Triaphin 250 mg./ 1 g Powder for solution for injection.

TRIAPHIN is indicated for the treatment of the following infections when caused by susceptible organisms:

• Bacterial septicaemia caused by methicillin-sensitive Staphylococcus aureus (MSSA), Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae, or Klebsiella pneumoniae.
• Meningitis caused by Haemophilus influenzae, Neisseria meningitidis, or Streptococcus pneumoniae.
• Intra-abdominal infections caused by Escherichia coli, Klebsiella pneumonia, Clostridium species (Note: most strains of Clostridium difficile are resistant) or Peptostreptococcus species.
• Skin and skin structure infections caused by methicillin-sensitive Staphylococcus aureus (MSSA), Streptococcus pyogenes, Streptococcus viridans group, Escherichia coli, Enterobacter cloacae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Morganella morganii, Pseudomonas aeruginosa, Serratia marcescens, or Peptostreptococcus species.
• Bone and joint infections caused by methicillin-sensitive Staphylococcus aureus (MSSA), Streptococcus pneumoniae, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, or Enterobacter species.
• Renal and urinary tract infections (complicated and uncomplicated) caused by Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii or Klebsiella pneumoniae.
• Respiratory tract infections caused by Streptococcus pneumoniae, methicillin-sensitive Staphylococcus aureus (MSSA), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Escherichia coli, Enterobacter aerogenes, Proteus mirabilis, or Serratia marcescens.
• Ear, nose and throat infections (acute bacterial otitis media) caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase-producing strains), or Moraxella catarrhalis (including beta-lactamase-producing strains).
• Uncomplicated gonorrhoea (cervical/urethral and rectal) caused by Neisseria gonorrhoeae, including both penicillinase- and non-penicillinase-producing strains, and pharyngeal gonorrhoea caused by non-penicillinase-producing strains of Neisseria gonorrhoeae.
• Surgical prophylaxis: The pre-operative administration of a single 1 g dose of TRIAPHIN may reduce the incidence of post-operative infections.

Posology

Standard dosage

Adults and children over 12 years: 1 - 2 g ceftriaxone once daily (every 24 hours). In severe cases or in infections caused by moderately sensitive organisms, the dosage may be increased to 4 g, once daily. Refer below to special dosage instructions for other patient populations.

Duration of therapy

The duration of therapy varies according to the course of the disease. Administration of TRIAPHIN should be continued for a minimum of 48 to 72 hours after the patient has become afebrile or evidence of bacterial eradication has been obtained.

Combination therapy

Synergy between TRIAPHIN and aminoglycosides has been demonstrated with many Gram-negative bacteria under experimental conditions. Although enhanced activity of such combinations is not always predictable, it should be considered in severe, life threatening infections due to microorganisms such as Pseudomonas aeruginosa. Due to chemical incompatibility between TRIAPHIN and aminoglycosides, the two medicines must be administered separately at the recommended dosages. Chemical incompatibility with TRIAPHIN has also been observed with IV administration of amsacrine, vancomycin and fluconazole.

Special dosage instructions

Paediatric population

Neonates, infants and children up to 12 years: The following dosage schedules are recommended for once daily administration:

• Neonates (up to 14 days): 20 u2013 50 mg/kg bodyweight once daily. The daily dose should not exceed 50 mg/kg. TRIAPHIN is contraindicated in premature neonates up to a postmenstrual age of 41 weeks (gestational age + chronological age) (see section 4.3).
• TRIAPHIN is contraindicated in neonates (u2264 28 days) if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone-calcium (see sections 4.3, 4.4 and 4.8).
• For neonates, infants and children (15 days to 12 years): 20 u2013 80 mg/kg once daily. For children with bodyweights of 50 kg or more, the usual adult dose should be used.
• Intravenous doses of u2265 50 mg/kg bodyweight, in infants and children up to 12 years of age should be given by infusion over at least 30 minutes. In neonates, intravenous doses should be given over 60 minutes to reduce the potential risk of bilirubin encephalopathy.
• Meningitis: In bacterial meningitis in infants and children, treatment begins with doses of 100 mg/kg (up to a maximum of 4 g) once daily. As soon as the causative organism has been identified and its sensitivity determined, the dosage can be reduced accordingly. For children with bodyweights of 50 kg or more, the usual adult dosage should be used.

