Abilify Maintena^™

(aripiprazole)

Abilify Maintena™ (aripiprazole) for Extended-Release Injectable Suspension

INDICATION
Abilify Maintena is an atypical antipsychotic indicated for the treatment of schizophrenia.

• Efficacy was demonstrated in a placebo-controlled, randomized-withdrawal maintenance trial in patients with schizophrenia and additional support for efficacy was derived from oral aripiprazole trials.

IMPORTANT SAFETY INFORMATION      

Contraindication: Known hypersensitivity reaction to aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis.

Cerebrovascular Adverse Events, Including Stroke: Increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, have been reported in clinical trials of elderly patients with dementia-related psychosis treated with oral aripiprazole.

Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex sometimes referred to as NMS may occur with administration of antipsychotic drugs, including Abilify Maintena. Rare cases of NMS occurred during aripiprazole treatment. Signs and symptoms of NMS include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (e.g., irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available.

Tardive Dyskinesia (TD): The risk of developing TD (a syndrome of abnormal, involuntary movements) and the potential for it to become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase. The syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. Prescribing should be consistent with the need to minimize TD. There is no known treatment for established TD, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.

Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that include:

• Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics including aripiprazole. Patients with diabetes should be regularly monitored for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.

• Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics. There were no significant differences between aripiprazole- and placebo-treated patients in the proportion with changes from normal to clinically significant levels for fasting/nonfasting total cholesterol, fasting triglycerides, fasting low-density lipoproteins (LDLs), and fasting/nonfasting high-density lipoproteins (HDLs).

• Weight Gain: Weight gain has been observed. Clinical monitoring of weight is recommended.

Orthostatic Hypotension: Aripiprazole may cause orthostatic hypotension. Abilify Maintena should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions which would predispose them to hypotension.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia, neutropenia, and agranulocytosis have been reported. Patients with a history of clinically significant low white blood cell (WBC) count or drug-induced leukopenia/neutropenia should have their complete blood count monitored frequently during the first few months of therapy while receiving Abilify Maintena. In such patients, consider discontinuation of Abilify Maintena at the first sign of a clinically significant decline in WBC count in the absence of other causative factors.

Seizures/Convulsions: Abilify Maintena should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Potential for Cognitive and Motor Impairment: Abilify Maintena may impair judgment, thinking, or motor skills. Instruct patients to avoid operating hazardous machinery including automobiles until they are certain Abilify Maintena does not affect them adversely.

Body Temperature Regulation: Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic agents. Advise patients regarding appropriate care in avoiding overheating and dehydration. Appropriate care is advised for patients who may exercise strenuously, may be exposed to extreme heat, receive concomitant medication with anticholinergic activity, or are subject to dehydration.

Dysphagia: Esophageal dysmotility and aspiration have been associated with Abilify Maintena; use caution in patients at risk for aspiration pneumonia.

Alcohol: Advise patients to avoid alcohol while taking Abilify Maintena.

Concomitant Medication: Dosage adjustments are recommended in patients who are CYP2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors for greater than 14 days. If the CYP3A4 inhibitor or CYP2D6 inhibitor is withdrawn, the Abilify Maintena dosage may need to be increased. Avoid the concomitant use of CYP3A4 inducers with Abilify Maintena for greater than 14 days because the blood levels of aripiprazole are decreased and may be below the effective levels. Dosage adjustments are not recommended for patients with concomitant use of CYP3A4 inhibitors, CYP2D6 inhibitors or CYP3A4 inducers for less than 14 days.

Most commonly observed adverse reaction: The safety profile of Abilify Maintena is expected to be similar to that of oral aripiprazole. In patients who tolerated and responded to oral aripiprazole and single-blind Abilify Maintena and were then randomized to receive Abilify Maintena or placebo injections, the incidence of adverse reactions was similar between the two treatment groups. The adverse reaction ≥ 5% incidence and at least twice the rate of placebo for oral aripiprazole vs placebo, respectively, was:

• Akathisia (8% vs 4%) in adult patients with schizophrenia.

Injection Site Reactions: In the open-label, stabilization phase of a study with Abilify Maintena in patients with schizophrenia, the percent of patients reporting any injection site-related adverse reaction was 6.3% for Abilify Maintena-treated patients.

