NOVACTAM is indicated for the treatment of infections due to susceptible strains of the designated microorganisms in the conditions listed below.

Skin and Skin Structure Infections caused by beta‑lactamase producing strains of Staphylococcus aureus, Escherichia coli,* Klebsiella spp.* (including K. pneumoniae*), Proteus mirabilis,* Bacteroides fragilis,* Enterobacter spp.,* and Acinetobacter calcoaceticus.*

NOTE: For information on use in pediatric patients (see sections 4.4 Special warnings and precautions for use and 5.1 Pharmacodynamic properties).

Intra‑Abdominal Infections caused by beta‑lactamase producing strains of Escherichia coli, Klebsiella spp. (including K. pneumoniae*), Bacteroides spp. (including B. fragilis), and Enterobacter spp.*

Gynecological Infections caused by beta‑lactamase producing strains of Escherichia coli,* and Bacteroides spp.* (including B. fragilis*).

* Efficacy for this organism in this organ system was studied in fewer than 10 infections.

While NOVACTAM is indicated only for the conditions listed above, infections caused by ampicillin‑susceptible organisms are also amenable to treatment with NOVACTAM due to its ampicillin content. Therefore, mixed infections caused by ampicillin‑susceptible organisms and beta‑lactamase producing organisms susceptible to NOVACTAM should not require the addition of another antibacterial.

Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify the organisms causing infection and to determine their susceptibility to NOVACTAM.

Therapy may be instituted prior to obtaining the results from bacteriological and susceptibility studies when there is reason to believe the infection may involve any of the beta‑lactamase producing organisms listed above in the indicated organ systems. Once the results are known, therapy should be adjusted if appropriate.

To reduce the development of drug-resistant bacteria and maintain effectiveness of NOVACTAM and other antibacterial drugs, NOVACTAM 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.

NOVACTAM may be administered by either the IV or the IM routes.

For IV administration, the dose can be given by slow intravenous injection over at least 10–15 minutes or can also be delivered in greater dilutions with 50–100 mL of a compatible diluent as an intravenous infusion over 15–30 minutes.

NOVACTAM may be administered by deep intramuscular injection. (see DIRECTIONS FOR USE-Preparation for Intramuscular Injection section).

The recommended adult dosage of NOVACTAM is 1.5 g (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) to 3 g (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) every six hours. This 1.5 to 3 g range represents the total of ampicillin content plus the sulbactam content of NOVACTAM, and corresponds to a range of 1 g ampicillin/0.5 g sulbactam to 2 g ampicillin/1 g sulbactam. The total dose of sulbactam should not exceed 4 grams per day.

Pediatric Patients 1 Year of Age or Older: The recommended daily dose of NOVACTAM in pediatric patients is 300 mg per kg of body weight administered via intravenous infusion in equally divided doses every 6 hours. This 300 mg/kg/day dosage represents the total ampicillin content plus the sulbactam content of NOVACTAM, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of NOVACTAM administered via intramuscular injection in pediatric patients have not been established. Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations, and the total dose of sulbactam should not exceed 4 grams per day. The course of intravenous therapy should not routinely exceed 14 days. In clinical trials, most children received a course of oral antimicrobials following initial treatment with intravenous NOVACTAM. (see section 5.1 Pharmacodynamic properties).

Impaired Renal Function

In patients with impairment of renal function the elimination kinetics of ampicillin and sulbactam are similarly affected, hence the ratio of one to the other will remain constant whatever the renal function. The dose of NOVACTAM in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

NOVACTAM Dosage Guide for Patients with Renal Impairment

When only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.

  Males                        weight (kg) ´ (140 – age)

                                      72 ´ serum creatinine

Females            0.85 ´ above value

Animal Pharmacology: While reversible glycogenosis was observed in laboratory animals, this phenomenon was dose- and time-dependent and is not expected to develop at the therapeutic doses and corresponding plasma levels attained during the relatively short periods of combined ampicillin/sulbactam therapy in man.

WARNINGS

Hypersensitivity

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. These reactions are more apt to occur in individuals with a history of penicillin hypersensitivity and/or hypersensitivity reactions to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before therapy with a penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, and other allergens. If an allergic reaction occurs, NOVACTAM should be discontinued and the appropriate therapy instituted.

