Natravox/Natravox Injection

Natravox/Natravox Injection

amoxicillin + clavulanic acid

Manufacturer:

Natrapharm

Distributor:

Natrapharm
Full Prescribing Info
Contents
Co-amoxiclav: Amoxicillin and clavulanic acid.
Description
Natravox: Each 250 mg/125 mg and 500 mg/125 mg tablet contains amoxicillin 250 mg and 500 mg, respectively and clavulanic acid 125 mg.
Each 125 mg/31.25 mg, 250 mg/62.5 mg, 400 mg/57 mg and 600 mg/42.9 mg oral suspension contains amoxicillin 125 mg, 250 mg, 400 mg and 600 mg, respectively and clavulanic acid 31.25 mg, 62.5 mg, 57 mg and 42.9 mg, respectively.
Natravox Injection: 500 mg/100 mg: Each powder vial contains amoxicillin sodium equivalent to 500 mg amoxicillin and potassium clavulanate equivalent to 100 mg clavulanic acid.
1000 mg/200 mg: Each powder vial contains amoxicillin sodium equivalent to 1000 mg amoxicillin and potassium clavulanate equivalent to 200 mg clavulanic acid.
These powder vials are for reconstitution as an intravenous injection or infusion
Action
Pharmacology: Pharmacokinetics: Natravox: Absorption and Fate: Amoxicillin and clavulanate potassium are well-absorbed from the gastrointestinal tract after oral administration. Approximately 50-70% of the amoxicillin and approximately 25-40% of the clavulanic acid are excreted unchanged in urine during the first 6 hrs after administration of 10 mL of 250 mg/5 mL co-amoxiclav suspension.
Neither component of co-amoxiclav is highly protein bound; clavulanic acid has been found to be approximately 25% bound to human serum and amoxicillin 18% bound.
Amoxicillin diffuses readily into most body tissues and fluids with the exception of the brain and spinal fluid. The results of experiments involving the administration of clavulanic acid to animals suggest that this compound, like amoxicillin, is well distributed in body tissues.
Microbiology: Antimicrobial Actions: Co-amoxiclav is an antibacterial combination consisting of amoxicillin (as sodium) and the beta-lactamase inhibitor, clavulanic acid (as potassium clavulanate).
Amoxicillin is the 4-hydroxy analogue of ampicillin. Amoxicillin hinders the cell wall synthesis of sensitive bacteria and is bactericidal against many Gram-positive and Gram-negative bacteria. It is active against all penicillin-sensitive bacteria: Streptococci and most strains of pneumococci, gonococci and meningococci are sensitive. Bacteria that produce beta-lactamase (e.g. most of the staphylococci) are resistant. Amoxicillin is also active against strains of Haemophilus influenza that do not produce beta-lactamase. Amoxicillin is inactivated by β-lactamases and complete cross-resistance has been reported between amoxicillin and ampicillin. The spectrum of activity of amoxicillin may be extended by use with a β-lactamase inhibitor eg, clavulanic acid. As well as reversing resistance to amoxicillin in β-lactamase producing strains of species otherwise sensitive, clavulanic acid has also been reported to enhance the activity of amoxicillin against several species not generally considered sensitive. These have included: Bacteroides, Legionella and Nocardia spp, Haemophilus influenzae, Moraxella catarrhalis and Pseudomonas pseudomallei.
Clavulanic acid has a beta-lactam structure resembling that of penicillin nucleus, except that the fused thiazolidine ring of the penicillins is replaced by an oxazolidine ring. In general, clavulanic acid has only weak antibacterial activity. It is potent progressive inhibitor of plasmid-mediated and some chromosomal beta-lactamases produced by Gram-negative bacteria including Haemophilus ducreyi, H. influenzae, Neisseria gonorrhoeae, Moraxella catarrhalis (Branhamella catarrhalis), Bacteroides fragilis and some Enterobacteriaceae. It is also an inhibitor of the beta-lactamases produced by Staphylococcus aureus. Clavulanic acid can permeate bacterial cell walls and can therefore inactivate both extracellular enzymes and those that are bound to the cell. Its mode of action depends on the particular enzyme inhibited, but it generally acts as a competitive, and often irreversible, inhibitor. Clavulanic acid consequently enhances the activity of penicillin and cephalosporin antibacterials against many resistant strains of bacteria. However, it is generally less effective against chromosomally medicated type 1 beta-lactamases: therefore, many Citrobacter, Enterobacter, Morganella and Serratia spp. And Pseudomonas aeruginosa remain resistant. Some plasmid-mediated extended-spectrum beta lactamases in Klebsiella pneumoniae, some other Enterobacteriaceae, and Ps. aeruginosa are also not inhibited by beta-lactamases inhibitors.
