Teriparatide

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous:

Forteo: 600 mcg/2.4 mL (2.4 mL) [contains metacresol]

Pharmacology

Mechanism of Action

Teriparatide is a recombinant formulation of endogenous parathyroid hormone (PTH), containing a 34-amino-acid sequence which is identical to the N-terminal portion of this hormone. The pharmacologic activity of teriparatide, which is similar to the physiologic activity of PTH, includes stimulating osteoblast function, increasing gastrointestinal calcium absorption, and increasing renal tubular reabsorption of calcium. Treatment with teriparatide results in increased bone mineral density, bone mass, and strength. In postmenopausal females, teriparatide has been shown to decrease osteoporosis-related fractures.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: ~0.12 L/kg

Metabolism

Hepatic (nonspecific proteolysis)

Excretion

Urine (as metabolites)

Time to Peak

Serum: ~30 minutes

Half-Life Elimination

IV: 5 minutes; SubQ: ~1 hour

Use in Specific Populations

Special Populations: Renal Function Impairment

In patients with severe renal impairment (CrCl less than 30 mL/min), the AUC and half-life increased 73% and 77%, respectively. Maximum serum concentration was not increased.

Special Populations: Gender

Systemic exposure is approximately 20% to 30% lower in males.

Use: Labeled Indications

Osteoporosis: Treatment of osteoporosis in postmenopausal females who are at high risk for fracture (defined as history of osteoporotic fracture or multiple risk factors for fracture); treatment to increase bone mass in males with primary or hypogonadal osteoporosis who are high risk for fracture; treatment of males and females with glucocorticoid-induced osteoporosis associated with chronic systemic glucocorticoids with a prednisone dosage of ≥5 mg/day (or equivalent) at a high risk for fracture. May also be used in patients who have failed or are intolerant to other available osteoporosis therapy.

Limitations of use: Cumulative lifetime duration of teriparatide and any other parathyroid hormone therapy (eg, abaloparatide) should not exceed 2 years.

Contraindications

Hypersensitivity to teriparatide or any component of the formulation

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

Dosage and Administration

Dosing: Adult

Note:Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate; however, use caution to avoid hypercalcemia (Licata 2005). Assess serum calcium prior to initiation; avoid use in patients with preexisting hypercalcemia or hypercalcemic disorder.

Osteoporosis, glucocorticoid induced (alternative agent): Note: Alternative agent if bisphosphonate therapy is not appropriate. Avoid use in women who are pregnant, who plan on becoming pregnant, or who are not using effective birth control (ACR [Buckley 2017]).

SubQ: 20 mcg once daily.

Osteoporosis, treatment (males and postmenopausal females): Note: Use typically reserved for reduction of vertebral and nonvertebral fractures in patients with very high fracture risk (eg, previous severe or multiple vertebral fractures), or as an alternative agent in patients for whom first-line therapies are not tolerated or ineffective (ES [Eastell 2019]).

SubQ: 20 mcg once daily.

Discontinuation/interruption of therapy: Because the benefits of anabolic therapy are quickly lost after discontinuation, it is generally recommended to initiate antiresorptive therapy (bisphosphonate or alternative) to maintain bone density gains following a course of teriparatide (AACE/ACE [Camacho 2016]; ES [Eastell 2019]).

Duration of therapy: Fracture reduction efficacy has been demonstrated over a period of 18 to 24 months (Geusens 2018; Neer 2001). Cumulative lifetime duration of teriparatide and any other parathyroid hormone therapy (eg, abaloparatide) should not exceed 2 years.

Dosing: Geriatric

Refer to adult dosing.

Administration

SubQ: Initial administration should occur under circumstances in which the patient may sit or lie down, in the event of orthostasis.

Inject into the thigh or abdominal wall. Administer without regard to meals or time of day. May administer dose immediately following removal from the refrigerator. Each teriparatide delivery device can be used for up to 28 days after the first injection. Note: The 3 mL prefilled pen [Canadian product] must be primed prior to each dose.

