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Drug Safety-related Labeling Changes (SrLC)

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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.

BONSITY (NDA-211939)

(TERIPARATIDE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

11/16/2023 (SUPPL-4)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Osteosarcoma

Additions and/or revisions underlined:

An increase in the incidence of osteosarcoma (a malignant bone tumor) was observed in male and female rats treated with teriparatide. Osteosarcoma has been reported in patients treated with teriparatide in the post marketing setting; however, an increased risk of osteosarcoma has not been observed in observational studies in humans. There are limited data assessing the risk of osteosarcoma beyond 2 years of teriparatide use [see Dosage and Administration (2.3), Adverse Reactions (6.2), Nonclinical Toxicology (13.1)].

Avoid BONSITY use in patients with (these patients are at increased baseline risk of osteosarcoma):

Open epiphyses (pediatric and young adult patients) (BONSITY is not approved in pediatric patients) [see Use in Specific Populations (8.4)].
Metabolic bone diseases other than osteoporosis, including Paget's disease of the bone.
Bone metastases or a history of skeletal malignancies.
Prior external beam or implant radiation therapy involving the skeleton.
Hereditary disorders predisposing to osteosarcoma.

5.2 Hypercalcemia and Cutaneous Calcification

Additions and/or revisions underlined:

Hypercalcemia

Teriparatide has not been studied in patients with pre-existing hypercalcemia. Teriparatide may cause hypercalcemia and may exacerbate hypercalcemia in patients with pre-existing hypercalcemia [see Adverse Reactions (6.1, 6.2)]. Avoid BONSITY in patients known to have an underlying hypercalcemic disorder, such as primary hyperparathyroidism.

Risk of Cutaneous Calcification Including Calciphylaxis

Serious reports of calciphylaxis and worsening of previously stable cutaneous calcification have been reported in the post-marketing setting in patients taking teriparatide. Risk factors for development of calciphylaxis include underlying autoimmune disease, kidney failure, and concomitant warfarin or systemic corticosteroid use. Discontinue BONSITY in patients who develop calciphylaxis or worsening of previously stable cutaneous calcification.

5.3 Risk of Urolithiasis

Additions and/or revisions underlined:

In clinical trials, the frequency of urolithiasis was similar in patients treated with teriparatide and patients treated with placebo. However, teriparatide has not been studied in patients with active urolithiasis. If BONSITY-treated patients have pre-existing hypercalciuria or suspected/known active urolithiasis, consider measuring urinary calcium excretion. Consider the risks and benefits of use in patients with active or recent urolithiasis because of the potential to exacerbate this condition.

5.4 Orthostatic Hypotension

Additions and/or revisions underlined:

BONSITY should be administered initially under circumstances in which the patient can sit or lie down if symptoms of orthostatic hypotension occur. In short-term clinical pharmacology studies of teriparatide in healthy volunteers, transient episodes of symptomatic orthostatic hypotension were observed in 5% of volunteers. Typically, these events began within 4 hours of dosing and resolved (without treatment) within a few minutes to a few hours. When transient orthostatic hypotension occurred, it happened within the first several doses, it was relieved by placing the person in a reclining position, and it did not preclude continued treatment.

5.5 Risk of Digoxin Toxicity

Additions and/or revisions underlined:

Hypercalcemia may predispose patients to digitalis toxicity because teriparatide transiently increases serum calcium. Consider the potential onset of signs and symptoms of digitalis toxicity when BONSITY is used in patients receiving digoxin [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

6 Adverse Reactions

6.2 Postmarketing Experience

Additions and/or revisions underlined:

…

Adverse Reactions from Observational Studies to Assess Incidence of Osteosarcoma

Two osteosarcoma surveillance safety studies (U.S. claims-based database studies) were designed to obtain data on the incidence rate of osteosarcoma among teriparatide-treated patients. In these two studies, three and zero osteosarcoma cases were identified among 379,283 and 153,316 teriparatide users, respectively. The study results suggest a similar risk for osteosarcoma between teriparatide users and their comparators. However, the interpretation of the study results calls for caution owing to the limitations of the data sources which do not allow for complete measurement and control for confounders.

7 Drug Interactions

7.1 Digoxin

Additions and/or revisions underlined:

Sporadic case reports have suggested that hypercalcemia may predispose patients to digitalis toxicity. Teriparatide may transiently increase serum calcium. Consider the potential onset of signs and symptoms of digitalis toxicity when BONSITY is used in patients receiving digoxin [see Warnings and Precautions (5.5), Clinical Pharmacology (12.3)].

8 Use in Specific Populations

8.2 Lactation

Additions and/or revisions underlined:

Risk Summary

It is not known whether teriparatide is excreted in human milk, affects human milk production, or has effects on the breast fed infant. Avoid BONSITY use in women who are breastfeeding.

8.5. Geriatric Use

Additions and/or revisions underlined:

Of the patients who received teriparatide in the osteoporosis trial of 1637 postmenopausal women, 75% were 65 years of age and older and 23% were 75 years of age and older. Of the patients who received teriparatide in the trial of 437 men with primary or hypogonadal osteoporosis, 39% were 65 years of age and over and 13% were 75 years of age and over. Of the 214 patients who received teriparatide in the glucocorticoid induced osteoporosis trial, 28% were 65 years of age and older and 9% were 75 years of age and older. No overall differences in safety or effectiveness of teriparatide have been observed between patients 65 years of age and older and younger adult patients.

8.7 Renal Impairment

Additions and/or revisions underlined:

In 5 patients with severe renal impairment (CrCl <30 mL/minute), the AUC and T1/2 of teriparatide were increased by 73% and 77%, respectively. Maximum serum concentration of teriparatide was not increased. It is unknown whether teriparatide alters the underlying metabolic bone disease seen in chronic renal impairment [see Clinical Pharmacology (12.3)].

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Advise the patient to read the FDA-approved patient labeling (Medication Guide and the User Manual) before starting BONSITY and each time the prescription is renewed. Failure to follow the instructions may result in inaccurate dosing.

Osteosarcoma

Patients should be made aware that in rats, teriparatide caused an increase in the incidence of osteosarcoma (a malignant bone tumor). Although cases of osteosarcoma have been reported in patients using teriparatide, no increased risk of osteosarcoma was observed in adult humans treated with teriparatide [see Warnings and Precautions (5.1)].

…

Orthostatic Hypotension

When initiating BONSITY treatment, instruct patients to be prepared to immediately sit or lie down during or after administration in case they feel lightheaded or have palpitations after the injection. Instruct patients to sit or lie down until the symptoms resolve. If symptoms persist or worsen, instruct patients to consult a healthcare provider before continuing treatment [see Warnings and Precautions (5.4)].

…

Use of Delivery Device (Pen)

Instruct patients and caregivers who administer BONSITY on how to properly use the delivery device (refer to User Manual), to properly dispose of needles, and not to share their delivery device with other patients. Instruct patients and caregivers who administer BONSITY that the contents of the delivery device should not be transferred to a syringe.

Inform patients that each BONSITY delivery device can be used for up to 28 days. After the 28- day use period, instruct patients to discard the BONSITY delivery device, even if it still contains some unused solution.Instruct patients not to use BONSITY after the expiration date printed on the delivery device and packaging.

MEDICATION GUIDE

Extensive additions and revision, please refer to label for complete information.