OPAT Drug Monographs - Leeds Formulary

Written by: Kelly Atack- Advanced Clinical Pharmacist for Infection & Travel Medicine Checked by: Pharmacy Infection Team Authorised by: IAPG Date: 20/12/19 Version 4

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OPAT Drug Monographs


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Contents

Page number Title 3 OPAT Team Contacts 4-7 General Information 8 Flow Chart for Supply of

Medicines 9 Monographs 10 Amoxicillin 12 Liposomal Amphotericin B

(Ambisome) 14 Anidulafungin 16 Amikacin 19 Aztreonam 21 Benzylpenicillin 23 Ceftazidime 25 Ceftriaxone 27 Ciprofloxacin 30 Co-amoxiclav 32 Daptomycin 35 Ertapenem 37 Flucloxacillin 39 Fluconazole 42 Fosfomycin 44 Meropenem 46 Piperacillin/tazobactam 49 Teicoplanin 53 Temocillin 55 Tigecycline 57 References


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OPAT Team Contacts Consultants Dr Jane Minton: 07786250834 ext 65468 Nurse Specialist Lizzie Ware (OPAT team leader): 07917091155 ext 66250 Debbie Booker: 07917091155 ext 66250 Shona Carton: 07917091155 ext 66250 Pharmacist Kelly Atack: 80-4351 ext 64846 Annabelle Waterhouse: 80- 5167 ext 66233 Pharmacy Technician Shazia Nazir: 80-1661 Community CIVAS Nurses 07960727267 0113 272 8620 Please note that referrals must be approved by the LTHT OPAT team Lloyds: Tel: 0345 2636 123


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General Information Please note that this document is for use in Leeds Teaching Hospitals NHS Trust only. This document contains information on the most commonly used antibiotics, antifungals and antivirals at home but please contact us to discuss any drugs not featured.

Access

Peripheral cannulas

o The patient should be discharged with their cannula in situ

o Community nurses can cannulate patients

o Lloyds nurses are also able to cannulate patients

PICC (peripherally inserted central catheter) lines

o Inserted by OPAT nurse specialist or in theatres

o Should be flushed with 10ml of sodium chloride 0.9% before and after

a dose. Note that the community nursing team do not require a supply

of these flushes. These flushes will be supplied to the Lloyds nurses

via a Lloyds prescription, which the OPAT pharmacists will facilitate.

o A volumetric pump should be used to administer infusions as PICC

lines are prone to occlusions.

o May have one or two lumens

o If not being used for more than two days, PICC lines need each lumen

locking weekly with heparin 50 units in 5ml. An outpatient/Lloyds

prescription will be required to supply this.

o Required for continuous infusions, such as flucloxacillin, that are

administered over 24 hours. They can also be used for intermittent

infusions.

Midline

o Inserted by OPAT nurse specialist and medical staff above an FY1,

provided they have had training.

o Peripheral venous catheter

Patients may also have long term central lines in situ, such as Hickman lines.

Please refer to the Central Venous Catheter guidelines on Leeds Health

Pathways for more information.

Administration

Consider whether the medicine can be administered as a bolus or as an

infusion


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If the medicine requires administration as an infusion, consider the infusion

time as this may affect nursing visits and the number of patients we can

accept onto the service

Supply of Medicines on Discharge (for patients being discharged to Leeds OPAT)-

see flow chart on page 8

Community nursing team

o Require a supply of medicines via eDAN or Lloyds Homecare

o Supply a maximum of two weeks of intravenous antimicrobials on

discharge on an eDAN.

o Supply the full course of oral antimicrobials on an eDAN.

o Some antimicrobials such as flucloxacillin devices will require obtaining

from Lloyds. The OPAT pharmacist will facilitate this prescription but

the drug must be listed on the eDAN. The source must be assigned as

“DC-other”. Please comment in the pharmacy notes to GP section of

the eDAN ‘This patient has been discharged on a course of IV

antibiotics to be administered by the OPAT team. The infusion devices

have been supplied by Lloyds.’

o If an intravenous antimicrobial is supplied on an eDAN, then please

ensure a maximum of two weeks of diluents and fluids used for

reconstitution are supplied.

o Sodium chloride flushes do not need supplying.

Lloyds nursing team

o Require intravenous antimicrobials supplying via Lloyds prescriptions

o Intravenous antimicrobials must be listed on the eDAN. The source

must be assigned as “DC-other”. Please comment in the pharmacy

notes to GP section of the eDAN ‘This patient has been discharged on

a course of IV antibiotics to be administered by the OPAT team. The

infusion devices have been supplied by Lloyds.’

o Lloyds prescriptions will be facilitated by the OPAT pharmacist

o Any oral antimicrobials should be supplied as normal via the patient’s

eDAN.

o If validating a Lloyds prescription, please ensure the full course is

supplied, including sodium chloride 0.9% 10ml pre and post dose

flushes.

For any courses longer than two weeks, the supply of intravenous

antimicrobials, and diluents will be continued by the OPAT team via outpatient

prescriptions.


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The Lloyds prescriptions require an ancilliaries and equipment list with the

medicine request. They also require a registration form if the patient has not

used the Lloyds service previously. This will be completed by the OPAT team.

Please note that delivery time for Lloyds prescriptions are approximately 48

hours but this may be longer over bank holidays and weekends.

Supply of Medicines on Discharge for patients being discharged to other OPAT

services outside of Leeds

Please contact each service to ask what they would like to be supplied. They

may require the full course of intravenous antibiotics and flushes.

Anaphylaxis

Please note that generally anaphylaxis kits are not provided to the community

nursing teams, as they carry adrenaline they can administer in an emergency.

The community nursing team can administer first doses of antimicrobials in a

patient’s home environment.

Nursing Capacity

We accept patients with three times daily dosing if we have capacity, so

please refer these patients to us

When the community nursing team is up to capacity, we can use the Lloyds

nursing service and have also trained patients and their carers to administer

intravenous medicines.

Note that both Lloyds and community nurses can go into, residential homes,

nursing homes and hospices.

If a patient is out of area, it is likely that an OPAT team will be in their area

that can provide a service. Contact our OPAT team for contact details of other

services

Some patients can also attend OPAT clinic, which is situated just outside of

J20 on level 9 of Gledhow wing.

Blood monitoring

The OPAT team review patient’s blood results including FBC, U&Es, LFT’s,

CRP and any therapeutic drug monitoring levels at least weekly at the virtual

OPAT ward round.

Note that community nurses can take bloods


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Lloyds nurses can also take bloods but require OrderComms requests, as

well as instructions on where to take the bloods when they have been taken.

The OPAT specialist nurse will facilitate this.

Storage of Medicines

Patients can store their intravenous antimicrobials that require refrigeration

storage in their own fridge, providing the medicines are placed on a shelf

away from food products and the temperature can be monitored.

Fridges can also be supplied by Lloyds.

Medicines requiring storage at room temperature should be kept out of reach

of children and pets. They should also be kept in a dry environment.

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Flow Chart for Supply of Medicines for Leeds OPAT Patients

Patient referred to Leeds OPAT

Patient reviewed by OPAT nurse and doctor and

accepted onto the service. Acceptance is documented in

the medical notes or documented on PPM+.

OPAT nursing team inform the ward of discharge date.

Patient to be discharged with Leeds community OPAT team

Patient to attend Leeds OPAT clinic

Patient to be discharged with Lloyds nursing service

Dispense maximum of two weeks of IV antimicrobials along with appropriate diluents. Do not supply flushes.

Dispense maximum of two weeks of IV antimicrobials along with appropriate diluents. Do not supply flushes. NB: OPAT clinic nurses can access medicines, however if no antimicrobials are to be supplied please discuss with OPAT nursing team first.

Prescription will be written by OPAT pharmacist for full supply of IV antibiotics and flushes. If the patient has an online pharmaceutical care record, please to check to see whether this has been recorded here. If not, please bleep OPAT pharmacist to check.

