Prednisolone

Pronunciation: pred-NIS-oh-lone
Generic Name: Prednisolone
Brand Name: Millipred DP

Prednisolone is used for:

Treating allergies, arthritis, breathing problems (eg, asthma), certain blood disorders, collagen diseases (eg, lupus), certain eye diseases (eg, keratitis), cancer (eg, leukemia), endocrine problems (eg, adrenocortical insufficiency), intestinal problems (eg, ulcerative colitis), swelling due to certain conditions, or skin conditions (eg, psoriasis). It may also be used for other conditions as determined by your doctor.

Prednisolone is a corticosteroid. It works by modifying the body's immune response to various conditions and decreasing inflammation.

Do NOT use Prednisolone if:

• you are allergic to any ingredient in Prednisolone


• you have a systemic fungal infection, a certain type of malaria, inflammation of the optic nerve, or herpes infection of the eye


• you are scheduled to have a live or attenuated live vaccination (eg, smallpox)


• you are taking mifepristone

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

Before using Prednisolone:

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

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


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


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


• if you have a history of heart problems (eg, congestive heart failure), heart attack, high blood pressure, kidney problems, liver problems, diabetes, seizures, an underactive thyroid, adrenal gland problems, fluid retention (eg, swelling of the hands, ankles, or feet), or any mental or mood problems


• if you have or have recently had a fungal, bacterial, viral, or other type of infection; herpes infection of the eye; chickenpox; measles; or shingles


• if you have HIV infection or tuberculosis (TB) infection, or if you have had ever had a positive TB skin test


• if you have any stomach problems (eg, ulcers), intestinal problems (eg, blockage, perforation, or infection; unexplained diarrhea; diverticulitis; ulcerative colitis), recent intestinal surgery, or inflammation of the esophagus


• if you have weak bones (eg, osteoporosis) or muscle problems (eg, myasthenia gravis)


• if you have had a recent vaccination (eg, smallpox)

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

• Clarithromycin, cyclosporine, estrogens (eg, estradiol), oral contraceptives (eg, birth control pills), or ketoconazole because they may increase the risk of Prednisolone's side effects


• Barbiturates (eg, phenobarbital), carbamazepine, ephedrine, hydantoins (eg, phenytoin), or rifampin because they may decrease Prednisolone's effectiveness


• Anticholinesterases (eg, pyridostigmine), aspirin, diuretics (eg, hydrochlorothiazide, furosemide), methotrexate, mifepristone, quinolone antibiotics (eg, ciprofloxacin), ritodrine, or live or attenuated live vaccines because the risk of their side effects may be increased by Prednisolone


• Anticoagulants (eg, warfarin), hydantoins (eg, phenytoin), or killed or inactivated vaccines because their effectiveness may be decreased by Prednisolone

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

How to use Prednisolone:

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

• Take Prednisolone by mouth with food.


• Prednisolone comes as a dose pack with specific instructions as to when to take the medicine or how much to take each time. It is very important to follow these instructions as closely as possible. Do not miss any doses.


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

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

Important safety information:

• Avoid alcohol while you are using Prednisolone.


• Prednisolone may lower the ability of your body to fight infection. Avoid contact with people who have colds or infections. Tell your doctor if you notice signs of infection like fever, sore throat, rash, or chills.


• If you have not had chickenpox, shingles, or measles, avoid contact with anyone who does.


• If you are taking Prednisolone regularly over a long period of time, carry an ID card at all times that says you take Prednisolone.


• Do not receive a live vaccine (eg, measles, mumps, smallpox) while you are taking Prednisolone. Talk with your doctor before you receive any vaccine.


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


• Diabetes patients - Prednisolone may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• Lab tests, including adrenal function tests, may be performed while you use Prednisolone. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Caution is advised when using Prednisolone in CHILDREN; they may be more sensitive to its effects.


• Corticosteroids may affect growth rate in CHILDREN and teenagers in some cases. They may need regular growth checks while they take Prednisolone.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Prednisolone while you are pregnant. Prednisolone is found in breast milk. If you are or will be breast-feeding while you use Prednisolone, check with your doctor. Discuss any possible risks to your baby.

If you are on long-term or high dosage therapy and you suddenly stop taking Prednisolone, you may have WITHDRAWAL symptoms, including fever, vomiting, appetite loss, diarrhea, nausea, dizziness, weight loss, weakness, general body discomfort, joint or muscle pain.

Possible side effects of Prednisolone:

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

Acne; clumsiness; dizziness; facial flushing; feeling of a whirling motion; general body discomfort; headache; increased appetite; increased sweating; nausea; nervousness; sleeplessness; upset stomach.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); black, tarry stools; changes in body fat; changes in menstrual period; changes in skin color; chest pain; easy bruising or bleeding; increased hunger, thirst, or urination; mental or mood changes (eg, depression); muscle pain, weakness, or wasting; seizures; severe nausea or vomiting; shortness of breath; signs of infection (eg, fever, chills, persistent sore throat); sudden severe dizziness or headache; swelling of ankles, feet, or hands; tendon or bone pain; thinning of skin; unusual skin sensation; unusual weight gain; vision changes or other eye problems; vomit that looks like coffee grounds.

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

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Prednisolone:

Store Prednisolone at room temperature, between 68 and 77 degrees F (20 and 25 degrees C), in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Prednisolone out of the reach of children and away from pets.

General information:

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


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


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


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

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

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Prednisolone resources

• Prednisolone Use in Pregnancy & Breastfeeding
• Drug Images
• Prednisolone Drug Interactions
• Prednisolone Support Group
• 13 Reviews for Prednisolone - Add your own review/rating

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Prevnar

pneumococcal 7-valent vaccine

Dosage Form: injection, suspension
Pneumococcal 7-valent Conjugate Vaccine

(Diphtheria CRM197 Protein)

Prevnar®

FOR PEDIATRIC USE ONLY

Rx only

For Intramuscular Injection Only

DESCRIPTION

Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein), Prevnar®, is a sterile solution of saccharides of the capsular antigens of Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F individually conjugated to diphtheria CRM197 protein. Each serotype is grown in soy peptone broth. The individual polysaccharides are purified through centrifugation, precipitation, ultrafiltration, and column chromatography. The polysaccharides are chemically activated to make saccharides which are directly conjugated to the protein carrier CRM197 to form the glycoconjugate. This is effected by reductive amination. CRM197 is a nontoxic variant of diphtheria toxin isolated from cultures of Corynebacterium diphtheriae strain C7 (β197) grown in a casamino acids and yeast extract-based medium. CRM197 is purified through ultrafiltration, ammonium sulfate precipitation, and ion-exchange chromatography. The individual glycoconjugates are purified by ultrafiltration and column chromatography and are analyzed for saccharide to protein ratios, molecular size, free saccharide, and free protein.

The individual glycoconjugates are compounded to formulate the vaccine, Prevnar®. Potency of the formulated vaccine is determined by quantification of each of the saccharide antigens, and by the saccharide to protein ratios in the individual glycoconjugates.

Prevnar® is manufactured as a liquid preparation. Each 0.5 mL dose is formulated to contain: 2 μg of each saccharide for serotypes 4, 9V, 14, 18C, 19F, and 23F, and 4 μg of serotype 6B per dose (16 μg total saccharide); approximately 20 μg of CRM197 carrier protein; and 0.125 mg of aluminum per 0.5 mL dose as aluminum phosphate adjuvant.

After shaking, the vaccine is a homogeneous, white suspension.

