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Renal cell metastatic temsirolimus

 Ranitidine recall:

The TGA has suspended the registration of all ranitidine medicines. Further information is available from the TGA safety alert. Ranitidine is included as a default premedication in eviQ protocols and alternative approaches should be considered based on assessment of individual patients, institutional policy and availability of alternative drugs [e.g. famotidine - see ID 3264 Premedication for prophylaxis of taxane hypersensitivity reactions (infusion related reactions and anaphylaxis)]. Refer to BOPA Position Statement - H2 antagonists in paclitaxel pre-medication regimens for more information.

Check for clinical trials in this patient group. Link to Australian Clinical Trials website

The anticancer drug(s) in this protocol have been updated with the ADDIKD guideline recommendations (if applicable). Recommendations may differ from other protocols which have not been updated. For further information refer to the dedicated eviQ ADDIKD guideline webpage.

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Cycle 1 and further cycles

Drug Dose Route Day
Temsirolimus 25 mg IV infusion 1
Frequency:
7 days 
Cycles:
Continuous until disease progression or unacceptable toxicity
Drug status:

Temsirolimus is TGA registered but not PBS listed

Cost:
Not available "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au). These costs are reviewed and updated on eviQ at 6 monthly intervals. Anti-cancer drugs that are not included on the PBS do not have a cost included in eviQ protocols.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

Where oral drugs are available on the PBS for both 30- and 60-day prescriptions, the unit cost for the 30-day supply is used.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 and further cycles

Day 1
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
Promethazine 12.5 mg (IV) 30 minutes before treatment
Ranitidine 50 mg (IV) in 50 mL to 100 mL sodium chloride 0.9% over 15 to 20 minutes 30 minutes before treatment
Temsirolimus 25 mg (IV infusion) in 250 mL sodium chloride 0.9% over 30 to 60 minutes (in non-PVC containers only)
Frequency:
7 days 
Cycles:
Continuous until disease progression or unacceptable toxicity

Cycle 1 and further cycles

Drug Dose Route Day
Temsirolimus 25 mg IV infusion 1
Frequency:
7 days 
Cycles:
Continuous until disease progression or unacceptable toxicity
Drug status:

Temsirolimus is TGA registered but not PBS listed

Cost:
Not available "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au). These costs are reviewed and updated on eviQ at 6 monthly intervals. Anti-cancer drugs that are not included on the PBS do not have a cost included in eviQ protocols.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

Where oral drugs are available on the PBS for both 30- and 60-day prescriptions, the unit cost for the 30-day supply is used.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 and further cycles

Day 1
Metoclopramide 10 mg (PO)

one tablet when necessary (maximum of 30 mg/24 hours, up to 5 days)
Promethazine 12.5 mg (IV) 30 minutes before treatment
Ranitidine 50 mg (IV) in 50 mL to 100 mL sodium chloride 0.9% over 15 to 20 minutes 30 minutes before treatment
Temsirolimus 25 mg (IV infusion) in 250 mL sodium chloride 0.9% over 30 to 60 minutes (in non-PVC containers only)
Frequency:
7 days 
Cycles:
Continuous until disease progression or unacceptable toxicity
Venous access required

IV cannula (IVC) or central venous access device (CVAD) is required to administer this treatment.

Read more about central venous access device line selection
Hypersensitivity/infusion related reaction

High risk with temsirolimus.

Read more about Hypersensitivity reaction
Premedication

The product information states that premedication is required for this treatment.

Please refer to the treatment schedule for suggested premedication regimen. This may be substituted to reflect institutional policy.
Emetogenicity LOW

Suggested default antiemetics have been added to the treatment schedule, and may be substituted to reflect institutional policy.

Ensure that patients also have sufficient antiemetics for breakthrough emesis:

Metoclopramide 10 mg three times a day when necessary (maximum of 30 mg/24 hours, up to 5 days) OR

Prochlorperazine 10 mg PO every 6 hours when necessary.

Read more about preventing anti-cancer therapy induced nausea and vomiting
Infections

Patients may be immunosuppressed and should be carefully observed for the occurrence of infections, including opportunistic infections.
Pneumonitis

There have been cases of non-specific interstitial pneumonitis, including rare fatal reports, occurring in patients who have received this treatment.

