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Tuesday 2 October 2012

Ibandronate Sodium

Class: Bone Resorption Inhibitors
VA Class: HS900
Chemical Name: [1-Hydroxy-3-(methylpentylamino)propylidene]diphosphonate trihydrogen sodium monohydrate
Molecular Formula: C₉H₂₂NNaO₇
CAS Number: 138926-19-9
Brands: Boniva

Special Alerts:

[Posted 07/21/2011] ISSUE: FDA notified healthcare professionals and patients about its ongoing review of data from published studies to evaluate whether use of oral bisphosphonate drugs is associated with an increased risk of cancer of the esophagus. FDA has not concluded that taking an oral bisphosphonate drug increases the risk of esophageal cancer. There are insufficient data to recommend endoscopic screening of asymptomatic patients. FDA will continue to evaluate all available data supporting the safety and effectiveness of bisphosphonate drugs and will update the public when more information becomes available.

BACKGROUND: Oral bisphosphonates are commonly used for the prevention and treatment of osteoporosis as well as to treat other bone diseases such as Paget’s disease. There have been conflicting findings from studies evaluating the risk of esophageal cancer. Esophagitis and other esophageal events have been reported, particularly in patients who do not follow the specific directions for use of oral bisphosphonates. See the Data Summary in the Drug Safety Communication for additional details at: .

RECOMMENDATION: Patients should talk with their healthcare professional about the benefits and risks of taking oral bisphosphonates and how long they should expect to take them. Patients should talk with their healthcare professional if they develop swallowing difficulties, chest pain, new or worsening heartburn, or have trouble or pain when swallowing. Patients should be instructed to carefully follow the directions for use of the oral bisphosphonate drug they are prescribed. 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 ibandronate sodium 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

Uses for Ibandronate Sodium

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.

Osteoporosis

Prevention of osteoporosis in postmenopausal women.¹ Risk factors include a family history of osteoporosis, early menopause, previous fracture, high bone turnover, reduced bone mineral density (≥1 standard deviation below premenopausal mean), thin body frame, white or Asian race, excessive alcohol intake, treatment with certain drugs (e.g., corticosteroids), low dietary calcium or vitamin D intake, sedentary lifestyle, and cigarette smoking.¹ ⁵ ⁶ ⁸ ¹⁸

Treatment of osteoporosis in postmenopausal women.¹ ³ ⁷

Ibandronate Sodium 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.

Oral: Provide supplemental calcium and vitamin D¹ ⁷ if dietary intake is inadequate.¹ ¹⁸

IV: Supplemental calcium and vitamin D required regardless of the adequacy of dietary intake of calcium and vitamin D.⁷ ¹⁸

Administration

Oral Administration

Administer orally with a full glass (180–240 mL) of plain water ≥60 minutes prior to the first food, beverage (other than plain water), or other orally administered drug or supplement (including vitamins, antacids, and calcium) of the day.¹ ⁴ ⁵ ¹⁶ (See Food under Pharmacokinetics.)

Avoid lying down for ≥60 minutes following administration.¹ ⁵

Do not to suck or chew tablets; potential for oropharyngeal ulceration.¹ ⁵ (See GI Effects under Cautions.)

If a morning daily oral dose is missed, do not take missed dose later that same day.⁵ Resume the regular schedule the next day.¹ ⁵

When administered monthly, take tablets in the morning on the same day each month.¹ ^a If a monthly dose is missed and the next scheduled dose is more than 7 days away, take the missed dose the next morning after it is remembered and resume the regular schedule.¹ ^a If the next scheduled dose is 1–7 days away, maintain the regular schedule;¹ do not take more than one 150-mg tablet within the same week.¹ ^a

IV Administration

Administer by IV injection once every 3 months by a health-care professional.⁷

Injection must only be administered IV.¹ ⁷ ¹⁸ Safety and efficacy of IV injection administered by other routes not established.⁷

If a dose is missed, reschedule administration with a health-care professional as soon as possible.⁷ ⁸ Schedule subsequent injections at 3-month intervals; should not be administered more often than once every 3 months.⁷ ⁸

Administration Risks

Take care to avoid intra-arterial or paravenous injection as such administration could result in tissue damage.⁷

Rate of Administration

Administer IV over a period of 15–30 seconds.⁷ ⁸

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 ibandronate sodium (as the monosodium monohydrate); dosage expressed in terms of ibandronate.¹ ⁷

Adults

Osteoporosis

Prevention in Postmenopausal Women

Oral

2.5 mg once daily.¹ Alternatively, a dosage of 150 mg once monthly may be considered.¹

Osteoporosis

Treatment in Postmenopausal Women

Oral

2.5 mg once daily or 150 mg once monthly.¹

IV

3 mg once every 3 months.⁷

Special Populations

Hepatic Impairment

Dosage adjustments not necessary.¹ ⁷

Renal Impairment

Oral

Dosage adjustments not necessary in patients with mild to moderate renal impairment (Cl_cr ≥30 mL/minute); use not recommended in patients with severe renal impairment (Cl_cr <30 mL/minute).¹ ⁴ ¹⁸

IV

Should not be administered to patients with severe renal impairment (Cl_cr <30 mL/minute, S_cr >2.3 mg/dL).⁷ ¹⁸

Geriatric Patients

Dosage adjustments not necessary.¹ ⁷

Cautions for Ibandronate Sodium

Contraindications

Uncorrected hypocalcemia.¹ ⁵ ⁷ ⁸

Known hypersensitivity to ibandronate or any ingredient in the formulation.¹ ⁵ ⁷ ⁸

Oral: Inability to stand or sit upright for ≥60 minutes.¹ ⁵

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.

GI Effects

Adverse upper GI effects (e.g., dysphagia, esophagitis, esophageal or gastric ulcer) reported with oral bisphosphonates.¹ ² (See Administration under Dosage and Administration.)

Route of Administration

Injection must be administered IV by a health-care professional; do not administer by non-IV (e.g., intra-arterial) routes.⁷ (See Administration Risks under Dosage and Administration.)

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.

Renal Effects

Possible renal toxicity (e.g., deterioration of renal function and, rarely, renal failure) with bisphosphonates.⁷ ¹² Risk may be greater in patients with coexisting conditions associated with renal impairment, concomitant therapy with other nephrotoxic drugs, preexisting renal disease, dehydration, dosage, infusion volume and rate, and multiple cycles of treatment.⁴ ⁷ ⁸ ⁹ ¹⁰ ¹¹

Use not recommended in patients with severe renal impairment (S_cr >2.3 mg/dL or Cl_cr <30 mL/minute).¹ ⁷

Assess risk factors predisposing patients to renal deterioration.⁷ ⁸ Measure S_cr prior to each IV dose.⁷ Withhold treatment if deterioration of renal function occurs.⁷

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 reported in patients receiving bisphosphonates.¹ ⁷ ¹³ Most cases associated with dental procedures (e.g., tooth extraction) in cancer patients, but some have occurred in patients with postmenopausal osteoporosis or other diagnoses.¹ ⁷ ¹³

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).¹³ ¹⁸ Such patients should avoid invasive dental procedures, if possible, during therapy.¹³ ¹⁸

