Escolar Documentos
Profissional Documentos
Cultura Documentos
Class: Hormone/Bisphosphonates
Action Inhibits bone resorption and increases bone density.
Route/Dosage
Interactions
Adverse Reactions
PATIENT CARE
CONSIDERATIONS
Administration/Storage
Avoid high calcium food, vitamins with mineral supplements, and antacids
high in metals within 2 hr of dosing.
Take 30 min before first meal, medication, or drink of the day. Take with 6
to 8 oz of plain water only.
Instruct patient to take medication with plain water 30 min before the first
food or drink of the day.
Take medication with a full glass of water. Patient should not lie down for
30 min following administration.
Have patient take supplemental calcium (1500 mg) and vitamin D (400 IU
PO daily) if dietary intake is not adequate.
Administrasi / Storage
Divide dosis jika GI marah terjadi.
Hindari makanan tinggi kalsium, vitamin dengan suplemen mineral,
dan antasida tinggi dalam logam dalam 2 jam dari dosis.
Ambil 30 menit sebelum makan pertama, obat-obatan, atau
minuman hari. Ambil dengan 6 sampai 8 ons air putih saja.
Simpan pada suhu kamar dalam wadah tertutup baik.
Penilaian / Intervensi
Mendapatkan riwayat pasien.
Kaji reaksi hipersensitivitas.
Kaji insufisiensi ginjal berat sebelum pemberian.
Overdosis: TANDA & GEJALA
Hipokalsemia, hypophosphatemia, GI atas efek samping
Ahfs
Introductory Information
Synthetic bisphosphonate; bone resorption inhibitor.1, 2, 3, 4, a
Class: 92:24 Bone Resorption Inhibitors; hs900 (VA primary)
Brands: Fosamax, Fosamax Plus D (combination)
Generic Name: Alendronate Sodium
CAS Number: 121268-17-5
Chemical Name: (4-Amino-1-hydroxybutylidene)bis-phosphonic acid,
monosodium salt, trihydrate
Molecular Formula: C4H13NO7P23H2ONa
Investigational Drug Number: G-704,650, MK-217
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: [Web].
professional if they develop new hip or thigh pain or have any concerns with their
medications. For more information visit the FDA website at: [Web] and [Web].
[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: [Web], and [Web].
REMS:
FDA approved a REMS for alendronate to ensure that the benefits of a drug
outweigh the risks. However, FDA later rescinded REMS requirements. See the
FDA REMS page ([Web]) or the ASHP REMS Resource Center ([Web]).
Uses
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
Alendronate is used for prevention of osteoporosis in postmenopausal women1, 24,
25
with risk factors for development of osteoporosis.1, 41, 46, 47, 50, 51, 52, 53, 62 Risk
factors include premature ovarian failure; family history of osteoporosis; small,
slim body frame; endocrine disorders (e.g., thyrotoxicosis, hyperparathyroidism,
Cushing's syndrome, hyperprolactinemia, insulin-dependent diabetes mellitus);
cigarette smoking; excessive alcohol use; sedentary lifestyle; low body weight;
moderately low body mass; low dietary calcium intake; or Caucasian or Asian
race.1, 41, 46, 47, 50, 51, 52, 53, 62
Alendronate is used alone or in fixed combination with cholecalciferol (vitamin
D3) for treatment of osteoporosis in postmenopausal women.1, 2, 3, 5, 6, 7, 8, 10, 11, 12, 13,
a
Corticosteroid-induced Osteoporosis
Alendronate is used for treatment of corticosteroid-induced osteoporosis in
patients receiving corticosteroids (daily dosage 5-7.5 mg of prednisone).1, 57, 58, 73,
78
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
Possible severe adverse esophageal effects (e.g., esophagitis, esophageal ulcers,
erosions, strictures, perforation).1, 16, 18, 20, 21, 23, a Monitor for any manifestations1, 16,
18, 20, 21, 23, a
and discontinue if dysphagia, odynophagia, new or worsening
heartburn, or retrosternal pain occurs.1, 20, 23, a
Cautious use recommended in patients with history of upper GI disease (e.g.,
dysphagia, esophageal diseases, gastritis, duodenitis, ulcers).1, 20, 23, a Gastric and
duodenal ulcers (some severe and with complications) reported in postmarketing
surveillance.1, a
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.
