicella. In this trial, infants received the primary series of Hib vaccine and the first two doses of Hepatitis B vaccine in the first year of life. After the dose of COMVAX, 97.8% of 368 infants developed >1.0 mcg/mL of anti-PRP and 99.2% developed ≥10 mIU/mL of anti-HBs.

Indications and Usage for Comvax Vaccine

COMVAX is indicated for vaccination against invasive disease caused by Haemophilus influenzae type b and against infection caused by all known subtypes of hepatitis B virus in infants 6 weeks to 15 months of age born of HBsAg negative mothers.

Infants born to HBsAg positive mothers should receive Hepatitis B Immune Globulin and Hepatitis B Vaccine (Recombinant) at birth and should complete the hepatitis B vaccination series given according to a particular schedule (see manufacturer's circular for Hepatitis B Vaccine [Recombinant]).

Infants born to mothers of unknown HBsAg status should receive Hepatitis B Vaccine (Recombinant) at birth and should complete the hepatitis B vaccination series given according to a particular schedule (see manufacturer's circular for Hepatitis B Vaccine [Recombinant]).

Vaccination with COMVAX should ideally begin at approximately 2 months of age or as soon thereafter as possible. In order to complete the three-dose regimen of COMVAX, vaccination should be initiated no later than 10 months of age. Infants in whom vaccination with a PRP-OMPC-containing product (i.e., PedvaxHIB, COMVAX) is not initiated until 11 months of age do not require three doses of PRP-OMPC; however, three doses of an HBsAg-containing product are required for complete vaccination against hepatitis B, regardless of age. For infants and children not vaccinated according to the recommended schedule see DOSAGE AND ADMINISTRATION.

COMVAX will not protect against invasive disease caused by Haemophilus influenzae other than type b or against invasive disease (such as meningitis or sepsis) caused by other microorganisms. COMVAX will not prevent hepatitis caused by other viruses known to infect the liver. Because of the long incubation period for hepatitis B, it is possible for unrecognized infection to be present at the time the vaccine is given. The vaccine may not prevent hepatitis B in such patients.

As with other vaccines, COMVAX may not induce protective antibody levels immediately following vaccination and may not result in a protective antibody response in all individuals given the vaccine.

Use With Other Vaccines

Immunogenicity results from open-labeled studies indicate that COMVAX can be administered concomitantly with DTP, DTaP, OPV, IPV, M-M-R II, and VARIVAX using separate sites and syringes for injectable vaccines (see CLINICAL PHARMACOLOGY).

Contraindications

Hypersensitivity to yeast or any component of the vaccine.

The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and on the etiology of the disease. The ACIP has recommended that immunization should be delayed during the course of an acute febrile illness.{63} All vaccines can be administered to persons with minor illnesses such as diarrhea, mild upper-respiratory infection with or without low-grade fever, or other low-grade febrile illness. Persons with moderate or severe febrile illness should be vaccinated as soon as they have recovered from the acute phase of the illness.

Warnings

Patients who develop symptoms suggestive of hypersensitivity after an injection should not receive further injections of the vaccine (see CONTRAINDICATIONS).

Precautions

General

General care is to be taken by the health-care provider for the safe and effective use of this product.

As for any vaccine, adequate treatment provisions, including epinephrine, should be available for immediate use should an anaphylactic or anaphylactoid reaction occur.

Use caution when vaccinating latex-sensitive individuals since the vial stopper contains dry natural latex rubber that may cause allergic reactions.

As reported with Haemophilus b Polysaccharide Vaccine and another Haemophilus b Conjugate Vaccine, cases of Haemophilus b disease may occur in the week after vaccination, prior to the onset of the protective effects of the vaccines.

The packaging stopper of this product contains natural rubber latex which may cause allergic reactions.

Instructions to Health-care Provider

The health-care provider should determine the current health status and previous vaccination history of the vaccinee.

The health-care provider should question the patient, parent or guardian about reactions to a previous dose of COMVAX, PedvaxHIB or other Haemophilus b conjugate vaccines or RECOMBIVAX HB or other hepatitis B vaccines.

Injection of a blood vessel should be avoided.

COMVAX should be given with caution in infants with bleeding disorders such as hemophilia or thrombocytopenia, with steps taken to avoid the risk of hematoma following the injection.

If COMVAX is used in persons with malignancies or those receiving immunosuppressive therapy or who are otherwise immunocompromised, the expected immune response may not be obtained.

COMVAX is not contraindicated in the presence of HIV infection.{68}

Information for Vaccine Recipients and Parents/Guardians

The health-care provider should provide the vaccine information required to be given with each vaccination to the patient, parent or guardian.

The health-care provider should inform the patient, parent or guardian of the benefits and risks associated with vaccination. For risks associated with vaccination, see WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS.

Laboratory Test Interactions

Sensitive tests (e.g., Latex Agglutination Kits) may detect PRP derived from the vaccine in the urine of some vaccinees for at least 30 days following vaccination with lyophilized PedvaxHIB{58}; in clinical studies with lyophilized PedvaxHIB, such children demonstrated a normal immune response to the vaccine. It is not known whether antigenuria will occur after vaccination with COMVAX.

Drug Interaction

Deferral of immunization may be considered in individuals receiving immunosuppressive therapy.

Carcinogenesis, Mutagenesis, Impairment of Fertility

COMVAX has not been evaluated for its carcinogenic or mutagenic potential, or its potential to impair fertility.

Pregnancy

Pregnancy Category C:

Animal reproduction studies have not been conducted with COMVAX. It is also not known whether COMVAX can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. COMVAX is not recommended for use in women of childbearing age.

Pediatric Use

Safety and effectiveness of COMVAX in infants below the age of 6 weeks and above the age of 15 months have not been established. However, studies have demonstrated that PedvaxHIB is safe and immunogenic when administered to infants and children up to the age of 71 months and RECOMBIVAX HB is safe and immunogenic in persons of all ages.

COMVAX should not be used in infants younger than 6 weeks of age because this will lead to a reduced anti-PRP response and may lead to immune tolerance (impaired ability to respond to su