Adverse reactions with disodium pamidronate are usually mild and transient. The most common adverse reactions are asymptomatic hypocalcaemia, influenza like symptoms and mild fever (an increase in body temperature of >1°C, which may last up to 48 hours). Fever usually resolves spontaneously and does not require treatment. Acute "influenza like" reactions usually occur only with the first disodium pamidronate infusion. Symptomatic hypocalcaemia is uncommon. Local soft tissue inflammation at the infusion site also occurs, especially at the highest dose (90 mg).
The frequency estimate for the adverse reactions below is as follows: Very common: (>1/10), common: (>1/100 and <1/10) uncommon: (>1/1000, <1/100), rare: (>1/10,000, <1/1000) and very rare: (<1/10,000), including isolated reports.
Body as a whole:
Very common: fever and influenza like symptoms sometimes accompanied by malaise, rigor, fatigue and flushes.
Very rare: allergic reaction (swollen and itchy eyes, runny nose and scratchy throat).
Very common: hypocalcaemia, hypophosphataemia.
Common: hypomagnesaemia, hypokalaemia, increase in serum creatinine.
Uncommon: abnormal liver function tests, increase in serum urea.
Very Rare: hyperkalaemia, hypernatraemia.
Common: anaemia, lymphocytopenia, thrombocytopenia.
Very rare: leucopenia.
One case of acute lymphoblastic leukaemia has been reported in a patient with Paget's disease. The causal relationship to the treatment or the underlying disease is unknown.
Very rare: left ventricular failure, dyspnoea, pulmonary oedema, congestive heart failure (oedema) due to fluid overload.
Central nervous system:
Common: headache, insomnia, symptomatic hypocalcaemia (paraesthesia, tetany), somnolescence.
Uncommon: lethargy, seizures, agitation, dizziness.
Very rare: confusion, visual hallucinations.
Common: nausea, vomiting, anorexia, abdominal pain, constipation, gastritis.
Common: reactions at the infusion site - pain, redness, swelling, induration, phlebitis, thrombophlebitis.
Common: transient bone pain, arthralgia, myalgia, generalised pain and skeletal pain.
Uncommon: muscle cramps.
Uncommon: acute renal failure.
Rare: focal segmental glomerulosclerosis, including the collapsing variant nephritic syndrome.
Very rare: hematuria, deterioration of pre-existing renal disease (see as follows).
Very rare: adult respiratory distress syndrome, interstitial pneumonitis.
Common: rash. Uncommon: pruritus.
Uncommon: uveitis (iritis, iridocyclitis).
Very rare: scleritis, episcleritis, xanthopsia.
Very rare: reactivation of herpes simplex and herpes zoster.
Other adverse reactions reported rarely in post-marketing use include: allergic reaction, anaphylactic shock (very rare), anaphylactic reactions, bronchospasm (dyspnoea) and Quincke's oedema.
Many of these undesirable effects may have been related to the underlying disease.
Tumour-induced hypercalcaemia and Paget's disease:
Deterioration of renal function has been noted in patients treated with bisphosphonates. Since many patients with tumour-induced hypercalcaemia have compromised renal function prior to receiving antihypercalcaemia therapy (see Precautions), it is difficult to estimate the role of the individual in bisphosphonates in subsequent changes in renal function. Deterioration of renal function (elevation of serum creatinine of >20% above baseline) which could not be readily explained in terms of pre-existing renal disease, prior nephrotoxic chemotherapies or compromised intravascular volume status has been noted in 7 cases of 404 patients treated with disodium pamidronate where these data have been reported. The role of disodium pamidronate in these changes in renal function is unclear, but merits cautious observation.
Bone metastases and multiple myeloma:
Deterioration of renal function (including renal failure) has been reported following long term treatment with disodium pamidronate in patients with multiple myeloma. However, underlying disease progression and/or concomitant complications were also present and therefore, a causal relationship with disodium pamidronate is unproven.
Uncommonly, cases of osteonecrosis (primarily of the jaws) have been reported predominantly in cancer patients treated with bisphosphonates. Many of these patients had signs of local infection including osteomyelitis and the majority of the reports refer to cancer patients following tooth extractions or other dental surgeries. Osteonecrosis of the jaws has multiple well documented risk factors including a diagnosis of cancer, concomitant therapies (e.g. chemotherapy, radiotherapy, corticosteroids) and co-morbid conditions (e.g. anaemia, coagulopathies, infection, pre-existing oral disease). Although causality has not been determined, it is prudent to avoid dental surgery as recovery may be prolonged (see Precautions).