Severe, occasionally incapacitating bone, joint, and/or muscle pain reported infrequently with bisphosphonate therapy.¹ ⁵ ⁷ ⁸ ¹⁸ Time to onset of symptoms varied from 1 day to several months after treatment initiation.¹ ⁷ ⁸ Such pain generally improves following discontinuance of the drug, but may recur upon subsequent rechallenge with the same drug or another bisphosphonate.¹ ⁵ ⁷ ⁸ ¹⁸

Metabolic Effects

Correct hypocalcemia, hypovitaminosis D, and other disturbances of bone and mineral metabolism before initiating therapy.¹ ⁷ ⁸ ¹⁸

Oral: If daily intake inadequate, administer supplemental calcium and vitamin D.¹ ¹⁸ ^a

IV: May cause a transient decrease in serum calcium concentrations.⁷ Supplemental calcium and vitamin D required regardless of the adequacy of dietary intake of calcium and vitamin D.⁷ ¹⁸

Specific Populations

Pregnancy

Category C. ¹ ⁷

Lactation

Distributed into milk in rats; not known whether distributed into human milk.¹ ⁷ Use caution.¹ ⁷

Pediatric Use

Safety and efficacy not established in children.¹ ⁷ ¹⁸ Not indicated for use in children.¹⁸

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.¹ ⁷ Consider age-related decreases in renal function.¹⁸

Renal Impairment

Oral: Use not recommended in patients with severe renal impairment (CL_cr <30 mL/minute).¹ ¹⁸

IV: Do not administer in patients with severe renal impairment (Cl_cr <30 mL/minute, S_cr >2.3 mg/dL).⁷ ¹⁸

Common Adverse Effects

Oral: Upper respiratory infection,¹ back pain,¹ dyspepsia,¹ ² ^a bronchitis,¹ pain in the extremities,¹ ^a abdominal pain,¹ diarrhea,¹ ^a headache,¹ hypertension,¹ pneumonia,¹ myalgia,¹ arthralgia,¹ urinary tract infection,¹ nausea.¹

IV: Arthralgia,⁷ ⁸ ¹⁶ ¹⁷ back pain,⁷ hypertension,⁷ abdominal pain.⁷

Interactions for Ibandronate Sodium

Does not induce or inhibit CYP isoenzymes (i.e., CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, or 3A4)⁴ ⁷ and is not metabolized.¹ ⁴ ⁷

Antacids or Mineral Supplements Containing Divalent Cations

Pharmacokinetic interaction (decreased absorption of ibandronate) when tablets are used concomitantly with antacids or mineral supplements containing divalent cations (e.g., aluminum, calcium, magnesium, iron).¹ ⁵ ^b Administer tablets ≥60 minutes prior to such drugs or supplements.¹ ⁵

Drugs Affecting Hepatic Microsomal Enzymes

Pharmacokinetic interactions unlikely.¹

Drugs Excreted through Renal Tubular Transport

Based on limited data in animals, not excreted through renal tubular transport.¹ ⁴ ⁷ Pharmacokinetic interaction unlikely.¹ ⁴

Nephrotoxic Agents

Potential pharmacologic interaction (increased risk of renal toxicity). ⁴ ⁷ ⁸ ⁹ ¹⁰ ¹¹ ¹² Assess patients taking concomitant nephrotoxic agents.¹ ⁷ (See Renal Effects under Cautions.)

Specific Drugs and Tests

Drug	Interaction	Comments
Bone-imaging agents	Potential to interfere with use of bone-imaging agents¹ ⁷
Histamine H₂-receptor antagonists	Increased oral bioavailability of ibandronate¹ ⁴ ^b No evidence of increased adverse upper GI effects¹ ¹⁸	Not considered clinically important¹ ⁴
Melphalan	Pharmacokinetic interaction unlikely with IV ibandronate⁷
NSAIAs	No evidence of increased adverse upper GI effects¹	Use concomitantly with caution¹
Prednisolone	Pharmacokinetic interaction unlikely with IV ibandronate⁷
Tamoxifen	Pharmacokinetic interaction unlikely with IV ibandronate¹ ⁷

Ibandronate Sodium Pharmacokinetics

Absorption

Bioavailability

Absolute (compared with IV administration) oral bioavailability about 0.6%.¹ ⁴ ¹⁶

Onset

Reduction in bone turnover evident within 1–3 months of treatment initiation; maximal effects observed at 6 months.¹ ⁷ ^b

Duration

Biochemical markers of bone turnover returned to baseline ≥12 months after treatment discontinuance.^b

Food

Bioavailability decreased by 90% when administered with a standard breakfast compared with administration under fasting conditions.¹ Bioavailability and effect on BMD reduced when food and beverages taken <60 minutes following oral administration.¹

Special Populations

In patients with renal impairment (Cl_cr 40–70 mL/minute), AUC is increased by 55% compared with that in patients with normal renal function (Cl_cr >90 mL/minute).⁷ Patients with severe renal impairment (Cl_cr <30 mL/minute) had >2-fold increase in AUC compared with exposure for healthy individuals.⁷ ^b

Distribution

Extent

Widely distributed throughout the body and redistributed to bone.⁴ ^b Subsequently, the drug is released systemically via bone turnover.¹ ⁴ Not known whether distributed into milk.⁷

Plasma Protein Binding

84–99.5% at therapeutic drug concentrations.¹ ⁴ ⁷ ^b

Elimination

Metabolism

No evidence of metabolism.⁷ ¹⁶

Elimination Route

Excreted in urine (50–60% of circulating dose) as unchanged drug and in feces (unabsorbed drug).¹ ⁴ ⁷ ^b

Half-life

Apparent oral terminal half-life is 37–157 hours; dose-dependent.¹

Apparent IV terminal half-life is 4.6–25.5 hours; dose-dependent.⁷

Special Populations

No race-related pharmacokinetic differences between Asians and whites; other races not studied.^b Pharmacokinetics not affected by gender.¹ ^b

Pharmacokinetics not evaluated in pediatric patients.¹ ^b Pharmacokinetics in patients with hepatic impairment not studied as ibandronate is not metabolized in the liver.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹

Parenteral

Injection

25°C (may be exposed to 15–30°C).⁷

Compatibility

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

Parenteral

Do not admix with calcium-containing solutions or other IV drugs.⁷

Actions

Incorporates into bone and selectively inhibits osteoclast-mediated bone resorption in a dose-dependent manner.¹ ⁴ ⁷ ^b

Reduces biochemical markers of bone resorption in patients with postmenopausal osteoporosis.¹ ⁷ ^b

Maintains or increases BMD² ³ ¹³ and increases bone mass in postmenopausal women.¹ ⁴ ⁵ ⁷

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 providing patient with a copy of the manufacturer’s patient information.¹ ⁷

Importance of adhering to recommended life-style modifications (e.g., exercise, calcium and vitamin D supplementation).¹ ⁵

Importance of correct oral administration (e.g., avoiding foods and beverages other than plain water [including mineral water] prior to administration, not lying down for ≥60 minutes following administration).¹ ⁵ ¹⁸ (See GI Effects under Cautions.)

