Download Billing and Coding Guide

Billing and
Coding Guide
Updated July 1, 2016
UPDATED INFORMATION:
Please see coding sections for updated
information regarding reimbursement for OTIPRIO.
Please see Indication and Important Safety Information for OTIPRIO
on page 4. Please see accompanying full Prescribing Information.
1
OTIPRIO™ (ciprofloxacin otic suspension) 6%
Disclaimer
This guide is intended solely for educational purposes regarding possible codes that may be available for
OTIPRIO. The information provided contains general reimbursement information only and represents Otonomy’s
understanding of current reimbursement policies as of July 1, 2016. This coding and reimbursement information
is subject to change and may become outdated. Information should not be construed as legal advice nor is it
advice about how to code, complete, bill, or submit any particular claim for payment. It is important to check
with the health plan directly to confirm coverage for individual patients. Information provided is not intended
to increase or maximize reimbursement by any payer.
Otonomy disclaims any responsibility for claims submitted by providers or physicians. The information provided
in this Guide is not a guarantee of coverage in any individual case. It is the provider’s and physician’s responsibility
to determine appropriate codes, charges, and modifiers, and to submit bills for services and products consistent
with what was rendered as well as the patient’s insurer requirements. Third-party payers may have different coverage
and reimbursement policies and coding requirements. Such policies can change over time. Providers are encouraged
to contact third-party payers for each patient to verify specific information on their coding policies. Please see Indication and Important Safety Information for OTIPRIO
on page 4. Please see accompanying full Prescribing Information.
2
Billing and Coding Guide
Contents
OTIPRIO Indications and Important Safety Information. . . . . . . . . . . . . . . . . . 4
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Reimbursement Overview. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Private/Commercial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Medicaid. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Medicare. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Coding for OTIPRIO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
HCPCS Level II Codes for OTIPRIO. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
About Transitional Pass-Through Payment . . . . . . . . . . . . . . . . . . . . . . . . . . 8
National Drug Code (NDC). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Coding for Physician Services . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Potential CPT® Codes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Potential ICD-9-CM and ICD-10-PCS Procedure Codes . . . . . . . . . . . . . . . 9
Coding for the Patient’s Disease/Condition. . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Potential ICD-10-CM Diagnosis Codes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Frequently Asked Questions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Please see Indication and Important Safety Information for OTIPRIO
on page 4. Please see accompanying full Prescribing Information.
3
OTIPRIO™ (ciprofloxacin otic suspension) 6%
INDICATIONS AND USAGE
OTIPRIOTM (ciprofloxacin otic suspension) 6% is a fluoroquinolone antibacterial indicated for the treatment
of pediatric patients with bilateral otitis media with effusion undergoing tympanostomy tube placement.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
OTIPRIO is contraindicated in patients with a history of hypersensitivity to ciprofloxacin, to other quinolones,
or to any of the components of OTIPRIO.
WARNINGS AND PRECAUTIONS
Potential for Microbial Overgrowth: OTIPRIO may result in overgrowth of nonsusceptible bacteria and fungi.
If such infections occur, institute alternative therapy.
ADVERSE REACTIONS
Adverse reactions (incidence at least 3%) that occurred in two Phase 3 trials with OTIPRIO vs sham were:
nasopharyngitis (5% vs 4%), irritability (5% vs 3%), and rhinorrhea (3% vs 2%).
USE IN SPECIFIC POPULATIONS
Pediatric Use: The safety and effectiveness of OTIPRIO in infants below six months of age have not
been established.
Please see accompanying full Prescribing Information.
4
Billing and Coding Guide
Introduction
Otonomy, Inc. has developed this reference guide to provide general billing and coding information related to
OTIPRIO for physician and hospital billing staff when used in the ambulatory surgical center (ASC), hospital
outpatient department (HOPD), or hospital inpatient setting. To assist you in preparing claims, this guide
contains the following:
u
Reimbursement Overview
u
Billing and Coding Information
u
Frequently Asked Questions (FAQs)
Reimbursement Overview
Coverage and coding guidelines for OTIPRIO and its administration will differ by insurer and are updated regularly.
In addition, payment rates may vary by insurer and are frequently established by the provider’s specific contract.
