Vigor

Vigor may be available in the countries listed below.

Ingredient matches for Vigor

Sildenafil

Sildenafil citrate (a derivative of Sildenafil) is reported as an ingredient of Vigor in the following countries:

• Argentina

International Drug Name Search

Calcitriolo DOC

Calcitriolo DOC may be available in the countries listed below.

Ingredient matches for Calcitriolo DOC

Calcitriol

Calcitriol is reported as an ingredient of Calcitriolo DOC in the following countries:

• Italy

International Drug Name Search

Bamyl

Bamyl may be available in the countries listed below.

Ingredient matches for Bamyl

Aspirin

Acetylsalicylic Acid is reported as an ingredient of Bamyl in the following countries:

• China


• Sweden

International Drug Name Search

Klacid Saft

Klacid Saft may be available in the countries listed below.

Ingredient matches for Klacid Saft

Clarithromycin

Clarithromycin is reported as an ingredient of Klacid Saft in the following countries:

• Germany

International Drug Name Search

Depakene

Generic Name: valproic acid (Oral route)

val-PROE-ik AS-id

Oral route(Syrup;Capsule, Liquid Filled;Capsule, Delayed Release)

Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid and its derivatives. Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity. Patients should be monitored closely and liver function tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months. Life-threatening pancreatitis has been reported in both children and adults receiving valproate. If pancreatitis is diagnosed, valproate should ordinarily be discontinued. Valproate can produce teratogenic effects such as neural tube defects (eg, spina bifida). Accordingly, the use of valproate products in women of childbearing potential requires that the benefits of its use be weighed against the risk of injury to the fetus .

Oral route(Tablet, Enteric Coated;Tablet, Extended Release;Capsule, Delayed Release)

Hepatotoxicity (some cases fatal), usually occurring during the first 6 months of treatment, has been reported in patients receiving valproic acid and its derivatives. Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity. Monitor patients closely, and perform liver function tests prior to therapy and at frequent intervals thereafter. Valproate can produce teratogenic effects such as neural tube defects (eg, spina bifida). Accordingly, the use of divalproex sodium in women of childbearing potential requires that the benefits of its use be weighed against the risk of injury to the fetus. Life-threatening pancreatitis has been reported in both children and adults receiving valproate. If pancreatitis is diagnosed, valproate should ordinarily be discontinued .

Commonly used brand name(s)

In the U.S.

• Depakene


• Depakote


• Depakote DR


• Depakote ER


• Depakote Sprinkles


• Stavzor

In Canada

• Alti-Valproic

Available Dosage Forms:

• Capsule, Delayed Release


• Syrup


• Capsule, Liquid Filled


• Tablet, Extended Release


• Tablet, Enteric Coated


• Tablet, Delayed Release

Therapeutic Class: Antimanic

Pharmacologic Class: Histone Deacetylase Inhibitor

Chemical Class: Valproic Acid (class)

Uses For Depakene

Valproic acid is used alone or together with other medicines to control certain types of seizures (convulsions) in the treatment of epilepsy. This medicine is an anticonvulsant that works in the brain tissue to stop seizures.

Valproic acid is also used to treat the manic phase of bipolar disorder (manic-depressive illness), and helps prevent migraine headaches.

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

Before Using Depakene

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 performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of valproic acid in children. However, safety and efficacy have not been established in children with epilepsy below 10 years of age; and in children with migraine below 12 years of age. Because of valproic acid's toxicity, use in children below 2 years of age requires extreme caution.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of valproic acid in the elderly. However, elderly patients are more likely to have unwanted effects (e.g., tremors or unusual drowsiness), which may require an adjustment in the dose for patients receiving valproic acid.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	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

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

Interactions with Medicines

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

Using this medicine with any of the following medicines is 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.

• Doripenem


• Ertapenem


• Imipenem


• Ketorolac


• Lamotrigine


• Meropenem


• Naproxen


• Primidone


• Vorinostat


• Warfarin

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.

• Acyclovir


• Aspirin


• Betamipron


• Carbamazepine


• Cholestyramine


• Clomipramine


• Erythromycin


• Ethosuximide


• Felbamate


• Fosphenytoin


• Ginkgo


• Lopinavir


• Lorazepam


• Mefloquine


• Nimodipine


• Nortriptyline


• Olanzapine


• Oxcarbazepine


• Panipenem


• Phenobarbital


• Phenytoin


• Rifampin


• Rifapentine


• Risperidone


• Ritonavir


• Rufinamide


• Topiramate


• Zidovudine

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:

• Brain disease, severe or


• Congenital metabolism disorders (born with a disease that affects metabolism) or


• Mental retardation with severe seizure disorders—Use with caution. May increase risk for more serious side effects.