Co-amoxiclav is bactericidal to a wide range of organisms including: Gram-Positive: Aerobes: Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, Staphylococcus aureus, Coagulase-negative staphylococci (including Staphylococcus epidermidis), Corynebacterium species, Bacillus anthracis, Listeria monocytogenes.
Anaerobes: Clostridium species, Peptococcus species, Peptostreptococcus.
Gram-Negative: Aerobes: Haemophilus influenzae, Moraxella catarrhalis (Branhamella catarrhalis), Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species, Salmonella species, Neisseria gonorrhoeae, Neisseria meningitidis, Vibrio cholerae, Pasteurella multocida.
Anaerobes: Bacteroides species, including B. fragilis.
Indications/Uses
Upper Respiratory Tract Infections (including ENT): Sinusitis, otitis media, recurrent tonsillitis. These infections are often caused by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes.
Lower Respiratory Tract Infections: Acute exacerbations of chronic bronchitis, bronchopneumonia, urinary-tract infections often caused by Streptococcus pneumonia, Haemophilus influenzae and Moraxella catarrhalis.
Genitourinary Tract and Abdominal Infections: In particular cystitis (especially when recurrent or complicated, but not prostatitis), septic abortion, pelvic or puerperal sepsis and intra-abdominal sepsis. These infections are often caused by Enterobacteriaceae (mainly Escherichia coli), Staphylococcus saprophyticus, Enterococcus species.
Skin and Soft Tissue Infections: In particular cellulitis, animal bites and severe dental abscess with spreading cellulites caused by Staphylococcus aureus, Streptococcus pyogenes and Bacteroides species.
Dosage/Direction for Use
Duration of therapy should be appropriate to the indication and should not exceed 14 days without review.
Natravox: Tablets are not recommended in children ≤12 years.
Since both 250 mg/125 mg and 500 mg/125 mg tablets contain the same amount of clavulanic acid, two 250 mg/125 mg tablets are not equivalent to one 500 mg/125 mg tablet. Therefore, two 250 mg/125 mg tablets should not be substituted for one 500 mg/125 mg tablet.
Adults: Usual Dose: Mild to Moderate Infections: 250 mg/125 mg tab 3 times a day or 500 mg/125 mg tab twice a day.
Severe Infections: 500 mg/125 mg tab 3 times a day.
Dental Infections: 250 mg/125 mg tab 3 times a day for 5 days or 500 mg/125 mg tab twice a day for 5 days.
Suspension: Children: Based on the amoxicillin component, Natravox suspension should be dosed as follows: Patients ≥3 months: Severe Infections, Otitis Media, Lower Respiratory Tract Infections: 125 mg/31.25 mg/5 mL and 250 mg/62.5 mg/5 mL: 40 mg/kg/day every 8 hrs.
400 mg/57 mg/5 mL: 45 mg/kg/day every 8 hrs.
Neonates and Infants <3 months: 125 mg/31.25 mg/5 mL and 250 mg/62.5 mg/5 mL: 30 mg/kg/day divided every 12 hrs (125 mg/5 mL suspension is recommended).
Less Severe Infections: 125 mg/31.25 mg/5 mL and 250 mg/62.5 mg/5 mL: 20 mg/kg/day every 8 hrs.
400 mg/57 mg/5 mL: 25 mg/kg/day every 8 hrs.
Treatment duration for otitis media is 10 days.
Natravox Injection: Dosages for the Treatment for Infection: Adults and Children over 12 years: Usually 1.2 g every eight hours. By intravenous injection (3-4 minutes) or intravenous infusion (30 minutes). In more serious infections, increase frequency to six-hour intervals.
Adult Dosage for Surgical Prophylaxis: The usual dose is 1.2 g Co-amoxiclav (Natravox) IV given at the induction of anaesthesia. Operations where there is a high risk of infection, e.g. colorectal surgery, may require three, and up to four, doses of 1.2 g Co-amoxiclav (Natravox) IV in a 24-hour period. These doses are usually given at 0, 8, 16 (and 24) hours. This regimen can be continued for several days if the procedure has a significantly increased risk of infection.
Clear clinical signs of infection at operation will require a normal course of intravenous or oral Co-amoxiclav (Natravox) therapy post-operatively.
Dosage in Renal Impairment: Adults: Mild Impairment (Creatinine Clearance >30 mL/min): No change in dosage.
