AVYCAZ^® (ceftazidime and avibactam)

INDICATIONS AND USAGE
Complicated Intra-Abdominal Infections (cIAI)
AVYCAZ^® (ceftazidime and avibactam), in combination with metronidazole, is indicated for the treatment of complicated intra-abdominal infections (cIAI) in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii complex, and Pseudomonas aeruginosa.

Complicated Urinary Tract Infections (cUTI), including Pyelonephritis
AVYCAZ (ceftazidime and avibactam) is indicated for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii complex, Proteus mirabilis, and Pseudomonas aeruginosa.

Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP)
AVYCAZ (ceftazidime and avibactam) is indicated for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible Gram-negative microorganisms: Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae.

Usage
To reduce the development of drug-resistant bacteria and maintain the effectiveness of AVYCAZ and other antibacterial drugs, AVYCAZ should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
AVYCAZ is contraindicated in patients with known serious hypersensitivity to the components of AVYCAZ (ceftazidime and avibactam), avibactam-containing products, or other members of the cephalosporin class.

• In a Phase 3 cIAI trial in adult patients, clinical cure rates were lower in a subgroup of patients with baseline creatinine clearance (CrCl) of 30 to less than or equal to 50 mL/min compared to those with CrCl greater than 50 mL/min. The reduction in clinical cure rates was more marked in patients treated with AVYCAZ plus metronidazole compared to meropenem-treated patients. Within this subgroup, patients treated with AVYCAZ received a 33% lower daily dose than is currently recommended for patients with CrCl of 30 to less than or equal to 50 mL/min. Clinical cure rate in patients with normal renal function/mild renal impairment (CrCl greater than 50 mL/min) was 85% (322/379) with AVYCAZ plus metronidazole vs 86% (321/373) with meropenem, and clinical cure rate in patients with moderate renal impairment (CrCl 30 to less than or equal to 50 mL/min) was 45% (14/31) with AVYCAZ plus metronidazole vs 74% (26/35) with meropenem. The decreased clinical response was not observed for patients with moderate renal impairment at baseline (CrCl 30 to less than or equal to 50 mL/min) in the Phase 3 cUTI trials or the Phase 3 HABP/VABP trial. Monitor CrCl at least daily in adult and pediatric patients with changing renal function and adjust the dosage of AVYCAZ accordingly.
•  Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterial drugs. Before therapy with AVYCAZ is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. Exercise caution if this product is to be given to a penicillin- or other beta-lactam-allergic patient because cross sensitivity among beta-lactam antibacterial drugs has been established. Discontinue the drug if an allergic reaction to AVYCAZ occurs. 
• Clostridioides difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial drugs, including AVYCAZ, 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 drugs. If CDAD is suspected or confirmed, antibacterials not directed against C. difficile should be discontinued, if possible. 
• Seizures, nonconvulsive status epilepticus (NCSE), encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported in patients treated with ceftazidime, particularly in the setting of renal impairment. Adjust dosing based on CrCl. 
• Prescribing AVYCAZ in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

ADVERSE REACTIONS
Adult cIAI, cUTI, and HABP/VABP Patients
The most common adverse reactions in adult patients with cIAI (≥5% when used with metronidazole) were diarrhea (8%), nausea (7%), and vomiting (5%). The most common adverse reactions in adult patients with cUTI (3%) were diarrhea and nausea. The most common adverse reactions in adult patients with HABP/VABP (≥5%) were diarrhea (15%) and vomiting (6%).

Pediatric Patients
The most common adverse reactions (>3%) in pediatric patients aged 3 months and older were vomiting, diarrhea, rash, and infusion site phlebitis.
The most common adverse reactions (>3%) in pediatric patients less than 3 months of age were vomiting and increased transaminases.

BOTOX^® (onabotulinumtoxinA)

IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNING

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WARNING: DISTANT SPREAD OF TOXIN EFFECT

Postmarketing reports indicate that the effects of BOTOX and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening, and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity, but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have an underlying condition that would predispose them to these symptoms. In unapproved uses and approved indications, cases of spread of effect have been reported at doses comparable to those used to treat cervical dystonia and spasticity and at lower doses.

INDICATIONS

Adult Bladder Dysfunction

Overactive Bladder

BOTOX^® (onabotulinumtoxinA) for injection is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency in adults who have an inadequate response to or are intolerant of an anticholinergic medication.

Detrusor Overactivity Associated With a Neurologic Condition

BOTOX is indicated for the treatment of urinary incontinence due to detrusor overactivity associated with a neurologic condition (eg, SCI, MS) in adults who have an inadequate response to or are intolerant of an anticholinergic medication.

Pediatric Detrusor Overactivity Associated With a Neurologic Condition

BOTOX is indicated for the treatment of neurogenic detrusor overactivity (NDO) in pediatric patients 5 years of age and older who have an inadequate response to or are intolerant of anticholinergic medication.

Chronic Migraine

BOTOX is indicated for the prophylaxis of headaches in adult patients with chronic migraine (≥15 days per month with headache lasting 4 hours a day or longer).

Limitations of Use

Safety and effectiveness have not been established for the prophylaxis of episodic migraine (14 headache days or fewer per month) in 7 placebo-controlled studies.

Spasticity

BOTOX is indicated for the treatment of spasticity in patients 2 years of age and older.

Limitations of Use

BOTOX has not been shown to improve upper extremity functional abilities or range of motion at a joint affected by a fixed contracture.

Cervical Dystonia

BOTOX is indicated for the treatment of adults with cervical dystonia to reduce the severity of abnormal head position and neck pain associated with cervical dystonia.

Blepharospasm and Strabismus

BOTOX is indicated for the treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorders in patients 12 years of age and older.

Primary Axillary Hyperhidrosis

BOTOX is indicated for the treatment of severe primary axillary hyperhidrosis that is inadequately managed with topical agents.

Limitations of Use

The safety and effectiveness of BOTOX for hyperhidrosis in other body areas have not been established. Weakness of hand muscles and blepharoptosis may occur in patients who receive BOTOX for palmar hyperhidrosis and facial hyperhidrosis, respectively. Patients should be evaluated for potential causes of secondary hyperhidrosis (eg, hyperthyroidism) to avoid symptomatic treatment of hyperhidrosis without the diagnosis and/or treatment of the underlying disease.

