Professional Drug Information > Zometa, Zoledronic Acid

Zoledronic Acid (Systemic)

VA CLASSIFICATION
Primary: HS 302

Commonly used brand name(s): Zometa.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Bone resorption inhibitor —

antihypercalcemic—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.


Accepted

Hypercalcemia, neoplasm–associated (treatment)—Zoledronic acid is indicated for the treatment of hypercalcemia of malignancy.^{01}{02}

Multiple myeloma (treatment)¹—Zoledronic acid is indicated for the treatment of multiple myeloma^{11}

Metastases, bone (treatment adjunct)—Zoledronic acid is indicated for the treatment of bone metastases from solid tumors in conjunction with standard antineoplastic therapy, ^{11}including bone metastases from breast carcinoma, ¹ prostate carcinoma,^{10}{11}{12} and other solid tumors. ^{1{04}{05}{06}{07}{08}{09}{10}{11}}

Note: Prostate cancer should have progressed after treatment with at least one hormonal therapy.^{11}
In Canada, this indication is restricted to osteoblastic or mixed osteoblastic/osteoclastic bone metastases from prostate cancer. ^{12}


Acceptance not established
The safety and efficacy of zoledronic acid in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor related conditions has not been established.^{01}{11}

¹ Not included in Canadian product labeling.

Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Molar mass—290.1 g/Mol^{01}

Solubility
    Zoledronic acid is highly soluble in 0.1N sodium hydroxide solution, sparingly soluble in water and 0.1N hydrochloric acid, and practically insoluble in organic solvents.^{01}


pH
    The pH of a 0.7% solution of zoledronic acid in water is approximately 2.0^{01}

Mechanism of action/Effect:

Zoledronic acid inhibits bone resorption. The antiresorptive mechanism is not fully understood and several factors are thought to contribute to this action. In vitro, zoledronic acid inhibits osteoclastic activity and induces osteoclast apoptosis. Osteoclastic resorption of mineralized bone and cartilage through its binding to bone is blocked by zoledronic acid. Increased osteoclastic activity and skeletal calcium release induced by various stimulatory factors released by tumors are inhibited by zoledronic acid.^{01}{03}

Absorption:

Area under the plasma concentration versus time curve (AUC) of zoledronic acid was dose proportional from 2 to 16 mg. The accumulation of zoledronic acid measured over three cycles was low, with mean AUC_0-24h ratios for cycles 2 and 3 versus 1 of 1.13 ± 0.30 and 1.16 ± 0.36, respectively.^{11}

Patients with mild, and moderate renal impairment showed an increased AUC of 15% and 43%, respectively. The risk of renal deterioration appears to increase with AUC, which is doubled at creatine clearance of 10 mL per min.
^{11}
Protein binding:

Approximately 22 % and independent of the concentration.^{01}{11}

Canadian product information states binding to human plasma protein is approximately 56%^{12}

Terminal Elimination—

146 hours^{11}{12}

Elimination:
    Renal—Approximately 44 %^{01}
    Renal clearance was 3.7 ± 2.0 liters per hour.^{11} Remainder is drug bound to bone, and is slowly released back into systemic circulation, giving rise to the 146 hour terminal half-life.^{01}{11}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients hypersensitive to any bisphosphonate may also be hypersensitive to zoledronic acid.^{01}{02}

Carcinogenicity

Standard lifetime carcinogenicity assays were conducted in mice and rats. Mice were given oral doses of zoledronic acid of 0.1, 0.5, or 2.0 mg/kg/day. There was an increased incidence of Harderian gland adenomas in males and females in all treatment groups (at doses ³0.002 times a human intravenous dose of 4 mg, based on a comparison of relative body surface areas). ^{01}

Rats were given oral doses of zoledronic acid of 0.1, 0.5, or 0.2 mg/kg/day. No increased incidence of tumors was observed (at doses £ 0.2 times the human intravenous dose of 4 mg, based on a comparison of relative body surface areas).^{01}

