Zometa

Generic Name: Zoledronic Acid
Class: Bone Resorption Inhibitors
VA Class: HS900
Chemical Name: [1-Hydroxy-2-(1H-imidazol-1-yl)ethylidene]bis-phosphonic acid monohydrate
Molecular Formula: C₅H₁₀N₂O₇P₂•H₂O
CAS Number: 165800-06-6

Special Alerts:

[Posted 09/01/2011] ISSUE: FDA notified healthcare professionals and patients of an update to the drug label for zoledronic acid (Reclast) regarding the risk of kidney failure. Cases of acute renal failure requiring dialysis or having a fatal outcome following Reclast use have been reported to FDA. The revised label states that Reclast is contraindicated in patients with creatinine clearance less than 35 mL/min or in patients with evidence of acute renal impairment. The label also recommends that healthcare professionals screen patients prior to administering Reclast in order to identify at-risk patients.

The Reclast Medication Guide for patients is being updated to contain information about the risk of severe kidney problems. In addition, the manufacturer of Reclast will issue a Dear Healthcare Provider letter to inform healthcare professionals about this risk.

BACKGROUND: Risk factors for developing renal failure include underlying moderate to severe renal impairment, use of kidney-damaging (nephrotoxic) or diuretic medications at the same time as Reclast, or severe dehydration occurring before or after Reclast is given. The risk of developing renal failure in patients with underlying renal impairment also increases with age.

These labeling changes are being made to the Reclast label only, although zoledronic acid, also sold as Zometa, is approved for treatment of cancer-related indications. Renal toxicity is already addressed in the Warnings and Precautions section of the Zometa label. Dose reductions for Zometa are provided for patients with renal impairment.

RECOMMENDATIONS: Reclast is contraindicated in patients with creatinine clearance less than 35 mL/min, or in patients with evidence of acute renal impairment. Healthcare professionals should screen patients prior to administering Reclast in order to identify at-risk patients. Healthcare professionals should also monitor renal function in patients who are receiving Reclast. For more information visit the FDA website at: and .

[Posted 10/13/2010] ISSUE: FDA is updating the public regarding information previously communicated describing the risk of atypical fractures of the thigh, known as subtrochanteric and diaphyseal femur fractures, in patients who take bisphosphonates for osteoporosis. This information will be added to the Warnings and Precautions section of the labels approved to treat osteoporosis, including alendronate (Fosamax), alendronate with cholecalciferol (Fosamax Plus D), risedronate (Actonel and Atelvia), risedronate with calcium carbonate (Actonel with Calcium), ibandronate (Boniva), tiludronate (Skelid), and zoledronic acid (Reclast) and their generic products. A Medication Guide will also be required to be given to patients when they pick up their bisphosphonate prescription.

BACKGROUND: Atypical subtrochanteric femur fractures are fractures in the bone just below the hip joint. Diaphyseal femur fractures occur in the long part of the thigh bone. These fractures are very uncommon and appear to account for less than 1% of all hip and femur fractures overall. Although it is not clear if bisphosphonates are the cause, these unusual femur fractures have been predominantly reported in patients taking bisphosphonates.

RECOMMENDATIONS: Patients should continue to take their medication unless told to stop by their healthcare professional. FDA recommends that healthcare professionals should discontinue potent antiresorptive medications (including bisphosphonates) in patients who have evidence of a femoral shaft fracture. For more information visit the FDA website at: and .

[Posted 03/11/2010] FDA notified healthcare professionals and patients that at this point, the data that FDA has reviewed have not shown a clear connection between bisphosphonate use and a risk of atypical subtrochanteric femur fractures. FDA is working with outside experts, including members of the recently convened American Society of Bone and Mineral Research Subtrochanteric Femoral Fracture Task Force, to gather more information and evaluate the issue further.

FDA recommends that healthcare professionals follow the recommendations in the drug label when prescribing oral bisphosphonates.

Patients should continue taking oral bisphosphonates unless told by their healthcare professional to stop. Patients should talk to their healthcare professional if they develop new hip or thigh pain or have any concerns with their medications. For more information visit the FDA website at: and .

[Posted 11/12/2008] FDA issued an update to the Agency’s review of safety data regarding the potential increased risk of atrial fibrillation in patients treated with a bisphosphonate drug. Bisphosphonates are a class of drugs used primarily to increase bone mass and reduce the risk for fracture in patients with osteoporosis, slow bone turnover in patients with Paget’s disease of the bone, and to treat bone metastases and lower elevated levels of blood calcium in patients with cancer. FDA reviewed data on 19,687 bisphosphonate-treated patients and 18,358 placebo-treated patients who were followed for 6 months to 3 years. The occurrence of atrial fibrillation was rare within each study, with most studies containing 2 or fewer events. Across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or non-serious atrial fibrillation was observed. Additionally, increasing dose or duration of bisphosphonate therapy was not associated with an increase rate of atrial fibrillation. Healthcare professionals should not alter their prescribing patterns for bisphosphonates and patients should not stop taking their bisphosphonate medication. For more information visit the FDA website at: , and .

[Posted 01/07/2008] FDA informed healthcare professionals and patients of the possibility of severe and sometimes incapacitating bone, joint, and/or muscle (musculoskeletal) pain in patients taking bisphosphonates. Although severe musculoskeletal pain is included in the prescribing information for all bisphosphonates, the association between bisphosphonates and severe musculoskeletal pain may be overlooked by healthcare professionals, delaying diagnosis, prolonging pain and/or impairment, and necessitating the use of analgesics. The severe musculoskeletal pain may occur within days, months, or years after starting a bisphosphonates. Some patients have reported complete relief of symptoms after discontinuing the bisphosphonate, whereas others have reported slow or incomplete resolution. The risk factors for and incidence of severe musculoskeletal pain associated with bisphosphonates are unknown.

Healthcare professionals should consider whether bisphosphonate use might be responsible for severe musculoskeletal pain in patients who present with these symptoms and consider temporary or permanent discontinuation of the drug. For more information visit the FDA website at: and .

[Posted 10/01/2007] FDA issued an early communication about the ongoing review of new safety data regarding the association of atrial fibrillation with the use of bisphosphonates. Bisphosphonates are a class of drugs used primarily to increase bone mass and reduce the risk for fracture in patients with osteoporosis, slow bone turnover in patients with Paget’s disease of the bone, treat bone metastases, and lower elevated levels of blood calcium in patients with cancer.

FDA reviewed spontaneous postmarketing reports of atrial fibrillation reported in association with oral and intravenous bisphosphonates and did not identify a population of bisphosphonate users at increased risk of atrial fibrillation. In addition, as part of the data review for the recent approval of once-yearly Reclast for the treatment of postmenopausal osteoporosis, FDA evaluated the possible association between atrial fibrillation and the use of Reclast (zoledronic acid). Most cases of atrial fibrillation occurred more than a month after drug infusion. Also, in a subset of patients monitored by electrocardiogram up to the 11th day following infusion, there was no significant difference in the prevalence of atrial fibrillation between patients who received Reclast and patients who received placebo.

Upon initial review, it is unclear how these data on serious atrial fibrillation should be interpreted. Therefore, FDA does not believe that healthcare providers or patients should change either their prescribing practices or their use of bisphosphonates at this time. For more information visit the FDA website at: and .