CLINICAL PHARMACOLOGY

S. pneumoniae is an important cause of morbidity and mortality in persons of all ages worldwide. The organism causes invasive infections, such as bacteremia and meningitis, as well as pneumonia and upper respiratory tract infections including otitis media and sinusitis. In children older than 1 month, S. pneumoniae is the most common cause of invasive disease.1 Data from community-based studies performed between 1986 and 1995, indicate that the overall annual incidence of invasive pneumococcal disease in the United States (US) is an estimated 10 to 30 cases per 100,000 persons, with the highest risk in children aged less than or equal to 2 years of age (140 to 160 cases per 100,000 persons).2,3 Children in group child care have an increased risk for invasive pneumococcal disease.4,5 Immunocompromised individuals with neutropenia, asplenia, sickle cell disease, disorders of complement and humoral immunity, human immunodeficiency virus (HIV) infections or chronic underlying disease are also at increased risk for invasive pneumococcal disease.5 S. pneumoniae is the most common cause of bacterial meningitis in the US.1 The annual incidence of pneumococcal meningitis in children between 1 to 23 months of age is approximately 7 cases per 100,000 persons.1 Pneumococcal meningitis in childhood has been associated with 8% mortality and may result in neurological sequelae (25%) and hearing loss (32%) in survivors.6

Acute otitis media (AOM) is a common childhood disease, with more than 60% of children experiencing an episode by one year of age, and more than 90% of children experiencing an episode by age 5. Prior to the US introduction of Prevnar® in the year 2000, approximately 24.5 million ambulatory care visits and 490,000 procedures for myringotomy with tube placement were attributed to otitis media annually.7,8 The peak incidence of AOM is 6 to 18 months of age.9 Otitis media is less common, but occurs, in older children. In a 1990 surveillance by the Centers for Disease Control and Prevention (CDC), otitis media was the most common principal illness diagnosis in children 2-10 years of age.10 Complications of AOM include persistent middle ear effusion, chronic otitis media, transient hearing loss, or speech delays and, if left untreated, may lead to more serious diseases such as mastoiditis and meningitis. S. pneumoniae is an important cause of AOM. It is the bacterial pathogen most commonly isolated from middle ear fluid, identified in 20% to 40% of middle ear fluid cultures in AOM.11,12 Pneumococcal otitis media is associated with higher rates of fever, and is less likely to resolve spontaneously than AOM due to either nontypeable H. influenzae or M. catarrhalis.13,14 Prior to the introduction of Prevnar®, the seven serotypes contained in the vaccine accounted for approximately 60% of AOM due to S. pneumoniae (12%-24% of all AOM).15

The exact contribution of S. pneumoniae to childhood pneumonia is unknown, as it is often not possible to identify the causative organisms. In studies of children less than 5 years of age with community-acquired pneumonia, where diagnosis was attempted using serological methods, antigen testing, or culture data, 30% of cases were classified as bacterial pneumonia, and 70% of these (21% of total community-acquired pneumonia) were found to be due to S. pneumoniae.16

In the past decade the proportion of S. pneumoniae isolates resistant to antibiotics has been on the rise in the US and worldwide. In a multi-center US surveillance study, the prevalence of penicillin and cephalosporin-nonsusceptible (intermediate or high level resistance) invasive disease isolates from children was 21% (range <5% to 38% among centers), and 9.3% (range 0%-18%), respectively. Over the 3-year surveillance period (1993-1996), there was a 50% increase in penicillin-nonsusceptible S. pneumoniae (PNSP) strains and a three-fold rise in cephalosporin-nonsusceptible strains.5 Although generally less common than PNSP, pneumococci resistant to macrolides and trimethoprim-sulfamethoxazole have also been observed. Day care attendance, a history of ear infection, and a recent history of antibiotic exposure, have also been associated with invasive infections with PNSP in children 2 months to 59 months of age.4,5 There has been no difference in mortality associated with PNSP strains.5,6 However, the American Academy of Pediatrics (AAP) revised the antibiotic treatment guidelines in 1997 in response to the increased prevalence of antibiotic-resistant pneumococci.17

Approximately 90 serotypes of S. pneumoniae have been identified based on antigenic differences in their capsular polysaccharides. The distribution of serotypes responsible for disease differ with age and geographic location.18

Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F have been responsible for approximately 80% of invasive pneumococcal disease in children <6 years of age in the US.15 These 7 serotypes also accounted for 74% of PNSP and 100% of pneumococci with high level penicillin resistance isolated from children <6 years with invasive disease during a 1993-1994 surveillance by the CDC.19

Results of Clinical Evaluations

Efficacy Against Invasive Disease

Efficacy was assessed in a randomized, double-blinded clinical trial in a multiethnic population at Northern California Kaiser Permanente (NCKP) from October 1995 through August 20, 1998, in which 37,816 infants were randomized to receive either Prevnar® or a control vaccine (an investigational meningococcal group C conjugate vaccine [MnCC]) at 2, 4, 6, and 12-15 months of age. Prevnar® was administered to 18,906 children and the control vaccine to 18,910 children. Routinely recommended vaccines were also administered which changed during the trial to reflect changing AAP and Advisory Committee on Immunization Practices (ACIP) recommendations. A planned interim analysis was performed upon accrual of 17 cases of invasive disease due to vaccine-type S. pneumoniae (August 1998). Ancillary endpoints for evaluation of efficacy against pneumococcal disease were also assessed in this trial.

Invasive disease was defined as isolation and identification of S. pneumoniae from normally sterile body sites in children presenting with an acute illness consistent with pneumococcal disease. Weekly surveillance of listings of cultures from the NCKP Regional Microbiology database was conducted to assure ascertainment of all cases. The primary endpoint was efficacy against invasive pneumococcal disease due to vaccine serotypes. The per protocol analysis of the primary endpoint included cases which occurred ≥14 days after the third dose. The intent-to-treat (ITT) analysis included all cases of invasive pneumococcal disease due to vaccine serotypes in children who received at least one dose of vaccine. Secondary analyses of efficacy against all invasive pneumococcal disease, regardless of serotype, were also performed according to these same per protocol and ITT definitions. Results of these analyses are presented in Table 1.

TABLE 1 Efficacy of Prevnar® Against Invasive Disease Due to S. pneumoniae in Cases Accrued From October 15, 1995 Through August 20, 1998 20,21

	Prevnar® Number of Cases	Control* Number of Cases	Efficacy	95% CI
Vaccine serotypes
Per protocol	0	17	100%	75.4, 100
Intent-to-treat	0	22	100%	81.7, 100
All pneumococcal serotypes
Per protocol	2	20	90.0%	58.3, 98.9
Intent-to-treat	3	27†	88.9%	63.8, 97.9
* Investigational meningococcal group C conjugate vaccine (MnCC). † Includes one case in an immunocompromised subject.

All 22 cases of invasive disease due to vaccine serotype strains in the ITT population were bacteremic. In addition, the following diagnoses were also reported: meningitis (2), pneumonia (2), and cellulitis (1).

Data accumulated through an extended follow-up period to April 20, 1999, resulted in a similar efficacy estimate (Per protocol: 1 case in Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein), Prevnar® group, 39 cases in control group; ITT: 3 cases in Prevnar® group, 49 cases in the control group).21

Efficacy Against Otitis Media

The efficacy of Prevnar® against otitis media was assessed in two clinical trials: a trial in Finnish infants at the National Public Health Institute and the invasive disease efficacy trial in US infants at Northern California Kaiser Permanente (NCKP).

The trial in Finland was a randomized, double-blind trial in which 1,662 infants were equally randomized to receive either Prevnar® or a control vaccine (Hepatitis B vaccine [Hep B]) at 2, 4, 6, and 12-15 months of age. All infants received a Diphtheria Tetanus Pertussis Vaccine - Haemophilus influenzae type b vaccine (DTP-Hib) combination vaccine concurrently at 2, 4, and 6 months of age, and Inactivated Poliovirus Vaccine (IPV) concurrently at 12 months of age. Parents of study participants were asked to bring their children to the study clinics if the child had respiratory infections or symptoms suggesting acute otitis media (AOM). If AOM was diagnosed, tympanocentesis was performed, and the middle ear fluid was cultured. If S. pneumoniae was isolated, serotyping was performed.

AOM was defined as a visually abnormal tympanic membrane suggesting effusion in the middle ear cavity, concomitantly with at least one of the following symptoms of acute infection: fever, ear ache, irritability, diarrhea, vomiting, acute otorrhea not caused by external otitis, or other symptoms of respiratory infection. A new visit or “episode” was defined as a visit with a study physician at which time a diagnosis of AOM was made and at least 30 days had elapsed since any previous visit for otitis media. The primary endpoint was efficacy against AOM episodes caused by vaccine serotypes in the per protocol population.

