Meropenem

Meropenem is an antibiotic that fights bacteria.

Meropenem is used to treat severe infections of the skin or stomach. Meropenem is also used to treat bacterial meningitis (infection of brain or spinal cord).

Meropenem may also be used for purposes not listed in this medication guide.

You should not use this medicine if you have a history of allergies to certain antibiotic medications, such as penicillin.

You should not use meropenem if you are allergic to it, or if you have a history of allergy to certain antibiotics, such as:

• amoxicillin, ampicillin, Augmentin, Timentin, Unasyn, Zosyn;
• cefdinir, cefprozil, cefuroxime, cephalexin, and other cephalosporin antibiotics;
• dicloxacillin, nafcillin, oxacillin, ticarcillin; or
• any penicillin antibiotic.

To make sure meropenem is safe for you, tell your doctor if you have:

• history of head injury or brain tumor;
• epilepsy or other seizure disorder; or
• kidney disease (or if you are on dialysis).

This medicine is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Meropenem can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• diarrhea that is watery or bloody;
• seizure (convulsions);
• sores or white patches in your mouth or throat (yeast infection or "thrush"); or
• pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating.

Common side effects may include:

• headache;
• mild diarrhea, constipation;
• nausea, vomiting; or
• mild skin rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Meropenem is a prescription medication used to treat serious skin and stomach infections and certain types of meningitis (irritation of the lining around the brain and spinal cord). Meropenem belongs to a group of drugs called carbapenem antibiotics, which work by attacking bacteria in the body. This medication comes in an injectable form to be given directly into the vein (IV) by a healthcare professional. It is usually given three times daily (every eight hours). In patients with certain kidney problems, it may be given less often.   Common side effects of meropenem include diarrhea, nausea and vomiting, and headache. Meropenem can also affect your neurological (brain) function, which can cause dizziness, fainting, or seizures. Do not drive or operate heavy machinery until you know how meropenem affects you.

Serious side effects have been reported with meropenem. See the “Meropenem Precautions” section.

Common side effects of meropenem include the following:

• diarrhea
• nausea and vomiting
• headache
• difficulty sleeping
• itching or rash

This is not a complete list of meropenem side effects. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

 

 

Tell your doctor if you are breastfeeding or plan to breastfeed.

Meropenem has been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from meropenem, a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered.

 

You should not use this medicine if you have a history of allergies to certain antibiotic medications, such as penicillin.

Antibacterial; carbapenem β-lactam antibiotic.1 2 3

Specific Drugs

Drug	Interaction	Comments
Aminoglycosides	In vitro evidence of synergistic antibacterial effects against Ps. aeruginosa1
Probenecid	Decreased renal tubular secretion of meropenem; increased meropenem concentrations and AUC and prolonged half-life1	Concomitant use not recommended1
Valproic acid	Valproic serum concentrations may be decreased to subtherapeutic concentrations; possible increased risk of seizures1 35 36 37	Use concomitantly with caution36 55

• It is used to treat bacterial infections.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Seizures.
• Stiff muscles, shakiness, or muscle movements that are not normal.
• A burning, numbness, or tingling feeling that is not normal.
• Feeling very tired or weak.
• Feeling confused.
• It is common to have diarrhea when taking meropenem. Rarely, a very bad form of diarrhea called Clostridium difficile (C diff)–associated diarrhea (CDAD) may occur. Sometimes, this has led to a deadly bowel problem (colitis). CDAD may happen while you are taking this medicine or within a few months after you stop taking it. Call your doctor right away if you have stomach pain or cramps, very loose or watery stools, or bloody stools. Do not try to treat loose stools without first checking with your doctor.

Probenecid

Probenecid competes with Meropenem for active tubular secretion, resulting in increased plasma concentrations of Meropenem. Co-administration of probenecid with Meropenem is not recommended.

Valproic Acid

Case reports in the literature have shown that co-administration of carbapenems, including Meropenem, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. Although the mechanism of this interaction is unknown, data from in vitro and animal studies suggest that carbapenems may inhibit the hydrolysis of valproic acid's glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing the serum concentrations of valproic acid. If administration of Meropenem for Injection I.V. is necessary, then supplemental anti-convulsant therapy should be considered [see Warnings and Precautions (5.3)].