Safety and effectiveness of BOTOX have not been established for the treatment of axillary hyperhidrosis in pediatric patients under age 18.

IMPORTANT SAFETY INFORMATION (continued)

CONTRAINDICATIONS

BOTOX is contraindicated in the presence of infection at the proposed injection site(s) and in patients who are hypersensitive to any botulinum toxin product or to any of the components in the formulation.

BOTOX is contraindicated for intradetrusor injection in patients with a urinary tract infection (UTI), or in patients with urinary retention, or post-void residual (PVR) urine volume >200 mL who are not routinely performing clean intermittent self-catheterization (CIC).

WARNINGS AND PRECAUTIONS

Spread of Toxin Effect

See Boxed Warning.

No definitive serious adverse event reports of distant spread of toxin effect associated with BOTOX for blepharospasm at the recommended dose (30 Units and below), severe primary axillary hyperhidrosis at the recommended dose (100 Units), strabismus, or for chronic migraine at the labeled doses have been reported.

Lack of Interchangeability Between Botulinum Toxin Products
The potency Units of BOTOX are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products and, therefore, Units of biological activity of BOTOX cannot be compared to nor converted into Units of any other botulinum toxin products assessed with any other specific assay method.

Serious Adverse Reactions With Unapproved Use

Serious adverse reactions, including excessive weakness, dysphagia, and aspiration pneumonia, with some adverse reactions associated with fatal outcomes, have been reported in patients who received BOTOX injections for unapproved uses. In these cases, the adverse reactions were not necessarily related to distant spread of toxin, but may have resulted from the administration of BOTOX to the site of injection and/or adjacent structures. In several of the cases, patients had preexisting dysphagia or other significant disabilities. There is insufficient information to identify factors associated with an increased risk for adverse reactions associated with the unapproved uses of BOTOX. The safety and effectiveness of BOTOX for unapproved uses have not been established.

Hypersensitivity Reactions

Serious and/or immediate hypersensitivity reactions have been reported. These reactions include anaphylaxis, serum sickness, urticaria, soft-tissue edema, and dyspnea. If such a reaction occurs, further injection of BOTOX should be discontinued and appropriate medical therapy immediately instituted. One fatal case of anaphylaxis has been reported in which lidocaine was used as the diluent, and consequently, the causal agent cannot be reliably determined.

Increased Risk of Clinically Significant Effects With Preexisting Neuromuscular Disorders

Individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis (ALS), or neuromuscular junction disorders (eg, myasthenia gravis or Lambert-Eaton syndrome) should be monitored when given botulinum toxin. Patients with known or unrecognized neuromuscular disorders or neuromuscular junction disorders may be at increased risk of clinically significant effects, including generalized muscle weakness, diplopia, ptosis, dysphonia, dysarthria, severe dysphagia, and respiratory compromise from therapeutic doses of BOTOX (see Warnings and Precautions).

Dysphagia and Breathing Difficulties

Treatment with BOTOX and other botulinum toxin products can result in swallowing or breathing difficulties. Patients with preexisting swallowing or breathing difficulties may be more susceptible to these complications. In most cases, this is a consequence of weakening of muscles in the area of injection that are involved in breathing or oropharyngeal muscles that control swallowing or breathing (see Boxed Warning).

Pulmonary Effects of BOTOX in Patients With Compromised Respiratory Status Treated for Spasticity or for Detrusor Overactivity Associated With a Neurologic Condition

Patients with compromised respiratory status treated with BOTOX for spasticity or detrusor overactivity associated with a neurologic condition should be monitored closely.

Corneal Exposure and Ulceration in Patients Treated With BOTOX for Blepharospasm

Reduced blinking from BOTOX injection of the orbicularis muscle can lead to corneal exposure, persistent epithelial defect, and corneal ulceration, especially in patients with VII nerve disorders.

Retrobulbar Hemorrhages in Patients Treated With BOTOX for Strabismus

During the administration of BOTOX for the treatment of strabismus, retrobulbar hemorrhages sufficient to compromise retinal circulation have occurred. It is recommended that appropriate instruments to decompress the orbit be accessible.

Bronchitis and Upper Respiratory Tract Infections in Patients Treated for Spasticity

Bronchitis was reported more frequently as an adverse reaction in adult patients treated for upper limb spasticity with BOTOX (3% at 251 Units to 360 Units total dose) compared to placebo (1%). In adult patients with reduced lung function treated for upper limb spasticity, upper respiratory tract infections were also reported more frequently as adverse reactions in patients treated with BOTOX (11% at 360 Units total dose; 8% at 240 Units total dose) compared to placebo (6%). In adult patients treated for lower limb spasticity, upper respiratory tract infections were reported more frequently as an adverse reaction in patients treated with BOTOX (2% at 300 Units to 400 Units total dose) compared to placebo (1%). In pediatric patients treated for upper limb spasticity, upper respiratory tract infections were reported more frequently as an adverse reaction in patients treated with BOTOX (17% at 6 Units/kg and 10% at 3 Units/kg) compared to placebo (9%). In pediatric patients treated for lower limb spasticity, upper respiratory tract infection was not reported with an incidence greater than placebo.

Autonomic Dysreflexia in Patients Treated for Detrusor Overactivity Associated With a Neurologic Condition

Autonomic dysreflexia associated with intradetrusor injections of BOTOX could occur in patients treated for detrusor overactivity associated with a neurologic condition and may require prompt medical therapy. In clinical trials, the incidence of autonomic dysreflexia was greater in adult patients treated with BOTOX 200 Units compared with placebo (1.5% vs 0.4%, respectively).

Urinary Tract Infections in Patients With Overactive Bladder

BOTOX increases the incidence of UTI. Clinical trials for overactive bladder excluded patients with more than 2 UTIs in the past 6 months and those taking antibiotics chronically due to recurrent UTIs. Use of BOTOX for the treatment of overactive bladder in such patients and in patients with multiple recurrent UTIs during treatment should only be considered when the benefit is likely to outweigh the potential risk.

Urinary Retention in Adults Treated for Bladder Dysfunction

Due to the risk of urinary retention, treat only patients who are willing and able to initiate catheterization posttreatment, if required, for urinary retention.