Dystonia is a class effect of antipsychotic drugs. Symptoms of dystonia may occur in susceptible individuals during the first days of treatment and at low doses.

Pregnancy/Nursing: Based on animal data, may cause fetal harm. Abilify Maintena should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Aripiprazole is excreted in human breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Click here for FULL PRESCRIBING INFORMATION, including Boxed WARNING, for Abilify Maintena.

© 2013 Otsuka America Pharmaceutical, Inc., Rockville, MD February 2013 0912W-4969B

Brilinta^™

ticagrelor tablets

BRILINTA is indicated to reduce the rate of thrombotic cardiovascular (CV) events in patients with acute coronary syndrome (ACS) (unstable angina, non–ST-elevation myocardial infarction, or ST-elevation myocardial infarction). BRILINTA has been shown to reduce the rate of a combined end point of CV death, myocardial infarction (MI), or stroke compared to clopidogrel. The difference between treatments was driven by CV death and MI with no difference in stroke. In patients treated with PCI, it also reduces the rate of stent thrombosis.

BRILINTA has been studied in ACS in combination with aspirin. Maintenance doses of aspirin >100 mg decreased the effectiveness of BRILINTA. Avoid maintenance doses of aspirin >100 mg daily.

IMPORTANT SAFETY INFORMATION ABOUT BRILINTA

WARNING: BLEEDING RISK

• BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal, bleeding
• Do not use BRILINTA in patients with active pathological bleeding or a history of intracranial hemorrhage
• Do not start BRILINTA in patients planned to undergo urgent coronary artery bypass graft surgery (CABG). When possible, discontinue BRILINTA at least 5 days prior to any surgery
• Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), CABG, or other surgical procedures in the setting of BRILINTA
• If possible, manage bleeding without discontinuing BRILINTA. Stopping BRILINTA increases the risk of subsequent cardiovascular events

WARNING: ASPIRIN DOSE AND BRILINTA EFFECTIVENESS

• Maintenance doses of aspirin above 100 mg reduce the effectiveness of BRILINTA and should be avoided. After any initial dose, use with aspirin 75 mg - 100 mg per day

CONTRAINDICATIONS

• BRILINTA is contraindicated in patients with a history of intracranial hemorrhage and active pathological bleeding such as peptic ulcer or intracranial hemorrhage. BRILINTA is contraindicated in patients with severe hepatic impairment because of a probable increase in exposure; it has not been studied in these patients. Severe hepatic impairment increases the risk of bleeding because of reduced synthesis of coagulation proteins. BRILINTA is also contraindicated in patients with hypersensitivity (e.g. angioedema) to ticagrelor or any component of the product

WARNINGS AND PRECAUTIONS

• Moderate Hepatic Impairment: Consider the risks and benefits of treatment, noting the probable increase in exposure to ticagrelor
• Premature discontinuation increases the risk of MI, stent thrombosis, and death
• Dyspnea was reported in 14% of patients treated with BRILINTA and in 8% of patients taking clopidogrel. Dyspnea resulting from BRILINTA is self-limiting. Rule out other causes
• BRILINTA is metabolized by CYP3A4/5. Avoid use with strong CYP3A inhibitors and potent CYP3A inducers. Avoid simvastatin and lovastatin doses >40 mg
• Monitor digoxin levels with initiation of, or any change in, BRILINTA therapy

ADVERSE REACTIONS

• The most commonly observed adverse reactions associated with the use of BRILINTA vs clopidogrel were Total Major Bleeding (11.6% vs 11.2%) and dyspnea (14% vs 8%)
• In clinical studies, BRILINTA has been shown to increase the occurrence of Holter-detected bradyarrhythmias. PLATO excluded patients at increased risk of bradycardic events. Consider the risks and benefits of treatment

Click for full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

Check back for more formulary kit information.