Special populations

Elderly

No dose adjustment of TRIAPHIN is required in patients u2265 65 years of age provided there is no severe renal and hepatic impairment.

Patients with hepatic impairment

In patients with liver damage there is no need for the dosage to be reduced provided renal function is not impaired.

Patients with renal impairment

In patients with impaired renal function there is no need to reduce the dosage of TRIAPHIN, provided hepatic function is not impaired. In cases of severe renal failure (creatinine clearance < 10 mL/min) the TRIAPHIN dosage should not exceed 2 g daily.

Patients with both hepatic impairment and renal impairment

In patients with both severe renal and hepatic dysfunction, the plasma concentrations of ceftriaxone should be determined at regular intervals and if necessary the dose should be adjusted. Clinical monitoring for safety and efficacy is advised.

Dialysis

TRIAPHIN is not removed by peritoneal- or haemodialysis. In patients undergoing dialysis no additional supplementary dosing is required following the dialysis. Plasma concentrations should however be monitored, to determine whether dosage adjustments are necessary, since the elimination rate in these patients may be altered.

Meningitis

For bacterial meningitis in adults, the recommended dose is 4 g daily. For dosages recommended in paediatrics, see section u201cPaediatric population: Meningitisu201d above.

Lyme borreliosis

50 mg/kg to a maximum of 2 g in children and adults, once daily for 14 days.

Gonorrhoea

In the treatment of uncomplicated gonorrhoea (penicillinase-producing and non-penicillinase-producing strains) a single IM dose of 250 mg is recommended.

Perioperative prophylaxis

A single dose of 1 to 2 g, depending on the risk of infection of 30 to 90 minutes prior to surgery. In colorectal surgery, administration of TRIAPHIN with or without a 5-nitroimidazole, e.g. ornidazole (separate administration, see Method of administration below) has been proven effective.

Method of administration

TRIAPHIN must be reconstituted prior to use and can be administered by intramuscular or intravenous injection or infusion. As a general rule the solutions should be used immediately after preparation. Reconstituted solutions retain their physical and chemical stability for 6 hours at room temperature (or 24 hours in the refrigerator at 2 - 8 u00b0C). The solutions range in colour from colourless / pale yellow to reddish orange, depending on the concentration and length of storage. The colouration of the solutions is of no significance for the efficacy or tolerance of the medicine.

Intramuscular Injection

TRIAPHIN must be injected well within the body of a relatively large muscle. It is recommended that not more than 1 g be injected at one site. If lidocaine (lignocaine) is used as the solvent, the resulting solution must never be administered intravenously (see section 4.3).

Intravenous Injection

The intravenous administration should be given over two to four minutes.

Intravenous infusion

The infusion should be given over a period of at least 30 minutes.

Ceftriaxone solutions should not be mixed with or piggybacked into solutions containing other antimicrobial drugs or into diluent solutions other than those listed above, owing to possible incompatibility. For instructions on reconstitution of the product before administration, see section 6.6. For incompatibilities, see section 6.2.