REMS:

FDA approved a REMS for zoledronic acid to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Synthetic bisphosphonate; bone resorption inhibitor.^{1 4 5}

Uses for Zometa

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Hypercalcemia Associated with Malignancy

Used in conjunction with achievement and maintenance of adequate hydration for the treatment of moderate to severe hypercalcemia (albumin-corrected serum calcium concentration ≥12 mg/dL) associated with malignant neoplasms.^{1 2 3 5}

Retreatment may be considered in patients with recurrent or refractory disease.^{1 2 3}

Bone Metastases of Solid Tumors and Osteolytic Lesions of Multiple Myeloma

Used as an adjunct to antineoplastic therapy for the treatment of osteolytic bone metastases of solid tumors and osteolytic lesions of multiple myeloma.^{1 7}

Second-line therapy of bone metastases associated with prostate cancer in patients with disease progression following one or more hormonal therapies.^{1 3}

Prevention of Aromatase Inhibitor-associated Bone Loss in Postmenopausal Women

May be considered a reasonable choice (accepted, with possible conditions) in postmenopausal women with early-stage breast cancer receiving aromatase inhibitor therapy† who have no additional risk factors and in whom BMD is at least 2.5 standard deviations below normal (T-scores at or below -2.5) either at baseline or during aromatase inhibitor therapy.^{27 10005}

May be considered a reasonable choice (accepted, with possible conditions) on an individualized basis in postmenopausal women with early-stage breast cancer receiving aromatase inhibitor therapy† who have moderate osteopenia (T-scores at or below -2) and have a history of a prior fracture or another clinically important risk factor (e.g., age, maternal history of fracture, low weight or body mass index) or lifestyle-related factor as defined by WHO; such women are at moderate to high risk for fracture development.²⁷

Prevention of Aromatase Inhibitor-associated Bone Loss in Premenopausal Women

Use not fully established because of unclear risk/benefit.²⁷ Improvements in BMD observed in premenopausal women with early-stage breast cancer receiving zoledronic acid concurrently with an aromatase inhibitor-gonadotropin-releasing hormone agonist regimen†.¹⁰⁰⁰⁴ However, long-term follow-up needed, especially as women enter menopause, to establish whether zoledronic acid is associated with clinically important fracture reduction.¹⁰⁰⁰⁴

Zometa Dosage and Administration

General

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Monitor hematocrit and hemoglobin regularly.¹

  
  


• 
  

  Evaluate S_cr prior to administration of each dose.^{1 3} (See Renal Effects under Cautions.)

  
  


• 
  

  Carefully monitor standard hypercalcemia-related metabolic parameters (e.g., serum concentrations of calcium, phosphate, magnesium, other electrolytes) following initiation of therapy.¹

  
  

Hypercalcemia Associated with Malignancy

• 
  

  Adequately hydrate patients prior to treatment initiation and throughout treatment.^{1 3} Avoid overhydration, especially in patients at risk for the development of heart failure.^{1 3} Attempt to restore urine output to 2 L/day throughout treatment.¹

  
  

Bone Metastases of Solid Tumors and Osteolytic Lesions of Multiple Myeloma

• 
  

  Supplemental calcium (500 mg of elemental calcium daily) and a multivitamin containing vitamin D (400 units daily) is recommended in patients with multiple myeloma or bone metastases associated with solid tumors.^{1 7} (See Metabolic Effects under Cautions.)

  
  

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion.^{1 3 7}

Must be diluted prior to administration.¹

Dilution

Withdraw the appropriate volume of zoledronic acid concentrate needed to provide the prescribed dose (see Table 1) from the 5-mL vial and dilute in 100 mL of 0.9% sodium chloride or 5% dextrose injection.¹ Increased risk of renal impairment or failure associated with smaller infusion volumes (e.g., 50 mL).^{3 4 7}

To avoid inadvertent injection of the concentrated solution, do not store the undiluted concentrate in a syringe.¹

Table 1. Zoledronic Acid Dose and Corresponding Volume of Concentrate for Dilution

Zoledronic Acid Dose	Volume of Concentrate to be Diluted
4 mg	5 mL
3.5 mg	4.4. mL
3.3 mg	4.1 mL
3 mg	3.8 mL

Rate of Administration

Administer by IV infusion over ≥15 minutes.^{1 3 7} Rapid IV infusion rates (5 minutes) are associated with an increased risk of renal impairment and renal failure.^{1 3 4 7}

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as zoledronic acid (as the monohydrate); dosage expressed in terms of the anhydrous drug.^{1 1}

Adults

Hypercalcemia Associated with Malignancy

IV

4 mg as a single dose in patients with an albumin-corrected serum calcium concentration of ≥12 mg/dL.^{1 3}

Consider retreatment if serum calcium concentrations do not return to normal or do not remain normal.¹ Initial dose can be repeated ≥7 days after treatment initiation to allow full response to initial dose.¹

Bone Metastases of Solid Tumors and Osteolytic Lesions of Multiple Myeloma

IV

4 mg once every 3–4 weeks in patients with baseline Cl_cr >60 mL/minute.^{1 3} Optimum duration of such therapy is not known, but has been used at the recommended interval for 4–12 months.^{1 3 7}

If renal function deteriorates (defined as an increase in S_cr of ≥0.5 mg/dL) in patients with a baseline S_cr of <1.4 mg/dL, withhold therapy until S_cr returns to within 10% of baseline levels.^{1 3 7} Reinitiate therapy at the same dosage used prior to treatment interruption.^{1 3 7}

Prevention of Aromatase Inhibitor-associated Bone Loss† in Postmenopausal Women

IV

Dosage of 4 mg once every 6 months has been used in clinical trials in women with early-stage breast cancer.¹⁰⁰⁰¹

Prescribing Limits

Adults

Hypercalcemia Associated with Malignancy

IV

Maximum 4 mg as a single dose.^{1 3 5 7} Safety and efficacy of >1 course of retreatment not established.^{2 3}

Bone Metastases of Solid Tumors and Osteolytic Lesions of Multiple Myeloma

IV

Maximum 4 mg as a single dose.^{1 3 5 7}

Special Populations

Hepatic Impairment

No dosage recommendations at this time.¹

Renal Impairment

Hypercalcemia Associated with Malignancy

IV

Dosage adjustments are not necessary in patients with mild to moderate renal impairment (S_cr <4.5 mg/dL).¹

Bone Metastases of Solid Tumors and Osteolytic Lesions of Multiple Myeloma

IV

In patients with mild to moderate renal impairment (baseline Cl_cr of 30–60 mL/minute), lower initial dosages of zoledronic acid are recommended.¹ (See Table 2.)

Table 2. Initial Dosage in Adults with Bone Metastases of Solid Tumors and Osteolytic Lesions of Multiple Myeloma Based on Renal Function

Calculated Clcr (mL/minute)	IV Dosage
>60	4 mg every 3–4 weeks
50–60	3.5 mg every 3–4 weeks
40–49	3.3 mg every 3–4 weeks
30–39	3 mg every 3–4 weeks

If renal function deteriorates (defined as an increase in S_cr of ≥1 mg/dL) in patients with a baseline S_cr of ≥1.4 mg/dL, withhold therapy until S_cr returns to within 10% of baseline levels.^{1 3 7} Reinitiate therapy at the same dosage that was used prior to the treatment interruption.¹ Studies in this patient population included individuals with S_cr <3 mg/dL.^{1 3 7}

Geriatric Patients

No dosage recommendations at this time.¹

Cautions for Zometa

Contraindications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Known hypersensitivity to zoledronic acid, other bisphosphonates, or any ingredient in the formulation.^{1 2}

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Fetal/Neonatal Morbidity

May cause fetal harm; use not recommended in pregnant women, and women of childbearing potential should avoid conception during therapy.¹ (See Advice to Patients.)