Learn more about BRILINTA at www.BRILINTAtouchpoints.com

2450306  2/13

ELIQUIS^®

(apixaban)

INDICATION

ELIQUIS is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

• Active pathological bleeding
• Severe hypersensitivity reaction to ELIQUIS (apixaban) (i.e., anaphylactic reactions)

WARNING AND PRECAUTIONS

• Increased Risk of Stroke with Discontinuation of ELIQUIS: Discontinuing ELIQUIS in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from ELIQUIS to warfarin in clinical trials in patients with nonvalvular atrial fibrillation. If ELIQUIS must be discontinued for a reason other than pathological bleeding, consider coverage with another anticoagulant.
• Bleeding Risk: ELIQUIS increases the risk of bleeding and can cause serious, potentially fatal bleeding. Concomitant use of drugs affecting hemostasis increases the risk of bleeding including aspirin and other anti-platelet agents, other anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs, and NSAIDs. Patients should be made aware of signs or symptoms of blood loss and instructed to immediately report to an emergency room. Discontinue ELIQUIS in patients with active pathological hemorrhage.
  
  There is no established way to reverse the anticoagulant effect of apixaban, which can be expected to persist for about 24 hours after the last dose (i.e., about two half-lives). A specific antidote for ELIQUIS is not available. Because of high plasma protein binding, apixaban is not expected to be dialyzable. Protamine sulfate and vitamin K would not be expected to affect the anticoagulant activity of apixaban. There is no experience with antifibrinolytic agents (tranexamic acid, aminocaproic acid) in individuals receiving apixaban. There is neither scientific rationale for reversal nor experience with systemic hemostatics (desmopressin and aprotinin) in individuals receiving apixaban. Use of procoagulant reversal agents such as prothrombin complex concentrate, activated prothrombin complex concentrate, or recombinant factor VIIa may be considered but has not been evaluated in clinical studies. Activated charcoal reduces absorption of apixaban thereby lowering apixaban plasma concentrations.
• Prosthetic Heart Valves: The safety and efficacy of ELIQUIS has not been studied in patients with prosthetic heart valves and is not recommended in these patients.

ADVERSE REACTIONS

The most common and most serious adverse reactions reported with ELIQUIS (apixaban) were related to bleeding.

DISCONTINUATIONS FOR SURGERY AND OTHER INTERVENTIONS

ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding. ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be noncritical in location and easily controlled.

DRUG INTERACTIONS

• Strong Dual Inhibitors of CYP3A4 and P-gp: Inhibitors of CYP3A4 and P-gp increase exposure to apixaban and increase the risk of bleeding. Decrease the dose of ELIQUIS to 2.5 mg twice daily when coadministered with drugs that are strong dual inhibitors of CYP3A4 and P-gp, (e.g., ketoconazole, itraconazole, ritonavir, or clarithromycin). In patients already taking ELIQUIS at a dose of 2.5 mg twice daily, avoid coadministration with strong dual inhibitors of CYP3A4 and P-gp.

• Strong Dual Inducers of CYP3A4 and P-gp: Inducers of CYP3A4 and P-gp decrease exposure to apixaban and increase the risk of stroke. Avoid concomitant use of ELIQUIS with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such drugs will decrease exposure to apixaban.

• Anticoagulants and Antiplatelet Agents: Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding. APPRAISE-2, a placebo-controlled clinical trial of apixaban in high-risk post-acute coronary syndrome patients treated with aspirin or the combination of aspirin and clopidogrel, was terminated early due to a higher rate of bleeding with apixaban compared to placebo.

PREGNANCY CATEGORY B

There are no adequate and well-controlled studies of ELIQUIS in pregnant women. Treatment is likely to increase the risk of hemorrhage during pregnancy and delivery. ELIQUIS should be used during pregnancy only if the potential benefit outweighs the potential risk to the mother and fetus.

ELIQUIS is available in 2.5 and 5 mg tablets.

Please see Full Prescribing Information, including Boxed WARNING.

ELIQUIS is a registered trademark of Bristol-Myers Squibb Company.

© 2013 Bristol-Myers Squibb Company. All rights reserved. 

Fortesta^® Gel

(testosterone)

INDICATION
FORTESTA^® (testosterone) Gel is an androgen indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone:

• Primary hypogonadism (congenital or acquired) – testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol, heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH)) above the normal range
• Hypogonadotropic hypogonadism (congenital or acquired) – idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low serum testosterone concentrations but have gonadotropins in the normal or low range

Important limitations of use: Safety and efficacy of FORTESTA Gel in males <18 years old have not been established.