It is a best practice to contact your patient’s health insurance company directly to ensure that you have the
most recent local billing, coding, and coverage policy information, as well as answer any payment inquiries.
Codes allow healthcare providers to communicate with insurance companies to facilitate the reimbursement
process and explain why the patient needed treatment, what drugs and services were provided, and where
services were rendered. Coding guidelines may differ by insurer and are often updated regularly to reflect the
addition and deletion of applicable codes. The following table provides an overview of the different codes
and their description that may be applicable when billing for items and services related to OTIPRIO.
Code Set
Description/Purpose
CPT®1 Codes
(Level I HCPCS Codes)
Numeric coding system used to report medical services and procedures provided by healthcare professionals;
includes CPT® E/M codes, which are numeric codes used to report office visit services provided by physicians
HCPCS Level II Codes
Alpha-numeric coding system used to report specific drugs, supplies, and other healthcare equipment
ICD-9-CM/ICD-10-CM
Diagnosis Codes
Numeric and alpha-numeric codes used to report diagnosis
ICD-9-CM/ICD-10-PCS
Procedure Codes
Numeric and alpha-numeric codes used to report procedures, services, devices, and drugs in acute-care
hospitals and other facility-based settings
NDC
Numeric product identifier used to report human drugs
Revenue Codes
Numeric codes used by hospitals to report services and supplies to specific cost centers
Legend
CPT®: Current Procedural Terminology
HCPCS: Healthcare Common Procedure Coding System
ICD-9-CM: International Classification of Diseases, 9th Revision, Clinical Modification
ICD-10-CM: International Classification of Diseases, 10th Revision, Clinical Modification
ICD-10-PCS: International Classification of Diseases, 10th Revision, Procedure Coding System
NDC: National Drug Code
CPT® copyright 2014 American Medical Association. All rights reserved.
CPT® is a registered trademark of the American Medical Association.
1
Please see Indication and Important Safety Information for OTIPRIO
on page 4. Please see accompanying full Prescribing Information.
5
OTIPRIO™ (ciprofloxacin otic suspension) 6%
In addition, coverage and payment will also vary based on individual patient insurance parameters and provider
contracts. An overview of the major insurer types is provided below.
Private/ Commercial
Private insurance coverage policies for OTIPRIO and its administration may vary. Each private insurer determines
its own coverage policies for drugs and procedures. In addition, most insurers offer multiple plans; coverage for
procedures and/or drugs may vary depending on the details of that exact plan.
Medicaid
In general, state Medicaid programs will cover drugs for their FDA-approved indications. It will be important to
understand your state Medicaid program’s specific coverage criteria for OTIPRIO and its administration as each
state’s Medicaid agency determines its own coverage and payment policies. Medicaid recipients may also have
the opportunity to enroll in managed care organizations (MCOs) offered in a particular state. Typically, Managed
Medicaid guidelines for coverage are similar to private or commercial insurers and often vary by plan.
Medicare
Traditional or fee-for-service Medicare consists of beneficiaries who receive their medical benefits through
the following:
u Medicare
Part A: Inpatient services, hospitalizations, hospice care, skilled nursing facility stays, and some
home health services
u Medicare
Part B: Physician and outpatient services, durable medical equipment (DME), and some home
health care, laboratory service
Currently, there is no Medicare national coverage determination (NCD) for OTIPRIO. As with most Part B
covered drugs, local Medicare contractors have the discretion to develop local coverage determinations
(LCDs) if necessary.
Formal published guidelines may be developed for certain products and procedures when insurers are concerned
about appropriate utilization and costs; published policies regarding coverage for OTIPRIO may not be available.
Contacting each patient’s insurance company to understand the specific guidelines for OTIPRIO is recommended.
Please see Indication and Important Safety Information for OTIPRIO
on page 4. Please see accompanying full Prescribing Information.
6
Billing and Coding Guide
Coding for OTIPRIO
Regardless of the setting of care in which the drug was administered, most payers require providers to list
an HCPCS code and the NDC code on the claim form when billing for a particular drug.
HCPCS Level II Codes for OTIPRIO
Most payers recognize Healthcare Common Procedure Coding System (HCPCS) Level II national codes to
identify and report drugs.