In the NCKP invasive disease efficacy trial, the effectiveness of Prevnar® in reducing the incidence of otitis media was assessed from the beginning of the trial in October 1995 through April 1998. During this time, 34,146 infants were randomized to receive either Prevnar® (N=17,070), or the control, an investigational meningococcal group C conjugate vaccine (N=17,076), at 2, 4, 6, and 12-15 months of age.

Physician visits for otitis media were identified by physician coding of outpatient encounter forms. Because visits may have included both acute and follow-up care, a new visit or “episode” was defined as a visit that was at least 21 days following a previous visit for otitis media (at least 42 days, if the visit appointment was made > 3 days in advance). Data on placement of ear tubes were collected from automated databases. No routine tympanocentesis was performed, and no standard definition of otitis media was used by study physicians. The primary otitis media endpoint was efficacy against all otitis media episodes in the per protocol population.

Table 2 presents the per protocol and intent-to-treat results of key otitis media analyses for both studies. The per protocol analyses include otitis media episodes that occurred ≥14 days after the third dose. The intent-to-treat analyses include all otitis media episodes in children who received at least one dose of vaccine.

TABLE 2 Efficacy of Prevnar® Against Otitis Media in the Finnish and NCKP Trials 20,21,22,23

	Per Protocol		Intent-to-Treat
	Vaccine Efficacy Estimate*	95% Confidence Interval	Vaccine Efficacy Estimate*	95% Confidence Interval
Finnish Trial	N=1632		N=1662
AOM due to Vaccine Serotypes	57%	44, 67	54%	41, 64
All culture-confirmed pneumococcal   AOM regardless of serotype	34%	21, 45	32%	19, 42
NCKP Trial	N=23,746		N=34,146
All Otitis Media Episodes regardless of etiology†	7%	4, 10	6%	4, 9
* All vaccine efficacy estimates in the table are statistically significant. † The vaccine efficacy against all AOM episodes in the Finnish trial, while not reaching statistical significance, was 6% (95% CI: -4, 16) in the per protocol population and 4% (95% CI: -7, 14) in the intent-to-treat population.

The vaccine efficacy against AOM episodes due to vaccine-related serotypes (6A, 9N, 18B, 19A, 23A), also assessed in the Finnish trial, was 51% (95% CI: 27, 67) in the per protocol population and 44% (95% CI: 20, 62) in the intent-to-treat population. The vaccine efficacy against AOM episodes caused by serotypes unrelated to the vaccine was -33% (95% CI: -80, 1) in the per protocol population and -39% (95% CI: -86, -3) in the intent-to-treat population, indicating that children who received Prevnar® appear to be at increased risk of otitis media due to pneumococcal serotypes not represented in the vaccine, compared to children who received the control vaccine. However, vaccination with Prevnar® reduced pneumococcal otitis media episodes overall.

Several other otitis media endpoints were also assessed in the two trials. Recurrent AOM, defined as 3 episodes in 6 months or 4 episodes in 12 months, was reduced by 9% in both the per protocol and intent-to-treat populations (95% CI: 3, 15 in per protocol and 95% CI: 4, 14 in intent-to-treat) in the NCKP trial. This observation was supported by a similar trend, although not statistically significant, seen in the Finnish trial. The NCKP trial also demonstrated a 20% reduction (95% CI: 2, 35) in the placement of tympanostomy tubes in the per protocol population and a 21% reduction (95% CI: 4, 34) in the intent-to-treat population.

Data from the NCKP trial accumulated through an extended follow-up period to April 20, 1999, in which a total of 37,866 children were included (18,925 in Prevnar® group and 18,941 in MnCC control group), resulted in similar otitis media efficacy estimates for all endpoints.24

Immunogenicity

Routine Schedule

Subjects from a subset of selected study sites in the NCKP efficacy study were approached for participation in the immunogenicity portion of the study on a volunteer basis. Immune responses following three or four doses of Prevnar® or the control vaccine were evaluated in children who received either concurrent Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed and Haemophilus b Conjugate Vaccine (Diphtheria CRM197 Protein Conjugate), (DTP-HbOC), or Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP), and Haemophilus b Conjugate Vaccine (Diphtheria CRM197 Protein Conjugate), (HbOC) vaccines at 2, 4, and 6 months of age. The use of Hepatitis B (Hep B), Oral Polio Vaccine (OPV), Inactivated Polio Vaccine (IPV), Measles-Mumps-Rubella (MMR), and Varicella vaccines were permitted according to the AAP and ACIP recommendations.

Table 3 presents the geometric mean concentrations (GMC) of pneumococcal antibodies following the third and fourth doses of Prevnar® or the control vaccine when administered concurrently with DTP-HbOC vaccine in the efficacy study.

TABLE 3 Geometric Mean Concentrations (μg/mL) of Pneumococcal Antibodies Following the Third and Fourth Doses of Prevnar® or Control* When Administered Concurrently With DTP-HbOC in the Efficacy Study 20,21

Serotype	Post dose 3 GMC† (95% CI for Prevnar®)		Post dose 4 GMC‡ (95% CI for Prevnar®)
	Prevnar®§	Control*	Prevnar®§	Control*
	N=88	N=92	N=68	N=61
4	1.46 (1.19, 1.78)	0.03	2.38 (1.88, 3.03)	0.04
6B	4.70 (3.59, 6.14)	0.08	14.45 (11.17, 18.69)	0.17
9V	1.99 (1.64, 2.42)	0.05	3.51 (2.75, 4.48)	0.06
14	4.60 (3.70, 5.74)	0.05	6.52 (5.18, 8.21)	0.06
18C	2.16 (1.73, 2.69)	0.04	3.43 (2.70, 4.37)	0.07
19F	1.39 (1.16, 1.68)	0.09	2.07 (1.66, 2.57)	0.18
23F	1.85 (1.46, 2.34)	0.05	3.82 (2.85, 5.11)	0.09
* Control was investigational meningococcal group C conjugate vaccine (MnCC). † Mean age of Prevnar® group was 7.8 months and of control group was 7.7 months. N is slightly less for some serotypes in each group. ‡ Mean age of Prevnar® group was 14.2 months and of control group was 14.4 months. N is slightly less for some serotypes in each group. § p<0.001 when Prevnar® compared to control for each serotype using a Wilcoxon's test.

In another randomized study (Manufacturing Bridging Study, 118-16), immune responses were evaluated following three doses of Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein), Prevnar® administered concomitantly with DTaP and HbOC vaccines at 2, 4, and 6 months of age, IPV at 2 and 4 months of age, and Hep B at 2 and 6 months of age. The control group received concomitant vaccines only. Table 4 presents the immune responses to pneumococcal polysaccharides observed in both this study and in the subset of subjects from the efficacy study that received concomitant DTaP and HbOC vaccines.

TABLE 4 Geometric Mean Concentrations (μg/mL) of Pneumococcal Antibodies Following the Third Dose of Prevnar® or Control* When Administered Concurrently With DTaP and HbOC in the Efficacy Study† and Manufacturing Bridging Study20,21,25

	Efficacy Study		Manufacturing Bridging Study
Serotype	Post dose 3 GMC‡ (95% CI for Prevnar®)		Post dose 3 GMC§ (95% CI for Prevnar®)
	Prevnar® ll	Control*	Prevnar® ll	Control*
	N=32	N=32	N=159	N=83
4	1.47 (1.08, 2.02)	0.02	2.03 (1.75, 2.37)	0.02
6B	2.18 (1.20, 3.96)	0.06	2.97 (2.43, 3.65)	0.07
9V	1.52 (1.04, 2.22)	0.04	1.18 (1.01, 1.39)	0.04
14	5.05 (3.32, 7.70)	0.04	4.64 (3.80, 5.66)	0.04
18C	2.24 (1.65, 3.02)	0.04	1.96 (1.66, 2.30)	0.04
19F	1.54 (1.09, 2.17)	0.10	1.91 (1.63, 2.25)	0.08
23F	1.48 (0.97, 2.25)	0.05	1.71 (1.44, 2.05)	0.05
* Control in efficacy study was investigational meningococcal group C conjugate vaccine (MnCC) and in Manufacturing Bridging Study was concomitant vaccines only. † Sufficient data are not available to reliably assess GMCs following 4 doses of Prevnar® when administered with DTaP in the NCKP efficacy study. ‡ Mean age of the Prevnar® group was 7.4 months and of the control group was 7.6 months. N is slightly less for some serotypes in each group. § Mean age of the Prevnar® group and the control group was 7.2 months. ll p<0.001 when Prevnar® compared to control for each serotype using a Wilcoxon's test in the efficacy study and two-sample t-test in the Manufacturing Bridging Study.