In patients who are not catheterizing, PVR urine volume should be assessed within 2 weeks posttreatment and periodically as medically appropriate up to 12 weeks, particularly in patients with multiple sclerosis or diabetes mellitus. Depending on patient symptoms, institute catheterization if PVR urine volume exceeds 200 mL and continue until PVR falls below       200 mL. Instruct patients to contact their physician if they experience difficulty in voiding as catheterization may be required.

‍Overactive Bladder
In clinical trials, 6.5% of patients (36/552) initiated CIC for urinary retention following treatment with BOTOX 100 Units, as compared to 0.4% of patients (2/542) treated with placebo. The median duration of catheterization for patients treated with BOTOX 100 Units was 63 days (minimum 1 day to maximum 214 days), as compared to a median duration of 11 days (minimum 3 days to maximum 18 days) for patients receiving placebo.

Patients with diabetes mellitus treated with BOTOX were more likely to develop urinary retention than nondiabetics. In clinical trials, 12.3% of patients (10/81) with diabetes developed urinary retention following treatment with BOTOX 100 Units vs 0% of patients (0/69) treated with placebo. In patients without diabetes, 6.3% of patients (33/526) developed urinary retention following treatment with BOTOX 100 Units vs 0.6% of patients (3/516) treated with placebo.

‍Adult Detrusor Overactivity Associated With a Neurologic Condition
In clinical trials, 30.6% of adult patients (33/108) who were not using CIC prior to injection required catheterization for urinary retention following treatment with BOTOX 200 Units, as compared to 6.7% of patients (7/104) treated with placebo. The median duration of postinjection catheterization for these patients treated with BOTOX 200 Units (n = 33) was 289 days (minimum 1 day to maximum 530 days), as compared to a median duration of 358 days (minimum 2 days to maximum 379 days) for patients receiving placebo (n = 7).

Among adult patients not using CIC at baseline, those with multiple sclerosis were more likely to require CIC postinjection than those with spinal cord injury.

Human Albumin and Transmission of Viral Diseases

This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases and variant Creutzfeldt-Jakob disease (vCJD). There is a theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD), but if that risk actually exists, the risk of transmission would also be considered extremely remote. No cases of transmission of viral diseases, CJD, or vCJD have ever been identified for licensed albumin or albumin contained in other licensed products.

ADVERSE REACTIONS

Adverse reactions to BOTOX for injection are discussed in greater detail in the following sections: Boxed Warning, Contraindications, and Warnings and Precautions.

Overactive Bladder

The most frequently reported adverse reactions for overactive bladder occurring within 12 weeks of injection include UTI (BOTOX 18%, placebo 6%); dysuria (BOTOX 9%, placebo 7%); urinary retention (BOTOX 6%, placebo 0%); bacteriuria (BOTOX 4%, placebo 2%); and residual urine volume (BOTOX 3%, placebo 0%).

A higher incidence of UTI was observed in patients with diabetes mellitus treated with BOTOX 100 Units and placebo than nondiabetics.

The incidence of UTI increased in patients who experienced a maximum PVR urine volume ≥200 mL following BOTOX injection compared to those with a maximum PVR <200 mL following BOTOX injection, 44% vs 23%, respectively.

Adult Detrusor Overactivity Associated With a Neurologic Condition

The most frequently reported adverse reactions within 12 weeks of BOTOX injection for detrusor overactivity associated with a neurologic condition include UTI (BOTOX 24%, placebo 17%); urinary retention (BOTOX 17%, placebo 3%); and hematuria (BOTOX 4%, placebo 3%).

The following adverse event rates were reported at any time following initial injection and prior to reinjection or study exit (median duration of 44 weeks of exposure): UTIs (49%), urinary retention (17%), constipation (4%), muscular weakness (4%), dysuria (4%), fall (3%), gait disturbance (3%), and muscle spasm (2%).

Pediatric Detrusor Overactivity Associated With a Neurologic Condition

The most frequently reported adverse reactions during the 12 weeks following BOTOX injection of 200 Units for pediatric detrusor overactivity associated with a neurologic condition include bacteriuria (20%), UTI (7%), leukocyturia (7%), and hematuria (3%).

The most common adverse reactions in patients who received BOTOX 6 Units/kg and less than a total dose of 200 Units were UTI, bacteriuria, and hematuria.

These patients were not adequately managed with at least one anticholinergic agent and were using CIC at baseline.

Chronic Migraine

The most frequently reported adverse reactions following injection of BOTOX for chronic migraine vs placebo include, respectively, neck pain (9% vs 3%); headache (5% vs 3%); eyelid ptosis (4% vs <1%); migraine (4% vs 3%); muscular weakness (4% vs <1%); musculoskeletal stiffness (4% vs 1%); bronchitis (3% vs 2%); injection-site pain (3% vs 2%); musculoskeletal pain (3% vs 1%); myalgia (3% vs 1%); facial paresis (2% vs 0%); hypertension (2% vs 1%); and muscle spasms (2% vs 1%).

Adult Upper Limb Spasticity

The most frequently reported adverse reactions following injection of BOTOX for upper limb spasticity include pain in extremity, muscular weakness, fatigue, nausea, and bronchitis.

Adult Lower Limb Spasticity

The most frequently reported adverse reactions following injection of BOTOX for lower limb spasticity include arthralgia, back pain, myalgia, upper respiratory tract infection, and injection-site pain.

Pediatric Upper Limb Spasticity

The most frequently reported adverse reactions following injection of BOTOX in pediatric upper limb spasticity include upper respiratory tract infection (includes upper respiratory tract infection and viral upper respiratory tract infection), injection-site pain, nausea, constipation, rhinorrhea, nasal congestion, and seizure (includes seizure and partial seizure).

Pediatric Lower Limb Spasticity

The most frequently reported adverse reactions following injection of BOTOX in pediatric lower limb spasticity include injection-site erythema, injection-site pain, oropharyngeal pain, ligament sprain, skin abrasion, and decreased appetite.

Cervical Dystonia

The most frequently reported adverse reactions following injection of BOTOX for cervical dystonia include dysphagia (19%), upper respiratory infection (12%), neck pain (11%), and headache (11%).