Further supply of IV antimicrobials will be made weekly through prescriptions written by OPAT team and delivered by Boots

Further supply of IV antimicrobials will be ordered through the inpatient dispensary by OPAT pharmacist


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Drug Monographs


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Amoxicillin

Indications Group A streptococcus Dose

Dose 1-2grams up to 4 hourly depending on indication.

Dose in Renal Impairment 250mg-1gram every EIGHT HOURS (maximum of 6grams in endocarditis) if CrCl <10mL/minute

Side effects

Incidence Effect

Common or Very Common

Anaphylaxis, angioedema, diarrhoea, fever, hypersensitivity reactions,

joint pains, rashes, serum sickness-like reaction, urticaria, nausea and

vomiting

Uncommon

Rare Cerebral irritation, CNS toxicity (including convulsions), coagulation

disorders, encephalopathy, haemolytic anaemia, interstitial nephritis,

leucopenia, thrombocytopenia

Very rare agranulocytosis

Frequency Unknown

Antibiotic-associated colitis

Interactions

Drug name Interaction Information

Coumarins An interaction between broad-spectrum penicillins and coumarins has not been demonstrated in studies, but common experience in anticoagulant clinics is that INR can be altered

Allopurinol Increased risk of rash when amoxicillin given with allopurinol

Methotrexate Penicillins reduce excretion of methotrexate (increased risk of toxicity)

Phenindione An interaction between broad-spectrum penicillins and


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phenindione has not been demonstrated in studies, but common experience in anticoagulant clinics is that INR can be altered

Tetracyclines Effects of penicillins possibly antagonised by tetracyclines

Please note that this is not an exhaustive list. Please refer to the online BNF or discuss with your pharmacist. Monitoring FBC, U&Es, LFTs Administration

Reconstitution Add 5mL of water for injections to a 250mg vial, add 10mL of water for injections to a 500mg vial, add 20mL of water for injections to a 1000mg vial

Further Dilution Add reconstituted solution to 100mL of sodium chloride 0.9%

Duration of Administration Administer as an intravenous infusion over 30-60 minutes.

Microbiology or Infectious Diseases approval required? No Storage Do not store above 25◦C What to supply on an eDAN for Leeds OPAT patients

Amoxicillin vials

Water for injections for reconstitution

Sodium chloride 0.9% 100mL bags for dilution


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Liposomal Amphotericin B (Ambisome)- administered in clinic only

Indications Leishmaniasis Dose

Dose NOTE 1mg test dose should be administered prior to first dose. 1-5mg/kg ONCE DAILY depending on indication

Dose in Renal Impairment 1-3mg/kg ONCE DAILY

Side effects

Incidence Effect


Abdominal pain, abnormal liver function (discontinue treatment),

anaemia, arrhythmias, blood disorders, blood pressure changes,

cardiovascular effects, chest pain, diarrhoea, disturbances in renal

function, dyspnoea, electrolyte disturbances, febrile reactions,

headache, hypokalaemia, hypomagnesaemia, nausea, rash, renal

tubular acidosis, thrombocytopenia, vomiting

Uncommon Anaphylactoid reactions, bronchospasm, convulsions, diplopia,

encephalopathy, hearing loss, neurological disorders, peripheral

neuropathy, tremor

Rare

Very rare

Frequency Unknown

Anorexia, arthralgia, myalgia, Stevens-Johnson syndrome, toxic

epidermal necrolysis


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Interactions


Arsenic Trioxide Increased risk of ventricular arrhythmias when amphotericin give with arsenic trioxide

Cardiac glycosides

Hypokalaemia caused by amphotericin increases cardiac toxicity with cardiac glycosides

Ciclosporin Increased risk of nephrotoxicity when amphotericin given with ciclosporin

Corticosteroids Increased risk of hypokalaemia when amphotericin given with corticosteroids- avoid concomitant use unless corticosteroids needed to control reactions

Flucytosine Amphotericin increases the risk of toxicity when given with flucytosine. Manufacturer makes no recommendation.

Sodium stibogluconate

Possible increased risk of arrhythmias when amphotericin given after sodium stibogluconate- manufacturer of sodium stibogluconate advises giving 14 days apart

Tacrolimus Increased risk of nephrotoxicity when amphotericin given with tacrolimus


Reconstitution Prepared by pharmacy aseptics

Further Dilution Prepared by pharmacy aseptics

Duration of Administration Administer 1mg test dose over 10 minutes from the bag of prepared Ambisome. Wait for 30 minutes and if no severe allergic reaction or anaphylaxis, administer the remaining dose over 30 to 60 minutes. Doses over 5mg/kg should be administered over 120 minutes

Microbiology approval required? No Storage Store bags prepared by pharmacy aseptics in the fridge.


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Anidulafungin

Indications Candidaemia and invasive candidiasis in adult patients Dosing

Dose 200mg loading dose, then 100mg ONCE DAILY thereafter

Dose in Renal Impairment No adjustments required

Side effects

Incidence Effect


Blood pressure changes, Bronchospasm, convulsion, diarrhoea,

flushing, headache, hyperglycaemia, hypokalaemia, nausea, pruritus,

raised LFTs, cholestasis, raised serum creatinine, rash, vomiting

Uncommon Abdominal pain, Coagulopathy, , , injection-site pain, urticaria

Frequency Unknown

anaphylaxis

Interactions No interactions listed Monitoring FBC, U&Es, LFTs Administration

Reconstitution Each 100mg vial should be reconstituted with 30mL of Water for Injections. Can take five minutes for full reconstitution and clear solution to form

Further Dilution Dilute each 100mg vial in 100ml of sodium chloride 0.9%

Duration of Administration Infuse each 100mg over 90 minutes.

Microbiology or Infectious Diseases approval required? Yes Storage Vials must be stored between 2-8◦C


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What to supply on an eDAN for Leeds OPAT patients

Anidulafungin vials




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Amikacin

Indications Tuberculosis Dose

Dose 15mg/kg ONCE DAILY up to a maximum of 1gram as a single dose (may be increased in large muscular adults). After first two months, can be reduced to 15mg/kg three times a week.

Dose in Renal Impairment 12-15mg/kg TWO to THREE times a week if CrCl <50ml/minute

Adults >59 years

10mg/kg ONCE DAILY up to a maximum of 750mg as a single dose. After first two months, can be reduced to 10mg/kg three times a week.

Obese patients

Calculate adjusted body weight for dosing using IBW and 40% of excess weight.

Side effects

Incidence Effect


Uncommon Rash

Rare Antibiotic-associated colitis, electrolyte disturbances, hypocalcaemia,

hypokalaemia, hypomagnesaemia on prolonged therapy, nausea,

peripheral neuropathy, stomatitis, vomiting

Very rare Blood disorders, CNS effects, convulsions, encephalopathy, headache

Frequency Unknown

Auditory damage, impaired neuromuscular transmission, impaired

neuromuscular transmission, irreversible ototoxicity, nephrotoxicity,

transient myasthenic syndrome in patients with normal neuromuscular

function with large doses given during surgery, vestibular damage

Interactions


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Ciclosporin Increased risk of nephrotoxicity when aminoglycosides given with ciclosporin

Diuretics, Loop Increased risk of ototoxicity when aminoglycosides given with loop diuretics

Muscle Relaxants, non-depolarisin

Aminoglycosides enhance effects of non-depolarising muscle relaxants

Neostigmine Aminoglycosides antagonise effects of neostigmine

Platinum Compounds

Increased risk of nephrotoxicity and possibly of ototoxicity when aminoglycosides given with platinum compounds

Pyridostigmine Aminoglycosides antagonise effects of pyridostigmine

Suxamethonium Aminoglycosides enhance effects of suxamethonium

Tacrolimus Increased risk of nephrotoxicity when aminoglycosides given with tacrolimus

Vancomycin Increased risk of nephrotoxicity and ototoxicity when aminoglycosides given with vancomycin

Please note that this is not an exhaustive list. Please refer to the online BNF or discuss with your pharmacist. Monitoring FBC, U&Es, LFTs, audiometry, plasma concentration levels as below. Monitor renal function more frequently in elderly patients. Therapeutic Drug Monitoring

Target Level <5mg/L (trough) 25-35mg/L (peak)

Timing of Sample Pre-dose level Peak dose can be monitored at 60-120 minutes and 6 hours after infusion ends

Frequency of Level Peak serum level to be measured in the first weak and repeated if poor response to treatment. Trough serum level should be monitored weekly for the first 4 weeks and reduced to every 2 weeks when stable.