In all studies in which the immune responses to Prevnar® were contrasted to control, a significant antibody response was seen to all vaccine serotypes following three or four doses, although geometric mean concentrations of antibody varied among serotypes.20,21,23,25,26,27,28,29,30 The minimum serum antibody concentration necessary for protection against invasive pneumococcal disease or against pneumococcal otitis media has not been determined for any serotype. Prevnar® induces functional antibodies to all vaccine serotypes, as measured by opsonophagocytosis following three doses.30

Previously Unvaccinated Older Infants and Children

To determine an appropriate schedule for children 7 months of age or older at the time of the first immunization with Prevnar®, 483 children in 4 ancillary studies received Prevnar® at various schedules and were evaluated for immunogenicity. GMCs attained using the various schedules among older infants and children were comparable to immune responses of children, who received concomitant DTaP, in the NCKP efficacy study (118-8) after 3 doses for most serotypes, as shown in Table 5. These data support the schedule for previously unvaccinated older infants and children who are beyond the age of the infant schedule. For usage in older infants and children, see DOSAGE AND ADMINISTRATION.

TABLE 5 Geometric Mean Concentrations (μg/mL) of Pneumococcal Antibodies Following Immunization of Children From 7 Months Through 9 Years of Age With Prevnar®31

Age group, Vaccinations	Study	Sample Size(s)	4	6B	9V	14	18C	19F	23F
7-11 mo. 3 doses	118-12	22	2.34	3.66	2.11	9.33	2.31	1.60	2.50
	118-16	39	3.60	4.63	2.04	5.48	1.98	2.15	1.93
12-17 mo. 2 doses	118-15*	82-84†	3.91	4.67	1.94	6.92	2.25	3.78	3.29
	118-18	33	7.02	4.25	3.26	6.31	3.60	3.29	2.92
18-23 mo. 2 doses	118-15*	52-54†	3.36	4.92	1.80	6.69	2.65	3.17	2.71
	118-18	45	6.85	3.71	3.86	6.48	3.42	3.86	2.75
24-35 mo. 1 dose	118-18	53	5.34	2.90	3.43	1.88	3.03	4.07	1.56
36-59 mo. 1 dose	118-18	52	6.27	6.40	4.62	5.95	4.08	6.37	2.95
5-9 yrs. 1 dose	118-18	101	6.92	20.84	7.49	19.32	6.72	12.51	11.57
118-8, DTaP	Post dose 3	31-32†	1.47	2.18	1.52	5.05	2.24	1.54	1.48
Bold = GMC not inferior to 118-8, DTaP post dose 3 (one-sided lower limit of the 95% CI of GMC ratio ≥0.50). * Study in Navajo and Apache populations. † Numbers vary with serotype.

INDICATIONS AND USAGE

Prevnar® is indicated for active immunization of infants and toddlers against invasive disease caused by S. pneumoniae due to capsular serotypes included in the vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F). The routine schedule is 2, 4, 6, and 12-15 months of age.

The decision to administer Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein), Prevnar® should be based primarily on its efficacy in preventing invasive pneumococcal disease. As with any vaccine, Prevnar® may not protect all individuals receiving the vaccine from invasive pneumococcal disease.

Prevnar® is also indicated for active immunization of infants and toddlers against otitis media caused by serotypes included in the vaccine. However, for vaccine serotypes, protection against otitis media is expected to be substantially lower than protection against invasive disease. Additionally, because otitis media is caused by many organisms other than serotypes of S. pneumoniae represented in the vaccine, protection against all causes of otitis media is expected to be low.

(See CLINICAL PHARMACOLOGY for estimates of efficacy against invasive disease and otitis media).

For additional information on usage, see DOSAGE AND ADMINISTRATION.

This vaccine is not intended to be used for treatment of active infection.

CONTRAINDICATIONS

Hypersensitivity to any component of the vaccine, including diphtheria toxoid, is a contraindication to use of this vaccine.

WARNINGS

THIS VACCINE WILL NOT PROTECT AGAINST S. PNEUMONIAE DISEASE CAUSED BY SEROTYPES UNRELATED TO THOSE IN THE VACCINE, NOR WILL IT PROTECT AGAINST OTHER MICROORGANISMS THAT CAUSE INVASIVE INFECTIONS SUCH AS BACTEREMIA AND MENINGITIS OR NON-INVASIVE INFECTIONS SUCH AS OTITIS MEDIA.

This vaccine should not be given to infants or children with thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injection unless the potential benefit clearly outweighs the risk of administration. If the decision is made to administer this vaccine to children with coagulation disorders, it should be given with caution. (See DRUG INTERACTIONS.)

Immunization with Prevnar® does not substitute for routine diphtheria immunization.

PRECAUTIONS

Prevnar® is for intramuscular use only. Prevnar® SHOULD UNDER NO CIRCUMSTANCES BE ADMINISTERED INTRAVENOUSLY. The safety and immunogenicity for other routes of administration (eg, subcutaneous) have not been evaluated.

Fever, and rarely febrile seizure, have been reported in children receiving Prevnar®. For children at higher risk of seizures than the general population, appropriate antipyretics (dosed according to respective prescribing information) may be administered around the time of vaccination, to reduce the possibility of post-vaccination fever.

Minor illnesses, such as a mild respiratory infection with or without low-grade fever, are not generally contraindications to vaccination. The decision to administer or delay vaccination because of a current or recent febrile illness depends largely on the severity of the symptoms and their etiology. The administration of Prevnar should be postponed in subjects suffering from acute severe febrile illness.32,33

General

CARE IS TO BE TAKEN BY THE HEALTHCARE PROFESSIONAL FOR THE SAFE AND EFFECTIVE USE OF THIS PRODUCT.

1. PRIOR TO ADMINISTRATION OF ANY DOSE OF THIS VACCINE, THE PARENT OR GUARDIAN SHOULD BE ASKED ABOUT THE PERSONAL HISTORY, FAMILY HISTORY, AND RECENT HEALTH STATUS OF THE VACCINE RECIPIENT. THE HEALTHCARE PROFESSIONAL SHOULD ASCERTAIN PREVIOUS IMMUNIZATION HISTORY, CURRENT HEALTH STATUS, AND OCCURRENCE OF ANY SYMPTOMS AND/OR SIGNS OF AN ADVERSE EVENT AFTER PREVIOUS IMMUNIZATIONS IN THE CHILD TO BE IMMUNIZED, IN ORDER TO DETERMINE THE EXISTENCE OF ANY CONTRAINDICATION TO IMMUNIZATION WITH THIS VACCINE AND TO ALLOW AN ASSESSMENT OF RISKS AND BENEFITS.


2. BEFORE THE ADMINISTRATION OF ANY BIOLOGICAL, THE HEALTHCARE PROFESSIONAL SHOULD TAKE ALL PRECAUTIONS KNOWN FOR THE PREVENTION OF ALLERGIC OR ANY OTHER ADVERSE REACTIONS. This should include a review of the patient's history regarding possible sensitivity; the ready availability of epinephrine 1:1000 and other appropriate agents used for control of immediate allergic reactions; and a knowledge of the recent literature pertaining to use of the biological concerned, including the nature of side effects and adverse reactions that may follow its use.


3. Children with impaired immune responsiveness, whether due to the use of immunosuppressive therapy (including irradiation, corticosteroids, antimetabolites, alkylating agents, and cytotoxic agents), a genetic defect, HIV infection, or other causes, may have reduced antibody response to active immunization.32,33,34 (See DRUG INTERACTIONS.)