Importance of not taking vitamins, calcium, or antacids ≤60 minutes of taking oral ibandronate.¹ ⁵

Necessity of swallowing tablets whole, without chewing or sucking.¹ ⁵

Importance of reviewing how to resume therapy in the event of a missed dose.¹ ⁵ ⁷

Importance of discontinuing oral ibandronate and informing clinician if symptoms of esophageal disease (e.g., new or worsening dysphagia, difficulty or pain on swallowing, retrosternal pain, heartburn) develop.¹ ⁵

Importance of informing a clinician if severe bone pain, joint pain, muscular pain, or jaw problems develop.⁸ ^a

Importance of women informing clinicians if they are or plan to become pregnant or to plan to breast-feed.¹ ⁵ ⁸

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (vitamins, supplements, antacids), as well as any concomitant illnesses (e.g., preexisting dysphagia, esophageal disorders, renal impairment).¹ ⁵ ⁸

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.

Ibandronate Sodium
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	2.5 mg (of ibandronate)	Boniva (with povidone)	Roche (also promoted by GlaxoSmithKline)
		150 mg (of ibandronate)	Boniva (with povidone)	Roche (also promoted by GlaxoSmithKline)
	Injection, for IV use only	1 mg (of ibandronate) per mL	Boniva (available in prefilled syringe with needle and swabs)	Roche (also promoted by GlaxoSmithKline)

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.

Boniva 150MG Tablets (GENENTECH): 1/$128.99 or 3/$372.99

Boniva 3MG/3ML Kit (GENENTECH): 3/$469.97 or 9/$1,329.91

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.

References

1. Roche Laboratories. Boniva (ibandronate sodium) tablets prescribing information. Nutley, NJ; 2006 Aug.

2. McClung MR, Wasnich RD, Recker R et al. Oral daily ibandronate prevents bone loss in early postmenopausal women without osteoporosis. J Bone Miner Res. 2004; 19:11-8. [PubMed 14753731]

3. Chesnut CH, Skag A, Christiansen C et al. Effect of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res. 2004; 19:1241-9. [PubMed 15231010]

4. Barrett J, Worth E, Bauss F et al. Ibandronate: a clinical pharmacological and pharmacokinetic update. J Clin Pharmacol. 2004; 44:951-65. [IDIS 519745] [PubMed 15317823]

5. Roche Laboratories. Boniva (ibadronate sodium) tablets patient information. Nutley, NJ; 2005 Mar.

6. National Osteoporosis Foundation. Physician’s guide to prevention and treatment of osteoporosis. Washington, DC; 2000. From National Osteoporosis Foundation website ().

7. Roche Pharmceuticals. Boniva (ibandronate sodium) injection prescribing information. Nutley, NJ; 2006 Jan.

8. Roche Pharmceuticals. Boniva (ibandronate sodium) injection patient information. Nutley, NJ; 2006 Jan.

9. 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]

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

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

12. 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]

13. Migliorati CA, Casiglia J, Epstein J et al. Managing the care of patients with bisphosphonate-associated osteonecrosis: an American Academy of Oral Medicine position paper. J Am Dent Assoc. 2005; 136:1658-68. [PubMed 16383047]

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

15. Reginster JY, Adami S, Lakatos P et al. Efficacy and tolerability of once-monthy oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study. Ann Rheum Dis [serial online]. January 26, 2006. Available at .

16. Reginster JY. Oral and intravenous ibandronate in the management of postmenopausal osteoporosis: a comprehensive review. Curr Pharm Des. 2005; 11:3711-28. [PubMed 16305506]

17. Delmas PD, Adami S, Strugala C et al. Intravenous ibandronate injections in postmenopausal women with osteoporosis: one-year results form the dosing intravenous administration study. Arthritis Rheum. 2006; 54:1838-46. [PubMed 16729277]

18. Roche Pharmaceuticals, Nutley, NJ: Personal communication.

a. Roche Laboratories. Boniva (ibadronate sodium) tablets patient information. Nutley, NJ; 2006 Aug.

b. Kehoe T, Colman E. Boniva (Ibandronate sodium) FDA approval package, Medical review. NDA No. 21-455. Rockville, MD; 2003 May 16.

More Ibandronate Sodium resources

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Osteoporosis
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Friday 28 September 2012

Inatal Ultra

Generic Name: prenatal multivitamins (PRE nay tal VYE ta mins)

Brand Names: Advance Care Plus, Bright Beginnings, Cavan Folate, Cavan One, Cavan-Heme OB, Cenogen Ultra, CitraNatal Rx, Co Natal FA, Complete Natal DHA, Complete-RF, CompleteNate, Concept OB, Docosavit, Dualvit OB, Duet, Edge OB, Elite OB 400, Femecal OB, Folbecal, Folcaps Care One, Folivan-OB, Foltabs, Gesticare, Icar Prenatal, Icare Prenatal Rx, Inatal Advance, Infanate DHA, Kolnatal DHA, Lactocal-F, Marnatal-F, Maternity, Maxinate, Mission Prenatal, Multi-Nate 30, Multinatal Plus, Nata 29 Prenatal, Natachew, Natafort, Natelle, Neevo, Nestabs, Nexa Select with DHA, Novanatal, NovaStart, O-Cal Prenatal, OB Complete, OB Natal One, Ob-20, Obtrex DHA, OptiNate, Paire OB Plus DHA, PNV Select, PNV-Total, PR Natal 400, Pre-H-Cal, Precare, PreferaOB, Premesis Rx, PrenaCare, PrenaFirst, PrenaPlus, Prenatabs OBN, Prenatabs Rx, Prenatal 1 Plus 1, Prenatal Elite, Prenatal Multivitamins, Prenatal Plus, Prenatal S, Prenatal-U, Prenate Advanced Formula, Prenate DHA, Prenate Elite, Prenavite FC, PreNexa, PreQue 10, Previte Rx, PrimaCare, Pruet DHA, RE OB Plus DHA, Renate, RightStep, Rovin-NV, Se-Care, Se-Natal One, Se-Plete DHA, Se-Tan DHA, Select-OB, Seton ET, Strongstart, Stuart Prenatal with Beta Carotene, Tandem OB, Taron-BC, Tri Rx, TriAdvance, TriCare, Trimesis Rx, Trinate, Triveen-PRx RNF, UltimateCare Advance, Ultra-Natal, Vemavite PRX 2, VeNatal FA, Verotin-BY, Verotin-GR, Vinacal OR, Vinatal Forte, Vinate Advanced (New Formula), Vinate AZ, Vinate Care, Vinate Good Start, Vinate II (New Formula), Vinate III, Vinate One, Vitafol-OB, VitaNatal OB plus DHA, Vitaphil, Vitaphil Aide, Vitaphil Plus DHA, Vitaspire, Viva DHA, Vol-Nate, Vol-Plus, Vol-Tab Rx, Vynatal F.A., Zatean-CH, Zatean-PN

What are Inatal Ultra (prenatal multivitamins)?

There are many brands and forms of prenatal vitamin available and not all brands are listed on this leaflet.

Prenatal vitamins are a combination of many different vitamins that are normally found in foods and other natural sources.

Prenatal vitamins are used to provide the additional vitamins needed during pregnancy. Minerals may also be contained in prenatal multivitamins.

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

What is the most important information I should know about prenatal vitamins?

There are many brands and forms of prenatal vitamin available and not all brands are listed on this leaflet.

Never take more than the recommended dose of a multivitamin. Avoid taking any other multivitamin product within 2 hours before or after you take your prenatal vitamins. Taking similar vitamin products together at the same time can result in a vitamin overdose or serious side effects.