Administration

Reconstitution Already reconstituted

Further Dilution Dilute in 100mL of sodium chloride 0.9%

Duration of Administration Administer over 30-60 minutes

Microbiology or Infectious Diseases approval required? No


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Storage Do not store above 25◦C What to supply on an eDAN for Leeds OPAT patients

Amikacin vials



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Aztreonam

Indications CF exacerbations Upper UTIs Lower UTIs Currently in short supply, all other uses are on microbiology recommendation Dose

Dose 1gram TWICE DAILY up to 2grams THREE times DAILY depending on indication.

Dose in Renal Impairment 1-2grams loading dose, then reduce to 50% of appropriate normal dose if CrCl 10-30mL/min 1-2grams loading dose, then reduce to 25% of appropriate normal dose if CrCl <10mL/min

Side effects

Incidence Effect


Uncommon Blood creatinine increase

Rare Gastro-intestinal bleeding, antibiotic-associated colitis, jaundice,

hepatitis, hypotension, chest pain, dyspnoea, seizures, paraesthesia,

confusion, dizziness, asthenia, headache, insomnia, breast

tenderness, blood disorders (including thrombocytopenia and

neutropenia), myalgia, diplopia, tinnitus, halitosis, also reported

nausea, vomiting, abdominal pain, diarrhoea, mouth ulcers, taste

disturbances, flushing, bronchospasm, rash (including toxic epidermal

necrolysis and erythema multiforme), vertigo, convulsions, wheezing,

nasal congestion

Very rare

Frequency Unknown

Anaphylaxis, angioedema, bronchospasm, rash, abdominal pain, diarrhoea, erythema multiforme, flushing, mouth ulcers, nausea, pruritis, taste disturbances, toxic epidermal necrolysis, vomiting


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Interactions


Coumarins Aztreonam possibly enhances anticoagulant effect of coumarins


Reconstitution Reconstitute 500mg and 1gram vial using 10mL of water for injections. Shake immediately and vigorously. The reconstituted solution should be colourless to light straw yellow and may develop a slight pink tint on standing, however this does not affect the potency.

Further Dilution If for infusion dilute each 1gram vial in a minimum of 50mL of sodium chloride 0.9% or glucose 5%

Duration of Administration Administer as a slow bolus injection over 3 to 5 minutes or administer over 60 minutes if administering as an infusion

Microbiology or Infectious Diseases approval required? Yes, if not in guidelines stated above. Storage Do not store above 25°C What to supply on an eDAN for Leeds OPAT patients

Aztreonam vials


Sodium chloride 0.9% 100mL bags for dilution if administering as an

intravenous infusion.


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Benzylpenicillin Indications Endocarditis Cellulitis Meningitis Dosing

Dose 7.2 grams over 24 hours

Dose in Renal Impairment <10ml/min seek advice from OPAT team

Side effects

Incidence Effect


Jarisch-Herxheimer reaction, hypersensitivity to penicillin in the form of

rashes (all types), fever, and serum sickness may occur

Uncommon

Rare Anaphylactic reactions, central nervous system toxicity, including convulsions, haemolytic anaemia and granulocytopenia (neutropenia), agranulocytosis, leucopenia and thrombocytopenia, interstitial nephritis

Interactions


Acenocoumarol Benzylpenicillin potentially alters the anticoagulant effect of acenocoumarol. Manufacturer advises monitor INR and adjust dose

Oral contraceptives

Efficacy may be impaired under concomitant administration of benzylpenicillin which may result in unwanted pregnancy

Methotrexate There is reduced excretion of methotrexate (and therefore increased risk of methotrexate toxicity) when used with benzylpenicillin sodium.

Phenidione Benzylpenicillin is predicted to increase the risk of bleeding events when given with phenindione. Manufacturer makes no recommendation.

Probenecid Probenecid inhibits tubular secretion of benzylpenicillin sodium

Warfarin Benzylpenicillin potentially alters the anticoagulant effect of warfarin. Manufacturer advises monitor INR and adjust dose.


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Monitoring FBC, U&Es, LFTs. Intravenous Administration

Reconstitution In ready-made device

Further Dilution In ready-made device

Duration of Administration To be infused over 24 hours

Storage Store in a refrigerator (2-8◦C) What to supply on eDAN for Leeds OPAT patients

Nothing- will be supplied by Lloyds.


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Ceftazidime Indications CF exacerbations Dose

Dose 1-2grams every 8 hours depending on indication.

Dose in Renal Impairment Always give a loading dose of 1gram. If CrCl= 31-50mL/minute, give 1gram 12 hourly If CrCl= 16-30mL/minute, give 1gram 24 hourly If CrCl= 6-15mL/minute, give 500mg 24 hourly If CrCl= <5mL/minute, give 500mg 48 hourly

Side effects

Incidence Effect


Eosinophilia, thrombocytosis, phlebitis or thrombophlebitis, pain and

inflammation at injection site, diarrhoea, elevation in liver enzymes,

rash

Uncommon Candidiasis, neutropenia, leukopenia, thrombocytopenia, headache,

dizziness, nausea, diarrhoea, colitis, vomiting, pruritis. fever

Rare

Very rare Acute renal failure, interstitial nephritis

Frequency Unknown

agranulocytosis, allergic reactions, anaphylaxis, angioedema, drug

reaction with eosinophilia and systemic symptoms (DRESS), erythema

multiforme, haemolytic anaemia, lymphocytosis Stevens-Johnson

syndrome, toxic epidermal necrolysis, jaundice, paraesthesia, taste

disturbances


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Interactions


Coumarins Cephalosporins possibly enhance anticoagulant effect of coumarins.


Reconstitution For 500mg vials, use 5mL of water for injections to reconstitute the vial. For 1gram and 2gram vials, use 10mL of water for injections to reconstitute the vial. For 3gram vials, use 15mL of water for injections to reconstitute the vial.

Further Dilution For intravenous infusion, after the powder has fully dissolved, remove any excess air from the vial, then add to 50mL for 1-2gram vials of sodium chloride 0.9% or 75mL of sodium chloride 0.9% for 3gram vials.

Duration of Administration For intravenous injection, administer over 3 to 5 minutes as a slow bolus injection. For intravenous infusion, administer over 15 to 30 minutes.

Microbiology or Infectious Diseases approval required? Yes, unless recommended in guideline. Storage Do not store above 25◦C and keep in outer carton to protect from light until use. What to supply on an eDAN for Leeds OPAT patients

Ceftazidime vials

Water for injections for reconstitution.

Sodium chloride 0.9% 50mL for dilution


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Ceftriaxone

Indications Meningitis Gonnococcal infections Dose

Dose 1-4gram ONCE DAILY depending on indication.

Dose in Renal Impairment 2gram ONCE DAILY is the maximum dose for CrCl <10mL/minute

Side effects

Incidence Effect


Calcium ceftriaxone precipitates in gall bladder—consider

discontinuation if symptomatic, calcium ceftriaxone precipitates in urine

(particularly in very young, dehydrated or those who are immobilised)—

consider discontinuation if symptomatic, diarrhoea,

eosinophilia,leucopenia, loose stools, thrombocytopenia, hepatic

enzyme increased, rash.