IMPORTANT SAFETY INFORMATION
WARNING: SECONDARY EXPOSURE TO TESTOSTERONE

• Virilization has been reported in children who were secondarily exposed to testosterone gel
• Children should avoid contact with unwashed or unclothed application sites in men using FORTESTA Gel
• Healthcare providers should advise patients to strictly adhere to recommended instructions for use

• FORTESTA Gel is contraindicated in men with carcinoma of the breast or known or suspected prostate cancer and in women who are, or may become pregnant, or who are breast-feeding. FORTESTA Gel may cause fetal harm and serious adverse reactions to nursing infants
• Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH. Patients treated with androgens may be at an increased risk for prostate cancer. Evaluation of the patients for the presence of prostate cancer prior to initiating and during treatment with androgens is appropriate
• Avoid unintentional exposure of women or children to FORTESTA Gel. Secondary exposure to testosterone can produce signs of virilization. Signs of virilization and the possibility of secondary exposure should be brought to the attention of the HCP. FORTESTA Gel should be discontinued until the cause of virilization is identified
• To minimize the potential for transfer to others, strict adherence to the following is advised:
  • Children and women should avoid contact with unwashed or unclothed application site(s) in men using FORTESTA Gel
  • To minimize the potential for transfer to others, patients using FORTESTA Gel should apply the product as directed and strictly adhere to the following: 1) Wash hands with soap and water after application; 2) Cover the application site with clothing after the gel has dried; 3) Wash the application site thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated
  • If unwashed or uncovered skin to which FORTESTA Gel was applied comes in direct contact with the skin of another person, the area of contact should be washed with soap and water as soon as possible
• Increases of hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. An increase in red blood cell mass may increase the risk of thromboembolic events
• Due to lack of controlled evaluations in women and potential virilizing effects, FORTESTA Gel is not indicated for use in women
• Exogenous administration of androgens, including FORTESTA Gel, may lead to azoospermia through suppression of spermatogenesis, gynecomastia, sleep apnea (especially in those with risk factors such as obesity and chronic lung diseases), decreased concentrations of thyroxin-binding globulins, changes in insulin sensitivity or glycemic control (that may decrease insulin requirements in diabetic patients), and changes in anticoagulant activity
• Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal, or hepatic disease
• Use of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal or hepatic disease
• Monitor serum testosterone, prostate-specific antigen, hemoglobin, hematocrit, liver function tests, serum calcium concentrations, INR and prothrombin time, and lipid concentrations periodically. Changes may require dose adjustment or discontinuation of FORTESTA Gel
• Use FORTESTA Gel with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria)
• FORTESTA Gel is flammable until dry
• There are insufficient long-term data in geriatric patients using FORTESTA Gel to assess potential risks of cardiovascular disease and prostate cancer
• Do not apply FORTESTA Gel to the genitals
• The most common adverse reaction (incidence ≥3%) is skin reactions at the application site (16.1%)

Kombiglyze XR

(saxagliptin and metformin HCl extended-release)

Please click here to read the US Full Prescribing Information for KOMBIGLYZE XR (saxagliptin and metformin HCl extended-release 5/500•5/1000•2.5/1000 mg tablets), including Boxed WARNING about lactic acidosis, and Medication Guide.

LINZESS^™

linaclotide capsules

LINZESS^™ (linaclotide) capsules

LINZESS (linaclotide) is indicated in adults for the treatment of both irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC).
 

IMPORTANT SAFETY INFORMATION

Contraindications

• LINZESS is contraindicated in pediatric patients up to 6 years of age.
• LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

Warnings and Precautions
Pediatric Risk

• LINZESS is contraindicated in pediatric patients up to 6 years of age. In nonclinical studies, deaths occurred within 24 hours in young juvenile mice (1 to 3 week-old mice; approximately equivalent to human pediatric patients less than 2 years of age) following administration of one or two daily oral doses of linaclotide.
• Use of LINZESS should be avoided in pediatric patients 6 through 17 years of age. Linaclotide did not cause deaths in older juvenile mice (approximately equivalent to humans age 12 to 17 years). Although there were no deaths in older juvenile mice, given the deaths in young juvenile mice and the lack of clinical safety and efficacy data in pediatric patients, use of LINZESS should be avoided in pediatric patients 6 through 17 years of age.