Diagnosis
Consider other possible causes of osteoporosis before beginning alendronate.1, a
Metabolic Effects
Possible asymptomatic decreases in serum calcium and phosphate concentrations,
particularly in patients with Paget's disease and in those receiving corticosteroids;
ensure adequate calcium and vitamin D intake.1, a
Correct hypocalcemia and other disorders affecting mineral metabolism (e.g.,
vitamin D deficiency) before initiation of alendronate therapy;1, a administer
supplemental calcium and vitamin D if daily dietary intake is inadequate.1, 26, 27, 28,
29, 38, 46, 47, 48, 51, 52, 53
Monitor serum calcium and monitor for symptoms of
hypocalcemia during therapy.a
Fixed combination of alendronate and cholecalciferol (vitamin D3) is not
recommended for treatment of vitamin D deficiency (i.e., 25-hydroxyvitamin D
concentration <9 ng/mL).a Patients at risk for vitamin D insufficiency (e.g., GI
malabsorption syndromes) may require higher doses of vitamin D
supplementation; consider measurement of 25-hydroxyvitamin D.a
Vitamin D3 supplementation may increase risk of hypercalcemia and/or
hypercalciuria in patients with diseases associated with unregulated
Interaction
Comments
Wait at least 30 minutes
May interfere with absorption of after taking alendronate
alendronatea
before taking any other
oral medicationsa
Hormone
replacement therapy Potential increased effects on
(estrogens; estrogens bone mineral density1, 68, 69
and progestins)
Aspirin increased GI toxicity in
NSAIAs (e.g.,
clinical studies; no increase in
Use caution1, a
aspirin)
toxicity with concomitant
NSAIAs in one study1, a
No change in alendronate
Prednisone
bioavailability1, a
IV ranitidine doubled
Ranitidine
alendronate bioavailability1, a
Pharmacokinetics
Absorption
Bioavailability
Oral bioavailability of alendronate in women and men is 0.64 and 0.59%,
respectively.1, a
Bioavailability of alendronate sodium tablets and oral solution equivalent.1
Bioavailability of conventional tablets and fixed-combination tablets containing
cholecalciferol (2800 and 5600 units) equivalent.a
Onset
Decrease in bone resorption rate evident as early as 1 month.1, a
Food
Alendronate bioavailability decreased by 40% when administered 0.5-1 hour prior
to a meal, and by 60% when administered with coffee or orange juice.1, a
Bioavailability is negligible whether administered with or up to 2 hours after a
meal.1, a
Distribution
Extent
Alendronate is widely distributed after oral administration.c Subsequently,
redistributes rapidly to skeletal tissues.c, a Mean steady-state volume of
distribution, exclusive of bone, is 28 L.1, a, c
Plasma Protein Binding
Alendronate: Approximately 78%.1, a
Elimination
Metabolism
No evidence of metabolism of alendronate.1, c
Elimination Route
Urinary excretion is the sole means of elimination of alendronate.1, 3, a, b
Half-life
Terminal half-life of alendronate >10 years, reflecting release from bone.1, 2, 3, 4, 11,
a
Special Populations
In patients with renal impairment, clearance of alendronate likely to be reduced.1, a
Somewhat greater accumulation in bone expected.1, a
Stability
Storage
Oral
Tablets
Alendronate: Tight containers at 15-30C.1
Alendronate/cholecalciferol fixed combination: 20-25C (may be exposed to 1530C).a Keep tablets in sealed blisters until immediately before use.a Protect from
moisture and light.a
Oral Solution
Alendronate: 15-30C.1 Do not freeze.1
Actions
Alendronate incorporates into bone and selectively inhibits osteoclast-mediated
bone resorption in a dose-dependent manner.1, 2, 3, 4, 5, 8, 9, 10
Alendronate increases bone mineral density.1, 8, 24, 58, 66, 69, 70, 72, 73, 74, 78, a
Pharmacologically inactive while incorporated into bone matrix.1, 2, 3, 4, 11, a
Continuous administration required for activity.1, 2, 3, 4, 11, a
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 a copy of the manufacturer's patient information.1, 17, 20, 21,
23, a
Importance of correct administration (e.g., avoiding foods and beverages other than
plain water, not lying down for 30 minutes following administration, avoiding
administering at bedtime or before arising for the day).1, 20, a, e
Importance of swallowing tablets whole, without chewing or sucking.20, a, e
Importance of discontinuing and informing clinician if symptoms of esophageal
disease (e.g., difficulty or pain on swallowing; retrosternal, abdominal or
esophageal pain; new or worsening heartburn) develop.1, 20, 23, a, e
Importance of adhering to recommended lifestyle modifications (e.g., weightbearing exercise, calcium and vitamin D consumption, avoidance of excessive
cigarette smoking and/or alcohol consumption).1, a, e
Importance of women informing clinicians if they are or plan to become pregnant
or plan to breast-feed.1, a
Importance of informing clinicians of existing or contemplated concomitant
therapy, including prescription and OTC drugs, as well as any concomitant
illnesses.1, a
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.
