Filgrastim parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations of filgrastim.
Drugs List
Therapeutic Indications
Uses
Congenital neutropenia with a history of severe or recurrent infections
Cyclic neutropenia with a history of severe or recurrent infections
Idiopathic neutropenia with a history of severe or recurrent infections
Mobilisation of peripheral blood progenitor cells following chemotherapy
Mobilisation of peripheral blood progenitor cells for autologous infusion
Neutropenia in advanced HIV infection
Reduction in the duration of neutropenia following bone marrow transplant
Reduction of neutropenia-related risk of infection with cytotoxic drugs
Unlicensed Uses
Glycogen storage disease 1b
Neonatal neutropenia
Dosage
Filgrastim must not be used to increase the dose of cytotoxic chemotherapy beyond established dosage regimes.
Filgrastim therapy should only be given in collaboration with an oncology centre experienced in granulocyte-colony stimulating factor (G-CSF) treatment and haematology, with the necessary diagnostic and monitoring facilities.
The peripheral blood progenitor cells (PBPCs) mobilisation and apheresis procedures should be performed in collaboration with an oncology-haematology centre with acceptable experience in this field and where the monitoring of haematopoietic progenitor cells can be correctly performed.
Whilst the doses stated below are those recommended by the manufacturer, local protocols for the relevant indication should be consulted.
Adults
Established cytotoxic chemotherapy
Recommended dose is 5 micrograms (0.5 million units)/kg/day.
In trials a subcutaneous dose of 230 micrograms/square metre/day (4 to 8.4 microgram/kg/day) was used.
The first dose should be administered at least 24 hours after cytotoxic chemotherapy. Filgrastim may be given as a daily subcutaneous injection or as a daily intravenous infusion diluted in 5% glucose infusion given over 30 minutes. The subcutaneous route is preferred in most cases as there is some evidence from a study of single dose administration that intravenous dosing may shorten the duration of effect. The clinical relevance of this in multiple dose administration is unclear.
Following established chemotherapy for solid tumours, lymphomas, and lymphoid leukaemias, this time is expected to be up to 14 days. Following treatment of acute myeloid leukaemia this is expected to be considerably longer (up to 38 days) varying according to type, dose and schedule of cytotoxic chemotherapy used.
A transient increase in neutrophil counts is typically seen 1 to 2 days after initiation of filgrastim therapy. However, for sustained response, filgrastim therapy should not be discontinued before the expected nadir has passed and the neutrophil count recovered to the normal range. Discontinuation of filgrastim therapy before the expected neutrophil nadir is not recommended.
Myeloablative therapy followed by bone marrow transplantation
Recommended starting dose is 10 micrograms (1 million units)/kg/day.
This may be given as:
(1) Intravenous infusion over 30 minutes
(2) Continuous intravenous infusion over 24 hours
(3) Continuous 24 hour subcutaneous infusion
Filgrastim should be diluted in 20 ml of 5% glucose injection.
The first dose should be administered at least 24 hours after cytotoxic chemotherapy and not within 24 hours of bone marrow infusion.
Once the neutrophil nadir has been passed, the daily dose of filgrastim should be titrated against the neutrophil response as follows:
Neutrophil count greater than 1 x 10 to the power of 9 per litre for 3 consecutive days: Reduce to 5 micrograms (0.5 million units)/kg/day
If absolute neutrophil count (ANC) remains greater than 1 x 10 to the power of 9 per litre for 3 more consecutive days: Discontinue filgrastim
If the ANC decreases to less than 1 x 10 to the power of 9 per litre during the treatment period, the dose of filgrastim should be re-escalated.
Mobilisation of peripheral blood progenitor cells (PBPCs) in patients undergoing myelosuppressive or myeloablative therapy followed by autologous PBPC transplantation
Used alone:
Recommended dose is 10 micrograms (1 million units)/kg/day as a 24 hour subcutaneous continuous infusion or a single daily subcutaneous injection for 5 to 7 consecutive days.
For infusions, filgrastim should be diluted in 20 ml of 5% glucose solution.
