Identification

Summary

Teriparatide is a recombinant parathyroid hormone used for the treatment of osteoporosis.

Brand Names
Forsteo, Forteo
Generic Name
Teriparatide
DrugBank Accession Number
DB06285
Background

Teriparatide is a recombinant parathyroid hormone (PTH) analog and a potent osteoanabolic agent.2 It is made up of the first amino(N)-terminal 34 amino acids of the human PTH.2 First approved in the United States in November 2002 and Europe in April 2003,3 teriparatide makes the first approved drug in a new category of osteoporosis therapy called anabolic therapy.2 Teriparatide is used in the treatment of osteoporosis in men and women.4,5

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Hormones
Protein Chemical Formula
C181H291N55O51S2
Protein Average Weight
4117.715 Da
Sequences
>Sequence
SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF
References:
  1. KEGG DRUG: Teriparatide [Link]
Download FASTA Format
Synonyms
  • PTH (1-34)
  • PTH 1-34
  • Teriparatida
  • Teriparatide
  • Teriparatide recombinant human
External IDs
  • LY 333334
  • LY-333334
  • LY333334
  • ZT-034

Pharmacology

Indication

Teriparatide is indicated:

  • for the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined herein as having a history of osteoporotic fracture or multiple risk factors for fracture) or who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, teriparatide reduces the risk of vertebral and nonvertebral fractures.4,5
  • to increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy.4,5
  • for the treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy.4,5
Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug events
Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
Pharmacodynamics

Teriparatide is a PTH analog that works to stimulate bone formation in both men and women. It increases skeletal mass, increases markers of bone formation such as bone-specific alkaline phosphatase (BSAP) and procollagen I carboxy-terminal propeptide (PICP), and increases bone strength.4

Like endogenous PTH, teriparatide affects calcium and phosphate homeostasis. It causes a transient increase in serum calcium levels and increases urinary calcium excretion. In clinical trials, it also produced transient phosphaturia and mild transient reductions in serum phosphorus concentration.4

Mechanism of action

Parathyroid hormone (PTH) is an endogenous hormone that regulates calcium and phosphate metabolism in bone and kidney. It regulates bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption. It mediates its physiological actions by binding to the PTH receptors.4 Excess PTH - such as in certain disease states like hyperparathyroidism - can cause increased osteoclast activity and accelerated bone resorption. Interestingly, the effects of PTH depend on the dose and pattern of exposure of PTH to the bone. Continuous exposure to PTH promotes bone resorption, whereas intermittent exposure to low-dose PTH can induce bone formation more favourably than bone resorption.2

Similarly, teriparatide's skeletal effects depend upon the systemic exposure pattern. Once-daily administration of teriparatide stimulates new bone formation on trabecular and cortical (periosteal and/or endosteal) bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity.4 Teriparatide mediates its osteoanabolic actions by binding to the N-terminal moiety to PTH type 1 receptors (PTH type 1R), which are G-protein coupled receptors expressed on various cells, including osteoblasts, osteocytes, and renal tubular cells.2 Binding of teriparatide to PTH receptors on osteoblasts activates the downstream PKA- and PKC-dependent signaling pathways that promotes anabolic effects on bone.1,2 For example, teriparatide increases expression of pro-osteoclastogenic cytokines like receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor. It also upregulates transcriptional expression of pro-osteoblastogenic growth factors like insulin-like growth factor 1 (IGF1) and fibroblast growth factor 2 (FGF2). Teriparatide also downregulates the synthesis of sclerostin, which is a negative regulator of bone formation. It also promotes the differentiation of osteoblasts.2

TargetActionsOrganism
UParathyroid hormone/parathyroid hormone-related peptide receptor
ligand
Humans
Absorption

The absolute bioavailability is approximately 95%. The peptide reaches peak serum concentrations about 30 minutes after subcutaneous injection of a 20 mcg dose and declines to non-quantifiable concentrations within three hours.4

Volume of distribution

The volume of distribution following intravenous injection is approximately 0.12 L/kg. Teriparatide is not expected to accumulate in bone or other tissues.4

Protein binding

There is no information available.

