Primaxin IV

Call your doctor for instructions if you miss a dose of imipenem and cilastatin.

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

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

Call your doctor at once if you have:

• severe stomach pain, diarrhea that is watery or bloody;

• upper stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• a seizure (convulsions);

• fever; or

• a light-headed feeling, like you might pass out.

Common side effects may include:

• pain where the medicine was injected;

• dizziness, drowsiness;

• nausea, vomiting, diarrhea;

• itching, rash; or

• swollen tongue.

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.

In the U.S.

• Primaxin IM
• Primaxin IV

Available Dosage Forms:

• Powder for Solution

Therapeutic Class: Antibiotic

Pharmacologic Class: Beta-Lactam

Chemical Class: Carbapenem

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

This medicine has been tested in a limited number of children 12 years of age and older and, in effective doses, has not been reported to cause different side effects or problems in children than it does in adults.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of imipenem and cilastatin in the elderly with use in other age groups, this medicine is not expected to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Cholera Vaccine, Live
• Ganciclovir
• Theophylline
• Valganciclovir
• Valproic Acid

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Cyclosporine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Central nervous system (CNS) disorders (for example, brain disease or history of seizures)—Patients with nervous system disorders, including seizures, may be more likely to have side effects

• Kidney disease—Patients with kidney disease may be more likely to have side effects

This section provides information on the proper use of a number of products that contain imipenem and cilastatin. It may not be specific to Primaxin IV. Please read with care.

To help clear up your infection completely, imipenem and cilastatin combination must be given for the full time of treatment, even if you begin to feel better after a few days. Also, this medicine works best when there is a constant amount in the blood or urine. To help keep the amount constant, it must be given on a regular schedule.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form:
  • For bacterial infections:
    • Adults and children 12 years of age and over—250 milligrams (mg) to 1 gram injected into a vein every six to eight hours; or 500 to 750 mg injected into a muscle every twelve hours, depending on how severe your infection is.
    • Children up to 12 years of age—Use and dose must be determined by your doctor.

Some patients may develop tremors or seizures while receiving this medicine. If you already have a history of seizures and you are taking anticonvulsants, you should continue to take them unless otherwise directed by your doctor.

In some patients, imipenem and cilastatin combination may cause diarrhea.

• Severe diarrhea may be a sign of a serious side effect. Do not take any diarrhea medicine without first checking with your doctor . Diarrhea medicines may make your diarrhea worse or make it last longer.
• For mild diarrhea, diarrhea medicine containing kaolin (e.g., Kaopectate liquid) or attapulgite (e.g., Kaopectate tablets, Diasorb) may be taken. However, other kinds of diarrhea medicine should not be taken. They may make your diarrhea worse or make it last longer.
• If you have any questions about this or if mild diarrhea continues or gets worse, check with your health care professional.

Lower Respiratory Tract Infections

PRIMAXIN for intravenous use is indicated for the treatment of lower respiratory tract infections caused by susceptible strains of Staphylococcus aureus (penicillinase-producing isolates), Acinetobacter species, Enterobacter species, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella species, Serratia marcescens.

Urinary Tract Infections (complicated and uncomplicated)

PRIMAXIN is indicated for the treatment of urinary tract infections (complicated and uncomplicated) caused by susceptible strains of Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing isolates), Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa.

Intra-Abdominal Infections

PRIMAXIN is indicated for the treatment of intra-abdominal infections caused by susceptible strains of Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing isolates), Staphylococcus epidermidis, Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii, Proteus species, Pseudomonas aeruginosa, Bifidobacterium species, Clostridium species, Eubacterium species, Peptococcus species, Peptostreptococcus species, Propionibacterium species, Bacteroides species including B. fragilis, Fusobacterium species.

Gynecologic Infections

PRIMAXIN is indicated for the treatment of gynecologic infections caused by susceptible strains of Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing isolates), Staphylococcus epidermidis, Streptococcus agalactiae (Group B streptococci), Enterobacter species, Escherichia coli, Gardnerella vaginalis, Klebsiella species, Proteus species, Bifidobacterium species, Peptococcus species, Peptostreptococcus species, Propionibacterium species, Bacteroides species including B. fragilis.