Hepatotoxicity

Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of NOVACTAM. Hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment.

Severe Cutaneous Adverse Reactions

NOVACTAM may cause severe skin reactions, such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), dermatitis exfoliative, erythema multiforme, and Acute generalized exanthematous pustulosis (AGEP). If patients develop a skin rash they should be monitored closely and NOVACTAM discontinued if lesions progress (see section 4.3 Contraindications and 4.8 undesirable effects sections).

Clostridium difficile-Associated Diarrhea

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including NOVACTAM, 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 treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

PRECAUTIONS

General: A high percentage of patients with mononucleosis who receive ampicillin develop a skin rash. Thus, ampicillin class antibacterial should not be administered to patients with mononucleosis. In patients treated with NOVACTAM the possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Pseudomonas or Candida), the drug should be discontinued and/or appropriate therapy instituted.

Prescribing NOVACTAM in the absence of 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.

Information for Patients:

Patients should be counseled that antibacterial drugs including NOVACTAM should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When NOVACTAM is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken 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 NOVACTAM or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibacterial which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterial, 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.  If this occurs, patients should contact their physician as soon as possible.

Drug/Laboratory Test Interactions:

Administration of NOVACTAM will result in high urine concentration of ampicillin. High urine concentrations of ampicillin may result in false positive reactions when testing for the presence of glucose in urine using Clinitest™, Benedict’s Solution or Fehling’s Solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix™ or Testape™) be used. Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol‑glucuronide, conjugated estrone and estradiol has been noted. This effect may also occur with NOVACTAM.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Long‑term studies in animals have not been performed to evaluate carcinogenic or mutagenic potential.

Probenecid decreases the renal tubular secretion of ampicillin and sulbactam. Concurrent use of probenecid with NOVACTAM may result in increased and prolonged blood levels of ampicillin and sulbactam. The concurrent administration of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to patients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia present in these patients. There are no data with NOVACTAM and allopurinol administered concurrently.

NOVACTAM and aminoglycosides should not be reconstituted together due to the in vitro inactivation of aminoglycosides by the ampicillin component of NOVACTAM.

Pediatric Use: The safety and effectiveness of NOVACTAM have been established for pediatric patients one year of age and older for skin and skin structure infections as approved in adults. Use of NOVACTAM in pediatric patients is supported by evidence from adequate and well‑controlled studies in adults with additional data from pediatric pharmacokinetic studies, a controlled clinical trial conducted in pediatric patients and post-marketing adverse events surveillance. (see sections 5.2  pharmacokinetic properties , and 4.1 Therapeutic indication, 4.8 Undesirable effects, 4.2 Posology and method of administration , and 5.4 Clinical Studies ).

The safety and effectiveness of NOVACTAM have not been established for pediatric patients for intra-abdominal infections.

Pregnancy:

Reproduction studies have been performed in mice, rats, and rabbits at doses up to ten (10) times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to NOVACTAM. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. (see section 4.4 Special warnings and precautions for use).

Labor and Delivery:

Studies in guinea pigs have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions, and duration of contractions. However, it is not known whether the use of NOVACTAM in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary.

Nursing Mothers:

Low concentrations of ampicillin and sulbactam are excreted in the milk; therefore, caution should be exercised when NOVACTAM is administered to a nursing woman.

Not relevant.

Adult Patients: NOVACTAM is generally well tolerated. The following adverse reactions have been reported in clinical trials.

Local Adverse Reactions

Pain at IM injection site – 16%

Pain at IV injection site – 3%

Thrombophlebitis – 3%

Phlebitis – 1.2%

Systemic Adverse Reactions

The most frequently reported adverse reactions were diarrhea in 3% of the patients and rash in less than 2% of the patients.

Additional systemic reactions reported in less than 1% of the patients were: itching, nausea, vomiting, candidiasis, fatigue, malaise, headache, chest pain, flatulence, abdominal distension, glossitis, urine retention, dysuria, edema, facial swelling, erythema, chills, tightness in throat, substernal pain, epistaxis and mucosal bleeding.

Pediatric Patients: Available safety data for pediatric patients treated with NOVACTAM demonstrate a similar adverse events profile to those observed in adult patients. Additionally, atypical lymphocytosis has been observed in one pediatric patient receiving NOVACTAM.