• Hypersensitivity: known hypersensitivity to ceftriaxone or to any other cephalosporins. Patients with previous hypersensitivity reactions to penicillin and other beta lactam medicines may be at greater risk of hypersensitivity to ceftriaxone (see section 4.4).
• Lidocaine/lignocaine: contraindications to lidocaine/lignocaine must be excluded before intramuscular injection of TRIAPHIN when lidocaine (lignocaine) solution is used as a solvent (see section 4.2). See the contraindications section in the professional information of lidocaine (lignocaine). TRIAPHIN solutions containing lidocaine (lignocaine) should never be administered intravenously.
• Premature neonates: TRIAPHIN is contraindicated in premature neonates up to postmenstrual age of 41 weeks (gestational age + chronological age).
• Hyperbilirubinaemic newborns: hyperbilirubinaemic newborns, should not be treated with TRIAPHIN. In vitro studies have shown that TRIAPHIN can displace bilirubin from its binding to serum albumin leading to a possible risk of bilirubin encephalopathy in these patients.
• Neonates and calcium containing IV solutions: TRIAPHIN is contraindicated in neonates (u2264 28 days) if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition, because of the risk of precipitation of ceftriaxone-calcium. A small number of cases of fatal outcomes with calcium-ceftriaxone precipitates in the lungs and kidneys have been reported at autopsy in both term and preterm neonates receiving TRIAPHIN and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both TRIAPHIN and calcium-containing fluids and in some a precipitate was observed in the intravenous infusion line. At least one fatality has been reported in a neonate to whom TRIAPHIN and calcium-containing fluids were administered at different time points via different intravenous lines; no crystalline material was observed at autopsy in this neonate. There have been no similar reports in patients other than neonates (see sections 4.2, 4.4 and 4.8).

Interaction with calcium containing products

TRIAPHIN must not be mixed or administered simultaneously with calcium-containing solutions or products, even via different infusion lines. TRIAPHIN and IV calcium-containing solutions or products must not be administered within 48 hours of each other. Precipitation of ceftriaxone-calcium may occur when TRIAPHIN is mixed with calcium-containing solutions in the same IV administration line. TRIAPHIN must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site.

Fatal outcomes have been reported in neonates receiving TRIAPHIN and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both TRIAPHIN and calcium-containing fluids and in some a precipitate was observed in the intravenous infusion line. At least one fatality has been reported in a neonate in whom TRIAPHIN and calcium-containing fluids were administered at different time points via different intravenous lines. In some cases, times of administration of ceftriaxone and calcium-containing solutions differed (see sections 4.2, 4.3, 4.5 and 4.8).

Do not use diluents containing calcium, such as Ringeru2019s lactate solution or Hartmannu2019s solution to reconstitute TRIAPHIN. Precipitate formation can result.

There are no reports to date of intravascular or pulmonary precipitations in patients, other than neonates, treated with ceftriaxone and calcium-containing IV solutions. However, the theoretical possibility exists for an interaction between ceftriaxone and calcium-containing IV solutions in patients other than neonates. Therefore, TRIAPHIN and calcium-containing solutions, including continuous calcium-containing infusions such as parenteral nutrition, should not be mixed or co-administered to any patients irrespective of age even via different infusion lines at different sites. As a further theoretical consideration and based on 5 half-lives of ceftriaxone, TRIAPHIN and IV calcium-containing solutions should not be administered within 48 hours of each other in any patient (see sections 4.2, 4.3, 4.5 and 4.8).

No data are available on potential interaction between TRIAPHIN and oral calcium-containing products or interaction between intramuscular TRIAPHIN and calcium-containing products (IV or oral).

Hypersensitivity reactions

Serious and occasionally fatal hypersensitivity reactions have been reported (see section 4.8). In case of severe hypersensitivity reactions, treatment with TRIAPHIN must be discontinued immediately and adequate emergency measures must be initiated. Before beginning treatment, it should be established whether the patient has a history of severe hypersensitivity reactions to ceftriaxone, to other cephalosporins or to any other type of beta-lactam agent. Caution should be used if TRIAPHIN is given to patients with a history of non-severe hypersensitivity to other beta-lactam agents.

Severe cutaneous adverse reactions (Stevens Johnson syndrome or Lyell's syndrome/toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms (DRESS)) which can be life-threatening or fatal have been reported in association of ceftriaxone treatment; however, the frequency of these events is not known (see section 4.8).

Paediatric population

Safety and effectiveness of TRIAPHIN in neonates, infants and children have been established for the dosages described under section 4.2. Studies have shown that TRIAPHIN, like some other cephalosporins, can displace bilirubin from serum albumin. TRIAPHIN is contraindicated in neonates (especially prematures) at risk of developing bilirubin encephalopathy (see section 4.3).