Many multivitamin products also contain minerals such as calcium, iron, magnesium, potassium, and zinc. Minerals (especially taken in large doses) can cause side effects such as tooth staining, increased urination, stomach bleeding, uneven heart rate, confusion, and muscle weakness or limp feeling. Read the label of any multivitamin product you take to make sure you are aware of what it contains.

Seek emergency medical attention if you think you have used too much of this medicine. An overdose of vitamins A, D, E, or K can cause serious or life-threatening side effects and can also harm your unborn baby. Certain minerals contained in a prenatal multivitamin may also cause serious overdose symptoms or harm to the baby if you take too much.

Overdose symptoms may include stomach pain, vomiting, diarrhea, constipation, loss of appetite, hair loss, peeling skin, tingly feeling in or around your mouth, changes in menstrual periods, weight loss, severe headache, muscle or joint pain, severe back pain, blood in your urine, pale skin, and easy bruising or bleeding.

Do not take this medication with milk, other dairy products, calcium supplements, or antacids that contain calcium. Calcium may make it harder for your body to absorb certain ingredients of the multivitamin.

What should I discuss with my healthcare provider before taking prenatal vitamins?

Many vitamins can cause serious or life-threatening side effects if taken in large doses. Do not take more of this medication than directed on the label or prescribed by your doctor.

Before taking prenatal vitamins, tell your doctor about all of your medical conditions.

You may need to continue taking prenatal vitamins if you breast-feed your baby. Ask your doctor about taking this medication while breast-feeding.

How should I take prenatal vitamins?

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

Never take more than the recommended dose of prenatal vitamins.

Take your prenatal vitamin with a full glass of water.

Swallow the regular tablet or capsule whole. Do not break, chew, crush, or open it.

The chewable tablet must be chewed or allowed to dissolve in your mouth before swallowing. You may also allow the chewable tablet to dissolve in drinking water, fruit juice, or infant formula (but not milk or other dairy products). Drink this mixture right away.

Use prenatal vitamins regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Store at room temperature away from moisture and heat. Keep prenatal vitamins in their original container. Storing vitamins in a glass container can ruin the medication.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

What should I avoid while taking prenatal vitamins?

Avoid taking any other multivitamin product within 2 hours before or after you take your prenatal vitamins. Taking similar vitamin products together at the same time can result in a vitamin overdose or serious side effects.

Avoid the regular use of salt substitutes in your diet if your multivitamin contains potassium. If you are on a low-salt diet, ask your doctor before taking a vitamin or mineral supplement.

Prenatal vitamins 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.

When taken as directed, prenatal vitamins are not expected to cause serious side effects. Less serious side effects may include:

upset stomach;

headache; or

unusual or unpleasant taste in your mouth.

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 prenatal vitamins?

Vitamin and mineral supplements can interact with certain medications, or affect how medications work in your body. Before taking a prenatal vitamin, tell your doctor if you also use:

diuretics (water pills);

heart or blood pressure medications;

tretinoin (Vesanoid);

isotretinoin (Accutane, Amnesteen, Clavaris, Sotret);

trimethoprim and sulfamethoxazole (Cotrim, Bactrim, Gantanol, Gantrisin, Septra, TMP/SMX); or

an NSAID (non-steroidal anti-inflammatory drug) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Cataflam, Voltaren), indomethacin (Indocin), meloxicam (Mobic), and others.

This list is not complete and other drugs may interact with prenatal vitamins. 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 Inatal Ultra resources

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

Inatal Ultra Prescribing Information (FDA)

Cal-Nate MedFacts Consumer Leaflet (Wolters Kluwer)

CareNatal DHA MedFacts Consumer Leaflet (Wolters Kluwer)

CitraNatal 90 DHA MedFacts Consumer Leaflet (Wolters Kluwer)

CitraNatal Assure Prescribing Information (FDA)

CitraNatal Harmony Prescribing Information (FDA)

Concept DHA Prescribing Information (FDA)

Docosavit Prescribing Information (FDA)

Duet DHA with Ferrazone MedFacts Consumer Leaflet (Wolters Kluwer)

Folbecal MedFacts Consumer Leaflet (Wolters Kluwer)

Folcal DHA Prescribing Information (FDA)

Folcaps Care One Prescribing Information (FDA)

Gesticare DHA Prescribing Information (FDA)

Gesticare DHA MedFacts Consumer Leaflet (Wolters Kluwer)

Inatal Advance Prescribing Information (FDA)

Multi-Nate DHA Prescribing Information (FDA)

Multi-Nate DHA Extra Prescribing Information (FDA)

MultiNatal Plus MedFacts Consumer Leaflet (Wolters Kluwer)

Natelle One Prescribing Information (FDA)

Neevo Caplets MedFacts Consumer Leaflet (Wolters Kluwer)

Neevo DHA MedFacts Consumer Leaflet (Wolters Kluwer)

OB Complete 400 MedFacts Consumer Leaflet (Wolters Kluwer)

Paire OB Plus DHA Prescribing Information (FDA)

PreNexa Prescribing Information (FDA)

PreNexa MedFacts Consumer Leaflet (Wolters Kluwer)

PreferaOB Prescribing Information (FDA)

Prenatal Plus Prescribing Information (FDA)

Prenatal Plus Iron Prescribing Information (FDA)

Prenate Elite tablets

Prenate Elite MedFacts Consumer Leaflet (Wolters Kluwer)

Prenate Elite Prescribing Information (FDA)

Prenate Essential Prescribing Information (FDA)

PrimaCare Advantage MedFacts Consumer Leaflet (Wolters Kluwer)

PrimaCare ONE capsules

PrimaCare One MedFacts Consumer Leaflet (Wolters Kluwer)

Renate DHA Prescribing Information (FDA)

Se-Natal 19 Prescribing Information (FDA)

Se-Natal 19 Chewable Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

Tandem DHA Prescribing Information (FDA)

Tandem OB Prescribing Information (FDA)

TriAdvance Prescribing Information (FDA)

Triveen-One MedFacts Consumer Leaflet (Wolters Kluwer)

Triveen-PRx RNF Prescribing Information (FDA)

UltimateCare ONE NF Prescribing Information (FDA)

Ultra NatalCare MedFacts Consumer Leaflet (Wolters Kluwer)

Vinate AZ Prescribing Information (FDA)

Vitafol-One MedFacts Consumer Leaflet (Wolters Kluwer)

Zatean-CH Prescribing Information (FDA)

Compare Inatal Ultra with other medications

Vitamin/Mineral Supplementation during Pregnancy/Lactation

Where can I get more information?

Your pharmacist can provide more information about prenatal vitamins.

See also: Inatal Ultra side effects (in more detail)

Wednesday 26 September 2012

Torisel

Generic Name: temsirolimus (Intravenous route)

tem-sir-OH-li-mus

Commonly used brand name(s)

In the U.S.

Torisel

Available Dosage Forms:

Solution

Therapeutic Class: Antineoplastic Agent

Uses For Torisel

Temsirolimus injection is an anticancer medicine that is used to treat advanced kidney cancer.

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

Before Using Torisel

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 temsirolimus injection in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies on the relationship of age to the effects of temsirolimus injection have not been performed in the geriatric population. However, elderly patients are more likely to have diarrhea, edema (swelling), and pneumonia, which may require caution in patients receiving temsirolimus injection.