• Liver disease or


• Urea cycle disorder (genetic disorder)—Should not be used in patients with these conditions.

• Pancreatitis (inflammation of the pancreas) or


• Thrombocytopenia (low platelet count)—May make these conditions worse.

Proper Use of valproic acid

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

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine comes with a medication guide and patient information insert. Read and follow the instructions in the insert carefully. Ask your doctor if you have any questions.

Swallow the delayed-release capsules and oral capsules whole with a full glass of water. Do not split, crush, or chew it. You may take this medicine with food.

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 forms (capsules, delayed-release capsules, and solution):
  
  • For seizures:
    
    • Adults and children 10 years of age or older—Dose is based on body weight and must be determined by your doctor. At first, the usual dose is 10 to 15 milligrams (mg) per kilogram (kg) of body weight a day to start. Your doctor may increase your dose gradually every week by 5 to 10 mg per kg of body weight if needed. However, the dose is usually not more than 60 mg per kg of body weight a day. If the total dose a day is greater than 250 mg, it is usually divided into smaller doses and taken two or more times during the day.
    
    
    • Children below 10 years of age—Use and dose must be determined by your doctor.
    
    
  
  


• For oral dosage form (delayed-release capsules):
  
  • For mania:
    
    • Adults—At first, 750 milligrams (mg) once a day, usually divided in smaller doses. Your doctor may increase your dose as needed.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For migraine:
    
    • Adults—At first, 250 milligrams (mg) two times a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 1000 mg a day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

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

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

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

Precautions While Using Depakene

It is very important that your doctor check your progress closely while you are using this medicine to see if it is working properly and to allow for a change in the dose. Blood tests may be needed to check for any unwanted effects.

Using this medicine while you are pregnant (especially during first trimester) 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.

It is very important to take folic acid before getting pregnant and during early pregnancy to lower chances of harmful side effects to your unborn baby. Ask your doctor or pharmacist for help if you are not sure how to choose a folic acid product.

Liver problems may occur while you are using this medicine. Stop using this medicine and check with your doctor right away if you are having more than one of these symptoms: abdominal pain or tenderness; clay-colored stools; dark urine; decreased appetite; fever; headache; itching; loss of appetite; nausea and vomiting; skin rash; swelling of the feet or lower legs; unusual tiredness or weakness; or yellow eyes or skin.

Pancreatitis may occur while you are using this medicine. Tell your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness.

Check with your doctor right away if you are having unusual drowsiness, dullness, tiredness, weakness or feelings of sluggishness, changes in mental status, or vomiting. These may be symptoms of a serious condition called hyperammonemic encephalopathy.

Valproic acid may cause some people to become dizzy, lightheaded, drowsy, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.

Do not stop taking this medicine without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping completely.

Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. The results of some tests may be affected by this medicine.

Valproic acid may cause serious allergic reactions that affect several parts of the body (e.g., liver or kidney). Check with your doctor right away if you have more than one of the following symptoms: fever; dark urine; headache; rash; stomach pain; swollen lymph glands in the neck, armpit, or groin; unusual tiredness; or yellow eyes or skin.

This medicine will add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for hay fever or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; barbiturates or medicine for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are taking this medicine.

Check with your doctor if you have unusual drowsiness, dullness, tiredness, weakness; or feeling of sluggishness; confusion; low body temperature; or loss of consciousness while taking this medicine.

Valproic acid may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you notice any of these adverse effects, tell your doctor right away.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Depakene 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