Moderate Impairment (Creatinine Clearance 10-30 mL/min): 1.2 g IV stat., followed by 600 mg IV 12 hourly.
Severe Impairment (Creatinine Clearance <10 mL/min): 1.2 g IV stat., followed by 600 mg IV 24 hourly. Dialysis decreases serum concentrations of Natravox and an additional 600 mg IV dose may need to be given during dialysis and at the end of dialysis.
Dosage in Hepatic Impairment: Dose with caution; monitor hepatic function at regular intervals.
There are, as yet, insufficient data on which to base a dosage recommendation.
Each 1.2 g vial of Co-amoxiclav (Natravox) IV contains 1.0 mmoL of potassium and 2.7 mmoL of sodium (approximately).
Administration: Natravox: Swallow whole without chewing. To minimize potential GI intolerance, administer at the start of a meal. The absorption of co-amoxiclav is optimized when taken at the start of a meal.
Natravox Injection: Co-amoxiclav (Natravox) IV vials should be given by slow intravenous injection over a period of three to four minutes. It may be injected directly into a vein or via a drip tube.
Overdosage
Cases of overdosages are usually asymptomatic. Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. They may be treated symptomatically with attention to the water electrolyte balance. Co-amoxiclav may be removed from the circulation by haemodialysis.
During the administration of high doses of co-amoxiclav, adequate fluid intake and urinary output should be maintained to minimize the possibility of amoxicillin crystalluria.
Amoxicillin crystalluria, in some cases leading to renal failure, has been observed.
Contraindications
Co-amoxiclav is contraindicated in patients with a history of allergic reactions to any penicillin. It is also contraindicated in patients with a previous history of amoxicillin-potassium clavulanate-associated cholestatic jaundice/hepatic dysfunction.
Special Precautions
Changes in liver function tests have been observed in some patients receiving Co-amoxiclav. The clinical significance of these changes is uncertain but Co-amoxiclav should be used with caution in patients with evidence of hepatic dysfunction.
Cholestatic jaundice, which may be severe, but is usually reversible, has been reported rarely. Signs and symptoms may not become apparent for several weeks after treatment has ceased.
In patients with reduced urine output crystalluria has been observed very rarely, predominantly with parenteral therapy. During administration of high doses of amoxicillin it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria. Amoxicillin has been reported to precipitate in bladder catheters after intravenous administration of large doses. A regular check of potency should be maintained.
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity.
Erythematous rashes have been associated with glandular fever in patients receiving amoxicillin.
Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.
Natravox: Renal function should be monitored in patients with moderate to severe renal impairment and co-amoxiclav dosage should be adjusted.
Treatment with co-amoxiclav may give rise to a maculopapular rash during therapy or within a few days after completion. The incidence of maculopapular rash is especially high in patients suffering from infectious mononucleosis.
The use of this antibiotic may lead to the selection of resistant strains of organisms and sensitivity testing should, therefore, be carried out whenever possible, to demonstrate the appropriateness of therapy. Monilial overgrowth eg, vaginitis and thrush have been reported.
Treatment with co-amoxiclav can cause gastrointestinal symptoms eg, diarrhea, nausea and vomiting which are dose-related and can be minimized by administering the drug at the start of a meal. In addition, as these symptoms are especially related to the potassium clavulanate component, where these gastrointestinal symptoms occur and a higher concentration of amoxicillin is required, consideration should be given to administering the additional amoxicillin separately.
Natravox Injection: In patients with renal impairment, dosage should be adjusted according to the degree of impairment.
If the parenteral administration of high doses is necessary, the sodium content must be taken into account in patients on a sodium restricted diet.
Use in Pregnancy: Natravox: There are, however, no adequate studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Natravox should be used during pregnancy only if clearly needed.
Use in Lactation: Natravox: Amoxicillin-class antibiotics are excreted in the milk; therefore, caution should be exercised when co-amoxiclav is administered to a nursing mother.
Use In Pregnancy & Lactation
Reproduction studies in animals (mice and rats) with orally and parenterally administered Co-amoxiclav have shown no teratogenic effects. In a single study in women with preterm, premature rupture of the foetal membrane (pPROM), it was reported that prophylactic treatment with Co-amoxiclav may be associated with an increased risk of necrotising enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy, especially during the first trimester, unless considered essential by the physician.
Co-amoxiclav may be administered during the period of lactation. With the exception of the risk of sensitisation, associated with the excretion of trace quantities in breast milk, there are no known detrimental effects for the breast-fed infant.