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 receiving 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

Atazanavir

Bacillus of Calmette and Guerin Vaccine, Live

Carbamazepine

Clarithromycin

Dexamethasone

Indinavir

Influenza Virus Vaccine, Live

Itraconazole

Ketoconazole

Measles Virus Vaccine, Live

Mumps Virus Vaccine, Live

Nefazodone

Nelfinavir

Phenobarbital

Phenytoin

Poliovirus Vaccine, Live

Rifabutin

Rifampin

Ritonavir

Rotavirus Vaccine, Live

Rubella Virus Vaccine, Live

Saquinavir

Smallpox Vaccine

St John's Wort

Telithromycin

Typhoid Vaccine

Varicella Virus Vaccine

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

Proper Use of Torisel

Medicines used to treat cancer are very strong and can have many side effects. Before receiving this medicine, make sure you understand all the risks and benefits. It is important for you to work closely with your doctor during your treatment.

You will receive this medicine while you are in a hospital or cancer treatment center. A nurse or other trained health professional will give you this medicine. This medicine is given through a needle placed in one of your veins. The medicine must be injected slowly, so your IV tube will need to stay in place for 30 to 60 minutes.

You will receive a medicine to prevent allergic reactions (e.g., diphenhydramine, Benadryl®) before you receive this medicine.

Precautions While Using Torisel

It is very important that your doctor check your progress at regular visits to see if the medicine is working properly. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Men and women should use an effective form of birth control during treatment with temsirolimus and for at least 3 months after stopping treatment. If you think you have become pregnant while using this medicine, tell your doctor right away.

Temsirolimus may cause a serious type of allergic reaction called anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Tell your doctor right away if you have a rash; itching; swelling of the face, tongue, and throat; trouble with breathing; or chest pain after you get the injection.

This medicine may cause flushing, headaches, and lightheadedness or faintness, while you are receiving the injection or within 24 hours after you receive it. Check with your doctor or nurse right away if you have any of these symptoms.

This medicine may increase the amount of sugar in your blood. Check with your doctor right away if you have increased thirst or urination. Your doctor may give you insulin or other medicines that can lower the amount of sugar in your blood.

While you are being treated with temsirolimus, and after you stop treatment with it, do not have any immunizations (vaccinations) without your doctor's approval. Temsirolimus 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 get live vaccines (e.g., nasal flu virus vaccine, measles, mumps, rubella, oral polio vaccine, BCG, yellow fever, varicella, or TY21a typhoid vaccine). Try to avoid being around persons who have received live vaccines. Do not get close to them, and do not stay in the same room with them for very long. If you cannot take these precautions, you should consider wearing a protective face mask that covers the nose and mouth.

Treatment with temsirolimus may also increase the chance of getting other infections. If you can, avoid people with colds or other infections. If you think you are getting a cold or other infection, check with your doctor.

This medicine may cause a serious lung problem. Check with your doctor immediately if you are having tightness in the chest, shortness of breath, difficulty with breathing, or wheezing.

Temsirolimus may increase your cholesterol and fats in the blood. If this condition occurs, your doctor may give you some medicines that can lower the amount of cholesterol and fats in the blood.

Check with your doctor right away if you start having severe abdominal or stomach burning, cramps, or pains; bloody or black, tarry stools; diarrhea; fever; nausea; or vomiting of material that looks like coffee grounds. These could be symptoms of a serious bowel problem.

This medicine may increase your chance of having acute kidney disease that is not related to the worsening of your kidney cancer. Talk to your doctor about this risk.

This medicine may affect the way your body heals from cuts and wounds. Make sure any doctor who treats you knows that you are using this medicine. You may need to stop using this medicine several weeks before and after having surgery.

Grapefruit and grapefruit juice may increase the effects of temsirolimus by increasing the amount of medicine in your blood. You should not eat grapefruit or drink grapefruit juice while receiving this medicine.

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.

Torisel 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 or nurse immediately if any of the following side effects occur:

More common

Bladder pain

bloody nose

bloody or cloudy urine

body aches or pain

chest pain

congestion

cough or hoarseness

cracked lips

diarrhea

difficult or labored breathing

difficult, burning, or painful urination

difficulty with swallowing

dryness or soreness of the throat

fever or chills

frequent urge to urinate

headache

lack or loss of strength

lower back or side pain

shortness of breath

sneezing

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

stomach pain

stuffy or runny nose

swelling of the hands, ankles, feet, or lower legs

swelling or puffiness of the face

tender, swollen glands in the neck

tightness in the chest

voice changes

vomiting

wheezing

Incidence not known

Blistering, peeling, or loosening of the skin

convulsions

dark-colored urine

itching

joint or muscle pain

muscle cramps or spasms

muscle stiffness

pain or redness at the injection site

pale skin at injection site

red skin lesions, often with a purple center

red, irritated eyes

unusual tiredness or weakness

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

Abdominal or stomach cramps

black, tarry stools

feeling that others are watching you or controlling your behavior

feeling that others can hear your thoughts

feeling, seeing, or hearing things that are not there

loss of bladder control

muscle spasm or jerking of all extremities

severe mood or mental changes

severe vomiting, sometimes with blood

sudden loss of consciousness

tenderness, pain, swelling, warmth, skin discoloration, and prominent superficial veins over the affected area

unusual behavior

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

Back pain

blemishes on the skin

change in taste

difficulty having a bowel movement (stool)

difficulty with moving

discoloration of the fingernails or toenails

dry skin

loss of appetite

loss of taste

nausea

pain in the joints

pimples

rash

sleeplessness

swollen joints

trouble with sleeping

unable to sleep

weight loss

Less common

Discouragement

feeling sad or empty

irritability

loss of interest or pleasure

tiredness

trouble concentrating

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: Torisel side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Torisel resources

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

Torisel Prescribing Information (FDA)

Torisel Consumer Overview

Torisel Monograph (AHFS DI)

Torisel MedFacts Consumer Leaflet (Wolters Kluwer)

Temsirolimus Professional Patient Advice (Wolters Kluwer)

Compare Torisel with other medications

Renal Cell Carcinoma

Monday 24 September 2012

Cefaclor Extended Release Tablets

CEFACLOR EXTENDED-RELEASE TABLETS USP, 500 mg

1087

Rx only

Cefaclor Extended Release Tablets Description

Cefaclor, USP, the active ingredient in cefaclor extended-release tablets USP, is a semisynthetic cephalosporin antibiotic for oral administration. Cefaclor, USP, is chemically designated as 3-chloro-7-D-(2-phenylglycinamido)-3-cephem-4-carboxylic acid monohydrate. The cefaclor extended-release tablets formulation of cefaclor differs pharmacokinetically from the immediate-release formulation of cefaclor.

C15H14ClN3O4S • H2O M.W. 385.82

Each cefaclor extended-release tablet contains cefaclor monohydrate equivalent to 500 mg (1.36 mmol) anhydrous cefaclor. In addition, each extended-release tablet contains the following inactive ingredients: FD&C Blue #2 - indigo carmine lake, hypromellose, magnesium stearate, mannitol, polyethylene glycol, povidone and titanium dioxide.