Blepharospasm

The most frequently reported adverse reactions following injection of BOTOX for blepharospasm include ptosis (21%), superficial punctate keratitis (6%), and eye dryness (6%).

Strabismus

The most frequently reported adverse events following injection of BOTOX for strabismus include ptosis (1% after inferior rectus injections, 16% after horizontal rectus injections, and 38% after superior rectus injections) and vertical deviation (17%).

Primary Axillary Hyperhidrosis

The most frequently reported adverse events (3%-10% of adult patients) following injection of BOTOX for severe primary axillary hyperhidrosis in double-blind studies include injection-site pain and hemorrhage, nonaxillary sweating, infection, pharyngitis, flu syndrome, headache, fever, neck or back pain, pruritus, and anxiety.

Postmarketing Experience

Adverse reactions that have been identified during postapproval use of BOTOX are discussed in greater detail in Postmarketing Experience (Section 6.3 of the Prescribing Information).

There have been spontaneous reports of death, sometimes associated with dysphagia, pneumonia, and/or other significant debility or anaphylaxis, after treatment with botulinum toxin. There have also been reports of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. Some of these patients had risk factors, including cardiovascular disease. The exact relationship of these events to the botulinum toxin injection has not been established.

DRUG INTERACTIONS

Co-administration of BOTOX and other agents interfering with neuromuscular transmission (eg, aminoglycosides, curare-like compounds) should only be performed with caution as the effect of the toxin may be potentiated. Use of anticholinergic drugs after administration of BOTOX may potentiate systemic anticholinergic effects. The effect of administering different botulinum neurotoxin products at the same time or within several months of each other is unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin. Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of BOTOX.

Please see BOTOX^® full Prescribing Information, including Boxed Warning and Medication Guide.

DALVANCE^® (dalbavancin) Important Information

INDICATION AND USAGE
DALVANCE^® (dalbavancin) for injection is indicated for the treatment of adult and pediatric patients with acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible strains of Gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group (including S. anginosus, S. intermedius, S. constellatus) and Enterococcus faecalis (vancomycin-susceptible isolates).

To reduce the development of drug-resistant bacteria and maintain the effectiveness of DALVANCE and other antibacterial agents, DALVANCE should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

IMPORTANT SAFETY INFORMATION
Contraindications
DALVANCE is contraindicated in patients with known hypersensitivity to dalbavancin.

Warnings and Precautions
Hypersensitivity Reactions
Serious hypersensitivity (anaphylactic) and skin reactions have been reported with glycopeptide antibacterial agents, including DALVANCE. Exercise caution in patients with known hypersensitivity to glycopeptides due to the possibility of cross-sensitivity. If an allergic reaction occurs, treatment with DALVANCE should be discontinued.

Infusion-related Reactions
Rapid intravenous infusion of DALVANCE can cause reactions, including flushing of the upper body, urticaria, pruritus, rash, and/or back pain.

Hepatic Effects
ALT elevations with DALVANCE treatment were reported in clinical trials.

Clostridioides difficile-associated Diarrhea
Clostridioides difficile-associated diarrhea (CDAD) has been reported with nearly all systemic antibacterial agents, including DALVANCE, with severity ranging from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs.

Development of Drug-resistant Bacteria
Prescribing DALVANCE in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Adverse Reactions
The most common adverse reactions in adult patients treated with DALVANCE in Phase 2/3 trials were nausea (5.5%), headache (4.7%), and diarrhea (4.4%). The most common adverse reaction that occurred in more than 1% of pediatric patients was pyrexia (1.2%).

• There are no adequate and well-controlled studies with DALVANCE use in pregnant or nursing women. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for DALVANCE and any adverse effects on the breast-fed child from DALVANCE or from the underlying maternal condition.
• In patients with renal impairment whose known creatinine clearance (CLcr) is less than 30 mL/min and who are not receiving regularly scheduled hemodialysis, the recommended regimen of DALVANCE is 1125 mg, administered as a single dose, or 750 mg followed one week later by 375 mg. No dosage adjustment is recommended for patients receiving regularly scheduled hemodialysis, and DALVANCE can be administered without regard to the timing of hemodialysis. There is insufficient information to recommend dosage adjustment for pediatric patients younger than 18 years of age with CLcr less than 30 mL/min/1.73m2.
• Caution should be exercised when prescribing DALVANCE to patients with moderate or severe hepatic impairment (Child-Pugh Class B or C) as no data are available to determine the appropriate dosing in these patients.

Please see full Prescribing Information.

DURYSTA^® (bimatoprost intracameral implant) Important Information

INDICATIONS AND USAGE 

DURYSTA^® (bimatoprost intracameral implant) is indicated for the reduction of intraocular pressure (IOP) in patients with open angle glaucoma (OAG) or ocular hypertension (OHT).

IMPORTANT SAFETY INFORMATION

Contraindications

DURYSTA^® is contraindicated in patients with: active or suspected ocular or periocular infections; corneal endothelial cell dystrophy (e.g., Fuchs’ Dystrophy); prior corneal transplantation or endothelial cell transplants (e.g., Descemet’s Stripping Automated Endothelial Keratoplasty [DSAEK]); absent or ruptured posterior lens capsule, due to the risk of implant migration into the posterior segment; hypersensitivity to bimatoprost or to any other components of the product.

Warnings and Precautions

The presence of DURYSTA^® implants has been associated with corneal adverse reactions and increased risk of corneal endothelial cell loss. Administration of DURYSTA^® should be limited to a single implant per eye without retreatment. Caution should be used when prescribing DURYSTA^® in patients with limited corneal endothelial cell reserve.

DURYSTA^® should be used with caution in patients with narrow iridocorneal angles (Shaffer grade < 3) or anatomical obstruction (e.g., scarring) that may prohibit settling in the inferior angle.

Macular edema, including cystoid macular edema, has been reported during treatment with ophthalmic bimatoprost, including DURYSTA^® intracameral implant. DURYSTA^® should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema.

Prostaglandin analogs, including DURYSTA^®, have been reported to cause intraocular inflammation. DURYSTA^® should be used with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated.

