Dapto Medis 500 mg

/ Pharma Medis

cSSSI without concurrent Staphylococcus aureus bacteraemia (SAB): daptomycin 500 mg, 4 mg/kg is administered intravenously in 0.9% sodium chloride or Lactated ringers injection once every 24 hours for 7-14 days or until the infection is resolved.

Dosage in Patients with Staphylococcus aureus Bloodstream Infections (Bacteremia), Including Those with Right-Sided Infective Endocarditis, Caused by Methicillin- Susceptible and Methicillin-Resistant Isolates: daptomycin 500 mg, 6 mg/kg intravenously in 0.9% sodium chloride or Lactated ringers injection once every 24 hours for 2 to 6 weeks. There are limited safety data for the use of daptomycin 500 mg, for more than 28 days of therapy. In the Phase 3 trial, there were a total of 14 adult patients who were treated with daptomycin for more than 28 days.

This medical product is administered intravenously in 0.9 % sodium chloride or Lacteted ringers injection. daptomycin should not be used more frequently than once a day.
One ml provides 50 mg of daptomycin after reconstitution with 10 ml of sodium chloride 9 mg/ml (0.9 %) solution.
One ml provides 10 mg after dilution in Lactated ringers injection (for infusion bags).

Creatine phosphokinase (CPK) levels must be measured at baseline and at regular intervals (at least weekly) during treatment.
Renal impairment: The recommended dosage regimen for daptomycin 500 mg in adult patients with CLCR less than 30 mL/min, including adult patients on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), is 4 mg/kg (cSSSI) or 6 mg/kg (S. aureus bloodstream infections) once every 48 hours. When possible, daptomycin should be administered following the completion of hemodialysis on hemodialysis days.
Method of administration
In adults, daptomycin 500 mg is given by intravenous infusion and administered over a 30-minute period or by intravenous injection and administered over a 2-minute period.
See prescribing information for full details.

Treatment of infections
* Complicated skin and skin structure infections
* Complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of the following Gram-positive bacteria: Staphylococcus aureus (including methicillin-resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subsp. equisimilis, and Enterococcus faecalis (vancomycin-susceptible isolates only).
* Staphylococcus aureus Bloodstream Infections (Bacteremia), Including those with Right-Sided Infective Endocarditis, caused by Methicillin-Susceptible and Methicillin-Resistant Isolates Staphylococcus aureus bloodstream infections (bacteremia), including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates.
* Combination therapy may be clinically indicated if the documented or presumed pathogens include Gram negative or anaerobic organisms.

Hypersensitivity to the active substance or to any of the excipients

Anaphylaxis/hypersensitivity reactions
Anaphylaxis/hypersensitivity reactions have been reported with daptomycin. If an allergic reaction to daptomycin mg occurs, discontinue use and institute appropriate therapy.
Deep-seated infections
Patients with deep-seated infections should receive any required surgical interventions (e.g. debridement, removal of prosthetic devices, valve replacement surgery) without delay.
Non-susceptible micro-organisms
The use of antibacterials may promote the overgrowth of non-susceptible micro-organisms. If superinfection occurs during therapy, appropriate measures should be taken.
Clostridioides difficile-associated diarrhoea
Clostridioides difficile-associated diarrhoea (CDAD) has been reported with Daptomycin. If CDAD is suspected or confirmed, daptomycin mg may need to be discontinued and appropriate treatment instituted as clinically indicated.
Drug/laboratory test interactions
False prolongation of prothrombin time (PT) and elevation of international normalised ratio (INR) have been observed when certain recombinant thromboplastin reagents are utilised for the assay.
Creatine phosphokinase and myopathy
Increases in plasma creatine phosphokinase (CPK; MM isoenzyme) levels associated with muscular pains and/or weakness and cases of myositis, myoglobinaemia and rhabdomyolysis have been reported during therapy with daptomycin.
Plasma CPK should be measured at baseline and at regular intervals (at least once weekly) during therapy in all patients. CPK should be measured more frequently (e.g. every 2-3 days at least during the first two weeks of treatment) in patients who are at higher risk of developing myopathy. For example, patients with any degree of renal impairment (creatinine clearance < 80 ml/min).
Peripheral neuropathy
Patients who develop signs or symptoms that might represent a peripheral neuropathy during therapy with daptomycin should be investigated and consideration should be given to discontinuation of daptomycin.
Eosinophilic pneumonia
Eosinophilic pneumonia has been reported in patients receiving daptomycin. In most reported cases associated with daptomycin, patients developed fever, dyspnoea with hypoxic respiratory insufficiency, and diffuse pulmonary infiltrates or organising pneumonia. The majority of cases occurred after more than 2 weeks of treatment with daptomycin and improved when daptomycin was discontinued and steroid therapy was initiated. Recurrence of eosinophilic pneumonia upon re-exposure has been reported. Patients who develop these signs and symptoms while receiving daptomycin should undergo prompt medical evaluation, including, if appropriate, bronchoalveolar lavage, to exclude other causes (e.g. bacterial infection, fungal infection, parasites, other medicinal products). Daptomycin should be discontinued immediately and treatment with systemic steroids should be initiated when appropriate.
Severe cutaneous adverse reactions
Severe cutaneous adverse reactions (SCARs) including drug reaction with eosinophilia and systemic symptoms (DRESS) and vesiculobullous rash with or without mucous membrane involvement (Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN)), which could be life-threatening or fatal, have been reported with daptomycin. If signs and symptoms suggestive of these reactions appear, daptomycin should be discontinued immediately and an alternative treatment should be considered. If the patient has developed a severe cutaneous adverse reaction with the use of daptomycin, treatment with daptomycin must not be restarted in this patient at any time.
Tubulointerstitial nephritis
Tubulointerstitial nephritis (TIN) has been reported in post-marketing experience with daptomycin. Patients who develop fever, rash, eosinophilia and/or new or worsening renal impairment while receiving daptomycin should undergo medical evaluation. If TIN is suspected, daptomycin should be discontinued promptly and appropriate therapy and/or measures should be taken.
Renal impairment
Renal impairment has been reported during treatment with daptomycin. Severe renal impairment may in itself also pre-dispose to elevations in daptomycin levels which may increase the risk of development of myopathy.
An adjustment of daptomycin dose interval is needed for adult patients whose creatinine clearance is < 30 ml/min. The safety and efficacy of the dose interval adjustment have not been evaluated in controlled clinical trials and the recommendation is mainly based on pharmacokinetic modelling data. This medical product should only be used in such patients when it is considered that the expected clinical benefit outweighs the potential risk.
In addition, regular monitoring of renal function is advised during concomitant administration of potentially nephrotoxic agents, regardless of the patient’s pre-existing renal function.
Obesity
In obese subjects with Body Mass Index (BMI) > 40 kg/m2 but with creatinine clearance > 70 ml/min, the AUC0-∞ daptomycin was significantly increased (mean 42 % higher) compared with non-obese matched controls. There is limited information on the safety and efficacy of daptomycin in the very obese and so caution is recommended. However, there is currently no evidence that a dose reduction is required.
Sodium
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

