Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
Lines  
1.  
PROPOSED PROFESSIONAL INFORMATION FOR NUVITAB 100 AND 400  
References  
SCHEDULING STATUS  
S4  
2.  
3.  
4.  
5.  
6.  
7.  
8.  
9.  
1 NAME OF THE MEDICINE  
NUVITAB 100 (film coated tablets)  
NUVITAB 400 (film coated tablets)  
2 QUALITATIVE AND QUANTITATIVE COMPOSITION  
NUVITAB 100: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg.  
NUVITAB 400: Each film coated tablet contains Imatinib mesylate equivalent to 400 mg.  
NUVITAB is sugar-free.  
10.  
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12.  
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For the full list of excipients see Section 6.1  
3 PHARMACEUTICAL FORM  
NUVITAB 100: White to off white coloured, round, bevel edged scored tablets  
debossed with H on one side and 19 on the other side, 1 and 9 separated by a score line.  
NUVITAB 400: White to off white coloured, capsule shaped, bevel edged scored  
film coated tablets, debossed with H on one side and 20 on the other side, 2 and 0  
separated by a score line.  
4 CLINICAL PARTICULARS  
4.1 Therapeutic indications  
•
NUVITAB is indicated for the treatment of patients with newly diagnosed  
Philadelphia chromosome positive chronic myeloid leukaemia (CML) as well as for  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
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the treatment of patients with CML in blast crisis, accelerated phase, or in chronic  
phase after failure of interferon-alpha therapy.  
•
•
NUVITAB is also indicated for the treatment of adult patients with  
unresectable and/or metastatic malignant gastrointestinal stromal tumours (GIST).  
The effectiveness of NUVITAB is based on overall haematologic and  
cytogenetic response rates and progression-free survival in CML and objective  
response rates in GIST (see section 5.1). Safety and efficacy have not been  
demonstrated for more than 14 months in first-line therapy of CML. There are no  
controlled trials demonstrating increased survival  
4.2 Posology and method of administration  
Posology  
Therapy should be initiated by a medical practitioner experienced in the treatment of  
patients with chronic myeloid leukaemia or GIST respectively.  
Dosage in CML:  
The recommended dosage of NUVITAB is 400 mg/day for patients in chronic  
phase CML and 600 mg/day for patients in accelerated phase or blast crisis.  
Treatment should be continued as long as the patient continues to benefit.  
Dose increase from 400 mg to 600 mg in patients with chronic phase disease, or from 600  
mg to a maximum of 800 mg (given as 400 mg twice daily) in patients in accelerated  
phase or blast crisis may be considered in the absence of severe adverse drug reaction  
and severe non-leukaemia-related neutropenia or thrombocytopenia in the following  
circumstances: disease progression (at any time); failure to achieve a satisfactory  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
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haematological response after at least 3 months of treatment; loss of a previously  
achieved haematological response.  
Dosing in children should be on the basis of body surface area (mg/m2). Doses of 260  
mg/m2 and340 mg/m2 daily are recommended for children with chronic phase CML and  
advanced phases CML, respectively. However, the total daily dose in children should not  
exceed adult equivalent doses of 400 and 600 mg, respectively. Treatment can be given  
as a once daily dose or alternatively the daily dose may be split into two administrations –  
one in the morning and one in the evening. The dose recommendation is currently based  
on a small number of paediatric patients (see sections 5.1 and 5.2). There is no  
experience with the use of NUVITAB in children below 3 years of age.  
Dosage in GIST:  
The recommended dose of NUVITAB is 400 mg/day for patients with  
unresectable and/or metastatic, malignant GIST. A dose increase from 400 mg to 600 mg  
for patients may be considered in the absence of adverse medicine reactions if  
assessments demonstrate an insufficient response to therapy. Treatment with [PRODUCT  
NAME] in GIST patients should be continued until disease progression. Dose  
adjustments for adverse reactions in CML and GIST patients.  
Non-haematological adverse reactions:  
If a severe non-haematological adverse reaction develops with NUVITAB use,  
treatment must be withheld until the event has resolved. Thereafter, treatment can be  
resumed as appropriate depending on the initial severity of the event.  
If elevation in bilirubin >3x institutional upper limit of normal (IULN) or liver transaminases  
>5x IULN occur, NUVITAB should be withheld until bilirubin levels are returned  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
78.  
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to < 1.5 x IULN and transaminase levels to < 2.5 x IULN. Treatment with [PRODUCT  
NAME] may then be continued at a reduced daily dose. In adults the dose should be  
reduced from 400 to 300 mg or from 600 to 400 mg, or from 800 mg to 600 mg, and in  
children from 340 to 260 mg/m2/day.  
Haematological adverse reactions:  
Dose reduction or treatment interruption for severe neutropenia and thrombocytopenia are  
recommended as indicated in table below.  
Dose adjustments for neutropenia and thrombocytopenia:  
Chronic  
phase CML  
(Starting dose 400  
ANC < 1,0 x  
109/L and  
1. Stop NUVITAB until ANC ≥ 1,5 x 109/L  
and platelets ≥ 75 x 109/l.  
platelets  
2. Resume treatment with NUVITAB at  
dose of 400 mg2.  
mg2  
< 50 x 109/L  
3. In the event of recurrence of ANC < 1.0  
x109/l and/or platelets < 50 x109/l,  
repeat step 1 and resume NUVITAB at  
reduced dose of 300 mg4.  