Uncommon Anaemia, blood creatinine increased, coagulopathy, dizziness, genital

fungal infection, granulocytopenia, headache,injection site pain,

nausea, phlebitis, pruritis, pyrexia, vomiting

Rare Bronchospasm, chills, glycosuria, haematuria, oedema,

pseudomembranous colitis, urticaria

Very rare

Frequency Unknown

Acute generalised exanthematous, agranulocytosis, , anaphylaxis,

confusion, convulsion, diarrhoea, disturbances in liver enzymes,

dizziness, erythema multiforme, eosinophilia, glossitis, gall bladder

precipitation, haemolytic anaemia, hallucinations, headache,

hyperactivity, hypertonia, hypersensitivity, kernicterus, leucopenia,

nausea, nervousness, pruritus, rashes, renal precipitation (reversible),

reversible interstitial nephritis, serum sickness-like reactions with


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rashes, fever and arthralgia, sleep disturbances, stomatitis, stevens-

Johnson syndrome, superinfection, thrombocytopenia, toxic epidermal

necrolysis, transient cholestatic jaundice, transient hepatitis, urticaria,

vomiting, oliguria, pancreatitis, pustulosis, vertigo

Interactions


Coumarins Cephalosporins possibly enhance the anticoagulant effect of warfarin

Please note that this is not an exhaustive list. Please refer to the online BNF or discuss with your pharmacist. Monitoring FBC, U&Es, LFTs. Therapeutic Drug Monitoring Not required Administration

Reconstitution For 1gram vials- add 10ml of Water for Injections to reconstitute the vial For 2gram vials- add 40ml of sodium chloride 0.9% or glucose 5% to reconstitute the vial

Further Dilution If the vials are without hangers the dose can be drawn up into a 50mL syringe and administered via a syringe pump.

Duration of Administration For doses of 1gram-<4gram give over 30minutes For doses of >4gram give each 2gram vial over 30 minutes (total infusion time= 60 minutes)

Microbiology or Infectious Diseases approval required? Yes outside of the above indications Storage Do not store above 25◦C What to supply on an eDAN for Leeds OPAT patients

Ceftriaxone vials

Water for injections for reconstitution if 1gram vials

Sodium chloride 0.9% 50mL bags or glucose 5% 50mL bags for dilution


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Ciprofloxacin

Indications Acute Cholecystitis and Cholangitis Acute Diverticulitis Intra abdominal infections Epiglottitis Complicated rhinosinusitis Hospital acquired pneumonia Ventilator acquired pneumonia Infected parapneumonic effusions and empyema Acute bacterial prostatitis Native valve endocarditis Neutropenic sepsis Necrotising (malignant) otitis externa Cellulitis Pyelonephritis Dose

Dose 400mg 8-12 hourly depending on indication.

Dose in Renal Impairment 50-100% of the dose if CrCl= 10-30mL/minute 50% of the dose if CrCl= <10mL/minute. Note 100% of the dose can be used in exceptional circumstances for short periods.

MHRA advice:

Disabling, long-lasting or potentially irreversible adverse reactions affecting musculoskeletal and nervous systems have been reported very rarely with fluoroquinolone antibiotics. Healthcare professionals are advised to inform patients to stop treatment at the first signs of a serious adverse reaction, such as tendinitis or tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy, and CNS effects, and to contact their doctor immediately

There is a small increased risk of aortic aneurysm and dissection. Seek immediate medical attention if sudden-onset severe abdominal, chest, or back pain develops

Side effects

Incidence Effect

Common or Very

Diarrhoea, , nausea, , pain or phlebitis at injection site


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Common

Uncommon , , arthralgia, asthenia, , decreased appetite, , dizziness, dyspepsia,

eosinophilia, fever, flatulence, gastrointestinal and abdominal pains, ,

headache, increase in transaminases, increased bilirubin, ,

musculoskeletelal pain , mycotic super infections, psychomotor

hyperactivity / agitation, pruritis, rash, renal impairment, sleep

disturbances, taste disorders, urticaria, vomiting

Rare Anxiety, abnormal dreams, allergic reaction, allergic oedema /

angioedema, anaemia antibiotic-associated colitis, arthritis, confusion

and disorientation, cholestatic icterus, crystalluria, depression,

disturbances in hearing, dyspnoea, haematuria, hallucinations, hearing

loss / hearing impaired, hepatic dysfunction, hepatitis, hypotension,

hyperglycaemia, hypoglycaemia, increased amylase, increased muscle

tone and cramping, , leukopenia, neutropenia, myalgia, , renal failure,

abnormal dreams, , hyperglycaemia, hypoaesthesia, hypoglycaemia,

hypotension, oedema, par- and dysaesthesia, pancreatitis,

photosensitivity reactions, seizures, sweating, syncope, tachycardia,

thrombocytopenia, thrombocytaemia, tinnitus, tremor, tubulointerstitial

nephritis, vasodilation, vertigo, visual disturbances

Very rare Agranulocytosis, anaphylactic reaction, bone marrow depression (life-

threatening), serum sickness-like reaction, haemolytic anaemia,

pancytopenia (life-threatening)

Interactions


Agomelatine Avoidance of ciprofloxacin advised by manufacturer of agomelatine

Aminophylline Ciprofloxacin increases plasma concentration of aminophylline

Artemether with Lumefantrine

Avoidance of quinolones advised by manufacturer of artemether with lumefantrine

Bosutinib Ciprofloxacin possibly increases the plasma concentration of bosutinib- manufacturer of bosutinib advises avoid or consider reducing the dose of bosutinib

Clozapine Ciprofloxacin increased the concentration of clozapine. Monitor for


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side effects

Ciclosporin Increased risk of nephrotoxicity when quinolones given with ciclosporin

Duloxetine Ciprofloxacin inhibits metabolism of duloxetine- avoid concomitant use

Ibrutinib Ciprofloxacin possibly increases the plasma concentration of ibrutinib- reduce dose of ibrutinib

NSAIDs Possible increased risk of convulsions when quinolones given with NSAIDs

Theophylline Ciprofloxacin increases plasma concentration of theophylline

Tizanidine Ciprofloxacin increases plasma concentration of tizanidine (increased risk of toxicity)

Please note that this is not an exhaustive list. Please refer to the online BNF or discuss with your pharmacist. Monitoring FBC, U&Es, LFTs, QT interval if on medicines that can also prolong QT Administration

Reconstitution Already in solution

Further Dilution Already in solution

Duration of Administration Administer 200mg dose over 30 minutes and 400mg dose over 60 minutes

Microbiology or Infectious Diseases approval required? No Storage Do not store above 25◦C What to supply on an eDAN for Leeds OPAT patients Ciprofloxacin bottles


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Co-amoxiclav Indications Respiratory Tract Infections Bone and joint infections Genito-urinary and abdominal infections Cellulitis Dose

Dose 1.2 grams THREE times a day

Dose in Renal Impairment CrCl= 10-30mL/minute use 1.2g TWICE a day CrCl= <10mL/minute use 1.2 g stat followed by 600 mg every 8 hours or 1.2 g every 12 hours.

