Daptomycin

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications:

• Complicated skin and skin structure infections caused by susceptible Gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus dysgalactiae subsp. equisimilis
• Staphylococcus aureus bloodstream infections (bacteraemia), including those with right-sided infective endocarditis (SAB/RIE), caused by methicillin-susceptible and methicillin-resistant isolates

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Breastfeeding

Cautions

• Renal impairment
• Severe hepatic impairment
• Prosthetic valve infections or left-sided infective endocarditis due to Staphylococcus aureus
• Deep-seated infections
• Myopathy or risk factors for myopathy
• Obese patients
• Children
• Pregnancy
• Enterococcal infections
• Clostridium difficile- associated diarrhoea
• Peripheral neuropathy
• Eosinophilic pneumonia

Forms avail. in SA and covered in this monograph: inj

Dosages below include:

• International manufacturer recommendations
• South African manufacturer recommendations

Infections caused by: Gram positive bacteria; Staphylococcus aureus including methicillin-resistant Staphylococcus aureus, Staphylococcus haemolyticus, Coagulase negative staphylococci, Streptococcus agalactiae, Streptococcus dysgalactiae subsp equisimilis, Streptococcus pyogenes, Group G streptococci, Clostridium perfringens, Peptostreptococcus spp, S. epidermidis (R), Staph coag-neg (R)

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

International manufacturer recommendations

Complicated skin and soft-tissue infections (cSSTI)
- Without concurrent Staphylococcus aureus bacteraemia (SAB)

• IV: 4mg/kg, dly; Treatment duration: 7-14 days or until the infection is resolved

- With concurrent Staphylococcus aureus bacteraemia (SAB)

• IV: 6mg/kg, dly

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The duration of therapy may need to be longer than 14 days in accordance with the perceived risk of complications in the individual patient

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Known or suspected right-sided infective endocarditis due to Staphylococcus aureus

• IV: 6mg/kg, dly

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The duration of therapy should be in accordance with available official recommendations

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Daptomycin is administered intravenously in 0.9% sodium chloride. Daptomycin should not be used more frequently than once a day

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Creatine phosphokinase (CPK) levels must be measured at baseline and at regular intervals (at least weekly) during treatment

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Daptomycin is given by IV infusion and administered over a 30mins
OR
IV injection and administered over a 2mins

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South African manufacturer recommendations

Complicated skin and skin structure infections

• IV: 4mg/kg, dly as an infusion over 30min; Treatment duration: 7-14 days

Staphylococcus aureus bacteraemia including right-sided infective endocarditis

• IV: 6mg/kg, dly as an infusion over 30min; Treatment duration: 2-6 weeks

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The duration of treatment may be longer than 14 days in accordance with the perceived risk of complications in the individual patients

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Daptomycin should not be dosed more frequently than once a day

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Administer in 0.9% sodium chloride

Forms avail. in SA and covered in this monograph: inj

Paed. dosages below include:

• International manufacturer recommendations
• South African manufacturer recommendations

Infections caused by: Gram positive bacteria; Staphylococcus aureus including methicillin-resistant Staphylococcus aureus, Staphylococcus haemolyticus, Coagulase negative staphylococci, Streptococcus agalactiae, Streptococcus dysgalactiae subsp equisimilis, Streptococcus pyogenes, Group G streptococci, Clostridium perfringens, Peptostreptococcus spp, S. epidermidis (R), Staph coag-neg (R)

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

International manufacturer recommendations

Complicated skin and soft-tissue infections (cSSTI)
- Without concurrent Staphylococcus aureus bacteraemia (SAB)

• <2 year: Not established for use
• Between 2-6 years: 9mg/kg, dly, over 60mins; Treatment duration: Up to 14 days
• Between 7-11 years: 7mg/kg, dly, over 30mins; Treatment duration: Up to 14 days
• Between 12-17 years: 5mg/kg, dly, over 30mins; Treatment duration: Up to 14 days
• ≥17 years: See adult dosage

Complicated skin and soft-tissue infections (cSSTI)
- With concurrent Staphylococcus aureus bacteraemia (SAB)

• <1 year: Not established for use
• 1-2 years: 12 mg/kg, dly over 60 mins
• Between 2-6 years: 12mg/kg, dly, over 60mins
• Between 7-11 years: 9mg/kg, dly, over 30mins
• Between 12-17 years: 7mg/kg, dly, over 30mins
• ≥17 years: See adult dosage

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Minimum duration of daptomycin for paediatric SAB should be in accordance with the perceived risk of complications in the individual patient. The duration of daptomycin may need to be >14 days in accordance with the perceived risk of complications in the individual patient

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In the paediatric SAB study, the mean duration of IV daptomycin was 12 days, with a range of 1-44 days. The duration of therapy should be in accordance with available official recommendations

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Daptomycin is administered intravenously in 0.9% sodium chloride. Daptomycin should not be used more frequently than once a day

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Creatine phosphokinase (CPK) levels must be measured at baseline and at regular intervals (at least weekly) during treatment

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See, Additional prescribing points