• Black, tarry stools


• bleeding gums


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


• blood in the urine or stools


• confusion


• cough or hoarseness


• crying


• delusions


• dementia


• depersonalization


• diarrhea


• difficult or labored breathing


• dysphoria


• euphoria


• fever or chills


• general feeling of discomfort or illness


• headache


• joint pain


• loss of appetite


• lower back or side pain


• mental depression


• muscle aches and pains


• nausea


• nervousness


• painful or difficult urination


• paranoia


• pinpoint red spots on the skin


• quick to react or overreact emotionally


• rapid weight gain


• rapidly changing moods


• runny nose


• shakiness in the legs, arms, hands, or feet


• shivering


• shortness of breath


• sleepiness or unusual drowsiness


• sore throat


• sweating


• tightness in the chest


• tingling of the hands or feet


• trembling or shaking of the hands or feet


• trouble with sleeping


• unusual bleeding or bruising


• unusual tiredness or weakness


• unusual weight gain or loss


• vomiting


• wheezing

Less common

• Abnormal dreams


• absence of or decrease in body movement


• anxiety


• bloody nose


• bloody or cloudy urine


• blurred vision


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


• change in personality


• change in walking and balance


• changes in patterns and rhythms of speech


• chest pain


• chills


• clumsiness or unsteadiness


• cold sweats


• constipation


• darkened urine


• degenerative disease of the joint


• difficult, burning, or painful urination


• difficulty with moving


• discouragement


• dizziness


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


• dry mouth


• excessive muscle tone


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


• fear


• feeling of warmth or heat


• feeling sad or empty


• flushing or redness of the skin, especially on the face and neck


• frequent urge to urinate


• heavy non-menstrual vaginal bleeding


• hyperventilation


• increased need to urinate


• indigestion


• irritability


• lack of appetite


• lack of coordination


• large, flat, blue, or purplish patches in the skin


• leg cramps


• lip smacking or puckering


• loss of bladder control


• loss of interest or pleasure


• loss of strength or energy


• multiple swollen and inflamed skin lesions


• muscle pain or stiffness


• muscle tension or tightness


• normal menstrual bleeding occurring earlier, possibly lasting longer than expected


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


• passing urine more often


• pounding in the ears


• puffing of the cheeks


• rapid or worm-like movements of the tongue


• rapid weight gain


• restlessness


• seeing, hearing, or feeling things that are not there


• shakiness and unsteady walk


• slurred speech


• small red or purple spots on the skin


• sweating


• swollen joints


• tiredness


• trouble with concentrating


• trouble with speaking


• twitching


• uncontrolled chewing movements


• uncontrolled movements of the arms and legs


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


• vomiting of blood or material that looks like coffee grounds


• yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

• Change in consciousness


• fainting


• loss of consciousness


• slow or irregular heartbeat

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

More common

• Acid or sour stomach


• belching


• body aches or pain


• change in vision


• congestion


• continuing ringing or buzzing or other unexplained noise in the ears


• hair loss or thinning of the hair


• hearing loss


• heartburn


• impaired vision


• lack or loss of strength


• loss of memory


• problems with memory


• rash


• seeing double


• sleeplessness


• tender, swollen glands in the neck


• trouble with swallowing


• unable to sleep


• uncontrolled eye movements


• voice changes


• weight gain


• weight loss

Less common

• Absent, missed, or irregular menstrual periods


• back pain


• burning, dry, or itching eyes


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


• coin-shaped lesions on the skin


• cough producing mucus


• cramps


• dandruff


• discharge or excessive tearing


• dry skin


• earache


• excess air or gas in the stomach or intestines


• eye pain


• feeling of constant movement of self or surroundings


• full feeling


• heavy bleeding


• increased appetite


• itching of the vagina or genital area


• itching skin


• loss of bowel control


• neck pain


• oily skin


• pain


• pain during sexual intercourse


• pain or tenderness around the eyes and cheekbones


• passing gas


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


• redness or swelling in the ear


• redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid


• redness, swelling, or soreness of the tongue


• sensation of spinning


• sneezing


• stiff neck


• stopping of menstrual bleeding


• thick, white vaginal discharge with no odor or with a mild odor

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: Depakene 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 Depakene resources

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

• Depakene Prescribing Information (FDA)


• Depakene MedFacts Consumer Leaflet (Wolters Kluwer)


• Valproic Acid Monograph (AHFS DI)


• Depacon MedFacts Consumer Leaflet (Wolters Kluwer)


• Depacon Prescribing Information (FDA)


• Stavzor Prescribing Information (FDA)


• Stavzor Delayed-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)


• Stavzor Consumer Overview

Compare Depakene with other medications

• Bipolar Disorder
• Hyperekplexia
• Schizoaffective Disorder
• Seizure Prevention
• Seizures

Luften

Luften may be available in the countries listed below.

Ingredient matches for Luften

Clozapine

Clozapine is reported as an ingredient of Luften in the following countries:

• Indonesia

International Drug Name Search

Rotateq

rotavirus vaccine, live

Dosage Form: oral solution
FULL PRESCRIBING INFORMATION

Indications and Usage for Rotateq

Rotateq1 is indicated for the prevention of rotavirus gastroenteritis in infants and children caused by the serotypes G1, G2, G3, and G4 when administered as a 3-dose series to infants between the ages of 6 to 32 weeks. The first dose of Rotateq should be administered between 6 and 12 weeks of age [see Dosage and Administration (2)].

1

Registered trademark of MERCK & CO., Inc., Whitehouse Station, New Jersey 08889 USA

COPYRIGHT © 2006, 2007 MERCK & CO., Inc.

All rights reserved

Rotateq Dosage and Administration

FOR ORAL USE ONLY. NOT FOR INJECTION.

The vaccination series consists of three ready-to-use liquid doses of Rotateq administered orally starting at 6 to 12 weeks of age, with the subsequent doses administered at 4- to 10-week intervals. The third dose should not be given after 32 weeks of age [see Clinical Studies (14)].

There are no restrictions on the infant’s consumption of food or liquid, including breast milk, either before or after vaccination with Rotateq.

