Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
PROFESSIONAL INFORMATION FOR FOSAPREPITANT HETERO  
SCHEDULING STATUS  
S4  
1 NAME OF THE MEDICINE  
FOSAPREPITANT HETERO 150 mg, Lyophilised powder for solution for infusion  
2 QUALITATIVE AND QUANTITATIVE COMPOSITION  
Each vial contains 150 mg of fosaprepitant.  
FOSAPREPITANT HETERO contains sugar 375 mg lactose per ml.  
For a full list of excipients, see section 6.1.  
3 PHARMACEUTICAL FORM  
White to off white lyophilized cake or powder.  
4 CLINICAL PARTICULARS  
4.1 Therapeutic indications  
FOSAPREPITANT HETERO, in combination with other anti-emetic medicines, is indicated for the  
prevention of acute (0 to 24 hours) and delayed (> 24 to 120 hours) nausea and vomiting associated with  
initial and repeat courses of:  
•
•
highly emetogenic cancer chemotherapy (see section 4.2)  
moderately emetogenic cancer chemotherapy (see section 4.2).  
Initial__RJ_____  
Page 1 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
4.2 Posology and method of administration  
Posology  
FOSAPREPITANT HETERO is administered on Day 1 as an infusion over 20 to 30 minutes initiated  
approximately 30 minutes prior to chemotherapy. FOSAPREPITANT HETERO should be administered in  
conjunction with a corticosteroid and a 5-HT3 antagonist as specified in the tables below. The professional  
information for the co-administered 5-HT3 antagonist must be consulted prior to initiation of treatment with  
FOSAPREPITANT HETERO.  
Recommended dosing for the prevention of nausea and vomiting associated with highly  
emetogenic cancer chemotherapy:  
Highly emetogenic chemotherapy regimen  
Day 1  
Day 2  
Day 3  
Day 4  
FOSAPREPITANT  
HETERO  
150 mg IV  
None  
None  
None  
Dexamethasone**  
12 mg orally  
8 mg orally  
None  
8 mg orally twice  
daily  
8 mg orally twice  
daily  
5-HT3 antagonist  
See the  
None  
None  
professional  
information for  
the selected 5-  
HT3 antagonist for  
the appropriate  
dosing  
information  
Initial__RJ_____  
Page 2 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
**Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1 and in the  
morning on Days 2 through 4. Dexamethasone should also be administered in the evenings on Days 3 and  
4. The dose of dexamethasone accounts for drug interactions.  
Recommended dosing for the prevention of nausea and vomiting associated with moderately  
emetogenic cancer chemotherapy:  
Moderately emetogenic chemotherapy regimen  
Day 1  
FOSAPREPITANT  
HETERO  
150 mg IV  
Dexamethasone**  
5-HT3 antagonist  
12 mg orally  
See the professional information for the selected 5-HT3 antagonist for the  
appropriate dosing information  
**Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1. The dose  
of dexamethasone accounts for interactions.  
Special populations  
Elderly:  
No dosage adjustment is necessary for the elderly.  
Age, gender and race:  
No dosage adjustment is necessary based on age, gender, race or Body Mass Index (BMI).  
Renal impairment:  
Initial__RJ_____  
Page 3 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
No dosage adjustment is necessary for patients with severe renal insufficiency (creatinine clearance < 30  
ml/min) or for patients with end stage renal disease undergoing haemodialysis.  
Hepatic impairment:  
No dosage adjustment is necessary for patients with mild to moderate hepatic insufficiency (Child-Pugh  
score 5 to 9). There are no clinical data in patients with severe hepatic insufficiency (Child-Pugh > 9) (see  
section 4.4).  
Method of administration  
FOSAPREPITANT HETERO for intravenous administration is a lyophilised pro-drug of aprepitant.  
For single use only.  
Discard any unused portion.  
For preparation of FOSAPREPITANT HETERO see section 6.6.  
4.3 Contraindications  
•
•
Known hypersensitivity to aprepitant, polysorbate 80 or to any of the excipients of  
FOSAPREPITANT HETERO (see section 6.1).  
FOSAPREPITANT HETERO should not be used concurrently with pimozide or cisapride. Inhibition  
of cytochrome P450 isoenzyme 3A4 (CYP3A4) by aprepitant could result in elevated plasma  
concentrations of these medicines potentially causing serious or life-threatening reactions (see  
section 4.5).  
Initial__RJ_____  
Page 4 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
•
•
Co-administration with pimozide, terfenadine, astemizole or cisapride (see section 4.5).  
Pregnancy and lactation (see section 4.6).  
4.4 Special warnings and precautions for use  
Severe hepatic insufficiency  
Severe hepatic insufficiency (Child-Pugh score > 9).  
There are no clinical or pharmacokinetic data in patients with severe hepatic insufficiency. Caution should  
be exercised when FOSAPREPITANT HETERO is administered in these patients.  