Effective July 1, 2016, the Centers for Medicare & Medicaid Services (CMS) granted transitional pass-through
status for OTIPRIO. When pass-through status is granted, CMS creates a unique HCPCS code, or “C-Code,”
which billers can use to identify the drug on the claim form. For more information on pass-through payment,
please see page 8.
HCPCS Code
Description
C9479*
Instillation, ciprofloxacin otic suspension, 6 mg
J3490†
Unclassified drugs
*Note on reporting C9479: Each vial of C9479 contains 60 mg. If one single-use vial is used for both patient’s ears with the remainder of the drug in the vial
unused, then two units of C9479 should be reported on the claim form as administered to the patient; any discarded amount should be reported with the
JW modifier according to the Medicare Claims Processing Manual, Chapter 17, Drugs and Biologicals; Section 40, Discarded Drugs and Biologicals.
†Note on reporting J3490: If the patient’s insurer does not accept C9479, you may need to report OTIPRIO using J3490. Report only one unit of J3490
on the claim form per single-patient use vial. Do not bill wastage.
Please consult payer-specific guidelines for the appropriate code to use for OTIPRIO to communicate which
drug was provided and how much was administered.
Please see Indication and Important Safety Information for OTIPRIO
on page 4. Please see accompanying full Prescribing Information.
7
OTIPRIO™ (ciprofloxacin otic suspension) 6%
About Transitional Pass-Through Payment
Transitional pass-through status is a temporary payment policy granted by the Centers for Medicare & Medicaid
Services (CMS), the federal agency that administers the Medicare program. When a drug is granted pass-through
status by CMS, ambulatory surgery centers and other outpatient facilities are eligible to receive separate payment
for the drug, in addition to the payment received for the patient encounter for Medicare patients. Pass-through
status remains in effect for 2 to 3 years.
When pass-through status is granted, CMS creates a temporary, unique Healthcare Common Procedure Coding
System (HCPCS) code, or “C-Code,” which billers use to identify the drug on the claim form.
Pass-through status is applicable to Medicare patients only. However, some Medicaid and commercial plans may
allow providers that treat non-Medicare patients to use the C-Code when billing, in lieu of an unlisted “J-Code”
– and even more, some may recognize Medicare’s pass-through status policy and allow for separate payment for
drugs with pass-through status which would otherwise not be allowed separate reimbursement.
Ambulatory surgery centers (ASCs) and other hospital outpatient departments (HOPDs) may be eligible to receive
separate payment for OTIPRIO, in addition to the payment received for the patient encounter when providers bill
for OTIPRIO using HCPCS code C9479.
National Drug Code (NDC)
The FDA and the manufacturer assign drugs/biologics a unique, 3-segment number, known as the National Drug
Code (NDC). Many NDCs (including the one assigned to OTIPRIO) are displayed in a 10-digit format on the
FDA-approved product labelling. Proper billing for most payers or electronic data interchange systems requires
that the NDC be submitted in the 11-digit numeric 5-4-2 format (ie, 55555-4444-22). Converting a 10-digit NDC
to 11-digit format requires a strategically placed zero preceding the section that does not comply with the
5-4-2 format. Do not use hyphens when entering the actual data on your claim.
For example:
10-Digit Format
OTIPRIO
10-Digit NDC
11-Digit Format
OTIPRIO
11-Digit NDC
Reporting on
claim form
5-3-2
69251-201-01
5-4-2
69251-0201-01
69251020101
Please see Indication and Important Safety Information for OTIPRIO
on page 4. Please see accompanying full Prescribing Information.
8
Billing and Coding Guide
Coding for Physician Services
Coding procedures may vary depending on the setting of care. In the physician office, HOPD, and ASC, CPT® codes
are used to describe procedures. In the hospital inpatient department, billers are required to use ICD-10-PCS codes
to bill for procedures.
Potential CPT® Codes
Current Procedural Terminology (CPT®) codes are used to identify professional services (ie, drug administration).
According to the CPT® instructions for use of the CPT® codebook, select the name of the procedure or service that
accurately identifies the service performed. Do not select a CPT® code that merely approximates the service provided.
When provided during tube placement surgery, the administration of OTIPRIO is considered inclusive of the primary
procedure and therefore not coded separately. Providers should use the appropriate tympanostomy CPT® code that
best describes the services provided. Also, when performed bilaterally, report with modifier 50.
