Drugs List

Therapeutic Indications

Uses

Advanced renal cell carcinoma
Relapsed or refractory mantle cell lymphoma

First line treatment of patients with advanced renal cell carcinoma who have 3 to 6 prognostic factors.

Treatment of adult patients with relapsed and/or refractory mantle cell lymphoma [MCL].

Administration

To be administered as an intravenous infusion administered over 30 to 60 minutes after dilution.

The use of an infusion pump is the preferred method of administration to ensure accurate delivery of the medicinal product.

Contraindications

Children under 18 years
Breastfeeding
Moderate hepatic impairment - if treating mantle cell lymphoma
Pregnancy

Precautions and Warnings

Neutrophil count below 1.0 x 10 to the power of 9 / L
Patients over 65 years
Platelet count below 50 x 10 to the power of 9 / L
Recent anticoagulant therapy
Recent surgery
Alcoholism
Central nervous system neoplasm
Diabetes mellitus
Epileptic disorder
Hepatic impairment
Severe hepatic impairment & baseline platelets above 100x10 to power of 9
Severe renal impairment

Administration of live vaccines is not recommended
Advise ability to drive/operate machinery may be affected by side effects
Chest X-ray or CT advised prior to initiation, then as clinically indicated
Premedication with antihistamine recommended
Prophylaxis for pneumocystis jiroveci pneumonia recommended
Treatment to be prescribed under the supervision of a specialist
Contains alcohol
Contains propylene glycol: may cause irritation
Consult local policy on the safe use of anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor platelet count weekly
Diabetic control may need adjustment
Monitor blood glucose
Monitor cholesterol and triglyceride levels
Monitor for signs and symptoms of interstitial lung disease
Monitor levels of hepatic enzymes and bilirubin
Monitor neutrophil count weekly
Monitor patient for infusion-associated reactions (IARs)
Monitor patient for signs of serious infection
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report excessive thirst or increased urination
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Immunosuppressive drugs may increase risk of malignancy
Risk of developing opportunistic infections
Discontinue if angioneurotic oedema occurs
Interrupt treatment if severe infusion reaction occurs
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Male: May cause infertility
Male & female: Ensure adequate contraception during treatment
Advise patient of risk of bleeding
Advise patient on appropriate sun protection methods
Advise patient to avoid exposure to sunlight and UV rays during treatment

Hypersensitivity reactions, including anaphylactic reactions have occurred during temsirolimus administration. If a hypersensitivity reaction develops despite the antihistamine premedication the infusion should be stopped and the patient should be observed for 30 to 60 minutes. The treatment may be restarted at the discretion of the physician with the administration of an H1-receptor antagonist, if not previously administered and/or H2-receptor antagonist approximately 30 minutes before restarting the temsirolimus infusion. The infusion may then be resumed at a slower rate (up to 60 minutes).

Both diabetic and non-diabetic patients have experienced an increase in blood glucose levels during temsirolimus treatment. Blood glucose should be monitored carefully during treatment and patients should be advised to report excessive thirst or any increase in the volume or frequency of urination.

There have been cases of interstitial pneumonitis occurring in patients who received weekly intravenous temsirolimus. Therefore patients should be monitored for respiratory symptoms such as cough, dyspnoea and fever. It is also recommended, prior to treatment, that patients undergo baseline radiographic assessment by lung computed tomography scan or chest radiograph.

Pregnancy and Lactation

Pregnancy

Temsirolimus is contraindicated during pregnancy.

There are no adequate data from the use of temsirolimus in pregnant women.
Studies in rats and rabbits have shown reproductive toxicity, embryo/foetotoxicity occurred in the forms of mortality and reduced foetal weights. The potential risk for humans is unknown.

The effect of concurrent therapies must also be considered.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Temsirolimus is contraindicated in breastfeeding.

It is not know whether temsirolimus is excreted in human breast milk. The excretion of temsirolimus in milk has not been studied in animals. However sirolimus (the main metabolite of temsirolimus) is excreted in the milk of lactating rats. It is not known whether sirolimus is excreted in human milk.