Bacterial Septicemia

PRIMAXIN is indicated for the treatment of bacterial septicemia caused by susceptible strains of Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing isolates), Enterobacter species, Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, Serratia species, Bacteroides species including B. fragilis.

Bone and Joint Infections

PRIMAXIN is indicated for the treatment of bone and joint infections caused by susceptible strains of Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing isolates), Staphylococcus epidermidis, Enterobacter species, Pseudomonas aeruginosa.

Skin and Skin Structure Infections

PRIMAXIN is indicated for the treatment of skin and skin structure infections caused by susceptible strains of Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing isolates), Staphylococcus epidermidis, Acinetobacter species, Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa, Serratia species, Peptococcus species, Peptostreptococcus species, Bacteroides species including B. fragilis, Fusobacterium species.

Endocarditis

PRIMAXIN is indicated for the treatment of endocarditis caused by susceptible strains of Staphylococcus aureus (penicillinase-producing isolates).

Limitations of Use

• PRIMAXIN is not indicated in patients with meningitis because safety and efficacy have not been established.
• PRIMAXIN is not recommended in pediatric patients with CNS infections because of the risk of seizures [see Dosage and Administration (2.2), Warnings and Precautions (5.2), and Use in Specific Populations (8.4)].
• PRIMAXIN is not recommended in pediatric patients less than 30 kg with impaired renal function, as no data are available [see Use in Specific Populations (8.4), and Dosage and Administration (2.2)].
• Periodic assessment of organ system functions, including renal, hepatic and hematopoietic, is advisable during prolonged therapy.

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of PRIMAXIN and other antibacterial drugs, PRIMAXIN 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 or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

For Injection PRIMAXIN is a sterile powder mixture for reconstitution in single-dose containers including vials and ADD-Vantage® vials containing:

• 250 mg imipenem (anhydrous equivalent) and 250 mg cilastatin sodium
• 500 mg imipenem (anhydrous equivalent) and 500 mg cilastatin sodium

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. These reactions are more likely to occur in individuals with a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another beta-lactam. Before initiating therapy with PRIMAXIN, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams and other allergens. If an allergic reaction to PRIMAXIN occurs, discontinue the drug immediately. Serious anaphylactic reactions require immediate emergency treatment as clinically indicated.

Seizure Potential

Seizures and other CNS adverse experiences, such as confusional states and myoclonic activity, have been reported during treatment with PRIMAXIN, especially when recommended dosages were exceeded [see Adverse Reactions (6.1, 6.2)]. These experiences have occurred most commonly in patients with CNS disorders (e.g., brain lesions or history of seizures) and/or compromised renal function [see Use in Specific Populations (8.6)]. However, there have been reports of CNS adverse experiences in patients who had no recognized or documented underlying CNS disorder or compromised renal function.

Anticonvulsant therapy should be continued in patients with known seizure disorders. If focal tremors, myoclonus, or seizures occur, patients should be evaluated neurologically, placed on anticonvulsant therapy if not already instituted, and the dosage of PRIMAXIN re-examined to determine whether it should be decreased or the antibacterial drug discontinued.

Increased Seizure Potential Due to Interaction with Valproic Acid

Case reports in the literature have shown that co-administration of carbapenems, including PRIMAXIN, 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. Increasing the dose of valproic acid or divalproex sodium may not be sufficient to overcome this interaction. The concomitant use of PRIMAXIN and valproic acid/divalproex sodium is generally not recommended. Antibacterials other than carbapenems should be considered to treat infections in patients whose seizures are well controlled on valproic acid or divalproex sodium. If administration of PRIMAXIN is necessary, supplemental anti-convulsant therapy should be considered [see Drug Interactions (7.3)]. Close adherence to the recommended dosage and dosage schedules is urged, especially in patients with known factors that predispose to convulsive activity.

Clostridium difficile-Associated Diarrhea (CDAD)

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including PRIMAXIN, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD.

Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Development of Drug-Resistant Bacteria

As with other antibacterial drugs, prolonged use of PRIMAXIN may result in overgrowth of nonsusceptible organisms. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Prescribing PRIMAXIN 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.