Mutagenicity

Zoledronic acid was not genotoxic in the Ames bacterial mutagenicity assay, in the Chinese hamster ovary cell assay, or in the Chinese hamster gene mutation assay, with or without metabolic activation. Zoledronic acid was not genotoxic in the in vivo rat micronucleus assay.^{01}{11}{12}

Pregnancy/Reproduction
Fertility—
Female rats were given subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg/day beginning 15 days before mating and continuing through gestation. Effects observed in the high dose group (with systemic exposure of 1.2 times the human systemic exposure following an intravenous dose of 4 mg, based on an AUC comparison) included inhibition of ovulation and a decrease in the number of pregnant rats. Effects observed in both the mid-dose group (with systemic exposure of 0.2 times the human systemic exposure following an intravenous dose of 4 mg, based on an AUC comparison) and the high-dose group included an increase in preimplantation losses and a decrease in the number of implantations and live fetuses.^{01}

Pregnancy—
Adequate and well controlled studies in humans have not been done. Studies in animals have shown that zoledronic acid causes an adverse effect on the fetus.^{01}

In female rats given subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg/day beginning 15 days before mating and continuing through gestation, the number of stillbirths was increased and survival of neonates was decreased in the mid- and high-dose groups (³0.2 times the human systemic exposure following an intravenous dose of 4 mg, based on an AUC comparison). Adverse maternal effects were observed in all dose groups (with a systemic exposure of ³0.7 times the human systemic exposure following an intravenous dose of 4 mg, based on an AUC comparison) and included dystocia and periparturient mortality in pregnant rats allowed to deliver. Maternal mortality may have been related to drug-induced inhibition of skeletal calcium mobilization, resulting in periparturient hypocalcemia. This appears to be a bisphosphonate class effect.^{01}

In pregnant rats given a subcutaneous dose of zoledronic acid of 0.1, 0.2, or 0.4 mg/kg/day during gestation, adverse fetal effects were observed in the mid- and high-dose groups (with systemic exposures of 2.4 and 4.8 times, respectively, the human systemic exposure following an intravenous dose of 4 mg, based on an AUC comparison). These adverse effects included increases in pre- and post-implantation losses, decreases in viable fetuses, and fetal skeletal, visceral, and external malformations. Fetal skeletal effects observed in the high-dose group included unossified or completely ossified bones, thickened, curved or shortened bones, wavy ribs and shortened jaw. Other adverse fetal effects observed in the high-dose group included reduced lens, rudimentary cerebellum, reduction or absence of liver lobes, reduction of lung lobes, vessel dilation, cleft palate and edema. Skeletal variations were also observed in the high-dose group and included reduced body weights and food consumption.^{01}

In pregnant rabbits given subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg/day during gestation (£ 0.5 times the human intravenous dose of 4 mg, based on a comparison of body surface areas). Maternal mortality and abortion occurred in all treatment groups (at doses ³ 0.05 times the human intravenous dose of 4 mg, based on a comparison of body surface areas). Adverse maternal effects were associated with, and may have been caused by drug induced hypocalcemia. ^{01}

FDA Pregnancy Category ^{01}D ^{11}

Breast-feeding

Since it is not known whether zoledronic acid is distributed into the breast milk, caution should be used when zoledronic acid is administered to nursing women.^{01}

Pediatrics

No information is available on the relationship of age to the effects of zoledronic acid in the pediatric population. Safety and efficacy have not been established. ^{01}


Geriatrics


Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of zoledronic acid in the elderly. However, elderly patients are more likely to have age-related problems such as renal function impairment,^{03} which may require caution in patients receiving zoledronic acid.^{01}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Aminoglycosides    (concomitant use with zoledronic acid may have an additive effect to lower serum calcium level for prolonged periods.^{01}{02})


Loop diuretics    (concomitant use with zoledronic acid may cause an increased risk of hypocalcemia.^{01})


Thalidomide    (concomitant use with zoledronic acid may increase the risk of renal dysfunction^{11})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Hypersensitivity to zoledronic acid or other bisphosphonates, or any of the excipients in the formulation^{01}
» Renal function, severe impairment    (Bone metastases: administration of zoledronic acid to patients with severe renal impairment (serum creatine > 3.0 mg per dL) is not recommended due to the risk of significant deterioration of renal function which may progress to renal failure^{11}.)