Metabolism

No metabolism studies have been performed with teriparatide. Peripheral metabolism of PTH is believed to occur by non-specific enzymatic mechanisms in the liver.4

Route of elimination

No excretion studies have been performed with teriparatide. It is believed to be excreted via the kidneys.4

Half-life

The half-life of teriparatide in serum was approximately one hour following subcutaneous administration.4

Clearance

Systemic clearance of teriparatide is approximately 62 L/hour in women and 94 L/hour in men. It exceeds the rate of normal liver plasma flow, consistent with both hepatic and extra-hepatic clearance.4

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
Toxicity

The subcutaneous and intravenous lethal dose (LD) in rats are 1000 µg/m3 and 300 µg/m3, respectively.6

Few post-marketing reports illustrate cases of medication errors where patients accidentally received up to a single 800 mcg dose of teriparatide, which is 40 times the recommended dose. Patients experienced nausea, weakness or lethargy, and hypotension. No deaths have been reported from teriparatide overdose. Additional signs, symptoms, and complications of overdosage may include a delayed hypercalcemic effect, vomiting, dizziness, and headache.4

There is no specific antidote for a teriparatide overdosage. Treatment of suspected overdosage should include discontinuation of teriparatide, monitoring of serum calcium and phosphorus, and implementation of appropriate supportive measures, such as hydration.4

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcalabrutinibThe therapeutic efficacy of Teriparatide can be decreased when used in combination with Acalabrutinib.
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Teriparatide.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Teriparatide.
AfatinibThe therapeutic efficacy of Teriparatide can be decreased when used in combination with Afatinib.
AldesleukinThe therapeutic efficacy of Teriparatide can be decreased when used in combination with Aldesleukin.
AlectinibThe therapeutic efficacy of Teriparatide can be decreased when used in combination with Alectinib.
Aminosalicylic acidThe therapeutic efficacy of Teriparatide can be decreased when used in combination with Aminosalicylic acid.
AmphetamineThe risk or severity of adverse effects can be increased when Amphetamine is combined with Teriparatide.
AvapritinibThe therapeutic efficacy of Teriparatide can be decreased when used in combination with Avapritinib.
AxitinibThe therapeutic efficacy of Teriparatide can be decreased when used in combination with Axitinib.
Identify potential medication risks
Easily compare up to 40 drugs with our drug interaction checker.
Get severity rating, description, and management advice.
Learn more
Food Interactions
  • Take with or without food.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Teriparatide acetate9959P4V12N99294-94-7Not applicable
International/Other Brands
Forsteo (Eli Lilly and Company)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ForsteoInjection, solution20 μg/80μlSubcutaneousEli Lilly Nederland B.V.2020-12-23Not applicableEU flag
ForsteoInjection, solution20 μg/80μlSubcutaneousEli Lilly Nederland B.V.2020-12-23Not applicableEU flag
ForteoInjection, solution250 ug/1mLSubcutaneousPhysicians Total Care, Inc.2005-09-062009-11-21US flag
ForteoInjection, solution250 ug/1mLSubcutaneousEli Lilly and Company2002-11-26Not applicableUS flag
ForteoInjection, solution750 ug/3mLSubcutaneousEli Lilly and Company2006-11-152006-11-15US flag
ForteoSolution250 mcg / mLSubcutaneousEli Lilly & Co. Ltd.2004-07-15Not applicableCanada flag
LivogivaInjection, solution20 ?g/80?lSubcutaneousTheramex Ireland Limited2021-01-12Not applicableEU flag
LivogivaInjection, solution20 ?g/80?lSubcutaneousTheramex Ireland Limited2021-01-12Not applicableEU flag
MovymiaInjection, solution20 ?g/80?lSubcutaneousStada Arzneimittel Ag2020-12-16Not applicableEU flag
MovymiaInjection, solution20 ?g/80?lSubcutaneousStada Arzneimittel Ag2020-12-16Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-teriparatide InjectionSolution250 mcg / mLSubcutaneousApotex CorporationNot applicableNot applicableCanada flag
Teva-teriparatide InjectionSolution250 mcg / mLSubcutaneousTEVA Canada Limited2020-07-08Not applicableCanada flag

Categories

ATC Codes
H05AA02 — Teriparatide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
10T9CSU89I
CAS number
52232-67-4

