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Drugs List
Therapeutic Indications
Dosage
Administration
Contraindications
Precautions and Warnings
Pregnancy and Lactation
Side Effects
Monograph

Dosage

Adults
Patients with Renal Impairment
Patients with Hepatic Impairment

Tumour induced hypercalcaemia

Rehydrate patients before and during treatment with 0.9% w/v sodium chloride injection.
Total dose of pamidronate disodium depends on the patient's initial serum calcium levels.

Initial serum calcium

Up to 3mmol/L: 15mg to 30mg total dose.
3 to 3.5mmol/L: 30mg to 60mg total dose.
3.5 to 4mmol/L: 60mg to 90mg total dose.
Over 4mmol/L: 90mg total dose.

The total dose may be administered as a single infusion or in multiple infusions over two to four consecutive days.
Maximum dose per treatment course: 90mg.
A further dose may be given if serum calcium levels have not returned to normal. Treatment can be repeated whenever hypercalcaemia recurs, although evidence suggests pamidronate disodium may become less effective with multiple treatments.

A significant decrease in serum calcium levels is usually observed 24 to 48 hours after administration and normalisation of values is generally seen within three to seven days.

Osteolytic lesions and bone pain in bone metastases associated with breast cancer

90mg every four weeks (or every three weeks if necessary to coincide with chemotherapy).

Osteolytic lesions and bone pain in multiple myeloma

90mg every four weeks.

Paget's disease of bone

Total dose: 180mg given either as:
30mg once a week for six weeks
OR
60mg every other week for 6 weeks.
Clinical experience suggests that adverse effects are more common after the first dose. Consequently, if 60mg regime is to be used, an additional initial dose of 30mg is recommended, followed by 60mg every other week (i.e. total dose 210mg).

Dilute doses 30mg or 60mg in 125 or 250ml 0.9% w/v sodium chloride injection respectively. The infusion rate must not exceed 60mg/hour (1mg/minute).

These doses may be repeated every six months until remission is achieved. If disease severity requires, then a maximum dose of 360mg (as 60mg doses every other week) per course may be repeated every six months until remission.

Doses may also be repeated if relapse occurs.

Precautions and Warnings

Always dilute with a calcium free solution prior to slow intravenous infusion.

Patients must be adequately hydrated prior to and during treatment with pamidronate disodium. This is especially important in patients receiving diuretic therapy.

Bisphosphonates have been associated with a reduction in renal function with potential for renal failure. This may occur after the initial dose or during long term treatment. Due to the risk of clinically significant deterioration in renal function, single doses of disodium pamidronate should not exceed 90mg and recommended infusion times should be observed. Disodium pamidronate is primarily excreted by the kidney. Therefore, adverse effects may be greater in patients with impaired renal function.

Monitor renal function in all patients, e.g. serum creatinine and clinical renal function parameters prior to each dose of sodium pamidronate. Withhold treatment if renal function deteriorates in patients with bone metastases or multiple myeloma ( see Dosage - Renal impairment ).

Renal function - creatinine clearance less than 30ml/min. Avoid in patients with creatinine clearance less than 30ml/minute unless for life threatening tumour induced hypercalcaemia where the benefit outweighs the potential risk.

Convulsions may be precipitated in patients with tumour induced hypercalcaemia due to electrolyte changes during effective treatment.

In patients with cardiac disease (especially the elderly) additional saline overload may precipitate cardiac failure (left ventricular failure or congestive heart failure). Fever (influenza-like symptoms) may also contribute to this deterioration.

History of thyroid surgery. These patients may be more susceptible to developing hypocalcaemia due to relative hypoparathyroidism.

Monitor blood counts regularly in patients with anaemia, leukopenia or thrombocytopenia.

Caution in patients on a sodium controlled diet. Each 90mg dose of pamidronate disodium contains 0.65mmol of sodium. This will be increased if infusion if given in saline.

Severe hepatic impairment. ( See Dosage - Hepatic Impairment ).

Patients at risk of calcium or vitamin D deficiency e.g. Paget's disease or multiple myeloma - give oral supplements to minimise the risk of hypocalcaemia.

Children under 18 years - pamidronate disodium is not licensed for use in this age group, however, it has been used in the management of severe forms of osteogenesis imperfecta and other causes of osteoporosis in children. (See Dosage - Children).

