Drugs List

Therapeutic Indications

Uses

Idiopathic thrombocytopenic purpura

Administration

For subcutaneous injection only.

Patients who have a stable platelet count of equal to or more than 50 x 10 to the power of 9/L for at least 4 weeks without dose adjustment may be eligible for self-administration of romiplostim once trained. After the first 4 weeks of self-administration, the patient should again be supervised while reconstituting and administering romiplostim. Only patients who demonstrate the ability to reconstitute and self-administer romiplostim are allowed to continue to do so.

Self-administration of romiplostim is not allowed in paediatric patients.

Contraindications

Children under 1 year
Breastfeeding
Pregnancy

Precautions and Warnings

Females of childbearing potential
Predisposition to thromboembolic disease
Chronic hepatic disorder
Hepatic impairment - Child-Pugh score greater than 6
Renal impairment
Splenectomy

Advise ability to drive/operate machinery may be affected by side effects
Not all available brands are licensed for all age groups
Treatment to be initiated and supervised by a specialist
Record name and batch number of administered product
Blood counts should be performed before and periodically during treatment
Initial dose should be based on actual body weight
Perform peripheral blood smear prior to and during treatment
Children: Monitor body weight every 12 weeks
Investigate patients developing a sudden lack of response to treatment
Monitor platelet counts monthly after first month of treatment
Monitor platelets weekly until minimum 50x10 to the power of 9/L
Thrombocytopenia likely to reoccur upon discontinuation of treatment
Interrupt treatment if platelet count above 250x10 to the power of 9/L
Discontinue if platelet count is insufficient after 4 weeks at max dose
Female: Ensure adequate contraception during treatment

Platelet counts should be assessed weekly until a stable platelet count (equal to or more than 50 x 10 to the power of 9/L for at least 4 weeks without dose adjustment) has been achieved. Platelet counts should be assessed monthly thereafter. A loss of response or failure to maintain a platelet response to romiplostim within the recommended dosing range should be investigated.

Patients should be monitored and managed when discontinuing romiplostim. There is an increased risk of bleeding if romiplostim is discontinued in the presence of anticoagulants or antiplatelet drugs. It is recommended that ITP treatment be restarted according to current treatment guidelines if treatment with romiplostim is discontinued.

A positive benefit/risk for romiplostim is only established for the treatment of thrombocytopenia associated with chronic immune thrombocytopenic purpura (ITP) and romiplostim must not be used in other clinical conditions associated with thrombocytopenia. Romiplostim must not be used for the treatment of thrombocytopenia due to Myelodysplastic Syndromes (MDS) or any other cause of thrombocytopenia other than ITP outside of clinical trials. In clinical trails using romiplostim in patients with MDS, there were reported cases of transient increases in blast cell counts and cases of progression to acute myeloid leukaemia.

The diagnosis of ITP in adults and elderly patients should have been confirmed by the exclusion of other clinical entities presenting with thrombocytopenia, in particular the diagnosis of MDS must be excluded. A bone marrow aspirate and biopsy should normally have been done over the course of the disease and treatment, particularly in patients over 60 years of age, for those with systemic symptoms or abnormal signs such as increased peripheral blast cells.

If a loss of efficacy and abnormal peripheral blood smear occur, treatment with romiplostim should be discontinued, physical examination should be performed and bone marrow biopsy with appropriate staining for reticulin should be considered. If efficacy is maintained but abnormal peripheral blood smear is observed consideration should be given to a bone marrow biopsy and alternative ITP treatment options.

Concurrent anaemia and leucocytosis (within a 4-week window) may occur in patients regardless of splenectomy status, but have been seen more often in patients who have had a prior splenectomy. Monitoring of these parameters should be considered in patients treated with romiplostim.

Pregnancy and Lactation

Pregnancy

Romiplostim is contraindicated in pregnancy.

Safety in human pregnancy has not been established.

Animal studies have shown transplacental passage, increased foetal platelet counts, post-implantation loss and a slight increase in peri-natal pup mortality.

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

Romiplostim is contraindicated in breastfeeding.

To date, safety in human breastfeeding has not been established. It is unknown if romiplostim is excreted in human milk. A risk to the suckling child cannot be excluded.

