Usage
Pamidronate is prescribed for the following medical conditions:
- Hypercalcemia of Malignancy: Elevated blood calcium levels associated with cancer.
- Osteolytic Bone Metastases: Bone lesions caused by the spread of cancer.
- Multiple Myeloma: A cancer of plasma cells in the bone marrow.
- Paget’s Disease of Bone: A chronic bone disorder that disrupts the normal cycle of bone breakdown and rebuilding.
Pharmacological Classification: Pamidronate is classified as a bisphosphonate.
Mechanism of Action: Pamidronate inhibits osteoclast activity, the cells responsible for bone resorption. This reduces bone breakdown and turnover, lowering serum calcium levels in hypercalcemia and decreasing skeletal complications from metastases and myeloma.
Alternate Names
- International Nonproprietary Name (INN): Pamidronate disodium
- Brand Names: Aredia, Pamisol, Medac Disodium Pamidronate, pms-PAMIDRONATE (and others, depending on the region)
How It Works
Pharmacodynamics: Pamidronate primarily acts on bone tissue by inhibiting osteoclast activity. It binds to hydroxyapatite crystals in bone, preventing their dissolution and reducing bone resorption. This leads to a decrease in serum calcium levels.
Pharmacokinetics:
- Absorption: Administered intravenously, so absorption is not applicable in the traditional sense. The drug rapidly distributes to bone tissue.
- Metabolism: Minimal hepatic metabolism.
- Elimination: Primarily renal excretion of the unchanged drug.
Mode of Action: Pamidronate’s mode of action involves binding to hydroxyapatite crystals in bone. While the exact mechanism isn’t fully understood, it’s believed to interfere with osteoclast function by:
- Disrupting intracellular signaling pathways necessary for osteoclast formation and activity.
- Promoting osteoclast apoptosis (programmed cell death).
- Impairing osteoclast adhesion to the bone surface.
Receptor Binding, Enzyme Inhibition, Neurotransmitter Modulation: Pamidronate does not primarily act through receptor binding, enzyme inhibition, or neurotransmitter modulation. Its main effect is through direct interaction with bone mineral and interference with osteoclast activity.
Elimination Pathways: Pamidronate is primarily eliminated via renal excretion as the unchanged drug.
Dosage
Standard Dosage
Adults:
- Hypercalcemia of Malignancy:
- Moderate (corrected serum calcium 12-13.5 mg/dL): 60-90 mg as a single intravenous infusion over 2-24 hours.
- Severe (corrected serum calcium >13.5 mg/dL): 90 mg as a single intravenous infusion over 2-24 hours.
- Osteolytic Bone Metastases/Multiple Myeloma: 90 mg intravenous infusion every 4 weeks (may be given every 3 weeks to coincide with chemotherapy).
- Paget’s Disease: 180-210 mg total dose per course. May be given as 30 mg once weekly for 6 weeks or 60 mg every other week for 3 doses.
Children:
- Dosing for children is not standardized and should be determined on a case-by-case basis by the physician.
- Limited data suggest a range of 1-1.5 mg/kg/day for several consecutive days, usually given as a slow infusion.
- Careful monitoring of serum calcium and other electrolytes is crucial in pediatric patients.
Special Cases:
- Elderly Patients: Dose adjustments are not typically required, but close monitoring of renal function is advised. Start at lower dose ranges and monitor for adverse reactions.
- Patients with Renal Impairment:
- Mild to Moderate: No dose adjustment necessary.
- Severe (creatinine clearance < 30 mL/min): Avoid use unless benefits outweigh risks.
- Patients with Hepatic Dysfunction: No dose adjustment needed for mild to moderate impairment. Use with caution in severe hepatic dysfunction.
- Patients with Comorbid Conditions: Monitor closely and adjust as needed based on individual patient factors.
Clinical Use Cases Pamidronate’s intravenous route is mainly indicated for conditions affecting bone metabolism or calcium homeostasis, rather than clinical settings like intubation, surgical procedures, mechanical ventilation, or emergency scenarios. Its slow infusion administration and specific therapeutic actions are not generally suited for these acute care settings.
Dosage Adjustments
Adjustments may be necessary for renal or hepatic impairment as outlined above. Closely monitor patients with other conditions impacting drug clearance or calcium balance.