Since FOSAPREPITANT HETERO is rapidly converted to aprepitant (a weak to moderate inhibitor of  
CYP3A4), FOSAPREPITANT HETERO should be used with caution in patients receiving concomitant  
medicines that are primarily metabolised through CYP3A4; some chemotherapy medicines are metabolised  
by CYP3A4 (see section 4.5).  
Weak inhibition of CYP3A4 by FOSAPREPITANT HETERO could result in elevated plasma concentrations  
of these concomitant medicines (see section 4.5). Concomitant administration of FOSAPREPITANT  
HETERO , with strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nefazodone, troleandomycin,  
clarithromycin, ritonavir, nelfinavir) should be approached with caution. The effect of oral aprepitant on the  
pharmacokinetics of orally administered CYP3A4 substrates is greater than the effect of oral aprepitant on  
the pharmacokinetics of intravenously administered CYP3A4 substrates (see section 4.5).  
Hypersensitivity  
Immediate hypersensitivity reactions including flushing, erythema, dyspnoea and anaphylaxis/anaphylactic  
shock have occurred during or soon after infusion of FOSAPREPITANT HETERO. These hypersensitivity  
reactions have generally responded to discontinuation of the infusion and administration of appropriate  
Initial__RJ_____  
Page 5 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
therapy. It is not recommended to re-initiate the infusion in patients who experience hypersensitivity  
reactions.  
Infusion site reactions (ISRs) have been reported with the use of FOSAPREPITANT HETERO (see  
section 4.8). The majority of severe ISRs including thrombophlebitis and vasculitis, were reported with  
concomitant vesicant (e.g. anthracycline-based) chemotherapy administration, particularly when associated  
with extravasation. Necrosis was also reported in some patients with concomitant vesicant chemotherapy.  
Warfarin  
Co-administration of FOSAPREPITANT HETERO with warfarin may result in a clinically significant  
decrease in the International Normalised Ratio (INR) or prothrombin time.  
In patients on chronic warfarin therapy, the INR should be closely monitored in the 2 week period,  
particularly at 7 to 10 days following initiation of FOSAPREPITANT HETERO with each chemotherapy  
cycle (see section 4.5).  
Hormonal contraceptives  
The efficacy of hormonal contraceptives during and for 28 days after administration of FOSAPREPITANT  
HETERO may be reduced. Alternative or back-up methods of contraception should be used during  
treatment with fosaprepitant and for 1 month following the last dose (see section 4.5).  
Use in the elderly  
In clinical studies, the efficacy and safety of aprepitant in the elderly (65 years and older) were comparable  
to those seen in younger patients (younger than 65 years).  
Initial__RJ_____  
Page 6 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
No dosage adjustment is necessary in elderly patients.  
Lactose warning  
FOSAPREPITANT HETERO contains lactose. Patients with rare hereditary problems of galactose  
intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.  
Paediatric population  
Safety and efficacy of FOSAPREPITANT HETERO in paediatric patients have not been established.  
4.5 Interaction with other medicine and other forms of interaction  
When administered intravenously, fosaprepitant is rapidly converted to aprepitant. Therefore, interactions  
following administration of FOSAPREPITANT HETERO are likely to occur with medicines that interact with  
oral aprepitant. The following information was derived from studies conducted with oral aprepitant and  
studies conducted with fosaprepitant co-administered with dexamethasone, midazolam or diltiazem.  
Aprepitant is a substrate, a weak to moderate inhibitor and an inducer of CYP3A4. Aprepitant is also an  
inducer of CYP2C9.  
FOSAPREPITANT HETERO, given as a single dose, is a weak inhibitor of CYP3A4, and thereby may  
increase the plasma concentrations of co-administered medicines that are metabolised through CYP3A4. It  
does not induce CYP3A4. It is anticipated that FOSAPREPITANT HETERO would cause less or no greater  
induction of CYP2C9 than that caused by the administration of oral aprepitant.  
Initial__RJ_____  
Page 7 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
FOSAPREPITANT HETERO should not be used concurrently with pimozide or cisapride. Inhibition of  
CYP3A4 by aprepitant could result in elevated plasma concentrations of these medicines, potentially  
causing serious or life-threatening reactions (see section 4.3).  
Aprepitant has been shown to induce the metabolism of S(-) warfarin and tolbutamide, which are  
metabolised through CYP2C9. Co-administration of FOSAPREPITANT HETERO with these medicines or  
other medicines that are known to be metabolised by CYP2C9, such as phenytoin, may result in lower  
plasma concentrations of these medicines.  
FOSAPREPITANT HETERO is unlikely to interact with medicines that are substrates for the P-glycoprotein  
transporter, as demonstrated by the lack of interaction of oral aprepitant with digoxin in a clinical drug  
interaction study.  
