Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
PROFESSIONAL INFORMATION FOR DOCETAXEL HETERO  
SCHEDULING STATUS  
S4  
1. NAME OF THE MEDICINE  
DOCETAXEL 20 mg/mL HETERO (Solution for infusion)  
DOCETAXEL 80 mg/4 mL HETERO (Solution for infusion)  
DOCETAXEL 160 mg/8 mL HETERO (Solution for infusion)  
2. QUALITATIVE AND QUANTITATIVE COMPOSITION  
Each ml of concentrate contains 20 mg docetaxel anhydrous.  
One vial of 1 ml of concentrate contains 20 mg of docetaxel.  
One vial of 4 ml of concentrate contains 80 mg of docetaxel.  
One vial of 8 ml of concentrate contains 160 mg of docetaxel.  
For the full list of excipients, see section 6.1.  
3. PHARMACEUTICAL FORM  
Concentrate for solution for infusion.  
The concentrate is a brownish yellow to pale yellow colour solution.  
4. CLINICAL PARTICULARS  
4.1 Therapeutic indications  
4.1.1  
Breast cancer:  
DOCETAXEL HETERO, in combination with doxorubicin, is indicated for the treatment of patients with  
locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for  
this condition.  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 1 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
DOCETAXEL HETERO monotherapy is indicated for the treatment of patients with locally advanced  
or metastatic breast cancer, after failure of cytotoxic therapy.  
DOCETAXEL HETERO, in combination with capecitabine, is indicated for the treatment of patients  
with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous  
therapy should have included an anthracycline.  
4.1.2  
Non-small cell lung cancer:  
DOCETAXEL HETERO, in combination with cisplatin, is indicated for the treatment of patients with  
unresectable, locally advanced or metastatic non-small cell lung cancer, who have not previously  
received chemotherapy for this condition.  
DOCETAXEL HETERO is indicated for the treatment of patients with locally advanced or metastatic  
non-small cell lung cancer, even after failure of platinum-based chemotherapy.  
4.1.3  
Ovarian cancer:  
DOCETAXEL HETERO is indicated, after failure of first-line or subsequent chemotherapy, for  
treatment of metastatic carcinoma of the ovary.  
4.1.4  
Prostate cancer:  
DOCETAXEL HETERO, in combination with prednisone or prednisolone, is indicated for the  
treatment of patients with androgen-independent (hormone refractory) metastatic prostate cancer.  
4.2 Posology and method of administration  
Posology:  
A premedication consisting of a corticosteroid (see below for prostate cancer), such as oral  
dexamethasone 16 mg per day (e.g. 8 mg twice daily) for 3 days, starting one day prior to  
DOCETAXEL HETERO administration, unless contra-indicated, can be used. For prostate cancer,  
given the concurrent use of prednisone or prednisolone, the recommended premedication regimen is  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 2 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
oral dexamethasone 8 mg administered 12 hours, 3 hours and 1 hour before the DOCETAXEL  
HETERO infusion.  
DOCETAXEL HETERO is administered as a one-hour infusion every three weeks.  
4.2.1  
Breast cancer:  
In first-line treatment, DOCETAXEL HETERO 75 mg/m2 is administered in combination therapy with  
doxorubicin (50 mg/m2).  
For second-line monotherapy for previously treated patients, the recommended dosage of  
DOCETAXEL HETERO therapy is 100 mg/m2.  
In combination with capecitabine, the recommended dose of DOCETAXEL HETERO is 75 mg/m2  
every three weeks, combined with capecitabine at 1250 mg/m2 orally twice daily (within 30 minutes  
after a meal) for 2 weeks followed by a 1-week rest period. For capecitabine dose calculation  
according to body surface area, see capecitabine’s approved prescribing information.  
4.2.2  
Non-small cell lung cancer:  
In combination therapy (chemotherapy-naïve patients):  
The recommended dosage regimen is DOCETAXEL HETERO 75 mg/m2 immediately followed by  
cisplatin 75 mg/m2 over 30 – 60 minutes.  
In monotherapy (for previously treated patients):  
The recommended dosage of DOCETAXEL HETERO therapy is 100 mg/m2 as a single medicine.  
4.2.3  
Ovarian cancer:  
The recommended dosage of DOCETAXEL HETERO therapy is 100 mg/m2.  
4.2.4  
Prostate cancer:  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 3 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
The recommended dose of DOCETAXEL HETERO is 75 mg/m2. Prednisone or prednisolone 5 mg  
orally twice daily is administered continuously.  
Patients should be observed closely, especially during the first and second infusion of DOCETAXEL  
HETERO, because of the risk of hypersensitivity reactions.  
Dosage adjustments during treatment:  
General:  
ONLY the medical practitioner can modify the schedule of administration.  
DOCETAXEL HETERO should be administered when the neutrophil count is ≥ 1500 cells/mm3.  
Patients who experienced either febrile neutropenia, neutrophil count <500 cells/mm3 for more than  
one week, severe or cumulative cutaneous reactions or severe neurosensory signs and/or symptoms  
during DOCETAXEL HETERO therapy, should have the dosage of DOCETAXEL HETERO reduced  
during the subsequent cycle, from 100 mg/m2 to 75 mg/m2 and/or from 75 mg/m2 to 60 mg/m2. If the  
patient continues to experience these reactions at 60 mg/m2, treatment should be discontinued.  