Accelerated  
phase CML  
and blast  
crisis  
ANC < 0,5 x  
109/L and or  
platelets  
1. Check whether cytopenia is related to  
leukaemia (marrow aspirate or biopsy).  
2. If cytopenia is unrelated to leukaemia,  
reduce dose of NUVITAB to 400 mg2.  
3. If cytopenia persists for 2 weeks, reduce  
further to 300 mg4.  
< 10 x 109/L  
(starting  
dose 600  
mg3)  
4. If cytopenia persists for 4 weeks and is  
still unrelated to leukaemia, stop  
NUVITAB until ANC ≥ 1 x109/l and  
platelets ≥ 20 x109/l, then resume  
treatment at 300 mg4.  
ANC = absolute neutrophil count  
1occurring after at least 1 month of treatment  
2 or 260 mg/m2 in children  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
104.  
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123.  
124.  
125.  
126.  
127.  
128.  
129.  
3 or 340 mg/m2 in children  
4 or 200 mg/m2 in children  
Special populations  
Hepatic insufficiency  
Since no clinical studies were conducted with NUVITAB in patients with  
decreased liver function, no specific advice concerning dosing adjustment can be given.  
Since imatinib is mainly metabolised through the liver, exposure to NUVITAB  
is expected to increase if liver function is impaired and NUVITAB should be used  
with caution in patients with hepatic impairment (see sections 4.4 and 4.8).  
Renal insufficiency  
Imatinib and its metabolites are not significantly excreted via the kidney. Since the renal  
clearance of imatinib is negligible, a decrease in total body clearance is not expected in  
patients with renal insufficiency. However, in severe renal insufficiency caution is  
recommended.  
Elderly patients  
No significant age related pharmacokinetic differences have been observed in adult  
in clinical trials, which included over 20 % of patients age 65 and older. No specific dose  
recommendation is necessary in the elderly.  
Children:  
There is no experience with the use of NUVITAB in children below 3 years of  
age.  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
130.  
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149.  
150.  
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154.  
155.  
Method of administration:  
The prescribed dose should be administered orally, once daily with a meal and a large  
glass of water. For patients unable to swallow the film-coated tablets, the tablets may be  
dispersed in a glass of water or apple juice. The required number of tablets should be  
placed in the appropriate volume of beverage (approximately 50 ml for a 100 mg tablet,  
and 200 ml for a 400 mg tablet) and stirred with a spoon. The suspension should be  
administered immediately after complete disintegration of the tablet(s)  
4.3 Contraindications  
NUVITAB is contraindicated in those patients with a known hypersensitivity to  
imatinib or any of the excipients.  
The safety in pregnancy and lactation has not been established (see section 4.6).  
4.4 Special warnings and precautions for use  
Cerebrovascular adverse events  
Cerebrovascular adverse events identified as class related adverse events have  
occurred in patients treated with tyrosine kinase inhibitor (TKI) containing medicines.  
These class related cerebrovascular adverse events, shared to a variable degree by all  
TKIs including imatinib, are cerebrovascular accident (CA), transient ischaemic attack  
(TIA), ischaemic stroke (IS), and cerebral infarction (CI. These cerebrovascular events  
may occur in patients on treatment with TKIs with or without risk factors for these  
events and may occur at any time during treatment with TKIs.  
Patients on treatment with TKI containing medicine should be carefully monitored, and  
relevant risk factors managed to reduce the risk for these class related cerebrovascular  
adverse events.  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
156.  
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180.  
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Treatment with TKI containing medicines should be discontinued, and alternative  
treatment options be considered in patients who develop these class related  
cerebrovascular adverse events.  
Patients with cardiac disease:  
Patients with cardiac disease, risk factors for cardiac failure or history of renal failure  
should be monitored carefully, and any patient with signs or symptoms consistent with  
cardiac or renal failure should be evaluated and treated.  
In patients with hypereosinophilic syndrome (HES) with occult infiltration of HES cells  
within the myocardium, isolated cases of cardiogenic shock/left ventricular dysfunction  
have been associated with HES cell degranulation upon the initiation of imatinib  
therapy.The condition was reported to be reversible with the administration of systemic  
steroids,circulatory support measures and temporarily withholding imatinib. A careful  
assessment of the benefit/risk of imatinib therapy should be considered in the  
HES/CEL population before treatment initiation.  
Myelodysplastic/myeloproliferative diseases with PDGFR gene re-arrangements could  
be associated with high eosinophil levels. Evaluation by a cardiology specialist,  
performance of an echocardiogram and determination of serum troponin should  
therefore be considered in patients with HES/CEL, and in patients with MDS  
(Myelodysplastic syndromes)/MPD associated with high eosinophil levels before  
imatinib is administered. If either is abnormal, follow-up with a cardiology specialist and  
the prophylactic use of systemic steroids (1–2 mg/kg) for one to two weeks  
concomitantly with imatinib should be considered at the initiation of therapy.  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
182.  
183.  
184.  
185.  
186.  
187.  
188.  
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195.  
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199.  
200.  
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203.  
204.  
205.  
206.  
207.  
Gastrointestinal effects  
To minimise the risk of gastrointestinal disturbances, NUVITAB should be  
taken with food and a large glass of water (see section 4.2). Co-administration of  
NUVITAB with other medicines may potentially cause interactions (see  
section 4.5).  
Although the aetiology is currently unknown, special caution is required when using  
paracetamol.  
