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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics |
For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP |
Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP |
Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG |
Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
FOSAMAX (NDA-020560)
(ALENDRONATE SODIUM)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
02/03/2026 (SUPPL-73)
5 Warnings and Precautions
5.5 Atypical Fractures Including Femoral Fractures
Subsection title revised
Additions and/or revisions underlined:
Atypical, low-energy, or low trauma fractures of the femoral shaft have been reported during treatment with bisphosphonates, including alendronate, in patients with osteoporosis. Atypical femur and other fractures most commonly occur with minimal or no trauma to the affected area. These fractures occurred anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution. Atypical fractures of other bones have also been reported. They may be bilateral. There fractures can also occur in osteoporotic patients who have not been treated with bisphosphonates. Concomitant treatment with glucocorticoid may also induce these fractures.
Prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs was reported by patients.
Any patient with a history of bisphosphonate exposure who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Bony pain in other locations should also be considered for evaluation of atypical fracture. Patients presenting with an atypical fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Risk/benefit of continuing bisphosphonate therapy should be re-evaluated in these patients and interruption of bisphosphonate therapy should be considered.
6 Adverse Reactions
Newly added information
The following clinically significant adverse drug reactions are described elsewhere in the labeling:
Upper Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.1)
Mineral Metabolism [see Warnings and Precautions (5.2)]
Musculoskeletal Pain [see Warnings and Precautions (5.3)]
Osteonecrosis of the Jaw [see Warnings and Precautions (5.4)]
Atypical Fractures Including Femoral Fractures [see Warnings and Precautions (5.5)]
Renal Impairment [see Warnings and Precautions (5.6)]
Glucocorticoid-Induced Osteoporosis [see Warnings and Precautions (5.7)]
6.2 Postmarketing Experience
Additions and/or revisions underlined:
The following adverse reactions have been identified during post-approval use of FOSAMAX or bisphosphonate products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
. . .
Musculoskeletal: bone, joint, and/or muscle pain, occasionally severe, and incapacitating [see Warnings and Precautions (5.3)]; joint swelling; low-energy femoral shaft and subtrochanteric fractures, and atypical fractures of other bones [see Warnings and Precautions (5.5)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or revisions underlined:
What is the most important information I should know about FOSAMAX? FOSAMAX can cause serious side effects including:
. . .
5. Unusual breaks in thigh and other bones
. . .
5. Unusual breaks in thigh and other bones.
Some people have had unusual bone breaks, including thigh bone when taking FOSAMAX. A break in the thigh bone can feel like a new pain in your hip, groin, or thigh. People taking FOSAMAX can also have breaks in other bones.
. . .
08/16/2019 (SUPPL-70)
8 Use in Specific Populations
LactationAdditions and/or revisions underlined:
Risk Summary
It is not known whether alendronate is present in human breast milk, affects human milk production, or has effects on the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for FOSAMAX and any potential adverse effects on the breastfed child from FOSAMAX or from the underlying maternal condition.
PLLR Conversion
Additions and/or revisions underlined:
Risk Summary
Available data on the use of FOSAMAX in pregnant women are insufficient to inform a drug-associated risk of adverse maternal or fetal outcomes. Discontinue FOSAMAX when pregnancy is recognized.
In animal reproduction studies, daily oral administration of alendronate to rats from before mating through the end of gestation or lactation showed decreased postimplantation survival and decreased pup body weight gain starting at doses equivalent to less than half of the highest recommended 40 mg clinical daily dose (based on body surface area, mg/m2). Oral administration of alendronate to rats during organogenesis resulted in reduced fetal ossification starting at doses 3 times the 40 mg clinical daily dose. No similar fetal effects were observed in pregnant rabbits dosed orally during organogenesis at doses equivalent to approximately 10 times the 40 mg clinical daily dose.
Delayed or failed delivery of offspring, protracted parturition, and late pregnancy maternal and fetal deaths due to maternal hypocalcemia occurred in rats at oral doses as low as one tenth the 40 mg clinical daily dose (see Data).
Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a period of years. The amount of bisphosphonate incorporated into adult bone and available for release into the systemic circulation is directly related to the dose and duration of bisphosphonate use. Consequently, based on the mechanism of action of bisphosphonates, there is a potential risk of fetal harm, predominantly skeletal, if a woman becomes pregnant after completing a course of bisphosphonate therapy. The impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on the risk has not been studied.
The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the
U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data
Animal Data
Reproduction studies in rats dosed orally from before mating to the end of gestation or lactation showed decreased postimplantation survival starting at 2 mg/kg/day and decreased body weight gain starting at 1 mg/kg/day, doses equivalent to less than half the 40 mg clinical daily dose based on body surface area, mg/m2. Incidence of incomplete fetal ossification in vertebral, skull, and sternebral bones were increased in rats dosed orally during organogenesis starting at 10 mg/kg/day (approximately 3 times the 40 mg clinical daily dose). No similar fetal effects were observed in pregnant rabbits dosed orally during organogenesis at up to 35 mg/kg/day (equivalent to approximately 10 times the 40 mg clinical daily dose).
Both total and ionized calcium decreased in pregnant rats dosed orally with 15 mg/kg/day alendronate (approximately 4 times the 40 mg clinical daily dose) resulting in delays and failures of delivery. Protracted parturition due to maternal hypocalcemia was observed when rats were treated from before mating through gestation starting at 0.5 mg/kg/day (approximately one tenth the 40 mg clinical daily dose). Maternotoxicity (late pregnancy deaths) also occurred in female rats treated orally with 15 mg/kg/day (approximately 4 times the 40 mg clinical daily dose) for varying gestational time periods. These maternal deaths were lessened but not eliminated by cessation of treatment. Calcium supplementation in the drinking water or by subcutaneous minipump to rats dosed orally with 15 mg/kg/day alendronate could not ameliorate the hypocalcemia or prevent the dystocia-related maternal and neonatal deaths. However, intravenous calcium supplementation prevented maternal, but not neonatal deaths.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication GuideAdditions or revisions underlined:
Who should not take FOSAMAX? Do not take FOSAMAX if you:
· Have certain problems with your esophagus, the tube that connects your mouth with your stomach
· Cannot stand or sit upright for at least 30 minutes
· Have low levels of calcium in your blood
· Are allergic to FOSAMAX or any of its ingredients. A list of ingredients is at the end of this leaflet.
Additions and/or revisions underlined:
Advise the patient to read the FDA-approved patient labeling (Medication Guide).