Abaloparatide

JFDA label: Tymlos

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

• Osteoporosis

Contraindications

Source: Lexicomp

• There are no contraindications listed in the manufacturer's labeling Absolute

Adverse Reactions

Cardiac disorders (4)

Common orthostatic hypotension · Palpitations · sinus tachycardia · tachycardia

Nervous system disorders (3)

Common Dizziness · fatigue · headache

Renal and urinary disorders (1)

Very Common Hypercalciuria

Immune system disorders (1)

Very Common Antibody development

Metabolism and nutrition disorders (2)

Very Common Increased uric acid

Common Hypercalcemia

Gastrointestinal disorders (2)

Common Nausea · upper abdominal pain

General disorders and administration site conditions (3)

Very Common Erythema at injection site

Common pain at injection site · Swelling at injection site

Dosing

Source: Lexicomp

Warnings & Precautions

Source: Lexicomp

Hypercalcemia

May cause or exacerbate hypercalcemia; use is not recommended in patients with preexisting hypercalcemia or with an underlying hypercalcemic disorder (eg, primary hyperparathyroidism).

Orthostatic hypotension

May cause orthostatic hypotension. Transient orthostatic hypotension usually occurs within 4 hours of dosing.

Osteosarcoma

In animal studies, abaloparatide 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, bone metastases or skeletal malignancies, hereditary disorders predisposing to osteosarcoma, unexplained elevation of alkaline phosphatase, prior external beam or implant radiation therapy involving the skeleton, or in patients with open epiphyses). Disease-related concerns:

Urolithiasis

Use may cause hypercalciuria; use with caution in patients with active or recent urolithiasis because of risk of exacerbation. Other warnings/precautions:

Appropriate use

Use for >2 years during a patient's lifetime is not recommended.

Pregnancy & Lactation

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]); serum calcium; consider measuring biochemical markers of bone turnover

Chemistry & Properties

CAS	247062-33-5
PubChem CID	76943386

SMILES

CCC(C)C(C(=O)NC(CCC(=O)N)C(=O)NC(CC(=O)O)C(=O)NC(CC(C)C)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCC(=O)O)C(=O)NC(CC(C)C)C(=O)NC(CC(C)C)C(=O)NC(CCC(=O)O)C(=O)NC(CCCCN)C(=O)NC(CC(C)C)C(=O)NC(CC(C)C)C(=O)NC(C)(C)C(=O)NC(CCCCN)C(=O)NC(CC(C)C)C(=O)NC(CC1=CN=CN1)C(=O)NC(C(C)O)C(=O)NC(C)C(=O)N)NC(=O)C(CO)NC(=O)C(CCCCN)NC(=O)CNC(=O)C(CCCCN)NC(=O)C(CC(=O)O)NC(=O)C(CC2=CN=CN2)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCC(=O)N)NC(=O)C(CC3=CN=CN3)NC(=O)C(CCC(=O)O)NC(=O)C(CO)NC(=O)C(C(C)C)NC(=O)C(C)N

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	3.158 h
Volume of distribution	0.069 L/kg
Protein binding	-51.1%
BBB penetrant	No

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)OAT3 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (2, DDInter)

Interacting drug	Severity	Management
Calcipotriol (topical)	moderate
Calcitriol (topical)	moderate

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Tymlos	Tablet 80 mcg MCL	(1 PFP)	ORIENT DRUG STORE CO	—