One or two leukapheresis on days 5 and 6 are often sufficient. In other circumstances, additional leukapheresis may be necessary. Filgrastim dosing should be maintained until the last leukapheresis.
After myelosuppressive chemotherapy:
Recommended dose is 5 micrograms (0.5 million units)/kg/day by subcutaneous injection from the first day after completion of chemotherapy until the expected neutrophil nadir is passed and the neutrophil count has returned to the normal range.
Leukapheresis should be performed during the period when the absolute neutrophil count (ANC) rises from less than 0.5 x 10 to the power of 9 per litre to greater than 5 x 10 to the power of 9 per litre. For patients who have not had extensive chemotherapy, one leukapheresis is often sufficient. In other circumstances, additional leukapheresis are recommended.
Mobilisation of peripheral blood progenitor cells (PBPCs) in normal donors before allogeneic peripheral blood progenitor cell transplantation
Recommended dose is 10 microgram (1 million units)/kg/day by subcutaneous injection for 4 to 5 consecutive days.
Leukapheresis should be started at day 5 and continued until day 6 if needed in order to collect 4 x 10 to the power of 6 CD34+ cells/kg recipient bodyweight.
Safety and efficacy of filgrastim has not been assessed in normal donors aged less than 16 or over 60 years.
Severe chronic neutropenia
Congenital neutropenia - Starting dose of 12 micrograms (1.2 million units)/kg/day by subcutaneous injection in single or divided doses.
Idiopathic or cyclic neutropenia - Starting dose of 5 micrograms (0.5 million units)/kg/day by subcutaneous injection in single or divided doses.
Administer daily by subcutaneous injection until the neutrophil count has reached and can be maintained at more than 1.5 x 10 to the power of 9 per litre. When the response has been obtained, the minimal effective dose to maintain this level should be established. Long term daily administration is required to maintain an adequate neutrophil count.
After 1 to 2 weeks of therapy, the initial dose may be doubled or halved depending on the patient's response. Subsequently, the dose may be adjusted individually every 1 to 2 weeks to maintain the average neutrophil count between 1.5 x 10 to the power of 9 per litre and 10 x 10 to the power of 9 per litre. A faster schedule of dose escalation may be considered in patients presenting with severe infections.
The long term safety of filgrastim administration above 24 microgram (2.4 million unit)/kg/day in patients with severe chronic neutropenia has not been established. In clinical trials 97% of patients who responded had a complete response at doses less than or equal to 24 microgram/kg/day.
HIV infection
Reversal of neutropenia - Starting dose of 1 microgram (0.1 million units)/kg/day by subcutaneous injection adjusted up to a maximum of 4 micrograms (0.4 million unit)/kg/day until a normal neutrophil count is reached and can be maintained (ANC greater than 2 x 10 to the power of 9 per litre). In clinical studies greater than 90% of patients responded in a median of 2 days. A small number of patients (less than 10%) may need up to 10 micrograms (1 million units)/kg/day.
Maintenance of normal neutrophil counts - When reversal of neutropenia has been achieved, the minimal effective dose to maintain a normal neutrophil count should be established.
Initial dose adjustment to alternate day dosing with 300 micrograms (30 million units)/day by subcutaneous injection is recommended.
Further dose adjustment may be necessary to maintain the neutrophil count at more than 2 x 10 to the power of 9 per litre. Long term administration may be required to maintain the ANC at more than 2 x 10 to the power of 9 per litre. In clinical studies, dosing with 300 micrograms (30 million units)/day on 1 to 7 days per week (median frequency of 3 days/week) was required.
Elderly
Clinical trials have included a small number of elderly patients, however, studies have not been performed in this group and therefore specific dosage recommendations cannot be made.
Mobilisation of peripheral blood progenitor cells (PBPCs) in normal donors before allogeneic peripheral blood progenitor cell transplantation
The safety and efficacy of filgrastim has not been assessed in normal donors aged over 60 years.