Immune mediated haemolytic anaemia

An immune mediated haemolytic anaemia has been observed in patients receiving cephalosporin class antibacterials including TRIAPHIN (see section 4.8). Severe cases of haemolytic anaemia, including fatalities, have been reported during TRIAPHIN treatment in both adults and children. If a patient develops anaemia while on ceftriaxone, the diagnosis of a cephalosporin-associated anaemia should be considered and ceftriaxone discontinued until the aetiology is determined.

Use of lidocaine (lignocaine)

In case a lidocaine (lignocaine) solution is used as a solvent, ceftriaxone solutions must only be used for intramuscular injection. Contraindications to lidocaine (lignocaine), warnings and other relevant information as detailed in the Professional Information of lidocaine (lignocaine) must be considered before use (see section 4.3). The lidocaine (lignocaine) solution should never be administered intravenously.

Colitis / Overgrowth of non-susceptible microorganisms

Antibacterial medicine-associated colitis and pseudo-membranous colitis have been reported with nearly all antibacterial agents, including ceftriaxone such as in TRIAPHIN, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of TRIAPHIN (see section 4.8). Careful medical history is necessary since colitis has been reported to occur over two months after the administration of antibacterial medicines, such as TRIAPHIN. Discontinuation of therapy with TRIAPHIN and the administration of specific treatment for Clostridium difficile should be considered. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated. Medicines that inhibit peristalsis should not be given.

Superinfections with non-susceptible micro-organisms

may occur as with other antibacterial agents.

Severe renal and hepatic insufficiency

In severe renal and hepatic insufficiency, close clinical monitoring for safety and efficacy is advised (see section 4.2).

Antibacterial spectrum

Ceftriaxone has a limited spectrum of antibacterial activity and may not be suitable for use as a single agent for the treatment of some types of infections unless the pathogen has already been confirmed (see section 4.2).

In polymicrobial infections, where suspected pathogens include organisms resistant to ceftriaxone, administration of an additional antibiotic should be considered.

Biliary lithiasis

When shadows are observed on sonograms, consideration should be given to the possibility of precipitates of calcium ceftriaxone. Shadows, which have been mistaken for gallstones, have been detected on sonograms of the gallbladder and have been observed more frequently at ceftriaxone doses of 1 g per day and above. Caution should be particularly considered in the paediatric population. Such precipitates disappear after discontinuation of ceftriaxone therapy. Precipitates of calcium-ceftriaxone have been occasionally associated with symptoms. In symptomatic cases, conservative nonsurgical management is recommended and discontinuation of ceftriaxone treatment should be considered by the doctor based on specific benefit risk assessment (see section 4.8).

Biliary stasis

Cases of pancreatitis, possibly of biliary obstruction aetiology, have been reported in patients treated with TRIAPHIN (see section 4.8). Most patients presented with risk factors for biliary stasis and biliary sludge e.g. preceding major therapy, severe illness and total parenteral nutrition. A trigger or cofactor of TRIAPHIN-related biliary precipitation cannot be ruled out.

Renal lithiasis

Cases of renal lithiasis have been reported, which is reversible upon discontinuation of ceftriaxone (see section 4.8). In symptomatic cases, sonography should be performed. Use in patients with history of renal lithiasis or with hypercalciuria should be considered by the medical doctor based on specific benefit risk assessment.

Jarisch-Herxheimer reaction (JHR)

Some patients with spirochete infections may experience a Jarisch-Herxheimer reaction (JHR) shortly after TRIAPHIN treatment is started. JHR is usually a self-limiting condition or can be managed by symptomatic treatment. TRIAPHIN treatment should not be discontinued if such reaction occurs.