Combination therapy with DOCETAXEL HETERO for non-small cell lung cancer: For patients  
who were dosed initially at DOCETAXEL HETERO 75 mg/m2 in combination with cisplatin, and whose  
nadir of platelet count during the previous course of therapy was < 25000 cells/mm3, or in patients  
who experience febrile neutropenia, or in patients with serious non-haematological toxicities, the  
DOCETAXEL HETERO dosage in subsequent cycles should be reduced to 65 mg/m2. For cisplatin  
dosage adjustments, see the approved prescribing information.  
Combination therapy with DOCETAXEL HETERO for breast cancer: Patients who receive  
adjuvant therapy for breast cancer and who experience febrile neutropenia may receive Granulocyte-  
colony stimulating factor (G-CSF) in all subsequent cycles. Patients who continue to experience this  
reaction should remain on G-CSF and have their DOCETAXEL HETERO dose reduced to 60 mg/m2.  
If G-CSF is not used, the DOCETAXEL HETERO dose should be reduced from 75 to 60 mg/m2.  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 4 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
For capecitabine dose modifications when combined with DOCETAXEL HETERO, see capecitabine’s  
approved prescribing information.  
For patients developing the first appearance of grade 2 toxicity which persists at the time of the next  
DOCETAXEL HETERO/capecitabine treatment, delay treatment until resolved to grade 0 – 1, and  
resume at 100 % of the original dose. For patients developing the second appearance of grade 2  
toxicity, or the first appearance of grade 3 toxicity, at any time during the treatment cycle, delay  
treatment until resolved to grade 0 – 1, then resume treatment with DOCETAXEL HETERO 55 mg/m2.  
For any subsequent appearances of toxicities, or any grade 4 toxicities, discontinue the DOCETAXEL  
HETERO dose.  
For DOCETAXEL HETERO dose modifications due to hepatic impairment, see section 4.4.  
Special populations:  
Patients with hepatic impairment:  
Patients with bilirubin > ULN should generally not receive DOCETAXEL HETERO. Also, patients with  
AST and/or ALT > 1,5 x ULN concomitant with alkaline phosphatase > 2,5 x ULN should generally not  
receive DOCETAXEL HETERO.  
Children:  
The safety and effectiveness of DOCETAXEL HETERO in children have not been established (see  
section 4.3).  
Elderly:  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 5 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
Based on a population pharmacokinetic analysis, there are no special instructions for use in the  
elderly.  
For capecitabine dosage reduction when combined with DOCETAXEL HETERO, see capecitabine’s  
approved prescribing information.  
Method of administration:  
DOCETAXEL HETERO should be administered by intravenous infusion only.  
DOCETAXEL HETERO concentrate or infusion solution should be visually inspected prior to use.  
Solutions containing a precipitate should be discarded. Do not admix with other medicines.  
4.3 Contraindications  
•
DOCETAXEL HETERO is contraindicated in patients who have a history of hypersensitivity to the  
active substance docetaxel, polysorbate 80 or to any of the excipients listed in section 6.1.  
Patients with baseline neutrophil count of < 1,500 cells/mm3.  
•
•
DOCETAXEL HETERO should not be used in patients with severe liver impairment (see sections  
4.2 and 4.4).  
•
•
Contraindications for other medicines also apply, when combined with DOCETAXEL HETERO.  
DOCETAXEL HETERO is contraindicated in pregnancy and lactation as docetaxel is teratogenic  
in animals (see section 4.6)  
•
The safe use in children has not been established.  
4.4 Special warnings and precautions for use  
DOCETAXEL HETERO (docetaxel) concentrate for infusion should be administered under the  
supervision of a qualified medical practitioner experienced in the use of antineoplastic agents.  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 6 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
Appropriate management of complications is possible only when adequate diagnostic and treatment  
facilities are readily available.  
The incidence of treatment-related mortality associated with DOCETAXEL HETERO therapy is  
increased in patients with abnormal liver function and in patients receiving higher doses.  
DOCETAXEL HETERO should generally not be given to patients with serum bilirubin > upper limit of  
normal (ULN), or to patients with AST and/or ALT > 1,5 x ULN concomitant with alkaline phosphatase  
> 2,5 x ULN. Patients with elevations of bilirubin or abnormalities of transaminase concurrent with  
alkaline phosphatase are at increased risk for the development of grade 4 neutropenia, febrile  
neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity and toxic  
death. Patients with isolated elevations of transaminase > 1,5 x ULN may have a higher rate of febrile  
neutropenia grade 4, but may not have an increased incidence of toxic death.  
Bilirubin, AST or ALT and alkaline phosphatase values should be obtained prior to each cycle of  
DOCETAXEL HETERO therapy and reviewed by the treating medical doctor.  
DOCETAXEL HETERO therapy should not be given to patients with neutrophil counts of < 1 500  
cells/mm3. In order to monitor the occurrence of neutropenia, which may be severe and result in  
infection, frequent blood cell counts should be performed on all patients receiving DOCETAXEL  
HETERO. Severe hypersensitivity reactions characterised by hypotension and/or bronchospasm, or  
generalised rash/erythema may occur in 2,2 % (2/92) of patients who received the recommended 3-  
day dexamethasone premedication. Hypersensitivity reactions requiring discontinuation of the  
DOCETAXEL HETERO infusion may occur in patients who did not receive premedication. These  
reactions may resolve after discontinuation of the infusion and the administration of appropriate  
therapy.  
DOCETAXEL HETERO must not be given to patients who have a history of severe hypersensitivity  
reactions to docetaxel or to other medicines formulated with polysorbate 80.  