Read more about pulmonary toxicity associated with anti-cancer drugs.
Hyperglycaemia

Hyperglycaemia has been observed with this treatment. Close monitoring of blood sugar levels is recommended. Initiation of antidiabetic therapy may be required. In patients with pre-existing diabetes, dose adjustment of oral antidiabetic medications or insulin may be required.
Hyperlipidaemia

Hyperlipidaemia is a common adverse event. Dose adjustment or initiation of lipid-lowering agents may be required.
Wound healing

This treatment may impair wound healing and temporary interruption of treatment is recommended in patients undergoing major surgical procedures. Resume treatment based on clinical judgement of adequate wound healing.
Blood tests

FBC, EUC, eGFR, LFTs, BSL and lipid studies at  baseline, repeat FBC weekly, EUC, eGFR and LFTs monthly. Repeat lipid studies and BSL as clinically indicated.
Hepatitis B screening and prophylaxis

Routine screening for HBsAg and anti-HBc is NOT usually recommended for patients receiving this treatment.

Read more about hepatitis B screening and prophylaxis in cancer patients requiring cytotoxic and/or immunosuppressive therapy
Vaccinations

Live vaccines are contraindicated in cancer patients receiving immunosuppressive therapy and/or who have poorly controlled malignant disease.

Refer to the recommended schedule of vaccination for immunocompromised patients, as outlined in the Australian Immunisation Handbook.

Read more about COVID-19 vaccines and cancer.
Fertility, pregnancy and lactation

Cancer treatment can have harmful effects on fertility and this should be discussed with all patients of reproductive potential prior to commencing treatment. There is a risk of foetal harm in pregnant women. A pregnancy test should be considered prior to initiating treatment in females of reproductive potential if sexually active. It is important that all patients of reproductive potential use effective contraception whilst on therapy and after treatment finishes. Effective contraception methods and adequate contraception timeframe should be discussed with all patients of reproductive potential. Possibility of infant risk should be discussed with breastfeeding patients.

Read more about the impact of cancer treatment on fertility
Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the anti-cancer regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient preferences.Suggested dose modifications are based on clinical trial findings, product information, published guidelines and reference committee consensus . The dose reduction applies to each individual dose and not to the total number of days or duration of treatment cycle unless stated otherwise. Non-haematological gradings are based on Common Terminology Criteria for Adverse Events (CTCAE) unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.

Note: Temsirolimus is converted to sirolimus by CYP3A4. Sirolimus is the active agent, which binds to and selectively inhibits mTORC1 (mammalian target of rapamycin complex 1). It does not bind to mTORC2. Inhibition is reversible and activity is related to duration of exposure above a critical concentration. Sirolimus is extensively metabolised in the liver. It is a P-gp substrate and is also metabolised by CYP3A4. Renal elimination of both compounds is minimal.

Haematological toxicity
ANC x 109/L (pre-treatment blood test)
less than 1.0 Delay treatment until recovery and consider reducing temsirolimus by 5 mg for subsequent cycles
Febrile neutropenia Delay treatment until recovery and consider reducing temsirolimus by 5 mg for subsequent cycles
Platelets x 109/L (pre-treatment blood test)
75 to less than 100 Refer to local institutional guidelines; it is the view of the expert clinicians that treatment should continue if patient is clinically well
50 to less than 75 Delay treatment until recovery
less than 50 Delay treatment until recovery and consider reducing temsirolimus by 5 mg for subsequent cycles
Kidney dosing recommendations 
No dose modification necessary
Hepatic impairment
Hepatic dysfunction
Severe Patients with severe hepatic dysfunction were excluded from the trial
Mucositis and stomatitis
Grade 3 Delay treatment until toxicity has resolved to Grade 2 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: Reduce temsirolimus by 5 mg
2nd occurrence: Reduce temsirolimus by a further 5 mg
3rd occurrence: Omit temsirolimus
Grade 4 Omit temsirolimus
Diarrhoea
Grade 3 Delay treatment until toxicity has resolved to Grade 2 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: Reduce temsirolimus by 5 mg
2nd occurrence: Reduce temsirolimus by a further 5 mg
3rd occurrence: Omit temsirolimus
Grade 4 Omit temsirolimus

The drug interactions shown below are not an exhaustive list. For a more comprehensive list and for detailed information on specific drug interactions and clinical management, please refer to the specific drug product information and the following key resources: 

For more information see References & Disclaimer.