Encephalopathy

Encephalopathy has been reported with the use of ceftriaxone, such as in TRIAPHIN (see section 4.8), particularly in elderly patients with severe renal impairment (see section 4.2) or central nervous system disorders. If ceftriaxone-associated encephalopathy is suspected (e.g. decreased level of consciousness, altered mental state, myoclonus, convulsions), discontinuation of TRIAPHIN should be considered.

Long term treatment: Blood monitoring

During prolonged treatment a complete blood count should be performed at regular intervals.

Influence on diagnostic tests

In patients treated with TRIAPHIN the Coombs' test may become falsely positive. TRIAPHIN, like other antibiotics, may result in false-positive test results for galactosemia. Likewise, nonenzymatic methods for the glucose determination in urine may give false positive results. For this reason, urine-glucose determination during therapy with TRIAPHIN should be done enzymatically.

The presence of ceftriaxone may falsely lower estimated blood glucose values obtained with some blood glucose monitoring systems. Please refer to instructions for use for each system. Alternative testing methods should be used if necessary.

Excipient sodium

Each TRIAPHIN 250 mg vial contains less than 1 mmol sodium (23 mg) per 250 mg vial, i.e. is essentially u201csodium freeu201d. Each TRIAPHIN 1 g vial contains approximately 83 mg of sodium per 1 g ceftriaxone, equivalent to 4,15 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Calcium-containing products

TRIAPHIN should not be added to solutions containing calcium. Do not use diluents containing calcium such as Ringeru2019s lactate solution or Hartmannu2019s solution to reconstitute TRIAPHIN vials, or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when TRIAPHIN is mixed with calcium-containing solutions in the same IV administration line. TRIAPHIN must not be administered simultaneously with calcium containing IV solutions, including continuous calcium containing infusions such as parenteral nutrition via a Y-site (see sections 4.2, 4.3, 4.4 and 4.8).

There have been no reports of an interaction between ceftriaxone and oral calcium-containing products or interaction between intramuscular ceftriaxone and calcium-containing products (intravenous or oral).

Anticoagulants

Concomitant use of TRIAPHIN with Vitamin K antagonists may increase the risk of bleeding. Coagulation parameters should be monitored frequently, and the dose of the anticoagulant adjusted accordingly, both during and after treatment with TRIAPHIN (see section 4.8).

Aminoglycosides

There is conflicting evidence regarding a potential increase in renal toxicity of aminoglycosides when used with cephalosporins including TRIAPHIN. The recommended monitoring of aminoglycoside levels and renal function in clinical practice should be closely adhered to in such cases.

Laboratory tests

In patients treated with ceftriaxone the Coombs' test may become false positive. TRIAPHIN may result in false positive tests for galactosemia. Likewise, nonezymatic methods for the glucose determination in urine may give false positive results. For this reason urine glucose determination during therapy with TRIAPHIN should be done enzymatically. TRIAPHIN may interfere with the Jaffe method of measuring creatinine concentrations and may produce falsely high values; this should be borne in mind when measuring renal function. The presence of TRIAPHIN may falsely lower estimated blood glucose values obtained with some blood glucose monitoring systems. Please refer to instructions for use for each system. Alternative testing methods should be used if necessary.

Chloramphenicol

In an in vitro study antagonistic effects have been observed with the combination of chloramphenicol and TRIAPHIN. The clinical relevance of this finding is unknown.

Probenecid

The elimination of TRIAPHIN is not altered by probenecid.

Diuretics

No impairment of renal function has been observed after concurrent administration of large doses of TRIAPHIN and potent diuretics (e.g. furosemide).

Alcohol

No effects similar to that of disulfiram has been demonstrated after administration of alcohol with TRIAPHIN. TRIAPHIN does not contain an N-methyl-thiotetrazole moiety associated with possible ethanol intolerance and bleeding problems.

Antibacterial medicines

There may be antagonism between TRIAPHIN and bacteriostatic antibacterial medicines.

Pregnancy

Ceftriaxone crosses the placental barrier. Safety in human pregnancy has not been established. Reproductive studies in animals have shown no evidence of embryotoxicity, fetotoxicity, teratogenicity, birth or perinatal and postnatal development. In primates, no embryotoxicity or teratogenicity has been observed.