Osteonecrosis of the jaw has been reported in cancer patients taking bisphosphonate regimens often with concurrent chemotherapy and corticosteroids. These cases have mainly been associated with dental procedures such as tooth extraction and many have shown signs of local infection including osteomyelitis.

There is an increased risk of osteonecrosis of the jaw depending on tumour type (advanced breast cancer and multiple myeloma) or dental status (periodontal disease and poorly fitting dentures).

Perform dental examination with appropriate preventative procedures prior to pamidronate disodium therapy in patients with risk factors (cancer chemotherapy, corticosteroids or poor oral hygiene).

Invasive dental procedures should be avoided in patients taking bisphosphonates. Advise patients to inform their dentist that they are taking bisphosphonates and should not undergo invasive dental procedures. There is no data available to suggest discontinuation of bisphosphonate treatment prior to dentistry reduces the risk of osteonecrosis of the jaw. Recovery from such procedures is likely to be prolonged.

Severe and occasionally incapacitating bone, joint and muscle pain have been reported in patients taking bisphosphonates. Onset of symptoms varied from the first day of treatment to several months after initiating therapy. Discontinuation of treatment has been shown to relieve pain and improve symptoms. Rechallenging treatment with disodium pamidronate may cause recurrence of symptoms.

Osteonecrosis of the external auditory canal has been reported very rarely with bisphosphonates, mainly in association with long term therapy (2 years or longer). Risk factors include steroid use and chemotherapy and/or local risk factors as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms including chronic ear infections.

Atypical stress fractures of the proximal femoral shaft with poor healing have been reported for treatment with another bisphosphonate, alendronic acid. Limited data exists regarding a relationship for other bisphosphonates and atypical stress fractures. However, the possibility of atypical stress fractures cannot be excluded. Patients who develop atypical stress fractures should discontinue treatment and receive no further bisphosphonate treatment.

CSM Warnings

The CHM recommends the following:

Atypical stress fractures of the proximal femoral shaft with poor healing have been reported rarely with long-term bisphosphate treatment;

Patients should be re-evaluated periodically based on an assessment of the benefits and risks of the bisphosphate treatment, especially after 5 years or more of treatment;

Patients should report any new thigh, hip or groin pain during treatment with a bisphosphonate;

Discontinuation of bisphosphonate treatment in patients suspected to have an atypical femoral fracture should be considered after an assessment of the benefits and risks of continued treatment.

Pregnancy and Lactation

Pregnancy

Contraindicated.

Animal studies have shown reproduction toxicological effects and although the significance to humans is unknown, pamidronate should not be used in human pregnancy. If treatment has been discontinued before pregnancy, the very long elimination half life from bone indicates that women treated with a bisphosphonate will have detectable concentrations of the drug for a prolonged interval. If exposure occurs during gestation, detailed ultrasound examination of the foetal skeleton appears to be warranted (Briggs) although Schaeffer states that accidental use of a single dose does not justify interruption of the pregnancy or additional diagnostic procedures.

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 14-17 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

Contraindicated.

It is not known whether disodium pamidronate passes to human milk. Pamidronate disodium does pass into the milk of lactating rats.

However, the extremely low oral bioavailability of bisphosphonates in the non-fasting state implies that systemic levels in the nursing infant should be negligible.

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

Presentation

Powder and solvent for concentrate for solution for infusion containing 15mg pamidronate disodium
Powder and solvent for concentrate for solution for infusion containing 30mg pamidronate disodium
Powder and solvent for concentrate for solution for infusion containing 90mg pamidronate disodium

Concentrate for solution for infusion containing 60mg/10ml pamidronate disodium
Concentrate for solution for infusion containing 90mg/10ml pamidronate disodium

Concentrate for solution for infusion containing 15mg/5ml pamidronate disodium
Concentrate for solution for infusion containing 30mg/10ml pamidronate disodium
Concentrate for solution for infusion containing 60mg/20ml pamidronate disodium
Concentrate for solution for infusion containing 90mg/30ml pamidronate disodium

Concentrate for solution for infusion containing 15mg/1ml pamidronate disodium
Concentrate for solution for infusion containing 30mg/2ml pamidronate disodium
Concentrate for solution for infusion containing 60mg/4ml pamidronate disodium
Concentrate for solution for infusion containing 90mg/6ml pamidronate disodium