Cefaclor Extended Release Tablets - Clinical Pharmacology

Pharmacokinetics

The cefaclor extended-release tablet formulation of cefaclor is pharmacokinetically different from the cefaclor immediate-release capsule formulation of cefaclor. (See TABLE 1.) No direct comparisons with the suspension formulation of cefaclor have been conducted; therefore, there are no data with which to compare the pharmacokinetic properties of the extended-release tablet formulation and the suspension formulation. Until further data are available, the pharmacokinetic equivalence of the extended-release tablet and the suspension formulations should NOT be assumed.

Absorption and Metabolism

The extent of absorption (AUC) and the maximum plasma concentration (Cmax) of cefaclor from cefaclor extended-release tablets are greater when the extended-release tablet is taken with food.

[NOTE: The extent of absorption (AUC) of cefaclor from cefaclor immediate-release capsules is unaffected by food intake; however, when cefaclor immediate-release capsules are taken with food, the Cmax is decreased.]

There is no evidence of metabolism of cefaclor in humans.

Comparative Serum Pharmacokinetics

Serum pharmacokinetic parameters for cefaclor extended-release tablets and cefaclor immediate-release capsules are shown in the table below.

TABLE 1: COMPARATIVE PHARMACOKINETICS OF CEFACLOR IMMEDIATE-RELEASE CAPSULES VS. CEFACLOR EXTENDED-RELEASE TABLETS IN FASTING AND FED STATES
Parameter	Cefaclor Extended-Release Tablets		Cefaclor Extended-Release Tablets		Cefaclor Immediate-Release Capsules
	375 mg		500 mg		2 x 250 mg
	fed	fast	fed	fast	fed	fast
	n = 10		n = 16	n = 16	n = 15	n = 16
Cmax	3.7 (1.1)	NA	8.2 (4.2)	5.4 (1.6)	9.3 (2.7)	16.8 (4.7)
Tmax	2.7 (1.0)	NA	2.5 (0.8)	1.5 (0.7)	1.5 (0.6)	0.9 (0.4)
AUC	9.9 (2.2)	NA	18.1 (4.2)	14.8 (4.0)	20.5 (2.8)	19.2 (5.0)
(± 1 standard deviation)
NA = data not available

No drug accumulation was noted when cefaclor extended-release tablets were given twice daily.

The plasma half-life in healthy subjects is independent of dosage form and averages approximately 1 hour.

Food Effect on Pharmacokinetics

When cefaclor extended-release tablets are taken with food, the AUC is 10% lower while the Cmax is 12% lower and occurs 1 hour later compared to cefaclor immediate-release capsules. In contrast, when cefaclor extended-release tablets are taken without food, the AUC is 23% lower while the Cmax is 67% lower and occurs 0.6 hours later, using an equivalent milligram dose of cefaclor immediate-release capsules as a reference. Therefore, cefaclor extended-release tablets should be taken with food.

Special Populations

Renal Insufficiency

In patients with reduced renal function, the serum half-life of cefaclor is slightly prolonged. In those with complete absence of renal function, the plasma half-life of the intact molecule is 2.3 to 2.8 hours. Excretion pathways in patients with markedly impaired renal function have not been determined. Hemodialysis shortens the half-life by 25% to 30%.

Geriatric Patients

In elderly subjects (over age 65) with normal serum creatinine values, higher peak plasma concentrations and AUCs have been observed. This is considered to be primarily a result of an age-related decrement in renal function, and has no apparent clinical significance. Therefore, dosage adjustment is not necessary in elderly subjects with normal serum creatinine values.

Microbiology

Cefaclor has in vitro activity against a broad range of gram-positive and gram-negative bacteria. The bactericidal action of cefaclor results from inhibition of cell-wall synthesis. Cefaclor is stable in the presence of some bacterial ß-lactamases; consequently, some ß-lactamase-producing organisms may be susceptible to cefaclor.

Cefaclor extended-release tablets have been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Gram-positive aerobes:

Staphylococcus aureus

Streptococcus pneumoniae

Streptococcus pyogenes

NOTE: Cefaclor is inactive against methicillin-resistant staphylococci.

Gram-negative aerobes:

Haemophilus influenzae (non-ß-lactamase-producing strains only)

Moraxella catarrhalis (including ß-lactamase-producing strains)

The following in vitro data are available, but their clinical significance is unknown. Cefaclor exhibits in vitro minimum inhibitory concentrations (MICs) of 8 mcg/mL or less (systemic susceptibility breakpoint) against most (≥ 90%) strains of the following microorganisms; however, the safety and effectiveness of cefaclor extended-release tablets in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials.

Gram-positive aerobes:

Staphylococcus epidermidis

Gram-negative aerobes:

Haemophilus parainfluenzae

Klebsiella pneumoniae

Anaerobic bacteria:

Peptococcus niger

Peptostreptococci

Propionibacterium acnes

NOTE: Acinetobacter calcoaceticus, Enterobacter spp., Entercoccus spp., Morganella morganii, Proteus vulgaris, Providencia spp., Pseudomonas spp., and Serratia spp. are resistant to cefaclor.

Susceptibility Testing

Dilution Techniques

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method1 (broth, agar, or microdilution) or equivalent with standardized inoculum concentrations and standardized amounts of cefaclor powder. The MIC values should be interpreted according to the following criteria:

MIC (mcg/mL)	Interpretation
≤ 8	Susceptible (S)
16	Intermediate (I)
≥ 32	Resistant (R)

A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in blood reaches the concentrations usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard cefaclor powder should provide the following MIC values:

* Broth microdilution tests performed using Haemophilus Test Medium (HTM)1
Microorganism		MIC range (mcg/mL)
E. coli	ATCC 25922	1 to 4
E. faecalis	ATCC 29212	> 32
S. aureus	ATCC 29213	1 to 4
H. influenzae	ATCC 49766*	1 to 4

Diffusion Techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30 mcg cefaclor to test the susceptibility of microorganisms to cefaclor.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30 mcg cefaclor disk should be interpreted according to the following criteria:

Zone diameter (mm)	Interpretation
≥ 18	Susceptible (S)
15 to 17	Intermediate (I)
≤ 14	Resistant (R)

When testing*H. Influenzae, the following interpretive criteria should be used:

Zone diameter (mm)	Interpretation
≥ 20	Susceptible (S)
17 to 19	Intermediate (I)
≤ 16	Resistant (R)

* Disk susceptibility tests performed using Haemophilus Test Medium (HTM)2

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for cefaclor.

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30 mcg cefaclor disk should provide the following zone diameters in these laboratory test quality control strains:

* Disk susceptibility tests performed using Haemophilus Test Medium (HTM)2
Microorganism		Zone diameter (mm)
E. coli	ATCC 25922	23 to 27
S. aureus	ATCC 25923	27 to 31
H. influenzae*	ATCC 49766	25 to 31

Indications and Usage for Cefaclor Extended Release Tablets

To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefaclor extended-release tablets USP and other antibacterial drugs, cefaclor extended-release tablets USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

The safety and effectiveness of cefaclor extended-release tablets in treating some of the indications and pathogens for which other formulations of cefaclor are approved have NOT been established. When administered at the recommended dosages and durations of therapy, cefaclor extended-release tablets are indicated for the treatment of patients with the following mild to moderate infections when caused by susceptible strains of the designated organisms. (See DOSAGE AND ADMINISTRATION and CLINICAL STUDIES sections.)