CPT® Code
Description
69433
Tympanostomy (requiring insertion of ventilating tube), local or topical anesthesia
69436
Tympanostomy (requiring insertion of ventilating tube), general anesthesia
Potential ICD-9-CM and ICD-10-PCS Procedure Codes
ICD-9-CM and ICD-10-PCS codes are typically used to bill for procedures performed on inpatients. Effective
October 1, 2015, all Health Insurance Portability and Accountability Act (HIPAA)-covered entities were required
to transition from the ICD-9-CM coding system and bill procedures using ICD-10-PCS.
There is no category-specific code for drugs administered via intratympanic administration. Hospitals may
therefore choose the code that best describes the procedure. Below is a list of the existing ICD-9-CM code and
the ICD-10-PCS Crosswalk that may be applicable for describing the administration of OTIPRIO when administered
during tube placement surgery.
ICD-9-CM Procedure Code
ICD-10-PCS
3E0B7GC Introduction of other therapeutic substance into ear, via natural or artificial opening
20.94 Injection of tympanum
3E0B3GC Introduction of other therapeutic substance into ear, percutaneous approach
3E0BXGC Introduction of other therapeutic substance into ear, external approach
099500Z Drainage of right middle ear with drainage device, open approach
20.01 Myringotomy with
insertion of tube
099600Z Drainage of left middle ear with drainage device, open approach
099770Z Drainage of right tympanic membrane with drainage device, via natural or artificial opening
099870Z Drainage of left tympanic membrane with drainage device, via natural or artificial opening
Please see Indication and Important Safety Information for OTIPRIO
on page 4. Please see accompanying full Prescribing Information.
9
OTIPRIO™ (ciprofloxacin otic suspension) 6%
Coding for the Patient’s Disease/Condition
Potential ICD-10-CM Diagnosis Codes
ICD-10-CM diagnosis codes are used to report diseases and conditions and identify why a patient needs treatment.
OTIPRIO is indicated for the treatment of pediatric patients with bilateral otitis media with effusion undergoing
tympanostomy tube placement. The following ICD-9-CM diagnosis codes and the equivalent ICD-10-CM crosswalk
below are examples of some codes that may be appropriate to describe a patient’s chief complaint.
Diagnosis Code System
Code
Description
ICD-9-CM
381.00
Acute nonsuppurative otitis media, unspecified
ICD-9-CM
382.00
Acute suppurative otitis media without spontaneous rupture of ear drum
ICD-10-CM
H65.191–H65.199
Other acute nonsuppurative otitis media
ICD-10-CM
H66.001–H66.009
Acute suppurative otitis media without spontaneous rupture of ear drum
Please see Indication and Important Safety Information for OTIPRIO
on page 4. Please see accompanying full Prescribing Information.
10
Billing and Coding Guide
Frequently Asked Questions
Q1: What HCPCS code do I use to bill for OTIPRIO?
Effective July 1, 2016, the Centers for Medicare & Medicaid Services (CMS) granted transitional pass-through status
for OTIPRIO. When pass-through status is granted, CMS creates a unique Healthcare Common Procedure Coding
System (HCPCS) code, or “C-Code,” which billers can use to identify the drug on the claim form. Some insurers
will not accept C-Codes and require providers to bill using an unclassified HCPCS code or “unlisted J-Code” when
a permanent “J-Code” is not available. These coding options are available on page 7 of the billing and coding guide.
Please consult payer-specific guidelines for the appropriate code to use for OTIPRIO to communicate which drug
was provided and how much was administered.
Q2: My patient’s insurer won’t allow me to bill using the OTIPRIO C-Code and says I must bill using
the unclassified HCPCS drug code J3490. What else do I need to know about coding OTIPRIO with
an unclassified HCPCS drug code?
OTIPRIO was approved in 2015. Not all insurers will be familiar with OTIPRIO. Hence, the product may be billed
using an unclassified drug code until OTIPRIO is assigned its own product-specific code.2 The patient’s insurer may
need more information if they are unfamiliar with OTIPRIO; therefore, the provider’s billing staff should be prepared
to submit the following information if requested:
u
Drug name (brand/generic)
u
Route of administration
u
Drug strength and dosage
u
11-digit National Drug Code (NDC)
u
Customized letter of medical necessity
u
Invoice
u
FDA approval letter
u
Package insert
u
Chart notes
u
Laboratory test results
u Patient
u
medical history and documentation of medical necessity
Prior therapies
u Supporting
peer-reviewed medical journals and other clinical literature
Unclassified codes do not have “unit values” and are generally reported as “1 Unit” on the claim form or its electronic equivalent,
regardless of the amount of drug administered. Check payer guidelines for appropriate reporting of units for an unclassified code.