Renal Effects

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Renal toxicity (e.g., deterioration of renal function and potential renal failure)^{1 2 3 4 7} has occurred following administration of higher than recommended doses.¹ Renal impairment also has occurred after administration of the usual dose (4 mg) infused over the recommended infusion period (15 minutes)^{1 11} and after administration of the usual initial dose.¹

Risk of adverse renal effects depends on coexisting conditions, concomitant nephrotoxic therapy, preexisting renal disease, dosage, infusion volume and rate, dehydration, and multiple cycles of treatment.^{1 2 3 4 5 7} Such risk factors should be identified and managed.¹ Weigh the risks versus the potential benefits of subsequent treatment in patients with hypercalcemia of malignancy and severe renal impairment if renal function deteriorates during therapy.¹

Monitor S_cr and assess possible deterioration in renal function prior to each dose.^{1 3}

General Precautions

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Metabolic Effects

Possible hypocalcemia, hypophosphatemia, or hypomagnesemia.¹

Carefully monitor standard hypercalcemia-related metabolic parameters (e.g., serum concentrations of calcium, phosphate, magnesium, and potassium) following initiation of therapy.^{1 3} Institute short-term supplemental therapy if hypocalcemia, hypophosphatemia, or hypomagnesemia occurs.^{1 3}

Musculoskeletal Effects

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Osteonecrosis and osteomyelitis of the jaw have been reported in cancer patients receiving bisphosphonates.^{1 12 13 14} Most patients were receiving concurrent chemotherapy and corticosteroids^{1 13 14} and the majority of cases were associated with dental procedures (e.g., tooth extraction).^{1 12 13 14}

A dental examination with appropriate preventive dentistry recommended prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, corticosteroids, poor oral hygiene).^{1 12 13} Avoid invasive dental procedures if possible during therapy in such patients.^{1 13}

Severe, occasionally incapacitating bone, joint, and/or muscle pain have been reported infrequently.¹ The time to the onset of symptoms varied from 1 day to several months after treatment initiation.¹ Such pain improves following discontinuance of the drug and may recur upon subsequent rechallenge.¹

Hematologic Effects

Possible anemia; monitor hematocrit and hemoglobin regularly throughout treatment.¹

Respiratory Effects

Possible bronchoconstriction in aspirin-sensitive asthmatic patients.¹ Use with caution in such patients.¹

Specific Populations

Pregnancy

Category D.¹ (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Not known if zoledronic acid is distributed into milk; discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established.¹ Because of long-term retention in bone, use recommended only if the potential benefit from the drug outweighs the possible risk.¹

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.¹

Possible age-related impaired renal function.¹ Careful renal function monitoring recommended.¹

Renal Impairment

Possible renal toxicity.¹

Use in patients with hypercalcemia of malignancy and severe renal impairment only after consideration of other treatment options.^{1 3} Carefully weigh the possible benefits and risks of therapy.^{1 3} Use not recommended in patients with bone metastases and severe renal impairment.^{1 3} (See Renal Effects under Cautions.)

Common Adverse Effects

Patients with hypercalcemia of malignancy: Fever,^{1 2 3 5} nausea,^{1 2 3 5} constipation,^{1 2 3 5} anemia,^{1 2 3 5} dyspnea,^{1 2 3 5} diarrhea,^{1 2 3} progression of cancer,^{1 3} abdominal pain,^{1 2 3} insomnia,^{1 2 3} vomiting,^{1 2 3} urinary tract infection,^{1 3} anxiety,¹ hypophosphatemia,¹ confusion,^{1 2 3 5} agitation,¹ moniliasis,¹ hypokalemia,^{1 2 3 5} skeletal pain,^{1 3} cough,¹ hypotension,¹ hypomagnesemia.¹

Patients with bone metastases of solid tumors and osteolytic lesions of multiple myeloma: Nausea,^{1 3 5 7} fatigue,^{1 3 7} anemia,^{1 3 5 7} vomiting,^{1 3 7} fever,^{1 3 5 7} constipation,^{1 3 5 7} dyspnea,^{1 3 5 7} diarrhea,^{1 3 7} myalgia,¹ cough,^{1 7} edema of the lower extremities,^{1 7} arthralgia,^{1 3 7} headache,^{1 3 7} dizziness,^{1 3} weight loss,^{1 3 7} paresthesia,^{1 3} depression,^{1 3} abdominal pain,^{1 3} dehydration,^{1 3} limb pain,¹ decreased appetite,¹ neutropenia,^{1 3} urinary tract infection,^{1 3} hypoesthesia,^{1 3} anxiety,¹ alopecia,^{1 7} dermatitis,^{1 3} rigors,^{1 3} thrombocytopenia,³ dyspepsia,¹ upper respiratory tract infection.¹

Interactions for Zometa

Does not inhibit CYP isoenzymes.¹

Nephrotoxic Agents

Potential pharmacologic interaction (increased risk of renal toxicity).¹ Use concomitantly with caution.¹ (See Renal Effects under Cautions.)

Specific Drugs

Drug	Interaction	Comments
Aminoglycosides	Potential for additive effect in lowering serum calcium concentrations1	Such effect not reported1
Loop diuretics	Increased risk of hypocalcemia1	Use caution1
Thalidomide	Potential for increased risk of renal dysfunction in patients with multiple myeloma1

Zometa Pharmacokinetics

Absorption

Onset

Hypercalcemia of malignancy: Normocalcemia usually is apparent within 7–10 days.^{1 2 3}

Duration

Hypercalcemia of malignancy: Median time to recurrence (time to last corrected serum calcium concentration of <11.6 mg/dL) was 30 days.¹

Prostate cancer: Bone-related complications not observed within 10.5 months of therapy.¹

Bone metastases of breast cancer and osteolytic lesions of multiple myeloma: Median time to first bone-related complication was 373 days.¹

Bone metastases of solid tumors other than breast or prostate cancer: Median time to the first bone-related complication was 230 days.¹

Special Populations

In adults with mild or moderate renal impairment, the AUC is increased 15 or 43%, respectively, compared with patients with normal renal function.¹

Distribution

Extent

Distributes rapidly to skeletal tissues.¹ Subsequently, the drug is released systemically via bone turnover.¹ Not known whether distributed into breast milk.¹

Plasma Protein Binding

Approximately 22%.¹

Elimination

Metabolism

No evidence of metabolism.¹

Elimination Route

In patients with cancer and bone metastases, excreted in urine (39% within 24 hours) as unchanged drug.¹

Half-life

Terminal half-life is 146 hours.¹

Special Populations

Pharmacokinetics not evaluated in patients with hepatic impairment and in pediatric patients.¹

Pharmacokinetics not affected by age or race in patients with cancer and bone metastases.¹

Stability

Storage

Parenteral

Solution for Injection

25°C (may be exposed to 15–30°C).¹ Following dilution, 2–8°C; use within 24 hours.¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Do not admix with other agents.¹

Solution Compatibility¹

Compatible
Dextrose 5% in water
Sodium chloride 0.9%
Incompatible
Ringer’s injection, lactated

Actions

• 
  

  Incorporates into bone and selectively inhibits osteoclast-mediated bone resorption.^{1 4 5}

  
  


• 
  

  Inhibits increased osteoclastic activity and skeletal calcium release induced by tumors.¹

  
  


• 
  

  Decreases serum calcium and phosphorus and increases urinary calcium and phosphorus excretion in patients with hypercalcemia of malignancy.¹

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 3} Advise women of childbearing potential to avoid pregnancy.¹ If pregnant, apprise of potential fetal hazard.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

  
  


• 
  

  Importance of advising patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Zoledronic Acid

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, concentrate, for IV infusion	4 mg (of anhydrous zoledronic acid) per 5 mL	Zometa	Novartis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Reclast 5MG/100ML Solution (NOVARTIS): 100/$1,137.19 or 300/$3,282.53

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Novartis. Zometa (zoledronic acid) injection prescribing information. East Hanover, NJ; 2005 Apr.

