Foscarnet parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Solution for infusion containing foscarnet
Drugs List
Therapeutic Indications
Uses
Mucocutaneous H.simplex(HSV) unresponsive to aciclovir in immunocompromised
Treatment of cytomegalovirus (CMV) retinitis in patients with AIDS
Dosage
Adults
Induction treatment of cytomegalovirus retinitis
Inital dose: 60mg/kg every 8 hours as intermittent infusions, for two to three weeks. Alternatively, 90mg/kg every 12 hours for two to three weeks.
Maintenance dose: 60mg/kg daily, increased to 120mg/kg daily if tolerated.
Mucocutaneous Herpes Simplex Virus
40mg/kg over 1 hour, every 8 hours as intermittent infusions, for two to three weeks or until the lesions have healed.
Children
Cytomegalovirus disease (unlicensed)
Children aged 1 month to 18 years:
Inital dose: 60mg/kg every 8 hours by intravenous infusion for two to three weeks.
Maintenance dose: 60mg/kg daily and increase to 90mg/kg to 120mg/kg daily if tolerated.
Mucocutaneous Herpes Simplex Virus (unlicensed)
Children aged 1 month to 18 years:
40mg/kg every 8 hours by intravenous infusion for two to three weeks or until the lesions heal.
Patients with Renal Impairment
The dose must be reduced in patients with renal insufficiency according to the creatinine clearance level as described in the table below.
CMV retinitis induction treatment
Creatinine clearance greater than 1.6 ml/kg/minute - 60 mg/kg every 8 hours.
Creatinine clearance between 1.6 and 1.4 ml/kg/minute - 55 mg/kg every 8 hours.
Creatinine clearance between 1.4 and 1.2 ml/kg/minute - 49 mg/kg every 8 hours.
Creatinine clearance between 1.2 and 1.0 ml/kg/minute - 42 mg/kg every 8 hours.
Creatinine clearance between 1.0 and 0.8 ml/kg/minute - 35 mg/kg every 8 hours.
Creatinine clearance between 0.8 and 0.6 ml/kg/minute - 28 mg/kg every 8 hours.
Creatinine clearance between 0.6 and 0.4 ml/kg/minute - 21 mg/kg every 8 hours.
Creatinine clearance less than 0.4 ml/kg/minute - treatment not recommended.
Mucocutaneous HSV induction treatment
Creatinine clearance greater than 1.6 ml/kg/minute - 40mg/kg every 8 hours.
Creatinine clearance between 1.6 and 1.4 ml/kg/minute - 37 mg/kg every 8 hours.
Creatinine clearance between 1.4 and 1.2 ml/kg/minute - 33 mg/kg every 8 hours.
Creatinine clearance between 1.2 and 1.0 ml/kg/minute - 28 mg/kg every 8 hours.
Creatinine clearance between 1.0 and 0.8 ml/kg/minute - 24 mg/kg every 8 hours.
Creatinine clearance between 0.8 and 0.6 ml/kg/minute - 19 mg/kg every 8 hours.
Creatinine clearance between 0.6 and 0.4 ml/kg/minute - 14 mg/kg every 8 hours.
Creatinine clearance less than 0.4 ml/kg/minute - treatment not recommended.
CMV retinitis maintenance treatment
Creatinine clearance greater than 1.6 ml/kg/minute - 60mg/kg once daily.
Creatinine clearance between 1.6 and 1.4 ml/kg/minute - 55 mg/kg once daily.
Creatinine clearance between 1.4 and 1.2 ml/kg/minute - 49 mg/kg once daily.
Creatinine clearance between 1.2 and 1.0 ml/kg/minute - 42 mg/kg once daily.
Creatinine clearance between 1.0 and 0.8 ml/kg/minute - 35 mg/kg once daily.
Creatinine clearance between 0.8 and 0.6 ml/kg/minute - 28 mg/kg once daily.
Creatinine clearance between 0.6 and 0.4 ml/kg/minute - 21 mg/kg once daily.
Creatinine clearance less than 0.4 ml/kg/minute - treatment not recommended.
The Renal Drug Handbook suggests the following doses for patients with renal impairment:
GFR 20-50 ml/minute - 28 mg/kg every 8 hours.
GFR 10-20 ml/minute - 15 mg/kg every 8 hours.
GFR less than 10 ml/minute - 6mg/kg every 8 hours.
Additional Dosage Information
Hydration with 0.5 to 1 litre of sodium chloride 0.9% is recommended with each infusion to reduce renal toxicity.
The infusion time should not be shorter than 1 hour.
Administration
For intravenous infusion only via a central venous line or peripheral vein.
Handling
Foscarnet is an irritant so should it come into contact with skin or mucus membrane, rinse and clean the area.
Foscarnet should be handled aseptically.