Drugs List

pamidronate disodium 15mg/1ml concentrate for solution for infusion

pamidronate disodium 15mg/5ml concentrate for solution for infusion

pamidronate disodium 30mg/10ml concentrate for solution for infusion

pamidronate disodium 30mg/2ml concentrate for solution for infusion

pamidronate disodium 60mg/20ml concentrate for solution for infusion

pamidronate disodium 60mg/4ml concentrate for solution for infusion

pamidronate disodium 90mg/10ml concentrate for solution for infusion

pamidronate disodium 90mg/30ml concentrate for solution for infusion

pamidronate disodium 90mg/6ml concentrate for solution for infusion

Therapeutic Indications

Uses

Tumour-induced hypercalcaemia
Paget's disease of bone
Treatment of osteolytic lesions and bone pain in multiple myeloma
Treatment of osteolytic lesions and bone pain in bone metastasis associated with breast cancer

Dosage

Dilute before use. Give as slow intravenous infusion; rate must not exceed 60mg/hour. (See Administration).

Adults

Tumour induced hypercalcaemia
Rehydrate patients before and during treatment with 0.9% w/v sodium chloride injection.
Total dose of pamidronate disodium depends on the patient's initial serum calcium levels.
Initial serum calcium
Up to 3mmol/L: 15mg to 30mg total dose.
3 to 3.5mmol/L: 30mg to 60mg total dose.
3.5 to 4mmol/L: 60mg to 90mg total dose.
Over 4mmol/L: 90mg total dose.

A significant decrease in serum calcium levels is usually observed 24 to 48 hours after administration and normalisation of values is generally seen within three to seven days.

Osteolytic lesions and bone pain in bone metastases associated with breast cancer
90mg every four weeks (or every three weeks if necessary to coincide with chemotherapy).

Osteolytic lesions and bone pain in multiple myeloma
90mg every four weeks.

Paget's disease of bone
Total dose: 180mg given either as:
30mg once a week for six weeks
OR
60mg every other week for 6 weeks.
Clinical experience suggests that adverse effects are more common after the first dose. Consequently, if 60mg regime is to be used, an additional initial dose of 30mg is recommended, followed by 60mg every other week (i.e. total dose 210mg).

Dilute doses 30mg or 60mg in 125 or 250ml 0.9% w/v sodium chloride injection respectively. The infusion rate must not exceed 60mg/hour (1mg/minute).

Doses may also be repeated if relapse occurs.

Patients with Renal Impairment

Disodium pamidronate is primarily excreted by the kidney. Therefore, adverse effects may be greater in patients with impaired renal function.

In patients with suspected renal impairment the infusion rate should not exceed 20mg/hour.

Manufacturer advises avoid in patients with creatinine clearance less than 30ml/minute unless for life threatening tumour induced hypercalcaemia where the benefit outweighs the potential risk.

Bone metastases and multiple myeloma patients experiencing renal deterioration should have their dose of pamidronate disodium withheld until renal function returns to within 10% of baseline value. Renal deterioration is defined as:

Increase of 0.5mg/dL in patients with normal baseline serum creatinine.
Increase of 1mg/dL in patients with abnormal baseline serum creatinine.

Patients with Hepatic Impairment

Mild to moderate hepatic impairment: No dose adjustment is necessary as drug accumulation is not expected.
Severe hepatic impairment: No information is available therefore, caution is required when administering pamidronate disodium to these patients.

Administration

For slow intravenous infusion (not exceeding 60mg/hour) only after dilution as described below. A relatively large vein should be used to minimise local reactions at the infusion site.

Handling

From a microbiological point of view, the product should be used immediately. If not used immediately, in use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 degrees C, unless dilution has taken place in controlled and validated aseptic conditions.

Reconstitution

Powder must be diluted with 0.9% w/v sodium chloride injection or 5% w/v glucose injection after initial reconstitution with provided ampoule of sterile water for injections.
Ensure the powder is completely dissolved before the reconstituted solution is withdrawn for dilution in accordance with the instructions below.

Concentrate for solution for infusion must be diluted using a calcium-free solution (0.9% sodium chloride injection or 5% glucose injection) prior to use.
The concentration of pamidronate disodium in the infusion solution must not exceed 90mg/250ml (some manufacturers state 60mg/250ml).

Compatibilities

Sodium chloride 0.9% injection

Glucose 5% injection

Incompatibilities

Pamidronate disodium must not be mixed with calcium containing solutions such as Ringer's solution.

Contraindications

Pregnancy (see Pregnancy)
Breastfeeding (see Lactation)