Drugs List

Therapeutic Indications

Uses

Carcinoma in situ of bladder: Prophylaxis
Carcinoma in situ of bladder: Treatment
Urothelial carcinoma: Prophylaxis

Treatment of carcinoma in situ of bladder.
Prophylaxis of carcinoma in situ of bladder.
Prophylaxis of urothelial carcinoma limited to mucosa: Ta G1-G2 if multifocal and/or recurrent tumour and Ta G3.
Prophylaxis of urothelial carcinoma in lamina propria but not the muscular of the bladder (T1).

Dosage

The content of one vial is required for one bladder instillation.

Treatment of carcinoma in situ of bladder
Induction therapy
One instillation per week for 6 consecutive weeks.

Maintenance therapy
After induction therapy one of the following treatment schedules may be chosen.

One instillation per month for 12 months.
or
3 instillations at weekly intervals at month 3, 6, 12, 18, 24, 30 and 36 (total of 27 instillation given over 3 years).

Prophylaxis of carcinoma in situ of bladder
Induction therapy
One instillation per week for 6 consecutive weeks.

In intermediate and high-risk tumours this should be followed by maintenance therapy.

Maintenance therapy
After induction therapy one of the following treatment schedules may be chosen.

One instillation per month for 12 months.
or
3 instillations at weekly intervals at month 3, 6, 12, 18, 24, 30 and 36 (total of 27 instillation given over 3 years).

Prophylaxis of urothelial carcinoma
Induction therapy
One instillation per week for 6 consecutive weeks.

In intermediate and high-risk tumours this should be followed by maintenance therapy.

Maintenance therapy
After induction therapy one of the following treatment schedules may be chosen.

One instillation per month for 12 months.
or
3 instillations at weekly intervals at month 3, 6, 12, 18, 24, 30 and 36 (total of 27 instillation given over 3 years).

Administration

For intravesical instillation.

The patient should not drink any fluid for a period of 4 hours prior to the instillation and for the 2 hours while the instillation remains in the bladder.

The bladder must be completely emptied before the instillation. The BCG instillation is introduced into the bladder by means of a catheter at low pressure. The BCG suspension should remain in the bladder for a period of 2 hours if possible. During this period the suspension should have sufficient contact with the entire mucosal surface of the bladder. Therefore the patient should be mobilised as much as possible. After 2 hours the patient should void the instillation in a sitting position.

In the case of no specific contraindication, a hyperhydration is recommended for 48 hours after following each instillation.

Contraindications

Children under 18 years
History of bladder radiotherapy
History of systemic BCG infection
Immunosuppression
Immunosuppressive treatment including radiotherapy
Traumatic transurethral catheterisation in the previous 3 weeks
Breastfeeding
Immunodeficiency syndromes
Pregnancy
Tuberculosis
Urinary tract infection

Precautions and Warnings

In-vivo prostheses
Pyrexia
Small bladder volume
Arterial aneurysm
Haematuria

Advise ability to drive/operate machinery may be affected by side effects
Delay treatment for 2-3 weeks after TUR or biopsy of bladder lesions
Do not administer & delay treatment by 3 weeks if catheterisation traumatic
Prior to starting therapy rule out active tuberculosis
Product contains viable organisms - treat as infectious material
Determine patient's reactivity to tuberculin prior to administration
Advise patient to report incidences of fever
Discontinue treatment permanently if systemic BCG infection occurs
Interrupt therapy if urinary tract infection occurs
Withhold treatment until gross haematuria resolves
Male & female: Barrier contraception required until 1 week after treatment
Advise patient on hyperhydration after treatment
Advise patients to avoid close contact with recent BCG vaccinees

Patients with positive HLA-B27 could have an increase of the occurrence of reactive arthritis or Reiter's syndrome.

BCG infection of aneurysms and prosthetic devices (including arterial grafts, cardiac devices, and artificial joints) have been reported following intravesicular administration of BCG. The risk of these ectopic BCG infections has not been determined, but is considered to be very small. The benefits of BCG therapy must carefully be weighed against the possibility of an ectopic BCG infection in patients with pre-existing arterial aneurysms or prosthetic devices of any kind.

Pregnancy and Lactation

Pregnancy

BCG bladder instillation is contraindicated in pregnancy.

There are no adequate data from the use of BCG bladder instillation in pregnant women. Reproductive animal studies have not been performed.

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

BCG bladder instillation is contraindicated in breastfeeding.

There are no adequate data from the excretion of these bacteria in breast milk.

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

Abscess
Anaemia
Arthralgia
Arthritis
BCG infection
Bladder contracture
Bladder inflammation
Chills
Conjunctivitis
Cystitis
Cytopenia
Epididymitis
Epididymo-orchitis
Fever
Fistulae
Genital irritation
Genital pain
Granulomatous chorioretinitis
Hepatitis
Hypersensitivity reactions
Hypotension
Increased urinary frequency
Infections
Influenza-like symptoms
Lymphadenitis
Macroscopic haematuria
Malaise
Nausea
Osteomyelitis
Pain on micturition
Peritonitis
Pneumonitis
Prostatitis
Pulmonary granuloma
Rash
Reiter's syndrome
Renal abscess
Urinary obstruction
Urinary tract infections
Uveitis
Vomiting

Presentation

Bladder installation containing Bacillus Calmette Guerin bacteria RIVM strain derived from seed 1173-P2 (2 x 10 to the power of 8 to 3 x 10 to the power of 9 viable units)

Drugs List

Therapeutic Indications

Uses

Carcinoma in situ of bladder: Prophylaxis
Carcinoma in situ of bladder: Treatment
Urothelial carcinoma: Prophylaxis

Treatment of carcinoma in situ of bladder.
Prophylaxis of carcinoma in situ of bladder.
Prophylaxis of urothelial carcinoma limited to mucosa: Ta G1-G2 if multifocal and/or recurrent tumour and Ta G3.
Prophylaxis of urothelial carcinoma in lamina propria but not the muscular of the bladder (T1).