Fluid retention  
Incidences of severe fluid retention (ascites, pleural effusion, pulmonary oedema, and  
oedema) have been reported. It is therefore recommended that patients be weighed at  
regular intervals. Unexpected rapid weight gain calls for careful investigation and  
appropriate supportive care and therapeutic measures should be undertaken as  
necessary. In clinical trials, these events occurred at an increased incidence in elderly  
patients and in those with a past history of cardiac disease.  
Gastrointestinal and intra-tumoural haemorrhages  
Reports from clinical trials showed that 5,4 % of GIST patients had gastrointestinal  
haemorrhage, while 2,7 % of patients were reported to have experienced  
haemorrhages at the site of tumour deposits. The tumour haemorrhages occurred  
either intra-abdominally or intrahepatically, depending on the anatomical location of  
tumour lesions.Gastrointestinal tumour sites may have contributed to reports of  
gastrointestinal haemorrhage in this patient population.  
Hepatic insufficiency:  
Since imatinib is mainly metabolised through the liver, exposure to NUVITAB  
is expected to increase if liver function is impaired and NUVITAB should be  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
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used with caution in patients with hepatic impairment (see section 4.8). In patients with  
hepatic dysfunction (mild, moderate or severe), peripheral blood counts and liver  
enzymes should be carefully monitored (see sections 4.2, 4.8 and 5.2). It should be  
noted that GIST patients may have hepatic metastases which could lead to hepatic  
impairment.  
Cases of liver injury, including hepatic failure and hepatic necrosis, have been  
observed with imatinib. When imatinib is combined with high dose chemotherapy  
regimens, an increase in serious hepatic reactions has been detected. Hepatic function  
should be monitored in circumstances where imatinib is combined with chemotherapy  
regimens also known to be associated with hepatic dysfunction (see sections 4.5 and  
4.8).  
Hypothyroidism:  
Hypothyroidism have been reported in thyroidectomy patients undergoing  
levothyroxine replacement during treatment with NUVITAB (see section 4.5).  
Thyroid stimulating hormone (TSH) levels should be closely monitored in such patients.  
Tumour lysis syndrome:  
Due to the possible occurrence of tumour lysis syndrome (TLS), correction of  
dehydration and treatment of high uric acid levels are recommended prior to initiation  
of NUVITAB (see section 4.8).  
Hepatitis B reactivation:  
Reactivation of hepatitis B in patients who are chronic carriers of this virus has  
occurred after these patients received BCR-ABL tyrosine kinase inhibitors. Some  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
234.  
235.  
236.  
237.  
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239.  
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243.  
244.  
245.  
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resulted in acute hepatic failure or fulminant hepatitis leading to liver transplantation or  
a fatal outcome. Patients should be tested for HBV infection before initiating treatment  
with NUVITAB. Experts in liver disease and in the treatment of hepatitis B  
should be consulted before treatment is initiated in patients with positive hepatitis B  
serology (including those with active disease) and for patients who test positive for  
HBV infection during treatment.Carriers of HBV who require treatment with [PRODUCT  
NAME] should be closely monitored for signs and symptoms of active HBV infection  
throughout therapy and for several months following termination of therapy (see  
section 4.8).  
Laboratory tests:  
It is necessary to regularly perform complete blood counts during NUVITAB  
therapy. NUVITAB treatment has been associated with neutropenia or  
thrombocytopenia. In CML patients. However, the development of these cytopenias is  
dependent on the stage of the disease being treated and they occur more frequently in  
patients with accelerated phase CML or blast crisis as compared to chronic phase CML  
patients. NUVITAB treatment may be interrupted or the NUVITAB  
dose reduced, as per the recommendations under Posology and method of  
administration. Liver function (transaminases, bilirubin, alkaline phosphatase) should  
be monitored regularly in patients receiving NUVITAB.  
In patients with impaired renal function, imatinib plasma exposure seems to be higher  
than that in patients with normal renal function, probably due to an elevated plasma  
level of alpha-acid glycoprotein (AGP), an imatinib-binding protein, in these patients.  
Patients with renal impairment should be given the minimum starting dose. Patients  
with severe renal impairment should be treated with caution. The dose can be reduced  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
260.  
261.  
262.  
263.  
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if not tolerated (see sections 4.2 and 5.2).  
Long-term treatment with imatinib may be associated with a decline in renal function.  
Renal function should, therefore, be evaluated prior to the start of imatinib therapy and  
closely monitored during therapy, with particular attention to those patients exhibiting  
risk factors for renal dysfunction. If renal dysfunction is observed, appropriate  
management and treatment should be prescribed in accordance with standard  
treatment guidelines.  
Phototoxicity  
Exposure to direct sunlight should be avoided or minimised due to the risk of  
phototoxicity associated with imatinib treatment. Patients should be instructed to use  
measures such as protective clothing and sunscreen with high sign protection factor  
(SPF).  
Paediatric population:  
Growth retardation was reported in children and pre-adolescents receiving imatinib. In  
CML paediatric population, a statistically significant decrease in median height  
standard deviation scores after 12 and 24 months of treatment was reported in two  
small subsets irrespective of pubertal status or gender. Close monitoring of growth in  
children under imatinib treatment is recommended (see section 4.8).  
4.5 Interaction with other medicines and other forms of interaction  
Medicines that may alter NUVITAB plasma concentrations:  
Medicines that may increase NUVITAB plasma concentrations: Substances  
that inhibit the cytochrome P450 isoenzyme CYP3A4 activity (e.g. ketoconazole,  
itraconazole, erythromycin, clarithromycin) could decrease metabolism  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
286.  