Children
Severe chronic neutropenia (SCN) and cancer settings
(See Dosage; Adult)
65% of the patients studied in the SCN trial program were under 18 years of age. The efficacy of treatment was clear for this age group, which included most patients with congenital neutropenia. There were no differences in the safety profiles for paediatric patients treated for severe chronic neutropenia.
Data from clinical studies in paediatric patients indicate that the safety and efficacy of filgrastim are similar in both adults and children receiving cytotoxic chemotherapy.
Dosage suggestions in paediatric patients are the same as those in adults receiving myelosuppressive cytotoxic chemotherapy.
Mobilisation of peripheral blood progenitor cells (PBPCs) in normal donors before allogeneic peripheral blood progenitor cell transplantation
Safety and efficacy of filgrastim has not been assessed in normal donors aged less than 16 years.
Glycogen Storage Disease Type 1b (unlicensed)
5 microgram/kg/day subcutaneous injection, adjusted as required.
Neonates
Neutropenia (unlicensed)
Manufacturer states safety and efficacy in autoimmune neutropenia has not been established.
An alternative source suggests a dose of 10 micrograms/kg/day by subcutaneous injection. If white cell count exceeds 50 x 10 to the power of 9 per litre, therapy should be discontinued.
Administration
Administer by subcutaneous injection, continuous subcutaneous infusion or intravenous infusion.
The preferred route depends on the indication.
Contraindications
Chronic myeloid leukaemia
Hereditary fructose intolerance
Myelodysplastic syndrome
Severe congenital neutropenia with abnormal cytogenetics
Precautions and Warnings
Children under 16 years if used for mobilisation of PBPC in normal donors
Neonates
Patients over 60 if used for mobilisation of PBPC in normal donors
Autoimmune neutropenia
Breastfeeding
History of pulmonary infiltrates
Malignancy with myeloid characteristics
New onset acute myeloid leukaemia in patients below 55 years
Osteoporosis
Pregnancy
Premalignant myeloid disorder
Recent history of pneumonia
Secondary acute myeloid leukaemia
Sickle cell disease
Sickle cell trait
Do not perform leukapheresis on anticoagulated/haemostasis-defective donors
Incidence of thrombocytopenia and anaemia not reduced by treatment
Administer at least 24 hours after bone marrow infusion
Advise ability to drive/operate machinery may be affected by side effects
Do not administer less than 24 hours after cytotoxic chemotherapy
Treat underlying infection causing neutropenia concurrently
Treat underlying lymphoma causing neutropenia concurrently
Treatment to be initiated and supervised by a specialist
Needle cover contains a derivative of latex in some brands
Presentations with sorbitol unsuitable in hereditary fructose intolerance
If dilution is required, use only 5% glucose
Record name and batch number of administered product
Consider splenic rupture if patient has abdominal or shoulder pain
Monitor bone density if used >6 months in osteoporotic bone disease
Monitor for occurrence of anaemia
Monitor for symptoms of Capillary Leak Syndrome
Monitor for transient increases in myeloid progenitors
Monitor haematocrit values
Monitor long-term safety of normal donors
Monitor neutrophil count
Monitor normal donors until haematological indices return to normal
Monitor spleen size
Perform morphological and cytogenic bone marrow examinations 12 monthly
Perform regular urinalysis
Perform regular white blood cell and platelet counts
Advise patient to seek medical advice if signs/symptoms of aortitis occur
Antibodies to ingredient may develop
Seek urgent medical attention if symptoms of Capillary Leak Syndrome occur
May affect bone imaging results
Discontinue if adult respiratory distress syndrome occurs
Discontinue if leukaemia occurs
Discontinue if myelodysplastic syndrome occurs
Discontinue if serious allergic or anaphylactic reaction occurs
Discontinue or reduce dose if glomerulonephritis occurs
If aortitis is suspected it can usually be diagnosed by CT scan and generally resolves after withdrawal of filgrastim.
Hypersensitivity, including anaphylactic reactions, occurring on initial or subsequent treatment have been reported in patients treated with filgrastim. Permanently discontinue filgrastim in patients with clinically significant hypersensitivity. Do not administer filgrastim to patients with a history of hypersensitivity to filgrastim or pegfilgrastim. As with all therapeutic proteins, there is a potential for immunogenicity. Rates of generation of antibodies against filgrastim is generally low. Binding antibodies do occur as expected with all biologics; however, they have not been associated with neutralising activity at present.