Ophthalmic bimatoprost, including DURYSTA^® intracameral implant, has been reported to cause changes to pigmented tissues, such as increased pigmentation of the iris. Pigmentation of the iris is likely to be permanent. Patients who receive treatment should be informed of the possibility of increased pigmentation. While treatment with DURYSTA^® can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly.

Intraocular surgical procedures and injections have been associated with endophthalmitis. Proper aseptic technique must always be used with administering DURYSTA^®, and patients should be monitored following the administration.

Adverse Reactions

In controlled studies, the most common ocular adverse reaction reported by 27% of patients was conjunctival hyperemia. Other common adverse reactions reported in 5%-10% of patients were foreign body sensation, eye pain, photophobia, conjunctival hemorrhage, dry eye, eye irritation, intraocular pressure increased, corneal endothelial cell loss, vision blurred, iritis, and headache.

Please see accompanying full Prescribing Information, or visit https://www.rxabbvie.com/pdf/durysta_pi.pdf

JUVÉDERM^® Collection of Fillers Important Information

INDICATIONS
JUVÉDERM^® VOLUMA^® XC injectable gel is indicated for deep (subcutaneous and/or supraperiosteal) injection for cheek augmentation to correct age-related volume deficit in the mid-face, for augmentation of the chin region to improve the chin profile, and for supraperiosteal injection to augment the temple region to improve moderate to severe temple hollowing in adults over the age of 21.

JUVÉDERM^® VOLUX^® XC injectable gel is indicated for subcutaneous and/or supraperiosteal injection for improvement of jawline definition in adults over the age of 21 with moderate to severe loss of jawline definition.

JUVÉDERM^® VOLLURE^® XC injectable gel is indicated for injection into the mid-to-deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds) in adults over the age of 21.

JUVÉDERM^® VOLBELLA^® XC injectable gel is indicated for injection into the lips for lip augmentation and correction of perioral rhytids, and for the improvement of infraorbital hollowing in adults over the age of 21.

JUVÉDERM^® Ultra Plus XC and JUVÉDERM^® Ultra XC injectable gels are indicated for injection into the mid-to-deep dermis for correction of moderate to severe facial wrinkles and folds (such as nasolabial folds).

JUVÉDERM^® Ultra XC injectable gel is also indicated for injection into the lips and perioral area for lip augmentation in adults over the age of 21.
 
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS

• Do not inject into blood vessels. Introduction of these products into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue fillers; for example, after insertion of the needle and just before injection, the plunger rod can be withdrawn slightly to aspirate and verify the needle is not intravascular, inject the product slowly, and apply the least amount of pressure necessary. Rare, but serious, adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms: changes in vision, signs of a stroke, blanching of the skin, unusual pain during or shortly after the procedure. Patients should receive prompt medical attention and, possibly, evaluation by an appropriate healthcare professional specialist should an intravascular injection occur.
• Product use at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present should be deferred until the underlying process has been controlled.

• To minimize the risk of potential complications, these products should only be used by healthcare professionals who are knowledgeable about the anatomy and the product(s) for use in indicated area(s), and who have appropriate training in facial anatomy, vasculature, safe injection techniques, and identification and management of potential adverse events, including intravascular complications
• The potential risks of soft tissue injections should be discussed with patients prior to treatment to ensure they are aware of signs and symptoms of complications
• The safety and effectiveness for the treatment of anatomic regions other than indicated areas for each product have not been established in controlled clinical studies.
  
• The safety for use of these products in patients with known susceptibility to keloid formation, hypertrophic scarring, and pigmentation disorders has not been studied
• The safety for use during pregnancy and in breastfeeding females has not been established
• The safety for use of JUVÉDERM^® VOLUMA^® XC has been established in patients between 35 and 65 years of age for cheek augmentation, 22 and 80 years of age for chin augmentation, and 32 and 82 years of age for improvement of temple hollowing
• The safety for use of JUVÉDERM^® Ultra Plus XC and JUVÉDERM^® Ultra XC in patients under 18 years, and the safety for use of JUVÉDERM^® VOLUX^® XC, JUVÉDERM^® VOLLURE^® XC, and JUVÉDERM^® VOLBELLA^® XC in patients under 22 years, has not been established
• Dermal filler implantation carries a risk of infection. Follow standard precautions
• Dermal fillers should be used with caution in patients on immunosuppressive therapy
• Patients taking medications that can prolong bleeding (such as aspirin, nonsteroidal anti-inflammatory drugs, and warfarin) may experience increased bruising or bleeding at treatment sites
• Patients who experience skin injury near the site of implantation may be at a higher risk for adverse events
• If laser treatment, chemical peel, or any other procedure based on active dermal response is considered after treatment, or before skin has healed from a procedure prior to treatment, there is a possible risk of eliciting an inflammatory reaction at the injection site
• The safety for use of JUVÉDERM^® VOLUMA^® XC injectable gel in patients with very thin skin in the mid-face has not been established
• The safety of using a cannula with JUVÉDERM^® VOLUMA^® XC for cheek augmentation in patients with Fitzpatrick Skin Types V and VI or to improve temple hollowing has not been established
• JUVÉDERM^® VOLUMA^® XC was not evaluated in subjects with significant skin laxity of the chin, neck, or jaw in the chin augmentation study
• The effect of JUVÉDERM^® VOLUMA^® XC injection into the chin on facial hair growth has not been studied
• Patients may experience late-onset adverse events with injectable gel implants, and late-onset nodules with use of JUVÉDERM^® VOLUMA^® XC
• Based on preclinical studies, patients should be limited to 20 mL of any JUVÉDERM^® injectable gel per 60 kg (132 lb) body mass per year. The safety of injecting greater amounts has not been established
• Injection of more than 9 mL of JUVÉDERM^® VOLUX^® XC for improvement of jawline definition has not been studied

ADVERSE EVENTS
The most common reported side effects for JUVÉDERM^® injectable gels were redness, swelling, pain, tenderness, firmness, lumps/bumps, bruising, discoloration, and itching. For JUVÉDERM^® VOLBELLA^® XC, dryness was also reported. The majority were mild or moderate in severity.

To report an adverse reaction with any product in the JUVÉDERM^® Collection, please call Allergan^® Product Support at 1-877-345-5372. Please visit rxabbvie.com for more information.