Breastfeeding

Safety in lactation has not been established. Low concentrations of ceftriaxone are excreted in human milk. Caution should be exercised when TRIAPHIN is administered to a breastfeeding woman.

Fertility

Reproductive studies in animals have shown no evidence of adverse effects on male or female fertility.

During treatment with TRIAPHIN, undesirable effects may occur (e.g. dizziness), which may influence the ability to drive and use machines (see section 4.8). Patients should be cautious when driving or operating machinery.

a) Summary of the safety profile

The most frequently reported adverse reactions for ceftriaxone are eosinophilia, leucopenia, thrombocytopenia, diarrhoea, rash, and hepatic enzymes increased.

b) Tabulated list of adverse reactions

The table below shows all adverse drug reactions (ADRs) observed during clinical trials and postmarket spontaneous reports with ceftriaxone.

System Organ Class

Frequency

Frequent

Less Frequent

Not known

Infections and infestations

Genital fungal infection, pseudo-membranous colitis

Superinfection

Blood and lymphatic system disorders

Eosinophilia, leucopenia, thrombocytopenia

Granulocytopenia, anaemia, coagulopathy

Haemolytic anaemia, agranulocytosis

Immune system disorders

Anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, hypersensitivity

Jarisch-Herxheimer reaction

Nervous system disorders

Headache, dizziness, encephalopathy

Convulsion

Ear and labyrinth disorders

Vertigo

Respiratory, thoracic and mediastinal disorders

Bronchospasm

Gastrointestinal disorders

Diarrhoea, loose stools

Nausea, vomiting

Pancreatitis, stomatitis, glossitis

Hepatobiliary disorders

Hepatic enzyme increased

Gall bladder precipitation, kernicterus, hepatitis cholestatic

Skin and subcutaneous tissue disorders

Rash

Pruritus, urticaria

Stevens Johnson Syndrome, toxic epidermal necrolysis, erythema multiforme, acute generalised exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS)

Renal and urinary disorders

Haematuria, glycosuria

Oliguria, renal precipitation (reversible)

General disorders and administration site conditions

Phlebitis, injection site pain, pyrexia, oedema, chills

Investigations

Blood creatinine increased

Coombs test false positive, galactosaemia test false positive, non enzymatic methods for glucose determination false positive

a Based on post-marketing reports. Since these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorised as not known.

b See section 4.4

c Usually reversible upon discontinuation of ceftriaxone

c. Description of selected adverse reactions

Interaction with calcium

Cases of ceftriaxone precipitation in the urinary tract have been reported, mostly in children treated with high doses (e.g. u2265 80 mg/kg/day) or total doses exceeding 10 grams) and who have other risk factors (e.g. dehydration, confinement to bed). This event may be asymptomatic or symptomatic, and may lead to ureteric obstruction and postrenal acute renal failure but is usually reversible upon discontinuation of TRIAPHIN.

Infections and infestations

Reports of diarrhoea following the use of ceftriaxone may be associated with Clostridium difficile. Appropriate fluid and electrolyte management should be instituted (see section 4.4).

Blood and lymphatic system disorders

Isolated cases of agranulocytosis (< 500/mm3) have been reported, most of them after 10 days of treatment and following total doses of 20 g or more. Coagulation disorders have been reported.

Renal and urinary disorders

Renal precipitation has been reported, mostly in children older than 3 years who have been treated with either high daily doses (e.g. u2265 80 mg/kg/day) or total doses exceeding 10 g and presenting with other risk factors (e.g. fluid restrictions, confinement to bed). This event may be symptomatic or asymptomatic, may lead to renal insufficiency, and is reversible upon discontinuation of TRIAPHIN.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8 Suspected adverse reactions can also be reported directly to the HCR via [email protected]

In the case of overdosage, plasma concentration would not be reduced by haemodialysis or peritoneal dialysis. There is no specific antidote. Treatment is symptomatic and supportive.