5-HT3 antagonists  
In clinical interaction studies, aprepitant, when given as regimen of 125 mg on Day 1 and 80 mg on Days 2  
and 3, did not have clinically important effects on the pharmacokinetics of ondansetron, granisetron or  
hydrodolasetron (the active metabolite of dolasetron).  
Corticosteroids  
Dexamethasone: FOSAPREPITANT HETERO administered as a single intravenous dose on Day 1  
increased the AUC0-24 h, of dexamethasone, a CYP3A4 substrate, by approximately 2,0-fold on Days 1 and  
2 when dexamethasone was co-administered as a single 8 mg oral dose on Days 1, 2 and 3. The oral  
dexamethasone dose on  
Initial__RJ_____  
Page 8 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
Days 1 and 2 should be reduced by approximately 50 % when co-administered with FOSAPREPITANT  
HETERO IV on Day 1 to achieve exposures of dexamethasone similar to those obtained when given  
without FOSAPREPITANT HETERO (see section 4.2).  
Methylprednisolone: Oral aprepitant, when given as a regimen of 125 mg on Day 1 and 80 mg/day on  
Days 2 and 3, increased the AUC of methylprednisolone, a CYP3A4 substrate, by 1,3-fold on Day 1 and by  
2,5-fold on Day 3, when methylprednisolone was co-administered intravenously as 125 mg on Day 1 and  
orally as 40 mg on Days 2 and 3.  
Chemotherapeutic medicines  
Caution and careful monitoring are advised in patients receiving etoposide, vinorelbine, docetaxel,  
ifosfamide, cyclophosphamide, irinotecan and paclitaxel or other chemotherapy medicines metabolised  
primarily by CYP3A4. Post-marketing events of neurotoxicity, a potential adverse reaction of ifosfamide,  
have been reported after aprepitant and ifosfamide co-administration (see section 4.4).  
Docetaxel  
In a separate pharmacokinetic study, oral aprepitant, (CINV regimen) did not influence the  
pharmacokinetics of docetaxel.  
Vinorelbine  
In a separate pharmacokinetic study, oral aprepitant (CINV regimen) did not influence the pharmacokinetics  
of vinorelbine.  
Warfarin  
Initial__RJ_____  
Page 9 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
A single 125 mg dose of oral aprepitant was administered on Day 1 and 80 mg/day on Days 2 and 3 to  
healthy subjects who were stabilised on chronic warfarin therapy.  
Although there was no effect of oral aprepitant on the plasma AUC of R(+) or S(-) warfarin determined on  
Day 3, there was a 34 % decrease in S(-) warfarin (a CYP2C9 substrate) trough concentration  
accompanied by a 14 % decrease in the prothrombin time [reported as International Normalised Ratio (or  
INR)] 5 days after completion of dosing with oral aprepitant. In patients on chronic warfarin therapy, the  
prothrombin time (INR) should be closely monitored in the 2-week period particularly at 7 to 10 days,  
following initiation of fosaprepitant with each chemotherapy cycle.  
Prothrombin time (INR) should be done more frequently while using FOSAPREPITANT HETERO.  
Tolbutamide  
Oral aprepitant, when given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, decreased the AUC of  
tolbutamide (a CYP2C9 substrate) by 23 % on Day 4, 28 % on Day 8 and 15 % on Day 15, when a single  
dose of tolbutamide 500 mg was administered orally prior to the administration of the 3-day regimen of oral  
aprepitant and on Days 4, 8 and 15.  
Diabetic patients using tolbutamide should be monitored for glucose changes.  
Oral contraceptives  
Aprepitant, when given once daily for 14 days as a 100 mg capsule with an oral contraceptive containing 35  
μg of ethinylestradiol and 1 mg of norethindrone, decreased the AUC of ethinylestradiol by 43 %, and  
decreased the AUC of norethindrone by 8 %.  
In another reported study, a single dose of an oral contraceptive containing ethinylestradiol and  
norethindrone was administered on Days 1 through 21 with oral aprepitant, given as a regimen of 125 mg  
Initial__RJ_____  
Page 10 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
on Day 8 and 80 mg/day on Days 9 and 10 with ondansetron 32 mg IV on Day 8 and oral dexamethasone  
given as 12 mg on Day 8 and 8 mg/day on Days 9, 10 and 11. In the study, the AUC of ethinylestradiol  
decreased by 19 % on Day 10 and there was as much as a 64 % decrease in ethinylestradiol trough  
concentrations during Days 9 through 21. While there was no effect of oral aprepitant on the AUC of  
norethindrone on Day 10, there was as much as a 60 % decrease in norethindrone trough concentrations  
during Days 9 through 21.  
The efficacy of hormonal contraceptives during and for 28 days after administration of FOSAPREPITANT  
HETERO may be reduced. Alternative or back-up methods of contraception should be used during  
treatment with fosaprepitant or aprepitant and for 1 month following the last dose.  