Do not mix the Rotateq vaccine with any other vaccines or solutions. Do not reconstitute or dilute [see Dosage and Administration (2.2)].

For storage instructions [see How Supplied/Storage and Handling (16.1)].

Each dose is supplied in a container consisting of a squeezable plastic dosing tube with a twist-off cap, allowing for direct oral administration. The dosing tube is contained in a pouch [see Dosage and Administration (2.2)].

Use with Other Vaccines

In clinical trials, Rotateq was administered concomitantly with other licensed pediatric vaccines [see Adverse Reactions (6.1), Drug Interactions (7.1), and Clinical Studies (14)].

Instructions for Use

To administer the vaccine:
	Tear open the pouch and remove the dosing tube.
	Clear the fluid from the dispensing tip by holding tube vertically and tapping cap.
	Open the dosing tube in 2 easy motions:
	1.   Puncture the dispensing tip by screwing cap clockwise       until it becomes tight.
	2.   Remove cap by turning it counterclockwise.
	Administer dose by gently squeezing liquid into infant's mouth toward the inner cheek until dosing tube is empty. (A residual drop may remain in the tip of the tube.)
	If for any reason an incomplete dose is administered (e.g., infant spits or regurgitates the vaccine), a replacement dose is not recommended, since such dosing was not studied in the clinical trials. The infant should continue to receive any remaining doses in the recommended series.
	Discard the empty tube and cap in approved biological waste containers according to local regulations.

Dosage Forms and Strengths

Rotateq, 2 mL for oral use, is a ready-to-use solution of live reassortant rotaviruses, containing G1, G2, G3, G4 and P1A[8] which contains a minimum of 2.0 – 2.8 x 106 infectious units (IU) per individual reassortant dose, depending on the serotype, and not greater than 116 x 106 IU per aggregate dose.

Each dose is supplied in a container consisting of a squeezable plastic dosing tube with a twist-off cap, allowing for direct oral administration. The dosing tube is contained in a pouch.

Contraindications

A demonstrated history of hypersensitivity to any component of the vaccine.

Infants who develop symptoms suggestive of hypersensitivity after receiving a dose of Rotateq should not receive further doses of Rotateq.

 Infants with Severe Combined Immunodeficiency Disease (SCID) should not receive Rotateq. Post-marketing reports of gastroenteritis, including severe diarrhea and prolonged shedding of vaccine virus, have been reported in infants who were administered Rotateq and later identified as having SCID [see Adverse Reactions (6.2)].

Warnings and Precautions

Immunocompromised Populations

No safety or efficacy data are available from clinical trials regarding the administration of Rotateq to infants who are potentially immunocompromised including:

• Infants with blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic system.


• Infants on immunosuppressive therapy (including high-dose systemic corticosteroids). Rotateq may be administered to infants who are being treated with topical corticosteroids or inhaled steroids.


• Infants with primary and acquired immunodeficiency states, including HIV/AIDS or other clinical manifestations of infection with human immunodeficiency viruses; cellular immune deficiencies; and hypogammaglobulinemic and dysgammaglobulinemic states. There are insufficient data from the clinical trials to support administration of Rotateq to infants with indeterminate HIV status who are born to mothers with HIV/AIDS.


• Infants who have received a blood transfusion or blood products, including immunoglobulins within 42 days.

 Vaccine virus transmission from vaccine recipient to non-vaccinated contacts has been reported [see Warnings and Precautions (5.4)].

Gastrointestinal Illness

No safety or efficacy data are available for administration of Rotateq to infants with a history of gastrointestinal disorders including infants with active acute gastrointestinal illness, infants with chronic diarrhea and failure to thrive, and infants with a history of congenital abdominal disorders, abdominal surgery, and intussusception. Caution is advised when considering administration of Rotateq to these infants.

Intussusception

Following administration of a previously licensed live rhesus rotavirus-based vaccine, an increased risk of intussusception was observed.{1} In the Rotavirus Efficacy and Safety Trial [REST] (n=69,625), the data did not show an increased risk of intussusception for Rotateq when compared to placebo. In post-marketing experience, cases of intussusception have been reported in temporal association with Rotateq. [See Adverse Reactions (6.1 and 6.2).]

Shedding and Transmission

Shedding of vaccine virus was evaluated among a subset of subjects in REST 4 to 6 days after each dose and among all subjects who submitted a stool antigen rotavirus positive sample at any time. Rotateq was shed in the stools of 32 of 360 [8.9%, 95% CI (6.2%, 12.3%)] vaccine recipients tested after dose 1; 0 of 249 [0.0%, 95% CI (0.0%, 1.5%)] vaccine recipients tested after dose 2; and in 1 of 385 [0.3%, 95% CI (<0.1%, 1.4%)] vaccine recipients after dose 3. In phase 3 studies, shedding was observed as early as 1 day and as late as 15 days after a dose. Transmission of vaccine virus was not evaluated in phase 3 studies.