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

Alcohol intolerance
Alopecia
Anaemia
Angioedema
Anorexia
Antibody formation
Aplastic anaemia
Arthralgia
Asthenia
Biopsy bone marrow abnormal
Blindness
Bone marrow failure
Breathing difficulties
Changes of blood pressure
Chest pain
Chills
Clonus
Contusion
Cough
Decreased appetite
Deep vein thrombosis (DVT)
Dehydration
Depression
Disturbances in accommodation
Dizziness
Dream abnormalities
Dry throat
Dysgeusia
Dysphasia
Dyspnoea
Ecchymosis
Erythromelalgia
Eye disorder
Eye pruritus
Fatigue
Feeling hot
Flushing
Gastro-intestinal disturbances
Gout
Haematochezia
Haemorrhage
Hair growth abnormal
Halitosis
Headache
Hypersensitivity reactions
Hypoaesthesia
Hypogeusia
Increase in lactate dehydrogenase
Increase in serum transaminases
Increased bone marrow reticulin
Increased heart rate
Increased lacrimation
Increased platelet count
Infections
Influenza-like symptoms
Insomnia
Irritability
Leukocytosis
Local reaction at injection site
Malaise
Migraine
Multiple myeloma
Muscle spasm
Musculoskeletal disturbances
Myalgia
Myelofibrosis
Myocardial infarction
Nasal congestion
Oedema
Pain
Painful extremities
Palpitations
Papilloedema
Paraesthesia
Peripheral ischaemia
Peripheral neuropathy
Phlebitis
Photosensitivity
Proteinuria
Pruritus
Pulmonary embolism
Pyrexia
Rash
Reduced platelet count
Rhinorrhoea
Rise in body temperature
Skin disorder
Skin odour changes
Splenomegaly
Stomatitis
Superficial tooth discolouration
Superficial vein thrombophlebitis
Thrombocythaemia
Thrombocytopenia
Thrombosis
Transverse sinus thrombosis
Vertigo
Visual disturbances
Weight changes

Presentation

Parenteral formulations of romiplostim.

This product has been produced by recombinant technology using E.coli.

Drugs List

Therapeutic Indications

Uses

Idiopathic thrombocytopenic purpura

Dosage

Not all available brands are licensed for all age groups.

Treatment should remain under the supervision of a specialist in haematological diseases.

Actual body weight at initiation of treatment should always be used when calculating dose of romiplostim.

In adults, future dose adjustments are based on changes in platelet count only.

In paediatric patients, future dose adjustments are based on changes in platelet counts and changes in body weight. Reassessment of body weight is recommended every 12 weeks.

Adults

Children

Additional Dosage Information

Administration

For subcutaneous injection only.

Patients who have a stable platelet count of equal to or more than 50 x 10 to the power of 9/L for at least 4 weeks without dose adjustment may be eligible for self-administration of romiplostim once trained. After the first 4 weeks of self-administration, the patient should again be supervised while reconstituting and administering romiplostim. Only patients who demonstrate the ability to reconstitute and self-administer romiplostim are allowed to continue to do so.

Self-administration of romiplostim is not allowed in paediatric patients.

Contraindications

Children under 1 year
Breastfeeding
Pregnancy

Precautions and Warnings

Females of childbearing potential
Predisposition to thromboembolic disease
Chronic hepatic disorder
Hepatic impairment - Child-Pugh score greater than 6
Renal impairment
Splenectomy

Advise ability to drive/operate machinery may be affected by side effects
Not all available brands are licensed for all age groups
Treatment to be initiated and supervised by a specialist
Record name and batch number of administered product
Blood counts should be performed before and periodically during treatment
Initial dose should be based on actual body weight
Perform peripheral blood smear prior to and during treatment
Children: Monitor body weight every 12 weeks
Investigate patients developing a sudden lack of response to treatment
Monitor platelet counts monthly after first month of treatment
Monitor platelets weekly until minimum 50x10 to the power of 9/L
Thrombocytopenia likely to reoccur upon discontinuation of treatment
Interrupt treatment if platelet count above 250x10 to the power of 9/L
Discontinue if platelet count is insufficient after 4 weeks at max dose
Female: Ensure adequate contraception during treatment

Platelet counts should be assessed weekly until a stable platelet count (equal to or more than 50 x 10 to the power of 9/L for at least 4 weeks without dose adjustment) has been achieved. Platelet counts should be assessed monthly thereafter. A loss of response or failure to maintain a platelet response to romiplostim within the recommended dosing range should be investigated.

