Drugs List

Therapeutic Indications

Uses

Bacteraemia
Complicated skin and soft tissue infections
Right-sided infective endocarditis due to S. aureus

Complicated skin and soft-tissue infections.
Right-sided infective endocarditis due to Staphylococcus aureus.
Staphylococcus aureus bacteraemia when associated with complicated skin and soft-tissue infections or right-sided infective endocarditis in adults, or complicated skin and soft-tissue infections in paediatric patients.
Daptomycin is active against Gram positive bacteria only. Where Gram negative and/or certain types of anaerobic bacteria are suspected, other appropriate antibacterials should be used concurrently.

Administration

Following reconstitution, daptomycin solution is given by intravenous infusion and administered over a 30 minute period, or by intravenous injection and administered over a 2 minute period.

In patients aged 7 to 17 years old, administer as an intravenous infusion over 30 minutes. In patients aged 1 to 6 years old, administer as an intravenous infusion over 60 minutes.

Contraindications

Children under 1 year
Breastfeeding

Precautions and Warnings

Creatine kinase levels over 5 times upper limit of normal
Obese patients with a BMI greater than 40kg/m2
Myopathy
Pregnancy
Renal impairment - creatinine clearance below 80ml/min
Severe hepatic impairment - Child-Pugh score greater than or equal to 10

Adjust dose interval in patients with creatinine clearance below 30ml/min
Consult national/regional policy on the use of anti-infectives
Not all available products are licensed for all age groups
Assess risk/benefit of treatment if symptoms of peripheral neuropathy occur
Monitor closely patient with pre-existing renal impairment
Monitor creatine kinase levels every 2 days in patients reporting myalgia
Monitor creatine kinase levels in all patients
Monitor for signs of superinfection with non-susceptible organisms
Monitor patient for signs of myopathy
May affect results of some laboratory tests
Discontinue if eosinophilic pneumonia occurs
Discontinue if serious allergic or anaphylactic reaction occurs
Discontinue if unexplained myalgia and creatine kinase > 5 times ULN

Increased plasma creatine kinase (CPK; MM isoenzyme) levels associated with myalgia, muscular weakness, myositis, myoglobinaemia and rhabdomyolysis have been reported during daptomycin therapy. Therefore it is recommended that creatine kinase levels are monitored at baseline and at least once a week during therapy in ALL patients.

Patients with creatine kinase greater than 5 times the upper limit of normal at baseline may be at an increased risk of further increases during therapy with daptomycin. If daptomycin is given to these patients, creatine kinase levels should be monitored more frequently than once per week.

Creatine kinase levels should be monitored at least every 2 to 3 days during the first 2 weeks of therapy in patients with an increased risk of developing myopathy, including those with renal impairment (creatinine clearance less than 80ml/minute) and patients receiving concurrent medication associated with myopathy.

Creatine kinase levels should be monitored every 2 days in patients experiencing unexplained myalgia, muscle tenderness, muscle weakness or cramps. If creatine kinase levels exceed 5 times the upper limit of normal in the presence of unexplained muscle symptoms, daptomycin should be discontinued.

Patients presenting with signs or symptoms suggestive of peripheral neuropathy should be investigated and the discontinuation of daptomycin should be considered.

Use with caution in severely obese patients (BMI > 40kg/metre squared) as safety and efficacy data are limited. There is no evidence that a reduction in dosage is necessary, although in such patients the AUC was significantly increased compared to non-obese patients.

Consider alternative antibacterial therapy if a focus of infection other than complicated infection of skin or soft tissue or with right-sided infective endocarditis is identified.

Note that the efficacy of daptomycin in the following conditions has not been demonstrated: prosthetic valve infections associated with Staphylococcus aureus; left-sided infective endocarditis associated with Staphylococcus aureus.