Diarrhea

• Diarrhea was the most common adverse reaction of LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. Severe diarrhea was reported in 2% of LINZESS-treated patients. The incidence of diarrhea was similar in the IBS-C and CIC populations.
• Patients should be instructed to stop LINZESS if severe diarrhea occurs and to contact their healthcare provider, who should consider dose suspension.

Adverse Reactions

• In IBS-C clinical trials, the most common adverse reactions in LINZESS-treated patients (incidence ≥2% and greater than placebo) were diarrhea (20% vs 3% placebo), abdominal pain (7% vs 5%), flatulence (4% vs 2%), headache (4% vs 3%), viral gastroenteritis (3% vs 1%) and abdominal distension (2% vs 1%).
• In CIC clinical trials, the most common adverse reactions in LINZESS-treated patients (incidence ≥2% and greater than placebo) were diarrhea (16% vs 5% placebo), abdominal pain (7% vs 6%), flatulence (6% vs 5%), upper respiratory tract infection (5% vs 4%), sinusitis (3% vs 2%) and abdominal distension (3% vs 2%).

Please also click here for full Prescribing Information.

Onglyza^®

(saxagliptin)

Please click here to read the US Full Prescribing Information and Medication Guide for ONGLYZA (saxagliptin).

PREVNAR 13^®

(Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM₁₉₇ Protein])

    INDICATIONS

• Prevnar 13^® is a vaccine indicated for active immunization for the prevention of disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F
• In adults 50 years and older for pneumococcal pneumonia and invasive disease. Indication is based on immune responses
• In children 6 weeks through 5 years for invasive pneumococcal disease and otitis media (caused by 7 of the 13 serotypes only [4, 6B, 9V, 14, 18C, 19F, and 23F])

    Limitations of Use and Effectiveness

• Prevnar 13^® will only help protect against S pneumoniae serotypes in the vaccine
• Effectiveness when administered <5 years after pneumococcal polysaccharide vaccine is not known

    IMPORTANT SAFETY INFORMATION

• Severe allergic reaction (eg, anaphylaxis) to any component of Prevnar 13^® or any diphtheria toxoid–containing vaccine is a contraindication
• Immunocompromised individuals or individuals with impaired immune responsiveness due to the use of immunosuppressive therapy may have reduced antibody response
• In adults, antibody responses to Prevnar 13^® were diminished when given with inactivated Influenza Virus Vaccine  
• In adults, the commonly reported solicited adverse reactions were pain, redness, and swelling at the injection site, limitation of arm movement, fatigue, headache, muscle or joint pain, decreased appetite, chills, or rash
• Apnea following intramuscular vaccination has been observed in some infants born prematurely. Vaccination of premature infants should be based on the infant’s medical status, and the potential benefits and risks
• In infants and toddlers, the most commonly reported serious adverse events were bronchiolitis (0.9%), gastroenteritis (0.9%), and pneumonia (0.9%)  
• In infants and toddlers, the most commonly reported solicited adverse reactions were injection site tenderness, redness, or swelling, irritability, decreased appetite, decreased or increased sleep, and fever

    Please click here for full Prescribing Information.

    *After downloading the PowerPoint^® file and opening, please select "Read Only" to view the content.

    PowerPoint is a registered trademark of Microsoft Corporation

    PSA513100-01

Quillivant XR™ CII

(methylphenidate HCl)

INDICATION

Quillivant XR is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). The efficacy of Quillivant XR was established in a 2-week, placebo-controlled trial in children aged 6 to 12 years with a diagnosis of ADHD. Accumulated efficacy data from other methylphenidate products were also considered.

IMPORTANT SAFETY INFORMATION

• Stroke and myocardial infarction have occurred in adults treated with CNS stimulants at recommended doses. Sudden death has occurred in children and adolescents with structural cardiac abnormalities and other serious cardiac problems, and in adults taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during treatment with Quillivant XR.

• CNS stimulants cause an increase in blood pressure (mean increase approximately 2-4 mm Hg) and heart rate (mean increase approximately 3-6 bpm). Some individuals may have larger increases. Monitor all patients for hypertension and tachycardia.

• Use of stimulants may cause psychotic or manic symptoms in patients with no prior history, or exacerbation of symptoms in patients with pre-existing psychiatric illness. Evaluate for bipolar disorder prior to Quillivant XR use.

• CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Growth should be monitored during treatment with stimulants, including Quillivant XR. Patients who are not growing or gaining weight as expected may need to have their treatment interrupted.

• Based on accumulated data from other methylphenidate products, the most common (≥5% and twice the rate of placebo) expected adverse reactions are appetite decreased, insomnia, nausea, vomiting, dyspepsia, abdominal pain, weight decreased, anxiety, dizziness, irritability, affect lability, tachycardia, and blood pressure increased. There is limited experience with Quillivant XR in controlled trials. Based on this limited experience, the adverse reaction profile of Quillivant XR appears similar to other methylphenidate extended-release products. The most common (≥2% in the Quillivant XR group and greater than placebo) adverse reactions reported in the Phase 3 controlled study conducted in 45 ADHD patients (aged 6-12 years) were affect lability (9%), excoriation (4%), initial insomnia (2%), tic (2%), decreased appetite (2%), vomiting (2%), motion sickness (2%), eye pain (2%), and rash (2%).

• Based on animal data, use of Quillivant XR during pregnancy may cause fetal harm. Quillivant XR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing mothers should be advised to discontinue drug or discontinue nursing, taking into consideration the importance of the drug to the mother.

Please see full Prescribing Information & Medication Guide, including BOXED WARNING regarding Abuse and Dependence.

RAVICTI^™

(glycerol phenylbutyrate)

INDICATIONS AND USAGE
RAVICTI is indicated for use as a nitrogen-binding agent for chronic management of adult and pediatric patients ≥2 years of age with UCDs who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. RAVICTI must be used with dietary protein restriction and, in some cases, dietary supplements (eg, essential amino acids, arginine, citrulline, protein-free calorie supplements).

LIMITATIONS OF USE:

• RAVICTI is not indicated for the treatment of acute hyperammonemia in patients with UCDs because more rapidly acting interventions are essential to reduce plasma ammonia levels.
• The safety and efficacy of RAVICTI for the treatment of N-acetylglutamate synthase (NAGS)deficiency has not been established.
• The use of RAVICTI in patients <2 months of age is contraindicated.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS:

• Patients less than 2 months of age. Children <2 months of age may have immature pancreatic exocrine function, which could impair hydrolysis of RAVICTI, leading to impaired absorption of phenylbutyrate and hyperammonemia.
• With known hypersensitivity to phenylbutyrate. Signs of hypersensitivity include wheezing,dyspnea, coughing, hypotension, flushing, nausea, and rash.

WARNINGS AND PRECAUTIONS:

• Neurotoxicity: Phenylacetate (PAA), a major metabolite of RAVICTI, may be toxic at levels ≥500μg/mL. Reduce RAVICTI dosage if symptoms of neurotoxicity, including vomiting, nausea,headache, somnolence, confusion, or sleepiness, are present in the absence of high ammonia or other intercurrent illnesses.
• Reduced Phenylbutyrate Absorption in Pancreatic Insufficiency or Intestinal Malabsorption:
  • Monitor ammonia levels closely.

ADVERSE EVENTS

• The most common adverse reactions (occurring in ≥10% of adult patients) reported during short-term and long-term treatment with RAVICTI were diarrhea, flatulence, and headache; and nausea, vomiting, diarrhea, decreased appetite, hyperammonemia, dizziness, headache and fatigue, respectively.
• Adverse events occurring in ≥10% of pediatric patients during long-term treatment with RAVICTI were upper abdominal pain, rash, nausea, vomiting, diarrhea, decreased appetite,hyperammonemia, and headache.

DRUG INTERACTIONS:

• Corticosteroids, valproic acid, or haloperidol: May increase plasma ammonia level. Monitor ammonia levels closely.
• Probenecid: May affect renal excretion of metabolites of RAVICTI, including PAGN and PAA.

SPECIAL POPULATION:

• Pregnancy: Based on animal data, may cause fetal harm.
• Nursing Mothers: Discontinue nursing or discontinue the drug.

Please see full Prescribing Information and Medication Guide for RAVICTI.