2
Please see Indication and Important Safety Information for OTIPRIO
on page 4. Please see accompanying full Prescribing Information.
11
OTIPRIO™ (ciprofloxacin otic suspension) 6%
Frequently Asked Questions (cont.)
Q3: What CPT® code do I use to bill for the administration of OTIPRIO in the ASC or HOPD?
When provided during tube placement surgery, the administration of OTIPRIO is considered inclusive of the
primary procedure and therefore not coded separately. Providers should use the appropriate tympanostomy
CPT® code (69433 or 69436) that best describes the services provided. Also, when performed bilaterally,
report with modifier 50.
It is important to remember that insurers’ billing and coding guidelines may vary. Please contact the patient’s
insurer if you have any questions related to coding.
Q4: How do I know if OTIPRIO is covered for my patient?
Otonomy does not anticipate that many payers will develop a formal policy regarding coverage for OTIPRIO.
In general, it is a good rule of thumb to contact each payer to verify coverage parameters prior to the procedure.
Q5: What is the reimbursement for OTIPRIO?
Reimbursement for OTIPRIO will be based on the contracted arrangement between the provider and the payer.
Please contact your patient’s insurer for specific information on payment rates and to understand how OTIPRIO
is reimbursed.
Please see Indication and Important Safety Information for OTIPRIO
on page 4. Please see accompanying full Prescribing Information.
12
For additional support or questions,
please visit www.OTIPRIO.com or contact
by e-mail at [email protected]
or by phone at 1-800-826-6411.
©2016 Otonomy, Inc. All rights reserved.
OTIPRIO is a trademark of Otonomy, Inc.
1-OTI16039-v1
Please see Indication and Important Safety Information for OTIPRIO
on page 4. Please see accompanying full Prescribing Information.
13
HIGHLIGHTS OF PRESCRIBING INFORMATION
----------------------DOSAGE FORMS AND STRENGTHS--------------------
These highlights do not include all the information needed to use OTIPRIO
safely and effectively. See full prescribing information for OTIPRIO.
Otic Suspension: Each OTIPRIO vial contains 1 mL of 6% (60 mg/mL) ciprofloxacin
otic suspension. (3)
------------------------------CONTRAINDICATIONS---------------------------
OTIPRIOTM (ciprofloxacin otic suspension), for intratympanic use
OTIPRIO is contraindicated in patients with a history of hypersensitivity to
ciprofloxacin, to quinolones, or to any component of OTIPRIO. (4)
Initial U.S. Approval: 1987
---------------------------INDICATIONS AND USAGE--------------------------
------------------------WARNINGS AND PRECAUTIONS----------------------
OTIPRIO is a fluoroquinolone antibacterial indicated for the treatment of pediatric
patients with bilateral otitis media with effusion undergoing tympanostomy tube
placement. (1)
Potential for Microbial Overgrowth: OTIPRIO may result in overgrowth of
non-susceptible bacteria and fungi. (5.1)
-----------------------DOSAGE AND ADMINISTRATION----------------------
------------------------------ADVERSE REACTIONS---------------------------
· OTIPRIO is for intratympanic administration only. (2.1)
The most frequently occurring adverse reactions (with an incidence rate greater
than 3%) were nasopharyngitis and irritability. (6.1)
· OTIPRIO is intended for single-patient use with two 0.1 mL doses available
in each vial. (2.1)
To report SUSPECTED ADVERSE REACTIONS, contact Otonomy at 1-800-826-6411
or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
· Administer OTIPRIO as a single intratympanic administration of one 0.1 mL
(6 mg) dose into each affected ear, following suctioning of the middle ear
effusion. (2.1)
See 17 for PATIENT COUNSELING INFORMATION.
· See Full Prescribing Information for directions for OTIPRIO dose preparation.