Contraindications
Neonates under 1 month
Breastfeeding
Long QT syndrome
Pregnancy
Torsade de pointes
Precautions and Warnings
Children 1 month to 18 years
Family history of long QT syndrome
Electrolyte imbalance
Haemodialysis
History of torsade de pointes
Renal impairment
Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Maintain adequate hydration of patient prior / during treatment
Accidental contact of soln with skin/mucous membranes-rinse well with water
Administer infusion slowly
Do not give other medication through the same intravenous line
Monitor electrolytes, esp. calcium + magnesium prior to during therapy
Consider monitoring ECG in patients at risk of QT prolongation
Monitor serum creatinine every second day (induction)/ weekly (maintenance)
Monitor serum electrolytes
Discontinue if overgrowth of resistant organisms occurs
Advise patient on good hygiene post-micturition to avoid genital irritation
Foscarnet should be used with caution in patients with reduced renal function. Since renal functional impairment may occur at any time during foscarnet administration, serum creatinine should be monitored every second day during induction therapy and once weekly during maintenance therapy, and appropriate dose adjustments should be performed according to renal function.
Due to foscarnet propensity to chelate bivalent metal ions, such as calcium, foscarnet administration may be associated with an acute decrease of ionised serum calcium, which may not be reflected in total serum calcium levels. The electrolytes, especially calcium and magnesium, should be assessed prior to and during therapy and deficiencies corrected.
When diuretics are indicated, thiazides are recommended.
Clinical unresponsiveness can appear which may be due to appearance of virus strains with decreased sensitivity towards foscarnet. Termination of treatment with foscarnet should then be considered.
Pregnancy and Lactation
Pregnancy
Foscarnet is contraindicated in pregnancy.
Animal studies on rats and rabbits have shown an increased frequency of skeletal malformations or variations (Briggs, 2011). If foscarnet is used during the first trimester, termination of pregnancy is not advocated, however a detailed ultrasound investigation may be considered (Schaefer, 2007). Due to the frequent occurrence of renal toxicity in adults and the lack of information about whether foscarnet crosses the placenta. The molecular weight (about 300 for the sodium salt) is low enough that passage to the fetus should be expected, foetal renal toxicity should be monitored if foscarnet is administered during pregnancy. This can be carried out by frequent testing of the foetus and close monitoring of the amniotic fluid volume (Briggs, 2011). Foscarnet does have genotoxic potential.
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
Foscarnet is contraindicated while breastfeeding. Animal studies on rats have shown that foscarnet is concentrated in their milk. Although it is unknown whether foscarnet passes into human milk it is suspected that it does (Hale, 2010). Also considering the HIV status of the patient and the transmission of HIV in breast milk foscarnet is contraindicated whilst breastfeeding (Schaefer, 2007).
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
Acute renal failure
Aggression
Agitation
Altered liver function tests
Anaphylactoid reaction
Angioedema
Anorexia
Anxiety
Aspartate aminotransferase increased
Asthenia
Chest pain
Chills
Confusion
Constipation
Convulsions
Creatine phosphokinase increased
Decrease in haemoglobin
Dehydration
Depression
Diabetes insipidus
Diarrhoea
Dizziness
Dyspepsia
Dysuria
ECG changes
Electrolyte disturbances
Elevated amylase levels
Elevated serum lipase
Erythema multiforme
Extravasation
Fatigue
Gamma glutamyl transferase (GGT) increased
Gastro-intestinal haemorrhage
Genital irritation
Genital ulceration
Glomerulonephritis
Granulocytopenia
Haematuria
Headache
Hyperphosphataemia
Hypersensitivity reactions including anaphylaxis
Hypertension
Hypoaesthesia
Hypocalcaemia (symptomatic)
Hypokalaemia
Hypomagnesaemia
Hyponatraemia
Hypophosphataemia
Hypotension
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Inflammation (injection site)
Involuntary muscle contractions
Leukopenia
Malaise
Metabolic acidosis
Muscle weakness
Myalgia
Myopathy
Myositis
Nausea
Nephrotic syndrome
Nervousness
Neuropathy
Neutropenia
Oedema
Pain / soreness (injection site)
Palpitations
Pancreatitis
Paraesthesia
Polyuria
Prolongation of QT interval
Proteinuria
Pruritus
Psychosis
Pyrexia
Rash
Renal impairment
Renal pain
Rhabdomyolysis
Sepsis
Serum creatinine increased
Stevens-Johnson syndrome
Tachycardia
Thrombocytopenia
Thrombophlebitis
Toxic epidermal necrolysis
Tremor
Urticaria
Ventricular arrhythmias
Vomiting
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: August 2013
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.
Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.
Summary of Product Characteristics: Foscavir. Clinigen healthcare Ltd. Revised June 2017.
The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.
NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 30 June 2017.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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