Aprepitant oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations containing aprepitant.
Drugs List
Therapeutic Indications
Uses
Chemotherapy induced nausea and vomiting
For the prevention of acute and delayed nausea and vomiting associated with highly emetogenic cisplatin-based cancer therapy.
Prevention of nausea and vomiting with moderately emetogenic cancer chemotherapy.
Given as part of combination antiemetic therapy.
Dosage
Aprepitant is administered for 3 days as part of a regimen that includes a 5-HT3 antagonist.
Adults
The recommended dose for both moderate and highly emetogenic chemotherapy is 125mg aprepitant on day 1 one hour before the start of chemotherapy, and 80mg once daily on days 2 and 3. The additional corticosteroid and 5-HT3 antagonist differ for the different chemotherapy regimens.
In clinical studies, the following regimen was used in highly emetogenic chemotherapy:
Day one: 125mg aprepitant orally one hour prior to chemotherapy and 12mg dexamethasone orally with 32mg ondansetron given intravenously, 30 minutes prior to chemotherapy.
Day two: 80mg aprepitant and 8mg dexamethasone orally in the morning.
Day three: 80mg aprepitant and 8mg dexamethasone orally in the morning.
Day four: 8mg dexamethasone orally in the morning.
In clinical studies, the following regimen was used in moderately emetogenic chemotherapy:
Day one : 125mg aprepitant orally one hour prior to chemotherapy and 12mg dexamethasone with 8mg ondansetron orally 30 to 60 minutes prior to chemotherapy. A second 8mg oral dose of ondansetron was given 8 hours following the first dose.
Day two: 80mg aprepitant orally in the morning.
Day three: 80mg aprepitant orally in the morning.
The dose of dexamethasone was chosen to allow for the drug interaction with aprepitant.
Refer to the full prescribing information for the co administered antiemetic agents.
Children
Children aged 12 years of age and older
The recommended dose of aprepitant capsules is:
Day one: 125mg as a single dose, one hour prior to chemotherapy.
Day two: 80mg as a single dose, one hour prior to chemotherapy.
Day three: 80mg as a single dose, one hour prior to chemotherapy.
If no chemotherapy is given on day 2 or 3 of treatment, aprepitant should be administered in the morning.
Consult the relevant product literature or monograph for dosing information of any concomitant therapy, such as 5-HT3 antagonists.
If a corticosteroid, is co-administered with aprepitant, the dose of the corticosteroid should be reduced by 50%.
Children aged between 6 months and 12 years of age, and not below 6 kg
Only aprepitant oral suspension is licensed in this patient group.
The recommended dose of aprepitant oral suspension is:
Day one: 3mg/kg (maximum dose 125mg) as a single dose, one hour prior to chemotherapy.
Day two: 2mg/kg (maximum dose 80mg) as a single dose, one hour prior to chemotherapy.
Day three: 3mg/kg (maximum dose 125mg) as a single dose, one hour prior to chemotherapy.
If no chemotherapy is given on day 2 or 3 of treatment, aprepitant should be administered in the morning.
Consult the relevant product literature or monograph for dosing information of any concomitant therapy, such as 5-HT3 antagonists.
If a corticosteroid, is co-administered with aprepitant, the dose of the corticosteroid should be reduced by 50%.
Contraindications
Children under 6 months
Children weighing less than 6kg
Acute porphyria
Breastfeeding
Hereditary fructose intolerance
Precautions and Warnings
Children under 12 years
Galactosaemia
Glucose-galactose malabsorption syndrome
Lactose intolerance
Moderate hepatic impairment
Pregnancy
Advise ability to drive/operate machinery may be affected by side effects
Not all formulations are suitable for all age groups/body weights
Preparation contains sucrose
Some formulations contain lactose
Monitor INR for 2 weeks after treatment in patients on warfarin therapy
Advise patient not to take St John's wort concurrently
Female: Non-hormonal contraception advised until 2 months after treatment
Female: Oral contraception may not be adequate during treatment
Aprepitant oral suspension must be prepared by healthcare professionals, including measurement of the dose.
Pregnancy and Lactation
Pregnancy
Use aprepitant with caution in pregnancy.
At the time of writing, there are no reports describing the use of aprepitant in human pregnancy, and the manufacturer therefore advises that it should not be used in pregnancy unless clearly necessary. The potential effects on reproduction of alterations in neurokinin regulation are unknown.
Animal studies have revealed low risk; reproduction studies in rats and rabbits at oral doses up to 1.6 and 1.4 times the human exposure respectively found no evidence of impaired fertility or foetal harm. It was found to be carcinogenic, but no mutagenicity was observed.
It is not known if aprepitant crosses the human placenta, but considered likely due to the molecular weight and elimination half life. Also, it crosses the placenta in rats and rabbits, and the human blood brain barrier, making it increasing likely that embryo/foetal exposure will occur in humans. The effect of this exposure is unknown, and Briggs (2011) suggests that until additional data becomes available, use should be restricted to the second and third trimesters. However, if inadvertent exposure occurs during organogenesis, the embryo/foetal risk appears to be low.
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
Aprepitant is contraindicated in breastfeeding.
The manufacturer contraindicates the use of aprepitant during breastfeeding. It is not known whether it is excreted in human milk, but it is excreted in the milk of lactating rats, and its molecular weight and elimination half life indicate human excretion is likely. The high plasma protein binding should limit the neonatal exposure, should excretion occur, but there is potential toxicity due to carcinogenic effects observed in animal studies.
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
Abdominal distension
Abdominal pain
Abnormal bowel sounds
Abnormal faeces
Acne
Anaemia
Anorexia
Anxiety
Asthenia
Bradycardia
Candidiasis
Cardiovascular disturbances
Chest discomfort
Chills
Cognitive impairment
Colitis
Confusion
Conjunctivitis
Constipation
Cough
Diarrhoea
Disorientation
Disturbances of appetite
Dizziness
Dream abnormalities
Dry mouth
Dysarthria
Dysgeusia
Dyspepsia
Dyspnoea
Dysuria
Eructation
Euphoria
Fatigue
Febrile neutropenia
Flatulence
Flushing
Gait abnormality
Gastroesophageal reflux disease
Glycosuria
Haematuria
Headache
Hiccups
Hyperglycaemia
Hyperhidrosis
Hypersensitivity reactions including anaphylaxis
Hypoaesthesia
Hyponatraemia
Increase in alkaline phosphatase
Increase in serum ALT/AST
Insomnia
Lethargy
Malaise
Miosis
Muscle cramps
Muscle weakness
Myalgia
Nausea
Neutropenic colitis
Oedema
Oropharyngeal pain
Palpitations
Perforating duodenal ulcer
Pharyngitis
Photosensitivity
Pollakiuria
Polydipsia
Polyuria
Postnasal drip
Pruritic rash
Pruritus
Rash
Reduced neutrophil count
Reduced visual acuity
Seborrhoea
Sensory disturbances
Skin lesions
Sneezing
Somnolence
Staphylococcal infection
Stevens-Johnson syndrome
Stomatitis
Sub-ileus
Thirst
Throat irritation
Tinnitus
Toxic epidermal necrolysis
Urticaria
Vomiting
Weight changes
Wheezing
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: October 2016
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) 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.
Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 07 October 2016.
Summary of Product Characteristics: Emend 80 mg and 125 mg hard capsules. Merck sharp & Dohme Ltd. Revised December 2015.
Summary of Product Characteristics: Emend 125 mg powder for oral suspension. Merck sharp & Dohme Ltd. Revised October 2017.
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