Severe fluid retention may occur in 6,5 % (6/92) of patients despite use of a 3-day dexamethasone  
premedication regimen. This is characterised by one or more of the following events: poorly tolerated  
peripheral oedema, generalised oedema, pleural effusion requiring urgent drainage, dyspnoea at rest,  
cardiac tamponade or pronounced abdominal distention (due to ascites).  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 7 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
The use of DOCETAXEL HETERO] should be confined to units specialised in the administration of  
cytotoxic chemotherapy and it should only be administered under the supervision of a qualified  
oncologist. Since significant hypersensitivity reactions may occur, appropriate supportive equipment  
should be available.  
During the infusion, it is recommended that vital functions should be closely monitored  
Premedication consisting of an oral corticosteroid, such as dexamethasone16 mg per day (e.g. 8 mg  
BID) for 3 days starting 1 day prior to docetaxel administration, unless contraindicated, can reduce the  
incidence and severity of fluid retention as well as the severity of hypersensitivity reactions. For  
prostate cancer, the premedication is oral dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before  
the docetaxel infusion (see section 4.2).  
Haematology:  
Neutropenia is the most frequent adverse reaction of DOCETAXEL HETERO and occurs in almost all  
patients. Severe neutropenia (grade 3 – 4) occurred in 99 % of patients on combination therapy with  
doxorubicin.  
Neutrophil nadirs occurred at a median of 7 days, but this interval may be shorter in heavily pre-  
treated patients. Frequent monitoring of complete blood counts should be conducted on all patients  
receiving DOCETAXEL HETERO. Patients should be retreated with DOCETAXEL HETERO only after  
neutrophils recover to a level ≥ 1500 cells/mm3 (see section 4.2). In the case of severe neutropenia  
(< 500 cells/mm3 for seven days or more) during a course of DOCETAXEL HETERO therapy, a  
reduction in dose for subsequent courses of therapy and the use of appropriate symptomatic  
measures are recommended.  
Hypersensitivity reactions:  
Patients should be observed closely for hypersensitivity reactions especially during the first and  
second infusions with DOCETAXEL HETERO. Hypersensitivity reactions may occur within a few  
minutes following the initiation of the infusion of DOCETAXEL HETERO, thus facilities for the  
treatment of hypotension and bronchospasm should be available. If hypersensitivity reactions occur,  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 8 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
minor symptoms such as flushing or localised cutaneous reactions do not require interruption of  
therapy. However, severe reactions, such as severe hypotension (with a reduction more than 20  
mmHg), bronchospasm or generalised rash/erythema require immediate discontinuation of  
DOCETAXEL HETERO and appropriate symptomatic therapy. Patients who have developed severe  
hypersensitivity reactions should not be re-challenged with DOCETAXEL HETERO. Patients who  
have previously experienced a hypersensitivity reaction to paclitaxel may be at risk to develop  
hypersensitivity reaction to DOCETAXEL HETERO, including more severe hypersensitivity reaction.  
These patients should be closely monitored during initiation of DOCETAXEL HETERO therapy.  
Cutaneous reactions:  
Localised skin erythema of the extremities (palms of the hands and soles of the feet) with oedema  
followed by desquamation has been observed during the use of docetaxel. Severe symptoms such as  
eruptions followed by desquamation which leads to interruption or discontinuation of docetaxel  
treatment were reported (see section 4.2).  
Severe Cutaneous Adverse Reactions (SCARs) such as Stevens-Johnson Syndrome (SJS), Toxic  
Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP) have been  
reported with docetaxel use. Patients should be informed about the signs and symptoms of serious  
skin manifestations and closely monitored. If signs and symptoms suggestive of these reactions  
appear discontinuation of docetaxel should be considered.  
Fluid retention:  
A premedication consisting of a corticosteroid, such as oral dexamethasone 16 mg per day (e.g. 8 mg  
twice daily) for 3 days, starting one day prior to DOCETAXEL HETERO administration, may reduce  
the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions.  
Patients with severe fluid retention, such as pleural effusion, pericardial effusion and ascites, should  
be monitored closely.  
Respiratory disorders:  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 9 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
Acute respiratory distress syndrome, interstitial pneumonia/ pneumonitis, interstitial lung disease,  
pulmonary fibrosis and respiratory failure have been reported and may be associated with fatal  
outcome. Cases of radiation pneumonitis have been reported in patients receiving concomitant  
radiotherapy.  
If new or worsening pulmonary symptoms develop, patients should be closely monitored, promptly  
investigated, and appropriately treated. Interruption of DOCETAXEL HETERO therapy is  
recommended until diagnosis is available. Early use of supportive care measures may help improve  
the condition. The benefit of resuming DOCETAXEL HETERO treatment must be carefully evaluated.  
Liver impairment:  
In patients treated with DOCETAXEL HETERO at 100 mg/m2 who have serum transaminase levels  
(ALT and/or AST) greater than 1,5 times the upper limit of the normal range (ULN) concurrent with  
serum alkaline phosphatase levels greater than 2,5 times ULN, there is a higher risk of developing  
severe adverse reactions, such as toxic deaths, including sepsis and gastrointestinal haemorrhage  
which can be fatal, febrile neutropenia, infections, thrombocytopenia, stomatitis and asthenia.  
Therefore, the recommended dose of DOCETAXEL HETERO in patients with elevated liver function  
tests (LFTs) is 75 mg/m2 and LFTs should be measured at baseline and before each cycle (see  
section 4.2).  
For patients with serum bilirubin levels > ULN and/or ALT and AST > 3,5 times the ULN concurrent  
with serum alkaline phosphatase levels > 6 times the ULN, no dose-reduction can be recommended,  
and DOCETAXEL HETERO should not be used unless strictly indicated.  