Midazolam  
FOSAPREPITANT HETERO administered as a single intravenous dose on Day 1 increased the AUC0-∞ of  
midazolam by approximately 1,8-fold on Day 1 and had no effect (1,0-fold) on Day 4 when midazolam was  
co-administered as a single oral dose of 2 mg on Days 1 and 4. FOSAPREPITANT HETERO IV is a weak  
CYP3A4 inhibitor as a single dose on Day 1 with no evidence of inhibition or induction of CYP3A4 observed  
on Day 4.  
In addition, when FOSAPREPITANT HETERO was administered as a dose of 100 mg over 15 minutes  
along with a single dose of midazolam 2 mg, the plasma AUC of midazolam was increased by 1,6-fold. This  
effect was not considered clinically important.  
Oral aprepitant increased the AUC of midazolam, by 2,3-fold on Day 1 and 3,3-fold on Day 5, when a single  
oral dose of midazolam 2 mg was co-administered on Day 1 and Day 5 of a regimen of oral aprepitant 125  
mg on Day 1 and 80 mg/day on Days 2 through 5. The potential effects of increased plasma concentrations  
of midazolam or other benzodiazepines metabolised via CYP3A4 (alprazolam, triazolam) should be  
considered when co-administering these medicines with FOSAPREPITANT HETERO.  
Initial__RJ_____  
Page 11 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
Immunosuppressants  
Following a single 150 mg fosaprepitant dose, a transient moderate increase for two days possibly followed  
by a mild decrease in exposure of immunosuppressants metabolised by CYP3A4 (e.g. ciclosporin,  
tacrolimus, everolimus and sirolimus) is expected. Given the short duration of increased exposure, dose  
reduction of the immunosuppressant based on Therapeutic Dose Monitoring is not recommended on the  
day of and the day after administration of fosaprepitant as in FOSAPREPITANT HETERO.  
Induction  
The fosaprepitant 150 mg single dose did not induce CYP3A4 on Days 1 and 4 in the midazolam  
interaction study. It is anticipated that FOSAPREPITANT HETERO would cause less or no greater  
induction of CYP2C9, CYP3A4, and glucuronidation than that caused by the administration of the 3-day  
oral aprepitant regimen, for which a transient induction with its maximum effect 6-8 days after first  
aprepitant dose has been observed. The 3-day oral aprepitant regimen resulted in an about 30-35 %  
reduction in AUC of CYP2C9 substrates and up to a 64 % decrease in ethinyl estradiol trough  
concentrations. Data are lacking regarding effects on CYP2C8 and CYP2C19. Caution is advised when  
warfarin, acenocoumarol, tolbutamide,  
phenytoin or other active substances that are known to be metabolised by CYP2C9 are administered with  
fosaprepitant as in FOSAPREPITANT HETERO.  
Effect of other medicines on the pharmacokinetics of aprepitant  
FOSAPREPITANT HETERO should be used with caution in patients receiving concomitant medicines,  
including chemotherapy medicines that are primarily metabolised through CYP3A4.  
Initial__RJ_____  
Page 12 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
Aprepitant is a substrate for CYP3A4; therefore, co-administration of FOSAPREPITANT HETERO with  
medicines that inhibit CYP3A4 activity may result in increased plasma concentrations of aprepitant.  
Consequently, concomitant administration of FOSAPREPITANT HETERO with strong CYP3A4 inhibitors  
(e.g. ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir) should be  
approached with caution. Because moderate CYP3A4 inhibitors (e.g. diltiazem) result in a 2-fold increase in  
plasma concentrations of aprepitant, concomitant administration should also be approached with caution.  
Aprepitant is a substrate for CYP3A4; therefore, co-administration of FOSAPREPITANT HETERO with  
medicines that strongly induce CYP3A4 activity (e.g. rifampicin, carbamazepine, phenytoin) may result in  
reduced plasma concentrations of aprepitant that may result in decreased efficacy of FOSAPREPITANT  
HETERO.  
Ketoconazole  
When a single 125 mg dose of oral aprepitant was administered on Day 5 of a 10-day regimen of 400  
mg/day of ketoconazole, a strong CYP3A4 inhibitor, the AUC of aprepitant increased approximately 5-fold  
and the mean terminal half-life of aprepitant increased approximately 3-fold. Concomitant administration of  
fosaprepitant or aprepitant with strong CYP3A4 inhibitors should be approached cautiously.  
Rifampicin  
When a single 375 mg dose of oral aprepitant was administered on Day 9 of a 14- day regimen of 600  
mg/day of rifampicin, a strong CYP3A4 inducer, the AUC of aprepitant decreased approximately 11-fold  
and the mean terminal half-life decreased approximately 3-fold. Co-administration of fosaprepitant or  
aprepitant with medicines that induce CYP3A4 activity may result in reduced plasma concentrations and  
decreased efficacy.  