Products in the JUVÉDERM^® Collection are available only by a licensed physician or properly licensed practitioner.

Please see Directions for Use or visit https://www.rxabbvie.com/pdf/juvederm-voluma-xc_dfu.pdf for JUVÉDERM^® VOLUMA^® XC
Please see Directions for Use or visit https://www.rxabbvie.com/pdf/juvederm-volux-xc_dfu.pdf for JUVÉDERM^® VOLUX^® XC
Please see Directions for Use or visit https://www.rxabbvie.com/pdf/juvederm-vollure-xc_dfu.pdf for JUVÉDERM^® VOLLURE^® XC
Please see Directions for Use or visit https://www.rxabbvie.com/pdf/juvederm-volbella_dfu.pdf for JUVÉDERM^® VOLBELLA^® XC
Please see Directions for Use or visit https://www.rxabbvie.com/pdf/juvederm-ultra-plus-xc_dfu.pdf for JUVÉDERM^® Ultra Plus XC
Please see Directions for Use or visit https://www.rxabbvie.com/pdf/juvederm-ultra-xc_dfu.pdf for JUVÉDERM^® Ultra XC

LILETTA^® (levonorgestrel-releasing intrauterine system) 

IMPORTANT SAFETY INFORMATION

Who is not appropriate for LILETTA

Use of LILETTA is contraindicated in women with the following: pregnancy; for use as post-coital contraception; congenital or acquired uterine anomaly, including leiomyomas, that distorts the uterine cavity and would be incompatible with correct intrauterine system (IUS) placement; known or suspected breast cancer or other hormone-sensitive cancer, now or in the past; known or suspected uterine or cervical malignancy; acute liver disease or liver tumor; untreated acute cervicitis or vaginitis, including lower genital tract infections (eg, bacterial vaginosis), until infection is controlled; postpartum endometritis or infected abortion in the past 3 months; unexplained uterine bleeding; a current IUS; acute pelvic inflammatory disease (PID); conditions increasing susceptibility to pelvic infection; or hypersensitivity to any component of LILETTA.

Clinical considerations for use and removal of LILETTA

Use LILETTA with caution after careful assessment in women with coagulopathy or taking anticoagulants; migraine, focal migraine with asymmetrical visual loss, or other symptoms indicating transient cerebral ischemia; exceptionally severe or frequent headache; marked increase of blood pressure; or severe arterial disease such as stroke or myocardial infarction. Consider removing LILETTA 
if the following arise during use: uterine or cervical malignancy or jaundice. Because irregular bleeding/spotting is common during the first months of LILETTA use, exclude endometrial pathology (polyps or cancer) prior to the insertion of LILETTA in women with persistent or uncharacteristic bleeding. If the threads are not visible or are significantly shortened, they may have broken or retracted into the cervical canal or uterus. If LILETTA is displaced (eg, expulsed or perforated the uterus), remove it.

Pregnancy-related risks with LILETTA

If pregnancy should occur with LILETTA in place, remove the IUS because leaving it in place may increase the risk of spontaneous abortion and preterm labor. Removal or manipulation may result in pregnancy loss. Evaluate women for ectopic pregnancy because the likelihood of a pregnancy being ectopic is increased. Tell women about the signs of ectopic pregnancy and associated risks, including loss of fertility. Women with a history of ectopic pregnancy, tubal surgery, or pelvic infection have a higher risk of ectopic pregnancy.

Educate her about PID or endometritis

Insertion of LILETTA is contraindicated in the presence of known or suspected PID or endometritis. IUSs have been associated with an increased risk of PID, most likely due to organisms being introduced into the uterus during insertion. In the LILETTA contraception study, one woman diagnosed with PID and two women diagnosed with endometritis developed the infection within a week of insertion. One endometritis case was diagnosed at 39 days after insertion. The remaining 11 cases of PID and endometritis were diagnosed more than 6 months after insertion, including one at 30 days after IUS removal. In the HMB study, one woman was diagnosed with PID about 5 months after LILETTA insertion. Counsel women who use LILETTA to notify a healthcare provider if they develop lower abdominal or pelvic pain, fever, chills, unusual or malodorous discharge, unexplained bleeding, genital lesions or sores, or dyspareunia. PID and endometritis are often associated with sexually transmitted infections (STIs); LILETTA does not protect against STIs, including HIV. PID or endometritis may be asymptomatic but still result in tubal damage and its sequelae. Inform women about the possibility of PID or endometritis and that these infections can cause tubal damage leading to ectopic pregnancy or infertility, or infrequently can necessitate hysterectomy, or cause death.

Expect changes in bleeding patterns with LILETTA

Spotting and irregular or heavy bleeding may occur during the first 3 to 6 months. Periods may become shorter and/or lighter thereafter. Cycles may remain irregular, become infrequent, or even cease. Consider pregnancy, including ectopic pregnancy, if menstruation does not occur within 6 weeks of the onset of previous menstruation. If a significant change in bleeding develops during prolonged use, conduct diagnostic tests to assess possible endometrial pathology.

Be aware of other serious complications and most common adverse reactions

Some serious complications with IUSs like LILETTA are sepsis, perforation, and expulsion. Severe infection or sepsis, including Group A streptococcal sepsis (GAS), have been reported following insertion of LNG-releasing IUSs. Aseptic technique during insertion of LILETTA is essential to minimize serious infections such as GAS.

Perforation (total or partial, including penetration/embedment of LILETTA in the uterine wall or cervix) may occur, most often during insertion, although the perforation may not be detected until sometime later. Perforation may also occur at any time during use. Perforation may reduce contraceptive efficacy. If perforation is suspected, locate and remove LILETTA as soon as possible. Surgery may be required. Delayed detection or removal of LILETTA in case of perforation may result in migration outside the uterine cavity, adhesions, peritonitis, intestinal perforations, intestinal obstruction, abscesses, and erosion of adjacent viscera. The risk of perforation is increased if inserted in women who have fixed retroverted uteri, are postpartum, or are lactating. Delay LILETTA insertion a minimum of 4 weeks or until uterine involution is complete following a delivery or a second-trimester abortion.

