Teriparatide

H05A - Parathyroid hormones and analogues ATC H05AA02 Protein approved 2002 Parenteral Black-box warning

JFDA label: Osteopen

⚠ Black-Box Warning

Potential risk of osteosarcoma:

Mechanism of Action

Agonist of Parathyroid hormone/parathyroid hormone-related peptide receptor — Parathyroid hormone receptor agonist

Target	Action	Gene / class
Parathyroid hormone/parathyroid hormone-related peptide receptor efficacy	AGONIST	PTH1R

Indications

Approved

Glucocorticoid-induced osteoporosis
Osteoporosis in men
Osteoporosis in postmenopausal women

Contraindications

Source: Lexicomp

Additional contraindications (not in US labeling): Preexisting hypercalcemia Absolute
Hypersensitivity to teriparatide or any component of the formulation Absolute
bone metastases or history of skeletal malignancies Absolute
breast-feeding mothers Absolute
metabolic bone diseases other than primary osteoporosis (including hyperparathyroidism and Paget’s disease of the bone) Absolute
pediatric patients or young adults with open epiphysis Absolute
prior external beam or implant radiation therapy involving the skeleton Absolute
severe renal impairment Absolute
unexplained elevations of alkaline phosphatase Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (3)

Common angina pectoris · Orthostatic hypotension · syncope

Nervous system disorders (6)

Common anxiety · depression · Dizziness · headache · insomnia · vertigo

Immune system disorders (1)

Common Antibody development

Metabolism and nutrition disorders (1)

Common Hyperuricemia

Gastrointestinal disorders (4)

Common dyspepsia · gastritis · Nausea · vomiting

Musculoskeletal and connective tissue disorders (3)

Common Arthralgia · leg cramps · weakness

Infections and infestations (1)

Common Herpes zoster

Other (1)

Very Common Endocrine & metabolic: Hypercalcemia

Respiratory, thoracic and mediastinal disorders (4)

Common dyspnea · pharyngitis · pneumonia · Rhinitis

Dosing

Source: Lexicomp

Osteoporosis (men, postmenopausal women, glucocorticoid induced): SubQ: 20 mcg once daily; Note: Initial administration should occur under circumstances in which the patient may sit or lie down, in the event of orthostasis.

Refer to adult dosing.

No dosage adjustment necessary. Use in severe renal impairment is contraindicated in the Canadian labeling.

There is no dosage adjustment provided in the manufacturer’s labeling (has not been studied).

Warnings & Precautions

Source: Lexicomp

Orthostatic hypotension

May cause orthostatic hypotension. Transient orthostatic hypotension usually occurs within 4 hours of dosing and within the first several doses.

Osteosarcoma

In animal studies, teriparatide has been associated with an increase in osteosarcoma; risk was dependent on both dose and duration. Avoid use in patients with an increased risk of osteosarcoma (including Paget disease, prior radiation, unexplained elevation of alkaline phosphatase, prior external beam or implant radiation therapy involving the skeleton, or in patients with open epiphyses). Do not use in patients with bone metastases, a history of skeletal metastases, hyperparathyroidism, or preexisting hypercalcemia. Not for use in patients with metabolic bone disease other than osteoporosis. A voluntary patient registry has been established to collect information regarding osteosarcoma; patients are encouraged to enroll. Registry information may be obtained at www.forteoregistry.rti.org or by calling 866-382-6813. Disease-related concerns:

Renal impairment

Use in severe renal impairment is contraindicated in the Canadian labeling.

Urolithiasis

Use with caution in patients with active or recent urolithiasis because of risk of exacerbation. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Multiple-dose injection pens

According to the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC, 2012). Other warnings/precautions:

Appropriate use

Use of teriparatide for longer than 2 years is not recommended.

Appropriate use

Glucocorticoid-induced osteoporosis: For use in men and women at high risk of fracture, which is defined as a history of osteoporotic fracture or multiple risk factors for fracture. May also be used in patients who have failed or are intolerant to other available osteoporosis therapy.

Appropriate use

Osteoporosis in men: For use in men at high risk for fracture, which is defined as a history of osteoporotic fracture or multiple risk factors for fracture. May also be used in men who have failed or are intolerant to previous osteoporosis therapy.

Appropriate use

Postmenopausal osteoporosis: For use in women at high risk for fracture, which is defined as a history of osteoporotic fracture or multiple risk factors for fracture. May also be used in women who have failed or are intolerant of previous osteoporosis therapy. In postmenopausal women with osteoporosis, teriparatide reduces the risk of vertebral and nonvertebral fractures.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events were observed in animal studies; the effect on human fetal development has not been studied. Teriparatide is not indicated for use in pregnant or premenopausal women.

Lactation

It is not known if teriparatide is excreted in breast milk. According to the manufacturer, the decision to discontinue teriparatide or discontinue breast-feeding should take into account the exposure to the infant and the benefits of treatment to the mother.

LactMed: monitor the infant.

Monitoring

Clinical pearl	Orthostatic hypotension; urinary calcium (patients with suspected active urolithiasis or preexisting hypercalciuria); bone mineral density (BMD) should be evaluated 1 to 2 years after initiating therapy and every 2 years thereafter (NOF [Cosman 2014]); annual measurements of height and weight, assessment of chronic back pain; serum calcium and 25(OH)D; consider measuring biochemical markers of bone turnover

Clinical pearl

Orthostatic hypotension; urinary calcium (patients with suspected active urolithiasis or preexisting hypercalciuria); bone mineral density (BMD) should be evaluated 1 to 2 years after initiating therapy and every 2 years thereafter (NOF [Cosman 2014]); annual measurements of height and weight, assessment of chronic back pain; serum calcium and 25(OH)D; consider measuring biochemical markers of bone turnover

Chemistry & Properties

Formula	C181H291N55O51S2
Molecular weight	4117.79 g/mol
IUPAC name	(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]hexanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1,4-dioxobutan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-oxopentanoic acid
CAS	52232-67-4
PubChem CID	16133850
InChIKey	`OGBMKVWORPGQRR-UMXFMPSGSA-N`

SMILES

CC[C@H](C)[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)C(C)C)C(C)C

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	3.731 h
Volume of distribution	0.153 L/kg
Protein binding	-26.5%
BBB penetrant	No

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (6, DDInter)

Interacting drug	Severity	Management
Calcipotriol (topical)	moderate
Calcitriol (topical)	moderate
Digitoxin	moderate
Digoxin	moderate
Furosemide	minor
Hydrochlorothiazide	minor

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Osteopen	Tablet 20 mcg MCL	One PFP/1 PKG	/ Pharma International Company/Jordan / General	—