Special precautions in cancer patients
White blood cell counts of 100 x 10 to the power of 9 per litre or greater have been observed in less than 5% of patients receiving doses above 3 microgram (0.3 million units)/kg/day. No undesirable effects directly attributable to this degree of leucocytosis have been reported, but in view of the potential risks associated with severe leucocytosis, perform white blood cell counts at regular intervals during filgrastim treatment.
If leucocyte counts exceed 50 x 10 to the power of 9 per litre after the expected nadir, discontinue filgrastim immediately. However, during the period of administration for PBPCs (peripheral blood progenitor cells) mobilisation, discontinue filgrastim or reduce the dose if the leucocyte counts rise to more than 70 x 10 to the power of 9 per litre.
Use with caution in patients treated with high dose chemotherapy, because improved tumour outcome has not been demonstrated and intensified doses of chemotherapeutic agents may lead to increased toxicities including pulmonary, cardiac, neurologic and dermatologic effects according to the chemotherapeutic regimen.
Filgrastim alone does not preclude thrombocytopenia and anaemia due to myelosuppressive chemotherapy. The potential for the patient to receive higher doses of chemotherapy (i.e. full doses on the prescribed schedule), implies that the patient may be at greater risk of thrombocytopenia and anaemia. Monitor platelet count and haematocrit regularly and take particular care when administering single or combination chemotherapeutic agents that are known to cause severe thrombocytopenia.
The use of filgrastim-mobilised PBPCs have been shown to reduce the depth and duration of thrombocytopenia.
The effects of filgrastim in patients with substantially reduced myeloid progenitors have not been studied. Filgrastim acts primarily on neutrophil precursors to elevate neutrophil counts. Therefore, in patients with reduced precursors neutrophil response may be diminished (such as patients treated with extensive radiotherapy or chemotherapy, or those with bone marrow infiltration by tumour).
Special precautions in PBPC mobilisation
Following very extensive myelosuppressive therapy, patients may not show sufficient mobilisation of PBPC to achieve the recommended minimum yield (equal to or greater than 2 x 10 to the power of 6 CD34+ cells/kg) or acceleration of platelet recovery to the same degree.
The recommendation of a minimum yield of 2 x 10 to the power 6 CD34+ cells/kg is based on published experience for adequate haematologic reconstitution. Yields in excess appear to correlate with more rapid recovery, those below with slower recovery.
Some cytotoxic agents exhibit particular toxicities to the haematopoietic progenitor pool and may adversely affect progenitor mobilisation. Agents such as melphalan, carboplatin or carmustine (BCNU) administered over prolonged periods before attempts at progenitor mobilisation may reduce progenitor yield. However, administration of these agents with filgrastim has been shown to be effective for progenitor mobilisation.
When a peripheral blood progenitor cell transplantation is envisaged, it is advisable to plan the stem cell mobilisation procedure early in the treatment course. Pay particular attention to the number of progenitor cells mobilised in such patients before the administration of high dose chemotherapy and if yields are inadequate, as measured by the criteria above, consider alternative forms of treatment not requiring progenitor support.
Special precautions in PBPC mobilisation in normal donors
In normal donors, mobilisation of PBPC does not provide a direct clinical benefit and should be considered only for the purposes of allogeneic stem cell transplantation.
Donors should meet the normal clinical and laboratory eligibility criteria for stem cell donation, with particular respect to haematological values and infectious disease. Safety and efficacy have not been established in normal donors below 16 years of age or above 60 years of age.
If more than one leukapheresis is required, pay particular attention to donors with a platelet count less than 100 x 10 to the power of 9 per litre before the procedure and, in general, do not perform apheresis if the platelet count is less than 75 x 10 to the power of 9 per litre.
Transient thrombocytopenia (platelets less than 100 x 10 to the power 9 per litre) following filgrastim and leukapheresis was observed in 35% of patients.