Alendronate (Fosamax) for the treatment of Paget's disease of bone is available
only through Paget's Patient Support Program with Pharma Care Specialty
Pharmacy (800-238-7828 ext. 58197) distribution system for the 40-mg dosage
regimen.d
Alendronate Sodium
Routes Dosage Forms Strengths
Oral Solution
70 mg/75 mL (of alendronate)
Tablets
5 mg (of alendronate)
10 mg (of alendronate)
35 mg (of alendronate)
40 mg (of alendronate)
70 mg (of alendronate)
Fosamax
Merck
Fosamax
Merck
Fosamax
Merck
Fosamax
Merck
Fosamax
Merck
Brand
Names
Fosamax
Plus D
Fosamax
Plus D
Manufacturer
Merck
Merck
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS
Pharmacy. This pricing information was updated 10/2011. For the most current
and up-to-date pricing information, please visit www.drugstore.com. Actual costs
to patients will vary depending on the use of specific retail or mail-order
locations and health insurance copays.
Alendronate Sodium 10MG Tablets (TEVA PHARMACEUTICALS USA):
100/$240.00 or 300/$679.95
Alendronate Sodium 40MG Tablets (TEVA PHARMACEUTICALS USA):
30/$179.99 or 90/$489.95
Alendronate Sodium 5MG Tablets (TEVA PHARMACEUTICALS USA):
100/$255.98 or 300/$729.91
Tertunda revisi, materi dalam bagian ini harus dipertimbangkan dalam terang
informasi lebih lanjut baru-baru tersedia di pemberitahuan MedWatch di awal
risalah ini.
Tersedia sebagai natrium alendronate; Dosis dinyatakan dalam alendronate.1,
sebuah
Dewasa
osteoporosis
> Pencegahan postmenopause Osteoporosis
Oral: Alendronate 5 mg sekali sehari atau 35 mg sekali weekly.1
> Pengobatan Osteoporosis
Oral: Alendronate 10 mg sekali sehari atau 70 mg sekali seminggu pada pria dan
perempuan.1 pascamenopause
Alendronat / cholecalciferol tetap kombinasi: Biasanya, alendronate 70 mg dan
cholecalciferol 5600 unit sekali seminggu pada pria dan women.a
pascamenopause Atau, alendronate 70 mg dan cholecalciferol 2800 unit sekali
weekly.a
Osteoporosis kortikosteroid-induced
> Pencegahan Osteoporosis Kortikosteroid-induced
Oral: Alendronate 5 mg sekali sehari pada wanita pasca menopause yang
menerima terapi penggantian hormon (HRT), wanita premenopause, dan men.73,
78
Alendronate 10 mg sekali sehari pada wanita menopause tidak menerima HRT.78
Lanjutkan alendronate selama pasien terus menerima therapy.78 kortikosteroid
> Pengobatan Osteoporosis Kortikosteroid-induced
Oral: Alendronate 5 mg sekali sehari pada wanita pascamenopause yang
menerima HRT, wanita premenopause, dan men.1, 73, 78
Alendronate 10 mg sekali sehari pada wanita menopause tidak menerima HRT.1,
78
Lanjutkan alendronate selama pasien terus menerima therapy.78 kortikosteroid
Paget Penyakit Bone
Oral: Alendronate 40 mg sekali sehari selama 6 months.1
Sound-alike/look-alike issues:
Fosamax may be confused with Flomax
International issues:
Fosamax may be confused with Fisamox which is a brand name for
amoxicillin in Australia
Pronunciation
Fosamax
Canadian Brand Names
Apo-Alendronate; CO Alendronate; Dom-Alendronate; Fosamax; GenAlendronate; Novo-Alendronate; PHL-Alendronate; PHL-Alendronate-FC; PMSAlendronate; PMS-Alendronate-FC; ratio-Alendronate; Riva-Alendronate;
Sandoz Alendronate
Pharmacologic Category
Bisphosphonate Derivative
Use: Labeled Indications
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
No adjustment necessary.