2. Major P, Lortholary A, Han J et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol. 2001; 19:558-67. [IDIS 460631] [PubMed 11208851]

3. Novartis Pharmaceuticals, East Hanover, NJ; Personal communication.

4. Brown DL, Robbins R. Developments in the therapeutic applications of bisphosphonates. J Clin Pharmacol. 1999; 39:651-60. [IDIS 430233] [PubMed 10392318]

5. Cheer SM, Noble S. Zoledronic acid. Drugs. 2001; 61:799-805. [PubMed 11398911]

6. Anon. Zoledronate (Zometa). Med Lett Drugs Ther. 2001; 43:110-11. [PubMed 11740412]

7. Rosen LS, Gordon D, Kaminski M et al. Zoledronic acid versus 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; 7:377-87. [PubMed 11693896]

8. Green JR. Chemical and biological prerequisites for novel bisphosphonate molecules: Results of comparative preclinical studies. Semin Oncol. 2001; 28(Suppl. 6):4-10 [PubMed 11346859]

9. Plosker GL, Goa KL. Clodronate. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. Drugs. 1994; 47:945-82. [PubMed 7521833]

10. Coukell AJ, Markham A. Pamidronate. A review of its use in the management of osteolytic bone metastases, tumour-induced hypercalcaemia and Paget’s disease of bone. Drugs Aging. 1998; 12:149-68. [PubMed 9509293]

11. Bone HG, Santora AC. Ten years of alendronate treatment for osteoporosis in postmenopausal women. N Engl J Med. 2004; 351:191-2.

12. Ruggiero SL, Mehrotra B, Rosenberg TJ et al. Osteonecrosis of the jaw associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg. 2004; 62:527-34. [IDIS 518769] [PubMed 15122554]

13. Hohneker JA. Dear doctor letter regarding osteonecrosis of the jaw in patients with cancer receiving bisphophonates. East Hanover, NJ: Novartis; 2004 September 24.

14. Ruggiero SL, Mehrotra B. Ten years of alendronate treatment for osteoporosis in postmenopausal women. N Engl J Med. 2004; 351:191.

26. Eidtmann H, Bundred NJ, DeBoer R et al. The effect of zoledronic acid on aromatase inhibitor associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36 months follow up of ZO-FAST. Oral presentation at Annual San Antonio Breast Cancer Symposium. San Antonio, TX: 2008 Dec 12. Accessed from website on 12/15/2008.

27. Zoledronic Acid Final Determination. Published May 2008. From AHFS website.

28. Gnant M, Mlineritsch B, Luschin-Ebengreuth G et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density study. Lancet Oncol. 2008; 9:840-49. [PubMed 18718815]

10001. Brufsky A, Harker WG, Beck JT et al. Zoledronic acid inhibits adjuvant letrozole-induced bone loss in postmenopausal women with early breast cancer. J Clin Oncol. 2007; 25: 829-36. [PubMed 17159193]

10002. Brufsky A, Lund K, Cobb P et al. Twenty-four month follow-up of the effect of zoledronic acid on aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole. Poster presented at Annual San Antonio Breast Cancer Symposium. San Antonio, TX: 2006 Dec 16. Abstract 5060. Accessed from website on 4/29/2008.

10003. Mincey BA, Dentchev TG, Sloan JA et al. NO3CC- A randomized, controlled, open-label trial of upfront versus delayed zoledronic acid for prevention of bone loss in postmenopausal women with primary breast cancer starting letrozole after tamoxifen. J Clin Oncol. 2008; 26: Abstract No. 564.

10004. Gnant MF, Mlineritsch B, Luschin-Ebengreith G et al. Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2007; 25: 820-8. [PubMed 17159195]

10005. Hillner BE, Ingle JN, Chelebowski RT et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol. 2003; 21:4042-57. [IDIS 513063] [PubMed 12963702]

10006. Eastell R. Breast cancer and the risk of osteoporotic fracture: a paradox. J Clin Endocrinol Metab. 2007; 92: 42-3. [PubMed 17209223]

10007. Cummings SR, Bates D, Black DM. Clinical use of bone densitometry: scientific review. JAMA. 2002; 288: 1889-97. [PubMed 12377088]

10008. Wasnich RD, Miller PD. Antifracture efficacy of antiresorptive agents are related to changes in bone density. J Clin Endocrinol Metab. 2000; 85; 231-6. [PubMed 10634392]

10009. Hochberg MC, Greenspan S, Wasnich RD, et al. Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. J Clin Endocrinol Metab. 2002; 87: 1586-92. [PubMed 11932287]

10010. Phase III randomized study of immediate versus delayed zoledronate for prevention of bone loss in postmenopausal women with stage I-IIIA breast cancer initiating letrozole after prior treatment with tamoxifen. Accessed from website on June 4, 2008.

10011. US Food and Drug Administration (FDA). Guidance for preclinical and clinical evaluation of agents used in the prevention of postmenopausal osteoporosis. Rockville, MD: FDA; 1994 Apr.

10012. Gnant MF, Jakesz R, Mlineritsch B et al. Zoledronic acid effectively counteracts cancer treatment induced bone

Zostrix Neuropathy

Generic Name: capsaicin topical (kap SAY sin TOP i kal)

Brand Names: Axsain, Capsicum Oleoresin, Capsin, Capzasin Back and Body, Capzasin Quick Relief, Capzasin-HP, Capzasin-P, Castiva Warming, Dolorac, Icy Hot PM, Icy Hot with Capsaicin, Menthac Arthritis Cream with Capsaicin, Qutenza, Salonpas Gel-Patch, Salonpas Pain Patch with Capsaicin, Sloan's Liniment, Trixaicin, Trixaicin HP, Zostrix, Zostrix Diabetic Foot Pain, Zostrix Foot Pain, Zostrix Neuropathy, Zostrix Sports, Zostrix-HP

What is Zostrix Neuropathy (capsaicin topical)?

Capsaicin is the active ingredient in chili peppers that makes them hot. Capsaicin is used in medicated creams and lotions to relieve muscle or joint pain.

Capsaicin used on the body causes a sensation of heat that activates certain nerve cells. With regular use of capsaicin, this heating effect reduces the amount of substance P, a chemical that acts as a pain messenger in the body.

Capsaicin topical is used for temporary relief of muscle or joint pain caused by strains, sprains, arthritis, bruising, or backaches. Capsaicin topical is also used to treat nerve pain (neuralgia) in people who have had herpes zoster, or "shingles."

Capsaicin topical may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Zostrix Neuropathy (capsaicin topical)?

Do not use this medication if you are allergic to chili peppers, or if you have ever had an allergic reaction to capsaicin topical.

Ask a doctor or pharmacist about using capsaicin topical if you have any allergies or serious medical conditions. Do not use this medication on anyone younger than 18 years old without the advice of a doctor.

Capsaicin can cause a burning sensation, which is usually mild and should lessen over time with continued use. If the burning sensation causes significant discomfort, wash the treated skin area with soap and cool water. Stop using the medication and call your doctor if you have severe burning or redness where the medicine was applied.

Avoid getting capsaicin topical in your mouth or eyes or near your nose.

Do not apply to open wounds or irritated skin, and avoid getting the medicine on contact lenses, dentures, and other items that come into contact with sensitive areas of your body.

Seek emergency medical attention if you think you have used too much of this medicine, or if anyone has accidentally swallowed it. Accidental swallowing of capsaicin can cause problems with swallowing or breathing.

It may take up to 2 weeks of using this medicine regularly before your symptoms improve. For best results, keep using the medication as directed.

Call your doctor if your pain does not improve after using this medication for 7 days, or if your symptoms get worse or get better and then come back in a few days.