Patients should be monitored and managed when discontinuing romiplostim. There is an increased risk of bleeding if romiplostim is discontinued in the presence of anticoagulants or antiplatelet drugs. It is recommended that ITP treatment be restarted according to current treatment guidelines if treatment with romiplostim is discontinued.

A positive benefit/risk for romiplostim is only established for the treatment of thrombocytopenia associated with chronic immune thrombocytopenic purpura (ITP) and romiplostim must not be used in other clinical conditions associated with thrombocytopenia. Romiplostim must not be used for the treatment of thrombocytopenia due to Myelodysplastic Syndromes (MDS) or any other cause of thrombocytopenia other than ITP outside of clinical trials. In clinical trails using romiplostim in patients with MDS, there were reported cases of transient increases in blast cell counts and cases of progression to acute myeloid leukaemia.

The diagnosis of ITP in adults and elderly patients should have been confirmed by the exclusion of other clinical entities presenting with thrombocytopenia, in particular the diagnosis of MDS must be excluded. A bone marrow aspirate and biopsy should normally have been done over the course of the disease and treatment, particularly in patients over 60 years of age, for those with systemic symptoms or abnormal signs such as increased peripheral blast cells.

If a loss of efficacy and abnormal peripheral blood smear occur, treatment with romiplostim should be discontinued, physical examination should be performed and bone marrow biopsy with appropriate staining for reticulin should be considered. If efficacy is maintained but abnormal peripheral blood smear is observed consideration should be given to a bone marrow biopsy and alternative ITP treatment options.

Concurrent anaemia and leucocytosis (within a 4-week window) may occur in patients regardless of splenectomy status, but have been seen more often in patients who have had a prior splenectomy. Monitoring of these parameters should be considered in patients treated with romiplostim.

Pregnancy and Lactation

Pregnancy

Romiplostim is contraindicated in pregnancy.

Safety in human pregnancy has not been established.

Animal studies have shown transplacental passage, increased foetal platelet counts, post-implantation loss and a slight increase in peri-natal pup mortality.

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

Romiplostim is contraindicated in breastfeeding.

To date, safety in human breastfeeding has not been established. It is unknown if romiplostim is excreted in human milk. A risk to the suckling child cannot be excluded.

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

Alcohol intolerance
Alopecia
Anaemia
Angioedema
Anorexia
Antibody formation
Aplastic anaemia
Arthralgia
Asthenia
Biopsy bone marrow abnormal
Blindness
Bone marrow failure
Breathing difficulties
Changes of blood pressure
Chest pain
Chills
Clonus
Contusion
Cough
Decreased appetite
Deep vein thrombosis (DVT)
Dehydration
Depression
Disturbances in accommodation
Dizziness
Dream abnormalities
Dry throat
Dysgeusia
Dysphasia
Dyspnoea
Ecchymosis
Erythromelalgia
Eye disorder
Eye pruritus
Fatigue
Feeling hot
Flushing
Gastro-intestinal disturbances
Gout
Haematochezia
Haemorrhage
Hair growth abnormal
Halitosis
Headache
Hypersensitivity reactions
Hypoaesthesia
Hypogeusia
Increase in lactate dehydrogenase
Increase in serum transaminases
Increased bone marrow reticulin
Increased heart rate
Increased lacrimation
Increased platelet count
Infections
Influenza-like symptoms
Insomnia
Irritability
Leukocytosis
Local reaction at injection site
Malaise
Migraine
Multiple myeloma
Muscle spasm
Musculoskeletal disturbances
Myalgia
Myelofibrosis
Myocardial infarction
Nasal congestion
Oedema
Pain
Painful extremities
Palpitations
Papilloedema
Paraesthesia
Peripheral ischaemia
Peripheral neuropathy
Phlebitis
Photosensitivity
Proteinuria
Pruritus
Pulmonary embolism
Pyrexia
Rash
Reduced platelet count
Rhinorrhoea
Rise in body temperature
Skin disorder
Skin odour changes
Splenomegaly
Stomatitis
Superficial tooth discolouration
Superficial vein thrombophlebitis
Thrombocythaemia
Thrombocytopenia
Thrombosis
Transverse sinus thrombosis
Vertigo
Visual disturbances
Weight changes

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: November 2018

Reference Sources

Summary of Product Characteristics: Nplate vial. Amgen Ltd. Revised January 2021.

Summary of Product Characteristics: Nplate with Reconstitution Pack. Amgen Ltd. Revised January 2018.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 8 November 2018.