Acute bacterial exacerbations of chronic bronchitis due to Haemophilus influenzae (non-ß-lactamase-producing strains only), Moraxella catarrhalis (including ß-lactamase-producing strains) or Streptococcus pneumoniae.

NOTE: In view of the insufficient numbers of isolates of ß-lactamase-producing strains of Haemophilus influenzae that were obtained from clinical trials with cefaclor extended-release tablets for patients with acute bacterial exacerbations of chronic bronchitis or secondary bacterial infections of acute bronchitis, it was not possible to adequately evaluate the effectiveness of cefaclor extended-release tablets for bronchitis known, suspected, or considered potentially to be caused by ß-lactamase-producing H. influenzae.

Secondary bacterial infections of acute bronchitis due to Haemophilus influenzae (non-ß-lactamase-producing strains only), Moraxella catarrhalis (including ß-lactamase-producing strains), or Streptococcus pneumoniae. (See above NOTE.)

Pharyngitis and tonsillitis due to Streptococcus pyogenes.

NOTE: Only penicillin by the intramuscular route of administration has been shown to be effective in the prophylaxis of rheumatic fever. Cefaclor extended-release tablets are generally effective in the eradication of S. pyogenes from the oropharynx; however, data establishing the efficacy of cefaclor extended-release tablets for the prophylaxis of subsequent rheumatic fever are not available.

Uncomplicated skin and skin and structure infections due to Staphylococcus aureus (methicillin-susceptible).

NOTE: In view of the insufficient numbers of isolates of Streptococcus pyogenes that were obtained from clinical trials with cefaclor extended-release tablets for patients with uncomplicated skin and skin structure infections, it was not possible to adequately evaluate the effectiveness of cefaclor extended-release tablets for skin infections known, suspected, or considered potentially to be caused by S. pyogenes.

Contraindications

Cefaclor extended-release tablets are contraindicated in patients with known hypersensitivity to cefaclor and other cephalosporins.

Warnings

BEFORE THERAPY WITH CEFACLOR EXTENDED-RELEASE TABLETS IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFACLOR, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-SENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF AN ALLERGIC REACTION TO CEFACLOR EXTENDED-RELEASE TABLETS OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, INTRAVENOUS FLUIDS, INTRAVENOUS ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cefaclor and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increase morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Precautions

General

Prescribing cefaclor extended-release tablets USP in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Superinfection (overgrowth by non-susceptible organisms) should always be considered a possibility in a patient being treated with a broad spectrum antimicrobial. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Information for Patients

Patients should be counseled that antibacterial drugs including cefaclor extended-release tablets USP should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cefaclor extended-release tablets USP are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by cefaclor extended-release tablets USP or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Drug Interactions

Antacids

The extent of absorption of cefaclor extended-release tablets is diminished if magnesium or aluminum hydroxide-containing antacids are taken within 1 hour of administration; H2 blockers do not alter either the rate or the extent of absorption of cefaclor extended-release tablets.

Probenecid

The renal excretion of cefaclor is inhibited by probenecid.

Warfarin

There have been rare reports of increased prothrombin time with or without clinical bleeding in patients receiving cefaclor and warfarin concomitantly. No specific studies have been performed to rule in or rule out this potential drug/drug interaction.

Laboratory Test Interactions

Administration of cefaclor extended-release tablets may result in a false-positive reaction for glucose in the urine. This phenomenon has been seen in patients taking cephalosporin antibiotics when the test is performed using Benedict's and Fehling's solutions and also with Clinitest® tablets.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies in animals have not been performed to evaluate the carcinogenic or mutagenic potential for cefaclor. Reproduction studies have revealed no evidence of impaired fertility.

Usage in Pregnancy

Teratogenic Effect

Pregnancy category B

Reproduction studies using cefaclor have been performed in mice, rats and ferrets at doses up to 3 to 5 times the maximum human dose (1500 mg/day) based on mg/m2. These studies have revealed no harm to the fetus due to cefaclor. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, cefaclor extended-release tablets should be used during pregnancy only if clearly needed.

Labor and Delivery

Cefaclor extended-release tablets have not been studied for use during labor and delivery. Treatment should be given only if clearly needed.

Nursing Mothers

No studies in lactating women have been performed with cefaclor extended-release tablets. Small amounts of cefaclor (≤ 0.21 mcg/mL) have been detected in human milk following administration of single 500 mg doses of cefaclor extended-release tablets. The effect on nursing infants is not known. Caution should be exercised when cefaclor extended-release tablets are administered to a nursing woman.

Pediatric Use

Safety and effectiveness of cefaclor extended-release tablets in pediatric patients less than 16 years of age have not been established.

Geriatric Use

Healthy geriatric volunteers (≥ 65 years old) who received a single 750 mg dose of cefaclor extended-release tablets had 40% to 50% higher AUC and 20% lower renal clearance values when compared to healthy adult volunteers less than 45 years of age. These differences are considered to be primarily a result of age-related decreases in renal function. In clinical studies when geriatric patients received the usual recommended adult doses, clinical efficacy and safety were comparable to results in non-geriatric adult patients. No dosage changes are recommended for healthy geriatric patients.

Adverse Reactions

Clinical Trials

There were 3272 patients treated with multiple doses of cefaclor extended-release tablets in controlled clinical trials and an additional 211 subjects in pharmacology studies. There were no deaths in these trials thought to be related to toxicity from cefaclor extended-release tablets. Treatment was discontinued in 1.7% of patients due to adverse events thought to be possibly or probably drug-related.

The following adverse clinical and laboratory events were reported during the cefaclor extended-release tablets clinical trials conducted in North America at doses of 375 mg or 500 mg BID; however, relatedness of the adverse events to the drug was not assigned by clinical investigators during the trials (see TABLES 2 and 3).

TABLE 2: ADVERSE CLINICAL EVENTS - CEFACLOR EXTENDED-RELEASE TABLETS MULTIPLE DOSE DOSING REGIMENS CLINICAL TRIALS - NORTH AMERICA (n = 1400)
* n = 934 for these events (subset of female participants).
Incidence Equal to or Greater Than 1%	Event	Incidence
	Headache	4.9%
	Rhinitis	3.9%
	Diarrhea	3.8%
	Nausea	3.4%
	Vaginitis*	2.4%
	Vaginal Moniliasis*	2.2%
	Abdominal Pain	1.6%
	Cough Increased	1.5%
	Pharyngitis	1.4%
	Pruritus	1.4%
	Back Pain	1.0%

Adverse reactions occurring during the clinical trials with cefaclor extended-release tablets with an incidence of less than 1% but greater than 0.1% included the following (listed alphabetically):

Accidental injury, anorexia, anxiety, arthralgia, asthma, bronchitis, chest pain, chills, congestive heart failure, conjunctivitis, constipation, dizziness, dysmenorrhea, dyspepsia, dysuria, ear pain, edema, fever, flatulence, flu syndrome, gastritis, infection, insomnia, leukorrhea, lung disorder, maculopapular rash, malaise, menstrual disorder, myalgia, nausea and vomiting, neck pain, nervousness, nocturia, otitis media, pain, palpitation, peripheral edema, rash, respiratory disorder, sinusitis, somnolence, surgical procedure, sweating, tremor, urticaria, vomiting.