Partial or complete expulsion of LILETTA may occur, resulting in the loss of contraceptive protection. Expulsion risk is increased when inserted immediately after delivery; it appears to be increased with insertions after second-trimester abortion, based on limited data. Risk of expulsion is increased for patients with a history of HMB or greater than normal BMI at the time of insertion. Remove a partially expelled LILETTA. If expulsion has occurred, a new LILETTA may be inserted when there is reasonable certainty the patient is not pregnant.

Ovarian cysts may occur and are generally asymptomatic. Cysts may be accompanied by pelvic or abdominal pain or dyspareunia. Evaluate persistent ovarian cysts.

In the LILETTA contraception study, the most common adverse reactions (≥5% users) were vulvovaginal mycotic infections (20.2%), vaginal bacterial infections (19.2%), acne (15.5%), nausea or vomiting (10.5%), headache (10.1%), breast tenderness or pain (10.1%), abdominal discomfort or pain (10.0%), dyspareunia (9.6%), anxiety (9.6%), depression (9.1%), pelvic discomfort or pain (8.7%), dysmenorrhea (7.3%), mood changes (6.5%), back pain (6.5%), increased weight (6.1%), and vaginal discharge (5.8%). In the LILETTA HMB study, the adverse reaction profile was consistent with the adverse reaction profile in the contraception study.

Teach patients to recognize and immediately report signs or symptoms of the aforementioned conditions. Consider evaluating patients 4 to 6 weeks after LILETTA insertion and during routine care, or more often if clinically indicated. Check threads during each evaluation.

Natrelle^® Breast Implants IMPORTANT SAFETY INFORMATION

INDICATIONS

Natrelle^® Breast Implants are indicated for women for the following:

• Breast augmentation for women at least 22 years old for silicone-filled implants and breast augmentation for women at least 18 years old for saline-filled implants. This includes primary breast augmentation to increase the breast size, as well as revision surgery to correct or improve the result of a primary breast augmentation surgery
• Breast reconstruction. This includes primary reconstruction to replace breast tissue that has been removed due to cancer or trauma or that has failed to develop properly due to a severe breast abnormality. Breast reconstruction also includes revision surgery to correct or improve the result of a primary breast reconstruction surgery

• Women with active infection anywhere in their body
• Women with existing cancer or precancer of their breast who have not received adequate treatment for those conditions
• Women who are currently pregnant or nursing

• See Boxed Warning
• Avoid damage during surgery: Care should be taken to avoid the use of excessive force and to minimize handling of the implant. Forcing of implants through too small an opening or applying concentrated localized pressure on the implants may result in localized weakening of the breast implant shell, potentially leading to shell damage and possible implant rupture. An incision should be of appropriate length to accommodate the style, size, and profile of the implants. Use care when using surgical instruments in proximity with the breast implant
• Follow recommended fill volumes for saline implants to decrease possibility of shell wrinkling and crease-fold failure

• Autoimmune diseases (eg, lupus and scleroderma)
• A compromised immune system (eg, currently receiving immunosuppressive therapy)
• Planned chemotherapy or radiation following breast implant placement
• Conditions or medications that interfere with wound healing and blood clotting
• Reduced blood supply to breast tissue
• Clinical diagnosis of depression or other mental health disorders, including body dysmorphic disorder and eating disorders. Please discuss any history of mental health disorders prior to surgery. Patients with a diagnosis of depression, or other mental health disorders, should wait until resolution or stabilization of these conditions prior to undergoing breast implantation surgery

ADVERSE EVENTS
Possible adverse events with breast implant surgery include implant rupture with silicone implants, implant deflation with saline-filled implants, capsular contracture, reoperation, implant removal, pain, changes in nipple and breast sensation, infection, scarring, asymmetry, wrinkling, implant displacement/migration, implant palpability/visibility, breastfeeding complications, hematoma/seroma, implant extrusion, necrosis, delayed wound healing, infection, breast tissue atrophy/chest wall deformity, calcium deposits, and lymphadenopathy. Other systemic conditions have been reported with breast implants.

For more information, please see the full Directions for Use at www.allergan.com/products.

To report a problem with Natrelle^® Breast Implants, please call Allergan^® at 1-800-624-4261.

The sale and distribution of this device is restricted to users and/or user facilities that provide information to patients about the risks and benefits of this device in the form and manner specified in the approved labeling provided by Allergan^®.

OZURDEX^® (dexamethasone intravitreal implant)

Indications and Usage

Diabetic Macular Edema

OZURDEX^® (dexamethasone intravitreal implant) is a corticosteroid indicated for the treatment of diabetic macular edema.

Retinal Vein Occlusion

OZURDEX^® is a corticosteroid indicated for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).

Posterior Segment Uveitis

OZURDEX^® is indicated for the treatment of noninfectious uveitis affecting the posterior segment of the eye.

Dosage and Administration

FOR OPHTHALMIC INTRAVITREAL INJECTION. The intravitreal injection procedure should be carried out under controlled aseptic conditions. Following the intravitreal injection, patients should be monitored for elevation in intraocular pressure and for endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis without delay.

IMPORTANT SAFETY INFORMATION

Contraindications

Ocular or Periocular Infections: OZURDEX^® (dexamethasone intravitreal implant) is contraindicated in patients with active or suspected ocular or periocular infections including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases.

Glaucoma: OZURDEX^® is contraindicated in patients with glaucoma, who have cup to disc ratios of greater than 0.8.

Torn or Ruptured Posterior Lens Capsule: OZURDEX^® is contraindicated in patients whose posterior lens capsule is torn or ruptured because of the risk of migration into the anterior chamber. Laser posterior capsulotomy in pseudophakic patients is not a contraindication for OZURDEX^® use.

Hypersensitivity: OZURDEX^® is contraindicated in patients with known hypersensitivity to any components of this product.

Warnings and Precautions

Intravitreal Injection‐related Effects: Intravitreal injections, including those with OZURDEX^®, have been associated with endophthalmitis, eye inflammation, increased intraocular pressure, and retinal detachments. Patients should be monitored regularly following the injection.

Steroid‐related Effects: Use of corticosteroids including OZURDEX^® may produce posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses.

Corticosteroids are not recommended to be used in patients with a history of ocular herpes simplex because of the potential for reactivation of the viral infection.