What should I discuss with my healthcare provider before using Zostrix Neuropathy (capsaicin topical)?

Do not use this medication if you are allergic to chili peppers, or if you have ever had an allergic reaction to capsaicin topical.

Ask a doctor or pharmacist about using capsaicin topical if you have any allergies (especially to plants), or if you have a serious medical condition.

It is not known whether capsaicin topical will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. It is not known whether capsaicin topical passes into breast milk or if it could harm a nursing baby. Do not apply capsaicin topical to your breast area if you are breast-feeding a baby. Do not use this medication on anyone younger than 18 years old without the advice of a doctor.

How should I use Zostrix Neuropathy (capsaicin topical)?

Use this medication exactly as directed on the label, or as prescribed by your doctor. Do not use it in larger amounts or for longer than recommended.

Capsaicin can cause a burning sensation wherever it is applied. This sensation is usually mild and should gradually lessen over time with continued regular use of the medicine.

Do not apply capsaicin topical to open wounds, or to skin that is sunburned, windburned, dry, chapped, or otherwise irritated. Do not get this medication in your mouth or eyes, or near your nose where you might inhale it. If it does get into any of these areas, rinse thoroughly with water.

Also avoid getting this medication on contact lenses, dentures, and other items that come into contact with sensitive areas of your body.

To keep the medication from getting on your fingers when you apply it, you may use a rubber glove, finger cot, cotton ball, or clean tissue to apply the medicine.

Make sure your skin is clean and dry before you apply capsaicin topical.

When using capsaicin topical cream or lotion, apply a thin layer to the affected area and rub in gently until completely absorbed.

To use capsaicin topical liquid or stick, uncap the applicator and press it firmly on your skin to apply the medication. Massage gently onto the affected are until completely absorbed.

Capsaicin topical may be used up to 4 times daily or as directed on the medicine label.

To apply a capsaicin topical patch, remove the liner and apply the patch to your skin over the area of pain. Press the edges firmly into place. Remove the patch and apply a new patch 1 or 2 times daily if needed.

Wash your hands with soap and water immediately after applying capsaicin topical or handling the topical patch. If you have applied the medicine to your hands or fingers to treat pain in those areas, wait at least 30 minutes before washing your hands. Do not cover treated skin with a bandage or heating pad, which can increase the burning sensation. You may cover the skin with clothing.

Avoid taking a bath or shower within 1 hour before or after you apply capsaicin topical to your skin. Also avoid swimming or vigorous exercise. Warm water or perspiration can increase the burning sensation caused by capsaicin.

If the burning sensation caused by capsaicin is painful or causes significant discomfort, wash the treated skin area with soap and cool water.

It may take up to 2 weeks of using this medicine regularly before your symptoms improve. For best results, keep using the medication as directed. Pain relief should occur gradually as the substance P in your body is decreased in the nerve cells.

Call your doctor if your pain does not improve after using this medication for 7 days, or if your symptoms get worse or get better and then come back in a few days. Store capsaicin topical at room temperature away from moisture and heat, in a place where children and pets cannot get to it.

Capsaicin topical liquid is flammable. Do not use or store near fire or open flame.

What happens if I miss a dose?

Use the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not apply capsaicin more than 4 times in one day, or use extra medicine to make up a missed dose .

A missed dose of capsaicin topical will not cause harm but may make the medication less effective reducing substance P and relieving your pain.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222, especially if anyone has accidentally swallowed it.

Accidental swallowing of capsaicin can cause severe burning in or around the mouth, watery eyes, runny nose, and trouble swallowing or breathing.

Applying too much capsaicin topical to the skin can cause severe burning or redness.

What should I avoid while using Zostrix Neuropathy (capsaicin topical)?

Avoid inhaling the odor or dried residue of capsaicin topical. Inhaling capsaicin can cause coughing, sneezing, or watery eyes, and can irritate your throat or lungs.

Avoid touching your eyes, mouth, nose, genitals, or rectum until the medication has been washed off your hands. Also avoid handling food while the medication is still on your hands.

Avoid exposing treated skin to sunlight, sunlamps, tanning beds, or a hot tub. Capsaicin can cause a burning sensation that may be made worse by heat.

Do not use other medicated skin products, including muscle pain creams or lotions, on areas where you have applied capsaicin, unless your doctor has told you to.

Zostrix Neuropathy (capsaicin topical) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using capsaicin topical and call your doctor at once if you have a serious side effect such as:

• 
  

  severe burning or irritation where the medicine was applied;

  
  


• 
  

  skin redness where the medicine was applied; or

  
  


• 
  

  trouble breathing or swallowing (after accidental inhalation of capsaicin odor or dried residue).

  
  

Less serious side effects may include a mild burning sensation that can last for several hours or days, especially after your first use of capsaicin topical.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Zostrix Neuropathy (capsaicin topical)?

It is not likely that other drugs you take orally or inject will have an effect on topically applied capsaicin. But many drugs can interact with each other. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Zostrix Neuropathy resources

• Zostrix Neuropathy Side Effects (in more detail)
• Zostrix Neuropathy Use in Pregnancy & Breastfeeding
• Zostrix Neuropathy Drug Interactions
• 0 Reviews for Zostrix Neuropathy - Add your own review/rating

• Axsain Cream MedFacts Consumer Leaflet (Wolters Kluwer)


• Axsain Topical Advanced Consumer (Micromedex) - Includes Dosage Information


• Capzasin-P Cream MedFacts Consumer Leaflet (Wolters Kluwer)


• Qutenza Prescribing Information (FDA)


• Qutenza Consumer Overview


• Qutenza Patch MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Zostrix Neuropathy with other medications

• Burning Mouth Syndrome
• Diabetic Nerve Damage
• Osteoarthritis
• Pain
• Persisting Pain, Shingles

Where can I get more information?

• Your pharmacist can provide more information about capsaicin topical.

See also: Zostrix Neuropathy side effects (in more detail)

Zortress

Generic Name: everolimus (Oral route)

e-ver-OH-li-mus

Oral route(Tablet)

Zortress(R): Increased susceptibility to infection and the possible development of lymphoma and other malignancies may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of transplant patients should prescribe everolimus. Reduced doses of cyclosporine should be used in combination with everolimus in order to reduce renal dysfunction and monitoring of cyclosporine and everolimus whole blood trough concentrations is recommended. The use of everolimus has resulted an increase risk of graft loss within the first 30 days post-transplantation .

Commonly used brand name(s)

In the U.S.

• Afinitor


• Zortress

Available Dosage Forms:

• Tablet

Therapeutic Class: Immune Suppressant

Uses For Zortress

Everolimus is used to treat advanced (late-stage) kidney cancer in patients who have already been treated with other medicines (e.g., sorafenib, sunitinib) that did not work well.

Everolimus belongs to the group of medicines known as antineoplastics or cancer medicines. It works by interfering with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected, other unwanted effects will also occur. Some of these may be serious and must be reported to your doctor, while others may cause concern but may not be serious.

Everolimus is also used together with other medicines to lower the body's natural immunity in patients who receive kidney transplants. When a patient receives an organ transplant, the body's white blood cells will try to get rid of (reject) the transplanted organ. Everolimus works to suppress the immune system and prevents the white blood cells from getting rid of the transplanted organ.

This medicine is also used to treat subependymal giant cell astrocytoma (SEGA), a brain tumor seen in patients with an inherited condition called tuberous sclerosis (TS).

Everolimus is also used to treat a type of pancreatic cancer called pancreatic neuroendocrine tumor (PNET), that has advanced, metastatic (cancer that has spread), or cannot be treated with surgery.