Risk-benefit should be considered when the following medical problems exist
Asthma, aspirin–sensitive    (while not observed in zoledronic acid clinical trials, administration of other bisphosphonates has been associated with bronchoconstriction in aspirin–sensitive asthma patients.^{01})


Cardiac disease    (overhydration should be avoided when zoledronic acid is administered in patients with cardiac disease, especially in the elderly, because saline overload may precipitate cardiac failure.^{02})


» Renal function impairment    (Hypercalcemia of malignancy—treatment should be considered only if risks and benefits of treatment are evaluated in patients with serum creatinine > 400 micromole per L or > 4.5 mg per dL.^{11} Increased risk of renal adverse reactions due to zoledronic acid being primarily excreted by the kidney^{01}{02})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Calcium, serum and
Electrolytes, serum and ^{12}{11}
Magnesium, serum and
Phosphate, serum and
Potassium, serum    (determinations recommended periodically during therapy;^{01}{02} either serum ionized calcium or total serum calcium concentrations corrected [adjusted] for albumin should be monitored^{02})


Complete blood count with differential and
Hematocrit and
Hemoglobin    (determinations recommended periodically during therapy;^{01}{02} patients with pre-existing anemia, leukopenia, or thrombocytopenia should be assessed regularly^{02})


» Creatinine, serum and
Renal function    (determinations recommended prior to, during, and periodically after treatment; serum creatinine should be evaluated prior to each dose for patients requiring repeated treatment with zoledronic acid^{01}{02})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Anemia ( pale skin; troubled breathing; unusual bleeding or bruising; unusual tiredness or weakness)— disease state may be a contributing factor^{01}
    
asthenia (lack or loss of strength )^{01}
    
cancer progression
^{11}    
chest pain ^{01}{02}
    
dyspnea (shortness of breath, difficult or labored breathing; tightness in chest; wheezing)—disease state may be a contributing factor^{01}
    
granulocytopenia, pancytopenia, or thrombocytopenia (black, sticky stools; lower back or side pain; painful or difficult urination; unusual bleeding or bruising; unusual tiredness or weakness)^{01}
    
hypocalcemia ( convulsions; irregular heartbeats; mood or mental changes, confusion; muscle cramps or shaking of hands, arms, feet, legs, or face; numbness and tingling around the mouth, fingertips, or feet)^{01}{02}
    
hypokalemia ( convulsions; irregular heartbeat; nausea or vomiting ; mood changes; muscle pain or cramps )^{01}
    
hypomagnesemia ( muscle trembling or twitching)^{01}{02}
    
hypophosphatemia ( unusual tiredness or weakness )^{01}{02}
    
hypotension (blurred vision; confusion; dizziness, faintness, or lightheadedness when getting up from a lying or sitting position; suddenly sweating; unusual tiredness or weakness )^{11}
    
malignant neoplasm, aggravated ^{11}(worsening of cancer)
    
moniliasis ( skin rash; cracks in skin at the corners of mouth; soreness or redness around fingernails and toenails)^{01}
    
neutropenia (chills; cough; fever; sore throat; sores, ulcers, or white spots on lips or in mouth; swollen glands; black, tarry, stools; lower back or side pain; painful or difficult urination; pale skin; shortness of breath; unusual bleeding or bruising; unusual tiredness or weakness)^{11}
    
pleural effusion (chest pain; shortness of breath)^{01}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Abdominal pain — disease state may be a contributing factor^{01}
    
