MEDAC DISODIUM PAMIDRONATE

4). The total dose of pamidronate disodium to be used for a treatment course depends on the patient's initial serum calcium levels. The following guidelines are derived from clinical data on uncorrected calcium values. However, doses within the ranges given are also applicable for calcium values corrected for serum protein or albumin in rehydrated patients.

5 The total dose of pamidronate disodium may be administered either in a single infusion or in multiple infusions over 2 to 4 consecutive days. The maximum dose per treatment course is 90 mg for both initial and repeat courses. Higher doses did not improve clinical response.

A significant decrease in serum calcium is generally observed 24 to 48 hours after administration of pamidronate disodium, and normalisation is usually achieved within 3 to 7 days. If normocalcaemia is not achieved within this time, a further dose may be given.

The duration of the response may vary from patient to patient, and treatment can be repeated whenever hypercalcaemia recurs. Clinical experience to date suggests that pamidronate disodium may become less effective as the number of treatments increases.

Osteolytic lesions in multiple myeloma:

The recommended dose is 90 mg every 4 weeks.

Osteolytic lesions in bone metastases associated with breast cancer:

The recommended dose is 90 mg every 4 weeks. This dose may also be administered at 3 weekly intervals to coincide with chemotherapy if desired. Treatment should be continued until there is evidence of a substantial decrease in a patient’s general performance status.

2). As with other intravenous bisphosphonates, monitoring of renal function is recommended, for instance, measurements of serum creatinine prior to each dose of pamidronate disodium. In patients receiving pamidronate disodium for bone metastases or multiple myeloma who show evidence of deterioration in renal function, treatment with pamidronate disodium should be withheld until renal function returns to within 10 % of the baseline value.

5 mg/dl. 0 mg/dl. A pharmacokinetic study conducted in patients with cancer and normal or impaired renal function indicates that the dose adjustment is not necessary in mild (creatinine clearance 61 to 90 ml/min) to moderate renal impairment (creatinine clearance 30 to 60 ml/min).

In such patients, the infusion rate should not exceed 90 mg/4 h (approximately 20 to 22 mg/h). Hepatic impairment A pharmacokinetic study indicates that no dose adjustment is necessary in patients with mild to moderate abnormal hepatic function.

Pamidronate disodium has not been studied in patients with severe hepatic impairment. 4). 4). 9 % sodium chloride or 5 % glucose) before use. 4). 6. The infusion rate should never exceed 60 mg/hour (1 mg/min), and the concentration of pamidronate disodium in the infusion solution should not exceed 90 mg/250 ml.

A dose of 90 mg must usually be administered as a 2-hour infusion in a 250 ml solution for infusion. In patients with multiple myeloma and patients with tumour-induced hypercalcaemia, it is recommended that the infusion rate does not exceed 90 mg in 500 ml over 4 hours.

In order to minimise local reactions at the infusion site, the cannula should be inserted carefully into a relatively large vein. Pamidronate disodium should be given under the supervision of a physician with the facilities to monitor the clinical and biochemical effects.

Patients treated with Medac Disodium Pamidronate 3 mg/ml should be given the package leaflet and the patient reminder card. Use only freshly prepared and clear dilutions!

Adverse reactions to pamidronate disodium are usually mild and transient. The most common adverse reactions are asymptomatic hypocalcaemia and fever (an increase in body temperature of 1–2 °C), typically occurring within the first 48 hours of infusion.

Fever usually resolves spontaneously and does not require treatment. Acute “influenza-like” reactions usually occur only with the first pamidronate infusion. Local soft tissue inflammation at the infusion site occurs commonly (≥ 1/100 to < 1/10), especially at the highest dose.

4). Many of these patients were also receiving chemotherapy and corticosteroids and had signs of local infection including osteomyelitis. The majority of the reports refer to cancer patients following tooth extractions or other dental surgeries.

5 %). 6 %). The mechanism behind the increased incidence of atrial fibrillation in association with zoledronic acid and pamidronate treatment is unknown. Musculoskeletal and connective tissue disorders During post-marketing experience the following reactions have been reported (frequency rare): Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction).

Adverse reactions (Table 2) are ranked under headings of frequency, the most frequent first, using the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).

Table 2 Infections and infestations Very rare:

Reactivation of Herpes simplex, reactivation of Herpes zoster Blood and lymphatic system disorders Common: Anaemia, thrombocytopenia, lymphocytopenia Very rare: Leukopenia Immune system disorders Uncommon: Allergic reactions including anaphylactoid reactions, bronchospasm/dyspnoea, Quincke’s (angioneurotic) oedema Very rare: Anaphylactic shock Metabolism and nutrition disorders Very common: Hypocalcaemia, hypophosphataemia Common: Hypokalaemia, hypomagnesaemia Very rare: Hyperkalaemia, hypernatraemia Nervous system disorders Common: Symptomatic hypocalcaemia (paraesthesia, tetany), headache, insomnia, somnolence Uncommon: Seizures, agitation, dizziness, lethargy Very rare: Confusion, visual hallucinations Eye disorders Common: Conjunctivitis Uncommon: Uveitis (iritis, iridocyclitis) Very rare: Scleritis, episcleritis, xanthopsia Not known: Orbital inflammation Cardiac disorders Very rare: Left ventricular failure (dyspnoea, pulmonary oedema), congestive heart failure (oedema) due to fluid overload Not known: Atrial fibrillation Vascular disorders Common: Hypertension Uncommon: Hypotension Respiratory, thoracic and mediastinal disorders Very rare: Acute respiratory distress syndrome, interstitial lung disease Gastrointestinal disorders Common: Nausea, vomiting, anorexia, abdominal pain, diarrhoea, constipation, gastritis Uncommon: Dyspepsia Skin and subcutaneous disorders Common: Rash Uncommon: Pruritus Musculoskeletal and connective tissue disorders Common: Transient bone pain, arthralgia, myalgia Uncommon: Muscle cramps, osteonecrosis Rare: Atypical subtrochanteric and diaphyseal femoral fractures Very rare: Osteonecrosis of the external auditory canal (bisphosphonate class adverse reaction) Not known: Osteonecrosis of the jaw Renal and urinary disorders Uncommon: Acute renal failure Rare: Focal segmental glomerulosclerosis including the collapsing variant, nephrotic syndrome Very rare: Deterioration of pre-existing renal disease, haematuria, renal tubular disorder, tubulointerstitial nephritis, glomerulonephropathy General disorders and administration site conditions Very common: Fever and influenza-like symptoms sometimes accompanied by malaise, rigors, fatigue, and flushes Common: Reactions at the infusion site (pain, redness, swelling, induration, phlebitis, thrombophlebitis), general body pain Investigations Common: Increase in serum creatinine Uncommon: Abnormal liver function tests, increase in serum urea Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

2). Patients must be assessed prior to administration of Medac Disodium Pamidronate 3 mg/ml to assure that they are appropriately hydrated. This is especially important for patients receiving diuretic therapy. Standard hypercalcaemia-related metabolic parameters including serum calcium and phosphate should be monitored following initiation of therapy with Medac Disodium Pamidronate 3 mg/ml.

Patients who have undergone thyroid surgery may be particularly susceptible to develop hypocalcaemia due to relative hypoparathyroidism. Convulsions have been occurred in some patients with tumour-induced hypercalcaemia due to electrolyte changes associated with this condition and its effective treatment.

In patients with cardiac disease, especially in 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.

Patients with anaemia, leukopenia or thrombocytopenia should have regular haematology assessments. The safety and efficacy of pamidronate disodium in children and adolescents (< 18 years) has not been established. 65 mmol sodium per maximum dose (90 mg).

To be taken into consideration by patients on a controlled sodium diet. Renal insufficiency Bisphosphonates, including Medac Disodium Pamidronate 3 mg/ml, have been associated with renal toxicity manifested as deterioration of renal function and potential renal failure.

Renal deterioration, progression to renal failure and dialysis have been reported in patients after the initial dose or a single dose of Medac Disodium Pamidronate 3 mg/ml. Deterioration of renal function (including renal failure) has also been reported following long-term treatment with Medac Disodium Pamidronate 3 mg/ml in patients with multiple myeloma.

2), thus the risk of renal adverse reactions may be greater in patients with impaired renal function. 2). v. bisphosphonates renal monitoring is recommended, for instance, measurement of serum creatinine prior to each dose of Medac Disodium Pamidronate 3 mg/ml.

g. patients with multiple myeloma and/or tumour-induced hypercalcaemia), should have evaluations of standard laboratory and clinical parameters of renal function prior to each dose of Medac Disodium Pamidronate 3 mg/ml. 2). Medac Disodium Pamidronate 3 mg/ml should not be given with other bisphosphonates because their combined effects have not been investigated.

There is very little experience of the use of pamidronate disodium in patients receiving haemodialysis. 2). Calcium and vitamin D supplementation In the absence of hypercalcaemia, patients with predominantly lytic bone metastases or multiple myeloma, who are at risk of calcium or vitamin D deficiency, and patients with Paget’s disease of the bone, should be given oral calcium and vitamin D supplementation, in order to minimise the risk of hypocalcaemia.

Osteonecrosis of the jaw Osteonecrosis of the jaw (ONJ) has been reported in clinical trials and in the post- marketing setting in patients receiving pamidronate. The start of treatment or of a new course of treatment should be delayed in patients with unhealed open soft tissue lesions in the mouth except in medical emergency situations.

A dental examination with appropriate preventive dentistry and an individual benefit- risk assessment is recommended prior to treatment with bisphosphonates in patients with concomitant risk factors. g. g. tooth extractions) and poorly fitting dentures All patients should be encouraged to maintain good oral hygiene, undergo routine dental check-ups, and immediately report any oral symptoms such as dental mobility, pain or swelling, or non-healing of sores or discharge during treatment with Medac Disodium Pamidronate 3 mg/ml.

While on treatment, invasive dental procedures should be performed only after careful consideration and be avoided in close proximity to pamidronate administration. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition.

For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. The […]

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