(2.2)
Revised: 12/2015
11
12
FULL PRESCRIBING INFORMATION: CONTENTS*
1
2
3
4
5
6
8
INDICATIONS AND USAGE
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS
5.1 Potential for Microbial Overgrowth
ADVERSE REACTIONS
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
13
14
16
17
DESCRIPTION
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.3 Pharmacokinetics
12.4 Microbiology
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
CLINICAL STUDIES
HOW SUPPLIED/STORAGE AND HANDLING
PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information are not listed.
1
FULL PRESCRIBING INFORMATION
3
1
Otic Suspension: Each 1 mL of OTIPRIO contains a white, preservative-free, sterile
otic suspension consisting of 6% (60 mg/mL) ciprofloxacin in a single-patient use
glass vial.
INDICATIONS AND USAGE
OTIPRIO is indicated for the treatment of pediatric patients with bilateral otitis
media with effusion undergoing tympanostomy tube placement.
4
DOSAGE FORMS AND STRENGTHS
CONTRAINDICATIONS
2
DOSAGE AND ADMINISTRATION
2.1
Dosage and Important Administration Instructions
·
·
·
OTIPRIO is for intratympanic administration only.
OTIPRIO is intended for single-patient use, discard unused portion.
Administer OTIPRIO as a single intratympanic administration of one 0.1 mL
(6 mg) dose into each affected ear, following suctioning of middle ear
effusion.
5
WARNINGS AND PRECAUTIONS
5.1
Potential for Microbial Overgrowth
2.2
Preparation of OTIPRIO
6
ADVERSE REACTIONS
6.1
Clinical Trials Experience
OTIPRIO is contraindicated in patients with a history of hypersensitivity to
ciprofloxacin, to other quinolones, or to any of the components of OTIPRIO.
OTIPRIO may result in overgrowth of nonsusceptible bacteria and fungi. If such
infections occur, institute alternative therapy.
Directions for OTIPRIO dose preparation and handling is illustrated in Figure 1
below.
Because clinical studies are conducted under widely varying conditions,
adverse reaction rates observed in the clinical studies of a drug cannot be directly
compared to rates in the clinical studies of another drug and may not reflect the
rates observed in practice.
In two randomized, sham-controlled Phase 3 clinical trials, 530 pediatric patients
with bilateral otitis media with effusion undergoing tympanostomy tube placement
were treated with OTIPRIO or sham administered intra-operatively as a single
dose. The median age of the pediatric patients enrolled in the clinical trials was
1.5 years; 62% of patients were 6 months through 2 years of age and 38% of
patients were greater than 2 years of age.
Adverse reactions that occurred in at least 3% of OTIPRIO patients and at an
incidence greater than sham are presented in Table 1.
Figure 1: Directions for OTIPRIO Dose Preparation
STEP 1 Preparation
Materials needed:
1 vial of OTIPRIO (enough for 2 doses); Two 1 mL
luer lock syringes; Two 18G-21G preparation
needles; Two 20-24G, 2-3 inch blunt, flexible
administration needles; Alcohol pads; Optional:
ice pack and drape to keep OTIPRIO vial cold
Keep product cold during preparation. If
OTIPRIO thickens during preparation, place
the vial back in refrigeration.
Table 1:
Adverse Reactions
STEP 2 OTIPRIO Mixing
To keep the vial cold during shaking, hold
the OTIPRIO vial by the aluminum seal to
prevent gelation. Shake the vial for 5 to
8 seconds to mix well until a visually
homogenous suspension is obtained.
Always hold the vial by the aluminum
seal to prevent gelation.
Nasopharyngitis
Irritability
Rhinorrhea
OTIPRIO
(N=357)
Sham
(N=173)
5%
5%
3%
4%
3%
2%
8
USE IN SPECIFIC POPULATIONS
8.1
Pregnancy
Risk Summary
Animal reproduction studies have not been conducted with OTIPRIO. No adequate
and well-controlled studies have been performed in pregnant women. Because
of the negligible systemic exposure associated with clinical administration of
OTIPRIO, this product is expected to be of minimal risk for maternal and fetal
toxicity when administered to pregnant women.
STEP 3 OTIPRIO Removal
Using an 18-21G needle, withdraw 0.3 mL
of the suspension into the 1 mL syringe.
