Romiplostim

Registered South African indications:

• Chronic immune (idiopathic) thrombocytopenic purpura

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to E. coli derived proteins

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Discontinuation
• Known risk factors for thromboembolism
• Anaemia
• Leucocytosis
• Patients with RAEB-1 classification of myelodysplastic syndromes at baseline
• May impair ability to drive and operate machines

Forms avail. in SA and covered in this monograph: inj

Chronic immune (idiopathic) thrombocytopenic purpura
- Splenectomised patients who are refractory to other treatments

• SC: Initial: 1μg/kg weekly; Titrate by 1μg/kg weekly until platelet count > 50 x 10⁹/l; Max: 10μg/kg/week

---

May be considered as second line treatment for adult non-splenectomised patients where surgery is contraindicated

---

The 250μg powder for solution for injection should be reconstituted with 0,72ml sterile water for injection

---

The 500μg powder for solution for injection should be reconstituted with 1,2ml sterile water for injection

---

See additional prescribing points for dose adjustments

Not established for use in children below 18 years 

Pregnancy

• Caution; not recommended
• There are no or limited amount of data from the use of romiplostim in pregnant women
• Limited human data. Animal data suggest low risk
• Studies in animals have shown that romiplostim crossed the placenta and increased foetal platelet counts. Post implantation loss and a slight increase in peri-natal pup mortality also occurred in animal studies
• Romiplostim is not recommended during pregnancy and in women of childbearing potential not using contraception
• In a 2013 case report, a 28-year-old primigravid with chronic immune thrombocytopenic purpura conceived while receiving romiplostim. During the first trimester, her platelets were stable but, at week 14, thrombocytopenia associated with epistaxis developed. At about 34 weeks, labour was induced to deliver a 1.9kg male infant with Apgar scores of 8 at 1 and 5 minutes, respectively. The neonate's platelets decreased markedly within 8 hours of birth and treated with IV immunoglobulin and a platelet transfusion. Other problems in the infant, in addition to thrombocytopenia, were a grade III intraventricular haemorrhage, adrenal insufficiency, and phimosis. However, at 10 months, the infant was developmentally normal

Breastfeeding

• Caution; not recommended
• It is unknown wheter romiplostim or its metabolites are excreted in human milk
• The effect on a nursing infant is unknown. However, if excretion does occur, the protein might be digested in the infant's gut
• A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from romiplostim therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman

Fertility

• There is no data available on fertility

Renal Impairment

• Caution; no information available

Hepatic Impairment

• Moderate to severe: Caution; no dose adjustment recommended 
  Should not be used unless the expected benefit outweighs the risks. If deemed necessary, platelet count should be closely monitored to minimise the risk of thromboembolic complications

Elderly

• Caution; no dose adjustment recommended

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness
• Migraine
• Paraesthesia
• Clonus
• Dysgeusia
• Hypoaesthesia
• Hypogeusia
• Peripheral neuropathy
• Transverse sinus thrombosis
• Insomnia
• Depression
• Abnormal dreams
• Fatigue
• Irritability
• Feeling jittery

Cardiovascular Disorders

• Palpitations
• Myocardial infarction
• Increased heart rate
• Deep vein thrombosis
• Hypotension
• Peripheral embolism
• Peripheral ischaemia
• Phlebitis
• Superficial thrombophlebitis
• Thrombosis
• Erythromelalgia
• Chest pain
• Increased blood pressure

Respiratory Disorders

• Oropharyngeal pain
• Pulmonary embolism
• Cough
• Rhinorrhoea
• Dry throat
• Dyspnoea
• Nasal congestion
• Painful respiration
• Upper respiratory tract infection
• Rhinitis
• Influenza
• Nasopharyngitis
• Sinusitis

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Abdominal pain
• Constipation
• Dyspepsia
• Rectal haemorrhage
• Breath odour
• Dysphagia
• Gastro-oesophageal reflux disease
• Haematochezia
• Mouth haemorrhage
• Stomatitis
• Tooth discolouration
• Gastroenteritis

Hepatobiliary Disorders

• Portal vein thrombosis
• Increased transaminases

Genitourinary Disorders

• Proteinuria
• Vaginal haemorrhage

Endocrine and Metabolic Disorders

• Alcohol intolerance
• Anorexia
• Decreased appetite
• Dehydration
• Gout
• Weight increased
• Weight decreased
• Increased body temperature
• Increased lactate dehydrogenase

Musculoskeletal Disorders

• Arthralgia
• Myalgia
• Muscle spasms
• Pain in extremity
• Back pain
• Bone pain
• Muscle tightness
• Muscular weakness
• Shoulder pain
• Muscle twitching

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Ecchymosis
• Rash
• Alopecia
• Photosensitivity reaction
• Acne
• Contact dermatitis
• Dry skin
• Eczema
• Erythema
• Exfoliative rash
• Abnormal hair growth
• Prurigo
• Purpura
• Papular rash
• Pruritic rash
• Skin nodule
• Abnormal skin odour
• Urticaria
• Peripheral oedema
• Facial oedema
• Injection site reaction
• Contusion
• Flushing

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
• Angioedema
• Bone marrow disorder
• Thrombocytopenia
• Anaemia
• Aplastic anaemia
• Bone marrow failure
• Leukocytosis
• Splenomegaly
• Thrombocythaemia
• Increased platelet count  
• Abnormal platelet count
• Localised infection
• Multiple myeloma
• Myelofibrosis
• Influenza like illness
• Pyrexia

Sensory Disorders

• Vertigo
• Conjunctival haemorrhage
• Accommodation disorder
• Blindness
• Eye disorder
• Eye pruritus
• Increased lacrimation
• Papilloedema
• Visual disturbances
• Conjunctivitis
• Ear infection

• Other medicinal products for the treatment of idiopathic thrombocytopenic purpura
• Corticosteroids
• Danazol
• Azathioprine
• Anti-D immunoglobulin

• Peripheral blood smear
• Full blood count
• Differential white cell count  

Specific cases may require

• Bone marrow aspirate
• Platelet count

Dose adjustments

• Platelet count < 50 x 10⁹/l: Increase once weekly dose by 1μg/kg
• Platelet count >200 x 10⁹/l for 2 consecutive weeks: Decrease dose by 1μg/kg
• Platelet count >400 x 10⁹/l: Omit dose. Monitor platelet count weekly; when platelet count <200 x 10⁹/l resume dosing with once weekly dose reduced by 1μg/kg

Loss of response to romiplostim

• A loss of response or failure to maintain a platelet response with romiplostim treatment within the recommended dosing range should prompt a search for causative factors, including immunogenicity

Medication errors

• Overdose may result in an excessive increase in platelet counts associated with thrombotic/thromboembolic complications. If the platelet counts are excessively increased, decrease romiplostim and monitor platelet counts. Re-initiate treatment with romiplostim in accordance with dosing and administration recommendations
• Underdose may result in lower than expected platelet counts and potential for bleeding. Platelet counts should be monitored in patients receiving romiplstim

Romiplostim is an Fc-peptide fusion protein (peptibody) that signals and activates intracellular transcriptional pathways via the thrombopoietin (TPO) receptor (also known as cMpl) to increase platelet production. 

Injection (per 0.5ml) 250μg

• Nplate  (Amgen) originator