agitation (anxiety; nervousness; restlessness; irritability; dry mouth; shortness of breath; hyperventilation; trouble sleeping; irregular heartbeats; shaking)^{11}
    
alopecia (hair loss; thinning of hair)^{11}
    
anorexia ( loss of appetite ; weight loss)— disease state may be a contributing factor^{01}
    
anxiety (fear; nervousness)—disease state may be a contributing factor
^{11}    
arthralgias ( pain, swelling, or redness in joints; muscle pain or stiffness; difficulty in moving)^{01}{02}
    
back pain ^{11}
    
constipation —disease state may be a contributing factor^{01}
    
confusion
    
cough — disease state may be a contributing factor^{11}
    
dehydration ^{01}
    
depression ( discouragement; feeling sad or empty; irritability; lack of appetite; loss of interest or pleasure; tiredness; trouble concentrating; trouble sleeping )
^{11}    
dermatitis ( blistering, crusting, irritation, itching, or reddening of skin; cracked, dry, scaly skin; swelling)
^{11}    
diarrhea —disease state may be a contributing factor^{01}
    
dizziness ^{11}
    
dysphagia ( difficulty swallowing)^{01}
    
fatigue (unusual tiredness or weakness)^{{11}{12}
{11}}    
fever ^{01}{02}
    
headache ^{01}
    
hypoesthesia ( partial loss of feeling)^{11}{12}
    
insomnia (sleeplessness; trouble sleeping; unable to sleep)— disease state may be a contributing factor^{01}
    
leg edema (swelling of leg)^{01}
    
mucositis ( cracked lips; diarrhea; difficulty in swallowing; sores, ulcers, or white spots on lips, tongue, or inside mouth)
    
myalgia (joint pain; swollen joints; muscle aching or cramping; muscle pains or stiffness; difficulty in moving)^{11}
    
nausea —disease state may be a contributing factor^{01}{02}
    
paresthesia (burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings)^{11}
    
pyrexia (fever)^{11}
    
rigors ( feeling unusually cold, shivering)^{11}
    
skeletal pain — disease state may be a contributing factor^{01}{02}
    
somnolence (sleepiness or unusual drowsiness)^{01}
    
upper respiratory tract infection (ear congestion; nasal congestion; chills; cough; fever; sneezing; sore throat; body aches or pain; headache; loss of voice; runny nose; unusual tiredness or weakness; difficulty in breathing)^{11}
    
urinary tract infection (bladder pain; bloody or cloudy urine; difficult, burning, or painful urination; frequent urge to urinate; lower back or side pain)—disease state may be a contributing factor^{11}
    
vomiting —disease state may be a contributing factor^{01}{02}
    
weakness ^{11}
{11}
Incidence less frequent
    
Bradycardia ( chest pain or discomfort; lightheadedness, dizziness or fainting; shortness of breath; slow or irregular heartbeat; unusual tiredness)
    
hallucination ( seeing, hearing, or feeling things that are not there)
    
pruritus (itching skin)
    
taste perversion (change in taste; bad, unusual or unpleasant (after)taste)
    
thirst
^{11}{12}




Overdose
For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing).

Clinical effects of overdose
There has been no experience of acute overdose with zoledronic acid. It has been shown to cause clinically relevant reductions in serum levels of calcium, phosphorus, and magnesium.^{01}

In controlled clinical trails zoledronic acid has been shown to cause increased risk of renal toxicity when infused over 5 minutes rather than 15 minutes.^{01}
    
Hypocalcemia (convulsions; irregular heartbeats; mood or mental changes, confusion; muscle cramps or shaking of hands, arms, feet, legs, or face; numbness and tingling around the mouth, fingertips, or feet)
    
hypophosphatemia ( unusual tiredness or weakness)
    
hypomagnesemia ( drowsiness; loss of appetite; muscle twitching or trembling; nausea or vomiting; unusual tiredness or weakness^{01})


Treatment of overdose
There is no known specific antidote to zoledronic acid. Treatment is generally symptomatic and supportive. ^{01}

Reductions in serum levels of calcium, phosphorus, and magnesium should be corrected by intravenous administration of calcium gluconate, potassium or sodium phosphate, and magnesium sulfate, respectively.^{01}


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Zoledronic Acid (Systemic).

