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    Active Ingredient *
    Netupitant 300 mg
    Palonosetron (hydrochloride) 0.5 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Hard Capsules

    1

    partial basket chart 38593

    Dosage

    Adults: One 300 mg / 0.5 mg capsule should be administered approximately one hour prior to the start of each chemotherapy cycle. The recommended oral dexamethasone dose should be reduced by approximately 50 % when co-administered with this formulation.
    Elderly people: No dosage adjustment is necessary for elderly patients. Caution should be exercised when using this product in patients over 75 years, due to the long half-life of the active substances and the limited experience in this population.
    Paediatric population: The safety and efficacy of the drug in the paediatric population have not been established. No data are available.
    Renal impairment: Dosage adjustment is not considered necessary in patients with mild to severe renal impairment. Renal excretion for netupitant is negligible. Mild to moderate renal impairment does not significantly affect palonosetron pharmacokinetic parameters. Total systemic exposure to intravenous palonosetron increased by approximately 28% in severe renal impairment relative to healthy subjects. The pharmacokinetics of palonosetron or netupitant has not been studied in subjects with end-stage renal disease requiring hemodialysis and no data on the effectiveness or safety of the drug in these patients are available. Therefore use in these patients should be avoided.
    Hepatic impairment: No dosage adjustment is necessary for patients with mild or moderate hepatic impairment (Child-Pugh score 5-8). Limited data exist in patients with severe hepatic impairment (Child Pugh score ≥ 9). As use in patients with severe hepatic impairment may be associated with increased exposure of netupitant, this drug should be used with caution in these patients.
    Method of administration: For oral use. The hard capsule should be swallowed whole. It can be taken with or without food.


    Indications

    Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy.


    Contra-Indications

    Hypersensitivity to the active substances or to any of the excipients. Pregnancy.


    Special Precautions

    Constipation: As palonosetron may increase large bowel transit time, patients with a history of constipation or signs of subacute intestinal obstruction should be monitored following administration. Cases of constipation with faecal impaction requiring hospitalisation have been reported in association with palonosetron 0.75 mg.
    Serotonin syndrome: There have been reports of serotonin syndrome with the use of 5-HT3 antagonists either alone or in combination with other serotonergic medicinal products (including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs). Appropriate observation of patients for serotonin syndrome-like symptoms is advised.
    QT Prolongation: An ECG study was conducted in adult male and female healthy volunteers with oral netupitant either 200 or 600 mg administered in combination with oral palonosetron 0.5 or 1.5 mg, respectively. See prescribing information for full details.
    Chemotherapeutic agents that are substrates for CYP3A4: Netupitant is a moderate inhibitor of CYP3A4 and can increase the exposure of chemotherapeutic agents that are substrates for CYP3A4 e.g. Therefore, patients should be monitored for increased toxicity of chemotherapeutic agents that are substrates for CYP3A4, including irinotecan. Furthermore, netupitant may also affect the efficacy of chemotherapeutic agents that need activation by CYP3A4 metabolism.
    See prescribing information for full details.


    Side Effects

    Headache, constipation, fatigue.
    See prescribing information for full details.


    Drug interactions

    When this drug  is used concomitantly with another CYP3A4 inhibitor, netupitant plasma concentrations could be elevated. When this agent  is used concomitantly with medicinal products that induce CYP3A4 activity, netupitant plasma concentrations could be reduced and this may result in decreased efficacy. This product can increase plasma concentrations of concomitantly administered medicinal products that are metabolized via CYP3A4.
    Interaction with CYP3A4 substrates
    Dexamethasone: Co-administration of a single dose of 300 mg netupitant with a dexamethasone regimen (20 mg on Day 1, followed by 8 mg twice daily from Day 2 to Day 4) significantly increased the exposure to dexamethasone in a time and dose dependent manner.
    Erythromycin and Midazolam: Exposure to erythromycin and midazolam was increased approximately 1.3 and 2.4 fold, respectively, when each was co-administered with netupitant. These effects were not considered clinically important.
    Serotonergic medicinal products (e.g. SSRIs and SNRIs): There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic medicinal products (including SSRIs and SNRIs).


    Pregnancy and Lactation

    Pregnancy: There are no data about the use of netupitant in pregnant women. Women of childbearing potential should not be pregnant or become pregnant while on treatment with this drug. A pregnancy test should be performed on all pre-menopausal women prior to treatment. Women of childbearing potential must use effective contraception during therapy and up to one month after treatment with this medicinal product.
    Lactation: It is unknown whether palonosetron or netupitant are excreted in human milk.
    See prescribing information for full details.  


    Overdose

    No specific information is available on the treatment of overdose with this drug.  Netupitant doses up to 600 mg and palonosetron doses up to 6 mg have been used in clinical studies without any safety concerns. In case of overdose, the product should be discontinued and general supportive treatment and monitoring should be provided. Because of the antiemetic activity of netupitant and palonosetron, emesis induced by a medicinal product may not be effective. Dialysis studies have not been performed. However, due to the large volume of distribution of palonosetron and netupitant, dialysis is unlikely to be an effective treatment for overdose.


    Important notes

    Storage: Store below 30°C.

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