4. The use of pneumococcal conjugate vaccine does not replace the use of 23-valent pneumococcal polysaccharide vaccine in children ≥ 24 months of age with sickle cell disease, asplenia, HIV infection, chronic illness or who are immunocompromised. Data on sequential vaccination with Prevnar® followed by 23-valent pneumococcal polysaccharide vaccine are limited. (See PRECAUTIONS, Special Populations)


5. Since this product is a suspension containing an aluminum adjuvant, shake vigorously immediately prior to use to obtain a uniform suspension.


6. A separate sterile syringe and needle or a sterile disposable unit should be used for each individual to prevent transmission of hepatitis or other infectious agents from one person to another. Needles should be disposed of properly and should not be recapped.


7. Special care should be taken to prevent injection into or near a blood vessel or nerve.

Information for Parents or Guardians

Prior to administration of this vaccine, the healthcare professional should inform the parent, guardian, or other responsible adult of the potential benefits and risks to the patient (see ADVERSE REACTIONS and WARNINGS sections), and the importance of completing the immunization series unless contraindicated. Parents or guardians should be instructed to report any suspected adverse reactions to their healthcare professional. The healthcare professional should provide vaccine information statements prior to each vaccination.

DRUG INTERACTIONS

Children receiving therapy with immunosuppressive agents (large amounts of corticosteroids, antimetabolites, alkylating agents, cytotoxic agents) may not respond optimally to active immunization.33,34 (See PRECAUTIONS, General.)

As with other intramuscular injections, Prevnar® should be given with caution to children on anticoagulant therapy.

Simultaneous Administration with Other Vaccines

During clinical studies, Prevnar® was administered simultaneously with DTaP and HbOC, IPV, Hep B vaccines, MMR, and Varicella vaccine. Thus, the safety experience with Prevnar® reflects the use of this product as part of the routine immunization schedule.20,21,25,27,28,30

The immune response to routine vaccines when administered with Prevnar® (at separate sites) was assessed in 3 clinical studies in which there was a control group for comparison. Higher antibody levels (GMC) to Hib were observed after 3 doses of HbOC given with Prevnar in the infant series, compared to HbOC without Prevnar. After the 4th dose, Hib GMCs were lower when HbOC was given with Prevnar compared to control; however, over 97% of children receiving HbOC with Prevnar achieved a serum antibody concentration of ≥1 μg/mL. Although some inconsistent differences in response to pertussis antigens were observed, the clinical relevance is unknown. The response to 2 doses of IPV given concomitantly with Prevnar®, assessed 3 months after the second dose, was equivalent to controls for poliovirus Types 2 and 3, but lower for Type 1. In another study, over 98% of subjects achieved neutralizing antibody titers ≥1:8 for all polio types, following a third dose of IPV given concomitantly with Prevnar at 12 months of age.35 Seroresponse rates to measles, mumps and rubella were similar after MMR was given concomitantly with Prevnar at 12 months of age compared to seroresponse rates after MMR was given without Prevnar at 12 months of age.36 A clinical study demonstrated no interference with the immune response to varicella vaccine when administered concurrently with a 4th dose of Prevnar®.37

CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY

Prevnar® has not been evaluated for any carcinogenic or mutagenic potential, or impairment of fertility.

PREGNANCY

Pregnancy Category C

Animal reproductive studies have not been conducted with this product. It is not known whether Prevnar® can cause fetal harm when administered to a pregnant woman or whether it can affect reprod

Program Flavor Tabs

Dosage Form: FOR ANIMAL USE ONLY
Program Flavor Tabs

PROGRAM® (LUFENURON) Flavor Tabs®

Information for Dosing Dogs

The flavored once-a-month tablet that prevents and controls flea populations in dogs.

Introduction

Novartis Animal Health encourages you to take the time to read this package insert, which describes the use of PROGRAM® (lufenuron) Flavor Tabs® as a convenient monthly flea control treatment. Controlling flea infestations is very important to the health of your pet.

Warnings

Not for human use. Keep this and all drugs out of the reach of children.

Administration

TO ENSURE ADEQUATE ABSORPTION, ALWAYS ADMINISTER Program Flavor Tabs TO DOGS IMMEDIATELY AFTER OR IN CONJUNCTION WITH A NORMAL MEAL.

Be certain the dog consumes the entire tablet or tablets. As an alternative to direct dosing, tablets may be offered in food. Watch the dog closely following dosing to be sure the entire dose has been consumed. If it is not entirely consumed, redose once with the full recommended dose as soon as possible.

Treatment with Program Flavor Tabs may begin at any time of year. In geographic areas where flea infestations are seasonal, the treatment schedule should begin several weeks prior to the expected onset of infestations. Treatments should continue until the end of “flea season.” If there is risk of exposure to fleas year-round, then treatment should continue the entire year without interruption. Ask your veterinarian for details concerning your geographic area and the most effective treatment schedule for your pet.

Description

The active ingredient of Program Flavor Tabs is lufenuron, a benzoylphenyl-urea derivative classified as an insect development inhibitor (IDI).

As an insect development inhibitor, Program Flavor Tabs do not kill adult fleas but effectively and safely control flea populations on your pet by breaking the flea’s life cycle at the egg stage.

Indications

Program Flavor Tabs are labeled for use in dogs and puppies, four weeks of age and older, for the prevention and control of flea populations.

Lufenuron controls flea populations by preventing the development of flea eggs and does not kill adult fleas. You may also need to use a product that kills adult fleas.

PROGRAM Flavor Tabs may be used along with CAPSTAR® (nitenpyram) Tablets to provide a Flea Management System that kills adult fleas and prevents flea eggs from hatching. Please see the Supplemental Package Insert provided with this product for information about using the two products together.

Without concurrent use of an adulticide, adequate flea control may not be achieved in dogs that have repeated exposure to flea infested animals or environments.

Precautions

Program Flavor Tabs have no effect on adult fleas but act to immediately break the flea life cycle by preventing eggs from developing into adults. However, pre-existing immature fleas in the dog’s environment may continue to develop and emerge as adults after treatment with Program Flavor Tabs has begun. Based on results of clinical studies, this emergence generally occurs during the first 30-60 days. Therefore, if you pet already has a flea infestation before starting Program Flavor Tabs, noticeable results may not be observed until several weeks after dosing. In cooler climates, immature fleas may take longer to complete the life cycle and emerge as adults.

To speed control, products that kill adult fleas, like CAPSTAR Tablets may be used temporarily with Program Flavor Tabs, depending on the severity of the infestation. Your veterinarian can recommend the most effective treatment plan for your pet.

To ensure that your pet gets the greatest benefit from Program Flavor Tabs, you must administer the tablet or tablets once a month in conjunction with a normal meal. If you miss the 30-day interval, give Program Flavor Tabs immediately and resume your monthly dosing schedule. It is important to treat all dogs in the household. Fleas can reproduce on untreated pets and allow infestations to persist. All cats in the household should be treated with an approved product like lufenuron.

The active ingredient in Program Flavor Tabs is excreted in high concentrations in the milk, however, no resulting adverse effects have been recognized.

Flea Infestations on Dogs

Although other flea species my be found on dogs, the cat flea (Ctenocephalides felis) is the predominant flea associated with infestations on dogs in the United States. In addition to the common nuisance irritations associated with infestations, fleas can be responsible for medical problems in your pet such as flea allergy dermatitis (FAD), a skin reaction to flea bites. Fleas also transmit other parasites, including tapeworms. Controlling flea infestations is important to your pet’s health while also reducing the major and minor annoyances associated with these parasites.

The following diagram illustrates the flea’s life cycle and where Program Flavor Tabs acts to break this cycle.

Life Cycle of the Flea

Fleas can be a problem because they reproduce so rapidly. A single female flea may produce up to 2,000 eggs over her lifetime. Eggs hatch and can develop into adults within only three weeks. Adult female fleas feed by ingesting blood from your dog and subsequently lay eggs that drop off your dog’s coat. Within days, larvae hatch from the eggs and live undetected in your dog’s surroundings, such as the carpet, bedding and other unprotected areas. Flea larvae spin a cocoon, and when appropriately stimulated, a young adult flea emerges and jumps onto your dog to continue the life cycle.

