U.S. BRAND NAMES — Uroxatral®
PHARMACOLOGIC CATEGORY Alpha1 Blocker
DOSING: ADULTS — Benign prostatic hyperplasia (BPH): Oral: 10 mg once daily
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Bioavailability and maximum serum concentrations are increased by ~50% with mild, moderate, or severe renal impairment.
Note: Safety has not been evaluated in patients with creatinine clearances <30 mL/minute.
DOSING: HEPATIC IMPAIRMENT Mild hepatic impairment: Use has not been studied.
Moderate or severe hepatic impairment (Child-Pugh class B and C): Clearance is decreased 1/3 to 1/4 and serum concentration is increased three- to fourfold; use is contraindicated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, extended release, as hydrochloride: 10 mg
DOSAGE FORMS: CONCISE Tablet, extended release: Uroxatral™: 10 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Tablet should be swallowed whole; do not crush or chew. Administer once daily (with a meal); should be taken at the same time each day.
USE — Treatment of the functional symptoms of benign prostatic hyperplasia (BPH)
ADVERSE REACTIONS SIGNIFICANT 1% to 10%: Central nervous system: Dizziness (6%), fatigue (3%), headache (3%), pain (1% to 2%) Gastrointestinal: Abdominal pain (1% to 2%), constipation (1% to 2%), dyspepsia (1% to 2%), nausea (1% to 2%) Genitourinary: Impotence (1% to 2%) Respiratory: Upper respiratory tract infection (3%), bronchitis (1% to 2%), pharyngitis (1% to 2%), sinusitis (1% to 2%)
<1% (Limited to important or life-threatening): Angina pectoris (pre-existing CAD), angioedema, chest pain, diarrhea, edema, flushing, intraoperative floppy iris syndrome (with cataract surgery), priapism, pruritis, rash, rhinitis, tachycardia, urticaria
CONTRAINDICATIONS — Hypersensitivity to alfuzosin or any component of the formulation; moderate or severe hepatic insufficiency (Child-Pugh class B and C); potent CYP3A4 inhibitors (eg, itraconazole, ketoconazole, ritonavir)
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Angina: Discontinue if symptoms of angina occur or worsen. Floppy iris syndrome: Intraoperative floppy iris syndrome has been observed in cataract surgery patients who were on or were previously treated with alpha1-blockers; causality has not been established and there appears to be no benefit in discontinuing alpha-blocker therapy prior to surgery. Orthostatic hypotension/syncope: May cause significant orthostatic hypotension and syncope, especially with first dose; anticipate a similar effect if therapy is interrupted for a few days, if dosage is rapidly increased, or if another antihypertensive drug (particularly vasodilators) or a PDE5 inhibitor is introduced. Patients should be cautioned about performing hazardous tasks when starting new therapy or adjusting dosage upward.
Disease-related concerns: Hepatic impairment: Use with caution in patients with mild hepatic impairment; not recommended in moderate to severe impairment. Prostate cancer: Should rule out prostatic carcinoma before beginning therapy. Renal impairment: Use with caution in patients with renal impairment.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warning/precautions: Antihypertensive agent: Not intended for use as an antihypertensive drug.
DRUG INTERACTIONS — Substrate of CYP3A4 (major)
CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of alfuzosin. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.
CYP3A4 inhibitors: May increase the levels/effects of alfuzosin. Example inhibitors include azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, telithromycin, and verapamil. Concurrent use of itraconazole, ketoconazole, or ritonavir is contraindicated.
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Food increases the extent of absorption.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies; however, alfuzosin is not indicated for use in women.
LACTATION — Not indicated for use in women
DIETARY CONSIDERATIONS — Take following a meal at the same time each day.
PRICING — (data from drugstore.com)Tablet, 24-hour (Uroxatral) 10 mg (30): $76.49
MONITORING PARAMETERS — Urine flow; blood pressure
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Hypotension would be expected in case of overdose. Treatment is symptom-directed and supportive. Dialysis not likely to benefit.
CANADIAN BRAND NAMES — Xatral
INTERNATIONAL BRAND NAMES — Alfetim (HU); Alfusin (IN); Dalfaz (AR, ES, PL); Uroxatral (CL); Uroxatral OD (AR, UY); Uroxatral uno (DE); Xatral (AT, BE, BF, BJ, CA, CH, CI, CN, CZ, DK, ET, FI, FR, GB, GH, GM, GN, IE, IL, IT, KE, LR, MA, ML, MR, MU, MW, NE, NG, NL, SC, SD, SE, SL, SN, TZ, UG, ZA, ZM, ZW); Xatral LP (EC, FR, HK); Xatral OD (BR, CO, CR, DO, GT, HN, MX, NI, PA, PE, PH, PY, SV, VE); Xatral SR (AT, BG, EE, EG, IL, PK, SG); Xatral XL (ID, IL, KR, SG, TH); Xatral XR 10 (SG)
MECHANISM OF ACTION — An antagonist of alpha1-adrenoreceptors in the lower urinary tract. Smooth muscle tone is mediated by the sympathetic nervous stimulation of alpha1-adrenoreceptors, which are abundant in the prostate, prostatic capsule, prostatic urethra, and bladder neck. Blockade of these adrenoreceptors can cause smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of BPH.
PHARMACODYNAMICS / KINETICS Absorption: Decreased 50% under fasting conditions
Distribution: Vd: 3.2 L/kg
Protein binding: 82% to 90%
Metabolism: Hepatic, primarily via CYP3A4; metabolism includes oxidation, O-demethylation, and N-dealkylation; forms metabolites (inactive)
Bioavailability: 49% following a meal
Half-life elimination: 10 hours
Time to peak, plasma: 8 hours following a meal
Excretion: Feces (69%); urine (24%)
PATIENT INFORMATION — Do not take any new medication during therapy without consulting prescriber. Take exactly as directed, with a meal at the same time each day. Swallow tablet whole; do not crush or chew. May cause drowsiness, dizziness, impaired judgment (use caution when driving or engaging in tasks that require alertness until response to drug is known), or postural hypotension (use caution when rising from sitting or lying position or when climbing stairs). Report unusual chest pain, respiratory difficulty, or any persistent adverse reactions.
Saturday, March 15, 2008
Alfentanil
U.S. BRAND NAMES — Alfenta®
PHARMACOLOGIC CATEGORY Analgesic, Opioid
DOSING: ADULTS — Doses should be titrated to appropriate effects; wide range of doses is dependent upon desired degree of analgesia/anesthesia
Anesthesia: I.V.: Dose should be based on ideal body weight as follows (see table).
Adult Dosage Adjustments
Incremental injection in anesthesia 30 minutes: Initial dose (induction period): 8-20 mcg/kg Maintenance period (increments/infusion): 3-5 mcg/kg or 0.5-1 mcg/kg/minute Total dose: 8-40 mcg/kg Appropriate effects: Spontaneously breathing or assisted ventilation when required
Incremental injection in anesthesia of 30-60 minutes: Initial dose (induction period): 20-50 mcg/kg Maintenance period (increments/infusion): 5-15 mcg/kg Total dose: Up to 75 mcg/kg Appropriate effects: Assisted or controlled ventilation required. Attenuation of response to laryngoscopy and intubation.