Meropenem for Injection I.V. is supplied in 20 mL and 30 mL injection vials containing sufficient Meropenem to deliver 500 mg or 1 gram for intravenous administration, respectively. The dry powder should be stored at controlled room temperature 20° to 25°C (68° to 77°F) [see USP].

Unit of Sale	Strength	Each
NDC 0409-3505-01 Carton containing 25	500 mg per vial	NDC 0409-3505-11 Vial
NDC 0409-3506-01 Carton containing 25	1 gram per vial	NDC 0409-3506-11 Vial

• Counsel patients that antibacterial drugs including Meropenem for Injection I.V. should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Meropenem for Injection I.V. is prescribed to treat a bacterial infection, tell patients that although it is common to feel better early in the course of therapy, take the medication exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Meropenem for Injection I.V. or other antibacterial drugs in the future. • Counsel patients that diarrhea is a common problem caused by antibacterial drugs which usually ends when the antibacterial drug is discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible [see Warnings and Precautions (5.4)]. • Counsel patients to inform their physician if they are taking valproic acid or divalproex sodium. Valproic acid concentrations in the blood may drop below the therapeutic range upon co-administration with Meropenem for Injection I.V. If treatment with Meropenem for Injection I.V. is necessary and continued, alternative or supplemental anti-convulsant medication to prevent and/or treat seizures may be needed [see Warnings and Precautions (5.3)]. • Patients receiving Meropenem for Injection I.V. on an outpatient basis may develop adverse events such as seizures, headaches and/or paresthesias that could interfere with mental alertness and/or cause motor impairment. Until it is reasonably well established that Meropenem for Injection I.V. is well tolerated, patients should not operate machinery or motorized vehicles [see Warnings and Precautions (5.10)].

Manufactured for: Hospira, Inc.                                                                                                   
Lake Forest, IL 60045 USA

Made in India

LAB-0878-1.0

• Antibiotic, Carbapenem

Reduction in plasma clearance correlates with age-associated reduction in creatinine clearance (CrCl) (Craig 1997)

Bacterial meningitis: Treatment of bacterial meningitis in pediatric patients 3 months and older caused by Haemophilus influenzae, Neisseria meningitidis, and penicillin-susceptible isolates of Streptococcus pneumoniae.

Skin and skin structure infections, complicated: Treatment of complicated skin and skin structure infections in adults and pediatric patients 3 months and older caused by Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species.

Intra-abdominal infections: Treatment of complicated appendicitis and peritonitis in adult and pediatric patients caused by viridans group streptococci, E. coli, Klebsiella pneumoniae, P. aeruginosa, B. fragilis, B. thetaiotaomicron, and Peptostreptococcus species.

Bacterital meningitis

Based on the Infectious Disease Society of America (IDSA) guidelines for the management of bacterial meningitis, meropenem is an effective and recommended alternative agent for the treatment of meningitis due to Listeria monocytogenes, E. coli, other susceptible Enterobacteriaceae, P. aeruginosa, and methicillin-susceptible S. aureus.

Catheter-related blood stream infections

Based on the Infectious Disease Society of America (IDSA) Diagnosis and Management of Intravascular Catheter-Related Infection guidelines, meropenem given for catheter-related blood stream infections is effective and recommended in the management of this condition.

Cystic fibrosis, pulmonary exacerbation

Data from several randomized trials in patients with cystic fibrosis and infection with Pseudomonas aeruginosa treated with meropenem (with and without the use of tobramycin) supports the use of meropenem in the treatment of this condition [Blumer 2005], [Byrne 1995], [Latzin 2008]. Clinical experience also suggests the use of meropenem for pulmonary exacerbation in patients with cystic fibrosis [Chmiel 2014], [Zobell 2012]. Additional trials may be necessary to further define the role of meropenem in this condition.

Febrile neutropenia

Based on the Infectious Disease Society of America (IDSA) Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update, meropenem given for febrile neutropenia is effective and recommended in the management of this condition.