 Transmission of vaccine virus strains from vaccinees to non-vaccinated contacts has been observed post-marketing.

 The potential risk of transmission of vaccine virus should be weighed against the risk of acquiring and transmitting natural rotavirus.

Caution is advised when considering whether to administer Rotateq to individuals with immunodeficient close contacts such as:

• Individuals with malignancies or who are otherwise immunocompromised;


•  Individuals with primary immunodeficiency; or


• Individuals receiving immunosuppressive therapy.

Febrile Illness

Febrile illness may be reason for delaying use of Rotateq except when, in the opinion of the physician, withholding the vaccine entails a greater risk. Low-grade fever (<100.5°F [38.1°C]) itself and mild upper respiratory infection do not preclude vaccination with Rotateq.

Incomplete Regimen

The clinical studies were not designed to assess the level of protection provided by only one or two doses of Rotateq.

Limitations of Vaccine Effectiveness

Rotateq may not protect all vaccine recipients against rotavirus.

Post-Exposure Prophylaxis

No clinical data are available for Rotateq when administered after exposure to rotavirus.

Adverse Reactions

Clinical Studies Experience

71,725 infants were evaluated in 3 placebo-controlled clinical trials including 36,165 infants in the group that received Rotateq and 35,560 infants in the group that received placebo. Parents/guardians were contacted on days 7, 14, and 42 after each dose regarding intussusception and any other serious adverse events. The racial distribution was as follows: White (69% in both groups); Hispanic-American (14% in both groups); Black (8% in both groups); Multiracial (5% in both groups); Asian (2% in both groups); Native American (Rotateq 2%, placebo 1%); and Other (<1% in both groups). The gender distribution was 51% male and 49% female in both vaccination groups.

Because clinical trials are conducted under conditions that may not be typical of those observed in clinical practice, the adverse reaction rates presented below may not be reflective of those observed in clinical practice.

Serious Adverse Events

Serious adverse events occurred in 2.4% of recipients of Rotateq when compared to 2.6% of placebo recipients within the 42-day period of a dose in the phase 3 clinical studies of Rotateq. The most frequently reported serious adverse events for Rotateq compared to placebo were:

bronchiolitis                   (0.6% Rotateq vs. 0.7% Placebo),

gastroenteritis               (0.2% Rotateq vs. 0.3% Placebo),

pneumonia                    (0.2% Rotateq vs. 0.2% Placebo),

fever                              (0.1% Rotateq vs. 0.1% Placebo), and

urinary tract infection    (0.1% Rotateq vs. 0.1% Placebo).

Deaths

Across the clinical studies, 52 deaths were reported. There were 25 deaths in the Rotateq recipients compared to 27 deaths in the placebo recipients. The most commonly reported cause of death was sudden infant death syndrome, which was observed in 8 recipients of Rotateq and 9 placebo recipients.

Intussusception

In REST, 34,837 vaccine recipients and 34,788 placebo recipients were monitored by active surveillance to identify potential cases of intussusception at 7, 14, and 42 days after each dose, and every 6 weeks thereafter for 1 year after the first dose.

For the primary safety outcome, cases of intussusception occurring within 42 days of any dose, there were 6 cases among Rotateq recipients and 5 cases among placebo recipients (see Table 1). The data did not suggest an increased risk of intussusception relative to placebo.

Table 1: Confirmed cases of intussusception in recipients of Rotateq as compared with placebo recipients during REST

* Relative risk and 95% confidence interval based upon group sequential design stopping criteria employed in REST.
	Rotateq (n=34,837)	Placebo (n=34,788)
Confirmed intussusception cases within 42 days of any dose	6	5
Relative risk (95% CI) *	1.6 (0.4, 6.4)
Confirmed intussusception cases within 365 days of dose 1	13	15
Relative risk (95% CI)	0.9 (0.4, 1.9)

Among vaccine recipients, there were no confirmed cases of intussusception within the 42-day period after the first dose, which was the period of highest risk for the rhesus rotavirus-based product (see Table 2).

Table 2: Intussusception cases by day range in relation to dose in REST

	Dose 1		Dose 2		Dose 3		Any Dose
Day Range	Rotateq	Placebo	Rotateq	Placebo	Rotateq	Placebo	Rotateq	Placebo
1-7	0	0	1	0	0	0	1	0
1-14	0	0	1	0	0	1	1	1
1-21	0	0	3	0	0	1	3	1
1-42	0	1	4	1	2	3	6	5

All of the children who developed intussusception recovered without sequelae with the exception of a 9-month-old male who developed intussusception 98 days after dose 3 and died of post-operative sepsis. There was a single case of intussusception among 2,470 recipients of Rotateq in a 7-month-old male in the phase 1 and 2 studies (716 placebo recipients).