Nervous system:  
The development of severe peripheral neurotoxicity, including paraesthesia, dysaesthesia and pain,  
has been observed in patients and requires a reduction of dose. When symptoms persist, treatment  
should be stopped.  
Elderly:  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 10 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
An analysis of safety data in patients equal to or greater than 60 years of age treated with docetaxel  
and capecitabine combination therapy showed an increase in the incidence of treatment-related  
serious adverse events and early withdrawals from treatment due to adverse events compared to  
patients less than 60 years of age. In patients treated with docetaxel every three weeks the incidence  
of anaemia, infection, nail changes, anorexia, and weight loss occurred at rates > 10 % higher in  
patients who were 65 years of age.  
Cardiac toxicity:  
Heart failure has been observed in patients receiving docetaxel in combination with trastuzumab,  
particularly following anthracycline (doxorubicin or epirubicin)-containing chemotherapy. This may be  
moderate to severe and has been associated with death (see section 4.8).  
When patients are candidates for treatment with DOCETAXEL HETERO in combination with  
trastuzumab, they should undergo baseline cardiac assessment. Cardiac function should be further  
monitored during treatment (e.g. every three months) to help identify patients who may develop  
cardiac dysfunction.  
Ventricular dysrhythmia including ventricular tachycardia (sometimes fatal) has been reported in  
patients treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/ or  
cyclophosphamide (see section 4.8).  
Baseline cardiac assessment is recommended.  
Eye disorders:  
Cystoid macular oedema (CMO) has been reported in patients treated with docetaxel. Patients with  
impaired vision should undergo a prompt and complete ophthalmologic examination. In case CMO is  
diagnosed, DOCETAXEL HETERO treatment should be discontinued and appropriate treatment  
initiated (see section 4.8).  
Second primary malignancies:  
Second primary malignancies have been reported when docetaxel was given in combination with  
anticancer treatments known to be associated with second primary malignancies. Second primary  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 11 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
malignancies (including acute myeloid leukaemia, myelodysplastic syndrome and non-Hodgkin  
lymphoma) may occur several months or years after DOCETAXEL HETERO-containing therapy.  
Patients should be monitored for second primary malignancies (see section 4.8).  
Tumour Lysis Syndrome:  
Tumour lysis syndrome has been reported with docetaxel after the first or the second cycle (see  
section 4.8). Patients at risk of tumour lysis syndrome (e.g. with renal impairment, hyperuricemia,  
bulky tumour, rapid progression) should be closely monitored. Correction of dehydration and  
treatment of high uric acid levels are recommended prior to initiation of treatment.  
Others:  
Contraceptive measures must be taken by both men and women during and for at least six months  
after cessation of therapy.  
Additional cautions for use in adjuvant treatment of breast cancer:  
Complicated neutropenia:  
For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia of  
infection) G-CSF and dose reduction should be considered.  
Gastrointestinal reactions:  
Symptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without  
neutropenia, may be early manifestations of serious gastrointestinal toxicity and should be evaluated  
and treated promptly.  
Congestive heart failure (CHF):  
Patients should be monitored for symptoms of congestive heart failure during therapy and during  
follow up period. In patients treated with docetaxel, doxorubicin and cyclophosphamide (TAC) regimen  
for node positive breast cancer, the risk for CHF has been shown to be higher during the first year  
after treatment.  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 12 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
Leukaemia:  
In the docetaxel, doxorubicin and cyclophosphamide (TAC) treated patients, the risk of delayed  
myelodysplasia or myeloid leukaemia requires haematological follow-up.  
Patients with 4+ nodes:  
As the benefit observed in patient with 4+ nodes was not statistically significant on disease-free  
survival (DFS) and overall survival (OS), the positive benefit/risk ratio for TAC with 4+ nodes was not  
fully demonstrated at the final analysis.  
DOCETAXEL HETERO contains Ethanol:  
This medicine contains 0,5 mg Dehydrated alcohol (ethanol) in each vial. These effects may include  
feeling sleepy and changes in behaviour. It may also affect their ability to concentrate and take part in  
physical activities.  
4.5 Interaction with other medicines and other forms of interaction  
There have been no formal studies to evaluate the interactions of docetaxel.  
In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant  
administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the  
enzyme competitively) cytochromeP450-3A such as ciclosporin, ketoconazole, troleandomycin and  
erythromycin. As a result, caution should be exercised when treating patients with these medicines as  
concomitant therapy since there is a potential for a significant interaction.  
In case of combination with CYP3A4 inhibitors, the occurrence of DOCETAXEL HETERO adverse  
reactions may increase, as a result of reduced metabolism. The concomitant  
use of docetaxel with strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, clarithromycin,  
indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole) should be  
avoided.  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 13 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
Docetaxel is highly protein bound (> 95 %). Although the possible in vivo interaction of DOCETAXEL  
HETERO with concomitantly administered medicines has not been investigated formally, in vitro  
interactions with tightly protein-bound medicines such as erythromycin, diphenhydramine, propranolol,  
propafenone, phenytoin, salicylate, sulfamethoxazole and sodium valproate did not affect protein  
binding of docetaxel. In addition, dexamethasone did not affect protein binding of docetaxel.  
Docetaxel did not influence the binding of digitoxin.  
The pharmacokinetics of DOCETAXEL HETERO, doxorubicin and cyclophosphamide were not  
influenced by their co-administration.  
In the doxorubicin/docetaxel combination, the clearance of docetaxel was increased. Sorafenib may  
increase systemic exposure of docetaxel. An increased incidence of febrile neutropenia and  
gastrointestinal disorders, including fatalities, was reported in patients given docetaxel with  
doxorubicin, although others considered this high incidence unrepresentative of usual toxicity rates  
with this combination.  