8.2
STEP 4 Replace with the Administration Needle
Replace the needle with a 20-24G, 2-3 inch blunt,
flexible needle to be used for administration.
Lactation
Risk Summary
Ciprofloxacin is excreted in human milk with systemic administration. However,
because of the negligible systemic exposure after otic application, nursing infants
of mothers receiving OTIPRIO should not be affected.
8.4
Pediatric Use
The safety and effectiveness of OTIPRIO in infants below six months of age have
not been established.
The safety and effectiveness of OTIPRIO was established in 530 pediatric patients
with bilateral otitis media with middle ear effusion undergoing myringotomy with
tympanostomy tube placement. The median age of patients enrolled in the
clinical trials was 1.5 years; 62% of patients were 6 months through 2 years of
age and 38% of patients were greater than 2 years of age [see Adverse Reactions
(6.1) and Clinical Studies (14)].
STEP 5 Priming the Syringe
Prime the needle leaving a dose of
0.1 mL (0.1 cc).
STEP 6 Preparing Second Dose
for Bilateral Administration Only
Repeat Steps 3, 4, and 5 using the
same vial to prepare a second
syringe for the other ear and dispose
of the vial.
Use a different syringe for each ear.
After preparation, syringes can be kept
at room temperature or in the refrigerator
prior to administration.
Keep syringes on their side.
Discard syringes if not administered in 3 hours.
Adverse Reactions in Phase 3 Trials
11
DESCRIPTION
OTIPRIO (ciprofloxacin otic suspension) 6% contains the synthetic fluoroquinolone
antibacterial, ciprofloxacin. OTIPRIO is for intratympanic administration. OTIPRIO
is supplied as a white, preservative-free, sterile otic suspension of 6% (w/v)
ciprofloxacin in a neutral pH, buffered, isotonic solution in a single-patient use
glass vial with a rubber stopper containing 1 mL. The inactive ingredients are
poloxamer 407, sodium chloride, tromethamine, hydrochloric acid and water for
injection (WFI).
The thermosensitive suspension exists as a liquid at room temperature or below
and gels when warmed [see How Supplied/Storage and Handling (16)].
2
Fertility studies performed in rats at oral doses of ciprofloxacin up to
100 mg/kg/day revealed no evidence of impairment. This would be
approximately 80 times the maximum recommended clinical dose of ototopical
ciprofloxacin based upon body surface area, assuming total absorption of
ciprofloxacin from the ear of a patient treated with OTIPRIO.
Ciprofloxacin has the following nomenclature:
1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic
acid. Its empirical formula is C17H18FN3O3 and its molecular weight is 331.3.
Its chemical structure is as follows:
13.2 Animal Toxicology and/or Pharmacology
Guinea pigs dosed in the middle ear with OTIPRIO exhibited no drug-related
structural or functional changes of the cochlear hair cells.
14
Figure 2: Structure of Ciprofloxacin
12
CLINICAL STUDIES
Two randomized, multicenter, controlled clinical trials in 532 pediatric
patients with bilateral otitis media with effusion undergoing myringotomy
with tympanostomy tube placement evaluated the safety and efficacy of
OTIPRIO when administered intra-operatively as a single dose. The median age
of patients enrolled in the clinical trials was 1.5 years; 62% of patients were
6 months through 2 years of age and 38% of patients were greater than 2 years
of age. The efficacy endpoint for both trials was the cumulative proportion of
study treatment failures through Day 15, defined as the occurrence of any of the
following events: otorrhea as determined by a blinded assessor on or after 3 days
post-surgery, otic or systemic antibacterial drug use for any reason any time
post-surgery, as well as patients who missed visits or were lost-to-follow-up.
Table 2 presents the results from each Phase 3 trial.
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Ciprofloxacin is a fluoroquinolone antibacterial [see Microbiology (12.4)].
12.3 Pharmacokinetics
The plasma concentration of ciprofloxacin following bilateral administration of
0.1 mL OTIPRIO was not measured.
Table 2: Cumulative Proportion of Treatment Failures Through Day 15 in
Phase 3 Trials
12.4 Microbiology
Mechanism of Action
The bactericidal action of ciprofloxacin results from interference with the enzyme
DNA gyrase, which is needed for the synthesis of bacterial DNA.