287.  
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297.  
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and increase NUVITAB concentrations. Caution should be taken when  
administering NUVITAB with inhibitors of the CYP3A4 family.  
Medicines that may alter Imatinib plasma concentrations:  
Substances that inhibit the activity of the cytochrome P450 isoenzyme CYP3A4 activity  
(e.g. protease inhibitors such as indinavir, lopinavir/ritonavir, ritonavir, saquinavir,  
telaprevir, nelfinavir, boceprevir; azole antifungals including ketoconazole,  
itraconazole, posaconazole, voriconazole; certain macrolides such as erythromycin,  
telithromycin and clarithromycin) could reduce metabolism and increase imatinib  
concentrations. Co-administration of NUVITAB with a single dose of ketoconazole  
(a CYP3A4inhibitor) in healthy subjects significantly increases exposure to NUVITAB  
(mean Cmax and AUC + 26 % and + 40 %, respectively). Caution is required when  
NUVITAB is administered with inhibitors of the CYP3A4 family (see section 4.8).  
Grapefruit juice may also cause increases in the plasma concentrations of imatinib, as  
in NUVITAB and should be avoided.  
Medicines that may decrease NUVITAB plasma concentrations:  
Substances that induce CYP3A4 activity, could increase metabolism and decrease  
plasma levels of imatinib. Co-medicines which induce CYP3A4 activity [e.g.  
dexamethasone, carbamazepine, phenytoin, phenobarbitone, rifampicin, fosphenytoin,  
primidone or Hypericum perforatum (also known as St. John's Wort)] may significantly  
decrease exposure to NUVITAB. Coadministration of rifampicin and imatinib  
increased the imatinib oral-dose clearance by 3,8-fold. This represents significant  
reductions in the plasma AUC of 74%. In patients who require rifampicin or other  
CYP3A4 inducers, consideration should be given to alternative therapeutic medicines  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
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with less enzyme induction potential. Concomitant use of rifampicin or other strong  
CYP3A4 inducers and imatinib should be avoided. Similar results were observed in  
patients with malignant gliomas treated with NUVITAB while taking enzyme-  
inducing anti-epileptic medicines (EIAEDs) such as carbamazepine, oxcarbazepine  
and phenytoin. The plasma AUC for imatinib decreased by 37 % compared to patients  
not on EIAEDs.  
Medicines that may have their plasma concentration altered by [PRODUCT  
NAME]:  
The mean Cmax and AUC of simvastatin (CYP3A4 substrate) is increased 2- and 3,5-  
fold, respectively, when given with NUVITAB, indicating that [PRODUCT  
NAME] inhibits CYP3A4. Caution is therefore recommended when NUVITAB  
is given with CYP3A4 substrates with a narrow therapeutic window (e.g. ciclosporin or  
pimozide, tacrolimus, sirolimus, ergotamine, diergotamine, fentanyl, alfentanil,  
terfenadine, bortezomib, docetaxel and quinidine). Patients should be warned to avoid  
or restrict the use of both over-the-counter and prescription medicine containing  
paracetamol.  
Caution should therefore be exercised when using high doses of NUVITAB  
and paracetamol concomitantly.  
NUVITAB may increase plasma concentrations of other medicines  
metabolised by CYP3A4 (such as triazolo benzodiazepines, dihydropyridine calcium  
channel blockers, certain HMG-CoA reductase inhibitors, i.e. statins, etc.). In vitro,  
NUVITAB is also an inhibitor of CYP2C9 and CYP2C19 activity. Prothrombin  
time (PT) prolongation was seen following concurrent administration with warfarin.  
When administering warfarin, short-term PT monitoring is therefore required at the start  
M.R  
October 2021  
Initial: …………….  
Page 13 of 27  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
338.  
339.  
340.  
341.  
342.  
343.  
344.  
345.  
346.  
347.  
348.  
349.  
350.  
351.  
352.  
353.  
354.  
355.  
356.  
357.  
358.  
359.  
360.  
361.  
362.  
363.  
and end of NUVITAB therapy and when the dosage is altered. Alternatively,  
consideration should be given to the use of low-molecular weight heparin. [PRODUCT  
NAME] inhibits cytochrome P450 isoenzyme CYP2D6 activity in vitro at concentrations  
similar to those that influence CYP3A4 activity. There is therefore a potential increase  
in systemic exposure to CYP2D6 substrates when co-administered with [PRODUCT  
NAME]. Although no specific studies have been performed, caution is recommended.  
In Ph+ ALL patients, there is clinical experience of co-administering [PRODUCT  
NAME] with chemotherapy (see section 5.1), but interactions between imatinib and  
chemotherapy regimens are not well characterised. lmatinib adverse events, i.e.  
hepatotoxicity, myelosuppression or others, may increase and it has been reported that  
concomitant use with L-asparaginase could be associated with increased  
hepatotoxicity (see section 4.8). Therefore, the use of NUVITAB in  
combination requires special precaution.  
Simvastatin:  
The mean Cmax and AUC of simvastatin (CYP3A4 substrate) is increased 2 and 3,5-  
fold, respectively, when given with NUVITAB, indicating that [PRODUCT  
NAME] inhibits CYP3A4.  
Food  
Food intake had minimal impact on the absorption rate, therefore NUVITAB,  
can be taken with food (see section 4.2).  