Hematochezia

Hematochezia reported as an adverse experience occurred in 0.6% (39/6,130) of vaccine and 0.6% (34/5,560) of placebo recipients within 42 days of any dose. Hematochezia reported as a serious adverse experience occurred in <0.1% (4/36,150) of vaccine and <0.1% (7/35,536) of placebo recipients within 42 days of any dose.

Seizures

All seizures reported in the phase 3 trials of Rotateq (by vaccination group and interval after dose) are shown in Table 3.

Table 3: Seizures reported by day range in relation to any dose in the phase 3 trials of Rotateq

Day range	1-7	1-14	1-42
Rotateq	10	15	33
Placebo	5	8	24

Seizures reported as serious adverse experiences occurred in <0.1% (27/36,150) of vaccine and <0.1% (18/35,536) of placebo recipients (not significant). Ten febrile seizures were reported as serious adverse experiences, 5 were observed in vaccine recipients and 5 in placebo recipients.

Kawasaki Disease

In the phase 3 clinical trials, infants were followed for up to 42 days of vaccine dose. Kawasaki disease was reported in 5 of 36,150 vaccine recipients and in 1 of 35,536 placebo recipients with unadjusted relative risk 4.9 (95% CI 0.6, 239.1).

Most Common Adverse Events

Solicited Adverse Events

Detailed safety information was collected from 11,711 infants (6,138 recipients of Rotateq) which included a subset of subjects in REST and all subjects from Studies 007 and 009 (Detailed Safety Cohort). A Vaccination Report Card was used by parents/guardians to record the child’s temperature and any episodes of diarrhea and vomiting on a daily basis during the first week following each vaccination. Table 4 summarizes the frequencies of these adverse events and irritability.

Table 4: Solicited adverse experiences within the first week after doses 1, 2, and 3 (Detailed Safety Cohort)

* Temperature ≥100.5°F [38.1°C] rectal equivalent obtained by adding 1 degree F to otic and oral temperatures and 2 degrees F to axillary temperatures
Adverse experience	Dose 1		Dose 2		Dose 3
	Rotateq	Placebo	Rotateq	Placebo	Rotateq	Placebo
Elevated temperature*	n=5,616 17.1%	n=5,077 16.2%	n=5,215 20.0%	n=4,725 19.4%	n=4,865 18.2%	n=4,382 17.6%
	n=6,130	n=5,560	n=5,703	n=5,173	n=5,496	n=4,989
Vomiting	6.7%	5.4%	5.0%	4.4%	3.6%	3.2%
Diarrhea	10.4%	9.1%	8.6%	6.4%	6.1%	5.4%
Irritability	7.1%	7.1%	6.0%	6.5%	4.3%	4.5%

Other Adverse Events

Parents/guardians of the 11,711 infants were also asked to report the presence of other events on the Vaccination Report Card for 42 days after each dose.

Fever was observed at similar rates in vaccine (N=6,138) and placebo (N=5,573) recipients (42.6% vs. 42.8%). Adverse events that occurred at a statistically higher incidence (i.e., 2-sided p-value <0.05) within the 42 days of any dose among recipients of Rotateq as compared with placebo recipients are shown in Table 5.

Table 5: Adverse events that occurred at a statistically higher incidence within 42 days of any dose among recipients of Rotateq as compared with placebo recipients

Adverse event	Rotateq N=6,138	Placebo N=5,573
	n (%)	n (%)
Diarrhea	1,479 (24.1%)	1,186 (21.3%)
Vomiting	929 (15.2%)	758 (13.6%)
Otitis media	887 (14.5%)	724 (13.0%)
Nasopharyngitis	422 (6.9%)	325 (5.8%)
Bronchospasm	66 (1.1%)	40 (0.7%)

Safety in Pre-Term Infants

Rotateq or placebo was administered to 2,070 pre-term infants (25 to 36 weeks gestational age, median 34 weeks) according to their age in weeks since birth in REST. All pre-term infants were followed for serious adverse experiences; a subset of 308 infants was monitored for all adverse experiences. There were 4 deaths throughout the study, 2 among vaccine recipients (1 SIDS and 1 motor vehicle accident) and 2 among placebo recipients (1 SIDS and 1 unknown cause). No cases of intussusception were reported. Serious adverse experiences occurred in 5.5% of vaccine and 5.8% of placebo recipients. The most common serious adverse experience was bronchiolitis, which occurred in 1.4% of vaccine and 2.0% of placebo recipients. Parents/guardians were asked to record the child’s temperature and any episodes of vomiting and diarrhea daily for the first week following vaccination. The frequencies of these adverse experiences and irritability within the week after dose 1 are summarized in Table 6.