The most frequently reported adverse reactions (frequency common (≥ 1/100
to < 1/10)) are: Fungal infections, urinary tract infection, candida infection, anaemia, anxiety, insomnia, dizziness, headache, hypertension, hypotension, gastrointestinal and abdominal pain, nausea, vomiting, constipation, diarrhoea, flatulence, bloating and distension, liver function tests abnormal (increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP)), rash, pruritus, limb pain, serum creatine phosphokinase (CPK) increased, infusion site reactions, pyrexia, asthenia.

Daptomycin undergoes little to no Cytochrome P450 (CYP450)-mediated metabolism. It is unlikely that daptomycin will inhibit or induce the metabolism of medicinal products metabolised by the P450 system.
Tobramycin: small changes in the pharmacokinetics of daptomycin and tobramycin were observed during co-administration by intravenous infusion over a 30-minute period using a Daptomycin dose of 2 mg/kg, the changes were not statistically significant. The interaction between daptomycin and tobramycin with an approved dose of 500 mg is unknown. Caution is warranted when daptomycin 500 mg is co-administered with tobramycin.
There is limited experience regarding concomitant administration of daptomycin with other medicinal products that may trigger myopathy (e.g. HMG-CoA reductase inhibitors). However, some cases of marked rises in CPK levels and cases of rhabdomyolysis occurred in adult patients taking one of these medicinal products at the same time as daptomycin. It is recommended that other medicinal products associated with myopathy should if possible be temporarily discontinued during treatment with daptomycin unless the benefits of concomitant administration outweigh the risk. If co-administration cannot be avoided, CPK levels should be measured more frequently than once weekly and patients should be closely monitored for any signs or symptoms that might represent myopathy.
Daptomycin is primarily cleared by renal filtration and so plasma levels may be increased during co-administration with medicinal products that reduce renal filtration (e.g. NSAIDs and COX-2 inhibitors). In addition, there is a potential for a pharmacodynamic interaction to occur during co-administration due to additive renal effects. Therefore, caution is advised when daptomycin is co-administered with any other medicinal product known to reduce renal filtration.
See prescribing information for full details.

Pregnancy: No clinical data on pregnancies are available for daptomycin.
Lactation: In a single human case study, daptomycin was intravenously administered daily for 28 days to a nursing mother at a dose of 500 mg/day, and samples of the patient’s breast milk were collected over a 24-hour period on day 27. The highest measured concentration of daptomycin in the breast milk was 0.045 μg/ml, which is a low concentration. Therefore, until more experience is gained, breast-feeding should be discontinued when daptomycin is administered to nursing women.

In the event of overdose, supportive care is advised. Daptomycin is slowly cleared from the body by haemodialysis (approximately 15 % of the administered dose is removed over 4 hours) or by peritoneal dialysis (approximately 11 % of the administered dose is removed over 48 hours).

After reconstitution: The stability of the reconstituted solution in the vial is for 12 hours at 25°C and up to 48 hours at 2°C – 8°C.
After dilution: Stability of the diluted solution in infusion bags is for 12 hours at 25°C or 24 hours at 2°C – 8°C. The combined storage time (reconstituted solution in vial and diluted solution in infusion bag) should not exceed 12 hours at room temperature or 48 hours under refrigeration.
However, from a microbiological point of view the product should be used immediately.