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DORIBAX (doripenem for injection ) Powder, For Solution for Intravenous

2015-06-13 01:08:13 来源: 作者: 【大中小】浏览:988次评论:0条

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use DORIBAX ® safely and effectively. See full prescribing information for DORIBAX ® .
DORIBAX ® (doripenem for injection ) Powder, For Solution for Intravenous use
Initial U.S. Approval: 2007

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Doribax and other antibacterial drugs, Doribax should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. (12.4)
RECENT MAJOR CHANGES

Warnings and Precautions
• Increased Mortality in Ventilator-Associated Bacterial Pneumonia(5.1)
• Seizures (5.2)

01/2014
04/2013

INDICATIONS AND USAGE

DORIBAX® is a penem antibacterial indicated in the treatment of the following infections caused by designated susceptible bacteria:

Complicated intra-abdominal infections (1.1)
Complicated urinary tract infections, including pyelonephritis (1.2)

DOSAGE AND ADMINISTRATION

500 mg every 8 hours by intravenous infusion administered over one hour for patients ≥18 years of age. (2.1)
Dosage in patients with impaired renal function (2.2):

CrCl (mL/min)	Recommended Dose of DORIBAX®
> 50	No dosage adjustment necessary
≥ 30 to ≤ 50	250 mg IV (over 1 hour) every 8 hours
> 10 to < 30	250 mg IV (over 1 hour) every 12 hours

DOSAGE FORMS AND STRENGTHS

250 mg single use vial, 500 mg single use vial (3)
CONTRAINDICATIONS

Patients with known serious hypersensitivity to doripenem or to other drugs in the same class or patients who have demonstrated anaphylactic reactions to beta-lactams (4)
WARNINGS AND PRECAUTIONS

Increased mortality in ventilator-associated bacterial pneumonia patients. Doripenem is not indicated for ventilator-associated bacterial pneumonia (5.1)
Serious hypersensitivity (anaphylactic) reactions have been reported with carbapenems and other beta-lactams (5.2)
Seizures have been reported with carbapenems, including doripenem (5.3)
It has been shown that co-administration of DORIBAX® with valproic acid reduces the serum concentration of valproic acid. Patients with seizure disorders controlled with valproic acid or sodium valproate will therefore be at an increased risk for breakthrough seizures. (5.4)
Clostridium difficile-associated diarrhea (ranging from mild diarrhea to fatal colitis): eva luate if diarrhea occurs (5.5)

ADVERSE REACTIONS

Most common adverse reactions (≥ 5%) are headache, nausea, diarrhea, rash and phlebitis.(6)

To report SUSPECTED ADVERSE REACTIONS, contact Shionogi Inc. at 1-800-849-9707 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Interacting Drug	Interaction
Valproic acid	Doripenem reduced the serum concentrations of valproic acid to below the therapeutic concentration range in healthy subjects (7.1)
Probenecid	Reduces renal clearance of doripenem, resulting in increased doripenem concentrations (7.2, 12.3)
Drugs metabolized by cytochrome P450 enzymes	Doripenem neither inhibits nor induces major cytochrome P450 enzymes (12.3)

USE IN SPECIFIC POPULATIONS

Dosage adjustment is required in patients with moderately or severely impaired renal function (2.2, 12.3)
DORIBAX® has not been studied in pediatric patients. (8.4)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 2/2014

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

1.1 Complicated Intra-Abdominal Infections

1.2 Complicated Urinary Tract Infections, Including Pyelonephritis

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

2.2 Patients with Renal Impairment

2.3 Preparation of Solutions

2.4 Compatibility

2.5 Storage of Constituted Solutions

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Increased Mortality in Ventilator-Associated Bacterial Pneumonia

5.2 Hypersensitivity Reactions

5.3 Seizures

5.4 Interaction with Valproic Acid

5.5 Clostridium difficile-Associated Diarrhea

5.6 Development of Drug-Resistant Bacteria

5.7 Pneumonitis with Inhalational Use

6 ADVERSE REACTIONS

6.1 Adverse Reactions from Clinical Trials

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Valproic Acid

7.2 Probenecid

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Patients with Renal Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

12.4 Microbiology

13 NON-CLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility

14 CLINICAL STUDIES

14.1 Complicated Intra-Abdominal Infections

14.2 Complicated Urinary Tract Infections, Including Pyelonephritis

15 REFERENCES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

*: Sections or subsections omitted from the full prescribing information are not listed.