Table 6: Solicited adverse experiences within the first week of doses 1, 2, and 3 among pre-term infants

* Temperature ≥100.5°F [38.1°C] rectal equivalent obtained by adding 1 degree F to otic and oral temperatures and 2 degrees F to axillary temperatures
	Dose 1		Dose 2		Dose 3
Adverse event	Rotateq	Placebo	Rotateq	Placebo	Rotateq	Placebo
	N=127	N=133	N=124	N=121	N=115	N=108
Elevated temperature*	18.1%	17.3%	25.0%	28.1%	14.8%	20.4%
	N=154	N=154	N=137	N=137	N=135	N=129
Vomiting	5.8%	7.8%	2.9%	2.2%	4.4%	4.7%
Diarrhea	6.5%	5.8%	7.3%	7.3%	3.7%	3.9%
Irritability	3.9%	5.2%	2.9%	4.4%	8.1%	5.4%

Post-Marketing Experience

The following adverse events have been identified during post-approval use of Rotateq from reports to the Vaccine Adverse Event Reporting System (VAERS).

Reporting of adverse events following immunization to VAERS is voluntary, and the number of doses of vaccine administered is not known; therefore, it is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to vaccine exposure using VAERS data.

In post-marketing experience, the following adverse events have been reported following the use of Rotateq:

Gastrointestinal disorders:

   Intussusception (including death)

   Hematochezia

   Gastroenteritis with vaccine viral shedding in infants with Severe Combined Immunodeficiency Disease (SCID)

Skin and subcutaneous tissue disorders:

   Urticaria

Infections and infestations:

   Kawasaki disease

   Transmission of vaccine virus strains from vaccine recipient to non-vaccinated contacts.

Reporting Adverse Events

Parents or guardians should be instructed to report any adverse reactions to their health care provider.

Health care providers should report all adverse events to the U.S. Department of Health and Human Services' Vaccine Adverse Events Reporting System (VAERS).

VAERS accepts all reports of suspected adverse events after the administration of any vaccine, including but not limited to the reporting of events required by the National Childhood Vaccine Injury Act of 1986. For information or a copy of the vaccine reporting form, call the VAERS toll-free number at 1-800-822-7967 or report on line to www.vaers.hhs.gov.{2}

Drug Interactions

Immunosuppressive therapies including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to vaccines.

Concomitant Vaccine Administration

In clinical trials, Rotateq was administered concomitantly with diphtheria and tetanus toxoids and acellular pertussis (DTaP), inactivated poliovirus vaccine (IPV), H. influenzae type b conjugate (Hib), hepatitis B vaccine, and pneumococcal conjugate vaccine [see Clinical Studies (14)]. The safety data available are in the ADVERSE REACTIONS section [see Adverse Reactions (6.1)]. There was no evidence for reduced antibody responses to the vaccines that were concomitantly administered with Rotateq.

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category C: Animal reproduction studies have not been conducted with Rotateq. It is also not known whether Rotateq can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Rotateq is not indicated in women of child-bearing age and should not be administered to pregnant females.

Pediatric Use

Safety and efficacy have not been established in infants less than 6 weeks of age or greater than 32 weeks of age.

Data are available from clinical studies to support the use of Rotateq in pre-term infants according to their age in weeks since birth [see Adverse Reactions (6.1)].

Data are available from clinical studies to support the use of Rotateq in infants with controlled gastroesophageal reflux disease.

Rotateq Description

Rotateq is a live, oral pentavalent vaccine that contains 5 live reassortant rotaviruses. The rotavirus parent strains of the reassortants were isolated from human and bovine hosts. Four reassortant rotaviruses express one of the outer capsid proteins (G1, G2, G3, or G4) from the human rotavirus parent strain and the attachment protein (serotype P7) from the bovine rotavirus parent strain. The fifth reassortant virus expresses the attachment protein, P1A (genotype P[8]), herein referred to as serotype P1A[8], from the human rotavirus parent strain and the outer capsid protein of serotype G6 from the bovine rotavirus parent strain (see Table 7).

Table 7

Name of Reassortant	Human Rotavirus Parent Strains and Outer Surface Protein Compositions	Bovine Rotavirus Parent Strain and Outer Surface Protein Composition	Reassortant Outer Surface Protein Composition (Human Rotavirus Component in Bold)	Minimum Dose Levels (106 infectious units)
G1	WI79 – G1P1A[8]	WC3 - G6, P7[5]	G1P7[5]	2.2
G2	SC2 – G2P2[6]		G2P7[5]	2.8
G3	WI78 – G3P1A[8]		G3P7[5]	2.2
G4	BrB – G4P2[6]		G4P7[5]	2.0
P1A[8]	WI79 – G1P1A[8]		G6P1A[8]	2.3

The reassortants are propagated in Vero cells using standard cell culture techniques in the absence of antifungal agents.