After biting a Program Flavor Tabs treated dog, the female flea ingests lufenuron which is deposited in her eggs. Lufenuron prevents these flea eggs from developing into mature adults. This safe and convenient approach to flea control effectively breaks the flea’s life cycle and controls flea populations.

Dosage

Program Flavor Tabs are given orally, once a month at the recommended minimum dosage of 4.5 mg lufenuron per pound (10 mg/kg) of body weight.

Recommended Dosage Schedule

Body Weight	Dose	Lufenuron Per Tablet
Up to 10 lbs.	One tablet	45.0 mg
11 to 20 lbs.	One tablet	90.0 mg
21 to 45 lbs.	One tablet	204.9 mg
46 to 90 lbs.	One tablet	409.8 mg

Dogs over 90 lbs. should receive the appropriate combination of tablets.

*Please see supplemental insert in this package for concurrent dosing of Program Flavor Tabs and CAPSTAR Tablets.

Once a Month

Program Flavor Tabs will safely and effectively control flea infestations only if administered in conjunction with a normal meal on a monthly dosing schedule. To help you remember the monthly dosing, use the enclosed reminder stickers on the appropriate dates on your calendar.

Adverse Reactions

The following adverse reactions have been reported in dogs after giving Program Flavor Tabs: vomiting, depression/lethargy, pruritus (itchy, scratchy skin), urticaria (wheals, hives), diarrhea, anorexia (loss of appetite), and skin congestion (red skin).

How Supplied

Program Flavor Tabs are available in four tablet sizes (see Dosage section), formulated according to the weight of the dog. Each tablet size is available in color-coded packages of six tablets each.

Storage Conditions

Program Flavor Tabs should be stored at room temperature between 59º and 77ºF (15-25ºC).

Questions? Comments?

Please call 1-800-332-2761

Visit our website at www.petwellness.com

Manufactured for:      

Novartis Animal Health US, Inc.

Greensboro, NC 27408

PROGRAM, CAPSTAR, and Flavor Tabs are registered trademarks of Novartis AG.

NADA # 141-035, Approved by FDA

©2008 Novartis Animal Health US, Inc.

NAH/PRO-FT/PI/3

2003201

01/08

FLEA MANAGEMENT SYSYTEM

Supplemental Product Information

Information for Dosing Dogs

This insert describes the concurrent use of PROGRAM® (lufenuron) Flavor Tabs® and CAPSTAR® (nitenpyram) Tablets for the management of fleas on dogs and puppies. Please read the insert contained in each package for complete information on the individual products prior to dosing.

Warnings

Not for human use. Keep this and all drugs out of reach of children.

Directions

In dogs and puppies the concurrent use of Program Flavor Tabs and CAPSTAR Tablets is indicated to kill adult fleas and prevent eggs from hatching. The effects of Program Flavor Tabs, which prevent and control flea populations, and CAPSTAR Tablets, which treat flea infestations, are combined to provide a FLEA MANAGEMENT SYSTEM.

Step 1: Prevention and Control

Give Program Flavor Tabs once per month to prevent and control flea populations. Program Flavor Tabs contain lufenuron. Lufenuron controls flea populations by preventing the development of flea eggs and does not kill adult fleas. If a dog currently has a flea infestation, more rapid relief can be accomplished by adding CAPSTAR Tablets to the treatment as follows.

Step 2: Kill Adult Fleas

If your pet currently has a flea infestation, use CAPSTAR Tablets to kill adult fleas. CAPSTAR Tablets contain nitenpyram and are effective for the treatment of flea infestations. Nitenpyram starts killing adult fleas within 30 minutes of administration.

• Administer CAPSTAR Tablets once per week until adult fleas are no longer observed.
  


• For a severe flea infestation, administer CAPSTAR Tablets twice per week until adult fleas are no longer observed.
  


• Additional CAPSTAR Tablets may be administered as needed to kill the occasional adult flea picked up from infested environments.
  


• It is important to treat all cats (see reverse side of this insert) and dogs in the household. Fleas can reproduce on untreated pets and allow infestations to persist.

Dosage

The combination of Program Flavor Tabs and CAPSTAR Tablets should be administered according to the following schedule. Weigh the dog prior to administration to ensure proper dosage. Do not administer to dogs under 2 pounds.

Recommended Dosage Schedule

Body Weight	Dose	CAPSTAR once or twice weekly* (Nitenpyram per tablet)	Program Flavor Tabs once per month (Lufenuron per tablet)
2 to 10 lbs.	One Tablet	11.4 mg	45.0 mg
11 to 20 lbs.	One Tablet	11.4 mg	90.0 mg
21 to 25 lbs.	One Tablet	11.4 mg	204.9 mg
26 to 45 lbs.	One Tablet	57.0 mg	204.9 mg
46 to 90 lbs.	One Tablet	57.0 mg	409.8 mg
91 to 125 lbs.	One Tablet	57.0 mg	**

*If adult fleas are seen

** Dogs over 90 lbs. are provided the appropriate combination of Program Flavor Tabs.

Adverse Reactions

The following adverse reactions have been reported in dogs after giving Program Flavor Tabs: vomiting, depression/lethargy, pruritus (itch, scratchy skin), urticaria (wheals, hives), diarrhea, anorexia (loss of appetite), and skin congestion (red skin).

Other Information

The safety of the concurrent use of lufenuron, the active ingredient in Program Flavor Tabs and CAPSTAR Tablets has not been evaluated in puppies less than 11 weeks old.

Flea Infestations on Dogs

In addition to the common nuisance irritations associated with infestations, fleas can be responsible for skin conditions in the dog such as flea allergy dermatitis. Fleas also transmit other parasites, including tapeworms. The control of flea infestations is important to the pet’s health and reduces the problems associated with these parasites.

Program Flavor Tabs break the flea life cycle by inhibiting egg development. CAPSTAR Tablets kill adult fleas on the dog. The concurrent use of these two products provides an effective flea management system.

The following diagram illustrates the flea’s life cycle and where the combination of Program Flavor Tabs and CAPSTAR Tablets work:

Life Cycle of the Flea

A single female flea may produce up to 2,000 eggs over her lifetime. Eggs hatch and can develop into adults within only three weeks. Adult female fleas feed by ingesting blood from the pet and subsequently lay eggs, which drop off the pet’s coat. Within days, larvae hatch from the eggs and live undetected in the pet’s surroundings, such as the carpet and bedding. Flea larvae spin a cocoon, and when, appropriately stimulated, a young adult flea emerges and jumps onto the pet to continue the life cycle.

After reading this insert, if you have any questions about the concurrent use of Program Flavor Tabs and CAPSTAR Tablets in your dogs, please call Novartis Animal Health Veterinary Product Support at 1-800-332-2761.

Storage Conditions

Store Program Flavor Tabs and CAPSTAR Tablets as described on the individual product inserts.

Questions? Comments?

Please call 1-800-332-2761

Visit our website at www.petwellnesss.com

Manufactured for:      

Novartis Animal Health US, Inc.

Greensboro, NC 27408

NADA# 141-205, Approved by FDA

U.S. Patent # 5,750,548

©2008 Novartis Animal Health US, Inc.

PROGRAM, CAPSTAR, and Flavor Tabs are registered trademarks of Novartis AG.

NAH/PFT-FMS/PI/2

2003201

01/08

Information for Dosing Cats

The once-a-month flavored tablet that controls flea populations on cats.

Introduction

Novartis Animal Health encourages you to take the time to read this package insert which describes the use of PROGRAM® (lufenuron) Flavor Tabs® as a convenient monthly flea control treatment. Controlling flea infestations is very important to the health of your cat. After reading this insert, if you have any questions about Program Flavor Tabs, flea control, or medical problems associated with flea infestations, consult your veterinarian, who is your pet’s health care expert.