Dietary Considerations

Ensure adequate calcium and vitamin D intake; if dietary intake is inadequate, dietary supplementation is recommended. Females and males should consume:

Calcium: 1,000 mg/day (males: 50 to 70 years of age) or 1,200 mg/day (females ≥51 years of age and males ≥71 years of age) (IOM 2011; NOF [Cosman 2014]). Some clinicians have suggested limiting calcium to ≤1,000 mg/day in patients taking teriparatide (Licata 2005).

Vitamin D: 800 to 1,000 units/day (males and females ≥50 years of age) (NOF [Cosman 2014]). Recommended Dietary Allowance (RDA): 600 units/day (males and females ≤70 years of age) or 800 units/day (males and females ≥71 years of age) (IOM 2011).

Storage

Store refrigerated at 2°C to 8°C (36°F to 46°F); do not freeze (discard if freezing occurs). Protect from light. Discard pen 28 days after first injection, even if it still contains some unused solution. Do not use if solution is cloudy, colored, or contains solid particles.

Drug Interactions

There are no known significant interactions.

Test Interactions

Transiently increases serum calcium; maximal effect 4 to 6 hours postdose; generally returns to baseline ~16 hours postdose

Adverse Reactions

>10%: Endocrine & metabolic: Hypercalcemia (transient increases noted 4 to 6 hours postdose [women 11%; men 6%])

1% to 10%:

Cardiovascular: Orthostatic hypotension (5%; transient), angina pectoris (3%), syncope (3%)

Central nervous system: Dizziness (8%), headache (8%), insomnia (5%), anxiety (4%), depression (4%), vertigo (4%)

Endocrine & metabolic: Hyperuricemia (3%)

Gastrointestinal: Nausea (9% to 14%), gastritis (7%), dyspepsia (5%), vomiting (3%)

Immunologic: Antibody development (3% of women in long-term treatment; hypersensitivity reactions or decreased efficacy were not associated in preclinical trials)

Infection: Herpes zoster (3%)

Neuromuscular & skeletal: Arthralgia (10%), weakness (9%), leg cramps (3%)

Respiratory: Rhinitis (10%), pharyngitis (6%), dyspnea (4% to 6%), pneumonia (3% to 6%)

<1%, postmarketing and/or case reports: Anaphylaxis, angioedema, chest pain, dyspnea (acute), facial edema, hypercalcemia (>13 mg/dL), hypersensitivity reaction, injection site reactions (bruising, pain, swelling), mouth edema, muscle spasm, osteosarcoma, urticaria

Warnings/Precautions

Concerns related to adverse effects:

• Orthostatic hypotension: May cause orthostatic hypotension. Transient orthostatic hypotension usually occurs within 4 hours of dosing and within the first several doses.
• Osteosarcoma: [US Boxed Warning]: 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:

• 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).

Monitoring Parameters

Orthostatic hypotension; serum calcium (draw at least 16 hours after teriparatide dose); urinary calcium (patients with suspected active urolithiasis or preexisting hypercalciuria).

Bone mineral density (BMD) should be evaluated at baseline and ~1 to 2 years following initiation of therapy) (AACE/ACE [Camacho 2016]; ES [Eastell 2019]; NOF [Cosman 2014]); may consider monitoring biochemical markers of bone turnover (eg, serum P1NP) at baseline, 3 months, and 6 months to assess treatment response (ES [Eastell 2019]; Miller 2016).

Pregnancy

Pregnancy Considerations

Adverse events were observed in animal reproduction studies; consider discontinuing treatment once pregnancy is recognized.

Patient Education

What is this drug used for?

• It is used to treat soft, brittle bones (osteoporosis).

Frequently reported side effects of this drug

• Joint pain
• Loss of strength and energy
• Fatigue
• Nausea
• Diarrhea
• Constipation
• Runny nose
• Cough
• Throat irritation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe dizziness
• Passing out
• Severe headache
• Vision changes
• High calcium like weakness, confusion, fatigue, headache, nausea and vomiting, constipation, or bone pain
• Kidney stone like back pain, abdominal pain, or blood in the urine
• Muscle weakness
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.