Gynecologic and pelvis infection

Data from randomized trials support the use of meropenem in the treatment of gynecologic and pelvic infections (eg, endometritis, pelvic cellulitis, pelvic inflammatory disease, salpingitis) [Hemsell 1997], [Maggioni 1998]. Additional trials may be necessary to further define the role of meropenem in this condition.

Melioidosis (Burkholderia pseudomallei)

Melioidosis is a worldwide subtropic and tropic bacterial disease due to contact with Burkholderia pseudomallei contaminated water or soil [Lipsitz 2012]. Data from a limited number of patients treated with meropenem (case series of 63 patients in a single institution) suggest that meropenem may be beneficial for the treatment of this condition [Cheng 2004].

A DHHS Workshop on Treatment of and Postexposure Prophylaxis for Burkholderia pseudomallei and B. mallei infection also supports the use of meropenem as a second-line agent for initial treatment of melioidosis [Lipsitz 2012]. Additional data may be necessary to further define the role of meropenem for the treatment of melioidosis.

Pneumonia, hospital-acquired or ventilator-associated

Based on the Infectious Diseases Society of America and the American Thoracic Society (IDSA/ATS) guidelines for management of adults with hospital-acquired and ventilator-associated pneumonia, meropenem given for the empiric treatment of hospital-acquired or ventilator-associated pneumonia, alone or in combination with other antimicrobials (dependent on patient factors), is an effective and recommended treatment option in the management of this condition.

Prosthetic joint infection

Based on the Infectious Diseases Society of America (IDSA) Diagnosis and Management of Prosthetic Joint Infection: Clinical Practice Guideline, meropenem given for prosthetic joint infection is effective and recommended in the management of this condition.

Skin and soft tissue necrotizing infections

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), meropenem, in combination with an agent effective against methicillin resistant S. aureus (MRSA) (eg, vancomycin, linezolid, daptomycin), is an effective and recommended empiric treatment for polymicrobial (mixed) necrotizing infections of the skin, fascia, and muscle.

Surgical site Infection

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), meropenem is an effective and recommended option for treatment of surgical site infections occurring after intestinal or genitourinary tract surgery. Systemic antibacterials are not routinely indicated for surgical site infections, but may be beneficial (in conjunction with suture removal plus incision and drainage) in patients with significant systemic response (eg, temperature >38.5ºC, heart rate >110 beats per minute, erythema/induration extending >5 cm from incision, WBC >12,000/mm3).

Urinary tract infection

Data from a multicenter, randomized, parallel-group study support the use of meropenem in the treatment of complicated urinary tract infections [Cox 1995]. Clinical experience also suggests the utility of meropenem in the treatment of complicated urinary tract infections [Pallett 2010]. Additional data may be necessary to further define the role of meropenem in this condition.

Applies to meropenem: intravenous powder for injection, intravenous solution

General

In clinical trials (n=2904), this drug was discontinued in 1.2% of patients due to side effects; 5 deaths were possibly drug-related. In a review of 4872 patients, diarrhea, rash, nausea/vomiting, injection site inflammation, thrombocytosis and increased hepatic enzymes were reported most often.[Ref]

Gastrointestinal

Common (1% to 10%): Nausea, diarrhea, vomiting, constipation, gastrointestinal disorder, abdominal pain
Uncommon (0.1% to 1%): Oral moniliasis/candidiasis, flatulence, ileus, dyspepsia, intestinal obstruction
Frequency not reported: Clostridium difficile associated diarrhea, antibiotic-associated colitis, pseudomembranous colitis[Ref]

Nervous system

Common (1% to 10%): Headache
Uncommon (0.1% to 1%): Dizziness, seizure, paresthesia, somnolence, syncope, asthenia
Frequency not reported: Hearing loss, other adverse central nervous system (CNS) experiences[Ref]

Seizures and other adverse CNS experiences have been reported. They have occurred most commonly in patients with CNS disorders (e.g., history of seizures, brain lesions) or with bacterial meningitis and/or renal dysfunction.