Side effects

Incidence Effect


Diarrhoea

Uncommon Dizziness; dyspepsia; headache, nausea, vomiting, indigestion, raises

in AST and/ or ALT, skin rash, pruritis, urticaria

Rare Reversible leucopenia (including neutropenia), Thrombocytopenia,

Thrombophlebitis, erythema multiforme

Very rare

Frequency Unknown

Anaphylaxis, angioneurotic oedema, aseptic meningitis, convulsions,

colitis, haemorrhagic; crystalluria; reversible agranulocytosis,

hypersensitivity vasculitis; meningitis aseptic, haemolytic anaemia,

prolongation of bleeding time and prothrombin time, serum sickness-

like syndrome, hepatitis, cholestatic jaundice, steven- Johnson

syndrome, toxic epidermal necrolysis, bullous exfolative-dermatitis,

nephritis, crystalluria


31

Interactions



Allopurinol Increased risk of rash when amoxicillin given with allopurinol


Phenindione An interaction between broad-spectrum penicillins and phenindione has not been demonstrated in studies, but common experience in anticoagulant clinics is that INR can be altered

Monitoring FBC, U&Es, LFTs Administration

Reconstitution Reconstitute with water for injections adding 10mL to a 500/100mg vial and 20mL to a 1000/200mg vial

Further Dilution IV injection: Reconstituted solution can be given without further dilution IV infusion: Add the reconstituted 500/100mg solution to 50mL and the1000/200mg solution to 100mL of sodium chloride 0.9%

Duration of Administration IV injection: Give over 3-4 minutes. IV infusion: Dilute and give over 30-40 minutes

Storage Do not store above 25°C. What to supply on an eDAN for Leeds OPAT patients Co-amoxiclav vials Water for injection for reconstitution Sodium chloride 0.9% 50mL bags for dilution of 500/100mg solution or 100mL bags for 1000/200mg solution if to be administered by IV infusion


32

Daptomycin

Indications

Used for the following infections when beta-lactams, glycopeptides, clindamycin and oral linezolid can’t be used because of intolerance, contraindications, treatment failure or antimicrobial resistance:

Skin and soft tissue infections in adults caused by Gram positive organisms

Right-sided infective endocarditis [RIE] due to Staphylococcus aureus.

Staphylococcus aureus bloodstream infection when associated with cSSTI

Infective endocarditis caused by susceptible Gram positive organisms [including left sided Staphylococcus aureus endocarditis].

Bloodstream infection caused by susceptible Gram positive organisms (except where the primary infection is pulmonary).

Dose

Dose Daily dose varies between 4 mg/kg and 6mg/kg ONCE DAILY depending on indication.

Dose in Renal Impairment Dosage adjustments are required in patients with a creatinine clearance of <30ml/min, including those receiving haemodialysis or CAPD. The recommended dosing interval for patients with a creatinine clearance of <30ml/min is every 48 hours. Haemodialysis patients should receive their dose after the dialysis session. The mg/kg dosing regimen should reflect the clinical indication.

Obese patients

No dose adjustment required


33

Side effects

Incidence Effect


Anaemia, anxiety, asthenia, bloating and distension, candida,

constipation, diarrhoea dizziness, flatulence fungal infections,

gastrointestinal and abdominal pain, headache, hypertension,

hypotension, infusion site reactions, insomnia, infection, limb pain,

increased liver function tests abnormal, nausea, pruritus, pyrexia, rash,

serum creatine phosphokinase (CPK) increased, urinary tract infection,

vomiting

Uncommon Arthralgia, decreased appetite, dyspepsia, electrolyte imbalance,

eosinophilia, extrasystole, eye irritation, fatigue, flushes, fungaemia,

glossitis, hyperglycaemia, increased myoglobin, international

normalised ratio (INR) increased, leucocytosis, muscle cramps, ,

muscular weakness, muscle pain, myositis, paraesthesia, pain, renal

impairment, including renal failure and renal insufficiency, serum

creatinine increased, supraventricular tachycardia, serum lactate

dehydrogenase (LDH) increased, taste disorder, tremor,

thrombocythaemia, urticarial, vaginitis, vertigo

Rare Jaundice, prothrombin time (PT) prolonged

Very rare

Frequency Unknown

Acute generalised exanthematous pustulosis, Clostridium difficile-

associated, cough, diarrhoea, eosinophilic pneumonia, hypersensitivity,

peripheral neuropathy, rhabdomyolysis, thrombocytopaenia

Interactions


Ciclosporin Increased risk of myopathy when daptomycin with ciclosporin (preferably avoid concomitant use)

Fibrates Increased risk of myopathy when daptomycin with fibrates (preferably avoid concomitant use)

Statins Increased risk of myopathy when daptomycin with statins (preferably avoid concomitant use)


34

Please note that this is not an exhaustive list. Please refer to the online BNF or discuss with your pharmacist. Monitoring FBC, U&Es, LFTs, CK at baseline and weekly, muscular pain. NB If unexplained muscle pain, tenderness, weakness, or cramps develop during treatment, measure creatine kinase every 2 days, discontinue if unexplained muscular symptoms and creatine elevated markedly. Administration

Reconstitution For 350mg vial: Use 7mL of sodium chloride 0.9% to reconsitiute the vial For 500mg vial: Use 10mL of sodium chloride 0.9% to reconsitiute the vial

Further Dilution If being given as an infusion then further dilute with 50mL of sodium chloride 0.9%

Duration of Administration Bolus: Administer as an intravenous injection over 2 minutes Infusion: Administer as an intravenous infusion over 30 minutes.

Microbiology or Infectious Diseases approval required? Yes Storage Store in a refridgerator (2-8◦C) What to supply on an eDAN for Leeds OPAT patients

Daptomycin vials

Sodium chloride 0.9% for reconstitution

Sodium chloride 0.9% 50mL bags for dilution if being administered as an

intravenous infusion.


35

Ertapenem Indications Indications recommended by microbiology. Ertapenem is sometimes used as an alternative to meropenem as it can be used once daily. Please ensure that a discussion with infectious diseases or microbiology has taken place prior to switching as ertapenem does not have the exact same spectrum as meropenem. Dose

Dose 1gram ONCE daily

Dose in Renal Impairment Use 50-100% of dose if CrCl= 10-30mL/minute Use 50% of dose daily or 1gram THREE times a WEEK if CrCl= <10mL/minute

Side effects

Incidence Effect


Diarrhoea, elevations in ALT, AST, alkaline phosphatase, headache,

infused vein complication, injection-site reactions, nausea, pruritus,

phlebitis/thrombophlebitis raised platelet count, rash (also reported with

eosinophilia and systemic symptoms), vomiting

Uncommon Abdominal pain, acid regurgitation, anorexia, asthenia, bilirubin

increase, bradycardia, candidiasis chest pain, confusion,, constipation,

decreases in white blood cells/platelet count/neutrophils, dizziness,, dry

mouth, dyspepsia, dyspnoea, erythema, Extravasation, fatigue, fever,

fungal infection, extravasation, hypotension, Insomnia melaena,

oedema, Oral candidiasis, petechiae, pharyngeal discomfort, positive

Clostridium difficile toxin, pseudomembranous enterocolitis, raised

glucose, raised urine bacteria, serum creatinine increased, seizures,

sleep disturbances, taste disturbances, urticaria, vaginitis

Rare Abortion and genital bleeding, Agitation, allergy, anxiety, arrhythmia,

blood disorders, cholecystitis, cough, dermatomycosis, dermatitis,

depression, dysphagia, electrolyte disturbances, epistaxis, faecal

incontinence, haemorrhage, hypoglycaemia, increase in blood


36

pressure, injection site induration, jaundice, liver disorder, muscle

cramp, nasal congestion, neutropenia, pelvic peritonitis, Pneumonia,

postoperative wound infection, renal impairment, scleral disorder,

syncope, thrombocytopenia, tremor, urinary tract infection, wheezing

Frequency Unknown

Anaphylaxis, altered mental status, dyskinesia, gait disturbance,

hallucinations, muscular weakness, teeth staining

Interactions


Sodium Valproate

Carbapenems reduce plasma concentration of sodium valproate- avoid concomitant use

Valproic Acid Carbapenems reduce plasma concentration of valproic acid- avoid concomitant use


Reconstitution Use 10mL of water for injections or sodium chloride 0.9% to reconstitute the vial

Further Dilution Further dilute with 50mL of sodium chloride 0.9%

Duration of Administration Administer over 30 minutes

Microbiology or Infectious Diseases approval required? Yes Storage Do not store above 25◦C What to supply on an eDAN for Leeds OPAT patients

Ertapenem vials




37

Flucloxacillin Indications Breast abscess and mastitis Cellulitis Infected hip or knee replacements Infected long-term intravascular access devices Infected temporary central venous catheters and arterial catheters MSSA bacteraemia Native valve endocarditis Pre-septal and orbital cellulitis Septic arthritis of native joints Dose