Paediatric population  
Interaction studies have only been performed in adults.  
M.R  
October 2021  
Initial: …………….  
Page 14 of 27  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
364.  
365.  
366.  
367.  
368.  
369.  
370.  
371.  
372.  
373.  
374.  
375.  
376.  
377.  
378.  
379.  
380.  
381.  
382.  
383.  
384.  
385.  
386.  
387.  
388.  
389.  
4.6 Fertility, pregnancy and lactation  
Women of child-bearing potential  
Women of child-bearing potential must be advised to use effective contraception during  
treatment (see section 4.3).  
Pregnancy  
The safety in pregnancy and lactation has not been established.  
Breastfeeding  
It is unknown whether NUVITAB is excreted in human breast milk. A risk to  
the infants cannot be excluded. Breastfeeding should be discontinued during treatment  
with NUVITAB (see section 4.3).  
4.7 Effects on ability to drive and use machines  
Patients are advised that they may experience undesirable effects such as dizziness,  
somnolence, or blurred vision during treatment with NUVITAB (see section  
4.8). Therefore, caution should be recommended when driving a car or operating  
machinery.  
4.8 Undesirable effects  
a. Summary of the safety profile  
The most common side effects of any severity with at least a possible relation to  
NUVITAB are nausea, vomiting, diarrhoea, abdominal pain, abdominal  
distension, dyspepsia, gastro-oesophageal reflux, mouth ulceration, flatulence,  
constipation, headache, dizziness, paraesthesia, taste disturbance, insomnia,  
anorexia, blurred vision, conjunctivitis, increased lacrimation, dry eyes and lower limb  
M.R  
October 2021  
Initial: …………….  
Page 15 of 27  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
390.  
391.  
392.  
393.  
394.  
395.  
396.  
397.  
398.  
399.  
400.  
401.  
402.  
403.  
404.  
405.  
406.  
407.  
408.  
409.  
410.  
411.  
412.  
413.  
414.  
415.  
416.  
oedema (see section 4.4)  
b. Tabulated list of adverse reactions  
Infections and Infestations:  
Less frequent:  
Sepsis, pneumonia, herpes zoster, herpes simplex, upper  
respiratory tract infection, gastroenteritis.  
Neoplasms benign and malignant (including cysts and polyps):  
Less frequent: Intra-tumoural haemorrhage.  
Blood and lymphatic system disorders:  
Frequent:  
Neutropenia, thrombocytopenia, anaemia, febrile neutropenia,  
pancytopenia.  
Less frequent:  
Bone marrow depression, hyperbilirubinemia, eosinophilia,  
lymphadenopathy, lymphopenia, myelosuppression, thrombotic  
microangiopathy  
Immune system disorders:  
Frequent:  
Periorbital oedema.  
Metabolism and nutrition disorders:  
Frequent:  
Anorexia, lower limb oedema.  
Less frequent:  
Dehydration, gout, hyperuricaemia, hypokalaemia,  
hyperkalaemia, hypophosphataemia, increased appetite,  
decreased appetite, hyponatraemia.  
Psychiatric disorders:  
Less frequent:  
Anxiety, depression, decreased libido.  
Nervous system disorders:  
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October 2021  
Page 16 of 27  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
417.  
418.  
419.  
420.  
421.  
422.  
423.  
424.  
425.  
426.  
427.  
428.  
429.  
430.  
431.  
432.  
433.  
434.  
435.  
436.  
437.  
438.  
439.  
440.  
441.  
442.  
443.  
Frequent:  
Headache, dizziness, paraesthesia, taste disturbance,  
insomnia.  
Less frequent·  
Cerebral haemorrhage, peripheral neuropathy, syncope,  
hypoaesthesia, somnolence, migraine, memory impairment,  
cerebral oedema, increased intracranial pressure.  
Eye disorders:  
Frequent:  
Blurred vision, conjunctivitis, increased lacrimation, dry eyes.  
Less frequent:  
Orbital oedema, eye irritation, conjunctival haemorrhage,  
macular oedema, papilloedema, retinal haemorrhage.  
Ear and labyrinth disorders:  
Less frequent:  
Vertigo, tinnitus, hearing loss.  
Cardiac disorders:  
Less frequent:  
Cardiac failure, pulmonary oedema, haematoma, tachycardia,  
hypertension, hypotension, peripheral coldness, flushing.  
Cerebrovascular accident (CA), transient ischaemic attack  
(TIA), ischaemic stroke (IS), and cerebral infarction (CI)  
Frequency  
unknown  
Respiratory, thoracic and mediastinal disorders:  
Frequent:  
Epistaxis, dyspnoea.  
Less frequent:  
Pleural effusion, pharyngolaryngeal pain, cough.  
Gastrointestinal disorders:  
Frequent: Nausea, vomiting, diarrhoea, abdominal pain, abdominal  
distension, dyspepsia, gastro-oesophageal reflux, mouth  
ulceration, flatulence, constipation.  
M.R  
October 2021  
Initial: …………….  
Page 17 of 27  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
444.  
445.  
446.  
447.  
448.  
449.  
450.  
451.  
452.  
453.  
454.  
455.  
456.  
457.  
458.  
459.  
460.  
461.  
462.  
463.  
464.  
465.  
466.  
467.  
468.  
469.  
470.  
Less frequent:  
Gastrointestinal haemorrhage, gastric ulcer, melena, gastritis,  
eruptions, dry mouth, and colitis.  