Before you begin treatment with everolimus, you and your doctor should talk about the benefits this medicine will do as well as the risks of using it.

This medicine is available only with your doctor's prescription.

Before Using Zortress

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of everolimus in the pediatric population. Safety and efficacy have not been established.

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of everolimus to treat SEGA in children. However, safety and efficacy have not been established in children younger than 3 years of age.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of everolimus in the elderly.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	D	Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Adenovirus Vaccine Type 4, Live


• Adenovirus Vaccine Type 7, Live


• Amprenavir


• Aprepitant


• Atazanavir


• Bacillus of Calmette and Guerin Vaccine, Live


• Carbamazepine


• Clarithromycin


• Cyclosporine


• Diltiazem


• Efavirenz


• Erythromycin


• Fluconazole


• Fosamprenavir


• Indinavir


• Influenza Virus Vaccine, Live


• Itraconazole


• Ketoconazole


• Lovastatin


• Measles Virus Vaccine, Live


• Mumps Virus Vaccine, Live


• Nefazodone


• Nelfinavir


• Nicardipine


• Phenobarbital


• Phenytoin


• Poliovirus Vaccine, Live


• Posaconazole


• Rifabutin


• Rifampin


• Rifapentine


• Ritonavir


• Rotavirus Vaccine, Live


• Rubella Virus Vaccine, Live


• Saquinavir


• Simvastatin


• Smallpox Vaccine


• St John's Wort


• Telithromycin


• Typhoid Vaccine


• Varicella Virus Vaccine


• Verapamil


• Voriconazole


• Yellow Fever Vaccine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Blood clotting problems or


• Diabetes or


• Hepatitis B infection, history of or


• Hyperglycemia (high sugar in the blood) or


• Hyperlipidemia (high cholesterol in the blood) or


• Hypertriglyceridemia (high fat in the blood) or


• Hypoxia (low oxygen in the blood) or


• Lung or breathing problems or


• Lymphoma (cancer of the lymph glands) or


• Proteinuria (protein in the urine) or


• Skin cancer—Use with caution. May make these conditions worse.

• Galactose intolerance or


• Glucose-galactose malabsorption (a rare genetic disorder) or


• Lactose intolerance or


• Lapp lactase deficiency (a rare genetic disorder) or


• Liver disease, severe—Should not be used in patients with these conditions.

• Infection (e.g., bacteria, fungus, virus, or protozoa)—May decrease your body's ability to fight infection.

• Liver disease, mild to moderate—Use with caution. You may require a smaller dose. Talk with you doctor if you have concerns about this.

Proper Use of everolimus

This section provides information on the proper use of a number of products that contain everolimus. It may not be specific to Zortress. Please read with care.

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

If you have a kidney transplant, you might have to take this medicine for the rest of your life to prevent rejection of the kidney. Do not change your dose or stop taking this medicine without first checking with your doctor.

This medicine comes with a Medication Guide and a patient information leaflet. Read the information carefully and make sure you understand it before taking this medicine. If you have any questions, talk to your doctor.

Everolimus works best when there is a constant amount in the blood. You can keep the amount constant by taking the dose at the same time each day.

You may take this medicine with or without food. However, you should take it the same way (with or without food) each time.

Swallow the tablet whole with a glass of water. Do not break, crush, or chew it. If you accidentally break or crush the tablet, wash your hands with water right away.

If you cannot swallow the tablets, you may dissolve the tablets in a glass (30 mL) of water. Gently stir it before drinking the medicine. Rinse the glass with the same amount of water and swallow it immediately.

Grapefruits and grapefruit juice may increase the effects of everolimus by increasing the amount in the body. You should not eat grapefruit or drink grapefruit juice while you are taking this medicine.

If you have a kidney transplant, everolimus will be given together with another medicine that suppresses the immune system called cyclosporine. It should be taken at the same time with the cyclosporine capsules.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  
  • For advanced kidney cancer:
    
    • Adults—10 milligrams (mg) once a day. Your doctor may adjust your dose if needed.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For brain tumor or subependymal giant cell astrocytoma (SEGA):
    
    • Adults and children 3 years of age and older—Dose is based on body size and must be determined by your doctor. The starting dose is 2.5 to 7.5 milligrams (mg) once a day. Your doctor may adjust your dose if needed.
    
    
    • Children younger than 3 years of age—Use and dose must be determined by your doctor.
    
    
  
  
  • To prevent kidney transplant rejection:
    
    • Adults—At first, 0.75 milligram (mg) two times per day, spaced 12 hours apart. Your doctor may adjust your dose if needed.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For advanced pancreatic cancer or pancreatic neuroendocrine tumor (PNET):
    
    • Adults—10 milligrams (mg) once a day. Your doctor may adjust your dose if needed.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss a dose of this medicine, you may still take it up to 6 hours after the time you normally take it. However, if it is more than 6 hours, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Protect the medicine from direct light. Keep your medicine in the original package until you are ready to use it.

Precautions While Using Zortress

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control while you are using this medicine and for at least 8 weeks after stopping treatment. If you think you have become pregnant while using the medicine, tell your doctor right away.

If you are male and plan to have children, talk with your doctor before using this medicine. This medicine may decrease fertility in men.

This medicine may cause a serious lung problem called noninfectious pneumonitis. Stop using this medicine and check with your doctor right away if you have chest pain, chills, a cough, fever, shortness of breath, or troubled breathing.

Check with your doctor right away if you develop the following symptoms while using this medicine: agitation; coma; confusion; decreased urine output; depression; dizziness; headache; hostility; irritability; lethargy; muscle twitching; nausea; rapid weight gain; seizures; stupor; swelling of the face, ankles, or hands; or unusual tiredness or weakness. These may be symptoms of a serious kidney problem.

While you are being treated with everolimus, and after you stop taking it, it is important to talk to your doctor about the immunizations (vaccines) you should receive. Do not get any vaccine without your doctor's approval. Everolimus may lower your body's resistance and there is a chance you might get the infection the vaccine is meant to prevent. In addition, other persons living in your household should not receive certain vaccines since there is a chance they could pass the infection on to you. Talk to your doctor if you have questions about this.

Everolimus can temporarily lower the number of white blood cells in your blood, which increases the chance of getting an infection and prevents you from healing correctly after an injury. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.


• Check with your doctor immediately if you notice any unusual bleeding or bruising; black, tarry stools; blood in the urine or stools; or pinpoint red spots on your skin.


• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.


• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.


• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.


• Avoid contact sports or other situations where bruising or injury could occur.

This medicine may increase your risk for getting skin cancer. When you begin taking this medicine:

• Stay out of direct sunlight, especially between the hours of 10:00 a.m. and 3:00 p.m., if possible.


• Wear protective clothing, including a hat, and sunglasses.


• Apply a sunblock product that has a skin protection factor (SPF) of at least 15, or higher if you have a fair complexion.


• Apply a sunblock lipstick that has an SPF of at least 15 to protect your lips.


• Do not use sunlamps, tanning beds, or tanning booths.


• If you have any questions about this, check with your doctor.

Everolimus may cause a serious type of allergic reaction called angioedema. This may occur more often when it is used with certain heart and blood pressure medicines called ACE inhibitors (e.g., captopril [Capoten®], enalapril [Vasotec®], fosinopril [Monopril®], quinapril [Accupril®], or ramipril [Altace®]). Stop taking this medicine and tell your doctor right away if you have a rash; itching; a large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs; trouble with breathing; or chest tightness while you are using this medicine.

If you have a kidney transplant, this medicine may increase your risk for having a blood clot in the new kidney. This usually occurs within the first 30 days after the kidney transplant. Check with your doctor right away if you are making less urine, or if you have pain in your groin, lower back, side, or stomach; dark-colored urine; a fever; or nausea or vomiting.