Dose 8 grams over 24 hours

Dose in Renal Impairment Maximum of 4grams in 24 hours if CrCl <10mL/minute

Side effects

Incidence Effect


Minor gastrointestinal disturbances

Uncommon Rash, urticaria and purpura

Rare

Very rare Arthralgia, anaphylactic shock, angioneurotic oedema, erythema

multiforme, fever, haemolytic anaemia, hepatitis and cholestatic

jaundice, interstitial nephritis, metabolic acidosis, myalgia, neutropenia

(including agranulocytosis) and thrombocytopenia,

pseudomembranous colitis, Stevens-Johnson syndrome and toxic

epidermal necrolysis

Frequency Unknown

AGEP - acute generalized exanthematous pustulosis


38

Interactions


Coumarins Interaction hasn’t been demonstrated in studies, but it is common experience in anticoagulant clinics that the INR may be altered

Methotrexate Penicillins reduce the excretion of methotrexate and increase the risk of toxicity

Phenindione Interaction hasn’t been demonstrated in studies, but it is common experience in anticoagulant clinics that the INR may be altered





Microbiology or Infectious Diseases approval required? No Storage Store in a refrigerator (2-8◦C) What to supply on an eDAN for Leeds OPAT patients

Nothing- will be supplied by Lloyds.


39

Fluconazole

Indications Invasive candidiasis Dose

Dose 100mg-400mg ONCE DAILY depending on indication. Can use up to 800mg ONCE DAILY in some circumstances.

Dose in Renal Impairment If CrCl <50ml/min use 50% of the dose. If on dialysis, give 100% of the dose post-dialysis on dialysis days.

Side effects

Incidence Effect


Abdominal discomfort, diarrhoea, , headache, nausea, rash, Derranged Liver function teats: Increases in;alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, vomiting

Uncommon Anaemia, , angioedema (in children), asthenia, bilirubin increased, constipation, cholestasis, decreased appetite, dizziness, dry mouth, dyspepsia, fatigue, fever, flatulence, , insomnia, jaundice, malaise, myalgia, pruritus, paraesthesia, seizures, somnolence, sweating, taste disturbance, urticaria, vertigo,

Rare Alopecia, agranulocytosis,, anaphylaxis, leukopenia,

thrombocytopenia, neutropenia, hepatic disorders,

Hypercholesterolaemia, hypertriglyceridaemia, hypokalemia, tremor,

Torsade de pointes,QT prolongation, Stevens-Johnson syndrome, toxic

epidermal necrolysis, acute generalized exanthematous pustulosis,

dermatitis exfoliative angioedema, face oedema.

Very rare

Frequency Unknown

Drug reaction with eosinophilia and systemic symptoms (DRESS)

Interactions


Acenocoumarol Fluconazole increases the anticoagulant effect of acenocoumarol. Manufacturer advises monitor INR and adjust dose.

Alprazolam Fluconazole is predicted to increase the exposure to alprazolam.


40

Atorvastatin Possible increased risk of myopathy when fluconazole given with atorvastatin

Bosentan Fluconazole possibly increases plasma concentration of bosentan- avoid concomitant use

Bosutinib Fluconazole possibly increases plasma concentration of bosentan- avoid concomitant use or consider reducing dose of bosutinib

Bromocriptine Fluconazole is predicted to increase the exposure to bromocriptine.

Cabergoline Fluconazole is predicted to increase the exposure to cabergoline.

Carbamazepine Fluconazole possibly increases the concentration of carbamazepine avoid concomitant use or monitor carbamazepine concentrations

Ciclosporin Fluconazole inhibits metabolism of ciclosporin (increased plasma concentration)

Clopidogrel Fluconazole possibly reduces antiplatelet effect of clopidogrel

Cobimetinib Fluconazole is predicted to increase the exposure to cobimetinib.

Colchicine Fluconazole is predicted to increase the exposure to colchicine. Manufacturer advises adjust colchicine dose

Coumarins Fluconazole enhances anticoagulant effect of coumarins

Dasatinib Fluconazole is predicted to increase the exposure to dasatinib.

Domperidone Fluconazole increases the risk of QT-prolongation when given with domperidone. Manufacturer advises avoid.

Dronedarone Fluconazole is predicted to increase the exposure to dronedarone.

Eliglustat Fluconazole is predicted to increase the exposure to eliglustat. Manufacturer advises avoid or adjust dose—consult product literature.

Eplerenone Fluconazole is predicted to increase the exposure to eplerenone. Manufacturer advises adjust eplerenone dose.

Ergometrine Fluconazole is predicted to increase the risk of ergotism when given with ergometrine.

Ergotamine Fluconazole is predicted to increase the risk of ergotism when given with ergotamine.

Fluvastatin Fluconazole is predicted to increase the exposure to fluvastatin.

Ibrutinib Fluconazole possibly increases plasma concentration of ibrutinib- reduce dose of ibrutinib

Isavuconazole Fluconazole is predicted to increase the exposure to isavuconazole.

Ivabradine Fluconazole is predicted to increase the exposure to ivabradine. Manufacturer advises adjust ivadbradine dose.

Ivacaftor Fluconazole possibly increases plasma concentration of ivacaftor

Midazolam Fluconazole possibly increases plasma concentration of midazolam- risk of prolonged sedation

Mizolastine Fluconazole is predicted to increase the exposure to mizolastine.

Pimozide Fluconazole is predicted to increase the exposure to pimozide. Manufacturer advises avoid.


41

Piperaquine Fluconazole is predicted to increase the concentration of piperaquine.

Ranolazine Fluconazole is predicted to increase the exposure to ranolazine.

Rifabutin Fluconazole increases plasma concentration of rifabutin- consider reducing dose of rifabutin

Simeprevir Fluconazole possibly increases plasma concentration of simeprevir- manufacturer of simeprevir advises avoid concomitant use

Simvastatin Possible increased risk of myopathy when fluconazole given with simvastatin

Tacrolimus Fluconazole increases plasma concentration of tacrolimus- consider reducing dose of tacrolimus

Tadalafil Fluconazole is predicted to increase the exposure to tadalafil.

Vardenafil Fluconazole is predicted to increase the exposure to vardenafil. Manufacturer advises adjust dose.

Venetoclax Fluconazole is predicted to increase the exposure to venetoclax. Manufacturer advises avoid or adjust venetoclax dose.

Vinblastine Fluconazole is predicted to increase the exposure to vinblastine.

Vincristine Fluconazole is predicted to increase the exposure to vincristine.

Vindesine Fluconazole is predicted to increase the exposure to vindesine.

Vinflunine Fluconazole is predicted to increase the exposure to vinflunine.

Vinorelbine Fluconazole is predicted to increase the exposure to vinorelbine.

Warfarin Fluconazole increases the anticoagulant effect of warfarin. Manufacturer advises monitor INR and adjust dose.


Reconstitution Ready diluted

Further Dilution Ready diluted

Duration of Administration Administer as an infusion at a rate of 20mg/minute. For a 200mg dose, administer over 10 minutes. For a 400mg dose run two of the 200mg bottles consecutively i.e. 400mg over 20 minutes

Microbiology or Infectious Diseases approval required? No What to supply on an eDAN for Leeds OPAT patients

Fluconazole bottles


42

Fosfomycin

Indications As recommended by microbiology Dose

Dose 12-24grams in 2-4 divided doses depending on indication.

Dose in Renal Impairment Use 70% of the dose in 2-3 divided doses if CrCl 40mL/minute Use 60% of the dose in 2-3 divided doses if CrCl 30mL/minute Use 40% of the dose in 2-3 divided doses if CrCl 20mL/minute Use 20% of the dose in 2-3 divided doses if CrCl <10mL/minute

Side effects

Incidence Effect


Gastro-intestinal disturbances, injection site phlebitis

Uncommon Blood alkaline phosphatase, aspartate aminotransferase and alanine

aminotransferase increased, diarrhoea, nausea, vomiting,, decreased

appetite, dyspnoea, fatigue, headache, hypernatraemia, hypokalaemia,

oedema, rash, taste disturbances, vertigo

Rare Aplastic anaemia, eosinophilia

Very rare Anaphylactic shock, fatty liver, visual impairment.