Additional interactions  
Initial__RJ_____  
Page 13 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
Diltiazem: In patients with mild to moderate hypertension, infusion of 100 mg of fosaprepitant over 15  
minutes with diltiazem 120 mg 3 times daily, resulted in a 1,5-fold increase of aprepitant AUC and a 1,4 fold  
increase in diltiazem AUC. The pharmacokinetic effects resulted in a clinically meaningful decrease in  
diastolic blood pressure (decrease of 16,8 mm Hg with fosaprepitant versus 10,5 mm Hg without  
fosaprepitant) and may result in a clinically meaningful decrease in systolic blood pressure (decrease of  
24,4 mm Hg with fosaprepitant versus 18,8 mm Hg without fosaprepitant), but did not result in a clinically  
meaningful change in heart rate, or PR interval beyond those changes induced by diltiazem alone.  
In the same study, administration of aprepitant once daily, as a tablet formulation comparable to 230 mg of  
the capsule formulation, with diltiazem 120 mg 3 times daily for 5 days, resulted in a 2-fold increase of  
aprepitant AUC and a simultaneous 1,7-fold increase of diltiazem AUC. These pharmacokinetic effects did  
not result in clinically meaningful changes in ECG, heart rate, or blood pressure beyond those changes  
induced by diltiazem alone.  
Paroxetine: Co-administration of once daily doses of aprepitant, as a tablet formulation comparable to 85  
mg or 170 mg of the capsule formulation, with paroxetine 20 mg once daily, resulted in a decrease in AUC  
by approximately 25 % and Cmax, by approximately 20 % of both aprepitant and paroxetine.  
4.6 Fertility, pregnancy and lactation  
Contraception in males and females  
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 last dose of fosaprepitant (see sections 4.4 and 4.5).  
Pregnancy  
Initial__RJ_____  
Page 14 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
FOSAPREPITANT HETERO is contraindicated in pregnancy .  
Safety in pregnancy has not been established.  
Lactation  
FOSAPREPITANT HETERO is contraindicated in lactation.  
Mothers on treatment with FOSAPREPITANT HETERO should not breastfeed their infants.  
Aprepitant is excreted in the milk of lactating rats. It is not known whether aprepitant is excreted in human  
milk.  
Fertility  
The potential for effects of fosaprepitant and 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.  
4.7 Effects on ability to drive and use machines  
No studies of the effects of FOSAPREPITANT HETERO on the ability to drive and use of machines have  
been performed. However, certain side effects that have been reported with FOSAPREPITANT HETERO  
may affect some patient's ability to drive or operate machinery. Individual responses to FOSAPREPITANT  
HETERO may vary (see section 4.8).  
Initial__RJ_____  
Page 15 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
4.8 Undesirable effects  
Oral Aprepitant  
a) Summary of the safety profile  
Since FOSAPREPITANT HETERO is converted to aprepitant, those adverse experiences associated with  
aprepitant are also expected to occur with FOSAPREPITANT HETERO.  
The overall safety of fosaprepitant was evaluated in 1 600 individuals, and the overall safety of oral  
aprepitant was evaluated in approximately 6 500 individuals.  
Highly and moderately emetogenic chemotherapy (HEC/MEC):  
In a reported pooled analysis of the HEC and MEC studies the following medicine-related adverse  
experiences were reported in patients treated with the 3-day oral aprepitant regimen and at a greater  
incidence than standard therapy.  
b) Tabulated summary of adverse reactions  
System organ class  
Infections and  
Infestations  
Adverse reaction  
Candidiasis,  
Frequency  
Less frequent  
staphylococcal infection  
Blood and the  
Anaemia, febrile  
neutropenia  
Less frequent  
lymphatic system  
disorders  
Metabolism and  
nutrition disorders  
Psychiatric disorders  
Decreased appetite  
Polydipsia  
Frequent  
Less frequent  
Less frequent  
Anxiety, disorientation,  
euphoria  
Initial__RJ_____  
Page 16 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
b) Tabulated summary of adverse reactions  
System organ class  
Nervous system  
disorders  
Adverse reaction  
Headache, dizziness,  
somnolence, cognitive  
disorder, lethargy,  
dysgeusia  
Frequency  
Less frequent  
Eye disorders  
Ear and labyrinth  
disorders  
Conjunctivitis  
Less frequent  
Less frequent  
Tinnitus  
Cardiac disorders  
Palpitations, bradycardia,  
cardiovascular disorder  
Hot flushes/flushing  
Hiccups  
Less frequent  
Vascular disorders  
Respiratory, thoracic  
and mediastinal  
disorders  
Frequent  
Frequent  
Oropharyngeal pain,  
sneezing, cough, post-  
nasal drip, throat irritation  
Constipation, dyspepsia  
Eructation, nausea,  
gastroesophageal reflux  
disease, vomiting,  
Less frequent  
Gastrointestinal  
disorders  
Frequent  
Less frequent  
abdominal pain, dry  
mouth, flatulence, hard  
faeces, duodenal ulcer  
perforation, neutropenic  
colitis, stomatitis,  
abdominal distension.  