Seizures occurred more often in patients with moderately severe renal dysfunction.[Ref]

Hematologic

Common (1% to 10%): Anemia, hypochromic anemia, bleeding events (including gastrointestinal hemorrhage, melena, epistaxis, hemoperitoneum), thrombocythemia
Uncommon (0.1% to 1%): Increased platelets, increased eosinophils, decreased platelets, decreased hemoglobin, decreased hematocrit, decreased white blood cells, decreased prothrombin time, decreased partial thromboplastin time, leukocytosis, eosinophilia, thrombocytopenia, leukopenia, neutropenia
Postmarketing reports: Agranulocytosis, positive Coombs test (direct or indirect), hemolytic anemia[Ref]

Other

Shock occurred more often in patients with moderately severe renal dysfunction.[Ref]

Common (1% to 10%): Pain, inflammation, sepsis/septicemia, shock, accidental injury
Uncommon (0.1% to 1%): Chest pain, fever, back pain, chills, pelvic pain, peripheral edema, abdominal enlargement[Ref]

Local

Common (1% to 10%): Inflammation at the injection site, phlebitis/thrombophlebitis, pain at the injection site
Uncommon (0.1% to 1%): Injection site reactions, edema at the injection site[Ref]

Dermatologic

Common (1% to 10%): Rash (including diaper/nappy area moniliasis), pruritus
Uncommon (0.1% to 1%): Urticaria, sweating, skin ulcer
Postmarketing reports: Toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, erythema multiforme, severe skin reactions[Ref]

Respiratory

Common (1% to 10%): Apnea, pharyngitis, pneumonia
Uncommon (0.1% to 1%): Respiratory disorder, dyspnea, pleural effusion, asthma, increased cough, hypoxia, lung edema
Frequency not reported: Respiratory failure[Ref]

Cardiovascular

Heart failure occurred more often in patients with moderately severe renal dysfunction.[Ref]

Common (1% to 10%): Peripheral vascular disorder
Uncommon (0.1% to 1%): Heart failure, heart arrest, tachycardia, hypertension, myocardial infarction, pulmonary embolus, bradycardia, hypotension[Ref]

Hepatic

Common (1% to 10%): Increased transaminases
Uncommon (0.1% to 1%): Increased AST, increased ALT, increased bilirubin, hepatic failure, cholestatic jaundice/jaundice[Ref]

Metabolic

Common (1% to 10%): Hypoglycemia, increased alkaline phosphatase, increased lactate dehydrogenase
Uncommon (0.1% to 1%): Anorexia, hypervolemia, hypokalemia[Ref]

Renal

Kidney failure occurred more often in patients with moderately severe renal dysfunction.[Ref]

Uncommon (0.1% to 1%): Kidney failure, increased creatinine, increased BUN[Ref]

Psychiatric

Uncommon (0.1% to 1%): Insomnia, agitation/delirium, confusion, nervousness, hallucinations, anxiety, depression

Genitourinary

Uncommon (0.1% to 1%): Dysuria, vaginal moniliasis/candidiasis, urinary incontinence, red blood cells in urine[Ref]

Hypersensitivity

Frequency not reported: Serum sickness-like reactions, cross-sensitivity in penicillin-allergic and cephalosporin-allergic patients, anaphylaxis[Ref]

Musculoskeletal

Frequency not reported: Myalgia, arthralgia[Ref]

Some side effects of meropenem may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

1 g IV every 8 hours

Uses: As a single agent therapy for the treatment of complicated intraabdominal infections (including appendicitis and peritonitis) due to viridans group streptococci, E coli, Klebsiella pneumoniae, P aeruginosa, B fragilis, B thetaiotaomicron, Peptostreptococcus species

Infectious Diseases Society of America (IDSA) recommendations: 2 g IV every 8 hours for 7 to 21 days

Comments:
-Recommended as an alternative therapy

Administration advice:
-Adults: Administer by IV infusion over about 15 to 30 minutes; alternatively, doses of 1 g may be administered as an IV bolus injection over about 3 to 5 minutes.
-Pediatric patients 3 months or older: Administer as IV infusion over about 15 to 30 minutes or as an IV bolus injection over about 3 to 5 minutes; limited safety data available to support use of a 40 mg/kg (maximum of 2 g) bolus dose.
-Pediatric patients younger than 3 months: Administer as IV infusion over 30 minutes.
-Do not use flexible container in series connections.

