Aprepitant

Registered South African indications:

• Chemotherapy induced nausea and vomiting

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Coadministration with pimozide, terfenadine, astemizole or cisapride

Cautions

• Pregnancy
• Breastfeeding
• Moderate to severe hepatic impairment
• Porphyria
• Fructose intolerance
• Glucose-galactose malabsorption
• Sucrase-isomaltase insufficiency
• May impair ability to drive and operate machinery

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

Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately to highly emetogenic cancer chemotherapy (additional agent(s) required)

• Day 1: Oral (cap): 125mg, 1hr prior to chemotherapy
• Day 2-3: Oral (cap): 80mg, dly in morning

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Aprepitant is given as part of combination therapy, including a corticosteroid and a 5-HT3 antagonist

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The hard capsule should be swallowed whole taken with or without food

Not established for use in children below 12 years

Pregnancy

• Caution
• No clinical data on exposed pregnancies are available. The potential for reproductive toxicity of aprepitant has not been fully characterised, since exposure levels above the therapeutic exposure in humans at the 125 mg/80 mg dose could not be attained in animal studies
• These studies did not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development
• The potential effects on reproduction of alterations in neurokinin regulation are unknown
• Aprepitant should not be used during pregnancy unless clearly necessary

Breastfeeding

• Caution; not recommended 
• Aprepitant is excreted in the milk of lactating rats. It is not known whether aprepitant is excreted in human milk; therefore, breastfeeding is not recommended during treatment with aprepitant

Fertility

• The potential for effects of aprepitant on fertility has not been fully characterised because exposure levels above the therapeutic exposure in humans could not be attained in animal studies
• These fertility studies did not indicate direct or indirect harmful effects with respect to mating performance, fertility, embryonic/foetal development, or sperm count and motility
• The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration of aprepitant. Alternative non-hormonal back-up methods of contraception should be used during treatment with aprepitant and for 2 months following the last dose of aprepitant

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 

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

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

Cardiovascular Disorders

• Palpitations
• Bradycardia
• Cardiovascular disorder  
• Flushing
• Chest discomfort
• Oedema

Respiratory Disorders

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

Gastrointestinal Disorders

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

Hepatobiliary Disorders

• Increased alanine aminotransferase (ALT)
• Increased aminotransferase (AST)

Genitourinary Disorders

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

Endocrine and Metabolic Disorders

• Decreased appetite
• Deceased weight
• Polydipsia

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

Immune, Blood and Lymphatic System Disorders

• Candidiasis
• Staphylococcal infection
• Febrile neutropenia
• Anaemia
• Hypersensitivity reactions
• Anaphylaxis
• Decreased neutrophil count

Sensory Disorders

• Conjunctivitis
• Tinnitus

Others

• Increased blood alkaline phosphatase (ALP)

• CYP3A4 inducers
• Rifampicin
• Phenytoin
• Carbamazepine
• Phenobarbital
• CYP3A4 inhibitors
• Ketoconazole
• Itraconazole
• Voriconazole
• Posaconazole
• Clarithromycin
• Telithromycin
• Nefazodone
• Protease inhibitors
• CYP3A4 substrates
• Cyclosporine
• Tacrolimus
• Sirolimus
• Everolimus
• Alfentanil
• Diergotamine
• Ergotamine
• Fentanyl
• Quinidine
• Irinotecan
• Pimozide
• Terfenadine
• Astemizole
• Cisapride
• CYP2C9 substrates
• Warfarin
• Acenocoumarol
• Tolbutamide
• Hormonal contraceptives
• Agents that undergo glucuronidation
• Chemotherapeutic agents
• Etoposide
• Vinorelbine
• Ifosfamide
• Immunosuppressants
• Benzodiazepines
• Alprazolam
• Triazolam
• Midazolam
• 5-HT3 antagonists
• Diltiazem
• Paroxetine
• St John's Wort
• Corticosteroids
• Dexamethasone
• Methylprednisone

None routine. Specific cases may require

• International Normalised Ratio (INR)

Coadministration with hormonal contraceptives 

• The efficacy of hormonal contraceptives during and for 28 days after administration of aprepitant may be reduced. Alternative non-hormonal back-up methods of contraceptions should be used during treatment with aprepitant and for 2 months following the last dose of aprepitant

Aprepitant is a selective high affinity antagonist at human substance P neurokinin-1 (NK1) receptors with antiemetic activity.

Capsule 80mg

• Aprepitant 80 Eurolab (Eurolab)
• Emend (MSD) originator

Capsule 125mg

• Aprepitant 125 Eurolab (Eurolab)
• Emend (MSD) originator

Capsule 125mg/80mg

• Aprepitant Combipack Eurolab (Eurolab)
• Emend Combi Pack (MSD) originator