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South African manufacturer recommendations

Not established for use in children below 18 years

Pregnancy 

• Caution; not recommended
• Daptomycin should not be used during pregnancy unless clearly necessary i.e., only if the expected benefit outweighs the possible risk
• No clinical data on pregnancies is available for daptomycin
• Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embroyonal/foetal development, parturition or postnatal development

Breastfeeding 

• Contraindicated
• In a single human case study, Daptomycin was intravenously administered daily for 28 days to a nursing mother at a dose of 500mg/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 mcg/ml, which is a low concentration. Therefore, until more experience is gained, breastfeeding should be discontinued when daptomycin is administered to breastfeeding women

Fertility 

• No clinical data on fertility is available for daptomycin. Animal studies do not indicate direct or indirect harmful effects with respect to fertility

Renal Impairment

• Caution; dose adjustment recommended

Hepatic Impairment

• Severe: Caution; no information available

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Central Nervous System Disorders

• Anxiety
• Insomnia
• Dizziness
• Headache
• Paraesthesia
• Taste disorder
• Tremor
• Peripheral neuropathy
• Fatigue

Cardiovascular Disorders

• Supraventricular tachycardia
• Extrasystole
• Hypertension
• Hypotension
• Flushes

Respiratory Disorders

• Eosinophilic pneumonia
• Cough

Gastrointestinal Disorders

• Gastrointestinal pain
• Nausea and vomiting
• Constipation
• Diarrhoea
• Flatulence
• Bloating 
• Dyspepsia
• Glossitis

Hepatobiliary Disorders

• Increased alanine aminotransferase 
• Increased aspartate aminotransferase
• Increased alkaline phosphatase 
• Jaundice

Genitourinary Disorders

• Renal impairment
• Increased serum creatinine
• Vaginitis

Endocrine and Metabolic Disorders

• Decreased appetite
• Hyperglycaemia
• Electrolyte imbalance

Musculoskeletal Disorders

• Limb pain
• Increased serum creatine phosphokinase
• Myositis
• Increased myoglobin
• Muscular weakness
• Muscle pain
• Arthralgia
• Increased serum lactate dehydrogenase
• Rhabdomyolysis 

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritus
• Urticaria
• Infusion site reactions
• Acute generalised exanthematous pustulosis

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Thrombocythaemia
• Eosinophilia
• Increased international normalised ratio
• Prolonged prothrombin time
• Hypersensitivity
• Angioedema
• Drug rash with eosinophilia and systemic symptoms (DRESS)
• Pulmonary eosinophilia
• Vesicobullous rash with mucous membrane involvement 
• Anaphylaxis
• Infusion reactions 
• Fungal infections
• Urinary tract infection
• Candida infection
• Fungaemia
• Clostridium difficile-associated diarrhoea
• Pyrexia

Sensory Disorders

• Vertigo

• Tobramycin
• Medicinal products associated with myopathy
• Medicinal products known to reduce renal filtration

• Renal function
• Creatine phosphokinase
• Coagulation profile (in patients on warfarin)

Use in paediatric patients

• Paediatric patients below the age of one year should not be given daptomycin due to the risk of potential effects on muscular, neuromuscular and/or nervous systems (either peripheral and/or central) that were observed in neonatal dogs

Daptomycin for Children and Adolescents (Specialist recommendations) 

• The safety and efficacy of daptomycin in children and adolescents aged below 18 years with right-sided infective endocarditis (RIE) due to Staphylococcus aureus or with Staphylococcus aureus bacteraemia (SAB) when associated with RIE or with cSSTI have not been established. No recommendation on a dosing and/or therapeutic dose can be made

Administration directions

• Daptomycin In adults, daptomycin may be administered intravenously as an infusion over 30mins or as an injection over 2 mins
• Daptomycin should not be administered as a 2-minute injection to paediatric patients
• Paediatric patients 7-17 years old should receive daptomycin infused over 30 minutes. In paediatric patients <7 years old receiving a 9-12mg/kg dose, daptomycin should be administered over 60 mins

Preparation of the solution for infusion requires an additional dilution step as detailed below.

Daptomycin given as a 30 or 60-minute IV infusion

• A 50mg/ml concentration of daptomycin is obtained by reconstituting the lyophilised product with 10ml of sodium chloride 9mg/ml (0.9%) solution for injection
• The lyophilised product takes approximately 15 mins to dissolve. The fully reconstituted product will appear clear and may have a few small bubbles or foam around the edge of the vial
• To prepare daptomycin for intravenous infusion, please adhere to the following instructions:

- Aseptic technique should be used throughout to reconstitute lyophilised daptomycin.