Adverse Laboratory Changes

Adverse laboratory changes without regard to drug relationship that were reported during clinical trials were:

Hepatic: Increased AST (SGOT), ALT (SGPT), alkaline phosphatase, and LDH.

Hematologic: Decreased hemoglobin, hematocrit, RBC, WBC, neutrophils, lymphocytes, platelets and increased lymphocytes, monocytes, basophils, eosinophils, and platelets.

Blood Chemistry: Decreased serum albumin and total proteins.

Renal: Increased BUN and creatinine.

Urinalysis: Presence of RBC’s and hyaline casts in urine.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following have been identified during post-marketing use of ampicillin sodium/sulbactam sodium or other products containing ampicillin. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency, or potential causal connection to ampicillin sodium/sulbactam sodium.

Blood and Lymphatic System Disorders: Hemolytic anemia, thrombocytopenic purpura, and agranulocytosis have been reported. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Some individuals have developed positive direct Coombs Tests during treatment with NOVACTAM, as with other beta-lactam antibacterials.

Gastrointestinal Disorders: Abdominal pain, cholestatic hepatitis, cholestasis, hyperbilirubinemia, jaundice, abnormal hepatic function, melena, gastritis, stomatitis, dyspepsia, black “hairy” tongue, and Clostridium difficile associated diarrhea (see section 4.3 Contraindications and 4.4 Special warnings and precautions for use).

General Disorders and Administration Site Conditions: Injection site reaction

Immune System Disorders: Serious and fatal hypersensitivity (anaphylactic) reactions (See 4.4 Special warnings and precautions for use), Acute myocardial ischemia with or without myocardial infarction may occur as part of an allergic reaction.

Nervous System Disorders: Convulsion and dizziness

Renal and Urinary Disorders: Tubulointerstitial nephritis

Respiratory, Thoracic and Mediastinal Disorders: Dyspnea

Skin and Subcutaneous Tissue Disorders: Toxic epidermal necrolysis, Stevens‑Johnson syndrome, angioedema, Acute generalized exanthematous pustulosis (AGEP), erythema multiforme, exfoliative dermatitis, and urticaria (see section 4.3 Contraindications and 4.4 Special warnings and precautions for use).

Reporting of adverse reactions

Reporting suspected adverse reactions after marketing authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions according to their local requirements.

·        Saudi Arabia

NPC Contact Information:

National pharmacovigilance & Drug safety centre (NPC):

Please report adverse drug events to :

National Pharmacovigilance Centre ( NPC )

·   SFDA Call center : 19999

·   E-mail: npc.drug@sfda.gov.sa

Website :https://ade.sfda.gov.sa/ 

·        Other GCC States:

Please contact the relevant competent authority.

Neurological adverse reactions, including convulsions, may occur with the attainment of high CSF levels of beta‑lactams. Ampicillin may be removed from circulation by hemodialysis. The molecular weight, degree of protein binding and pharmacokinetics profile of sulbactam suggest that this compound may also be removed by hemodialysis.

Pharmacotherapeutic Group: Antibacterial agents for systemic use.

Penicillin combinations, including beta-lactamase inhibitors.

ATC code: J01CR01

Clinical Studies

Skin and Skin Structure Infections in Pediatric Patients: Data from a controlled clinical trial conducted in pediatric patients provided evidence supporting the safety and efficacy of NOVACTAM for the treatment of skin and skin structure infections. Of 99 pediatric patients evaluable for clinical efficacy, 60 patients received a regimen containing intravenous NOVACTAM, and 39 patients received a regimen containing intravenous cefuroxime. This trial demonstrated similar outcomes (assessed at an appropriate interval after discontinuation of all antimicrobial therapy) for NOVACTAM- and cefuroxime-treated patients:

Most patients received a course of oral antimicrobials following initial treatment with intravenous administration of parenteral antimicrobials. The study protocol required that the following three criteria be met prior to transition from intravenous to oral antimicrobial therapy: (1) receipt of a minimum of 72 hours of intravenous therapy; (2) no documented fever for prior 24 hours; and (3) improvement or resolution of the signs and symptoms of infection.

The choice of oral antimicrobial agent used in this trial was determined by susceptibility testing of the original pathogen, if isolated, to oral agents available. The course of oral antimicrobial therapy should not routinely exceed 14 days.

