Teriparatide

Usage

• Teriparatide is prescribed for the treatment of osteoporosis in postmenopausal women and men at high risk of fracture. This includes patients who have failed or are intolerant to other osteoporosis therapies. It is also indicated for osteoporosis associated with sustained systemic glucocorticoid therapy.
• Pharmacological classification: Teriparatide is classified as an anabolic agent, specifically a parathyroid hormone analog (PTH 1-34).
• Mechanism of Action: Teriparatide works by mimicking the biological effects of parathyroid hormone. Intermittent PTH administration, like daily injections of teriparatide, stimulates bone formation by increasing osteoblast activity more than osteoclast activity, leading to a net increase in bone mass.

Alternate Names

• International Nonproprietary Name (INN): Teriparatide
• Brand names: Forteo, Bonsity

How It Works

• Pharmacodynamics: Teriparatide’s primary effect is to increase bone formation. It stimulates osteoblast activity, leading to new bone deposition on trabecular and cortical bone surfaces. Teriparatide also increases intestinal calcium absorption and renal tubular reabsorption of calcium while increasing phosphate excretion.

• Pharmacokinetics: Teriparatide is administered subcutaneously and is rapidly absorbed. Peak serum concentrations are reached within 30 minutes to 1 hour. It has a short half-life of about 1 hour. Teriparatide is metabolized in the liver and kidneys.

• Mode of Action: Teriparatide binds to the PTH/PTHrP receptor, a G protein-coupled receptor expressed on osteoblasts and osteocytes. This binding initiates signaling cascades that result in increased osteoblast differentiation, proliferation, and activity, promoting bone formation.

• Elimination Pathways: Teriparatide is cleared through hepatic and renal metabolism.

Dosage

Standard Dosage

Adults:

• The standard dose is 20 mcg administered subcutaneously once daily into the thigh or abdomen.
• The maximum lifetime duration of treatment is 24 months. This 24-month course should not be repeated.

Children:

• Teriparatide is not recommended for use in children or young adults with open epiphyses due to an increased risk of osteosarcoma. Safety and efficacy have not been established in pediatric patients.

Special Cases:

• Elderly Patients: No dose adjustment is necessary based on age.

• Patients with Renal Impairment: No dose adjustment is recommended for mild to moderate renal impairment. Use with caution in moderate renal impairment. Teriparatide should not be used in patients with severe renal impairment.

• Patients with Hepatic Dysfunction: No studies have been performed in patients with hepatic impairment, but it is unlikely to have a clinically significant effect on systemic exposure to teriparatide.

• Patients with Comorbid Conditions: Use with caution in patients with urolithiasis or history of orthostatic hypotension. Monitor digoxin levels in patients receiving concomitant digoxin therapy. Supplement calcium and vitamin D if dietary intake is inadequate.

Clinical Use Cases

Teriparatide is not indicated for use in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary use is in the long-term management of osteoporosis to reduce fracture risk.

Side Effects

Common Side Effects:

• Nausea
• Headache
• Dizziness
• Leg cramps
• Pain, redness, or swelling at the injection site

Rare but Serious Side Effects:

• Osteosarcoma (bone cancer)
• Hypercalcemia
• Orthostatic hypotension
• Allergic reactions (including angioedema and anaphylaxis)

Long-Term Effects:

• Potential increased risk of osteosarcoma with prolonged use beyond 24 months

Adverse Drug Reactions (ADR):

• Hypercalcemia requiring dose reduction or discontinuation.
• Severe allergic reactions requiring immediate medical attention.

Contraindications

• Hypersensitivity to teriparatide or any of its components.
• Pre-existing hypercalcemia.
• Severe renal impairment.
• Metabolic bone diseases other than primary or glucocorticoid-induced osteoporosis (including Paget’s disease).
• Unexplained elevations of alkaline phosphatase.
• Prior external beam or implant radiation therapy involving the skeleton.
• Patients with skeletal malignancies or bone metastases.
• Pregnancy and breastfeeding.
• Open epiphyses (children and young adults).