Continuous infusion >45 minutes: Initial dose (induction period): 50-75 mcg/kg Maintenance period (increments/infusion): 0.5-3 mcg/kg/minute; average infusion rate: 1-1.5 mcg/kg/minute Total dose: Dependent on duration of procedure Appropriate effects: Assisted or controlled ventilation required. Some attenuation of response to intubation and incision, with intraoperative stability.
Anesthetic induction >45 minutes: Initial dose (induction period): 130-245 mcg/kg Maintenance period (increments/infusion): 0.5-1.5 mcg/kg/minute or general anesthetic Total dose: Dependent on duration of procedure Appropriate effects: Assisted or controlled ventilation required. Administer slowly (over 3 minutes). Concentration of inhalation agents reduced by 30% to 50% for initial hour.
DOSING: PEDIATRIC
(For additional information see "Alfentanil: Pediatric drug information")Children <12 years: Dose has not been established.
Children 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: 500 mcg/mL (2 mL, 5 mL, 10 mL) Alfenta®: 500 mcg/mL (2 mL, 5 mL, 10 mL, 20 mL)
DOSAGE FORMS: CONCISE Injection, solution [preservative free]: 500 mcg/mL (2 mL, 5 mL, 10 mL) Alfenta®: 500 mcg/mL (2 mL, 5 mL, 10 mL, 20 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer I.V. slowly over 3-5 minutes or by I.V. continuous infusion.
COMPATIBILITY — Stable in D5W, NS, LR, D5NS.
Y-site administration: Compatible: Cisatracurium, etomidate, gatifloxacin, linezolid, propofol, remifentanil. Incompatible: Amphotericin B cholesteryl sulfate complex, thiopental.
Compatibility in syringe: Compatible: Atracurium, midazolam, ondansetron.
USE — Analgesic adjunct given by continuous infusion or in incremental doses in maintenance of anesthesia with barbiturate or N2O or a primary anesthetic agent for the induction of anesthesia in patients undergoing general surgery in which endotracheal intubation and mechanical ventilation are required
ADVERSE REACTIONS SIGNIFICANT >10%: Cardiovascular: Bradycardia, peripheral vasodilation Central nervous system: Drowsiness, sedation, intracranial pressure increased Endocrine & metabolic: Antidiuretic hormone release Gastrointestinal: Nausea, vomiting, constipation Ocular: Miosis
1% to 10%: Cardiovascular: Cardiac arrhythmia, orthostatic hypotension Central nervous system: Confusion, CNS depression Ocular: Blurred vision
<1% (Limited to important or life-threatening): Convulsions, mental depression, paradoxical CNS excitation or delirium, dizziness, dysesthesia, rash, urticaria, itching, biliary tract spasm, urinary tract spasm, respiratory depression, bronchospasm, laryngospasm, physical and psychological dependence with prolonged use; cold, clammy skin
CONTRAINDICATIONS — Hypersensitivity to alfentanil hydrochloride, to narcotics, or any component of the formulation; increased intracranial pressure, severe respiratory depression
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Opioid agonist toxicities: Shares the toxic potentials of opiate agonists, and precautions of opiate agonist therapy should be observed.
Disease-related concerns: Bradyarrhythmias: Use with caution when administering to patients with bradyarrhythmias. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Obesity: Use with caution in patients who are morbidly obese. Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function.
Special populations: Neonates: Hypotension has occurred in neonates with respiratory distress syndrome. Pediatrics: Safety and efficacy have not been established in children <12 years old.
Other warnings/precautions: Rapid infusion: Inject slowly over 3-5 minutes; rapid I.V. infusion may result in skeletal muscle and chest wall rigidity, impaired ventilation, or respiratory distress/arrest; nondepolarizing skeletal muscle relaxant may be required. Trained individuals: Due to the high incidence of apnea, hypotension, tachycardia and muscle rigidity; it should be administered by individuals specifically trained in the use of anesthetic agents and should not be used in diagnostic or therapeutic procedures outside the monitored anesthesia setting; resuscitative and intubation equipment should be readily available.
RESTRICTIONS — C-II
DRUG INTERACTIONS — Substrate of CYP3A4 (major)
Dextroamphetamine: May enhance the analgesic effect of morphine and other opiate agonists.
Increased toxicity with CNS depressants (eg, benzodiazepines, barbiturates, tricyclic antidepressants), erythromycin, reserpine, beta-blockers.
CYP3A4 inhibitors: May increase the levels/effects of alfentanil. Example inhibitors include azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, telithromycin, and verapamil.
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Respiratory rate, blood pressure, heart rate
REFERENCE RANGE — 100-340 ng/mL (depending upon procedure)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include miosis, respiratory depression, seizures, and CNS depression. Treatment includes naloxone 2 mg I.V. (0.01 mg/kg for children), with repeat administration as necessary, up to a total of 10 mg. May precipitate withdrawal.
CANADIAN BRAND NAMES — Alfentanil Injection, USP; Alfenta®
INTERNATIONAL BRAND NAMES — Alfenil (KR); Alfenta (BR, CA); Alfentanil Injection, USP (CA); Brevafen (AR); Fanaxal (ES); Fentalim (IT); Rapifen (AE, AT, AU, BE, BG, BH, BR, CH, CL, CY, CZ, DE, DK, EG, FI, FR, GB, GR, HK, HR, HU, IE, IL, IQ, IR, IT, JO, KW, LB, LY, NL, NO, NZ, OM, PL, PT, PY, QA, RU, SA, SE, SY, TW, UY, VE, YE, ZA)
MECHANISM OF ACTION — Binds with stereospecific receptors at many sites within the CNS, increases pain threshold, alters pain perception, inhibits ascending pain pathways; is an ultra short-acting narcotic
PHARMACODYNAMICS / KINETICS Onset of action: Rapid
Duration (dose dependent): 30-60 minutes
Distribution: Vd: Newborns, premature: 1 L/kg; Children: 0.163-0.48 L/kg; Adults: 0.46 L/kg
Half-life elimination: Newborns, premature: 5.33-8.75 hours; Children: 40-60 minutes; Adults: 83-97 minutes
PHARMACOLOGIC CATEGORY Analgesic, Opioid
DOSING: ADULTS — Doses should be titrated to appropriate effects; wide range of doses is dependent upon desired degree of analgesia/anesthesia
Anesthesia: I.V.: Dose should be based on ideal body weight as follows (see table).
Adult Dosage Adjustments
Incremental injection in anesthesia 30 minutes: Initial dose (induction period): 8-20 mcg/kg Maintenance period (increments/infusion): 3-5 mcg/kg or 0.5-1 mcg/kg/minute Total dose: 8-40 mcg/kg Appropriate effects: Spontaneously breathing or assisted ventilation when required
Incremental injection in anesthesia of 30-60 minutes: Initial dose (induction period): 20-50 mcg/kg Maintenance period (increments/infusion): 5-15 mcg/kg Total dose: Up to 75 mcg/kg Appropriate effects: Assisted or controlled ventilation required. Attenuation of response to laryngoscopy and intubation.
Continuous infusion >45 minutes: Initial dose (induction period): 50-75 mcg/kg Maintenance period (increments/infusion): 0.5-3 mcg/kg/minute; average infusion rate: 1-1.5 mcg/kg/minute Total dose: Dependent on duration of procedure Appropriate effects: Assisted or controlled ventilation required. Some attenuation of response to intubation and incision, with intraoperative stability.