Discontinue or reduce dose if the leucocyte count rises to more than 70 x 10 to the power of 9 per litre.
Monitor long term safety of normal donors for at least 10 years as the risk of promotion of a malignant myeloid clone cannot be excluded.
Special precautions in recipients of allogeneic PBPC mobilised with filgrastim
Immunological reactions between the allogeneic PBPC graft and the recipient may be associated with an increased risk of acute and chronic graft versus host disease when compared with bone marrow transplantation.
Special precautions in severe chronic neutropenia (SCN patients)
Monitor platelet counts closely, especially during the first few weeks of therapy. Consider decreasing the dose of filgrastim or stopping therapy intermittently in patients who develop thrombocytopenia (that is, platelets consistently less than 100 x 10 to the power of 9 per litre).
Other blood cell changes occur, including anaemia and transient increases in myeloid progenitors, which require close monitoring of cell counts.
Take special care in the diagnosis of severe chronic neutropenias to distinguish them from other haematopoietic disorders such as aplastic anaemia, myelodysplasia and myeloid leukaemia. Perform complete blood cell counts with differential and platelet counts before treatment together with an evaluation of bone marrow morphology and karyotype.
If patients with severe chronic neutropenia develop abnormal cytogenetics, the risks and benefits of continuing filgrastim should be carefully evaluated. Discontinue treatment if myelodysplastic syndromes (MDS) or leukaemia occur.
Perform morphologic and cytogenetic bone marrow examinations at regular intervals, approximately every 12 months. It is currently unclear whether long term treatment will predispose to cytogenetic abnormalities, MDS or leukaemic transformations. MDS and leukaemias are natural complications of severe chronic neutropenia and the relationship to filgrastim is unclear.
Special precautions in patients with HIV infection
Closely monitor the absolute neutrophil count (ANC), particularly during the first few weeks of treatment. Some patients may respond very rapidly and with a considerable increase in neutrophil count to the initial dose of filgrastim. Measure the ANC daily for the first 2 or 3 days and thereafter at least twice per week for the first 2 weeks and then once per week or once every other week during maintenance therapy. During intermittent dosing with 300 micrograms (30 million units)/day of filgrastim, there can be wide fluctuations in the ANC over time. In order to determine the trough or nadir ANC, blood samples should be taken for ANC measurement immediately before any scheduled dosing with filgrastim.
Neutropenia may be due to bone marrow infiltrating opportunistic infections such as Mycobacterium avium complex or malignancies such as lymphoma. In patients with such infections or malignancy, consider appropriate therapy for treatment of the underlying condition, in addition to filgrastim for treatment of neutropenia. The effect of filgrastim on neutropenia due to bone marrow infiltrating infection or malignancy have not been well established.
Special precautions in sickle cell disease
Sickle cell crises (sometimes fatal) have occurred following filgrastim administration to patients with sickle cell trait or sickle cell disease. Exercise caution when considering the use of filgrastim in patients with sickle cell trait or sickle cell disease, and only administer if potential benefits outweigh possible risks.
Pregnancy and Lactation
Pregnancy
Use filgrastim with caution during pregnancy.
The manufacturer states that there are no or limited data from the use of filgrastim in pregnant women. There are reports that transplacental passage of filgrastim in pregnant women has been demonstrated. Studies in animals have shown reproductive toxicity. An increase in embryo-loss has been observed in rabbits at doses that were maternally toxic. Malformations have been seen. Briggs (2015) suggests that neither the animal or limited data from human pregnancies show a major risk for the human embryo or foetus from maternal filgrastim therapy and recommends that therapy is not withheld because of the pregnancy.
Lactation
Use filgrastim with caution during breastfeeding.
The manufacturer advises that the patient either discontinues filgrastim or discontinues breastfeeding. It is not known whether filgrastim is excreted in human milk, however, low levels are anticipated in milk due to the drug's properties. Filgrastim has been safely given orally to neonates and, as a protein, is digested in the gastrointestinal tract. Any filgrastim that is excreted into milk is unlikely to adversely affect the breastfed infant. Briggs (2015) suggests that filgrastim should not be withheld due to breastfeeding as the risk to the nursing infant is low to non existent.