There have been reports of patients developing eosinophilic pneumonia while receiving daptomycin with symptoms such as fever, dyspnoea with hypoxic respiratory insufficiency, and diffuse pulmonary infiltrates or organising pneumonia. Most cases occurred after more than 2 weeks of treatment and improved when daptomycin treatment was discontinued and steroid therapy initiated. Recurrence of eosinophilic pneumonia following re-exposure has been reported. Patients with symptoms suggestive of eosinophilic pneumonia should undergo prompt medical evaluation including, if appropriate, bronchoalveolar lavage to exclude other causes. Daptomycin should be discontinued and steroid therapy initiated when appropriate.

Pregnancy and Lactation

Pregnancy

Use daptomycin with caution in pregnancy.

Manufacturer advises use during pregnancy only if the potential benefit outweighs the possible risk.

At the time of writing, there are insufficient clinical data available regarding the use of daptomycin during pregnancy.

Animal studies do not indicate any direct, or indirect harmful effects with respect to pregnancy, embryo/foetal development, parturition or postnatal development.

It is not known whether daptomycin crosses the human placenta. The high molecular weight (about 1621) should limit passive transfer across the placenta, however, it cannot be ruled out (Briggs, 2015).

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Daptomycin is contraindicated in breastfeeding.

UK licensed product information recommends that breastfeeding should be discontinued during daptomycin therapy.

The limited information available indicates that daptomycin is excreted in breast milk in low amounts. However, it is not likely to be orally bioavailable, and absorption by the nursing infant is not expected. Modification of the infant's flora resulting in diarrhoea, C. difficile overgrowth and other gastrointestinal complaints are the potential concerns (Briggs, 2015).

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal INR
Abnormal liver function tests
Acute generalised exanthematous pustulosis
Anaemia
Anaphylaxis
Angioedema
Antibiotic-associated colitis
Anxiety
Arthralgia
Asthenia
Bloating
Candidiasis
Clostridium difficile diarrhoea
Constipation
Cough
Creatine phosphokinase increased
Decreased appetite
Diarrhoea
Dizziness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dyspepsia
Electrolyte disturbances
Eosinophilia
Eosinophilic pneumonia
Extrasystoles
Eye irritation
Fatigue
Flatulence
Flushing
Fungaemia
Fungal infection
Gastric distension
Gastro-intestinal pain
Glossitis
Headache
Hyperglycaemia
Hypersensitivity reactions
Hypertension
Hypotension
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increase in serum ALT/AST
Increased myoglobin
Infusion-related symptoms
Injection site reactions
Insomnia
Jaundice
Leukocytosis
Limb pain
Metallic taste
Muscle cramps
Muscle pain
Muscle weakness
Muscular fatigue
Myoglobinaemia
Myopathy
Myositis
Nausea
Oropharyngeal swelling
Overgrowth by non-susceptible organisms
Pain
Paraesthesia
Peripheral neuropathy
Prothrombin time increased
Pruritus
Pulmonary eosinophilia
Pyrexia
Rash
Renal failure
Renal impairment
Rhabdomyolysis
Rigors
Serum creatinine increased
Superinfections
Supraventricular tachycardia
Syncope
Tachycardia
Taste disturbances
Thrombocythaemia
Thrombocytopenia
Tremor
Urinary tract infections
Urticaria
Vaginitis
Vertigo
Vesiculo-bullous reactions
Vomiting
Wheezing

Presentation

Powder for solution for injection or infusion of daptomycin.

Drugs List

Therapeutic Indications

Uses

Bacteraemia
Complicated skin and soft tissue infections
Right-sided infective endocarditis due to S. aureus

Complicated skin and soft-tissue infections.
Right-sided infective endocarditis due to Staphylococcus aureus.
Staphylococcus aureus bacteraemia when associated with complicated skin and soft-tissue infections or right-sided infective endocarditis in adults, or complicated skin and soft-tissue infections in paediatric patients.
Daptomycin is active against Gram positive bacteria only. Where Gram negative and/or certain types of anaerobic bacteria are suspected, other appropriate antibacterials should be used concurrently.

Dosage

Daptomycin should not be used more frequently than once a day.