Anesthetic induction >45 minutes: Initial dose (induction period): 130-245 mcg/kg Maintenance period (increments/infusion): 0.5-1.5 mcg/kg/minute or general anesthetic Total dose: Dependent on duration of procedure Appropriate effects: Assisted or controlled ventilation required. Administer slowly (over 3 minutes). Concentration of inhalation agents reduced by 30% to 50% for initial hour.
DOSING: PEDIATRIC
(For additional information see "Alfentanil: Pediatric drug information")Children <12 years: Dose has not been established.
Children 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: 500 mcg/mL (2 mL, 5 mL, 10 mL) Alfenta®: 500 mcg/mL (2 mL, 5 mL, 10 mL, 20 mL)
DOSAGE FORMS: CONCISE Injection, solution [preservative free]: 500 mcg/mL (2 mL, 5 mL, 10 mL) Alfenta®: 500 mcg/mL (2 mL, 5 mL, 10 mL, 20 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer I.V. slowly over 3-5 minutes or by I.V. continuous infusion.
COMPATIBILITY — Stable in D5W, NS, LR, D5NS.
Y-site administration: Compatible: Cisatracurium, etomidate, gatifloxacin, linezolid, propofol, remifentanil. Incompatible: Amphotericin B cholesteryl sulfate complex, thiopental.
Compatibility in syringe: Compatible: Atracurium, midazolam, ondansetron.
USE — Analgesic adjunct given by continuous infusion or in incremental doses in maintenance of anesthesia with barbiturate or N2O or a primary anesthetic agent for the induction of anesthesia in patients undergoing general surgery in which endotracheal intubation and mechanical ventilation are required
ADVERSE REACTIONS SIGNIFICANT >10%: Cardiovascular: Bradycardia, peripheral vasodilation Central nervous system: Drowsiness, sedation, intracranial pressure increased Endocrine & metabolic: Antidiuretic hormone release Gastrointestinal: Nausea, vomiting, constipation Ocular: Miosis
1% to 10%: Cardiovascular: Cardiac arrhythmia, orthostatic hypotension Central nervous system: Confusion, CNS depression Ocular: Blurred vision
<1% (Limited to important or life-threatening): Convulsions, mental depression, paradoxical CNS excitation or delirium, dizziness, dysesthesia, rash, urticaria, itching, biliary tract spasm, urinary tract spasm, respiratory depression, bronchospasm, laryngospasm, physical and psychological dependence with prolonged use; cold, clammy skin
CONTRAINDICATIONS — Hypersensitivity to alfentanil hydrochloride, to narcotics, or any component of the formulation; increased intracranial pressure, severe respiratory depression
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Opioid agonist toxicities: Shares the toxic potentials of opiate agonists, and precautions of opiate agonist therapy should be observed.
Disease-related concerns: Bradyarrhythmias: Use with caution when administering to patients with bradyarrhythmias. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Obesity: Use with caution in patients who are morbidly obese. Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function.
Special populations: Neonates: Hypotension has occurred in neonates with respiratory distress syndrome. Pediatrics: Safety and efficacy have not been established in children <12 years old.
Other warnings/precautions: Rapid infusion: Inject slowly over 3-5 minutes; rapid I.V. infusion may result in skeletal muscle and chest wall rigidity, impaired ventilation, or respiratory distress/arrest; nondepolarizing skeletal muscle relaxant may be required. Trained individuals: Due to the high incidence of apnea, hypotension, tachycardia and muscle rigidity; it should be administered by individuals specifically trained in the use of anesthetic agents and should not be used in diagnostic or therapeutic procedures outside the monitored anesthesia setting; resuscitative and intubation equipment should be readily available.
RESTRICTIONS — C-II
DRUG INTERACTIONS — Substrate of CYP3A4 (major)
Dextroamphetamine: May enhance the analgesic effect of morphine and other opiate agonists.
Increased toxicity with CNS depressants (eg, benzodiazepines, barbiturates, tricyclic antidepressants), erythromycin, reserpine, beta-blockers.
CYP3A4 inhibitors: May increase the levels/effects of alfentanil. Example inhibitors include azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, telithromycin, and verapamil.
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Respiratory rate, blood pressure, heart rate
REFERENCE RANGE — 100-340 ng/mL (depending upon procedure)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include miosis, respiratory depression, seizures, and CNS depression. Treatment includes naloxone 2 mg I.V. (0.01 mg/kg for children), with repeat administration as necessary, up to a total of 10 mg. May precipitate withdrawal.
CANADIAN BRAND NAMES — Alfentanil Injection, USP; Alfenta®
INTERNATIONAL BRAND NAMES — Alfenil (KR); Alfenta (BR, CA); Alfentanil Injection, USP (CA); Brevafen (AR); Fanaxal (ES); Fentalim (IT); Rapifen (AE, AT, AU, BE, BG, BH, BR, CH, CL, CY, CZ, DE, DK, EG, FI, FR, GB, GR, HK, HR, HU, IE, IL, IQ, IR, IT, JO, KW, LB, LY, NL, NO, NZ, OM, PL, PT, PY, QA, RU, SA, SE, SY, TW, UY, VE, YE, ZA)
MECHANISM OF ACTION — Binds with stereospecific receptors at many sites within the CNS, increases pain threshold, alters pain perception, inhibits ascending pain pathways; is an ultra short-acting narcotic
PHARMACODYNAMICS / KINETICS Onset of action: Rapid
Duration (dose dependent): 30-60 minutes
Distribution: Vd: Newborns, premature: 1 L/kg; Children: 0.163-0.48 L/kg; Adults: 0.46 L/kg
Half-life elimination: Newborns, premature: 5.33-8.75 hours; Children: 40-60 minutes; Adults: 83-97 minutes
Alendronate and cholecalciferol
U.S. BRAND NAMES — Fosamax Plus D™
PHARMACOLOGIC CATEGORY Bisphosphonate DerivativeVitamin D Analog
DOSING: ADULTS — Osteoporosis: Oral: One tablet once weekly
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Clcr <35 mL/minute: Not recommended
DOSING: HEPATIC IMPAIRMENT — Alendronate: None necessary. Cholecalciferol: May not be adequately absorbed in patients who have malabsorption due to inadequate bile production.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: Fosamax Plus D™: 70/2800: Alendronate 70 mg and cholecalciferol 2800 int. units
DOSAGE FORMS: CONCISE Tablet: Fosamax Plus D™: 70/2800: Alendronate 70 mg and cholecalciferol 2800 int. units
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Alendronate must be taken with plain water (6-8 oz) first thing in the morning and 30 minutes before the first food, beverage, or other medication of the day. Patient should be instructed to stay upright (not to lie down) for at least 30 minutes and until after first food of the day (to reduce esophageal irritation).