TEFLARO^®

ceftaroline fosamil

TEFLARO^® (ceftaroline fosamil)

INDICATIONS AND USAGE

• TEFLARO is indicated for the treatment of community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Streptococcus pneumoniae (including cases with concurrent bacteremia), Staphylococcus aureus (methicillin-susceptible isolates only), Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli.
• TEFLARO is also indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca.
• To reduce the development of drug-resistant bacteria and maintain the effectiveness of TEFLARO and other antibacterial drugs, TEFLARO should be used to treat only ABSSSI or CABP that are proven or strongly suspected to be caused by susceptible bacteria. Appropriate specimens for microbiological examination should be obtained in order to isolate and identify the causative pathogens and to determine their susceptibility to ceftaroline. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

IMPORTANT SAFETY INFORMATION

Contraindications

• TEFLARO is contraindicated in patients with known serious hypersensitivity to ceftaroline or other members of the cephalosporin class. Anaphylaxis and anaphylactoid reactions have been reported with ceftaroline.

Warnings and Precautions

Hypersensitivity Reactions

• Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported with beta-lactam antibacterials. Before therapy with TEFLARO is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. If this product is to be given to a penicillin- or other beta-lactam-allergic patient, caution should be exercised because cross sensitivity among beta-lactam antibacterial agents has been clearly established.
• If an allergic reaction to TEFLARO occurs, the drug should be discontinued. Serious acute hypersensitivity (anaphylactic) reactions require emergency treatment with epinephrine and other emergency measures that may include airway management, oxygen, intravenous fluids, antihistamines, corticosteroids, and vasopressors as clinically indicated.

Clostridium difficile-associated Diarrhea

• Clostridium difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial agents, including TEFLARO, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterials not directed against C. difficile should be discontinued, if possible.

Direct Coombs’ Test Seroconversion

• Seroconversion from a negative to a positive direct Coombs’ test result occurred in 120/1114 (10.8%) of patients receiving TEFLARO and 49/1116 (4.4%) of patients receiving comparator drugs in the four pooled Phase 3 trials. No adverse reactions representing hemolytic anemia were reported in any treatment group. If anemia develops during or after treatment with TEFLARO, drug-induced hemolytic anemia should be considered. If drug-induced hemolytic anemia is suspected, discontinuation of TEFLARO should be considered and supportive care should be administered to the patient if clinically indicated.

Development of Drug-Resistant Bacteria

• Prescribing TEFLARO in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Adverse Reactions

• In the four pooled Phase 3 clinical trials, serious adverse events occurred in 98/1300 (7.5%) of patients receiving TEFLARO and 100/1297 (7.7%) of patients receiving comparator drugs. Treatment discontinuation due to adverse events occurred in 35/1300 (2.7%) of patients receiving TEFLARO and 48/1297 (3.7%) of patients receiving comparator drugs with the most common adverse events leading to discontinuation being hypersensitivity for both treatment groups at a rate of 0.3% in the TEFLARO group and 0.5% in the comparator group.
• No adverse reactions occurred in greater than 5% of patients receiving TEFLARO. The most common adverse reactions occurring in >2% of patients receiving TEFLARO in the pooled Phase 3 clinical trials were diarrhea, nausea, and rash.

Drug Interactions

• No clinical drug-drug interaction studies have been conducted with TEFLARO. There is minimal potential for drug-drug interactions between TEFLARO and CYP450 substrates, inhibitors, or inducers; drugs known to undergo active renal secretion; and drugs that may alter renal blood flow.

Use in Specific Populations

• TEFLARO has not been studied in pregnant women. Therefore, TEFLARO should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.
• It is not known whether ceftaroline is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when TEFLARO is administered to a nursing woman.
• Safety and effectiveness in pediatric patients have not been established.
• Because elderly patients, those ≥65 years of age, are more likely to have decreased renal function and ceftaroline is excreted primarily by the kidney, care should be taken in dose selection in this age group and it may be useful to monitor renal function. Dosage adjustment for elderly patients should therefore be based on renal function.
• Dosage adjustment is required in patients with moderate (CrCl >30 to ≤50 mL/min) or severe (CrCl ≥15 to ≤30 mL/min) renal impairment and in patients with end-stage renal disease (CrCl <15 mL/min).
• The pharmacokinetics of ceftaroline in patients with hepatic impairment have not been established.

Please see full Prescribing Information available at www.Teflaro.com