References

General References
  1. Stroup J, Kane MP, Abu-Baker AM: Teriparatide in the treatment of osteoporosis. Am J Health Syst Pharm. 2008 Mar 15;65(6):532-9. doi: 10.2146/ajhp070171. [Article]
  2. Vall H, Parmar M: Teriparatide . [Article]
  3. Quattrocchi E, Kourlas H: Teriparatide: a review. Clin Ther. 2004 Jun;26(6):841-54. doi: 10.1016/s0149-2918(04)90128-2. [Article]
  4. FDA Approved Drug Products: FORTEO (teriparatide) injection, for subcutaneous use [Link]
  5. EMA Approved Drug Products: Sondelbay (teriparatide) Subcutaneous Injection [Link]
  6. Eli Lilly and Company: Forteo (Teriparatide) MSDS [Link]
KEGG Drug
D06078
PubChem Substance
347910346
RxNav
32915
ChEMBL
CHEMBL525610
Therapeutic Targets Database
DAP000396
PharmGKB
PA451620
Drugs.com
Drugs.com Drug Page
Wikipedia
Teriparatide
MSDS
Download (24.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingDiagnosticPostmenopausal Osteoporosis / Type 2 Diabetes Mellitus1
4CompletedOtherPostmenopausal Osteoporosis1
4CompletedTreatmentAdult Degenerative Lumbar Scoliosis / Lumbar Spondylolisthesis / Spondylosis Lumbar1
4CompletedTreatmentAtypical Femoral Fractures / Osteoporosis1
4CompletedTreatmentBone Loss / Osteoporosis / Spinal Cord Injuries (SCI)1
4CompletedTreatmentHumeral Fractures1
4CompletedTreatmentOsteogenesis Imperfecta (OI)1
4CompletedTreatmentOsteoporosis10
4CompletedTreatmentOsteoporosis, Osteopenia1
4CompletedTreatmentPostmenopausal Osteoporosis10

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Eli Lilly & Co.
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
Injection, solutionSubcutaneous20 μg/80μl
SolutionSubcutaneous
Injection, solutionSubcutaneous250 ug/1mL
Injection, solutionSubcutaneous250 mcg/1ml
Injection, solutionSubcutaneous750 ug/3mL
SolutionSubcutaneous250 mcg / mL
Injection, solutionSubcutaneous
Injection, solutionSubcutaneous750 mcg/3ml
SolutionSubcutaneous250 mcg
Injection, solutionParenteral; Subcutaneous20 mcg/80mcL
Injection, solutionSubcutaneous20 mcg/80ml
Injection, solutionSubcutaneous20 ?g/80?l
SolutionSubcutaneous250 mcg/1ml
SolutionSubcutaneous750 mcg
Injection, solutionParenteral
Powder1 g/1g
Injection, solutionSubcutaneous250 mcg/ml
Injection, solutionParenteral; Subcutaneous20 MCG/80MCG
Injection, solutionSubcutaneous20 mcg/80mcL
SolutionSubcutaneous0.25 mg
Prices
Unit descriptionCostUnit
Forteo 750 mcg/3 ml pen295.26USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2314313No2005-02-082018-12-08Canada flag
CA2325371No2004-08-172019-08-19Canada flag
US6770623No2004-08-032018-12-08US flag
US6977077No2005-12-202019-08-19US flag
US7163684No2007-01-162019-08-19US flag
US7351414No2008-04-012019-08-19US flag
US7550434No2009-06-232018-12-08US flag
US7144861No2006-12-052018-12-08US flag
US7517334No2009-04-142025-03-25US flag

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Ligand
General Function
Protein self-association
Specific Function
This is a receptor for parathyroid hormone and for parathyroid hormone-related peptide. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatid...
Gene Name
PTH1R
Uniprot ID
Q03431
Uniprot Name
Parathyroid hormone/parathyroid hormone-related peptide receptor
Molecular Weight
66359.98 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  2. Ferrari SL, Behar V, Chorev M, Rosenblatt M, Bisello A: Endocytosis of ligand-human parathyroid hormone receptor 1 complexes is protein kinase C-dependent and involves beta-arrestin2. Real-time monitoring by fluorescence microscopy. J Biol Chem. 1999 Oct 15;274(42):29968-75. [Article]
  3. Vall H, Parmar M: Teriparatide . [Article]

Drug created at March 19, 2008 16:21 / Updated at August 18, 2022 01:37