pamidronate

Action and Spectrum

Mechanism of action 

The primary mechanism of action of pamidronate is it binds to the hydroxyapatite crystals of bone, which makes it hard for osteoclasts to break down the bone. This results in a decrease in bone resorption, an increase in bone density, and a reduction in the risk of fractures  

Spectrum 

• Osteoporosis: It is used to treat osteoporosis in postmenopausal women, as well as in men and in women who have had their ovaries surgically removed. 
• Paget’s disease of bone: It is used to treat Paget’s disease of bone, a condition in which the average balance of bone formation and bone resorption is disrupted, leading to abnormal bone growth. 
• Hypercalcemia of malignancy: It is used to treat hypercalcemia of malignancy, a condition that occurs when cancer cells release a hormone-like substance that causes an increase in calcium levels in the blood. 
• Osteolytic bone metastases: It is also used to treat osteolytic bone metastases, which are bone tumors that cause bone destruction. 

Drug Interaction

Adverse Reaction

Frequency defined:  

>10% 

Urinary tract infections 

Hypophosphatemia 

Hypomagnesemia 

Anemia 

Hypokalemia 

Hypocalcemia  

1-10% 

Seizures 

Frequency undefined 

Fever  

Pain at the injection site 

Cough 

Urinary tract infections 

Dyspnea 

Sinusitis 

Focal segmental glomerulosclerosis 

Osteonecrosis (primarily involving the jaw) reported predominantly in pts w/ cancer  

Post marketing reports 

Confusion 

Pruritis 

Rash 

Hyperkalemia 

Hematuria 

Anaphylactic reactions 

Interstitial lung disease 

Orbital inflammation 

Angioedema 

Conjunctivitis 

Black Box Warning

Contraindication / Caution

Contraindications 

• Hypersensitivity to pamidronate or any of its excipients 
• Severe renal impairment 
• Uncontrolled hypercalcemia (elevated levels of calcium in the blood) 
• Skeletal malignancy (cancer that affects the bones) 
• Pregnancy and breastfeeding 

Caution 

• Renal impairment: It should be used with caution in patients with moderate renal impairment, as the drug is eliminated from the body primarily by the kidneys. 
• Bone and joint pain: Some patients may experience bone and joint pain after receiving pamidronate. This is more likely to occur in patients with Paget’s disease and those who have received high doses of the drug. 
• Osteonecrosis of the jaw: Rarely, patients taking bisphosphonates, including pamidronate, have developed osteonecrosis of the jaw (ONJ), a condition characterized by the death of jawbone tissue. 
• Atrial fibrillation: some studies have reported an increased risk of atrial fibrillation in patients taking bisphosphonates, including pamidronate. 
• Infusion-related reactions: pamidronate is administered intravenously, and some patients may experience infusion-related reactions such as fever, chills, and flushing during treatment. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology 

All bisphosphonates are similar in their mechanism of action; they all bind to the hydroxyapatite crystals of bone and inhibit the activity of osteoclasts, leading to a decrease in bone resorption, an increase in bone density, and a reduction in the risk of fractures. They are used to treat conditions such as osteoporosis, Paget’s disease, and hypercalcemia of malignancy. 

Pharmacodynamics 

Specifically, pamidronate is a bisphosphonate drug, which means it works by inhibiting the activity of osteoclasts, the cells responsible for breaking down bone tissue. This leads to a decrease in bone resorption and an increase in bone density. 

pamidronate binds to the hydroxyapatite crystals of bone and inhibits the activity of osteoclasts by several mechanisms: 

• Inhibiting the formation of the ruffled border, an essential element of osteoclast’s resorptive activity. 
• Inducing apoptosis in osteoclasts 
• Inhibiting the activity of enzymes such as cathepsin K, which play a role in bone resorption. 

These actions led to decreased bone resorption and increased bone density, which can reduce the risk of fractures in conditions such as osteoporosis and Paget’s disease. pamidronate also affects hypercalcemia of malignancy by reducing osteoclast activity caused by the formation of bone metastases.  

Pharmacokinetics 

Absorption: It is poorly absorbed after oral administration, with an oral bioavailability of less than 1%. It is typically administered intravenously (IV) for maximum effect.   

Distribution: It is distributed to the bones after IV administration, with a volume of distribution of approximately 3 L/kg. 

Metabolism: It is not metabolized in the body and is eliminated unchanged.  

Elimination and Excretion:  The elimination of pamidronate is primarily by the kidneys, with a renal clearance of 49 mL/min. The half-life of the drug is 21-35 hours. It is excreted primarily in the urine. 

Adminstartion

Administration 

IV preparation 

the powder should be reconstituted by adding 10 mL of sterile water for injection (SWI) to the vial. The reconstituted solution can then be further diluted in 250-1000 mL of 1/2 normal saline (1/2NS), normal saline (NS), or 5% dextrose in water (D5W) before administration.  

IV incompatibilities 

The powder should be reconstituted by adding 10 mL of sterile water for injection (SWI) to the vial. The reconstituted solution can then be further diluted in 250-1000 mL of 1/2 normal saline (1/2NS), normal saline (NS), or 5% dextrose in water (D5W) before administration.  

IV administration 

The IV infusion should be given slowly over 2-24 hours. A longer infusion time may reduce the risk of nephrotoxicity (kidney damage) associated with using pamidronate. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: pamidronate 

Pronounced: [ PAM-i-DROE-nate ] 

Why do we use pamidronate? 

pamidronate is a bisphosphonate medication that is used to treat various bone-related conditions. The main uses of pamidronate include: 

• Osteoporosis: pamidronate is used to treat osteoporosis in postmenopausal women, as well as in men and in women who have had their ovaries surgically removed. It works by decreasing bone resorption and increasing bone density, which reduces the risk of fractures. 
• Paget’s disease: pamidronate is used to treat Paget’s disease of bone, a condition in which the average balance of bone formation and bone resorption is disrupted, leading to abnormal bone growth. It helps decrease bone resorption and increase bone density, reducing pain and improving mobility. 
• Hypercalcemia of malignancy: pamidronate is used to treat hypercalcemia of malignancy, a condition that occurs when cancer cells release a hormone-like substance that causes an increase in calcium levels in the blood. It works by decreasing bone resorption and reducing the activity of osteoclasts, which can help to lower calcium levels in the blood. 
• Osteolytic bone metastases: pamidronate is also used to treat osteolytic bone metastases, which are bone tumors that cause bone destruction. It works by decreasing bone resorption and reducing the activity of osteoclasts, which can help to slow the progression of the tumors and reduce the risk of fractures