Due to the potential for adverse reactions in nursing infants from temsirolimus, breastfeeding should be discontinued during therapy.

The effect of concurrent therapies must also be considered.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal distension
Abdominal pain
Acne
Ageusia
Anaemia
Anaphylaxis
Angioneurotic oedema
Anxiety
Aphthous stomatitis
Arthralgia
Asthenia
Back pain
Bowel perforation
Cataracts
Cerebral haemorrhage
Chest pain
Chills
Conjunctivitis
Cough
Decreased appetite
Decreased glucose tolerance
Dehydration
Depression
Diarrhoea
Dizziness
Dry skin
Dysgeusia
Dysphagia
Dyspnoea
Ecchymosis
Epistaxis
Exfoliative dermatitis
Febrile neutropenia
Folliculitis
Gastritis
Gastrointestinal bleeding
Gingivitis
Hypercholesterolaemia
Hyperglycaemia
Hyperlipaemia
Hypersensitivity reactions including anaphylaxis
Hypertension
Hypocalcaemia
Hypokalaemia
Hypophosphataemia
Increase in serum ALT/AST
Infections
Insomnia
Interstitial lung disease
Lacrimation disorder
Leucopenia
Lymphopaenia
Mucositis
Myalgia
Nail disorders
Nausea
Neutropenia
Oedema
Oral pain
Pain
Paraesthesia
Pericardial effusion
Pharyngitis
Pleural effusion
Pneumocystis jiroveci pneumonia
Pneumonia
Pneumonitis
Pruritus
Pulmonary embolism
Pyrexia
Rash
Renal failure
Rhabdomyolysis
Rhinitis
Sepsis
Serum creatinine increased
Somnolence
Stevens-Johnson syndrome
Stomatitis
Taste loss
Thrombocytopenia
Thromboembolism
Thrombophlebitis
Thrombosis
Upper respiratory tract infection
Urinary tract infections
Vomiting
Wound healing retarded

Presentation

Infusion containing temsirolimus

Drugs List

Therapeutic Indications

Uses

Advanced renal cell carcinoma
Relapsed or refractory mantle cell lymphoma

First line treatment of patients with advanced renal cell carcinoma who have 3 to 6 prognostic factors.

Treatment of adult patients with relapsed and/or refractory mantle cell lymphoma [MCL].

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Adults

Patients with Hepatic Impairment

Additional Dosage Information

Administration

To be administered as an intravenous infusion administered over 30 to 60 minutes after dilution.

The use of an infusion pump is the preferred method of administration to ensure accurate delivery of the medicinal product.

Contraindications

Children under 18 years
Breastfeeding
Moderate hepatic impairment - if treating mantle cell lymphoma
Pregnancy

Precautions and Warnings

Neutrophil count below 1.0 x 10 to the power of 9 / L
Patients over 65 years
Platelet count below 50 x 10 to the power of 9 / L
Recent anticoagulant therapy
Recent surgery
Alcoholism
Central nervous system neoplasm
Diabetes mellitus
Epileptic disorder
Hepatic impairment
Severe hepatic impairment & baseline platelets above 100x10 to power of 9
Severe renal impairment

Administration of live vaccines is not recommended
Advise ability to drive/operate machinery may be affected by side effects
Chest X-ray or CT advised prior to initiation, then as clinically indicated
Premedication with antihistamine recommended
Prophylaxis for pneumocystis jiroveci pneumonia recommended
Treatment to be prescribed under the supervision of a specialist
Contains alcohol
Contains propylene glycol: may cause irritation
Consult local policy on the safe use of anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor platelet count weekly
Diabetic control may need adjustment
Monitor blood glucose
Monitor cholesterol and triglyceride levels
Monitor for signs and symptoms of interstitial lung disease
Monitor levels of hepatic enzymes and bilirubin
Monitor neutrophil count weekly
Monitor patient for infusion-associated reactions (IARs)
Monitor patient for signs of serious infection
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report excessive thirst or increased urination
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Immunosuppressive drugs may increase risk of malignancy
Risk of developing opportunistic infections
Discontinue if angioneurotic oedema occurs
Interrupt treatment if severe infusion reaction occurs
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Male: May cause infertility
Male & female: Ensure adequate contraception during treatment
Advise patient of risk of bleeding
Advise patient on appropriate sun protection methods
Advise patient to avoid exposure to sunlight and UV rays during treatment