Temsirolimus
  Interaction Clinical management
CYP3A4 and P-gp inhibitors (e.g. amiodarone, aprepitant, azole-antifungals, ritonavir, lapatinib, nilotinib, sorafenib, macrolides, cyclosporin, grapefruit juice etc.) Increased toxicity of temsirolimus, and/or its metabolite sirolimus, possible due to reduced clearance Avoid combination or monitor for temsirolimus toxicity

If concomitant use cannot be avoided, consider reducing temsirolimus weekly dose from 25 mg to 12.5 mg
CYP3A4 and P-gp inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John’s wort, dexamethasone etc.) Reduced efficacy of temsirolimus, and/or its metabolite sirolimus, possible due to increased clearance Avoid combination or monitor for decreased clinical response to temsirolimus 

If concomitant use cannot be avoided, consider increasing temsirolimus weekly dose from 25 mg to 50 mg
Drugs undergoing P-gp-mediated elimination (e.g. digoxin, dabigatran, loperamide, phenytoin etc.) Increased effects/toxicity of these drugs possible due to inhibition of P-gp by temsirolimus resulting in reduced clearance Caution advised if combination used - monitor for increased effect/toxicity of interacting drugs
ACE inhibitors Risk of angioneurotic oedema (including delayed reactions occurring two months following initiation of therapy) Avoid combination
Potassium lowering drugs (e.g. thiazide diuretics, amphotericin) Additive risk of hypokalaemia with temsirolimus Avoid combination or monitor potassium level and for signs of hypokalaemia
General
  Interaction Clinical management
Warfarin Anti-cancer drugs may alter the anticoagulant effect of warfarin. Monitor INR regularly and adjust warfarin dosage as appropriate; consider alternative anticoagulant.
Direct oral anticoagulants (DOACs) e.g. apixaban, rivaroxaban, dabigatran

Interaction with both CYP3A4 and P-gp inhibitors /inducers.

DOAC and anti-cancer drug levels may both be altered, possibly leading to loss of efficacy or toxicity (i.e. increased bleeding).

Apixaban: avoid concurrent use with strong CYP3A4 and P‑gp inhibitors. If treating VTE, avoid use with strong CYP3A4 and P‑gp inducers. 

Rivaroxaban: avoid concurrent use with strong CYP3A4 and P‑gp  inhibitors.

Dabigatran: avoid combination with strong P‑gp inducers and inhibitors.

If concurrent use is unavoidable, monitor closely for efficacy/toxicity of both drugs.
Digoxin Anti-cancer drugs can damage the lining of the intestine; affecting the absorption of digoxin. Monitor digoxin serum levels; adjust digoxin dosage as appropriate.
Antiepileptics Both altered antiepileptic and anti-cancer drug levels may occur, possibly leading to loss of efficacy or toxicity. Where concurrent use of an enzyme-inducing antiepileptic cannot be avoided, monitor antiepileptic serum levels for toxicity, as well as seizure frequency for efficacy; adjust dosage as appropriate.
Also monitor closely for efficacy of the anti-cancer therapy.
Antiplatelet agents and NSAIDs Increased risk of bleeding due to treatment related thrombocytopenia. Avoid or minimise combination.
If combination deemed essential, (e.g. low dose aspirin for ischaemic heart disease) monitor for signs of bleeding.
Serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs e.g. paroxetine) and serotonin noradrenaline reuptake inhibitors (SNRIs e.g. venlafaxine) Increased risk of serotonin syndrome with concurrent use of 5-HT3 receptor antagonists (e.g. palonosetron, ondansetron, granisetron, tropisetron, dolasetron, etc.) Avoid combination.
If combination is clinically warranted, monitor for signs and symptoms of serotonin syndrome (e.g. confusion, agitation, tachycardia, hyperreflexia).
For more information link to TGA Medicines Safety Update
Vaccines Diminished response to vaccines and increased risk of infection with live vaccines. Live vaccines (e.g. BCG, MMR, zoster and varicella) are contraindicated in patients on immunosuppressive therapy. Use with caution in patients on non-immunosuppressive therapy.
For more information; refer to the recommended schedule of vaccination for cancer patients, as outlined in the Australian Immunisation Handbook

eviQ provides safe and effective instructions on how to administer cancer treatments. However, eviQ does not provide every treatment delivery option, and is unable to provide a comprehensive list of cancer treatment agents and their required IV line giving set/filter. There may be alternative methods of treatment administration, and alternative supportive treatments that are also appropriate. Please refer to the individual product information monographs via the TGA website for further information.