Adverse Reactions
Natravox: Amoxicillin/clavulanate potassium is generally well-tolerated. The majority of adverse effects observed in clinical trials were uncommon and of a mild and transitory nature and <3% of patients discontinued therapy because of drug-related adverse effects. The most frequently reported adverse effects were diarrhea/loose stools, nausea, skin rashes, urticaria, vomiting and vaginitis. The overall incidence of adverse effects, and in particular diarrhea, increased with the higher recommended dose. Other less frequently reported reactions include: Abdominal discomfort, flatulence and headache.
Gastrointestinal Reactions: Diarrhea, indigestion, nausea, gastritis, stomatitis, glossitis, black "hairy" tongue, vomiting and mucocutaneous candidiasis have been reported. Antibiotic-associated colitis (including pseudomembraneous colitis and hemorrhage colitis) has been reported rarely with its onset occurring during or after antibiotic treatment. Nausea, although uncommon, is more often associated with higher oral dosages. If gastrointestinal adverse effects occur with oral therapy, they may be reduced by taking co-amoxiclav at the start of meals.
Superficial tooth discoloration has been reported rarely, mostly with the suspension. It can usually be removed by brushing.
Renal and Urinary Tract Disorders: Crystalluria has been reported very rarely.
Genitourinary Effects: Vaginal itching, soreness and discharge may occur.
Hepatic Effects: Moderate and asymptomatic rises in aspartate transaminase (AST) and/or alanine transaminase (ALT) and alkaline phosphatases have been reported occasionally. Hepatitis and cholestatic jaundice have been reported rarely. These hepatic reactions have been reported more commonly with co-amoxiclav than with other penicillins.
After co-amoxiclav hepatic reactions have been reported more frequently in males and elderly patients, particularly those >65 years. The risk increases with duration of treatment >14 days. These reactions have been very rarely reported in children. Signs and symptoms usually occur during or shortly after treatment but in some cases, may not occur until several weeks after treatment has ended. Hepatic reactions are usually reversible but they may be severe and very rarely, deaths have been reported.
Hypersensitivity Reactions: Urticarial and erythematous skin rashes sometimes occur. Rarely erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis (AGEP), serum sickness-like syndrome and hypersensitivity vasculitis have been reported. Treatment should be discontinued if one of these disorders occurs. In common with other β-lactam antibiotics, angioedema and anaphylaxis have been reported. Interstitial nephritis can occur rarely.
Hematological Effects: As with other β-lactams, transient leukopenia (including neutropenia and agranulocytosis), thrombocytopenia and hemolytic anemia have been reported rarely. Prolongation of bleeding time and prothrombin time has also been reported rarely.
Central Nervous System (CNS) Effects: CNS effects have been seen very rarely. These include reversible hyperactivity, dizziness, headache and convulsions. Convulsions may occur with impaired renal function or in those receiving high doses.
Natravox Injection: Adverse reactions are uncommon and mainly of a mild and transitory nature.
Gastrointestinal Reactions: Diarrhea, indigestion, nausea, vomiting, and mucocutaneous candidiasis have been reported. Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis) has been reported rarely. Nausea, although uncommon, is more often associated with higher oral dosages. If gastrointestinal side effects occur with oral therapy they may be reduced by taking Co-amoxiclav at the start of meals.
Superficial tooth discolouration has been reported rarely, mostly with the suspension. It can usually be removed by brushing.
Renal and Urinary Tract Disorders: Crystalluria has been reported very rarely.
Genitourinary Effects: Vaginal itching, soreness and discharge may occur.
Hepatic Effects: Moderate and asymptomatic rises in AST and/or ALT and alkaline phosphatases have been reported occasionally. Hepatitis and cholestatic jaundice have been reported rarely. These hepatic reactions have been reported more commonly with Co-amoxiclav than with other penicillins.
After Co-amoxiclav hepatic reactions have been reported more frequently in males and elderly patients, particularly those over 65 years. The risk increases with duration of treatment longer than 14 days. These reactions have been very rarely reported in children. Signs and symptoms usually occur during or shortly after treatment but in some cases may not occur until several weeks after treatment has ended. Hepatic reactions are usually reversible but they may be severe and, very rarely, deaths have been reported.
Hypersensitivity Reactions: Urticarial and erythematous skin rashes sometimes occur. Rarely erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalised exanthematous pustulosis (AGEP), serum sickness-like syndrome and hypersensitivity vasculitis have been reported. Treatment should be discontinued if one of these disorders occurs. In common with other Beta-lactams antibiotics angioedema and anaphylaxis have been reported. Interstitial nephritis can occur rarely.