Storage requirements:
-Dry powder: Store at controlled room temperature 20C to 25C (68F to 77F)
-Constituted solution for IV bolus: If unable to use freshly prepared solution immediately, may store up to 3 hours at up to 25C (77F) or for 13 hours at up to 5C (41F)
-Solution for IV infusion when constituted with Sodium Chloride Injection 0.9%: If unable to use freshly prepared solution immediately, may store for 1 hour at up to 25C (77F) or 15 hours at up to 5C (41F)
-Solution for IV infusion when constituted with Dextrose Injection 5%: Freshly prepared solution should be used immediately.
-Do not freeze IV solutions.

Reconstitution/preparation techniques:
-For IV bolus: Constitute injection vials with sterile Water for Injection; shake to dissolve then let stand until clear.
-For IV infusion: May constitute infusion vials directly with compatible infusion fluid; alternatively, may constitute an injection vial, add the resulting solution to an IV container, then further dilute with an appropriate infusion fluid

IV compatibility:
-Compatible for IV bolus: Sterile Water for Injection
-Compatible for IV infusion: Sodium Chloride Injection 0.9%, Dextrose Injection 5%
-Compatibility with other drugs not established; this drug should not be mixed with or physically added to solutions containing other drugs.

General:
-Culture and susceptibility information should be considered when selecting treatment or, if no data are available, local epidemiology and susceptibility patterns may be considered when selecting empiric therapy.
-This drug is useful as presumptive therapy in the indicated condition before causative organism is identified due to broad spectrum of bactericidal activity.
-Concentration of solution for IV bolus: Up to 50 mg/mL
-Concentration of solution for IV infusion: Ranges from 1 to 20 mg/mL

Monitoring:
-General: Organ system functions (periodically during prolonged therapy)
-Hematologic: Hematopoietic organ system functions (periodically during prolonged therapy)
-Hepatic: Hepatic organ system functions (periodically during prolonged therapy)
-Renal: Renal organ system functions (periodically during prolonged therapy); renal function in elderly patients

Patient advice:
-Avoid missing doses and complete the entire course of therapy.
-Do not operate machinery or motorized vehicles until it is reasonable well established that this drug is well tolerated.

Summary of Use during Lactation

Although no information is available on the use of meropenem during breastfeeding, beta-lactams are generally not expected to cause adverse effects in breastfed infants. Occasionally, disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush, has been reported with beta-lactams, but these effects have not been adequately evaluated.

Drug Levels

Maternal Levels. A woman with a history of NYHA class I heart failure was 3 days postpartum and developed a urinary tract infection and was treated with cephalexin until it was found that the organism was resistant to extended-spectrum beta-lactams. On day 6 postpartum, meropenem 1 gram IV every 8 hours was started. Five samples of hindmilk were obtained from day 6 to day 9 postpartum over 37 hours. The highest measured level was 644 mcg/L and the lowest was 246 mcg/L. Over the collection period the average breastmilk level was 480 mcg/L. The average infant intake was estimated to be 71 mcg/kg daily, which was 0.13% of the weight-adjusted maternal dosage. The maximum infant intake was estimated to be 97 mcg/kg daily, which was 0.18% of the weight-adjusted maternal dosage[1]

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

A mother received meropenem 1 gram IV every 8 hours for 7 days while exclusively breastfeeding her newborn. When questioned later, she stated that her infant had no oral thrush, watery diarrhea, or diaper dermatitis that required antifungal therapy during the month following her meropenem therapy.[1]

An infant was breastfed (extent not stated) until the 4th month postpartum. At 2 months of age, his mother was given a 2-week course of tobramycin and meropenem (dosage not specified) for a cystic fibrosis exacerbation. The infant displayed no change in stool pattern during the maternal treatment and had normal renal function at 6 months of age.[2]

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

References

1. Sauberan JB, Bradley JS, Blumer J, Stellwagen LM. Transmission of meropenem in breast milk. Pediatr Infect Dis J. 2012;31:832-4. PMID: 22544050

2. Festini F, Ciuti R, Repetto T et al. Safety of breast-feeding during an IV tobramycin course for infants of CF women. Pediatr Pulmonol Suppl. 2004;27:288-9. Abstract. DOI: doi:10.1002/ppul.20143