USE — Treatment of osteoporosis in postmenopausal females; increase bone mass in males with osteoporosis
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to alendronate, other bisphosphonates, vitamin D derivatives, or any component of the formulation; hypocalcemia; abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia; inability to stand or sit upright for at least 30 minutes; malabsorption syndrome; evidence of vitamin D toxicity
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Bone/joint/muscle pain: Infrequently, severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy. Gastrointestinal mucosa irritation: May cause irritation to upper gastrointestinal mucosa. Esophagitis, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) have been reported with oral bisphosphonates; risk increases in patients unable to comply with dosing instructions. Use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition). Osteonecrosis of the jaw: Bisphosphonate therapy has been associated with osteonecrosis, primarily of the jaw; this has been observed mostly in cancer patients, but also in patients with postmenopausal osteoporosis and other diagnoses. Risk factors include a diagnosis of cancer, with concomitant chemotherapy, radiotherapy, or corticosteroids; anemia, coagulopathy, infection or pre-existing dental disease. Symptoms included nonhealing extraction socket or an exposed jawbone. There are no data addressing whether discontinuation of therapy reduces the risk of developing osteonecrosis. However, as a precautionary measure, dental exams and preventative dentistry should be performed prior to placing patients with risk factors on chronic bisphosphonate therapy. Invasive dental procedures should be avoided during treatment.
Disease-related concerns: Hypocalcemia/vitamin D deficiency: Before therapy initiation hypocalcemia and/or vitamin D deficiency must be corrected; ensure adequate calcium and vitamin D intake. Do not use to treat vitamin D deficiency. Hypercalcemia: May exacerbate hypercalcemia in certain disease states (eg, leukemia, lymphoma, sarcoidosis); monitor serum calcium levels. Renal impairment: Use with caution in patients with renal impairment (not recommended for use in patients with Clcr <35 mL/minute).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS — See individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — See individual agents.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have shown delays in delivery and fetal/neonatal death (secondary to hypocalcemia). Bisphosphonates are incorporated into the bone matrix and gradually released over time. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy. No animal data are available for the use of cholecalciferol in pregnancy; however, high-dose ergocalciferol has demonstrated abortifacient properties and aortic abnormalities in rabbits. There are no adequate and well-controlled studies in pregnant women.
LACTATION — Cholecalciferol enters breast milk; excretion of alendronate in breast milk unknown/use caution
DIETARY CONSIDERATIONS — Ensure adequate calcium and vitamin D intake. May require additional vitamin D supplementation, particularly in patients at risk for vitamin D deficiency (eg, malabsorption syndromes, chronically ill, >70 years of age). Wait at least 30 minutes after taking alendronate with cholecalciferol before taking any supplement. Must be taken with plain water first thing in the morning and at least 30 minutes before the first food or beverage of the day.
PRICING — (data from drugstore.com)Tablets (Fosamax Plus D) 70-2800 MG-UNIT (4): $79.70
MONITORING PARAMETERS — Alkaline phosphatase (measured periodically); urine and serum calcium, serum phosphorus, serum 25-hydroxy vitamin D; monitor pain and fracture rate; hormonal status (male and female) prior to therapy; bone mineral density (should be done prior to initiation of therapy and after 6-12 months of combined glucocorticoid and alendronate treatment)
REFERENCE RANGE Calcium (total): Adults: 9.0-11.0 mg/dL (2.05-2.54 mmol/L), may slightly decrease with aging
Phosphorus: 2.5-4.5 mg/dL (0.81-1.45 mmol/L)
25-hydroxyvitamin D: 10-80 ng/mL (higher during summer)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms may include anorexia, polyuria, polydipsia, lethargy, hypo-/hypercalcemia, hypophosphatemia, and upper GI adverse effects (eg, upset stomach, heartburn, esophagitis, gastritis, or ulcer). Treat with milk or antacids to bind alendronate. Hydration, systemic glucocorticoids, and reduction of calcium intake may be beneficial in correcting hypercalcemia. Dialysis would not be beneficial.
CANADIAN BRAND NAMES — Fosavance
INTERNATIONAL BRAND NAMES — Fosamax Plus (AR, HK, MX); Fosavance (AT, BE, BG, CA, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HU, IE, IT, NL, NO, PH, PT, RU, SE, TR); Maximus (PE)
MECHANISM OF ACTION — See individual agents.
PATIENT INFORMATION — Do not take more than the recommended amount. While taking this medication, your prescriber may want you to follow a special diet or take a calcium supplement. Follow this diet closely. Avoid taking magnesium supplements or magnesium-containing antacids. Early symptoms of hypercalcemia include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic taste, nausea, vomiting, cramps, diarrhea, muscle pain, bone pain, and irritability.
PHARMACOLOGIC CATEGORY Bisphosphonate DerivativeVitamin D Analog
DOSING: ADULTS — Osteoporosis: Oral: One tablet once weekly
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Clcr <35 mL/minute: Not recommended
DOSING: HEPATIC IMPAIRMENT — Alendronate: None necessary. Cholecalciferol: May not be adequately absorbed in patients who have malabsorption due to inadequate bile production.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: Fosamax Plus D™: 70/2800: Alendronate 70 mg and cholecalciferol 2800 int. units
DOSAGE FORMS: CONCISE Tablet: Fosamax Plus D™: 70/2800: Alendronate 70 mg and cholecalciferol 2800 int. units
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Alendronate must be taken with plain water (6-8 oz) first thing in the morning and 30 minutes before the first food, beverage, or other medication of the day. Patient should be instructed to stay upright (not to lie down) for at least 30 minutes and until after first food of the day (to reduce esophageal irritation).
USE — Treatment of osteoporosis in postmenopausal females; increase bone mass in males with osteoporosis
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to alendronate, other bisphosphonates, vitamin D derivatives, or any component of the formulation; hypocalcemia; abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia; inability to stand or sit upright for at least 30 minutes; malabsorption syndrome; evidence of vitamin D toxicity
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Bone/joint/muscle pain: Infrequently, severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy. Gastrointestinal mucosa irritation: May cause irritation to upper gastrointestinal mucosa. Esophagitis, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) have been reported with oral bisphosphonates; risk increases in patients unable to comply with dosing instructions. Use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition). Osteonecrosis of the jaw: Bisphosphonate therapy has been associated with osteonecrosis, primarily of the jaw; this has been observed mostly in cancer patients, but also in patients with postmenopausal osteoporosis and other diagnoses. Risk factors include a diagnosis of cancer, with concomitant chemotherapy, radiotherapy, or corticosteroids; anemia, coagulopathy, infection or pre-existing dental disease. Symptoms included nonhealing extraction socket or an exposed jawbone. There are no data addressing whether discontinuation of therapy reduces the risk of developing osteonecrosis. However, as a precautionary measure, dental exams and preventative dentistry should be performed prior to placing patients with risk factors on chronic bisphosphonate therapy. Invasive dental procedures should be avoided during treatment.
Disease-related concerns: Hypocalcemia/vitamin D deficiency: Before therapy initiation hypocalcemia and/or vitamin D deficiency must be corrected; ensure adequate calcium and vitamin D intake. Do not use to treat vitamin D deficiency. Hypercalcemia: May exacerbate hypercalcemia in certain disease states (eg, leukemia, lymphoma, sarcoidosis); monitor serum calcium levels. Renal impairment: Use with caution in patients with renal impairment (not recommended for use in patients with Clcr <35 mL/minute).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS — See individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — See individual agents.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal studies have shown delays in delivery and fetal/neonatal death (secondary to hypocalcemia). Bisphosphonates are incorporated into the bone matrix and gradually released over time. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy. No animal data are available for the use of cholecalciferol in pregnancy; however, high-dose ergocalciferol has demonstrated abortifacient properties and aortic abnormalities in rabbits. There are no adequate and well-controlled studies in pregnant women.