MICROBIOLOGY

Ampicillin is similar to benzyl penicillin in its bactericidal action against susceptible organisms during the stage of active multiplication. It acts through the inhibition of cell wall mucopeptide biosynthesis. Ampicillin has a broad spectrum of bactericidal activity against many gram‑positive and gram‑negative aerobic and anaerobic bacteria. (Ampicillin is, however, degraded by beta‑lactamases and therefore the spectrum of activity does not normally include organisms which produce these enzymes).

A wide range of beta‑lactamases found in microorganisms resistant to penicillins and cephalosporins have been shown in biochemical studies with cell free bacterial systems to be irreversibly inhibited by sulbactam. Although sulbactam alone possesses little useful antibacterial activity except against the Neisseriaceae, whole organism studies have shown that sulbactam restores ampicillin activity against beta‑lactamase producing strains. In particular, sulbactam has good inhibitory activity against the clinically important plasmid mediated beta‑lactamases most frequently responsible for transferred drug resistance. Sulbactam has no effect on the activity of ampicillin against ampicillin susceptible strains.

The presence of sulbactam in the NOVACTAM formulation effectively extends the antibacterial spectrum of ampicillin to include many bacteria normally resistant to it and to other beta‑lactam antibacterials. Thus, NOVACTAM possesses the properties of a broad‑spectrum antibacterial and a beta‑lactamase inhibitor.

While in vitro studies have demonstrated the susceptibility of most strains of the following organisms, clinical efficacy for infections other than those included in the Posology and method of administration section has not been documented.

Gram‑Positive Bacteria: Staphylococcus aureus (beta‑lactamase and non‑beta‑lactamase producing), Staphylococcus epidermidis (beta‑lactamase and non‑beta‑lactamase producing), Staphylococcus saprophyticus (beta‑lactamase and non‑beta‑lactamase producing), Streptococcus faecalis† (Enterococcus), Streptococcus pneumoniae† (formerly D. pneumoniae), Streptococcus pyogenes†, Streptococcus viridans†.

Gram‑Negative Bacteria: Hemophilus influenzae (beta‑lactamase and non‑beta‑lactamase producing), Moraxella (Branhamella) catarrhalis (beta‑lactamase and non‑beta‑lactamase producing), Escherichia coli (beta‑lactamase and non‑beta‑lactamase producing), Klebsiella  species (all known strains are beta‑lactamase producing), Proteus mirabilis (beta‑lactamase and non‑beta‑lactamase producing), Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Morganella morganii, and Neisseria gonorrhoeae (beta‑lactamase and non‑beta‑lactamase producing).

Anaerobes: Clostridium species,† Peptococcus species,† Peptostreptococcus species, Bacteroides species, including B. fragilis.

† These are not beta‑lactamase producing strains and, therefore, are susceptible to ampicillin alone.

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

Pharmacotherapeutic Group: Antibacterial agents for systemic use.

Penicillin combinations, including beta-lactamase inhibitors.

ATC code: J01CR01

Clinical Studies

Skin and Skin Structure Infections in Pediatric Patients: Data from a controlled clinical trial conducted in pediatric patients provided evidence supporting the safety and efficacy of NOVACTAM for the treatment of skin and skin structure infections. Of 99 pediatric patients evaluable for clinical efficacy, 60 patients received a regimen containing intravenous NOVACTAM, and 39 patients received a regimen containing intravenous cefuroxime. This trial demonstrated similar outcomes (assessed at an appropriate interval after discontinuation of all antimicrobial therapy) for NOVACTAM- and cefuroxime-treated patients:

Most patients received a course of oral antimicrobials following initial treatment with intravenous administration of parenteral antimicrobials. The study protocol required that the following three criteria be met prior to transition from intravenous to oral antimicrobial therapy: (1) receipt of a minimum of 72 hours of intravenous therapy; (2) no documented fever for prior 24 hours; and (3) improvement or resolution of the signs and symptoms of infection.

The choice of oral antimicrobial agent used in this trial was determined by susceptibility testing of the original pathogen, if isolated, to oral agents available. The course of oral antimicrobial therapy should not routinely exceed 14 days.