Haematological Effects: As with other Beta-lactams transient leucopenia (including neutropenia and agranulocytosis), thrombocytopenia and haemolytic anaemia have been reported rarely. Prolongation of bleeding time and prothrombin time has also been reported rarely.
CNS Effects: CNS effects have been seen very rarely. These include reversible hyperactivity, dizziness, headache and convulsions. Convulsions may occur with impaired renal function or in those receiving high doses.
Local: Thrombophlebitis at the site of injection has been reported occasionally.
Side Effects
Natravox: Transient hepatitis and cholestatic jaundice have been reported.
Allergic reactions may occur, presenting as a pruritic skin rash, an erythematous skin reaction, urticaria, angioedema, anaphylaxis or eosinophilia. Coombs' test may become positive. In this event, withdrawal of co-amoxiclav and the administration of an antihistamine will suffice in most cases. Should a serious anaphylactic reaction occur, co-amoxiclav should be discontinued and the patient treated with the usual agents: Adrenaline, corticosteroids and antihistamines.
Pseudomembranous colitis has been reported.
Rarely, erythema multiforme and Stevens-Johnson syndrome have been reported.
Drug Interactions
Probenecid decreases the renal tubular secretion of amoxicillin but does not affect clavulanic acid excretion. Concurrent use with co-amoxiclav may result in increased and prolonged blood levels of amoxicillin but not of clavulanic acid.
Co-amoxiclav may reduce the efficacy of oral contraceptives and patients should be warned accordingly.
Penicillins such as co-amoxiclav may decrease the removal of methotrexate from the body increasing the risk of toxicity.
Antibiotics such as co-amoxiclav may alter the effect of anticoagulants such as warfarin.
Natravox Injection: Intravenous administration can cause local irritation, induration and phlebitis at the injection site.
Caution For Usage
Natravox: Directions for Mixing Oral Suspension: Tap bottle until all powder flows freely. For a 60-mL suspension, add 50 mL water, while for a 70-mL suspension, add 58 mL water. Shake vigorously until the powder is evenly suspended. Prepare the suspension at the time of dispensing.
Natravox Injection: Incompatibilities: Co-amoxiclav injection should NOT be mixed or reconstituted with dextrose solution, sodium bicarbonate solution for injection, protein hydrolysates and other proteinaceous fluids, blood or plasma or with intravenous lipid emulsions.
If Co-amoxiclav is prescribed concurrently with an aminoglycoside, the antibiotics should not be mixed in the syringe, intravenous fluid container or giving set because loss of activity of the aminoglycoside can occur under these conditions.
Direction for Reconstitution: Co-amoxiclav (Natravox) 500 mg/100 mg IV: Dissolve the powder in 10 mL Water For Injection.
Co-amoxiclav (Natravox) 1000 mg/200 mg IV: Dissolve the powder in 20 mL Water For Injection.
For intravenous infusion: The reconstituted vial should be further diluted with the desired volume of a suitable infusion fluid.
Co-amoxiclav (Natravox) IV is less stable in infusions containing glucose, dextran or bicarbonate. Reconstituted solution should, therefore, not be added to such infusions but may be injected into the drip tubing over a period of three to four minutes.
NOTE: Co-amoxiclav (Natravox) IV vials are not suitable for intramuscular or subcutaneous administration.
Co-amoxiclav (Natravox) IV vials should be given by slow intravenous injection over a period of three to four minutes. It may be injected directly into a vein or via a drip tube.
Use reconstituted solution within 20 minutes. Discard any unused solution.
Storage
Natravox: Store in a cool dry place <25°C.
Once reconstituted, store suspension in a refrigerator at 2-8°C (but not frozen) and use within 7 days.
Natravox Injection: Store the dry powder in cool dry place store below 25°C.
MIMS Class
ATC Classification
J01CR02 - amoxicillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.
Presentation/Packing
Natravox: 375 mg tab (film-coated) 48's. 625 mg tab (film-coated) 40's. 156.25 mg/5 mL oral susp 60 mL. 228.5 mg/5 mL oral susp 70 mL. 312.5 mg/5 mL oral susp 60 mL. 457 mg/5 mL oral susp 35 mL, 70 mL. 642.9 mg/5 mL oral susp 50 mL, 70 mL, 100 mL.
Natravox Injection: 500 mg/100 mg powd for inj (vial) 1's. 1 g/200 mg powd for inj (vial) 1's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in