Hypersensitivity reactions, including anaphylactic reactions have occurred during temsirolimus administration. If a hypersensitivity reaction develops despite the antihistamine premedication the infusion should be stopped and the patient should be observed for 30 to 60 minutes. The treatment may be restarted at the discretion of the physician with the administration of an H1-receptor antagonist, if not previously administered and/or H2-receptor antagonist approximately 30 minutes before restarting the temsirolimus infusion. The infusion may then be resumed at a slower rate (up to 60 minutes).

Both diabetic and non-diabetic patients have experienced an increase in blood glucose levels during temsirolimus treatment. Blood glucose should be monitored carefully during treatment and patients should be advised to report excessive thirst or any increase in the volume or frequency of urination.

There have been cases of interstitial pneumonitis occurring in patients who received weekly intravenous temsirolimus. Therefore patients should be monitored for respiratory symptoms such as cough, dyspnoea and fever. It is also recommended, prior to treatment, that patients undergo baseline radiographic assessment by lung computed tomography scan or chest radiograph.

Pregnancy and Lactation

Pregnancy

Temsirolimus is contraindicated during pregnancy.

There are no adequate data from the use of temsirolimus in pregnant women.
Studies in rats and rabbits have shown reproductive toxicity, embryo/foetotoxicity occurred in the forms of mortality and reduced foetal weights. The potential risk for humans is unknown.

The effect of concurrent therapies must also be considered.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Temsirolimus is contraindicated in breastfeeding.

It is not know whether temsirolimus is excreted in human breast milk. The excretion of temsirolimus in milk has not been studied in animals. However sirolimus (the main metabolite of temsirolimus) is excreted in the milk of lactating rats. It is not known whether sirolimus is excreted in human milk.

Due to the potential for adverse reactions in nursing infants from temsirolimus, breastfeeding should be discontinued during therapy.

The effect of concurrent therapies must also be considered.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal distension
Abdominal pain
Acne
Ageusia
Anaemia
Anaphylaxis
Angioneurotic oedema
Anxiety
Aphthous stomatitis
Arthralgia
Asthenia
Back pain
Bowel perforation
Cataracts
Cerebral haemorrhage
Chest pain
Chills
Conjunctivitis
Cough
Decreased appetite
Decreased glucose tolerance
Dehydration
Depression
Diarrhoea
Dizziness
Dry skin
Dysgeusia
Dysphagia
Dyspnoea
Ecchymosis
Epistaxis
Exfoliative dermatitis
Febrile neutropenia
Folliculitis
Gastritis
Gastrointestinal bleeding
Gingivitis
Hypercholesterolaemia
Hyperglycaemia
Hyperlipaemia
Hypersensitivity reactions including anaphylaxis
Hypertension
Hypocalcaemia
Hypokalaemia
Hypophosphataemia
Increase in serum ALT/AST
Infections
Insomnia
Interstitial lung disease
Lacrimation disorder
Leucopenia
Lymphopaenia
Mucositis
Myalgia
Nail disorders
Nausea
Neutropenia
Oedema
Oral pain
Pain
Paraesthesia
Pericardial effusion
Pharyngitis
Pleural effusion
Pneumocystis jiroveci pneumonia
Pneumonia
Pneumonitis
Pruritus
Pulmonary embolism
Pyrexia
Rash
Renal failure
Rhabdomyolysis
Rhinitis
Sepsis
Serum creatinine increased
Somnolence
Stevens-Johnson syndrome
Stomatitis
Taste loss
Thrombocytopenia
Thromboembolism
Thrombophlebitis
Thrombosis
Upper respiratory tract infection
Urinary tract infections
Vomiting
Wound healing retarded

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: March 2016

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. Accessed on 7 March 2016.

Summary of Product Characteristics: Torisel concentrate for solution for infusion. Pfizer limited. Revised February 2017.