MICROBIOLOGY

Ampicillin is similar to benzyl penicillin in its bactericidal action against susceptible organisms during the stage of active multiplication. It acts through the inhibition of cell wall mucopeptide biosynthesis. Ampicillin has a broad spectrum of bactericidal activity against many gram‑positive and gram‑negative aerobic and anaerobic bacteria. (Ampicillin is, however, degraded by beta‑lactamases and therefore the spectrum of activity does not normally include organisms which produce these enzymes).

A wide range of beta‑lactamases found in microorganisms resistant to penicillins and cephalosporins have been shown in biochemical studies with cell free bacterial systems to be irreversibly inhibited by sulbactam. Although sulbactam alone possesses little useful antibacterial activity except against the Neisseriaceae, whole organism studies have shown that sulbactam restores ampicillin activity against beta‑lactamase producing strains. In particular, sulbactam has good inhibitory activity against the clinically important plasmid mediated beta‑lactamases most frequently responsible for transferred drug resistance. Sulbactam has no effect on the activity of ampicillin against ampicillin susceptible strains.

The presence of sulbactam in the NOVACTAM formulation effectively extends the antibacterial spectrum of ampicillin to include many bacteria normally resistant to it and to other beta‑lactam antibacterials. Thus, NOVACTAM possesses the properties of a broad‑spectrum antibacterial and a beta‑lactamase inhibitor.

While in vitro studies have demonstrated the susceptibility of most strains of the following organisms, clinical efficacy for infections other than those included in the Posology and method of administration section has not been documented.

Gram‑Positive Bacteria: Staphylococcus aureus (beta‑lactamase and non‑beta‑lactamase producing), Staphylococcus epidermidis (beta‑lactamase and non‑beta‑lactamase producing), Staphylococcus saprophyticus (beta‑lactamase and non‑beta‑lactamase producing), Streptococcus faecalis† (Enterococcus), Streptococcus pneumoniae† (formerly D. pneumoniae), Streptococcus pyogenes†, Streptococcus viridans†.

Gram‑Negative Bacteria: Hemophilus influenzae (beta‑lactamase and non‑beta‑lactamase producing), Moraxella (Branhamella) catarrhalis (beta‑lactamase and non‑beta‑lactamase producing), Escherichia coli (beta‑lactamase and non‑beta‑lactamase producing), Klebsiella  species (all known strains are beta‑lactamase producing), Proteus mirabilis (beta‑lactamase and non‑beta‑lactamase producing), Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Morganella morganii, and Neisseria gonorrhoeae (beta‑lactamase and non‑beta‑lactamase producing).

Anaerobes: Clostridium species,† Peptococcus species,† Peptostreptococcus species, Bacteroides species, including B. fragilis.

† These are not beta‑lactamase producing strains and, therefore, are susceptible to ampicillin alone.

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

Not Applicable.

Not Applicable.

When concomitant therapy with aminoglycosides is indicated, NOVACTAM and aminoglycosides should be reconstituted and administered separately, due to the in vitro inactivation of aminoglycosides by any of the aminopenicillins.

NOVACTAM sterile powder is to be stored below 30°C prior to reconstitution.

Novactam 1000/500 mg Vials:

Carton box containing 25 ml transparent glass (type I) vial of powder to make 6 ml solution with rubber stopper and Al flip-off cap and ampoules containing 5 ml Water for injection and insert leaflet. 

Keep out of the sight and reach of children.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

INSTRUCTIONS FOR USE:

General Dissolution Procedures: NOVACTAM sterile powder for intravenous and intramuscular use may be reconstituted with any of the compatible diluents described in this insert. Solutions should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for complete solubilization.

Preparation for Intravenous Use

Reconstitution of NOVACTAM, at the specified concentrations, with these diluents provide stable solutions for the time periods indicated in the following table: (After the indicated time periods, any unused portions of solutions should be discarded).

Preparation for Intramuscular Injection

Vials for intramuscular use may be reconstituted with Sterile Water for Injection USP, 0.5% Lidocaine Hydrochloride Injection USP or 2% Lidocaine Hydrochloride Injection USP. Consult the following table for recommended volumes to be added to obtain solutions containing 375 mg NOVACTAM per mL (250 mg ampicillin/125 mg sulbactam per mL). Note: Use only freshly prepared solutions and administer within one hour after preparation.

*There is sufficient excess present to allow withdrawal and administration of the stated volumes.