Calculations
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.
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.
Storage
Store tablets and oral solution at room temperature of 15C to 30C (59F to
86F). Keep in well-closed container.
Contraindications
Bisphosphonate Allergy
Warnings/Precautions
C
Pregnancy Considerations
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
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%.
Test Interactions
Assess history for any previous adverse response to bisphosphonates and ability to
comply with administration instructions. Use caution with renal impairment.
Correct any hypocalcemia prior to beginning treatment. Patients at risk for
osteonecrosis (eg, chemotherapy, corticosteroids, poor oral hygiene) should have
dental exams and necessary preventive dentistry should be done before beginning
Do not take any new medication during therapy unless approved by prescriber.
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 vitamin D). May cause
flatulence, bloating, nausea, or acid regurgitation; small, frequent meals may help.
Bone, joint, and/or muscle pain have been reported, especially at the beginning of
treatment; report persistent pain to prescriber. Report acute headache or gastric
pain, unresolved GI upset, or acid stomach. Pregnancy/breast-feeding
precautions: Inform prescriber if you are or intend to become pregnant. Consult
prescriber if breast-feeding.
Dosage Forms
Yes: Tablet
Pricing: U.S. (www.drugstore.com)
Solution (Fosamax)
70 mg/75 mL (75): $30.99
Tablets (Alendronate Sodium)
5 mg (100): $255.98
10 mg (100): $234.99
35 mg (4): $49.99
70 mg (4): $32.99
Tablets (Fosamax)
5 mg (30): $85.99
10 mg (30): $88.99
35 mg (4): $81.99
70 mg (4): $83.99
Mechanism of Action
Pharmacodynamics/Kinetics
the first doses of the bisphosphonate to first recognition of exposed bone either by
the patients or by the clinician, was 9.4 months for zoledronate (Zometa), 14.3
months for pamidronate (Aredia), and 12.1 months for pamidronate then to
zoledronate.
Information on Fosamax use in Australia and the incidence of ONJ has been
reported. A survey form was sent to all of the Australian members of the
Australian and New Zealand Association of Oral and Maxillofacial Surgeons
requesting cases that they had identified as ONJ in 2004 and 2005. The definition
of ONJ for the survey was an area of exposed bone in the jawbones that failed to
heal within 6 weeks in patients taking bisphosphonates for bone disease. The
frequency of ONJ in osteoporotic patients mainly on weekly oral alendronate was
1 in 8470 to 1 in 2260 (0.01% to 0.04%) patients. If extractions were carried out,
the calculated frequency was 1 in 1130 to 1 in 296 (0.09% to 0.34%) patients. The
minimum values in these cases were determined from the survey whereas the
maximum values were obtained from the extrapolation to the entire Australia of
the South Australian survey data. The median time to onset of ONJ in alendronate
patients was 24 months.