LACTATION — Cholecalciferol enters breast milk; excretion of alendronate in breast milk unknown/use caution
DIETARY CONSIDERATIONS — Ensure adequate calcium and vitamin D intake. May require additional vitamin D supplementation, particularly in patients at risk for vitamin D deficiency (eg, malabsorption syndromes, chronically ill, >70 years of age). Wait at least 30 minutes after taking alendronate with cholecalciferol before taking any supplement. Must be taken with plain water first thing in the morning and at least 30 minutes before the first food or beverage of the day.
PRICING — (data from drugstore.com)Tablets (Fosamax Plus D) 70-2800 MG-UNIT (4): $79.70
MONITORING PARAMETERS — Alkaline phosphatase (measured periodically); urine and serum calcium, serum phosphorus, serum 25-hydroxy vitamin D; monitor pain and fracture rate; hormonal status (male and female) prior to therapy; bone mineral density (should be done prior to initiation of therapy and after 6-12 months of combined glucocorticoid and alendronate treatment)
REFERENCE RANGE Calcium (total): Adults: 9.0-11.0 mg/dL (2.05-2.54 mmol/L), may slightly decrease with aging
Phosphorus: 2.5-4.5 mg/dL (0.81-1.45 mmol/L)
25-hydroxyvitamin D: 10-80 ng/mL (higher during summer)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms may include anorexia, polyuria, polydipsia, lethargy, hypo-/hypercalcemia, hypophosphatemia, and upper GI adverse effects (eg, upset stomach, heartburn, esophagitis, gastritis, or ulcer). Treat with milk or antacids to bind alendronate. Hydration, systemic glucocorticoids, and reduction of calcium intake may be beneficial in correcting hypercalcemia. Dialysis would not be beneficial.
CANADIAN BRAND NAMES — Fosavance
INTERNATIONAL BRAND NAMES — Fosamax Plus (AR, HK, MX); Fosavance (AT, BE, BG, CA, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HU, IE, IT, NL, NO, PH, PT, RU, SE, TR); Maximus (PE)
MECHANISM OF ACTION — See individual agents.
PATIENT INFORMATION — Do not take more than the recommended amount. While taking this medication, your prescriber may want you to follow a special diet or take a calcium supplement. Follow this diet closely. Avoid taking magnesium supplements or magnesium-containing antacids. Early symptoms of hypercalcemia include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic taste, nausea, vomiting, cramps, diarrhea, muscle pain, bone pain, and irritability.
Alendronate
U.S. BRAND NAMES — Fosamax®
PHARMACOLOGIC CATEGORY Bisphosphonate Derivative
DOSING: ADULTS — Note: Patients treated with glucocorticoids and those with Paget's disease should receive adequate amounts of calcium and vitamin D.
Osteoporosis in postmenopausal females: Oral: Prophylaxis: 5 mg once daily or 35 mg once weekly Treatment: 10 mg once daily or 70 mg once weekly
Osteoporosis in males: Oral: 10 mg once daily or 70 mg once weekly
Osteoporosis secondary to glucocorticoids in males and females: Oral: Treatment: 5 mg once daily; a dose of 10 mg once daily should be used in postmenopausal females who are not receiving estrogen.
Paget's disease of bone in males and females: Oral: 40 mg once daily for 6 months Retreatment: Relapses during the 12 months following therapy occurred in 9% of patients who responded to treatment. Specific retreatment data are not available. Following a 6-month post-treatment evaluation period, treatment with alendronate may be considered in patients who have relapsed based on increases in serum alkaline phosphatase, which should be measured periodically. Retreatment may also be considered in those who failed to normalize their serum alkaline phosphatase.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Clcr 35-60 mL/minute: None necessary.
Clcr <35 mL/minute: Alendronate is not recommended due to lack of experience.
DOSING: HEPATIC IMPAIRMENT — No adjustment necessary.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Note: Strength expressed as free acid
Solution, oral, as monosodium trihydrate: Fosamax™: 70 mg/75 mL [contains parabens; raspberry flavor]
Tablet, as sodium: Fosamax™: 5 mg, 10 mg, 35 mg, 40 mg, 70 mg
DOSAGE FORMS: CONCISE — Note: Strength expressed as free acid
Solution, oral: Fosamax®: 70 mg/75 mL
Tablet: Fosamax®: 5 mg, 10 mg, 35 mg, 40 mg, 70 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Alendronate must be taken with plain water (tablets 6-8 oz; oral solution follow with 2 oz) first thing in the morning and 30 minutes before the first food, beverage, or other medication of the day. Do not take with mineral water or with other beverages. Patients should be instructed to stay upright (not to lie down) for at least 30 minutes and until after first food of the day (to reduce esophageal irritation). Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.
USE — Treatment and prevention of osteoporosis in postmenopausal females; treatment of osteoporosis in males; Paget's disease of the bone in patients who are symptomatic, at risk for future complications, or with alkaline phosphatase 2 times the upper limit of normal; treatment of glucocorticoid-induced osteoporosis in males and females with low bone mineral density who are receiving a daily dosage 7.5 mg of prednisone (or equivalent)
ADVERSE REACTIONS SIGNIFICANT — Note: Incidence of adverse effects (mostly GI) increases significantly in patients treated for Paget's disease at 40 mg/day.
>10%: Endocrine & metabolic: Hypocalcemia (transient, mild, 18%); hypophosphatemia (transient, mild, 10%)
1% to 10%: Central nervous system: Headache (up to 3%) Gastrointestinal: Abdominal pain (1% to 7%), acid reflux (1% to 4%), dyspepsia (1% to 4%), nausea (1% to 4%), flatulence (up to 4%), diarrhea (1% to 3%), gastroesophageal reflux disease (1% to 3%), constipation (up to 3%), esophageal ulcer (up to 2%), abdominal distension (up to 1%), gastritis (up to 1%), vomiting (up to 1%), dysphagia (up to 1%), gastric ulcer (1%), melena (1%) Neuromuscular & skeletal: Musculoskeletal pain (up to 6%), muscle cramps (up to 1%)
<1% (Limited to important or life-threatening): Anastomotic ulcer, angioedema; bone, muscle, or joint pain (occasionally severe, considered incapacitating in rare cases); dizziness, duodenal ulcer, episcleritis, erythema, esophageal erosions, esophageal perforation, esophageal stricture, esophagitis, fever, flu-like syndrome, hypersensitivity reactions, hypocalcemia (symptomatic), joint swelling, lymphocytopenia, malaise, myalgia, oropharyngeal ulceration, osteonecrosis (jaw), peripheral edema, photosensitivity (rare), pruritus, rash, scleritis (rare), Stevens-Johnson syndrome, taste perversion, toxic epidermal necrolysis, urticaria, uveitis (rare), vertigo, weakness
CONTRAINDICATIONS — Hypersensitivity to alendronate, other bisphosphonates, or any component of the formulation; hypocalcemia; abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia; inability to stand or sit upright for at least 30 minutes; oral solution should not be used in patients at risk of aspiration
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Bone/joint/muscle pain: Infrequently, severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy. Gastrointestinal mucosa irritation: May cause irritation to upper gastrointestinal mucosa. Esophagitis, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) have been reported with oral bisphosphonates; risk increases in patients unable to comply with dosing instructions. Use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition). Osteonecrosis of the jaw: Bisphosphonate therapy has been associated with osteonecrosis, primarily of the jaw; this has been observed mostly in cancer patients, but also in patients with postmenopausal osteoporosis and other diagnoses. Risk factors include a diagnosis of cancer, with concomitant chemotherapy, radiotherapy, or corticosteroids; anemia, coagulopathy, infection, or pre-existing dental disease. Symptoms included nonhealing extraction socket or an exposed jawbone. There are no data addressing whether discontinuation of therapy reduces the risk of developing osteonecrosis; however, as a precautionary measure, dental exams and preventative dentistry should be performed prior to placing patients with risk factors on chronic bisphosphonate therapy. Invasive dental procedures should be avoided during treatment.