Adults

Children

Patients with Renal Impairment

Administration

Following reconstitution, daptomycin solution is given by intravenous infusion and administered over a 30 minute period, or by intravenous injection and administered over a 2 minute period.

In patients aged 7 to 17 years old, administer as an intravenous infusion over 30 minutes. In patients aged 1 to 6 years old, administer as an intravenous infusion over 60 minutes.

Contraindications

Children under 1 year
Breastfeeding

Precautions and Warnings

Creatine kinase levels over 5 times upper limit of normal
Obese patients with a BMI greater than 40kg/m2
Myopathy
Pregnancy
Renal impairment - creatinine clearance below 80ml/min
Severe hepatic impairment - Child-Pugh score greater than or equal to 10

Adjust dose interval in patients with creatinine clearance below 30ml/min
Consult national/regional policy on the use of anti-infectives
Not all available products are licensed for all age groups
Assess risk/benefit of treatment if symptoms of peripheral neuropathy occur
Monitor closely patient with pre-existing renal impairment
Monitor creatine kinase levels every 2 days in patients reporting myalgia
Monitor creatine kinase levels in all patients
Monitor for signs of superinfection with non-susceptible organisms
Monitor patient for signs of myopathy
May affect results of some laboratory tests
Discontinue if eosinophilic pneumonia occurs
Discontinue if serious allergic or anaphylactic reaction occurs
Discontinue if unexplained myalgia and creatine kinase > 5 times ULN

Increased plasma creatine kinase (CPK; MM isoenzyme) levels associated with myalgia, muscular weakness, myositis, myoglobinaemia and rhabdomyolysis have been reported during daptomycin therapy. Therefore it is recommended that creatine kinase levels are monitored at baseline and at least once a week during therapy in ALL patients.

Patients with creatine kinase greater than 5 times the upper limit of normal at baseline may be at an increased risk of further increases during therapy with daptomycin. If daptomycin is given to these patients, creatine kinase levels should be monitored more frequently than once per week.

Creatine kinase levels should be monitored at least every 2 to 3 days during the first 2 weeks of therapy in patients with an increased risk of developing myopathy, including those with renal impairment (creatinine clearance less than 80ml/minute) and patients receiving concurrent medication associated with myopathy.

Creatine kinase levels should be monitored every 2 days in patients experiencing unexplained myalgia, muscle tenderness, muscle weakness or cramps. If creatine kinase levels exceed 5 times the upper limit of normal in the presence of unexplained muscle symptoms, daptomycin should be discontinued.

Patients presenting with signs or symptoms suggestive of peripheral neuropathy should be investigated and the discontinuation of daptomycin should be considered.

Use with caution in severely obese patients (BMI > 40kg/metre squared) as safety and efficacy data are limited. There is no evidence that a reduction in dosage is necessary, although in such patients the AUC was significantly increased compared to non-obese patients.

Consider alternative antibacterial therapy if a focus of infection other than complicated infection of skin or soft tissue or with right-sided infective endocarditis is identified.

Note that the efficacy of daptomycin in the following conditions has not been demonstrated: prosthetic valve infections associated with Staphylococcus aureus; left-sided infective endocarditis associated with Staphylococcus aureus.

There have been reports of patients developing eosinophilic pneumonia while receiving daptomycin with symptoms such as fever, dyspnoea with hypoxic respiratory insufficiency, and diffuse pulmonary infiltrates or organising pneumonia. Most cases occurred after more than 2 weeks of treatment and improved when daptomycin treatment was discontinued and steroid therapy initiated. Recurrence of eosinophilic pneumonia following re-exposure has been reported. Patients with symptoms suggestive of eosinophilic pneumonia should undergo prompt medical evaluation including, if appropriate, bronchoalveolar lavage to exclude other causes. Daptomycin should be discontinued and steroid therapy initiated when appropriate.

Pregnancy and Lactation

Pregnancy

Use daptomycin with caution in pregnancy.

Manufacturer advises use during pregnancy only if the potential benefit outweighs the possible risk.