Hepato-biliary disorders:  
Frequent:  
Increased hepatic enzymes.  
Less frequent:  
Hepatitis, jaundice, hepatic failure, ascites.  
Skin and subcutaneous tissue disorders:  
Frequent:  
Periorbital oedema, dermatitis /eczema, rash, facial oedema,  
eyelid oedema, erythema multiforme, pruritus, dry skin, night  
sweats, alopecia.  
Less frequent:  
Petechiae, purpura, contusion, urticaria, increased sweating,  
onychoclasis, photosensitivity reaction, hypotrichosis, chellitis,  
skin hyperpigmentation, skin hypopigmentation, psoriasis,  
exfoliative dermatitis, bullous eruptions, angioedema, vesicular  
rash, Stevens-Johnson syndrome  
Musculoskeletal, connective tissue and bone disorders:  
Frequent:  
Muscle cramps and spasm, musculoskeletal pain, joint  
swelling.  
Less frequent:  
Sciatica, joint and muscle stillness, myalgia.  
Renal and urinary disorders:  
Less frequent: Renal failure, haematuria, renal pain, increased urinary  
frequency.  
Reproductive system and breast disorders:  
Less frequent: Gynaecomastia, breast enlargement nipple pain, sexual  
dysfunction, scrotal oedema, menorrhagia.  
General disorders and administrative site conditions:  
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October 2021  
Initial: …………….  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
471.  
472.  
473.  
474.  
475.  
476.  
477.  
478.  
479.  
480.  
481.  
482.  
483.  
484.  
485.  
486.  
487.  
488.  
489.  
490.  
491.  
492.  
493.  
494.  
495.  
496.  
Frequent:  
Fluid retention and oedema, fatigue, pyrexia, weakness,  
rigors.  
Less frequent:  
Haemorrhage, malaise, anasarca.  
Investigations:  
Frequent:  
Increased weight.  
Less frequent:  
Weight decreased, increased blood alkaline phosphatase,  
increased blood creatinine phosphokinase, increased blood  
lactate dehydrogenase, blood amylase increased, liver  
transaminase increased.  
c. Description of selected adverse reactions  
Laboratory test abnormalities:  
In all studies in patients with CML cytopenias, particularly neutropenia and  
thrombocytopenia, were consistently observed, with the suggestion of a higher  
frequency at higher doses > 750 mg. However, the development cytopenias is also  
evidently dependent on the disease stage. Cytopenias occur less frequently in patients  
with newly diagnosed CML than in the older CML patients. Grade 3 or 4 neutropenia’s  
(ANC < 1,0x109/l) and thrombocytopenia (platelet count< 50 x 109 /l) occur at a  
frequency between 4 and 8 times higher in patients with blast crisis and accelerated  
phase (58 to 82 % and 42 to 58 % for neutropenia and thrombocytopenia, respectively)  
as compared to newly diagnosed patients in chronic phase CML (14 % neutropenia  
and 7 % thrombocytopenia). In patients with newly diagnosed chronic phase CML  
grade 4 neutropenia (ANC < 0,5 x 109/l) and thrombocytopenia (platelet count <10 x  
109/l) were detected in 2 % and < 1 % of patients, respectively. The median duration of  
neutropenic episodes usually ranges from 2 to 3 weeks and thrombocytopenic  
M.R  
October 2021  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
497.  
498.  
499.  
500.  
501.  
502.  
503.  
504.  
505.  
506.  
507.  
508.  
509.  
510.  
511.  
512.  
513.  
514.  
515.  
516.  
517.  
518.  
519.  
520.  
521.  
522.  
episodes usually range from 3 to 4 weeks. These events can usually be managed with  
either a reduction in the dose or temporary withdrawal of NUVITAB  
treatment, but in rare cases may require permanent discontinuation of treatment.  
In GIST patients, grade 3 and 4 anaemia ware reportedly observed in 3,4 % and 0,7 %  
of patients, respectively. Anaemia may have been related to gastrointestinal or  
intratumoural haemorrhage in at least some of these patients. Grade 3 and 4  
neutropenia was observed in 4, 1 % and 3,4 % of patients, respectively, while 0,7 % of  
patients displayed grade 3 thrombocytopenia. Grade 4 thrombocytopenia was not  
observed in any patient. These reductions in WBC and neutrophil counts occurred  
mostly during the first six weeks of treatment, with values remaining relatively stable  
thereafter.  
Biochemistry:  
Severe elevation of transaminases or bilirubin occurred less frequently (< 3 % of  
patients) and was mostly managed with dose reduction or interruption (the median  
duration of such episodes was about one week). Permanent discontinuation of  
treatment due to liver laboratory abnormalities occurred in less than 0,5 % of patients.  
However, one patient with accelerated phase died of acute hepatic failure in which a  
medicine interaction with high doses of paracetamol could not be formally excluded  
(see section 4.5).  
d. Paediatric population  
Safety and efficacy have not been established in children below 3 years of age.  
e. Other special populations  
Gender/age  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
523.  
524.  
525.  
526.  
527.  
528.  
529.  
530.  
531.  
532.  
533.  
534.  
535.  
536.  
537.  
538.  
539.  
540.  
541.  
542.  
543.  
544.  
545.  
546.  
547.  
548.  
There was no apparent difference in the safety profile of NUVITAB  
concerning gender or age.  