Day 1

Approximate treatment time: 60 minutes

General patient assessment prior to each day of treatment.

Any toxicity grade 2 or greater may require dose reduction, delay or omission of treatment and review by medical officer before commencing treatment.

Prime IV line(s).

Insert IV cannula or access TIVAD or CVAD.

Temsirolimus

Prior to administration:
  • administer premedication at least 30 minutes before temsirolimus.
Administer temsirolimus:
  • via IV infusion over 30 to 60 minutes
  • use an inline filter with non- PVC tubing
  • protect from light
  • flush with ~ 50 mL of sodium chloride 0.9%
  • infusion should be completed within 6 hours from the commencement of the infusion
  • infusion sets and bags made of soft plastic such as ethylene vinyl acetate should not be used due to the potential to lose drug over time
  • if a patient develops a hypersensitivity reaction despite premedication, the infusion should be stopped and the patient should be observed for at least 30 to 60 minutes
  • if rechallenge indicated, premedicate patient and recommence temsirolimus at a slower rate (up to 60 minutes) .

Remove IV cannula and/or deaccess TIVAD or CVAD. 

Continue safe handling precautions until 7 days after completion of drug(s)

Discharge information

Antiemetics
  • Antiemetics as prescribed.
Patient information
  • Ensure patient receives patient information sheet.

The side effects listed below are not a complete list of all possible side effects for this treatment. Side effects are categorised into the approximate onset of presentation and should only be used as a guide.

Immediate (onset hours to days)
Hypersensitivity reaction

Anaphylaxis and infusion related reactions can occur with this treatment.

Read more about hypersensitivity reaction 
Nausea and vomiting

Read more about prevention of treatment induced nausea and vomiting

Early (onset days to weeks)
Neutropenia

Abnormally low levels of neutrophils in the blood. This increases the risk of infection. Any fever or suspicion of infection should be investigated immediately and managed aggressively. 

Read more about immediate management of neutropenic fever
Thrombocytopenia

A reduction in the normal levels of functional platelets, increasing the risk of abnormal bleeding.  

Read more about thrombocytopenia
Oral mucositis

Erythematous and ulcerative lesions of the gastrointestinal tract (GIT). It commonly develops following chemotherapy, radiation therapy to the head, neck or oesophagus, and high dose chemotherapy followed by a blood and marrow transplant (BMT).

Read more about oral mucositis
Diarrhoea

Read more about treatment induced diarrhoea
Anorexia

Loss of appetite accompanied by decreased food intake.

Read more about anorexia
Abdominal pain

Dull ache, cramping or sharp pains are common with some anti-cancer drugs. These are caused by either increased or decreased gastrointestinal motility and can be associated with diarrhoea or constipation.
Hyperlipidaemia and hypercholesterolaemia

Abnormally elevated levels of lipids and cholesterol in the blood.
Hyperglycaemia

High blood sugar, an excess of glucose in the blood stream.
Skin rash

Anti-cancer drugs can cause a number of changes in the skin with maculo-papular rash the most common type of drug-induced skin reaction. 

Read more about skin rash
Fluid retention and oedema

An excess amount of fluid around the cells, tissues or serous cavities of the body, leading to swelling.
Nephrotoxicity

Renal dysfunction resulting from damage to the glomeruli, tubules or renal vasculature.
Arthralgia and myalgia

Generalised joint pain or and/or stiffness and muscle aches, often worse upon waking or after long periods of inactivity. Can improve with movement. May be mild or severe, intermittent or constant and accompanied by inflammation. 

Read more about arthralgia and myalgia

Late (onset weeks to months)
Anaemia

Abnormally low levels of red blood cells (RBCs) or haemoglobin in the blood. 

Read more about anaemia
Nail changes

Hyperpigmentation, paronychia, onycholysis, splinter haemorrhage, pyogenic granuloma formation, subungal haematoma and subungal hyperkeratosis are some of the nail changes associated with anti-cancer drugs.   

Read more about nail toxicities
Pulmonary toxicity

Pulmonary toxicity may include damage to the lungs, airways, pleura and pulmonary circulation. 