If you are taking this medicine after a kidney transplant, it may increase your risk for developing a rare and serious virus infection called BK virus-associated nephropathy (BKVAN). The BK virus may affect how your kidneys work and cause a transplanted kidney to fail. Check with your doctor right away if you are having more than one of these symptoms: bloody urine; a decreased frequency or amount of urine; increased thirst; loss of appetite; lower back or side pain; nausea; swelling of the face, fingers, or lower legs; trouble with breathing; unusual tiredness or weakness; vomiting; or weight gain.

Everolimus may cause mouth ulcers and sores in some patients. Tell your doctor right away if you have pain, discomfort, or open sores in your mouth while you are using this medicine. You may use a special mouthwash or mouth gel to treat these ulcers. Ask your doctor what type of products to use.

This medicine may affect blood sugar levels. If you notice a change in the results of your blood or urine sugar tests or if you have any questions, check with your doctor.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (e.g., St. John's wort) or vitamin supplements.

Zortress Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

• Bloating or swelling of the face, arms, hands, lower legs, or feet


• bloody nose


• chest pain


• cough or hoarseness


• cracked lips


• decreased weight


• diarrhea


• difficult or labored breathing


• difficulty with swallowing


• fever or chills


• general feeling of discomfort or illness


• lower back or side pain


• painful or difficult urination


• rapid weight gain


• shortness of breath


• sores, ulcers, or white spots on the lips, tongue, or inside the mouth


• swelling or inflammation of the mouth


• thickening of bronchial secretions


• tightness in the chest


• tingling of the hands or feet


• troubled with breathing


• unusual weight gain or loss


• wheezing

Less common

• Bleeding after defecation


• bleeding gums


• bloody urine


• blurred vision


• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings


• coughing up blood


• decreased frequency or amount of urine


• decreased urine output


• dilated neck veins


• dry mouth


• extreme fatigue


• fast, pounding, or irregular heartbeat or pulse


• flushed, dry skin


• fruit-like breath odor


• headache


• increased blood pressure


• increased hunger


• increased menstrual flow or vaginal bleeding


• increased thirst


• increased urination


• irregular breathing


• loss of appetite


• loss of consciousness


• nausea


• nervousness


• nosebleeds


• paralysis


• pounding in the ears


• prolonged bleeding from cuts


• red or black, tarry stools


• red or dark brown urine


• runny nose


• slow heartbeat


• sore throat


• stomachache


• sweating


• uncomfortable swelling around the anus


• unexplained weight loss


• unusual tiredness or weakness


• vomiting


• weight gain

Incidence not known

• Agitation


• coma


• confusion


• depression


• dizziness


• hostility


• irritability


• lethargy


• muscle twitching


• rapid weight gain


• seizures


• stupor


• swelling of the face, ankles, or hands

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Abdominal or stomach pain


• change in taste


• dry skin


• itching skin


• lack or loss of strength


• loss of taste


• pain in the arms or legs


• rash


• sleeplessness


• trouble with sleeping


• unable to sleep

Less common

• Back pain


• blistering, peeling, redness, or swelling of the palms, hands, or bottoms of the feet


• bumps on the skin


• burning, dry, or itching eyes


• discharge or excessive tearing


• discoloration of the fingernails or toenails


• excess air or gas in the stomach or intestines


• flushing or redness of the skin


• full feeling


• jaw pain


• numbness, pain, tingling, or unusual sensations in the palms of the hands or bottoms of the feet


• passing gas


• redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid


• sleepiness or unusual drowsiness


• unusually warm skin

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Zortress side effects (in more detail)

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More Zortress resources

• Zortress Side Effects (in more detail)
• Zortress Dosage
• Zortress Use in Pregnancy & Breastfeeding
• Zortress Drug Interactions
• Zortress Support Group
• 0 Reviews for Zortress - Add your own review/rating

• Zortress Prescribing Information (FDA)


• Zortress MedFacts Consumer Leaflet (Wolters Kluwer)


• Zortress Consumer Overview


• Everolimus Professional Patient Advice (Wolters Kluwer)


• Afinitor Prescribing Information (FDA)


• Afinitor Monograph (AHFS DI)


• Afinitor Consumer Overview


• Afinitor MedFacts Consumer Leaflet (Wolters Kluwer)

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zolpidem

Generic Name: zolpidem (zole PI dem)

Brand Names: Ambien, Ambien CR, Edluar, Intermezzo, Zolpimist

What is zolpidem?

Zolpidem is a sedative, also called a hypnotic. It affects chemicals in your brain that may become unbalanced and cause sleep problems (insomnia).

Zolpidem is used to treat insomnia. The immediate-release forms of zolpidem are Ambien, Intermezzo, Edluar, and Zolpimist, which are used to help you fall asleep. The extended-release form of zolpidem is Ambien CR, which has a first layer that dissolves quickly to help you fall asleep, and a second layer that dissolves slowly to help you stay asleep.

Ambien, Edluar, and Zolpimist are used to help you fall asleep when you first go to bed. Intermezzo, is used to help you fall back to sleep if you wake up in the middle of the night and then have trouble sleeping.

Your doctor will determine which form of zolpidem is best for you.

Zolpidem may also be used for purposes not listed in this medication guide.

What is the most important information I should know about zolpidem?

Zolpidem may cause a severe allergic reaction. Stop taking zolpidem and get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Some people using this medicine have engaged in activity such as driving, eating, or making phone calls and later having no memory of the activity. If this happens to you, stop taking zolpidem and talk with your doctor about another treatment for your sleep disorder. Zolpidem may impair your thinking or reactions. You may still feel sleepy the morning after taking the medication. Wait at least 4 hours or until you are fully awake before you drive, operate machinery, pilot an airplane, or do anything that requires you to be awake and alert. Do not take this medicine if you have consumed alcohol during the day or just before bed. Zolpidem may be habit-forming and should be used only by the person it was prescribed for. Keep the medication in a secure place where others cannot get to it.

It is dangerous to try and purchase zolpidem on the Internet or from vendors outside of the United States. Medications distributed from Internet sales may contain dangerous ingredients, or may not be distributed by a licensed pharmacy. Samples of zolpidem purchased on the Internet have been found to contain haloperidol (Haldol), a potent antipsychotic drug with dangerous side effects. For more information, contact the U.S. Food and Drug Administration (FDA) or visit www.fda.gov/buyonlineguide.

What should I discuss with my healthcare provider before taking zolpidem?

Some people using this medicine have engaged in activity such as driving, eating, or making phone calls and later having no memory of the activity. If this happens to you, stop taking zolpidem and talk with your doctor about another treatment for your sleep disorder. You should not use this medication if you are allergic to zolpidem. Zolpidem tablets may contain lactose. Use caution if you are sensitive to lactose.

To make sure you can safely take zolpidem, tell your doctor if you have any of these other conditions:

• kidney disease;


• liver disease;


• 
  

  lung disease such as asthma, bronchitis, emphysema, or chronic obstructive pulmonary disease (COPD);

  
  


• 
  

  sleep apnea (breathing stops during sleep);

  
  


• 
  

  myasthenia gravis;

  
  


• 
  

  a history of depression, mental illness, or suicidal thoughts; or

  
  


• 
  

  a history of drug or alcohol addiction.

  
  

Zolpidem may be habit forming and should be used only by the person it was prescribed for. Never share zolpidem with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it. FDA pregnancy category C. It is not known whether zolpidem will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Zolpidem can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. The sedative effects of zolpidem may be stronger in older adults. Do not give this medicine to anyone younger than 18 years of age.