The reassortants are suspended in a buffered stabilizer solution. Each vaccine dose contains sucrose, sodium citrate, sodium phosphate monobasic monohydrate, sodium hydroxide, polysorbate 80, cell culture media, and trace amounts of fetal bovine serum. Rotateq contains no preservatives.

In the manufacturing process for Rotateq, a porcine-derived material is used. DNA from porcine circoviruses (PCV) 1 and 2 has been detected in Rotateq. PCV-1 and PCV-2 are not known to cause disease in humans.

Rotateq is a pale yellow clear liquid that may have a pink tint.

The plastic dosing tube and cap do not contain latex.

Rotateq - Clinical Pharmacology

Rotavirus is a leading cause of severe acute gastroenteritis in infants and young children, with over 95% of these children infected by the time they are 5 years old.{3} The most severe cases occur among infants and young children between 6 months and 24 months of age.{4}

Mechanism of Action

The exact immunologic mechanism by which Rotateq protects against rotavirus gastroenteritis is unknown [see Clinical Studies (14.6)]. Rotateq is a live viral vaccine that replicates in the small intestine and induces immunity.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

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

Clinical Studies

Overall, 72,324 infants were randomized in 3 placebo-controlled, phase 3 studies conducted in 11 countries on 3 continents. The data demonstrating the efficacy of Rotateq in preventing rotavirus gastroenteritis come from 6,983 of these infants from the US (including Navajo and White Mountain Apache Nations) and Finland who were enrolled in 2 of these studies: REST and Study 007. The third trial, Study 009, provided clinical evidence supporting the consistency of manufacture and contributed data to the overall safety evaluation.

The racial distribution of the efficacy subset was as follows: White (Rotateq 68%, placebo 69%); Hispanic-American (Rotateq 10%, placebo 9%); Black (2% in both groups); Multiracial (Rotateq 4%, placebo 5%); Asian (<1% in both groups); Native American (Rotateq 15%, placebo 14%); and Other (<1% in both groups). The gender distribution was 52% male and 48% female in both vaccination groups.

The efficacy evaluations in these studies included: 1) Prevention of any grade of severity of rotavirus gastroenteritis; 2) Prevention of severe rotavirus gastroenteritis, as defined by a clinical scoring system; and 3) Reduction in hospitalizations due to rotavirus gastroenteritis.

The vaccine was given as a three-dose series to healthy infants with the first dose administered between 6 and 12 weeks of age and followed by two additional doses administered at 4- to 10-week intervals. The age of infants receiving the third dose was 32 weeks of age or less. Oral polio vaccine administration was not permitted; however, other childhood vaccines could be concomitantly administered. Breast-feeding was permitted in all studies.

The case definition for rotavirus gastroenteritis used to determine vaccine efficacy required that a subject meet both of the following clinical and laboratory criteria: (1) greater than or equal to 3 watery or looser-than-normal stools within a 24-hour period and/or forceful vomiting; and (2) rotavirus antigen detection by enzyme immunoassay (EIA) in a stool specimen taken within 14 days of onset of symptoms. The severity of rotavirus acute gastroenteritis was determined by a clinical scoring system that took into account the intensity and duration of symptoms of fever, vomiting, diarrhea, and behavioral changes.

The primary efficacy analyses included cases of rotavirus gastroenteritis caused by serotypes G1, G2, G3, and G4 that occurred at least 14 days after the third dose through the first rotavirus season post vaccination.

Analyses were also done to evaluate the efficacy of Rotateq against rotavirus gastroenteritis caused by serotypes G1, G2, G3, and G4 at any time following the first dose through the first rotavirus season postvaccination among infants who received at least one vaccination (Intent-to-treat, ITT).

Rotavirus Efficacy and Safety Trial

Primary efficacy against any grade of severity of rotavirus gastroenteritis caused by naturally occurring serotypes G1, G2, G3, or G4 through the first rotavirus season after vaccination was 74.0% (95% CI: 66.8, 79.9) and the ITT efficacy was 60.0% (95% CI: 51.5, 67.1). Primary efficacy against severe rotavirus gastroenteritis caused by naturally occurring serotypes G1, G2, G3, or G4 through the first rotavirus season after vaccination was 98.0% (95% CI: 88.3, 100.0), and ITT efficacy was 96.4% (95% CI: 86.2, 99.6). See Table 8.

Table 8: Efficacy of Rotateq against any grade of severity of and severe* G1-4 rotavirus gastroenteritis through the first rotavirus season postvaccination in REST