Warnings

Not for human use. Keep this and all drugs out of the reach of children.

Administration

TO ENSURE ADEQUATE ABSORPTION, ALWAYS ADMINISTER Program Flavor Tabs IN CONJUNCTION WITH A NORMAL MEAL.

Be certain the cat consumes the entire tablet or tablets. The tablets can be broken prior to direct dosing for ease of administration to small cats and kittens. As an alternative to direct dosing, tablets can be broken and mixed into wet food. In multiple cat households, each cat should be treated separately to achieve adequate dosing. Watch the cat closely following dosing to be sure the entire dose has been consumed. If it is not entirely consumed, redose once with the full recommended dose as soon as possible.

Treatment with Program Flavor Tabs may begin at any time of year. Treatment should continue until the end of “flea season.” If there is risk of exposure to fleas year-round, then treatment should continue the entire year without interruption. Ask your veterinarian for details concerning your geographic area and the most effective treatment schedule for your cat.

Description

Program Flavor Tabs are available in two sizes of tablets for oral administration to cats and kittens according to their weight (see Dosage section). The active ingredient of Program Flavor Tabs is lufenuron, a benzoylphenyl-urea derivative classified as an insect development inhibitor (IDI).

As an insect development inhibitor, Program Flavor Tabs do not kill adult fleas, but effectively and safely control flea populations on your cat by breaking the flea’s life cycle at the egg stage.

Indications

Program Flavor Tabs are indicated for use in cats and kittens, four weeks of age and older, for the control of flea populations.

Lufenuron controls flea populations by preventing the development of flea eggs and does not kill adult fleas. You may also need to use a product that kills adult fleas.

Program Flavor Tabs may be used along with CAPSTAR® (nitenpyram) Tablets to provide a Flea Management System that kills adult fleas and prevents flea eggs from hatching. Please see the Supplemental Package insert provided with this product for information about using the two products together.

Without concurrent use of an adulticide, adequate flea control may not be achieved in cats that have repeated exposure to flea infested animals or environments.

Precautions

Program Flavor Tabs have no effect on adult fleas, but act to immediately break the flea life cycle by preventing eggs from developing into adults. However, pre-existing immature fleas in the cat’s environment my continue to develop and emerge as adults after treatment with Program Flavor Tabs has begun. Based on results of clinical studies, this emergence generally occurs during the first 30-60 days. Therefore, if your pet already has a flea infestation before starting Program Flavor Tabs, noticeable results may not be observed until several weeks after dosing. In cooler climates, immature fleas may take longer to complete the life cycle and emerge as adults.

To speed control, products that kill adult fleas, like CAPSTAR Tablets may be used temporarily with Program Flavor Tabs, depending on the severity of the infestation. Your veterinarian can recommend the most effective treatment plan for your pet.

To ensure that your pet gets the greatest benefit from Program Flavor Tabs, you must administer the tablet or tablets once a month in conjunction with a normal meal. If you miss the 30-day interval, administer Program Flavor Tabs immediately and resume your monthly dosing schedule. It is important to treat all cats in the household. Fleas can reproduce on untreated pets and allow infestations to persist. All dogs in the household should be treated with an approved product like lufenuron.

The active ingredient in Program Flavor Tabs is excreted in high concentrations in the milk, however, no resulting adverse effects have been recognized.

Flea Infestations on Cats

Although other flea species my be found on cats, the cat flea (Ctenocephalides felis) is the predominant flea associated with infestations on cats in the United States. In addition to the common nuisance irritations associated with infestations, fleas can be responsible for medical problems in your pet such as miliary dermatitis, a skin reaction to flea bites. Fleas also transmit other parasites, including tapeworms. Controlling flea infestations is important to your cat’s health while also reducing the major and minor annoyances associated with these parasites.

The following diagram illustrates the flea’s life cycle and where Program Flavor Tabs acts to break this cycle.

Life Cycle of the Flea

Fleas can be a problem because they reproduce so rapidly. A single female flea may produce up to 2,000 eggs over her lifetime. Eggs hatch and can develop into adults within only three weeks. Adult female fleas feed by ingesting blood from your cat and subsequently lay eggs that drop off your cat’s coat. Within days, larvae hatch from the eggs and live undetected in your cat’s surroundings, such as the carpet, bedding and other unprotected areas. Flea larvae spin a cocoon, and when appropriately stimulated, a young adult flea emerges and jumps onto your cat to continue the life cycle. After biting a Program Flavor Tabs treated cat, the female flea ingests lufenuron which is deposited in her eggs. Lufenuron prevents these eggs from hatching and developing into mature adults. This safe and convenient approach to flea control effectively breaks the flea’s life cycle and controls flea populations.

Dosage

Program Flavor Tabs are given orally, once a month, at the recommended minimum dosage of 13.6 mg lufenuron per pound (30 mg/kg) of body weight.

	Recommended Dosage Schedule
Body Weight	Dose	Lufenuron Per Tablet
Up to 6 lbs.	One tablet	90.0 mg
7 to 15 lbs.	One tablet	204.9 mg

Cats over 15 lbs. are provided the appropriate combination of tablets.

*Please see the supplemental insert in this package for concurrent dosing of Program Flavor Tabs and CAPSTAR Tablets.

Once a Month

Program Flavor Tabs will safely and effectively control flea infestations only if administered on a monthly dosing schedule. To help you remember the monthly dosing, use the enclosed reminder stickers on the appropriate dates on your calendar.

Adverse Reactions

The following adverse reactions have been reported in cats after giving Program Flavor Tabs: vomiting, depression/lethargy, anorexia (loss of appetite), diarrhea, hyperactivity, dyspnea (labored breathing), pruritus (itchy skin) and skin eruptions (rash).

How Supplied

Program Flavor Tabs are available in two tablet sizes (see Dosage section), formulated according to the weight of the cat. Each tablet size is available in color-coded packages of six tablets each.

Storage Conditions

Program Flavor Tabs should be stored at room temperature between 59º and 77ºF (15-25ºC).

Questions? Comments?

Please call 1-800-332-2761

Visit our website at www.petwellness.com

Manufactured for:      

Novartis Animal Health US, Inc.

Greensboro, NC 27408

PROGRAM, CAPSTAR, and Flavor Tabs are registered trademarks of Novartis AG.

NADA # 141-035, Approved by FDA

©2008 Novartis Animal Health US, Inc.

NAH/PRO-FT/PI/3

2003201

01/08

FLEA MANAGEMENT SYSYTEM

Supplemental Product Information

Information for Dosing CATS

This insert describes the concurrent use of PROGRAM® (lufenuron) Flavor Tabs® and CAPSTAR® (nitenpyram) Tablets for the management of fleas on cats and kittens. Please read the insert contained in each package for complete information on the individual products prior to dosing.

Warnings

Not for human use. Keep this and all drugs out of reach of children.

Directions

In cats and kittens the concurrent use of Program Flavor Tabs and CAPSTAR Tablets is indicated to kill adult fleas and prevent eggs from hatching. The effects of Program Flavor Tabs, which control flea populations, and CAPSTAR Tablets, which treat flea infestations, are combined to provide a FLEA MANAGEMENT SYSTEM.

Step 1: Prevention and Control

Give Program Flavor Tabs once per month to control flea populations. Program Flavor Tabs contain lufenuron. Lufenuron controls flea populations by preventing the development of flea eggs and does not kill adult fleas. If a cat currently has a flea infestation, more rapid relief can be accomplished by adding CAPSTAR Tablets to the treatment as follows.

Step 2: Kill Adult Fleas

If your pet currently has a flea infestation, use CAPSTAR Tablets to kill adult fleas. CAPSTAR Tablets contain nitenpyram and are effective for the treatment of flea infestations. Nitenpyram starts killing adult fleas within 30 minutes of administration.

• Administer CAPSTAR Tablets once per week until adult fleas are no longer observed.
  


• For a severe flea infestation, administer CAPSTAR Tablets twice per week until adult fleas are no longer observed.
  


• Additional CAPSTAR Tablets may be administered as needed to kill the occasional adult flea picked up from infested environments.
  