It is dangerous to try and purchase zolpidem on the Internet or from vendors outside of the United States. Medications distributed from Internet sales may contain dangerous ingredients, or may not be distributed by a licensed pharmacy. Samples of zolpidem purchased on the Internet have been found to contain haloperidol (Haldol), a potent antipsychotic drug with dangerous side effects. For more information, contact the U.S. Food and Drug Administration (FDA) or visit www.fda.gov/buyonlineguide.

How should I take zolpidem?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Zolpidem comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Never take Ambien, Edluar, or Zolpimist if you do not have a full 7 to 8 hours to sleep before being active again.

Do not take Intermezzo for middle-of-the-night insomnia unless you have 4 hours of sleep time left before being active.

Zolpidem is for short-term use only. Tell your doctor if your insomnia symptoms do not improve, or if they get worse after using this medication for 7 to 10 nights in a row. Do not take zolpidem for longer than 4 or 5 weeks without your doctor's advice. Do not stop using zolpidem suddenly after long-term use, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using the medicine.

Insomnia symptoms may also return after you stop taking zolpidem. These symptoms may seem to be even worse than before you started taking the medication. Call your doctor if you still have worsened insomnia after the first few nights without taking zolpidem.

Do not crush, chew, or break an Ambien CR tablet. Swallow the pill whole. Breaking the pill may cause too much of the drug to be released at one time.

Do not swallow the Edluar or Intermezzo tablet whole. Place the tablet under your tongue and allow it to dissolve in your mouth without water.

Spray Zolpimist directly into your mouth over your tongue. Prime the spray before the first use by pumping 5 test sprays into the air, away from your face. Prime the spray with 1 test spray if it has not been used for longer than 14 days.

Store at room temperature away from moisture and heat. Do not freeze. Keep the Zolpimist bottle upright when not in use.

See also: Zolpidem dosage (in more detail)

What happens if I miss a dose?

Since zolpidem is taken only at bedtime, you will not be on a frequent dosing schedule.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of zolpidem can be fatal when it is taken together with other medications that can cause drowsiness.

Overdose symptoms may include sleepiness, confusion, shallow breathing, feeling light-headed, fainting, or coma.

What should I avoid while taking zolpidem?

Zolpidem may impair your thinking or reactions. You may still feel sleepy the morning after taking the medication. Wait at least 4 hours or until you are fully awake before you drive, operate machinery, pilot an airplane, or do anything that requires you to be awake and alert.

Avoid taking zolpidem during travel, such as to sleep on an airplane. You may be awakened before the effects of the medication have worn off. Amnesia (forgetfulness) is more common if you do not get a full 7 to 8 hours of sleep after taking zolpidem.

Do not take this medicine if you have consumed alcohol during the day or just before bed.

Zolpidem side effects

Zolpidem may cause a severe allergic reaction. Stop taking zolpidem and get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Report any new or worsening symptoms to your doctor, such as: depression, anxiety, aggression, agitation, confusion, unusual thoughts, hallucinations, memory problems, changes in personality, risk-taking behavior, decreased inhibitions, no fear of danger, or thoughts of suicide or hurting yourself. Stop using zolpidem and call your doctor at once if you have a serious side effects:

• 
  

  chest pain, fast or irregular heartbeat, feeling short of breath;

  
  


• 
  

  trouble breathing or swallowing; or

  
  


• 
  

  feeling like you might pass out.

  
  

Less serious side effects may include:

• 
  

  daytime drowsiness, dizziness, weakness, feeling "drugged" or light-headed;

  
  


• 
  

  tired feeling, loss of coordination;

  
  


• 
  

  dry mouth, nose or throat irritation;

  
  


• 
  

  nausea, constipation, diarrhea, upset stomach;

  
  


• 
  

  stuffy nose, sore throat; or

  
  


• 
  

  headache, muscle pain.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Zolpidem Dosing Information

Usual Adult Dose for Insomnia:

Immediate release: 10 mg orally once a day immediately before bedtime. Alternatively, the dose may be administered as one 10 mg sublingual tablet placed under the tongue to disintegrate once a day immediately before bedtime. The sublingual tablet should not be swallowed or taken with water. The recommended duration of zolpidem therapy is generally 7 to 10 days. Each metered actuation (one spray) of zolpidem tartrate oral spray delivers 5 mg of zolpidem.

Controlled release: 12.5 mg orally once a day immediately before bedtime.

Sublingual: The recommended and maximum dose is 1.75 mg SL for women and 3.5 mg SL for men only once per night (to be taken only if the patient has at least 4 hours of bedtime remaining before the planned time of waking).

If zolpidem is used daily for more than a few weeks, abrupt discontinuation is not recommended. Such cessation may precipitate symptoms of withdrawal.

The safety of immediate release zolpidem has only been established for treatment regimens of up to five weeks. Administration of immediate release zolpidem for therapies longer than five weeks is therefore not recommended.

Usual Geriatric Dose for Insomnia:

Immediate release: 5 mg once a day immediately before bedtime. Alternatively, the dose may be administered as one 5 mg sublingual tablet placed under the tongue to disintegrate. The sublingual tablet should not be swallowed or taken with water. The recommended duration of zolpidem therapy is generally 7 to 10 days. The dosage can be titrated up to 10 mg nightly if necessary depending on patient response.

Controlled release: 6.25 mg orally once a day immediately before bedtime.

Sublingual: The recommended and maximum dose is 1.75 mg only once per night (to be taken only if the patient has at least 4 hours of bedtime remaining before the planned time of waking).

If zolpidem is used daily for more than a few weeks, abrupt discontinuation is not recommended. Such cessation may precipitate symptoms of withdrawal.

The safety of immediate release zolpidem has only been established for treatment regimens of up to five weeks. Administration of immediate release zolpidem for therapies longer than five weeks is therefore not recommended.

What other drugs will affect zolpidem?

You may need a lower dose of zolpidem if you take other medicines that make you sleepy (such as cold medicine, pain medication, muscle relaxants, and medicine for depression or anxiety). Tell your doctor if you are currently taking any of these medications.

Tell your doctor about all other medicines you use, especially:

• 
  

  chlorpromazine (Thorazine);

  
  


• 
  

  itraconazole (Sporanox), ketoconazole (Nizoral);

  
  


• 
  

  rifampin (Rifadin, Rimactane, Rifater); or

  
  


• 
  

  antidepressants such as imipramine (Tofranil), or sertraline (Zoloft).

  
  

This list is not complete and other drugs may interact with zolpidem. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More zolpidem resources

• Zolpidem Side Effects (in more detail)
• Zolpidem Dosage
• Zolpidem Use in Pregnancy & Breastfeeding
• Drug Images
• Zolpidem Drug Interactions
• Zolpidem Support Group
• 304 Reviews for Zolpidem - Add your own review/rating

• zolpidem Oral, Oromucosal Advanced Consumer (Micromedex) - Includes Dosage Information


• Zolpidem Prescribing Information (FDA)


• Zolpidem MedFacts Consumer Leaflet (Wolters Kluwer)


• Ambien Consumer Overview


• Ambien Monograph (AHFS DI)


• Ambien Prescribing Information (FDA)


• Ambien CR Extended-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Ambien CR Prescribing Information (FDA)


• Edluar Consumer Overview


• Edluar MedFacts Consumer Leaflet (Wolters Kluwer)


• Edluar Prescribing Information (FDA)


• Intermezzo Consumer Overview


• ZolpiMist Consumer Overview


• Zolpimist Prescribing Information (FDA)


• Zolpimist Oral Spray MedFacts Consumer Leaflet (Wolters Kluwer)

Compare zolpidem with other medications

• Insomnia

Where can I get more information?

• Your pharmacist can provide more information about zolpidem.

See also: zolpidem side effects (in more detail)