Dosage

The content of one vial is required for one bladder instillation.

Treatment of carcinoma in situ of bladder
Induction therapy
One instillation per week for 6 consecutive weeks.

Maintenance therapy
After induction therapy one of the following treatment schedules may be chosen.

One instillation per month for 12 months.
or
3 instillations at weekly intervals at month 3, 6, 12, 18, 24, 30 and 36 (total of 27 instillation given over 3 years).

Prophylaxis of carcinoma in situ of bladder
Induction therapy
One instillation per week for 6 consecutive weeks.

In intermediate and high-risk tumours this should be followed by maintenance therapy.

Maintenance therapy
After induction therapy one of the following treatment schedules may be chosen.

One instillation per month for 12 months.
or
3 instillations at weekly intervals at month 3, 6, 12, 18, 24, 30 and 36 (total of 27 instillation given over 3 years).

Prophylaxis of urothelial carcinoma
Induction therapy
One instillation per week for 6 consecutive weeks.

In intermediate and high-risk tumours this should be followed by maintenance therapy.

Maintenance therapy
After induction therapy one of the following treatment schedules may be chosen.

One instillation per month for 12 months.
or
3 instillations at weekly intervals at month 3, 6, 12, 18, 24, 30 and 36 (total of 27 instillation given over 3 years).

Administration

For intravesical instillation.

The patient should not drink any fluid for a period of 4 hours prior to the instillation and for the 2 hours while the instillation remains in the bladder.

The bladder must be completely emptied before the instillation. The BCG instillation is introduced into the bladder by means of a catheter at low pressure. The BCG suspension should remain in the bladder for a period of 2 hours if possible. During this period the suspension should have sufficient contact with the entire mucosal surface of the bladder. Therefore the patient should be mobilised as much as possible. After 2 hours the patient should void the instillation in a sitting position.

In the case of no specific contraindication, a hyperhydration is recommended for 48 hours after following each instillation.

Contraindications

Children under 18 years
History of bladder radiotherapy
History of systemic BCG infection
Immunosuppression
Immunosuppressive treatment including radiotherapy
Traumatic transurethral catheterisation in the previous 3 weeks
Breastfeeding
Immunodeficiency syndromes
Pregnancy
Tuberculosis
Urinary tract infection

Precautions and Warnings

In-vivo prostheses
Pyrexia
Small bladder volume
Arterial aneurysm
Haematuria

Advise ability to drive/operate machinery may be affected by side effects
Delay treatment for 2-3 weeks after TUR or biopsy of bladder lesions
Do not administer & delay treatment by 3 weeks if catheterisation traumatic
Prior to starting therapy rule out active tuberculosis
Product contains viable organisms - treat as infectious material
Determine patient's reactivity to tuberculin prior to administration
Advise patient to report incidences of fever
Discontinue treatment permanently if systemic BCG infection occurs
Interrupt therapy if urinary tract infection occurs
Withhold treatment until gross haematuria resolves
Male & female: Barrier contraception required until 1 week after treatment
Advise patient on hyperhydration after treatment
Advise patients to avoid close contact with recent BCG vaccinees

Patients with positive HLA-B27 could have an increase of the occurrence of reactive arthritis or Reiter's syndrome.

BCG infection of aneurysms and prosthetic devices (including arterial grafts, cardiac devices, and artificial joints) have been reported following intravesicular administration of BCG. The risk of these ectopic BCG infections has not been determined, but is considered to be very small. The benefits of BCG therapy must carefully be weighed against the possibility of an ectopic BCG infection in patients with pre-existing arterial aneurysms or prosthetic devices of any kind.

Pregnancy and Lactation

Pregnancy

BCG bladder instillation is contraindicated in pregnancy.

There are no adequate data from the use of BCG bladder instillation in pregnant women. Reproductive animal studies have not been performed.

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

BCG bladder instillation is contraindicated in breastfeeding.

There are no adequate data from the excretion of these bacteria in breast milk.

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

Abscess
Anaemia
Arthralgia
Arthritis
BCG infection
Bladder contracture
Bladder inflammation
Chills
Conjunctivitis
Cystitis
Cytopenia
Epididymitis
Epididymo-orchitis
Fever
Fistulae
Genital irritation
Genital pain
Granulomatous chorioretinitis
Hepatitis
Hypersensitivity reactions
Hypotension
Increased urinary frequency
Infections
Influenza-like symptoms
Lymphadenitis
Macroscopic haematuria
Malaise
Nausea
Osteomyelitis
Pain on micturition
Peritonitis
Pneumonitis
Prostatitis
Pulmonary granuloma
Rash
Reiter's syndrome
Renal abscess
Urinary obstruction
Urinary tract infections
Uveitis
Vomiting

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: February 2016

Reference Sources

Summary of Product Characteristics: BCG-medac, powder and solvent for solution for intravesical use. Medac. Revised February 2015.