1 INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of DORIBAX® and other antibacterial drugs, DORIBAX® should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting and modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

1.1 Complicated Intra-Abdominal Infections

DORIBAX® (doripenem for injection) is indicated as a single agent for the treatment of complicated intra-abdominal infections caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides caccae, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Streptococcus intermedius, Streptococcus constellatus and Peptostreptococcus micros.

1.2 Complicated Urinary Tract Infections, Including Pyelonephritis

DORIBAX® (doripenem for injection) is indicated as a single agent for the treatment of complicated urinary tract infections, including pyelonephritis caused by Escherichia coli including cases with concurrent bacteremia, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Acinetobacter baumannii.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

The recommended dosage of DORIBAX® is 500 mg administered every 8 hours by intravenous infusion over one hour in patients ≥18 years of age. The recommended dosage and administration by infection is described in Table 1:

Table 1: Dosage of DORIBAX® by Infection
* Duration includes a possible switch to an appropriate oral therapy, after at least 3 days of parenteral therapy, once clinical improvement has been demonstrated. † Duration can be extended up to 14 days for patients with concurrent bacteremia.
Infection	Dosage	Frequency	Infusion Time (hours)	Duration
Complicated intra-abdominal infection	500 mg	every 8 hours	1	5–14 days*
Complicated UTI, including pyelonephritis	500 mg	every 8 hours	1	10 days* †

2.2 Patients with Renal Impairment

Table 2: Dosage of DORIBAX® in Patients with Renal Impairment
* [see Preparation of 250 mg DORIBAX ® dose using the 250 mg vial and Preparation of 250 mg DORIBAX ® dose using the 500 mg vial ( 2.3)]
Estimated CrCl (mL/min)	Recommended Dosage Regimen of DORIBAX®
> 50	No dosage adjustment necessary
≥ 30 to ≤ 50	250 mg* administered intravenously (over 1 hour) every 8 hours
> 10 to < 30	250 mg* administered intravenously (over 1 hour) every 12 hours

The following formula may be used to estimate CrCl. The serum creatinine used in the formula should represent a steady state of renal function.

Males: Creatinine clearance (mL/min) =	weight (kg) × (140 - age in years) 72 × serum creatinine (mg/dL)
Females: Creatinine clearance (mL/min) =	0.85 × value calculated for males

DORIBAX® is hemodialyzable; however, there is insufficient information to make dose adjustment recommendations in patients on hemodialysis.

2.3 Preparation of Solutions

DORIBAX® does not contain a bacteriostatic preservative. Aseptic technique must be followed in preparation of the infusion solution.

To prepare DORIBAX® infusions in Baxter Minibag Plus™ infusion bags consult the infusion bag manufacturer's instructions.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to use whenever solution and container permit. DORIBAX® infusions range from clear, colorless solutions to solutions that are clear and slightly yellow. Variations in color within this range do not affect the potency of the product.

Preparation of 500 mg DORIBAX® dose using the 500 mg vial

Constitute the 500 mg vial with 10 mL of sterile water for injection or 0.9% sodium chloride injection (normal saline) and gently shake to form a suspension. The resultant concentration is approximately 50 mg/mL. CAUTION: THE CONSTITUTED SUSPENSION IS NOT FOR DIRECT INJECTION.
Withdraw the suspension using a syringe with a 21 gauge needle and add it to an infusion bag containing 100 mL of normal saline or 5% dextrose; gently shake until clear. The final infusion solution concentration is approximately 4.5 mg/mL.

Preparation of 250 mg DORIBAX® dose using the 250 mg vial

Constitute the 250 mg vial with 10 mL of sterile water for injection or 0.9% sodium chloride injection (normal saline) and gently shake to form a suspension. The resultant concentration is approximately 25 mg/mL. CAUTION: THE CONSTITUTED SUSPENSION IS NOT FOR DIRECT INJECTION.
Withdraw the suspension using a syringe with a 21 gauge needle and add it to an infusion bag containing either 50 or 100 mL of normal saline or 5% dextrose; gently shake until clear. The final infusion solution concentration is approximately 4.2 mg/mL (50 mL infusion bag) or approximately 2.3 mg/mL (100 mL infusion bag).

Preparation of 250 mg DORIBAX® dose using the 500 mg vial

Constitute the 500 mg vial with 10 mL of sterile water for injection or 0.9% sodium chloride injection (normal saline) and gently shake to form a suspension. The resultant concentration is approximately 50 mg/mL. CAUTION: THE CONSTITUTED SUSPENSION IS NOT FOR DIRECT INJECTION.