Rash, acne,  
Skin and subcutaneous  
tissue disorders  
Less frequent  
photosensitivity reaction,  
Initial__RJ_____  
Page 17 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
b) Tabulated summary of adverse reactions  
System organ class  
Adverse reaction  
hyperhidrosis,  
Frequency  
seborrhoea, skin lesion,  
pruritic rash, Stevens-  
Johnson syndrome/toxic  
epidermal necrolysis,  
pruritis, urticaria.  
Musculoskeletal and  
connective tissue  
disorder  
Muscle spasms, muscle  
weakness  
Less frequent  
Less frequent  
Renal and urinary  
disorders  
Dysuria, pollakisuria  
General disorders and  
administration site  
conditions  
Fatigue.  
Frequent  
Asthenia, malaise,  
oedema, chest  
Less frequent  
discomfort, gait  
disturbance.  
Investigations  
Increased ALT  
Frequent  
Increased AST,  
Less frequent  
increased blood alkaline  
phosphatase, increased  
urine output, positive red  
blood cells in urine,  
decreased blood sodium,  
decreased weight,  
glycosuria, decreased  
Initial__RJ_____  
Page 18 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
b) Tabulated summary of adverse reactions  
System organ class  
Adverse reaction  
Frequency  
neutrophil count.  
In another (CINV) study, Stevens-Johnson syndrome was reported as a serious adverse experience in a  
patient receiving aprepitant with cancer chemotherapy.  
Fosaprepitant  
a) Summary of the safety profile  
Moderately Emetogenic Chemotherapy  
In a reported active-controlled clinical trial in patients receiving MEC, safety was evaluated in 504 patients  
receiving a single dose of fosaprepitant 150 mg in combination with ondansetron and dexamethasone  
(fosaprepitant regimen) compared to 497 patients receiving ondansetron and dexamethasone alone  
(control regimen). As per the reported study, the following clinically important medicine-related adverse  
experiences were reported in patients treated with the fosaprepitant regimen and at a greater incidence  
than in the control group.  
Initial__RJ_____  
Page 19 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
System organ class  
Cardiac disorders  
Gastrointestinal  
disorders  
Adverse reaction  
Frequency  
Palpitations  
Less frequent  
Frequent  
Constipation  
abdominal distension,  
abdominal pain, upper  
abdominal pain,  
dyspepsia  
Less frequent  
General disorders and  
administration site  
condition  
Infusion site pain.  
Asthenia  
Frequent  
Less frequent  
Infections and  
Oral candidiasis  
Less frequent  
Less frequent  
Less frequent  
infestations  
Metabolism and  
nutrition disorders  
Respiratory, thoracic  
and mediastinal  
disorders  
Decreased appetite  
Cough, oropharyngeal  
pain, throat irritation  
Vascular disorders  
Hot flushes.  
Less frequent  
Highly Emetogenic Chemotherapy (HEC)  
In a reported active-controlled clinical study in patients receiving highly emetogenic chemotherapy, safety  
was evaluated for 1 143 patients receiving a single dose of FOSAPREPITANT HETERO 150 mg compared  
to 1 169 patients receiving the 3-day regimen of aprepitant powder for oral suspension. The safety profile  
was generally similar to that seen in the MEC study with fosaprepitant.  
Initial__RJ_____  
Page 20 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
The following additional clinically important medicine-related adverse experiences occurred with  
fosaprepitant 150 mg and have not been reported in earlier clinical studies with oral aprepitant or in the  
MEC study with fosaprepitant.  
System organ class  
General disorders and  
administration site  
conditions  
Adverse reaction  
Infusion site erythema,  
infusion site pruritus,  
infusion site induration.  
Erythema  
Frequency  
Less frequent  
Skin and subcutaneous  
tissue disorders  
Less frequent  
Less frequent  
Vascular disorders  
Flushing,  
thrombophlebitis  
(predominantly, infusion  
site thrombophlebitis).  
Other Reported Studies  
Abdominal pain upper, bowel sounds abnormal, constipation*, dysarthria, dyspnoea, hypoaesthesia,  
insomnia, miosis, nausea, sensory disturbance, stomach discomfort, sub-ileus*, visual acuity reduced,  
wheezing.  