Post marketing surveillance  
Not applicable  
Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicine is important. It  
allows continued monitoring of the risk/benefit ratio of the medicine. Healthcare providers  
are asked to report any suspected adverse reactions to SAHPRA via ‘6.04 Adverse Drug  
Reactions Form’ available online under SAHPRA’s publications at  
https://www.sahpra.org.za/documents/12e54dcaADRForms.pdf or to the Holder of  
Certificate of Registration through the mail, pvg.cdma@heterodrugs.com. By reporting  
adverse reactions you can help provide more information on the safety of [PRODUCT  
NAME].  
4.9 Overdose  
A patient with myeloid blast crisis who inadvertently took imatinib, as in [PRODUCT  
NAME], 1200 mg for 6 days developed grade 1 elevations of serum creatinine, grade 2  
ascites and elevated liver transaminase concentration, and grade 3 bilirubin elevations.  
Therapy was temporarily suspended and all abnormalities resolved completely within  
one week. Treatment was re-instated al a dose of 400 mg without recurrence of  
adverse events.  
Treatment:  
Should over dosage occur, the patient requires observation and appropriate supportive  
treatment should be provided.  
M.R  
October 2021  
Initial: …………….  
Page 21 of 27  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
549.  
550.  
551.  
552.  
553.  
554.  
555.  
556.  
557.  
558.  
559.  
560.  
561.  
562.  
563.  
564.  
565.  
566.  
567.  
568.  
569.  
570.  
571.  
572.  
573.  
574.  
5 PHARMACOLOGICAL PROPERTIES  
5.1 Pharmacodynamic properties  
A 34 Other  
Pharmacotherapeutic group: protein-tyrosine kinase inhibitor, ATC code: L01XE01  
Mechanism of action:  
Imatinib is a protein-tyrosine kinase inhibitor that potently inhibits the activity of the region-  
Abelson (Bcr-Abl) tyrosine kinase at the in vitro, cellular and in vivo levels.  
In vitro, imatinib selectively inhibits proliferation and induces apoptosis in Bcr-Abl positive  
line cells as well as fresh leukaemia cell cultures from patients with the Philadelphia  
chromosome abnormality in chronic myeloid leukaemia (CML) and acute lymphoblastic  
leukaemia (ALL) patients. In colony transformation assays using ex vivo peripheral blood  
and blood marrow samples, shows inhibitions of Bcr-Abl positive colonies from CML  
patients.  
In vivo, imatinib shows anti-tumour activity as a single medicine using Bcr-Abl positive  
tumour cells. Imatinib also inhibits the receptor tyrosine kinases for platelet derived growth  
factor (PDGF) and stem cell factor (SCF) - called c-Kit, and inhibits PDGF and CF  
mediated cellular events.  
In vitro, imatinib, inhibits proliferation and induces apoptosis in gastrointestinal stromal  
tumour (GIST) cells, which express an activating KIT mutation. Constructive activation of  
the platelet-derived growth factor receptor (PDGFR) or the Abl protein tyrosine kinase as a  
consequence of fusion to diverse partner proteins or constitutive production of PDGF have  
been implicated in the pathogenesis of myelodysplastic syndrome/myeloproliferative  
disorder (MDS/MPD), hypereosinophilic syndrome (HES)/chronic eosinophilic leukaemia  
(HES/CEL) and dermatofibrosarcoma protuberans (DFSP). In addition, constructive  
M.R  
October 2021  
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Page 22 of 27  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
575.  
576.  
577.  
578.  
579.  
580.  
581.  
582.  
583.  
584.  
585.  
586.  
587.  
588.  
589.  
590.  
591.  
592.  
593.  
594.  
595.  
596.  
597.  
598.  
599.  
activation of c-Kit or the PDGFR has been implicated in the pathogenesis of SM. Imatinib  
inhibits signalling and proliferation of cells driven by dysregulated PDGFR, c-Kit and Abl  
kinase activity.  
5.2 Pharmacokinetic Properties:  
The pharmacokinetics of imatinib have been evaluated over a dosage range of 25 to 1000  
mg. Plasma pharmacokinetic profiles were analyses on day 1 and either day 7 or day 28,  
by which time plasma concentrations achieved steady state.  
Absorption:  
Imatinib is well absorbed after oral doses with peak blood concentrations achieved within 2  
to 4 hours. Food intake had minimal impact on the absorption rate. The mean  
bioavailability is about 98 %.  
Distribution:  
At clinically relevant concentrations of imatinib, binding plasma proteins was approximately  
95 %.  
Biotransformation:  
The half-life of imatinib and its major active metabolites, N-demethylated piperazine  
derivative are 18 and 40 hours, respectively. The major enzyme responsible for the  
metabolism of imatinib is cytochrome P450 isoenzyme, CYP3A4. Isoenzyme CYP1A2,  
CYP2D6, CYP2C9 and CYP2C19 also play a minor role.  
Elimination:  
600.  
Imatinib is predominately eliminated via the faecal route, mostly as metabolites. About 81  
M.R  
October 2021  
Initial: …………….  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
601.  
602.  
603.  
604.  
605.  
606.  
607.  
608.  
609.  
610.  
611.  
612.  
613.  
614.  
615.  
616.  
617.  
618.  
619.  
620.  
621.  
622.  
623.  
624.  
625.  
626.  
% of a dose is eliminated within 7 days in the faeces (68 %) and urine (13 %). It is  
excreted mostly as metabolites, with only 25 % of the dose as unchanged medicine.  
