illnesshacker: Medical information and health advice you can trust.

Pamidronic Acid Contraindications, Pregnancy Category

Pamidronic Acid Contraindications is an amino- bisphosphonate with anti-resorptive and anti-hypercalcemic activities. Pamidronic acid binds to and adsorbs onto hydroxyapatite crystals in the bone matrix, thereby preventing osteoclast resorption. This agent also binds to and inhibits farnesyl pyrophosphate synthase, an enzyme that plays an important role in the mevalonate pathway. This inhibits the formation of isoprenoid metabolites that are substrates for protein prenylation. This prevents farnesylation and geranylgeranylation of proteins essential for osteoclast function, leading to the induction of apoptosis of osteoclasts. By preventing osteoclast-mediated bone resorption, pamidronic acid decreases bone turnover rate, stabilizes the bone matrix and reduces hypercalcemia.

Pamidronate Disodium is the disodium salt of the synthetic bisphosphonate pamidronate. Although its mechanism of action is not completely understood, pamidronate appears to adsorb to calcium phosphate crystals in bone, blocking their dissolution by inhibiting osteoclast-mediated bone resorption. This agent does not inhibit bone mineralization and formation.

Mechanism of Action of Pamidronic Acid

The mechanism of action of pamidronate is inhibition of bone resorption. Pamidronate adsorbs to calcium phosphate(hydroxyapatite) crystals in bone and may directly block dissolution of this mineral component of bone. In vitro studies also suggest that inhibition of osteoclast activity contributes to inhibition of bone resorption. Pamidronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate, and zoledronate) appear to act as analogs of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signaling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.

Pamidronate is in a class of drugs called bisphosphonates. Pamidronate reduces breakdown of the bones. Pamidronate is used in the treatment of Paget’s disease of bone; to reduce high levels of calcium in the blood associated with malignancy (cancer), and to reduce the breakdown of bone due to metastases of breast cancer or multiple myeloma

Indications of Pamidronic Acid

For the treatment of moderate or severe hypercalcemia associated with malignancy
Pamidronate disodium is approved to be given with chemotherapy to treat bone damage caused by Breast cancer that has metastasized(spread) to the bone.
Multiple myelomas that have metastasized to bone.
Pamidronate disodium is also approved to treat: Hypercalcemia(high blood levels of calcium) caused by malignant tumors.
Pamidronate disodium is also being studied in the treatment of other types of cancer.
Breast Cancer, Bone Metastases
Hypercalcemia
Hypercalcemia of Malignancy
Osteolytic Bone Lesions of Multiple Myeloma
Paget’s Disease

You Might Also Like Verapamil; Uses, Dosage, Side Effects, Interactions, Pregnancy

Contraindications of Pamidronic Acid

Surgery on the thyroid gland
Low amount of magnesium in the blood
Low amount of phosphate in the blood
Low amount of calcium in the blood
Extreme Loss of Body Water
Low amount of potassium in the blood
Inflammation of the Tissues Surrounding a Tooth
Kidney disease with a reduction in kidney function
Pregnancy
Decreased Blood Volume
Bone necrosis of the jaw bone
Invasive Dental Procedure
Allergies to Bisphosphonates

Dosage of Pamidronic Acid

Strengths: 3 mg/mL; 9 mg/mL; 30 mg; 90 mg; 60 mg; 6 mg/mL

Hypercalcemia of Malignancy

Moderate Hypercalcemia (corrected serum calcium of approximately 12 mg/dL to 13.5 mg/dL)

60 to 90 mg single intravenous infusion over 2 to 24 hours

Severe Hypercalcemia (corrected serum calcium greater than 13.5 mg/dL)

90 mg single intravenous infusion over 2 to 24 hours

Paget’s Disease

Moderate to severe Paget’s Disease of the Bone

30 mg intravenous infusion every day, administered over 4 hours for 3 consecutive days, for a total dose of 90 mg

Osteolytic Bone Lesions of Multiple Myeloma

90 mg intravenous infusion administered over 2 hours every 4 weeks
Duration of therapy: 24 months of therapy demonstrated overall benefits

Osteolytic Bone Metastases of Breast Cancer

90 mg intravenous infusion administered over 2 hours every 3 to 4 weeks
Duration of therapy: 24 months of therapy demonstrated overall benefits

Side Effects of Pamidronic Acid

The Most Common

Abdominal or stomach pain or tenderness
diarrhea
symptoms of heart problems (e.g., shortness of breath, swelling of the ankles or feet, chest pain, irregular heartbeat)
symptoms of liver problems (e.g., nausea, vomiting, abdominal pain, yellowing of the skin and eyes, itchy skin, dark urine)
symptoms of lung problems (e.g., shortness of breath or difficulty breathing, chest pain, cough)
symptoms of a severe allergic reaction (e.g., hives; difficulty breathing; swelling of the face, mouth, tongue, or throat)
signs of a severe skin reaction such as blistering, peeling, a rash covering a large area of the body, a rash that spreads quickly, or a rash combined with fever or discomfort

You Might Also Like Diclofenac Dosage, Warning, Pregnancy Safety

More Common

Acid or sour stomach
back pain
belching
cracked lips
diarrhea (mild)
dry skin
heartburn
indigestion
pain in the arms or legs
redness, swelling, or painful skin
scaling of the skin on the hands and feet
sores, ulcers, or white spots on the lips, tongue, or the inside of the mouth

Rare

Black, tarry stools
body aches or pain
burning, numbness, tingling, or painful sensations
burning pain on urination
chest pain
chills
cough
difficult or labored breathing
ear congestion
fever
headache
loss of voice
lower back or side pain
nasal congestion
painful or difficult urination
pale skin
red, swelling, or painful skin

Drug Interactions of Pamidronic Acid

Pamidronate may interact with following drugs, supplements & may change the efficacy of drugs

aminoglycosides (e.g., gentamicin, tobramycin)
angiogenesis inhibitors;
medications that prevent blood vessel growth in tumors (e.g., axitinib, bevacizumab, lenalidomide, pazopanib, regorafenib, sorafenib, sunitinib, thalidomide)
other bisphosphonates (e.g., alendronate, risedronate, etidronate)
deferasirox
nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen, ketoprofen)
proton pump inhibitors (e.g., lansoprazole, omeprazole)

Pregnancy Category

AU TGA pregnancy category: B3
US FDA pregnancy category: D

Pregnancy

This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Lactation

It is not known if pamidronate passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. The safety and effectiveness of using this medication have not been established for children.

You Might Also Like Diosmin - Uses, Dosage, Side Effects, Interactions