Disease-related concerns: Hypocalcemia: Before therapy initiation hypocalcemia must be corrected; ensure adequate calcium and vitamin D intake. Renal impairment: Use with caution in patients with renal impairment (not recommended for use in patients with Clcr <35 mL/minute).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS Aminoglycosides: May lower serum calcium levels with prolonged administration. Concomitant use may have an additive hypocalcemic effect.
Antacids: May decrease the absorption of bisphosphonate derivatives; should be administered at a different time of the day. Antacids containing aluminum, calcium, or magnesium are of specific concern.
Aspirin: May enhance the adverse/toxic effect of alendronate; specifically gastrointestinal adverse events.
Calcium salts: May decrease the absorption of bisphosphonate derivatives. Separate oral dosing in order to minimize risk of interaction.
Iron salts: May decrease the absorption of bisphosphonate derivatives. Only oral iron salts and oral bisphosphonates are of concern.
Magnesium salts: May decrease the absorption of bisphosphonate derivatives. Only oral magnesium salts and oral bisphosphonates are of concern.
Nonsteroidal anti-inflammatory drugs (NSAIDs): May enhance the gastrointestinal adverse/toxic effects (increased incidence of GI ulcers) of bisphosphonate derivatives.
Phosphate supplements: Bisphosphonate derivatives may enhance the hypocalcemic effect of phosphate supplements.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Avoid ethanol (may increase risk of osteoporosis and gastric irritation).
Food: All food and beverages interfere with absorption. Coadministration with caffeine may reduce alendronate efficacy. Coadministration with dairy products may decrease alendronate absorption. Beverages (especially orange juice and coffee) and food may reduce the absorption of alendronate as much as 60%.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Safety and efficacy have not been established in pregnant women. Animal studies have shown delays in delivery and fetal/neonatal death (secondary to hypocalcemia). Bisphosphonates are incorporated into the bone matrix and gradually released over time. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy. Based on limited case reports with pamidronate, serum calcium levels in the newborn may be altered if administered during pregnancy.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — Ensure adequate calcium and vitamin D intake; however, wait at least 30 minutes after taking alendronate before taking any supplement. Alendronate must be taken with plain water first thing in the morning and at least 30 minutes before the first food or beverage of the day.
PRICING — (data from drugstore.com)Solution (Fosamax) 70 mg/75mL (75): $27.99
Tablets (Fosamax) 5 mg (30): $79.31 10 mg (30): $85.99 35 mg (4): $72.99 70 mg (4): $77.61
MONITORING PARAMETERS — Alkaline phosphatase should be periodically measured; serum calcium and phosphorus; monitor pain and fracture rate; hormonal status (male and female) prior to therapy; bone mineral density (should be done prior to initiation of therapy and after 6-12 months of combined glucocorticoid and alendronate treatment)
REFERENCE RANGE — Calcium (total): Adults: 9.0-11.0 mg/dL (2.05-2.54 mmol/L), may slightly decrease with aging; phosphorus: 2.5-4.5 mg/dL (0.81-1.45 mmol/L)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include hypocalcemia, hypophosphatemia, and upper GI adverse events (upset stomach, heartburn, esophagitis, gastritis or ulcer). Treat with milk or antacids to bind alendronate. Dialysis would not be beneficial. Do not induce vomiting (due to the risk of esophageal irritation); keep fully upright.
CANADIAN BRAND NAMES — Apo-Alendronate®; CO Alendronate; Fosamax®; Gen-Alendronate; Novo-Alendronate; PMS-Alendronate; ratio-Alendronate; Riva-Alendronate
INTERNATIONAL BRAND NAMES — Aldrox (CL); Alenato (AR); Alend (KR); Alenmax (KR); Alexonal (ID); Alnax (PY); Apo-Alendronate (CA); Arendal (PE); Armol (CO); Bifemelan (CO); Bifosa (IN); Bolend (KR); Bonapex (EG); CO Alendronate (CA); Endronax (BR); Eucalen (CO); Fixopan (EC); Fosalan (IL); Fosamax (AN, AR, AT, AU, BB, BE, BG, BM, BR, BS, BZ, CA, CH, CL, CR, CZ, DE, DK, EC, EE, EG, ES, FI, FR, GB, GT, GY, HK, HN, HU, ID, IE, IT, JM, KR, MX, MY, NI, NL, NO, NZ, PA, PE, PH, PK, SE, SG, SR, SV, TH, TT, TW, VE, ZA); Fosaqueen (KR); Fosmin (PE); Fosval (PY); Gen-Alendronate (CA); Marvil (PE, UY); MaxiBone (IL); MaxiBone 70 (IL); Neobon (CO); Novo-Alendronate (CA); Osdron (BR); Osdronat (CO); Oseotenk (AR); Osficar (CO); Osteofar (ID); Osteofos (HK); Osteopor (UY); Osteosan (CL); Osteovan (CR); Osticalcin (CO); PMS-Alendronate (CA); Porosal (VE); ratio-Alendronate (CA); Riva-Alendronate (CA); Tibolene (CO); Voroste (ID)
MECHANISM OF ACTION — A bisphosphonate which inhibits bone resorption via actions on osteoclasts or on osteoclast precursors; decreases the rate of bone resorption, leading to an indirect increase in bone mineral density. In Paget's disease, characterized by disordered resorption and formation of bone, inhibition of resorption leads to an indirect decrease in bone formation; but the newly-formed bone has a more normal architecture.
PHARMACODYNAMICS / KINETICS Distribution: 28 L (exclusive of bone)
Protein binding: ~78%
Metabolism: None
Bioavailability: Fasting: 0.6%; reduced 60% with food or drink
Half-life elimination: Exceeds 10 years
Excretion: Urine; feces (as unabsorbed drug)
PATIENT INFORMATION — Take as directed, with a full glass of water first thing in the morning and at least 30 minutes before the first food or beverage of the day. Wait at least 30 minutes after taking alendronate before taking anything else. Stay in sitting or standing position for 30 minutes following administration and until after the first food of the day to reduce potential for esophageal irritation. Consult prescriber to determine necessity of lifestyle changes (eg, decreased smoking, decreased alcohol intake, dietary supplements of calcium, or increased dietary vitamin D).
PHARMACOLOGIC CATEGORY Bisphosphonate Derivative
DOSING: ADULTS — Note: Patients treated with glucocorticoids and those with Paget's disease should receive adequate amounts of calcium and vitamin D.