Frequency Unknown

angioedema, asthmatic attack, confusion, facial oedema, hepatitis,

jaundice, tachycardia, agranulocytosis, granulocytopenia, leucopenia,

pancytopenia, pruritis, pseudomembranous colitis, thrombocytopenia,

neutropenia, urticaria

Interactions There are no specific interactions listed for fosfomycin.


43


Reconstitution Reconstitute each 2gram vial with 49ml of glucose 5% Reconstitute each 4gram vial with 98ml of glucose 5%

Further Dilution Diluted as per reconstitution instructions

Duration of Administration Run each 2gram reconstituted dose over at least 15 minutes. Run each 4gram reconstituted dose over 30minutes. If dose 6gram or 8gram, then run the 2 appropriate bags consecutively- the total infusion time should be 60minutes for these doses.

Microbiology or Infectious Diseases approval required? No Storage Do not store above 25◦C. Protect the vials from light What to supply on an eDAN for Leeds OPAT patients

Fosfomycin vials

Glucose 5% 100mL bags for dilution


44

Meropenem

Indications Complicated intra-abdominal infections Neutropenic sepsis Ventilator associated pneumonia Complicated skin and soft tissue infections Complicated urinary tract infections Dose

Dose 500mg-2grams every 8 hours depending on indication.

Dose in Renal Impairment 500mg-2gram every 12 hours if CrCl= 26-50mL/minute 500mg-1gram every 12 hours or 500mg every 8 hours if CrCl= 10-25mL/minute 500mg-1gram every 24 hours if CrCl <10mL/minute

Side effects

Incidence Effect


Abdominal pain, diarrhoea, disturbances in liver function tests,

headache, inflammation, nausea, pain, pruritus, rash,

thrombocythaemia, vomiting

Uncommon Agranulocytosis, anaphylaxis, angioedema, antibiotic associated colitis,

blood bilirubin increased, blood creatinine and urea increased,

eosinophilia, haemolytic anaemia, leucopenia, paraesthesia, pain at

injection site, thrombocytopenia, urticaria, toxic epidermal necrolysis,

neutropenia, oral and vaginal candidiasis, Stevens Johnson syndrome,

erythema multiforme.

Rare Convulsions

Very rare

Frequency Unknown


45

Interactions


Sodium valproate

Carbapenems reduce plasma concentration of sodium valproate- avoid concomitant use

Valproic acid Carbapenems reduce plasma concentration of valproic acid- avoid concomitant use


Reconstitution Reconstitute each 500mg vial with 10mL of water for injections Reconstitute each 1gram vial with 20mL of water for injections

Further Dilution For doses of up to 1gram- can add to 50-100mL of sodium chloride 0.9% or glucose 5% if for infusion For doses of up to 2grams- can add to 100mL of sodium chloride 0.9% or glucose 5% if for infusion

Duration of Administration Can be administered as a slow bolus over 5 minutes. If administering as an infusion then infuse over 15-30 minutes. Infusion is the preferred method of administration and there is limited data in particular for administering doses of 2grams as a bolus.

Microbiology or Infectious Diseases approval required? No, unless outside of antimicrobial guidelines Storage Do not store above 30◦C What to supply on an eDAN for Leeds OPAT patients

Meropenem vials


Sodium chloride 0.9% 50mL or 100mL bags for dilution if administering as an

intravenous infusion


46

Piperacillin/Tazobactam

Indications Infective exacerbation of bronchiectasis and CF Appendicitis and diverticulitis in >65 years Infected temporary CVCs and arterial catheters in >65 years not recently treated with pip/tazo Infected long term intravascular access devices Neutropenic sepsis Hospital acquired pneumonia Spontaneous bacterial peritonitis Ventilator-associated pneumonia Diabetic foot infection Aspiration pneumonitis and aspiration pneumonia Sepsis of unknown source Sepsis - intraabdominal infection >65 years Acute bacterial prosatitis Necrotising otitis externa Any other indication recommended by microbiology Dose

Dose 4.5grams THREE times a day OR 13.5grams over 24 hours

Dose in Renal Impairment If CrCl <20ml/min then decrease dose to 4.5gram BD

Side effects

Incidence Effect


diarrhoea, rashes, , nausea, vomiting

Uncommon Blood creatinine increased, candidial superinfection, constipation, dyspepsia, headache, hypersensitivity, hypotension, injection-site reactions, insomnia, jaundice, leukopenia, liver function test abnormalities, neutropenia, phlebitis, pruritis, pyrexia, stomatitis, thrombocytopenia, thrombophlebitis, urticaria

Rare Abdominal pain, anaemia, anaphylaxis, arthralgia, bleeding time prolonged, cerebral irritation, chills, , deranged LFTs, dermatitis bullous, exanthema, , epistaxis, erythema multiforme, eosinophilia, flushing, haemolytic anaemia, hepatitis, , myalgia, pseudomembranous colitis, purpura, renal failure, thrombocytopenia, tubulonterstitial


47

nephritis,

Very rare Agranulocytosis, activated partial thromboplastin time prolonged, blood urea increased, coombs' direct test positive, Hypoglycaemia, hypokalaemia, pancytopenia, Steven-Johnson syndrome, thrombocythaemia, toxic epidermal necrolysis

Frequency Unknown

Interactions




Please note that this is not an exhaustive list. Please refer to the online BNF or discuss with your pharmacist. Monitoring FBC, U&Es, LFTs Administration Instructions for 4.5grams dose

Reconstitution Reconstitute the vial with 20mL of water for injections or sodium chloride 0.9%

Further Dilution Further dilute with 100mL of sodium chloride 0.9%

Duration of Administration Administer as an infusion over 30 minutes

Administration Instructions for 13.5grams dose




Microbiology or Infectious Diseases approval required? Yes if not in the aforementioned guidelines Storage Do not store above 25◦C What to supply on an eDAN for Leeds OPAT patients

Piperacillin/tazobactam vials

Water for injections or sodium chloride 0.9% 20ml ampoules for reconstitution


48



49

Teicoplanin

Indications and dose

Infection Loading dose Maintenance dose

Infective endocarditis 12mg/kg every 12 hours for three to five doses

12mg/kg once daily

Osteomyelitis Diabetic foot infections Septic arthritis of native joints Infected parapneumonic effusions and empyema Complicated intra-abdominal infections Neutropenic sepsis Spontaneous bacterial peritonitis Bacteraemias Infected “temporary” central venous catheters and arterial catheters

12mg/kg every 12 hours for three doses

12mg/kg once daily

Apiration pneumonitis and aspiration pneumonia Cellulitis Community acquired pneumonia Hospital acquired pneumonia Ventilator acquired pneumonia Exacerbations of CF Infected long term intravascular devices Acute parotitis Sinusitis Acute sore throat Otitis externa Otitis media and mastoiditis Breast abscesses and mastitis Community acquired rhinosinusitis

6mg/kg every 12 hours for three doses

6mg/kg once daily

The dose is based on actual body weight and is capped at 2g as a single dose

Maintenance Dose in Renal Impairment

HALVE daily dose on the FIFTH day of treatment if CrCl= 30-80mL/minute Use a THIRD of the daily dose on the FIFTH day of treatment if CrCl <30mL/minute


50

Three times weekly dosing Patients can also be administered teicoplanin three times weekly. For this dosing, use the dosing guidance in the table above based on renal function, then multiply the daily dose by 7 and divide by 3 for the three times weekly dose. Note maximum of 2grams as a single dose. For example, a 50 year old male patient weighing 60kg with a creatinine of 200 (CrCl= 34mL/minute). Daily dose= 400mg OD. Three times weekly dose= 900mg three times weekly. NB Both doses rounded to the nearest 100mg for ease of administration.