Pharmacokinetics in special populations:  
Plasma pharmacokinetics:  
After oral administration, the t½ is approximately 18 hours. The increase in mean AUC  
with increasing dose was linear and dose proportional in the range of 25 – 1000 mg  
Imatinib after oral administration. There was no change in the kinetics of imatinib on  
repeated dosing and accumulation was 1,5 to 2,5-fold at steady state when dosed once  
only. Age had little effect on the volume of distribution (12 % increase in patients > 65  
years old).  
The effect of body weight on the clearance of imatinib for a patient weighing 50 kg is  
expected to be 8,5 L/h, while a patient weighing 100 kg, the clearance will rise to 11,8 L/h.  
These changes warrant dose adjustment based on bodyweight (see section 4.2).  
Organ function impairment:  
Imatinib and its metabolites are not excreted via the kidney to a significant extent. It is  
expected that exposure to imatinib may increase if hepatic function is impaired. Since  
imatinib is metabolised in the liver, administration to patients with mild to moderate hepatic  
impairment should be given with caution (see section 4.2).  
Paediatric population:  
Dosing in children at 260 and 340 mg/m2/day achieved the same exposure,  
respectively, at doses of 400 and 600 mg in adult patients. The comparison of AUC (0-  
24) on day 8 and day 1 at 340 mg/m2/day dose level, revealed a 1,7-fold medicine  
accumulation after repeated once daily dosing. There is no experience with the use of  
M.R  
Initial: …………….  
October 2021  
Page 24 of 27  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
627.  
628.  
629.  
630.  
631.  
632.  
633.  
634.  
635.  
636.  
637.  
638.  
639.  
640.  
641.  
642.  
643.  
644.  
645.  
646.  
647.  
648.  
649.  
650.  
651.  
imatinib in children under 2 years of age (see section 4.2).  
5.3 Preclinical safety data  
Not applicable  
Environmental Risk Assessment:  
Imatinib Mesylate (Form – α) is a well-established active ingredient used in  
pharmaceutical preparations for human use. Given the anticipated pattern of use and  
disposal of the product, the environmental exposure of the active substance and  
metabolites are expected to be very limited. The use of Imatinib Tablets 100 mg and  
400 mg is not considered warranting any environmental concerns or requiring any  
special product labelling.  
6 PHARMACEUTICAL PARTICULARS  
6.1 List of excipients  
NUVITAB has the following ingredients:  
•
•
•
•
Magnesium stearate.  
Opadry white 03F58763  
Isopropyl alcohol  
Methylene chloride  
6.2 Incompatibilities  
Not applicable  
6.3 Shelf life  
36 months  
M.R  
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Page 25 of 27  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
652.  
653.  
654.  
655.  
656.  
657.  
658.  
659.  
660.  
661.  
662.  
663.  
664.  
665.  
666.  
667.  
668.  
669.  
670.  
671.  
672.  
673.  
674.  
675.  
676.  
677.  
6.4 Special precautions for storage  
Store at or below 25 °C.  
Keep bottle tightly closed.  
Protect from moisture.  
Store tablets in original container.  
6.5 Nature and contents of container  
•
•
•
NUVITAB 100 are packed into round, white opaque, HDPE bottles  
closed with a ribbed, child resistant white opaque polypropylene plastic cap with a  
pulp liner with opening illustrations embossed on top, enclosed with a desiccant  
canister that contains silica gel. Pack size: 30, 60, 90 or 120 tablets.  
Tablets may also be packed into hard tempering plain, silver Alu/Alu blister strips  
with HSL coating on the bright side in packs of 10 tablets per strip onto cold  
formable laminated film into an outer carton box. Pack size: 30, 60, 90 or 120  
tablets.  
NUVITAB 400 are packed into round, white opaque, HDPE bottles  
closed with a ribbed, child resistant white opaque polypropylene plastic cap with a  
pulp liner with opening illustrations embossed on top, enclosed with a desiccant  
canister that contains silica gel. Pack size: 20, 30 or 60 tablets.  
•
Tablets may also be packed into hard tempering plain, silver Alu/Alu blister  
strips with HSL coating on the bright side in packs of 10 tablets per strip onto  
cold formable laminated film into an outer carton box. Pack size: 20, 30 or 60  
M.R  
October 2021  
Initial: …………….  
Page 26 of 27  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: NUVITAB 100 and 400  
Dosage form and strength: Each film coated tablet contains Imatinib mesylate equivalent to 100 mg  
Each film coated tablet contains Imatinib mesylate equivalent to 400 mg  
678.  
679.  
680.  
681.  
682.  
683.  
684.  
685.  
686.  
687.  
688.  
689.  
690.  
691.  
692.  
693.  
694.  
695.  
696.  
697.  
tablets.  
HDPE bottle and blister packs are enclosed in an outer carton box.  
Not all pack sizes may be marketed.  
6.6 Special precautions for disposal and handling  
No special requirements  
7 HOLDERS OF CERTIFICATE OF REGISTRATION  
Hetero Drugs South Africa (Pty) Ltd.  
Jean Park Chambers  
52 Jean Avenue  
Building 6, Unit 17 & 18,  
Centurion 0157  
8 REGISTRATION NUMBER(S):  
NUVITAB 100 film coated tablets: 51/34/0145  
NUVITAB 400 film coated tablets: 51/34/0146  
9 DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION  
12 October 2021  
M.R  
October 2021  
Initial: …………….  
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