Limited data suggests an interaction between docetaxel and carboplatin. When combined with  
docetaxel, the clearance of carboplatin was about 50 % higher than values previously reported for  
carboplatin monotherapy.  
4.6 Fertility, pregnancy and lactation  
Women of childbearing potential / Contraception in males and females:  
An effective method of contraception should be used by both men and women during treatment and  
for at least 6 months after cessation of treatment.  
Pregnancy and Breastfeeding:  
Pregnancy and breastfeeding are contra-indications to the use of DOCETAXEL HETERO, as  
DOCETAXEL HETERO is teratogenic in animals (see section 4.3 and 4.4).  
Fertility:  
Men being treated with docetaxel are advised not to father a child during and up to 6 months after  
treatment and to seek advice on conservation of sperm prior to treatment.  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 14 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
4.7 Effects on ability to drive and use machines  
To avoid accidents, patients should be advised to exercise caution when driving or operating  
machinery if they develop dizziness, fatigue or weakness. DOCETAXEL HETERO may also cause  
visual disturbances and loss of consciousness, which can affect the ability to drive or use machines.  
4.8 Undesirable effects  
Summary of the safety profile:  
The most frequently reported adverse reactions with docetaxel are neutropenia, anaemia, alopecia,  
nausea, vomiting, stomatitis, diarrhoea and asthenia. The severity of adverse events of docetaxel may  
be increased when it is given in combination with other chemotherapeutic medicines.  
Tabulated summary of adverse reactions:  
System organ  
classes  
Frequency  
Adverse event  
Blood and lymphatic Frequent  
system disorders  
Bone marrow suppression and other haematological  
adverse reactions include neutropenia, febrile  
neutropenia,  
thrombocytopenia,  
anaemia  
and  
infections. Neutropenia is reversible and not  
cumulative. The median time to nadir is 7 days and the  
median duration of severe neutropenia (< 500  
cells/mm3) is 7 days. Fever in absence of infection,  
has been reported in patients with non-small cell lung  
cancer.  
Less frequent Bleeding episodes have occurred and were rarely  
associated with severe thrombocytopenia (< 50 000  
cells/mm3)  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 15 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
System organ  
classes  
Frequency  
Adverse event  
Immune  
system Frequent  
Hypersensitivity reactions may occur, usually within a  
few minutes following the start of the infusion of  
DOCETAXEL HETERO and are mostly mild to  
moderate.  
disorders  
Symptoms are flushing, rash with or without pruritus,  
chest tightness, back pain, dyspnoea and drug fever  
or chills.  
Severe reactions characterised by hypotension and/or  
bronchospasm  
or  
generalised  
rash/erythema,  
requiring therapeutic intervention, may occur. These  
may resolve after discontinuation of the infusion and  
institution of appropriate therapy.  
Metabolism  
and Less frequent Fluid accumulation: Peripheral oedema, pleural  
effusion,  
nutrition disorders  
pericardial effusion, ascites, increased capillary  
permeability and weight gain, have been reported. The  
peripheral oedema usually starts at the lower  
extremities and may become generalised with a  
weight gain of 3 kg or more after 4 cycles or a  
cumulative dose ≥ 400 mg/m2. Fluid retention is  
cumulative in incidence and severity.  
The onset of moderate and severe retention is delayed  
in patients with premedication compared with patients  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 16 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
System organ  
classes  
Frequency  
Adverse event  
without premedication. However, it has been reported  
in some patients during the early courses of therapy.  
The median time to fluid retention reversibility is 16,4  
weeks (range 0 to 42 weeks) in patients receiving the  
recommended premedication. Fluid retention has not  
been accompanied by acute episodes of oliguria or  
hypotension.  
Fluid retention has been less frequently reported in  
patients receiving the recommended premedication  
compared with patients without premedication.  
Dehydration and pulmonary oedema have been  
reported.  
Nervous  
system Frequent  
Neurosensory signs characterised by paraesthesia,  
dysaesthesia or pain, including burning, may occur.  
disorders  
Neuromotor  
events,  
mainly  
characterised  
by  
weakness, may occur.  
Cases of convulsion or transient loss of consciousness  
have been observed with DOCETAXEL HETERO  
administration. These reactions may appear during the  
infusion of DOCETAXEL HETERO.  
Eye disorders  
Less frequent Lacrimation, with or without conjunctivitis, individual  
cases of lacrimal duct obstruction resulting in  
excessive tearing, transient visual disturbances  
(flashes, flashing lights, scotomata), typically occurring  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 17 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
System organ  
classes  
Frequency  
Adverse event  
during medicine infusion and in association with  
hypersensitivity reactions.  
Cardiac disorders  
Less frequent Venous thromboembolic events, myocardial infarction,  
and hypertension have been reported.  
Other adverse events include left ventricular  
dysfunction, unstable angina, dysrhythmia, sinus  
tachycardia, atrial flutter or paroxysmal atrial  
tachycardia and hypotension.  
Respiratory,  
thoracic Frequent  
Dyspnoea may occur and is associated with acute  
hypersensitivity reactions, respiratory infections and  
cancerous lung involvement.  
and  
mediastinal  
disorders  
Less frequent Cough and epistaxis. Acute respiratory distress  
syndrome, interstitial pneumonia, pulmonary fibrosis  
and radiation recall phenomena have been reported.  
Gastrointestinal  
disorders  
Frequent  
Gastrointestinal effects, such as nausea, vomiting,  
diarrhoea and abdominal pain, constipation,  
stomatitis, oesophagitis and taste perversion.  