Read more about pulmonary toxicity associated with anti-cancer drugs

The evidence supporting this regimen comes from a three-arm multicenter, randomised phase III trial, reported by Hudes et alr

Between July 2003 to April 2005, 626 patients at high risk of relapse, were enrolled in the study. 209 were randomised to receive 25 mg of IV temsirolimus weekly, 207 to receive 3 million units of interferon alfa ( increasing to 18 million units ) subcutaneously three times a week, and 210 to receive a combination of 15 mg of temsirolimus weekly plus 6 million units of interferon alfa three times a week.

The primary end point was overall survival. Secondary end points were progression free survival, objective response rate and the clinical benefit rate.

The INTORSECT trial demonstrated no statistically significant progression free survival advantage for temsirolimus compared with sorafenib (4.3 vs 3.9 months repsecitvely P=0.19) or overall response rate following first line sunitinib. The difference in overall survival was significant in favour of sorafenib (stratified HR 1.31; 95% CI 1.05 to 1.63; two sided P=0.01). Median overall survival in the temsirolimus and sorafenib arms was 12.3 and 16.6 months respectively.r

Further to this the INTORACT trial demonstrated that temsirolimus/bevacizumab combination was not superior to interferon/bevacizumab for first line treatment in clear-cell metastatic renal cell carcinoma.r

Efficacy

Patients who received temsirolimus alone had longer overall survival (hazard ratio for death, 0.73; p=0.008) and progression free survival (p<0.001) than patients who received interferon alone.

Overall, the combination group did not differ significantly from that in the interferon group (hazard ratio, 0.96; p=0.70)

Hudesr Temsirolimus alone
(n=209)		 Interferon alfa alone
(n=207)		 Temsirolimus plus interferon alfa
(n=210)
Overall survival 10.9 months 7.3 months 8.4 months
Progression free survival* 3.8 months 1.9 months 3.7 months
Objective response rate 8.6% 4.8% 8.1%
Clinical benefit rate** 32.1% 15.5% 28.1%

* PFS as determined by the site investigators

**Objective response or stable disease for > 24 weeks

Kaplan-Meier Estimates of Overall Survival and Progression-free Survivalr

© New England Journal of Medicine 2007

Toxicity

Rash, peripheral oedema, hyperglycaemia and hyperlipidaemia were more common in the patients receiving temsirolimus, whereas asthenia was more common in the groups receiving interferon. There were fewer patients with grade 3 or 4 adverse events in the temsirolimus group (67%) than in the interferon group (78%)(p=0.02).

23% and 66% of the patients in the temsirolimus group required a dose reduction and dose delay respectivelyr

© New England Journal of Medicine 2007

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Version 6

Date Summary of changes
27/07/2023

Protocol updated with ADDIKD guideline recommendations.

PDF of previous protocol.

Version number changed to V.6.
16/02/2024 Drug cost updated to "not available".

Version 5

Date Summary of changes
23/03/2010 Approved and transferred to eviQ.
22/03/2011 New format to allow for export of protocol information.
Protocol version number changed to V.2.
Antiemetics and premedications added to the treatment schedule.
Emetogenicity changed to low as per MASCC guidelines 2010.
Additional Clinical Information, Key Prescribing table and Key Administration table combined into new section titled Clinical Considerations.
Drug specific information placed behind the drug name link.
16/01/2012 PHC view updated.
30/11/2012 Protocol reviewed at Medical Oncology Reference Committee meeting. No changes and next review in 2 years.
09/05/2014 Protocol reviewed by the Medical Oncology Reference Committee electronically. No changes. PHC view removed. Next review 2 years.
31/03/2017 Protocol discussed and decided to have a 5 year review period. Next due for review in 2019.
31/05/2017

Transferred to new eviQ website. Protocol version number changed to V.3.

Hepatitis screening changed to not recommended.
10/05/2018 Haematological dose modifications updated as per consensus of the expert clinician group. Version number changed to V.4.
27/03/2019 Protocol reviewed at Medical Oncology Reference Committee meeting on 15/03/2019. Patient information updated- your treatment and when to get help changed to less chemotherapy focused information. Version number changed to V.5. Next review in 5 years.
17/04/2020 "Ranitidine recall" flag added.
09/11/2021 Patient information title changed to "Kidney cancer advanced or metastatic".

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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Last reviewed:
Review due:

The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/91

20 Apr 2024