Osteoporosis in postmenopausal females: Oral: Prophylaxis: 5 mg once daily or 35 mg once weekly Treatment: 10 mg once daily or 70 mg once weekly
Osteoporosis in males: Oral: 10 mg once daily or 70 mg once weekly
Osteoporosis secondary to glucocorticoids in males and females: Oral: Treatment: 5 mg once daily; a dose of 10 mg once daily should be used in postmenopausal females who are not receiving estrogen.
Paget's disease of bone in males and females: Oral: 40 mg once daily for 6 months Retreatment: Relapses during the 12 months following therapy occurred in 9% of patients who responded to treatment. Specific retreatment data are not available. Following a 6-month post-treatment evaluation period, treatment with alendronate may be considered in patients who have relapsed based on increases in serum alkaline phosphatase, which should be measured periodically. Retreatment may also be considered in those who failed to normalize their serum alkaline phosphatase.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Clcr 35-60 mL/minute: None necessary.
Clcr <35 mL/minute: Alendronate is not recommended due to lack of experience.
DOSING: HEPATIC IMPAIRMENT — No adjustment necessary.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Note: Strength expressed as free acid
Solution, oral, as monosodium trihydrate: Fosamax™: 70 mg/75 mL [contains parabens; raspberry flavor]
Tablet, as sodium: Fosamax™: 5 mg, 10 mg, 35 mg, 40 mg, 70 mg
DOSAGE FORMS: CONCISE — Note: Strength expressed as free acid
Solution, oral: Fosamax®: 70 mg/75 mL
Tablet: Fosamax®: 5 mg, 10 mg, 35 mg, 40 mg, 70 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Alendronate must be taken with plain water (tablets 6-8 oz; oral solution follow with 2 oz) first thing in the morning and 30 minutes before the first food, beverage, or other medication of the day. Do not take with mineral water or with other beverages. Patients should be instructed to stay upright (not to lie down) for at least 30 minutes and until after first food of the day (to reduce esophageal irritation). Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.
USE — Treatment and prevention of osteoporosis in postmenopausal females; treatment of osteoporosis in males; Paget's disease of the bone in patients who are symptomatic, at risk for future complications, or with alkaline phosphatase 2 times the upper limit of normal; treatment of glucocorticoid-induced osteoporosis in males and females with low bone mineral density who are receiving a daily dosage 7.5 mg of prednisone (or equivalent)
ADVERSE REACTIONS SIGNIFICANT — Note: Incidence of adverse effects (mostly GI) increases significantly in patients treated for Paget's disease at 40 mg/day.
>10%: Endocrine & metabolic: Hypocalcemia (transient, mild, 18%); hypophosphatemia (transient, mild, 10%)
1% to 10%: Central nervous system: Headache (up to 3%) Gastrointestinal: Abdominal pain (1% to 7%), acid reflux (1% to 4%), dyspepsia (1% to 4%), nausea (1% to 4%), flatulence (up to 4%), diarrhea (1% to 3%), gastroesophageal reflux disease (1% to 3%), constipation (up to 3%), esophageal ulcer (up to 2%), abdominal distension (up to 1%), gastritis (up to 1%), vomiting (up to 1%), dysphagia (up to 1%), gastric ulcer (1%), melena (1%) Neuromuscular & skeletal: Musculoskeletal pain (up to 6%), muscle cramps (up to 1%)
<1% (Limited to important or life-threatening): Anastomotic ulcer, angioedema; bone, muscle, or joint pain (occasionally severe, considered incapacitating in rare cases); dizziness, duodenal ulcer, episcleritis, erythema, esophageal erosions, esophageal perforation, esophageal stricture, esophagitis, fever, flu-like syndrome, hypersensitivity reactions, hypocalcemia (symptomatic), joint swelling, lymphocytopenia, malaise, myalgia, oropharyngeal ulceration, osteonecrosis (jaw), peripheral edema, photosensitivity (rare), pruritus, rash, scleritis (rare), Stevens-Johnson syndrome, taste perversion, toxic epidermal necrolysis, urticaria, uveitis (rare), vertigo, weakness
CONTRAINDICATIONS — Hypersensitivity to alendronate, other bisphosphonates, or any component of the formulation; hypocalcemia; abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia; inability to stand or sit upright for at least 30 minutes; oral solution should not be used in patients at risk of aspiration
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Bone/joint/muscle pain: Infrequently, severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy. Gastrointestinal mucosa irritation: May cause irritation to upper gastrointestinal mucosa. Esophagitis, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) have been reported with oral bisphosphonates; risk increases in patients unable to comply with dosing instructions. Use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition). Osteonecrosis of the jaw: Bisphosphonate therapy has been associated with osteonecrosis, primarily of the jaw; this has been observed mostly in cancer patients, but also in patients with postmenopausal osteoporosis and other diagnoses. Risk factors include a diagnosis of cancer, with concomitant chemotherapy, radiotherapy, or corticosteroids; anemia, coagulopathy, infection, or pre-existing dental disease. Symptoms included nonhealing extraction socket or an exposed jawbone. There are no data addressing whether discontinuation of therapy reduces the risk of developing osteonecrosis; however, as a precautionary measure, dental exams and preventative dentistry should be performed prior to placing patients with risk factors on chronic bisphosphonate therapy. Invasive dental procedures should be avoided during treatment.
Disease-related concerns: Hypocalcemia: Before therapy initiation hypocalcemia must be corrected; ensure adequate calcium and vitamin D intake. Renal impairment: Use with caution in patients with renal impairment (not recommended for use in patients with Clcr <35 mL/minute).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS Aminoglycosides: May lower serum calcium levels with prolonged administration. Concomitant use may have an additive hypocalcemic effect.
Antacids: May decrease the absorption of bisphosphonate derivatives; should be administered at a different time of the day. Antacids containing aluminum, calcium, or magnesium are of specific concern.
Aspirin: May enhance the adverse/toxic effect of alendronate; specifically gastrointestinal adverse events.
Calcium salts: May decrease the absorption of bisphosphonate derivatives. Separate oral dosing in order to minimize risk of interaction.
Iron salts: May decrease the absorption of bisphosphonate derivatives. Only oral iron salts and oral bisphosphonates are of concern.
Magnesium salts: May decrease the absorption of bisphosphonate derivatives. Only oral magnesium salts and oral bisphosphonates are of concern.
Nonsteroidal anti-inflammatory drugs (NSAIDs): May enhance the gastrointestinal adverse/toxic effects (increased incidence of GI ulcers) of bisphosphonate derivatives.
Phosphate supplements: Bisphosphonate derivatives may enhance the hypocalcemic effect of phosphate supplements.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Avoid ethanol (may increase risk of osteoporosis and gastric irritation).
Food: All food and beverages interfere with absorption. Coadministration with caffeine may reduce alendronate efficacy. Coadministration with dairy products may decrease alendronate absorption. Beverages (especially orange juice and coffee) and food may reduce the absorption of alendronate as much as 60%.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Safety and efficacy have not been established in pregnant women. Animal studies have shown delays in delivery and fetal/neonatal death (secondary to hypocalcemia). Bisphosphonates are incorporated into the bone matrix and gradually released over time. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy. Based on limited case reports with pamidronate, serum calcium levels in the newborn may be altered if administered during pregnancy.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — Ensure adequate calcium and vitamin D intake; however, wait at least 30 minutes after taking alendronate before taking any supplement. Alendronate must be taken with plain water first thing in the morning and at least 30 minutes before the first food or beverage of the day.