1. The polypropylene flip-off cap should be removed to expose the central portions of the rubber stopper. Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface. Draw 10ml of sodium chloride 9mg/ml (0.9%) solution for injection into a syringe using a sterile transfer needle that is 21 gauge or smaller in diameter, or a needleless device, then slowly inject through the centre of the rubber stopper into the vial pointing the needle towards the wall of the vial
2. The vial should be gently rotated to ensure complete wetting of the product and then allowed to stand for 10mins
3. Finally the vial should be gently rotated/swirled for a few minutes as needed to obtain a clear reconstituted solution. Vigorous shaking/agitation should be avoided to prevent foaming of the product
4. The reconstituted solution should be checked carefully to ensure that the product is in solution and visually inspected for the absence of particulates prior to use. Reconstituted solutions of daptomycin range in colour from pale yellow to light brown
5. Slowly remove the reconstituted liquid (50mg daptomycin/ml) from the vial using a sterile needle that is 21 gauge or smaller in diameter
6. The reconstituted solution should then be diluted with sodium chloride 9mg/ml (0.9%) (typical volume 50ml)
7. Invert the vial of the sodium chloride solution in order to allow the solution to drain towards the stopper. Using a new syringe, insert the needle into the inverted vial. Keeping the vial inverted, position the needle tip at the very bottom of the solution in the vial when drawing the solution into the syringe. Before removing the needle from the vial, pull the plunger all the way back to the end of the syringe barrel in order to remove all of the solution from the inverted via
8. Replace needle with a new needle for the intravenous infusion
9. Expel air, large bubbles, and any excess solution in order to obtain the required dose
10. The reconstituted and diluted solution should then be infused intravenously over 30 or 60mins

The following have been shown to be compatible when added to daptomycin containing infusion solutions:
- Aztreonam
- Ceftazidime
- Ceftriaxone
- Gentamicin
- Fluconazole
_ Levofloxacin
- Dopamine
- Heparin
- Lidocaine

Daptomycin given as 2-minute intravenous injection

• Water should not be used for reconstitution of daptomycin for intravenous injection. Daptomycin should only be reconstituted with sodium chloride 9mg/ml (0.9%)
• A 50mg/ml concentration of daptomycin is obtained by reconstituting the lyophilised product with 10ml of sodium chloride 9mg/ml (0.9%) solution for injection
• The lyophilised product takes approximately 15mins to dissolve. The fully reconstituted product will appear clear and may have a few small bubbles or foam around the edge of the vial
• To prepare daptomycin for intravenous injection, please adhere to the following instructions:

- Aseptic technique should be used throughout to reconstitute lyophilised daptomycin

1. The polypropylene flip off cap should be removed to expose the central portions of the rubber stopper. Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface. Draw 10ml of sodium chloride 9mg/ml (0.9%) solution for injection into a syringe using a sterile transfer needle that is 21 gauge or smaller in diameter, or a needleless device, then slowly inject through the centre of the rubber stopper into the vial pointing the needle towards the wall of the vial
2. The vial should be gently rotated to ensure complete wetting of the product and then allowed to stand for 10mins
3. Finally the vial should be gently rotated/swirled for a few minutes as needed to obtain a clear reconstituted solution. Vigorous shaking/agitation should be avoided to prevent foaming of the product
4. The reconstituted solution should be checked carefully to ensure that the product is in solution and visually inspected for the absence of particulates prior to use. Reconstituted solutions of daptomycin range in colour from pale yellow to light brown
5. Slowly remove the reconstituted liquid (50mg daptomycin/ml) from the vial using a sterile needle that is 21 gauge or smaller in diameter
6. Invert the vial in order to allow the solution to drain towards the stopper. Using a new syringe, insert the needle into the inverted vial. Keeping the vial inverted, position the needle tip at the very bottom of the solution in the vial when drawing the solution into the syringe. Before removing the needle from the vial, pull the plunger all the way back to the end of the syringe barrel in order to remove all of the solution from the inverted vial
7. Replace needle with a new needle for the intravenous injection
8. Expel air, large bubbles, and any excess solution in order to obtain the required dose
9. The reconstituted solution should then be injected intravenously slowly over 2 mins

From a microbiological point of view, the product should be used immediately after reconstitution

Drug/Laboratory Test Interactions  

• False prolongation of prothrombin time (PT) and elevation of international normalised ration (INR) have been observed with certain recombinant thromboplastin reagents are utilised for the assay

Anticoagulant activity in patients receiving daptomycin and warfarin should be monitored for the first several days after therapy with daptomycin is initiated  

Daptomycin is a cyclic lipopeptide natural product that is active against Gram-positive bacteria only. The mechanism of action involves binding (in the presence of calcium ions) to bacterial membranes of both growing and stationary phase cells causing depolarisation and leading to a rapid inhibition of protein, DNA, and RNA synthesis. This results in bacterial cell death with negligible cell lysis.

Spectrum of activity: Gram positive bacteria; Staphylococcus aureus including methicillin-resistant Staphylococcus aureus, Staphylococcus haemolyticus, Coagulase negative staphylococci, Streptococcus agalactiae, Streptococcus dysgalactiae subsp equisimilis, Streptococcus pyogenes, Group G streptococci, Clostridium perfringens, Peptostreptococcus spp, S. epidermidis (R), Staph coag-neg (R)

Injection (per vial) 500mg

• Cubicin (MSD) originator
• Drymred 500 (Dr Reddy's)