*Reported in patients taking a higher dose of aprepitant  
Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued  
monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any  
suspected adverse reactions via the “6.04 Adverse Drug Reactions Reporting Form”, found online under  
SAHPRA’s publications: https://www.sahpra.org.za and to the Holder of certificate of registration through  
the mail: pvg.cdma@heterogroups.com.  
Initial__RJ_____  
Page 21 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
4.9 Overdose  
In the event of overdose, FOSAPREPITANT HETERO should be discontinued and general supportive  
treatment and monitoring should be provided.  
Aprepitant cannot be removed by haemodialysis.  
5 PHARMACOLOGICAL PROPERTIES  
5.1 Pharmacodynamic properties  
Category and Class: A.5.7.2 Anti-emetics and antivertigo preparations.  
Pharmacotherapeutic group: Antiemetics and antinauseants, ATC code: A04AD12.  
Fosaprepitant dimeglumine is a prodrug of aprepitant. When administered intravenously it is rapidly  
converted to aprepitant, a substance P neurokinin 1 (NK1) receptor antagonist.  
Its anti-emetic effects are attributable to aprepitant.  
NK1-receptor antagonists inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin,  
via central actions. Human Positron Emission Tomography (PET) studies with aprepitant have shown that it  
penetrates the brain and occupies brain NK1 receptors.  
5.2 Pharmacokinetic properties  
Absorption:  
Following a single intravenous 150 mg dose of fosaprepitant administered as a 20-minute infusion to  
healthy volunteers the mean AUC0-∞ of aprepitant was 35,0 μg.hr/ml and the mean maximal aprepitant  
concentration was 4,01 μg/ml.  
Initial__RJ_____  
Page 22 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
Distribution:  
Aprepitant is > 95 % bound to plasma proteins. The geometric mean apparent volume of distribution at  
steady-state (Vdss) is approximately 66 litres in humans.  
Aprepitant crosses the placenta and blood brain barrier.  
Biotransformation:  
Fosaprepitant is rapidly converted to aprepitant.  
In humans, fosaprepitant administered intravenously was rapidly converted to aprepitant within 30 minutes  
following the end of infusion. Fosaprepitant undergoes rapid and nearly complete conversion to aprepitant  
in the liver and other extra-hepatic human tissues including kidney, lung and ileum.  
Aprepitant undergoes further extensive metabolism. In healthy young adults, aprepitant accounts for  
approximately 24 % of the radioactivity in plasma over 72 hours following a single oral 300 mg dose of  
[14C]-aprepitant, indicating a substantial presence of metabolites in the plasma. Seven metabolites of  
aprepitant, which are only weakly active, have been identified in human plasma. The metabolism of  
aprepitant occurs largely via oxidation at the morpholine ring and its side chains. In vitro studies using  
human liver microsomes indicate that aprepitant is metabolised primarily by CYP3A4 with minor  
metabolism by CYPl A2 and CYP2Cl 9, and no metabolism by CYP2D6, CYP2C9 or CYP2E1.  
All metabolites observed in urine, faeces and plasma following an intravenous 100 mg [14C]-fosaprepitant  
dose were also observed following an oral dose of [14C]-aprepitant. Upon conversion of 245,3 mg of  
fosaprepitant dimeglumine (equivalent to 150 mg fosaprepitant free acid) to aprepitant, 23,9 mg of  
phosphoric acid and 95,3 mg of meglumine are liberated.  
Elimination:  
Initial__RJ_____  
Page 23 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
The apparent terminal half-life ranged from approximately 9 to 13 hours.  
Following administration of a single IV 100 mg dose of [14C]-fosaprepitant to healthy subjects, 57 % of the  
radioactivity was recovered in urine and 45 % in faeces. Aprepitant is eliminated primarily by metabolism;  
aprepitant is not renally excreted.  
Special population  
Elderly:  
Following oral administration of a single 125 mg dose of aprepitant on Day 1 and 80 mg once daily on Days  
2 through 5, the AUC0-24hr, of aprepitant was 21 % higher on Day 1 and 36 % higher on Day 5 in elderly (65  
years and older) relative to younger adults. The Cmax was 10 % higher on Day 1 and 24 % higher on Day 5  
in elderly relative to younger adults. These differences are not considered clinically meaningful. No dosage  
adjustment is necessary in elderly patients.  
Hepatic insufficiency:  
Fosaprepitant is metabolised in various extra-hepatic tissues; therefore hepatic insufficiency is not expected  
to alter the conversion of fosaprepitant to aprepitant.  
Oral aprepitant was well tolerated in patients with mild (Child-Pugh score 5 to 6) to moderate (Child-Pugh  
score 7 to 9) hepatic insufficiency. The pharmacokinetic changes are not considered clinically meaningful;  
therefore, no dosage adjustment is necessary in patients with mild to moderate hepatic insufficiency.  
There are no clinical or pharmacokinetic data in patients with severe hepatic insufficiency (Child-Pugh  
score > 9) (see section 4.4).  
