Fosaprepitant

Registered South African indications:

• Nausea and vomiting in cancer chemotherapy

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Coadministration with pimozide, terfenadine, astemizole or cisapride 
• Safety and efficacy in paediatric patients have not been established

Cautions

• Moderate to severe hepatic impairment
• Bolus injection
• Subcutaneous or intramuscular injection
• Infusion site reactions (ISRs)
• May impair ability to drive and operate machinery

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

Acute and delayed nausea and vomiting associated with initial and repeat courses of
- Highly emetogenic cancer chemotherapy (additional agents(s) required)
- Moderately emetogenic cancer chemotherapy (additional agents(s) required)

• IV: Day 1: 150mg infused over 20-30min, initiate 30min prior to chemotherapy

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See additional prescribing points

Not established for use in children below 18 years

Pregnancy

• Contraindicated
• For fosaprepitant and aprepitant, no clinical data on exposed pregancies are available
• The potential for reproductive toxicities of fosaprepitant and aprepitant have not been fully characterised since exposure levels above therapeutic exposure in humans could not be attained in animal studies
• These studies did not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, partruition or postnatal development
• The potential effects on reproduction of alterations in neurokinin regulation are unknown
• Fosaprepitant should not be used during pregnancy unless clearly necessary

Breastfeeding

• Contraindicated 
• Aprepitant is excreted in the milk of lactating rats after intravenous administration of fosaprepitant as well as after oral administration of aprepitant
• It is not known whether aprepitant is excreted in human milk
• Breastfeeding is therefore not recommended during treatment with fosaprepitant

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Mild: no dose adjustment recommended
• Moderate to severe: Caution; no information available 

Elderly            

• No dose adjustment recommended

Central Nervous System Disorders

• Headache
• Dizziness
• Somnolence
• Cognitive disorder
• Lethargy
• Dysgeusia
• Anxiety
• Disorientation
• Euphoric mood
• Fatigue
• Gait disturbance

Cardiovascular Disorders

• Palpitations
• Bradycardia
• Cardiovascular disorder
• Flushing
• Chest discomfort
• Increased blood pressure
• Oedema

Respiratory Disorders

• Hiccups
• Oropharyngeal pain
• Sneezing
• Cough
• Postnasal drip
• Throat irritation

Gastrointestinal Disorders

• Eructation
• Nausea and vomiting
• Gastroesophageal reflux disease
• Abdominal pain
• Dry mouth
• Flatulence
• Duodenal ulcer perforation
• Stomatitis
• Abdominal distension
• Hard faeces
• Neutropenic colitis
• Constipation
• Dyspepsia

Genitourinary Disorders

• Dysuria
• Pollakiuria
• Urine positive for red blood cells 
• Decreased blood sodium 
• Glucose present in urine 

Endocrine and Metabolic Disorders

• Decreased appetite
• Polydipsia
• Decreased weight 

Musculoskeletal Disorders

• Muscular weakness
• Muscle spasms

Skin and Subcutaneous Tissue Disorders

• Rash
• Acne
• Photosensitivity reaction
• Hyperhidrosis
• Seborrhoea
• Skin lesion
• Rash pruritic
• Stevens-Johnson Syndrome
• Toxic epidermal necrolysis
• Pruritus
• Urticaria
• Eyrthema
• Infusion site erythema
• Infusion site pruritis
• Infusion site pain
• Infusion site induration

Immune, Blood and Lymphatic System Disorders

• Febrile neutropenia
• Anaemia
• Decreased neutrophil count 
• Flushing
• Thrombophlebitis
• Infusion site thrombophlebitis
• Hypersensitivity reactions
• Anaphylactic reactions
• Candidiasis
• Staphylococcal infection

Sensory Disorders

• Conjunctivitis
• Tinnitus

Other

• Increased alanine aminotransferase 
• Increased aspartate aminotransferase 
• Increased blood alkaline phosphatase

• CYP3A4 inhibitors
• CYP3A4 inducers
• CYP3A4 substrates
• CYP2C9 inducers
• CYP2C9 substrates
• Corticosteroids (e.g. dexamethasone)
• Benzodiazepines (e.g. midazolam)
• Hormonal contraceptives
• Chemotherapeutic medicine agents
• Immunosuppressants
• 5-HT3 antagonists
• Pimozide
• Terfenadine
• Astemizole
• Cisapride 
• Diltiazem
• Etopside
• Vinorelbine
• Docetaxel
• Ifosfamide
• Cyclophosphamide
• Irinotecan
• Paclitaxel
• Paroxetine
• Dexamethasone 
• Warfarin
• Tolbutamide

None routine. Specific cases may require

• International normalization ratio (INR)

Administration directions

• Inject 5ml saline into the vial. Assure that saline is added to the vial along the vial wall in order to prevent foaming. Swirl the vial gently. Avoid shaking and jetting saline into the vial. After reconstitution, use only if the solution is a clear colourless or pale yellow to yellow solution, free from visible particles
• Prepare an infusion bag filled with 145ml of saline
• Withdraw the entire volume from the vial and transfer it into an infusion bag containing 145ml of saline to yield a total volume of 150ml. Gently invert the bag 2 to 3 times
• The reconstituted final medicine solution is stable for 24 hours at ambient room temperature (at or below 25 °C) and should be used within 24 hours after reconstitution. If not used immediately, in-use storage times should not be longer than 24 hours at 2 to 8 °C
• Fosaprepitant is incompatible with any solutions containing divalent cations (e.g. Ca²⁺, Mg²⁺), including Hartman’s and Lactated Ringer’s Solution
• Must not be reconstituted or mixed with solutions for which physical and chemical compatibility have not been established

Co-administration with Hormonal Contraceptives

• The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration of fosaprepitant
• Alternative non-hormonal back-up methods of contraception should be used during treatment with fosaprepitant and for 2 months following the use of fosaprepitant

Fosaprepitant is a prodrug of aprepitant. When administered intravenously it is rapidly converted to aprepitant, a substance P neurokinin 1 receptor antagonist. The contribution of fosaprepitant to the overall antiemetic effect has not fully been characterised, but a transient contribution during the initial phase cannot be ruled out. Aprepitant is a selective high-affinity antagonist at human substance P neurokinin 1 receptors. The pharmacological effect of fosaprepitant is attributed to aprepitant

Injection (per vial) 150mg

• Ivemend (MSD) originator