A study from a Harvard group, shows that there may be a decrease in the
incidence of ONJ in Fosamax users compared to the normal population, and
adds new data to the concerns about the Fosamax user and the risk of
developing ONJ. This new study used medical claims data from 714,217 people
with osteoporosis or cancer to identify diagnostic codes or procedural codes for
inflammatory conditions of the jaw, including osteonecrosis. Oral administration
of bisphosphonates (BPs) decreased the risk of inflammatory conditions of the
jaw. At the same time, intravenous administration significantly increased the risk
of adverse jaw outcomes. While the data from the oral BPs counters previous
reports, the intravenous BP data were consistent with reports showing the
increased risk of ONJ after intravenous BP use in cancer patients.
The study, published in the Journal of the American Dental Association (Cartsos,
2008), collected data from the medical claims for inflammatory condition of the
jaw (defined by the study authors as osteonecrosis of the jaw bone), from 20002006. There were 150 claims per 176,889 patients taking oral BPs, giving a ratio
of 0.85 claims per 1000 individuals. Among patients with no BP association, there
were more claims (339 claims per 263,352 patients) giving a ration of 1.3 claims
per 1000 individuals. When statistics were used to calculate significance with a
95% confidence level, there was a definite decrease in the incidence of jaw bone
adverse effects in the population taking oral BPs compared with those patients
who did not take oral BPS
The Food and Drug Administration (FDA) telah meninjau uji coba
terkontrol plasebo dari 7 bifosfonat saat ini dipasarkan di AS. Ulasan ini
AS Nama Merek
Fosamax
Nama Merek Kanada
Apo-Alendronate; CO Alendronate; Dom-Alendronate; Fosamax;
Gen-Alendronate; Novo-Alendronate; PHL-Alendronate; PHLAlendronate-FC; PMS-Alendronate; PMS-Alendronate-FC; RasioAlendronate; Riva-Alendronate; Sandoz Alendronate
farmakologis Kategori
Derivatif bisfosfonat
Gunakan: Indikasi Berlabel
Pengobatan dan pencegahan osteoporosis pada wanita
pascamenopause; pengobatan osteoporosis pada laki-laki; penyakit
Paget tulang pada pasien yang simtomatik, beresiko untuk komplikasi
masa depan, atau dengan alkali fosfatase 2 kali batas atas
normal; pengobatan osteoporosis diinduksi glukokortikoid pada laki-laki
dan perempuan dengan kepadatan mineral tulang yang rendah yang
menerima dosis harian 7,5 mg prednison (atau setara)
Dosis: Dewasa
Catatan: Pasien yang diobati dengan glukokortikoid dan orang-orang
dengan penyakit Paget harus menerima jumlah yang cukup kalsium
dan vitamin D.
Osteoporosis pada wanita postmenopause: Oral:
Profilaksis: 5 mg sekali sehari atau 35 mg sekali seminggu
Pengobatan: 10 mg sekali sehari atau 70 mg sekali seminggu
Osteoporosis pada laki-laki: Oral: 10 mg sekali sehari atau 70 mg sekali
seminggu
Osteoporosis sekunder untuk glukokortikoid pada laki-laki dan
perempuan: Oral: Pengobatan: 5 mg sekali sehari; dosis 10 mg sekali
sehari harus digunakan pada wanita pascamenopause yang tidak
menerima estrogen.
Penyakit Paget tulang pada laki-laki dan perempuan: Oral: 40 mg sekali
sehari selama 6 bulan
Penafsiran: Relaps selama 12 bulan setelah terapi terjadi pada 9% dari
pasien yang menanggapi pengobatan. Data penafsiran tertentu tidak
tersedia. Setelah periode evaluasi pasca perawatan 6 bulan,
pengobatan dengan alendronate dapat dipertimbangkan pada pasien
yang telah kambuh berdasarkan peningkatan fosfatase alkali serum,
yang harus diukur secara berkala. Penafsiran juga dapat
dipertimbangkan pada mereka yang gagal untuk menormalkan mereka
fosfatase alkali serum.
Dosis: Lansia
Mengacu pada dosis dewasa.
Dosis: Penurunan ginjal
ClCr 35-60 mL / menit: Tidak ada yang diperlukan.
ClCr <35 mL / menit: Alendronate tidak dianjurkan karena kurangnya
pengalaman.