• It is important to treat all dogs (see reverse side of this insert) and cats in the household. Fleas can reproduce on untreated pets and allow infestations to persist.

Dosage

The combination of Program Flavor Tabs and CAPSTAR Tablets should be administered according to the following schedule. Weigh the cat prior to administration to ensure proper dosage. Do not administer to cats under 2 pounds.

Recommended Dosage Schedule

Body Weight	Dose	CAPSTAR once or twice weekly* (Nitenpyram per tablet)	Program Flavor Tabs once per month (Lufenuron per tablet)
2 to 6 lbs.	One Tablet	11.4 mg	90.0 mg
7 to 15 lbs.	One Tablet	11.4 mg	204.9 mg
16 to 25 lbs.	One Tablet	11.4 mg	**

*If adult fleas are seen

** Cats over 15 lbs. are provided the appropriate combination of Program Flavor Tabs.

Adverse Reactions

The following adverse reactions have been reported in cats after giving Program Flavor Tabs: vomiting, depression/lethargy, anorexia (loss of appetite), diarrhea, hyperactivity, dyspnea (labored breathing), pruritus (itchy skin), and skin eruptions (rash).

Other Information

The safety of the concurrent use of Program Flavor Tabs and CAPSTAR Tablets has not been evaluated in kittens less than 7 months of age.

Flea Infestations on Cats

In addition to the common nuisance irritations associated with infestations, fleas can be responsible for skin conditions in the cat such as miliary dermatitis. Fleas also transmit other parasites, including tapeworms. The control of flea infestations is important to the pet’s health and reduces the problems associated with these parasites.

Program Flavor Tabs break the flea life cycle by inhibiting egg development. CAPSTAR Tablets rapidly kill adult fleas on the cat. The concurrent use of these two products provides an effective flea management system.

The following diagram illustrates the flea’s life cycle and where the combination of PROGRAM Flavor Tabs and CAPSTAR Tablets work:

Life Cycle of the Flea

A single female flea may produce up to 2,000 eggs over her lifetime. Eggs hatch and can develop into adults within only three weeks. Adult female fleas feed by ingesting blood form the pet and subsequently lay eggs, which drop off the pet’s coat. Within days, larvae hatch from the eggs and live undetected in the pet’s surroundings, such as the carpet and bedding. Flea larvae spin a cocoon, and, when appropriately stimulated, a young adult flea emerges and jumps onto the pet to continue the life cycle.

After reading this insert, if you have any questions about the concurrent use of Program Flavor Tabs and CAPSTAR Tablets in your cats, please call Novartis Animal Health Veterinary Product Support at 1-800-332-2761.

Storage Conditions

Store Program Flavor Tabs and CAPSTAR Tablets as described on the individual product inserts.

Questions? Comments?

Please call 1-800-332-2761

Visit our website at www.petwellness.com

Manufactured for:      

Novartis Animal Health US, Inc.

Greensboro, NC 27408

NADA# 141-205, Approved by FDA

U.S. Patent # 5,750,548

©2008 Novartis Animal Health US, Inc.

PROGRAM, CAPSTAR, and Flavor Tabs are registered trademarks of Novartis AG.

NAH/PRT-FMS/PI/2

2003201

01/08

PRINCIPAL DISPLAY PANEL

Package Label – 45 mg

FOR DOGS AND PUPPIES UP TO 10 lbs.

PROGRAM (Lufenuron) and Flavor Tabs

GIVE WITH A MEAL

Once-a-month Flavor Tabs for the prevention and control of flea populations in dogs.

KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN.

NADA # 141-035 Approved by the FDA Product # 30111

Net Contents: 6 Tablets 45 mg Lufenuron each

NOVARTIS

PRINCIPAL DISPLAY PANEL

Package Label – 90 mg

FOR DOGS AND PUPPIES 11 TO 20 lbs. / FOR CATS & KITTENS UP TO 6 LBS

PROGRAM (Lufenuron) and Flavor Tabs

GIVE WITH A MEAL

Once-a-month Flavor Tabs for the prevention and control of flea populations in dogs 

and for the control of flea populations in cats.

KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN.

NADA # 141-035  Approved by the FDA Product # 30121

Net Contents: 6 Tablets 90 mg Lufenuron each

NOVARTIS

ANIMAL HEALTH

 

PRINCIPAL DISPLAY PANEL

Package Label – 204.9 mg

FOR DOGS AND PUPPIES 21 TO 45 lbs. / FOR CATS & KITTENS 7 TO 15 lbs.

PROGRAM (Lufenuron) and Flavor Tabs

GIVE WITH A MEAL

Once-a-month Flavor Tabs for the prevention and control of flea populations in dogs

and control of flea populations in cats.

KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN.

NADA # 141-035  Approved by the FDA Product # 30131

Net Contents: 6 Tablets 204.9 mg Lufenuron each

NOVARTIS

ANIMAL HEALTH 

PRINCIPAL DISPLAY PANEL

Package Label – 409.8 mg

FOR DOGS AND PUPPIES 46 TO 90 lbs.

PROGRAM (Lufenuron) and Flavor Tabs

GIVE WITH A MEAL

Once-a-month Flavor Tabs for the prevention and control of flea populations in dogs.

KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN.

NADA # 141-035  Approved by the FDA Product # 30141

Net Contents: 6 Tablets 409.8 mg Lufenuron each

NOVARTIS

ANIMAL HEALTH 

PRINCIPAL DISPLAY PANEL – BULK PRODUCT

Bulk Product – 20 KILOGRAM DRUM

LUFENURON VET. VERY FINE

CGA 184699 B

PROD. No. 591710

Program Flavor Tabs  lufenuron  tablet

Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 58198-3011 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LUFENURON (LUFENURON) LUFENURON 45 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color BROWN (marble) Score no score Shape ROUND (biconvex) Size 8mm Flavor MEAT (Beef flavor) Imprint Code GHG;CGV Contains

Packaging # NDC Package Description Multilevel Packaging 1 58198-3011-1 1 BLISTER PACK In 1 BOX contains a BLISTER PACK 1 6 TABLET In 1 BLISTER PACK This package is contained within the BOX (58198-3011-1)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NADA	NADA141035	08/01/1998

Program Flavor Tabs  lufenuron  tablet

Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 58198-3012 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LUFENURON (LUFENURON) LUFENURON 90 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color BROWN (marble) Score no score Shape ROUND (biconvex) Size 10mm Flavor MEAT (Beef flavor) Imprint Code ACA;CGV Contains

Packaging # NDC Package Description Multilevel Packaging 1 58198-3012-1 1 BLISTER PACK In 1 BOX contains a BLISTER PACK 1 6 TABLET In 1 BLISTER PACK This package is contained within the BOX (58198-3012-1)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NADA	NADA141035	08/01/1998

Program Flavor Tabs  lufenuron  tablet

Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 58198-3013 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LUFENURON (LUFENURON) LUFENURON 204.9 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color BROWN (marble) Score no score Shape ROUND Size 12mm Flavor MEAT (Beef Flavor) Imprint Code GBG;CGV Contains

Packaging # NDC Package Description Multilevel Packaging 1 58198-3013-1 1 BLISTER PACK In 1 BOX contains a BLISTER PACK 1 6 TABLET In 1 BLISTER PACK This package is contained within the BOX (58198-3013-1)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NADA	NADA141035	08/01/1998

Program Flavor Tabs  lufenuron  tablet

Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 58198-3014 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LUFENURON (LUFENURON) LUFENURON 409.8 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color BROWN (marble) Score no score Shape ROUND Size 16mm Flavor MEAT (Beef Flavor) Imprint Code DDD;CGV Contains

Packaging # NDC Package Description Multilevel Packaging 1 58198-3014-1 1 BLISTER PACK In 1 BOX contains a BLISTER PACK 1 6 TABLET In 1 BLISTER PACK This package is contained within the BOX (58198-3014-1)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NADA	NADA141035	08/01/1998

LUFENURON  lufenuron  powder

Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 58198-8000 Route of Administration NOT APPLICABLE DEA Schedule

Active Ingredient/Active Moiety Ingredient Name