Gastrointestinal bleeding, anorexia.  
Occurrences of dehydration as a consequence of  
gastrointestinal events, gastrointestinal perforation,  
ischaemic colitis, colitis and neutropenic enterocolitis.  
Less frequent Ileus and intestinal obstruction.  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 18 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
System organ  
classes  
Frequency  
Adverse event  
Hepato-biliary  
disorders  
Less frequent Increases in serum levels of AST, ALT, bilirubin and  
alkaline phosphatase greater than 2,5 times ULN,  
hepatitis.  
Skin  
and Frequent  
tissue  
Reversible cutaneous reactions.  
subcutaneous  
disorders  
The cutaneous reactions are characterised by a rash,  
including localised eruptions mainly on the feet and  
hands, but also on the arms, face or thorax, and  
frequently  
associated  
with  
pruritus.  
Eruptions  
generally occurred within one week after the  
DOCETAXEL HETERO infusion.  
Nail disorders may occur. These are characterised by  
hypo- or hyperpigmentation and sometimes pain and  
onycholysis.  
Less frequent Severe symptoms, such as eruptions followed by  
desquamation, may lead  
to  
interruption  
or  
discontinuation of DOCETAXEL HETERO treatment.  
Bullous eruptions, such as erythema multiforme or  
Stevens-Johnson syndrome.  
Musculoskeletal  
connective  
and Frequent  
tissue  
Arthralgia and myalgia.  
disorders  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 19 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
System organ  
classes  
Frequency  
Adverse event  
General disorders and Frequent  
Infusion site reactions are generally mild and consist  
of hyperpigmentation, inflammation, redness or  
dryness of the skin, phlebitis or extravasation and  
swelling of the vein.  
administration  
conditions  
site  
Generalised or localised pain may occur, including  
chest pain without any cardiac or respiratory  
involvement.  
Other side-effects include alopecia and asthenia.  
Tabulated list of adverse reactions in combination therapy with DOCETAXEL HETERO  
System organ  
classes  
Frequency  
Breast cancer for  
docetaxel in  
Breast cancer for  
docetaxel in  
Metastatic  
castration-resistant  
prostate cancer for  
docetaxel in  
combination with  
doxorubicin and  
cyclophosphamide:  
combination with  
capecitabine:  
combination with  
prednisone or  
prednisolone  
Infections  
and Frequent  
Less  
Infection.  
---  
---  
Infection.  
---  
infestations  
Oral candidiasis.  
frequent  
Blood  
and Frequent  
Anaemia,  
---  
Anaemia,  
lymphatic system  
disorders  
neutropenia, fever  
neutropenia.  
in  
absence  
of  
infection,  
thrombocytopenia,  
febrile neutropenia,  
and  
neutropenic  
infection.  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 20 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
System organ  
classes  
Frequency  
Breast cancer for  
docetaxel in  
Breast cancer for  
docetaxel in  
Metastatic  
castration-resistant  
prostate cancer for  
docetaxel in  
combination with  
doxorubicin and  
cyclophosphamide:  
combination with  
capecitabine:  
combination with  
prednisone or  
prednisolone  
Less  
---  
---  
---  
---  
Thrombocytopenia,  
febrile neutropenia.  
---  
frequent  
Immune  
system Frequent  
Hypersensitivity  
reactions.  
---  
disorders  
Less  
frequent  
Allergic reactions.  
Fluid retention.  
Metabolism  
and Frequent  
Peripheral oedema, ---  
and weight gain or  
loss.  
nutrition disorders  
Less  
Lymph oedema.  
Dehydration,  
---  
frequent  
decreased weight.  
Paraesthesia.  
Nervous  
system Frequent  
Sensory  
Sensory neuropathy,  
motor neuropathy.  
disorders  
neuropathy,  
syncope.  
Less  
Neuro-cortical  
Dizziness,  
frequent  
adverse  
events, headache,  
motor neuropathy peripheral  
and  
neuropathy.  
neuro-cerebellar  
adverse events.  
---  
Eye disorders  
Frequent  
Increased  
lacrimation.  
---  
---  
Less  
Lacrimation  
disorder,  
Tearing.  
frequent  
conjunctivitis.  
Cardiac  
Cardiac disorders  
Less  
---  
Left  
dysfunction.  
Lower limb oedema. ---  
ventricular  
frequent  
dysrhythmias.  
Vasodilation.  
Hypotension,  
phlebitis  
Vascular disorders Frequent  
Less  
---  
---  
frequent  
Frequent  
---  
Sore throat.  
---  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 21 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
System organ  
classes  
Frequency  
Breast cancer for  
docetaxel in  
Breast cancer for  
docetaxel in  
Metastatic  
castration-resistant  
prostate cancer for  
docetaxel in  
combination with  
doxorubicin and  
cyclophosphamide:  
combination with  
capecitabine:  
combination with  
prednisone or  
prednisolone  
Respiratory,  
thoracic  
Less  
Cough.  
Dyspnoea, cough, Epistaxis,  
cough,  
and frequent  
and epistaxis. and dyspnoea.  
mediastinal  
disorders  
Gastrointestinal  
disorders  
Frequent  
Anorexia, nausea, Taste disturbance, Epistaxis,  
cough,  
stomatitis,  
vomiting,  
anorexia,  
and dyspnoea.  
decreased appetite,  
diarrhoea,  
perversion,  
constipation.  
taste stomatitis,  
diarrhoea, nausea,  
vomiting,  
constipation,  
abdominal pain, and  
dyspepsia.  
Less  
Abdominal pain.  
Alopecia,  
Upper  
abdominal ---  
frequent  
pain, dry mouth.  