Renal insufficiency  
Initial__RJ_____  
Page 24 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
A single 240 mg dose of oral aprepitant was administered to patients with severe renal insufficiency (CrCI <  
30 ml/min) and to patients with end stage renal disease (ESRD) requiring haemodialysis.  
In patients with severe renal insufficiency, the AUC0-∞ of total aprepitant (unbound and protein bound)  
decreased by 21 % and Cmax, decreased by 32 %, relative to healthy subjects. In patients with ESRD  
undergoing haemodialysis, the AUC0-∞ of total aprepitant decreased by 42 % and Cmax, decreased by 32 %.  
Due to modest decreases in protein binding of aprepitant in patients with renal disease, the AUC of  
pharmacologically active unbound aprepitant was not significantly affected in patients with renal  
insufficiency compared with healthy subjects. Haemodialysis conducted 4 or 48 hours after dosing had no  
significant effect on the pharmacokinetics of aprepitant; < 0,2 % of the dose was recovered in the dialysate.  
No dosage adjustment is necessary for patients with severe renal insufficiency or for patients with ESRD  
undergoing haemodialysis.  
Paediatric population  
Fosaprepitant has not been evaluated in patients below 18 years of age.  
6 PHARMACEUTICAL PARTICULARS  
6.1 List of excipients  
•
•
•
•
•
•
•
Edetate disodium  
Hydrochloric acid  
Lactose anhydrous  
Nitrogen  
Polysorbate 80  
Sodium hydroxide  
Water for injection  
Initial__RJ_____  
Page 25 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
6.2 Incompatibilities  
FOSAPREPITANT HETERO is incompatible with any solutions containing divalent cations (e.g. Ca2+,  
Mg2+), including Hartman's and Lactated Ringer's Solution. FOSAPREPITANT HETERO must not be  
reconstituted or mixed with solutions for which physical and chemical compatibility have not been  
established (see section 6.6).  
6.3 Shelf life  
Unopened vial: 24 months.  
Reconstituted solution for injection and infusion:  
The reconstituted final drug solution is stable for 24 hours at ambient room temperature at or below 25 °C.  
Although chemical and physical stability of reconstituted/diluted solutions has been demonstrated for 24  
hours at 2 - 8 °C, from a microbiological point of view, the product should be used immediately. If not used  
immediately, in-use storage times and conditions prior to use are the responsibility of the user and would  
normally not be longer than 24 hours, unless reconstitution / dilution has taken place in controlled and  
validated aseptic conditions.  
6.4 Special precautions for storage  
•
•
•
Store in a refrigerator (2 °C to 8 °C) after reconstitution, if not used immediately.  
For storage conditions after reconstitution and dilution solution, see section 6.3.  
Do not freeze the reconstituted solution.  
6.5 Nature and contents of container  
10 mL Type-I, round clear tubular glass vial with 13 mm grey coloured bromobutyl rubber stopper and 13  
Initial__RJ_____  
Page 26 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
mm orange colour aluminium flip off seal, packed in an outer carton.  
Pack size: 1 x 10 mL vial.  
6.6 Special precautions for disposal and other handling  
Preparation of FOSAPREPITANT HETERO for Injection  
1. Inject 5 ml 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.  
2. Prepare an infusion bag filled with 145 ml of saline.  
3. Withdraw the entire volume from the vial and transfer it into an infusion bag containing 145 ml of  
saline to yield a total volume of 150 ml. Gently invert the bag 2 to 3 times.  
FOSAPREPITANT HETERO should be inspected visually for particulate matter and discolouration before  
administration whenever solution and container permit.  
7 HOLDER OF CERTIFICATE OF REGISTRATION  
Hetero Drugs South Africa (Pty) Ltd  
Waterfall Corporate Campus  
Building No. 2, First floor  
74 Waterfall Drive  
Midrand  
2066  
Initial__RJ_____  
Page 27 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: [FOSAPREPITANT HETERO]  
Dosage form and strength: Lyophilised powder for solution for infusion and 150 mg/vial.  
API: Fosaprepitant dimeglumine  
Date of original submission: 23 Feb 2022  
Date of recommendation: 13 May 2024, received 24 May 2024  
Date of P&A recommendation: 28 May 2024  
Date of CC response 1: 24-June2024  
Date of response: 06 Aug 2024  
Clinical Approval 0001: Date to be indicated: 24-June-2024  
Date of notification of name approval: 11 Feb 2025.  
8 REGISTRATION NUMBER(S)  
57/5.7.2/0153  
9 DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION  
11 February 2025  
10 DATE OF REVISION OF THE TEXT  
Initial__RJ_____  
Page 28 of 28  
Date of clinical approval via email: 11 Feb 2025 for seq 0001.  
PEM approval: 6 Aug 2024 seq 0002.