Adverse Reactions

Diabetic Macular Edema

Ocular adverse reactions reported by greater than or equal to 1% of patients in the two combined 3-year clinical trials following injection of OZURDEX^® for diabetic macular edema include: cataract (68%), conjunctival hemorrhage (23%), visual acuity reduced (9%), conjunctivitis (6%), vitreous floaters (5%), conjunctival edema (5%), dry eye (5%), vitreous detachment (4%), vitreous opacities (3%), retinal aneurysm (3%), foreign body sensation (2%), corneal erosion (2%), keratitis (2%), anterior chamber inflammation (2%), retinal tear (2%), eyelid ptosis (2%). Non-ocular adverse reactions reported by greater than or equal to 5% of patients include: hypertension (13%) and bronchitis (5%).

Increased Intraocular Pressure: IOP elevation greater than or equal to 10 mm Hg from baseline at any visit was seen in 28% of OZURDEX^® patients versus 4% of sham patients. 42% of the patients who received OZURDEX^® were subsequently treated with IOP-lowering medications during the study versus 10% of sham patients.

The increase in mean IOP was seen with each treatment cycle, and the mean IOP generally returned to baseline between treatment cycles (at the end of the 6-month period).

Cataracts and Cataract Surgery: The incidence of cataract development in patients who had a phakic study eye was higher in the OZURDEX^® group (68%) compared with Sham (21%). The median time of cataract being reported as an adverse event was approximately 15 months in the OZURDEX^® group and 12 months in the Sham group. Among these patients, 61% of OZURDEX^® subjects versus 8% of sham-controlled subjects underwent cataract surgery, generally between Month 18 and Month 39 (Median Month 21 for OZURDEX^® group and 20 for Sham) of the studies.

Retinal Vein Occlusion and Posterior Segment Uveitis

Adverse reactions reported by greater than 2% of patients in the first 6 months following injection of OZURDEX^® for retinal vein occlusion and posterior segment uveitis include: intraocular pressure increased (25%), conjunctival hemorrhage (22%), eye pain (8%), conjunctival hyperemia (7%), ocular hypertension (5%), cataract (5%), vitreous detachment (2%), and headache (4%).

Increased IOP with OZURDEX^® peaked at approximately week 8. During the initial treatment period, 1% (3/421) of the patients who received OZURDEX^® required surgical procedures for management of elevated IOP.

Please see accompanying full Prescribing Information or visit https://www.rxabbvie.com/pdf/ozurdex_pi.pdf

SkinMedica^® Important Information

Most SkinMedica^® products are intended to meet the FDA's definition of a cosmetic product, an article applied to the human body to cleanse, beautify, promote attractiveness, and alter appearances. These SkinMedica^® products are not intended to be drug products that diagnose, treat, cure, or prevent any disease or condition. These products have not been approved by the FDA and the statements have not been evaluated by the FDA.

TEFLARO^® (ceftaroline fosamil) Injection Important Information

• TEFLARO^® (ceftaroline fosamil) is indicated in adult and pediatric patients (at least 34 weeks gestational age and 12 days postnatal age and older) 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.
• TEFLARO is also indicated in adult and pediatric patients 2 months of age and older 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.
• 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.

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

Warnings and Precautions

• Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported with beta-lactam antibacterial drugs. Before therapy with TEFLARO is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. Maintain clinical supervision if this product is to be given to a penicillin- or other beta-lactam-allergic patient, because cross sensitivity among beta-lactam antibacterial agents has been clearly established.
• If an allergic reaction to TEFLARO occurs, discontinue TEFLARO and institute appropriate treatment and supportive measures.

• Clostridioides 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.

• Neurological adverse reactions have been reported during postmarketing surveillance in patients treated with cephalosporins, including TEFLARO. These reactions include encephalopathy and seizures. Most cases occurred in patients with renal impairment who did not receive appropriate dosage adjustment. The neurological adverse reactions were reversible and resolved after discontinuation of TEFLARO or after hemodialysis. If neurological adverse reactions associated with TEFLARO therapy occur, consider discontinuing TEFLARO or making appropriate dosage adjustments in patients with renal impairment.

• In adults, 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 adult Phase 3 trials.
• In children, seroconversion from a negative to a positive direct Coombs’ test result occurred in 42/234 (17.9%) of patients receiving TEFLARO and 3/93 (3.2%) of patients receiving comparator drugs in the three pooled pediatric 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.

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

• In the four pooled adult Phase 3 clinical trials, serious adverse reactions 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 reactions 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 reactions 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.
• The most common adverse reactions occurring in >2% of patients receiving TEFLARO in the adult pooled Phase 3 clinical trials were diarrhea (5%), nausea (4%), and rash (3%).

• In the three pooled pediatric clinical trials, serious adverse reactions occurred in 10/257 (4%) of patients receiving TEFLARO and 3/102 (3%) of patients receiving comparator drugs. Treatment discontinuation due to adverse reactions occurred in 10/257 (3.9%) of patients receiving TEFLARO and 2/102 (2%) of patients receiving comparator drugs with the most common adverse reaction leading to discontinuation being rash in 2/257 (0.8%) of patients treated with TEFLARO.
• The most common adverse reactions occurring in ≥ 3% of patients receiving TEFLARO in the pooled pediatric clinical trials were diarrhea (8%), rash (7%), vomiting (5%), pyrexia (3%), and nausea (3%).

• 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.

• There have been no adequate and well-controlled studies with TEFLARO in pregnant or nursing women. TEFLARO should only be used if the potential benefit justifies the potential risk in these populations.
• Safety and effectiveness of TEFLARO for the treatment of ABSSSI in pediatric patients less than 34 weeks gestational age and less than 12 days postnatal age have not been established. Safety and effectiveness for the treatment of CABP in pediatric patients below the age of 2 months have not been established as no data are available.
• 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 adult patients with moderate (CrCl >30 to ≤50 mL/min) or severe (CrCl ≥15 to ≤30mL/min) renal impairment and in patients with end-stage renal disease (CrCl <15 mL/min). There is insufficient information to recommend a dosage regimen for pediatric patients with CrCl <50 mL/min/1.73m².
• The pharmacokinetics of ceftaroline in patients with hepatic impairment have not been established.

Please also see full Prescribing Information.