Side Effects
Acute febrile dermatosis (Sweet's syndrome)
Acute respiratory distress syndrome
Allergic reaction
Alopecia
Anaemia
Anaphylaxis
Angioedema
Anorexia
Aortitis
Arthralgia
Aspartate aminotransferase increased
Asthenia
Back pain
Bone pain
Bronchitis
Capillary leak syndrome
Chest pain
Constipation
Cough
Cutaneous vasculitis
Decrease in bone mineral density
Decreased appetite
Decreased blood glucose
Diarrhoea
Disturbance of fluid balance
Dizziness
Dyspnoea
Dysuria
Epistaxis
Erythema
Exacerbation of rheumatoid arthritis
Fatigue
Fever
Gamma glutamyl transferase (GGT) increased
Glomerulonephritis
Graft versus host disease
Haematuria
Haemoglobin decrease
Haemoptysis
Headache
Hepatomegaly
Hypersensitivity reactions
Hypertension
Hyperuricaemia
Hypoaesthesia
Hypotension
Hypoxia
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increased uric acid level
Injection site reactions
Insomnia
Interstitial lung disease
Interstitial pneumonia
Leucocytosis
Maculopapular rash
Malaise
Mucosal inflammation
Muscle spasm
Musculoskeletal pain
Myalgia
Nausea
Neck pain
Oral pain
Oropharyngeal pain
Osteoporosis
Pain
Painful extremities
Paraesthesia
Proteinuria
Pseudogout
Pulmonary haemorrhage
Pulmonary infiltrates
Pulmonary oedema
Rash
Respiratory failure
Sepsis
Sickle cell crisis
Sore throat
Splenic rupture
Splenomegaly
Thrombocytopenia
Upper respiratory tract infection
Urinary abnormalities
Urinary tract infections
Urticaria
Vascular disorders
Veno-occlusive disease
Vomiting
Weakness
Effects on Laboratory Tests
Increased haematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient abnormal bone scans. This should be considered when interpreting bone-imaging results.
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: September 2018
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
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.
MHRA Drug Safety Update September 2013
Available at: https://www.mhra.gov.uk
Last accessed: 13 September 2018
Summary of Product Characteristics: Accofil 12 MU/0.2 ml (0.6 mg/ml) solution for injection or infusion in pre-filled syringe. Accord Healthcare Limited. Revised October 2021.
Summary of Product Characteristics: Accofil 30 MU/0.5 ml (0.6 mg/ml) solution for injection or infusion. Accord Healthcare Limited. Revised May 2018.
Summary of Product Characteristics: Accofil 48 MU/0.5 ml (0.96 mg/ml) solution for injection. Accord Healthcare Limited. Revised May 2018.
Summary of Product Characteristics: Accofil 70 MU/0.73 ml (0.96 mg/ml) solution for injection or infusion in pre-filled syringe. Accord Healthcare Limited. Revised October 2021.
Summary of Product Characteristics: Neupogen 30 MU (0.3 mg/ml) solution for injection. Amgen Ltd. Revised July 2018.
Summary of Product Characteristics: Neupogen Singleject 30 MU (0.6 mg/ml). Amgen Ltd. Revised July 2018.
Summary of Product Characteristics: Neupogen Singleject 48 MU (0.96mg/ml). Amgen Ltd. Revised July 2018.
Summary of Product Characteristics: Nivestim 12 MU/ 0.2 ml solution for injection/infusion, Nivestim 30 MU/ 0.5 ml solution for injection/infusion, Nivestim 48MU/ 0.5 ml solution for injection/infusion. Hospira UK Ltd. Revised May 2020.
Summary of Product Characteristics: Zarzio 30 MU/0.5 ml and 48 MU/0.5 ml solution for injection or infusion in pre filled syringe. Sandoz Limited. Revised May 2018.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 15 September 2022
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Filgrastim Last revised: 31 July 2018.
Last accessed: 13 September 2018
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.