NOTE: One case of serum-sickness-like reaction was reported among the 3272 adult patients treated with cefaclor extended-release tablets during the controlled clinical trials. These reactions have also been reported with the use of cefaclor in other oral formulations and are seen more frequently in pediatric patients than in adults. These reactions are characterized by findings of erythema multiforme, rash, and other skin manifestations accompanied by arthritis/arthralgia, with or without fever, and differ from classic serum sickness in that there is infrequently associated lymphadenopathy and proteinuria, no circulating immune complexes and no evidence to date of sequelae of the reaction. While further investigation is ongoing, serum-sickness-like reactions appear to be due to hypersensitivity and more often occur during or following a second (or subsequent) course of therapy with cefaclor. Such reactions have been reported with overall occurrence ranging from 1 in 200 (0.5%) in one focused trial; to 2 in 8346 (0.024%) in overall clinical trials (with an incidence in pediatric patients in clinical trials of 0.055%); to 1 in 38,000 (0.003%) in spontaneous event reports. Signs and symptoms usually occur a few days after initiation of therapy and subside within a few days after cessation of therapy. Occasionally these reactions have resulted in hospitalization, usually of short duration (median hospitalization = 2 to 3 days, based on postmarketing surveillance studies). In those patients requiring hospitalization, the symptoms have ranged from mild to severe at the time of admission with more of the severe reactions occurring in pediatric patients.

TABLE 3: ADVERSE CLINICAL LABORATORY EVENTS CEFACLOR EXTENDED-RELEASE TABLETS MULTIPLE DOSE DOSING REGIMENS CLINICAL TRIALS – NORTH AMERICA
	Event	Incidence
Incidence Less Than 1%, but Greater Than 0.1%	Albumin decreased	0.3%
	Alkaline phosphatase increased	0.3%
	ALT/SGPT increased	0.3%
	Bilirubin total increased	0.3%
	Blood urea nitrogen (BUN) increased	0.2%
	Calcium decreased	0.7%
	Creatine phosphokinase increased	0.7%
	Creatinine increased	0.5%
	Eosinophils increased	0.3%
	Erythrocyte count decreased	0.3%
	GGT increased	0.2%
	Hemoglobin decreased	0.2%
	Lymphocytes decreased	0.3%
	Mean Cell Volume (MCV) increased	0.7%
	Neutrophils segmented decreased	0.3%
	Phosphorous increased	0.7%
	Platelet count decreased	0.3%
	Potassium increased	0.4%
	Sodium decreased	0.3%
	Sodium increased	0.4%

In Postmarketing Experience

In addition to the events reported during clinical trials with cefaclor extended-release tablets, the following adverse experiences are among those that have been reported during worldwide postmarketing surveillance: allergic reaction, anaphylactoid reaction, angioedema, face edema, hypotension, Stevens-Johnson syndrome, syncope, paresthesia, vasodilatation and vertigo.

Other Adverse Reactions Associated With Other Formulations of Cefaclor

In addition to the above, the following other adverse reactions and altered laboratory tests have been associated with cefaclor in other oral formulations:

Clinical

Severe hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and anaphylaxis, have been reported rarely. Anaphylactoid events may be manifested by solitary symptoms, including angioedema, edema (including face and limbs), paresthesias, syncope, or vasodilatation. Anaphylaxis may be more common in patients with a history of penicillin allergy. Rarely, hypersensitivity symptoms may persist for several months.

Symptoms of pseudomembranous colitis may appear either during or after antibiotic treatment. (See WARNINGS.)

Laboratory

Abnormal urinalysis, eosinophilia, leukopenia, neutropenia, transient elevations in AST, and transient thrombocytopenia have been reported.

Cephalosporin-Class Reactions

In addition to the adverse reactions listed above, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics:

Clinical

Confusion, erythema multiforme, genital pruritus, hepatic dysfunction including cholestasis, hemolytic anemia, reversible hyperactivity, hypertonia, and reversible interstitial nephritis.

Laboratory

Positive direct Coombs’ test.

Overdosage

The toxic symptoms following an overdose of cefaclor may include nausea, vomiting, epigastric distress, and diarrhea. The severity of the epigastric distress and the diarrhea are dose-related.

Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage. Consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed.

Although cefaclor is considered dialyzable, neither forced diuresis, peritoneal dialysis, hemodialysis, nor charcoal hemoperfusion have been demonstrated to be beneficial in an overdose of cefaclor.

Cefaclor Extended Release Tablets Dosage and Administration

The absorption of cefaclor extended-release tablets is enhanced when it is administered with food. (See CLINICAL PHARMACOLOGY.) Therefore, cefaclor extended-release tablets should be administered with meals (i.e., at least within one hour of eating). The extended-release tablets should not be cut, crushed, or chewed.

See INDICATIONS AND USAGE for information about patients for whom cefaclor extended-release tablets are indicated.

NOTE: 500 mg BID of cefaclor extended-release tablets is clinically equivalent to 250 mg TID of cefaclor immediate-release as a capsule in those indications listed in the INDICATIONS AND USAGE section of this label. 500 mg BID of cefaclor extended-release tablets is NOT equivalent to 500 mg TID of other cefaclor formulations.

Adults (age 16 years and older):

Type of Infection (as qualified in the INDICATIONS AND USAGE section of this labeling)	Total Daily Dose	Dose and Frequency	Duration
Acute Bacterial Exacerbations of Chronic Bronchitis due to H. influenzae (non-ß-lactamase-producing strains only). Moraxella catarrhalis (including ß-lactamase-producing strains), or Streptococcus pneumoniae (See INDICATIONS AND USAGE.)	1000 mg	500 mg q 12 hours	7 days
Secondary Bacterial Infection of Acute Bronchitis due to H. influenzae (non-ß-lactamase-producing strains only). M. catarrhalis (including ß-lactamase-producing strains), or S. pneumoniae (See INDICATIONS AND USAGE.)	1000 mg	500 mg q 12 hours	7 days
Pharyngitis and/or tonsillitis due to S. pyogenes	750 mg	375 mg q 12 hours	10 days
Uncomplicated Skin and Skin Structure Infections due to S. aureus (methicillin-susceptible strains) (See INDICATIONS AND USAGE.)	750 mg	375 mg q 12 hours	7 to 10 days

Elderly patients with normal renal function do not require dosage adjustments.

How is Cefaclor Extended Release Tablets Supplied

Cefaclor extended-release tablets USP, 500 mg (based on the anhydrous), are available as film-coated, oval-shaped, unscored, dark blue tablets, debossed with “93” on one side and “1087” on the other side. They are available in bottles of 100.

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

Clinical Studies

ACUTE BACTERIAL EXACERBATIONS OF CHRONIC BRONCHITIS AND SECONDARY BACTERIAL INFECTIONS OF ACUTE BRONCHITIS

In adequate and well-controlled clinical trials of cefaclor extended-release tablets in the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB) and secondary bacterial infections of acute bronchitis (SBIAB), only 4 evaluable patients with ABECB and no evaluable patients with SBIAB had infections caused by ß-lactamase-producing H. influenzae. Four patients do not provide adequate data upon which to judge clinical efficacy of cefaclor extended-release tablets against ß-lactamase-producing H. influenzae.

UNCOMPLICATED SKIN AND SKIN STRUCTURE INFECTIONS

Cefaclor extended-release tablets (375 mg Q12H) (n = 115) were compared to cefaclor immediate-release capsules (250 mg T