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to zoledronic acid or other bisphosphonates
Other medical problems, especially renal function impairment

Proper use of this medication

» Proper dosing

Precautions while using this medication
» Importance of renal function assessment before treatment and during treatment.

Follow-up
Periodic renal function monitoring post treatment


Side/adverse effects
Signs of potential side effects, especially aggravated malignant neoplasm, anemia, asthenia, cancer progression, chest pain, dyspnea, granulocytopenia, hypocalcemia, hypokalemia, hypomagnesia, hypophosphatemia, hypotension, moniliasis, neutropenia pancytopenia, pleural effusion, or thrombocytopenia


General Dosing Information
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.^{01}{02}

Strict adherence to the intravenous route is recommended for the parenteral administration of zoledronic acid.^{01}{02}

No clinical or pharmacokinetic data exists for patients with severe renal impairment and should be used in these patients only if the expected benefits outweighs the risk.^{01}{02}

Consideration should be given to the severity of, as well as the symptoms of, tumor-induced hypercalcemia when considering the use of zoledronic acid. Vigorous saline hydration (with or without loop diuretics) alone may be sufficient to treat mild, asymptomatic hypercalcemia.^{01}

Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Patients should be hydrated throughout the treatment, but over-hydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia.^{01}{02}

Retreatment Criteria—Retreatment with a 4 mg dose of zoledronic acid may be considered if serum calcium does not return to normal or remain normal after initial treatment. It is recommended that a minimum of 7 days elapse before retreatment to allow for full response to the initial dose. Serum creatinine must be evaluated prior to each dose. The potential risk for renal failure with subsequent dosing must be carefully weighed against the potential benefits of treatment and other treatment options. Consideration should be given as to whether the potential benefit of treatment outweighs the possible risk.^{01}{02}

The following criteria should be applied in patients requiring retreatment and who experience a decrease in renal function after the initial treatment.^{03}   • If patients have a normal serum creatinine prior to treatment but have an increase of 0.5 mg/dL within two weeks of their next dose the next dose should be withheld until the serum creatinine is at least within 10% of their baseline value.^{01}
   • If patients have an abnormal serum creatinine prior to treatment but have an increase of 1.0 mg/dL within two weeks of their next dose the next dose should be withheld until the serum creatinine is at least within 10% of their baseline value.^{01}
Note: Canadian manufacturer states that the recommended dose for retreatment is 8 mg.^{02}





Parenteral dosage form

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.


ZOLEDRONIC ACID FOR INJECTION

Usual Adult Dose
Hypercalcemia
Intravenous infusion, 4 mg given as a single dose over no less than 15 minutes.^{01}{02}

Metastases, bone from solid tumors^{11}
Multiple myeloma^{11}1
Intravenous infusion , 4 mg, in 100–mL solution, infused over 15 minutes every 3 to 4 weeks.^{04}{11}{12}

Daily administration of an oral calcium supplement of 500 mg and a multiple vitamin containing 400 IU of Vitamin D is recommended.^{11}

Note: Canadian product information states bone metastases specifically due to prostate cancer.^{12}



Note: Due to the risk of clinically significant deterioration in renal function, which may progress to renal failure, prescribing limits, and duration of infusion must be adhered to.^{01}


Usual adult prescribing limits
4 mg per dose, and it is recommended that there must be a minimum of 7 days before retreatment.^{01}

Note: Canadian manufacturer states that the recommended dose for retreatment is 8 mg.^{02}{12}


Usual Pediatric Dose
Safety and efficacy have not been established.^{01}

Usual Geriatric Dose
Dose selection for elderly patients should be cautious due to the greater frequency of geriatric-specific problems.^{01}