Side effects

Incidence Effect


Erythema, pain, pruritus, pyrexia, rash

Uncommon Anaphylactis, blood creatinine increased, bronchospasm, deafness,

deranged LFTs, diarrhoea, dizziness, eosinophilia, headache,

leucopenia, mild hearing loss, nausea, phlebitis, thrombocytopenia,

tinnitus, vestibular disorder, vomiting.

Rare Abscess, red man syndrome

Very rare

Frequency Unknown

Agranulocytosis, anaphylactic shock, angioedema, dermatitis

exfoliative, chills, drug reaction with eosinophilia and systemic

symptoms (DRESS), erythema multiforme, injection site absess,

neutropenia, renal failure, seizures, Stevens-Johnson syndrome:

superinfection, thrombophlebitis, toxic epidermal necrolysis, urticaria

Interactions There are no specific interactions listed for teicoplanin, however please take care when using alongside other nephrotoxic medicines. Monitoring FBC, U&Es, LFTs, teicoplanin levels


51

Therapeutic Drug Monitoring

Infection Target level

Infective endocarditis 30-40mg/L

Osteomyelitis Diabetic foot infections Septic arthritis of native joints Infected parapneumonic effusions and empyema Complicated intra-abdominal infections Neutropenic sepsis Spontaneous bacterial peritonitis Bacteraemias Infected “temporary” central venous catheters and arterial catheters

20-30mg/L

Apiration pneumonitis and aspiration pneumonia Community acquired pneumonia Hospital acquired pneumonia Ventilator acquired pneumonia Exacerbations of CF Infected long term intravascular devices Acute parotitis Sinusitis Acute sore throat Otitis externa Otitis media and mastoiditis Breast abscesses and mastitis Community acquired rhinosinusitis Cellulitis

15-30mg/L

Timing of Sample Trough level. Immediately prior to dose.

Frequency of Level On 5th day of new dose or weekly if no dose changes

Administration

Reconstitution Reconstitute using the 3.14mL vial of water for injections that comes with the teicoplanin vial. Add slowly to the vial of teicoplanin and rotate, to reduce foaming. If the vial does foam, leave it to stand before administering or further diluting. Only use clear or yellowish solutions. NOTE: The final concentration of the 200mg vial will be


52

66.6mg/mL, the final concentration of the 400mg vial will be 133.3mg/mL. Please take care when using different strength vials.

Further Dilution For doses over 800mg dilute in 100mL of sodium chloride 0.9%.

Duration of Administration For doses less than or equal to 800mg administer as a bolus over 3 to 5 minutes. For doses over 800mg administer as an infusion over 60 minutes.

Microbiology or Infectious Diseases approval required? No Storage Powder vial: No special storage conditions What to supply on an eDAN for Leeds OPAT patients

Teicoplanin vials (these already contain diluent)

Sodium chloride 0.9% 100mL bags for dilution if administering as an

intravenous infusion

Sodium chloride 0.9% 10mL ampoules if the dose is to be administered as a

bolus so the OPAT nurses can make the volume up to 10mL.


53

Temocillin Indications Hospital acquired pneumonia Any indication recommended by microbiology Dose

Dose 1-2gram every 12 hours depending on indication.

Dose in Renal Impairment 1gram every 12 hours if CrCl= 30-60mL/minute 1gram every 24 hours if CrCl= 10-30mL/minute 1gram every 48 hours or 500mg every 24 hours if CrCl <10mL/minute

Side effects

Incidence Effect


Diarrhoea; hypersensitivity; nausea; skin reactions; thrombocytopenia;

vomiting

Uncommon Antibiotic associated colitis; leucopenia

Rare Agranulocytosis; angioedema; haemolytic anaemia; hepatic disorders;

nephritis tubulointerstitial; neutropenia; seizure; severe cutaneous

adverse reactions (SCARs)

Very rare

Frequency Unknown

Interactions


Coumarins Interaction hasn’t been demonstrated in studies, but it is common experience in anticoagulant clinics that the INR may be altered

Methotrexate Penicillins reduce the excretion of methotrexate and increase the risk of toxicity

Phenindione Interaction hasn’t been demonstrated in studies, but it is common experience in anticoagulant clinics that the INR may be altered


54


Reconstitution Reconstitute each 1gram vial with 10mL water for injections to form a pale yellow solution Reconstitute each 2gram vial with 20mL water for injections to form a pale yellow solution

Further Dilution If administering as an infusion then dilute with 50-150mL of sodium chloride 0.9% or glucose 5%

Duration of Administration Administer over 3 to 4 minutes if administering as a bolus Administer over 30 to 40 minutes if administering as an infusion

Microbiology or Infectious Diseases approval required? Yes if not in the aforementioned guidelines Storage Store in the original package, in the refrigerator at 2-8◦C What to supply on an eDAN for Leeds OPAT patients

Temocillin vials


Sodium chloride 0.9% 50mL or 100mL bags or glucose 5% 50mL or 100mL

bags for dilution if administering as an intravenous infusion


55

Tigecycline

Indications Any indication approved by microbiology Dose

Dose 100mg stat, then reduce to 50mg TWICE DAILY

Dose in Renal Impairment No dose adjustment required

Dose in Hepatic Impairment

100mg stat, then reduce to 25mg TWICE DAILY in severe hepatic impairment.

Side effects

Incidence Effect


Abdominal pain, abscess, anorexia, bilirubinaemia: deranged LFTs,

diarrhoea, dizziness, dyspepsia, headache, hypoglycaemia,

hypoproteinaemia, impaired healing, infections, injection-site reactions,

nausea, phlebitis, pneumonia, prolonged activated partial

thromboplastin time, prolonged prothrombin time, pruritus, rash,

sepsis,vomiting

Uncommon cholestatic jaundice, increased international normalised ratio (INR),

liver injury, injection site inflammation and pain, pancreatitis,

thrombocytopenia,

Rare

Very rare

Frequency Unknown

Anaphylaxis, hepatic failure: hypofibrinogenaemia, Stevens-Johnson

syndrome:

Interactions


Coumarins Tigecycline possibly enhances anticoagulant effect of coumarins

Please note that this is not an exhaustive list. Please refer to the online BNF or discuss with your pharmacist.


56


Reconstitution Reconstitute with 5.3mL of sodium chloride 0.9%. Gently swirl the vial until the powder has dissolved. The solution should be inspected for the presence of particulate matter or green or black discolouration before use. Tigecycline should be yellow/orange in colour once reconstituted, if it is not, it should be discarded.

Further Dilution Withdraw 5mL of the reconstituted vial to a 100mL bag of sodium chloride 0.9% or glucose 5% for the 50mg dose Withdraw 10mL of the reconstituted vial to a 100mL bag of sodium chloride 0.9% or glucose 5% for the 100mg dose

Duration of Administration Administer over 30 to 60 minutes

Microbiology or Infectious Diseases approval required? Yes Storage Do not store above 25◦C

What to supply on an eDAN for Leeds OPAT patients

Tigecycline vials

Sodium chloride 0.9% ampoules for reconstitution

Sodium chloride 0.9% or glucose 5% 100mL bags for dilution

.


57

References

Electric Medicines Compendium

https://www.medicines.org.uk/emc/

Online BNF

https://www.medicinescomplete.com/mc/bnf/current/

LTHT Injectable Medicines Guide (Medusa)

http://medusa.wales.nhs.uk/LocalSelect.asp

Renal Drug Database

https://renaldrugdatabase.com/

TB Drug Monographs

http://www.tbdrugmonographs.co.uk/

https://www.medicines.org.uk/emc/

https://www.medicinescomplete.com/mc/bnf/current/

http://medusa.wales.nhs.uk/LocalSelect.asp

https://renaldrugdatabase.com/

http://www.tbdrugmonographs.co.uk/

OPAT Drug Monographs - Leeds Formulary

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Transcript of OPAT Drug Monographs - Leeds Formulary