PRICING — (data from drugstore.com)Solution (Fosamax) 70 mg/75mL (75): $27.99
Tablets (Fosamax) 5 mg (30): $79.31 10 mg (30): $85.99 35 mg (4): $72.99 70 mg (4): $77.61
MONITORING PARAMETERS — Alkaline phosphatase should be periodically measured; serum calcium and phosphorus; monitor pain and fracture rate; hormonal status (male and female) prior to therapy; bone mineral density (should be done prior to initiation of therapy and after 6-12 months of combined glucocorticoid and alendronate treatment)
REFERENCE RANGE — Calcium (total): Adults: 9.0-11.0 mg/dL (2.05-2.54 mmol/L), may slightly decrease with aging; phosphorus: 2.5-4.5 mg/dL (0.81-1.45 mmol/L)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include hypocalcemia, hypophosphatemia, and upper GI adverse events (upset stomach, heartburn, esophagitis, gastritis or ulcer). Treat with milk or antacids to bind alendronate. Dialysis would not be beneficial. Do not induce vomiting (due to the risk of esophageal irritation); keep fully upright.
CANADIAN BRAND NAMES — Apo-Alendronate®; CO Alendronate; Fosamax®; Gen-Alendronate; Novo-Alendronate; PMS-Alendronate; ratio-Alendronate; Riva-Alendronate
INTERNATIONAL BRAND NAMES — Aldrox (CL); Alenato (AR); Alend (KR); Alenmax (KR); Alexonal (ID); Alnax (PY); Apo-Alendronate (CA); Arendal (PE); Armol (CO); Bifemelan (CO); Bifosa (IN); Bolend (KR); Bonapex (EG); CO Alendronate (CA); Endronax (BR); Eucalen (CO); Fixopan (EC); Fosalan (IL); Fosamax (AN, AR, AT, AU, BB, BE, BG, BM, BR, BS, BZ, CA, CH, CL, CR, CZ, DE, DK, EC, EE, EG, ES, FI, FR, GB, GT, GY, HK, HN, HU, ID, IE, IT, JM, KR, MX, MY, NI, NL, NO, NZ, PA, PE, PH, PK, SE, SG, SR, SV, TH, TT, TW, VE, ZA); Fosaqueen (KR); Fosmin (PE); Fosval (PY); Gen-Alendronate (CA); Marvil (PE, UY); MaxiBone (IL); MaxiBone 70 (IL); Neobon (CO); Novo-Alendronate (CA); Osdron (BR); Osdronat (CO); Oseotenk (AR); Osficar (CO); Osteofar (ID); Osteofos (HK); Osteopor (UY); Osteosan (CL); Osteovan (CR); Osticalcin (CO); PMS-Alendronate (CA); Porosal (VE); ratio-Alendronate (CA); Riva-Alendronate (CA); Tibolene (CO); Voroste (ID)
MECHANISM OF ACTION — A bisphosphonate which inhibits bone resorption via actions on osteoclasts or on osteoclast precursors; decreases the rate of bone resorption, leading to an indirect increase in bone mineral density. In Paget's disease, characterized by disordered resorption and formation of bone, inhibition of resorption leads to an indirect decrease in bone formation; but the newly-formed bone has a more normal architecture.
PHARMACODYNAMICS / KINETICS Distribution: 28 L (exclusive of bone)
Protein binding: ~78%
Metabolism: None
Bioavailability: Fasting: 0.6%; reduced 60% with food or drink
Half-life elimination: Exceeds 10 years
Excretion: Urine; feces (as unabsorbed drug)
PATIENT INFORMATION — Take as directed, with a full glass of water first thing in the morning and at least 30 minutes before the first food or beverage of the day. Wait at least 30 minutes after taking alendronate before taking anything else. Stay in sitting or standing position for 30 minutes following administration and until after the first food of the day to reduce potential for esophageal irritation. Consult prescriber to determine necessity of lifestyle changes (eg, decreased smoking, decreased alcohol intake, dietary supplements of calcium, or increased dietary vitamin D).
Tuesday, March 11, 2008
Bidding For Buyers---Lessons From The Auction Block
If you think that E-bay has nothing to teach you, think again. Itdoesn’t matter much that you aren’t in the auction business andthat your website is entirely different in scope. What matters isthat the first place phenomenon of the Internet Revolution isE-bay. Its evolution is not just as a profitable e-business but anew culture of society. The lessons learned at E-bay might justget you off the surfboard and onto that ship you have been waitingto come in. This on-the-edge idea broke ground out of a humbleSilicon Valley apartment into a reality model of more than 10million registered users and sales to the tune of more than $100 anano-second. In other words, while you spent ten seconds readingthis sentence, they sold $1000 worth of merchandise. Yes, E-bayhas something to teach us all. For within their model are lessonsyou can learn and adopt in your own business, no matter what yourbusiness is.Practicality dictates a certain model in order for entrepreneurs toachieve success. Until, of course, a titan in thinking comes alongto blow that model to kingdom come and put in it’s place a newparadigm of thinking. Enter E-bay. Enter the non-conventional.But enter, ready to learn.The Courage of Ideas-E-bay started out as an idea in the brain of someone not sodifferent than you. One man, in an apartment got a creativeinspiration that he turned into the biggest reality of success theInternet has yet to see. What does this tell us? That it canhappen to you. I’m sure that the idea had its obstacles toovercome before it ever arrived at its current glory, but throughpersistence became real. Ideas have power once we fuel them.Believe in the future of your ideas and surround yourself withpeople that can support and nuture that belief.The Journey With Out A RoadmapSome business journey’s are not by the book, complete with businessplan and a clear vision of its destination. Many ideas evolve,change, and grow through continued inspiration and perspiration.This isn’t to say that the business plan is not important, butrather that flexibility is. Be ready to take a new road when theone you’re started down is not achieving your vision. Realize thatthis is the evolution of an inspired idea.Taking the Old, and Incorporating The NewBe prepared to blend both new E-commerce ideas with oldtried-and-true principles for a net result that will equal success.Don’t banish all of one theory for another, but rather mix whatworks. Affiliate programs with established marketing plans,advertising venues with email, etc. Be courageous, but wise.>From Business to CommunityCreate a place that others will talk about. It is the nature ofpeople to want to gather, so create a gathering place for people toshare ideas, make the deal, and communicate. The dynamics of theInternet is in its community and E-bay saw the value of this andbecame not just a community, but a society of it’s own.Body Parts Are Not For Sale—Making Good with Bad TimesWhile E-bay got press over body parts that were put on it’s sitefor sale, it wasn’t all bad. Yes, they obviously pulled theseauctions from the site once it came to their attention, but thepress it created did not hurt E-bay. In fact, it solidified themas THE online community of our time. The place to be, to go, tobookmark, and return. It drove more people to the site. Thelesson? Make good with bad times. Weather the situation, butcreate an event.Evolving ForwardRemember above all that change is what creates a forward moving,successful business. Never stay stagnant. Be aware of consumer’stastes, the change of trends in behavior, and constantly evolveyour plan.E-bay was an idea. We all have them. The question is what will youdo with the next one that pops into your head? You know thepotential now, and if you doubt it, visit E-bay to becomeconvinced.
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