Strength(s) usually available
U.S.—


4 mg per vial (Rx) [Zometa (mannitol, USP) (sodium citrate, USP)]^{01}

Canada—


4 mg per vial (Rx) [Zometa (mannitol, USP) (sodium citrate, USP)]^{02}

Packaging and storage:
Store at 25 °C (77 °F), excursions permitted between 15 and 30 °C (59 and 86 °F).^{01}

Preparation of dosage form:
Zoledronic acid is reconstituted by adding 5 mL of Sterile Water for Injection, USP to the vial. The drug must be completely dissolved before the solution is withdrawn.^{01}

The maximum recommended 4 mg dose must be further diluted in 100 mL of sterile 0.9% Sodium Chloride, USP, or 5% Dextrose Injection, USP.^{01}

Note: Canadian manufacturer states to prepare an infusion solution containing 8 mg of zoledronic acid, two vials are each reconstituted with 5 mL of Sterile Water for injection, .^{02}and is further diluted in 100 mL of sterile 0.9% Sodium Chloride, USP, or 5% Dextrose Injection, USP.^{12}


Stability:
If not used immediately, the solution should be refrigerated between 2 and 8 °C (36 and 46 °F). The total time between reconstitution, dilution, storage in the refrigerator, and end of administration must not exceed 24 hours.^{01}{02}

Incompatibilities:
Zoledronic acid for injection should not be mixed with calcium-containing infusion solutions, such as Lactated Ringer's solution.^{01}{02}

Zoledronic acid should be administered as a single intravenous solution in a separate line from all other drugs.^{01}{02}

Developed: 10/15/01
Revised: 10/21/2002

References

1. Product Information: Zometa®, zoledronic acid. Novartis Pharmaceuticals, East Hanover, NJ. (PI issued 8/2001)
   

2. Product Information: ^PrZometa®, zoledronic acid. Novartis Pharmaceuticals Canada Inc., Dorval, Quebec. (PI issued 8/2000) PI revised 1/2001.
   

3. USP Expert Committee review comments, 10/2001.
   

4. Reviewers' consensus on the use of zoledronic acid for the treatment of osteolytic bone metastases, 1/2/02.
   

5. Berenson JR, Rosen LS, Howell A, et al. Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases. Cancer 2001; 91(7): 1191-200.
   

6. Coleman RE, Seaman JJ. The role of zoledronic acid in cancer: clinical studies in the treatment and prevention of bone metastases. Semin Oncol 2001; 28(2 Suppl 6): 11-6.
   

7. Berenson JR. Zoledronic acid in cancer patients with bone metastases: results of Phase I and II trials. Semin Oncol 2001; 28(2 Suppl 6): 25-34.
   

8. Rosen LS, Gordon D, Kaminski M, et al. Zoledronic acid vs. pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J 2001; 7(5): 377-87.
   

9. Rosen L Gordon D, Tchekmedyian S, et al. Zometa® significantly increased the median time to first skeletal related event (SRE) in patients with osteolytic bone metastases from non-small cell lung cancer (NSCLC) and other solid tumors (OST). 2nd international Chicago symposium on malignancies of the chest, head and neck. Lung Cancer 2001; 34 (Suppl 1): S67.
   

10. Lipton A, Small E, Saad F, et al. The new bisphosphonate, Zometa ® (zoledronic acid) decreases skeletal complications in both lytic and blastic lesions: a comparison to pamidronate. Chemotherapy Foundation Symposium XIX innovative cancer therapy for tomorrow, 2001; New York, NY: 45-6 [Abst 34].
    

11. Product Information: Zometa®, zoledronic acid. Novartis Pharmaceuticals, East Hanover, NJ. (PI revised 02/2002) reviewed 09/2002.
    

12. Product Information: ^PrZometa®, zoledronic acid. Novartis Pharmaceuticals Canada Inc, Dorval, Quebec (PI revised 07/2002) reviewed 09/2002.
    

Link to this page

Printable Version

Email Page