Side Effects
Common Side Effects:
- Fever, fatigue, flu-like symptoms
- Gastrointestinal upset (nausea, vomiting, constipation, anorexia)
- Headache, dizziness
- Injection site reactions (pain, swelling, redness)
- Bone, joint, or muscle pain
Rare but Serious Side Effects:
- Ocular inflammation (uveitis, scleritis)
- Atrial fibrillation
- Osteonecrosis of the jaw (ONJ)
- Renal impairment
- Hypocalcemia
Long-Term Effects:
- ONJ with prolonged use
- Atypical femoral fractures
Adverse Drug Reactions (ADR):
- Severe hypocalcemia
- Anaphylaxis
- Severe bone, joint, or muscle pain
Contraindications
- Hypersensitivity to pamidronate or other bisphosphonates
- Pregnancy and breastfeeding
- Severe hypocalcemia
- Severe renal impairment
Drug Interactions
- Other nephrotoxic drugs (increased risk of renal impairment)
- Calcium supplements (reduced efficacy of pamidronate)
- Aminoglycosides (increased risk of hypocalcemia)
- Loop diuretics (increased risk of hypocalcemia)
Pregnancy and Breastfeeding
- Pregnancy: Contraindicated. May cause fetal skeletal abnormalities and other adverse effects.
- Breastfeeding: Contraindicated. Pamidronate may be excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Inhibits osteoclast activity, reducing bone resorption.
- Side Effects: Fever, fatigue, GI upset, injection site reactions, bone pain. Rarely: ocular inflammation, ONJ, renal impairment.
- Contraindications: Hypersensitivity, pregnancy, breastfeeding, severe hypocalcemia, severe renal impairment.
- Drug Interactions: Nephrotoxic drugs, calcium supplements, aminoglycosides, loop diuretics.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Varies based on indication and patient factors. See detailed dosage guidelines.
- Monitoring Parameters: Serum calcium, phosphate, creatinine, magnesium, complete blood count.
Popular Combinations
Pamidronate is often used in combination with chemotherapy for the management of bone metastases and multiple myeloma.
Precautions
- Adequate hydration is essential, especially in patients at risk of renal impairment.
- Dental examination prior to starting therapy and good oral hygiene are important to minimize the risk of ONJ.
- Monitor renal function closely.
- Monitor serum calcium and other electrolytes.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Pamidronate?
A: The dosage varies depending on the indication. Please refer to the detailed dosage guidelines section above, which covers dosing for adults, children, and special populations.
Q2: What is the mechanism of action of Pamidronate?
A: Pamidronate inhibits osteoclast activity, reducing bone resorption and decreasing serum calcium levels.
Q3: What are the common side effects of Pamidronate?
A: Common side effects include fever, fatigue, flu-like symptoms, GI upset, headache, and injection site reactions.
Q4: What are the serious side effects of Pamidronate?
A: Rare but serious side effects include ocular inflammation, atrial fibrillation, osteonecrosis of the jaw, renal impairment, and severe hypocalcemia.
Q5: Is Pamidronate safe during pregnancy and breastfeeding?
A: No, Pamidronate is contraindicated during both pregnancy and breastfeeding due to potential harm to the fetus/infant.
Q6: How is Pamidronate administered?
A: Pamidronate is administered intravenously as a slow infusion. It should never be given as a bolus injection.
Q7: What are the contraindications for using Pamidronate?
A: Contraindications include hypersensitivity to pamidronate or other bisphosphonates, pregnancy, breastfeeding, severe hypocalcemia, and severe renal impairment.
Q8: Does Pamidronate interact with other medications?
A: Yes, Pamidronate can interact with other medications, such as nephrotoxic drugs, calcium supplements, aminoglycosides, and loop diuretics. Consult the drug interactions section for more information.
Q9: What monitoring is required for patients receiving Pamidronate?
A: Regular monitoring of serum calcium, phosphate, creatinine, magnesium, and complete blood count is necessary for patients receiving Pamidronate.
Q10: What precautions should be taken when prescribing Pamidronate?
A: Ensure adequate hydration, conduct a dental examination prior to therapy, monitor renal function, and monitor serum electrolytes. Encourage good oral hygiene.