At the time of writing, there are insufficient clinical data available regarding the use of daptomycin during pregnancy.

Animal studies do not indicate any direct, or indirect harmful effects with respect to pregnancy, embryo/foetal development, parturition or postnatal development.

It is not known whether daptomycin crosses the human placenta. The high molecular weight (about 1621) should limit passive transfer across the placenta, however, it cannot be ruled out (Briggs, 2015).

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Daptomycin is contraindicated in breastfeeding.

UK licensed product information recommends that breastfeeding should be discontinued during daptomycin therapy.

The limited information available indicates that daptomycin is excreted in breast milk in low amounts. However, it is not likely to be orally bioavailable, and absorption by the nursing infant is not expected. Modification of the infant's flora resulting in diarrhoea, C. difficile overgrowth and other gastrointestinal complaints are the potential concerns (Briggs, 2015).

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal INR
Abnormal liver function tests
Acute generalised exanthematous pustulosis
Anaemia
Anaphylaxis
Angioedema
Antibiotic-associated colitis
Anxiety
Arthralgia
Asthenia
Bloating
Candidiasis
Clostridium difficile diarrhoea
Constipation
Cough
Creatine phosphokinase increased
Decreased appetite
Diarrhoea
Dizziness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dyspepsia
Electrolyte disturbances
Eosinophilia
Eosinophilic pneumonia
Extrasystoles
Eye irritation
Fatigue
Flatulence
Flushing
Fungaemia
Fungal infection
Gastric distension
Gastro-intestinal pain
Glossitis
Headache
Hyperglycaemia
Hypersensitivity reactions
Hypertension
Hypotension
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increase in serum ALT/AST
Increased myoglobin
Infusion-related symptoms
Injection site reactions
Insomnia
Jaundice
Leukocytosis
Limb pain
Metallic taste
Muscle cramps
Muscle pain
Muscle weakness
Muscular fatigue
Myoglobinaemia
Myopathy
Myositis
Nausea
Oropharyngeal swelling
Overgrowth by non-susceptible organisms
Pain
Paraesthesia
Peripheral neuropathy
Prothrombin time increased
Pruritus
Pulmonary eosinophilia
Pyrexia
Rash
Renal failure
Renal impairment
Rhabdomyolysis
Rigors
Serum creatinine increased
Superinfections
Supraventricular tachycardia
Syncope
Tachycardia
Taste disturbances
Thrombocythaemia
Thrombocytopenia
Tremor
Urinary tract infections
Urticaria
Vaginitis
Vertigo
Vesiculo-bullous reactions
Vomiting
Wheezing

Effects on Laboratory Tests

Interference between daptomycin and particular reagents used in some assays may occur. False prolongation of prothrombin time and elevated international normalised ratio (INR) have been observed in assays using certain recombinant thromboplastin reagents.
The possibility of false results can be reduced by obtaining blood samples for testing near the time of trough plasma concentrations of daptomycin (immediately before the daptomycin dose).

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: March 2018

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Cubicin 350mg powder for solution for injection or infusion. Merck Sharp & Dohme Limited. Revised August 2018.

Summary of Product Characteristics: Cubicin 500mg powder for solution for injection or infusion. Merck Sharp & Dohme Limited. Revised August 2018.

Summary of Product Characteristics: Daptomycin 350mg powder for solution for injection/infusion. Accord Healthcare Limited. Revised June 2018.

Summary of Product Characteristics: Daptomycin 500mg powder for solution for injection/infusion. Accord Healthcare Limited. Revised June 2018.

Summary of Product Characteristics: Daptomycin 350mg powder for solution for injection/infusion. Dr Reddy's laboratories (UK) Ltd. Revised September 2018.

Summary of Product Characteristics: Daptomycin 500mg powder for solution for injection/infusion. Dr Reddy's laboratories (UK) Ltd. Revised September 2018.

NICE Evidence Services Available at: www.nice.org.uk
Last accessed: 13 September 2018