Skin  
and Frequent  
skin Hand-foot  
Alopecia,  
nail  
subcutaneous  
toxicity, and nail syndrome, alopecia, changes.  
tissue disorders  
disorders.  
---  
and nail disorder.  
Less  
Dermatitis,  
erythema,  
rash Rash/desquamation.  
nail  
frequent  
discolouration, and  
onycholysis.  
Musculoskeletal,  
Frequent  
Less  
Myalgia, arthralgia.  
---  
Myalgia, arthralgia.  
Back pain.  
---  
connective tissue  
Myalgia, arthralgia.  
and  
bone  
frequent  
disorders  
Reproductive  
Frequent  
Amenorrhoea.  
---  
---  
system and breast  
disorders  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 22 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
System organ  
classes  
Frequency  
Breast cancer for  
docetaxel in  
Breast cancer for  
docetaxel in  
Metastatic  
castration-resistant  
prostate cancer for  
docetaxel in  
combination with  
doxorubicin and  
cyclophosphamide:  
combination with  
capecitabine:  
combination with  
prednisone or  
prednisolone  
General disorders Frequent  
and administrative  
site conditions  
Less  
Asthenia.  
Asthenia,  
fatigue,  
pyrexia, Fatigue.  
and  
weakness.  
---  
---  
---  
Pain  
in  
limb, ---  
frequent  
lethargy, and pain.  
Neutropenia,  
Investigations  
Frequent  
---  
---  
anaemia.  
Less  
Thrombocytopenia,  
hyperbilirubinaemia.  
frequent  
Description of selected adverse reactions:  
No information available.  
Reporting of side effects  
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 to SAHPRA via the “6.04  
Adverse Drug Reaction Reporting Form”, found online under SAHPRA’s publications:  
https://www.sahpra.org.za/Publications/Index/8 for reporting of side effects to the Holder of Certificate  
of Registration email pvg.cdma@heterodrugs.com.  
4.9 Overdose  
In case of overdose, the patient should be kept in a specialised unit and vital functions closely  
monitored. There is no known antidote for DOCETAXEL HETERO overdosage. The primary  
anticipated complications of overdosage would consist of neutropenia, mucositis, cutaneous reactions  
and paraesthesia.  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 23 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. Other  
appropriate symptomatic measures should be taken, as needed.  
5. PHARMACOLOGICAL PROPERTIES  
Category and class: A 26 Cytostatic agents.  
Pharmacotherapeutic group: Antineoplastic agents, plant alkaloids and other natural products,  
Taxanes, ATC Code: L01CD02  
5.1 Pharmacodynamic properties  
Docetaxel is an antineoplastic medicine which acts by promoting the assembly of tubulin into stable  
microtubules and by inhibiting their disassembly, which leads to a marked decrease in free tubulin.  
The binding of docetaxel to microtubules does not alter the number of protofilaments.  
Docetaxel has been shown in vitro to disrupt the microtubular network in cells, which is essential for  
vital mitotic and interphase cellular functions. Docetaxel was found to be cytotoxic in vitro against  
various murine and human tumour cell lines and against freshly excised human tumour cells in  
clonogenic assays.  
Docetaxel achieves high intracellular concentrations with a long cell residence time. In addition,  
docetaxel was found to be active on some, but not all, cell lines over-expressing the paraglycoprotein  
which is encoded by the multidrug resistance gene. In vivo, docetaxel is schedule independent.  
5.2 Pharmacokinetic properties  
Absorption:  
The pharmacokinetics of docetaxel have been evaluated in cancer patients after administration of 20-  
115 mg/m2 in phase I studies. The kinetic profile of docetaxel is dose independent and consistent with  
a three-compartment pharmacokinetic model with half-lives for the α, β and γ phases of 4 min, 36 min  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 24 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
and 11,1 h, respectively. The late phase is due, in part, to a relatively slow efflux of docetaxel from the  
peripheral compartment.  
Distribution:  
Following the administration of a 100 mg/m2 dose given as a one-hour infusion a mean peak plasma  
level of 3,7 μg/ml was obtained with a corresponding AUC of 4,6 h.μg/ml. Mean values for total body  
clearance and steady-state volume of distribution were 21 l/h/m2 and 113 L, respectively. Inter  
individual variation in total body clearance was approximately 50 %. Docetaxel is more than 95 %  
bound to plasma proteins.  
Elimination:  
Faecal excretion is the main route of elimination of docetaxel and its metabolites. Faecal and urinary  
excretions account for about 75 % and 6 % of the dose, respectively. Only a minor fraction of the dose  
is excreted as the parent compound. About 80 % of the radioactivity recovered in faeces is excreted in  
the first 48 hours as one major inactive metabolite and 3 minor inactive metabolites. Based on in vitro  
studies, isoenzymes of the cytochrome P450-3A subfamily appear to be involved in docetaxel  
metabolism.  
Clearance is primarily through CYP3A4 and CYP3A5 mediated hydroxylation, leading to inactive  
metabolites. Dexamethasone did not affect protein binding of docetaxel. When used in combination,  
docetaxel does not influence the clearance of doxorubicin and the plasma levels of doxorubicinol (a  
doxorubicin metabolite). However, the clearance of docetaxel was increased.  
Clearance of docetaxel in combination therapy with cisplatin was similar to that observed following  
monotherapy. The pharmacokinetic profile of cisplatin administered shortly after docetaxel infusion is  
similar to that observed with cisplatin  
alone.  