Trial 1 (N=266)
OTIPRIO Sham
Resistance
Bacterial resistance to fluoroquinolones can develop through chromosomallyor plasmid-mediated mechanisms. In vitro studies demonstrated cross-resistance
between ciprofloxacin and some fluoroquinolones. There is generally no crossresistance between ciprofloxacin and other classes of antibacterial agents, such
as beta-lactams or aminoglycosides.
Treatment Failure
Difference
(Sham –
OTIPRIO)
(95% CI)
25%
45%
20%
21%
45%
24%
(44/179) (39/87) (8%, 32%)2 (38/178) (40/88) (12%, 36%)2
Reason for Failure1
Antimicrobial Activity
Ciprofloxacin has been shown to be active against most isolates of the following
bacteria:
Gram-positive Bacteria
Staphylococcus aureus
Streptococcus pneumoniae
Gram-negative Bacteria
Haemophilus influenzae
Moraxella catarrhalis
Pseudomonas aeruginosa
13
Trial 2 (N=266)
Difference
(Sham – OTIPRIO Sham
OTIPRIO)
(95% CI)
Otorrhea
7%
11%
7%
27%
Otic antibacterial
drugs
6%
17%
5%
8%
Systemic
antibacterial drugs
2%
5%
3%
3%
Lost-to-follow-up
and missed visit
10%
11%
6%
7%
1 the earliest occurring treatment failure event, and patients were classified as
a treatment failure due only to that component for the remainder of the study
2 P-value <0.001 for Cochran-Mantel-Haenszel test (adjusted for age-group)
NONCLINICAL TOXICOLOGY
Administration of OTIPRIO did not lead to impairment in hearing function, middle
ear function or tube patency by Day 29.
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Eight in vitro mutagenicity tests have been conducted with ciprofloxacin, and the
test results are listed below:
Salmonella/Microsome Test (Negative)
Escherichia coli DNA Repair Assay (Negative)
Mouse Lymphoma Cell Forward Mutation Assay (Positive)
Chinese Hamster V79 Cell HGPRT Test (Negative)
Syrian Hamster Embryo Cell Transformation Assay (Negative)
Saccharomyces cerevisiae Point Mutation Assay (Negative)
Saccharomyces cerevisiae Mitotic Crossover and Gene Conversion Assay
(Negative)
Rat Hepatocyte DNA Repair Assay (Positive)
16
HOW SUPPLIED/STORAGE AND HANDLING
OTIPRIO is a sterile, preservative-free, otic suspension of 6% (60 mg/mL, w/v)
ciprofloxacin in a neutral pH buffered, isotonic solution containing poloxamer 407.
Each OTIPRIO carton contains 1 mL of 6% (60 mg/mL, w/v) ciprofloxacin in a 2 mL
single-patient use glass vial fitted with a rubber stopper. (NDC-69251-201-01)
OTIPRIO should be stored at 2 to 8°C (36 to 46°F) until prior to use to prevent
thickening during preparation. Protect from light. Store in the original carton
until dose preparation.
17
PATIENT COUNSELING INFORMATION
Advise patients and their caregiver(s) that there may be drainage from the ear
the first few days following ear tube surgery, but if the ear becomes painful, or
continuous ear discharge is noted, or the patient develops a fever, advise patients
and their caregiver(s) to consult their physician.
Thus, 2 of the 8 in vitro tests were positive, but results of the following 3 in vivo
test systems gave negative results:
Rat Hepatocyte DNA Repair Assay
Micronucleus Test (Mice)
Dominant Lethal Test (Mice)
Distributed by:
Otonomy, Inc.
San Diego, CA 92121
www.otiprio.com
OTIPRIOTM is a Trademark of Otonomy.
Long-term carcinogenicity studies in mice and rats have been completed for
ciprofloxacin. After daily oral doses of 750 mg/kg in mice and 250 mg/kg in rats
(for mice and rats respectively, approximately 300 and 200 times the maximum
recommended clinical dose of ototopical ciprofloxacin based upon body surface
area, assuming total absorption of ciprofloxacin from the ear of a patient treated
with OTIPRIO) were administered for up to 2 years, there was no evidence that
ciprofloxacin had any carcinogenic or tumorigenic effects in these species.
U.S. Patent Nos: 8,318,817 and 9,205,048
1-OTI15193
3