Studies evaluating the effect of capecitabine on the pharmacokinetics of docetaxel and vice versa  
showed no effect by capecitabine on the pharmacokinetics of docetaxel (Cmax and AUC) and no  
effect by docetaxel on the pharmacokinetics of the main capecitabine metabolite 5’-DFUR.  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 25 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
No effect on the pharmacokinetics of docetaxel was observed in a study of the effect of prednisone on  
the pharmacokinetics of docetaxel administered with standard dexamethasone premedication.  
6. PHARMACEUTICAL PARTICULARS  
6.1 List of excipients  
Polysorbate 80 (Montanox 80 LPI),  
Dehydrated alcohol (Ethanol) 100986 and,  
Nitrogen.  
6.2 Incompatibilities  
N/A  
6.3 Shelf life  
24 months  
6.4 Special precautions for storage  
Unopened vials should be stored between 2 °C and 8 °C, protected from bright light in the original  
package.  
Freezing does not adversely affect the product.  
The DOCETAXEL HETERO premix solution (10 mg docetaxel/ml) is stable for 8 hours in a  
refrigerator or at room temperature (at or below 25°C).  
The DOCETAXEL HETERO infusion solution must be administered as soon as possible after  
preparation.  
Discard any unused solution  
KEEP OUT OF REACH AND SITE OF CHILDREN.  
6.5 Nature and contents of container  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 26 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
DOCETAXEL HETERO 20 mg / mL:  
1x 5ml Glass Vial. 5 ml Clear tubular glass Vial with a 20 mm Serum GCB Rubber Stopper with  
Flurotec coating and a Blue Aluminium flip off seal.  
DOCETAXEL HETERO 80 mg / 4mL:  
1x 5ml Glass Vial. 5 ml Clear tubular glass Vial with a 20 mm Serum GCB Rubber Stopper with  
Flurotec coating and a White Aluminium flip off seal.  
DOCETAXEL HETERO 160 mg / 8mL:  
1x 5ml Glass Vial. 5 ml Clear tubular glass Vial with a 20 mm Serum GCB Rubber Stopper with  
Flurotec coating and a White Aluminium flip off seal.  
6.6 Special precautions for disposal and other handling  
Preparation of the solution for infusion:  
More than one vial of DOCETAXEL HETERO 20 mg/mL, 80 mg/4mL and 160 mg/8mL concentrate  
for solution for infusion may be necessary to obtain the required dose for the patient. Based on the  
required dose for the patient expressed in mg, aseptically withdraw the corresponding volume of 20  
mg/1 ml DOCETAXEL HETERO from the appropriate number of vials using graduated syringes fitted  
with a needle. For example, a dose of 160 mg docetaxel would require 8 ml of DOCETAXEL  
HETERO 20 mg/ml concentrate for solution for infusion.  
For doses below 192 mg of docetaxel, inject the required volume of DOCETAXEL HETERO 20 mg/  
1ml concentrate for solution for infusion into a 250 ml infusion bag or bottle containing either 250 ml of  
50 mg/ml (5 %) glucose solution for infusion or 9 mg/ml (0,9 %) sodium chloride solution for infusion.  
For doses exceeding 192 mg of DOCETAXEL HETERO more than 250 ml of the infusion solution is  
required, as a maximum concentration of DOCETAXEL HETERO is 0,74 mg per ml of infusion  
solution.  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 27 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
Mix the infusion bag or bottle manually using a rocking motion. The diluted solution be used within 8  
hours and should be aseptically administered as a 1-hour infusion at room temperature and normal  
lighting conditions. The total duration of manipulation from start of the preparation of the bag to the  
end of the infusion must not exceed 4 hours. Discard any unused solution.  
Recommendations for safe handling:  
Handling precautions for cytostatic agents should be followed:  
•
•
Only trained personnel should reconstitute the agent in a designated area.  
DOCETAXEL HETERO is an antineoplastic agent and, as with other potentially toxic compounds,  
caution should be exercised when handling it and preparing DOCETAXEL HETERO solutions.  
The work surface should be covered with disposable plastic-backed absorbent paper.  
Adequate protective gloves and clothing should be worn.  
•
•
•
If DOCETAXEL HETERO concentrate, premix solution or infusion solution should come into  
contact with the skin, wash immediately and thoroughly with soap and water. If DOCETAXEL  
HETERO concentrate, premix solution or infusion solution should come into contact with the eyes  
or mucous membranes wash immediately and thoroughly with water.  
•
•
The cytotoxic preparation must not be handled by pregnant staff.  
Adequate care and precautions should be taken in the disposal of items used to reconstitute the  
medicine.  
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.  
Tell: 012 644 1220.  
Email address: Nokuthula.n@heterodrugs.com  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 28 of 29  
Applicant/ PHCR: Hetero Drugs South Africa (Pty) Ltd  
Product Proprietary Name: DOCETAXEL xx HETERO  
Dosage Form and Strength: Solution for infusion. Each Vial contains 20mg/mL, 80mg/4mL, and 160mg/8mL of  
Docetaxel  
Date of final pi-pil approval: Clinical Approval: 6 Dec 2023 & PEM Approval response: 3 Jan 2024  
Registration Notification date: 30 July 2024  
8. REGISTRATION NUMBER(S)  
DOCETAXEL 20 mg/mL HETERO: 56/26/0759.756  
DOCETAXEL 80 mg/4 mL HETERO: 56/26/0760.757  
DOCETAXEL 160 mg/8 mL HETERO: 56/26/0761.758  
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION  
30 July 2024  
10. DATE OF REVISION OF THE TEXT  
N/A  
Final pi-pil approval: 3 Jan 2024 (30 July 2024)  
Initial: RJ  
Page 29 of 29