Drug Interactions

• Digoxin: Monitor for digoxin toxicity.
• Diuretics (e.g., furosemide, hydrochlorothiazide): May increase the risk of hypercalcemia.
• Hormonal contraceptives: May reduce the effectiveness of hormonal contraceptives.
• Rifampin: May reduce the effectiveness of teriparatide.
• Warfarin: Close monitoring of INR is necessary.
• Supplemental calcium and vitamin D: Should be used if dietary intake is inadequate.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Not assigned. Teriparatide is contraindicated during pregnancy.

• Fetal Risks: Animal studies have shown an increased risk of skeletal abnormalities and growth retardation.

• Breastfeeding: Teriparatide is contraindicated during breastfeeding due to the potential risk of osteosarcoma and unknown effects on the infant.

Drug Profile Summary

• Mechanism of Action: Stimulates bone formation by activating osteoblasts.
• Side Effects: Nausea, headache, dizziness, leg cramps, injection site reactions, hypercalcemia, osteosarcoma risk.
• Contraindications: Hypercalcemia, severe renal impairment, metabolic bone diseases, skeletal malignancies, prior radiation therapy, pregnancy, breastfeeding.
• Drug Interactions: Digoxin, diuretics, hormonal contraceptives, rifampin, warfarin.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: 20 mcg subcutaneous daily for a maximum of 24 months.
• Monitoring Parameters: Serum calcium (if indicated), bone mineral density.

Popular Combinations

• Calcium and Vitamin D supplementation.

Precautions

• General Precautions: Monitor for signs of hypercalcemia and orthostatic hypotension. Ensure adequate calcium and vitamin D intake.
• Pregnant Women: Contraindicated.
• Breastfeeding Mothers: Contraindicated.
• Children & Elderly: Not recommended for children or young adults with open epiphyses. No dosage adjustment needed for the elderly.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Teriparatide?

A: The recommended dosage for adults is 20 mcg subcutaneously once daily. Teriparatide is not recommended for children.

Q2: What is the maximum duration of Teriparatide treatment?

A: The maximum lifetime duration of treatment is 24 months. This course should not be repeated.

Q3: How is Teriparatide administered?

A: Teriparatide is administered as a subcutaneous injection into the thigh or abdomen. Patients should be instructed on proper injection technique.

Q4: What are the serious side effects of Teriparatide?

A: Serious side effects can include osteosarcoma (bone cancer), hypercalcemia, and allergic reactions.

Q5: Can Teriparatide be used during pregnancy or breastfeeding?

A: No, Teriparatide is contraindicated during both pregnancy and breastfeeding.

Q6: What should be done if a dose of Teriparatide is missed?

A: If a dose is missed, inject it as soon as possible. If it is almost time for the next dose, skip the missed dose and return to the regular dosing schedule. Do not double the dose.

Q7: How should Teriparatide be stored?

A: Store teriparatide in the refrigerator (2°C to 8°C). Do not freeze. The pen can be kept at room temperature for up to 28 days once it has been used for the first time. Discard any unused portion after 28 days of first use, even if there is still medicine left.

Q8: What are the common drug interactions with Teriparatide?

A: Teriparatide can interact with digoxin, diuretics, and hormonal contraceptives. Close monitoring is necessary when these medications are co-administered.

Q9: Can Teriparatide be used in patients with renal impairment?

A: Teriparatide should not be used in patients with severe renal impairment. Use with caution in moderate renal impairment. No dose adjustment is required for mild to moderate renal impairment.

Q10: What are the signs of hypercalcemia to monitor for in patients taking Teriparatide?

A: Signs and symptoms of hypercalcemia can include nausea, vomiting, constipation, abdominal pain, muscle weakness, confusion, and increased thirst and urination. If these occur, prompt evaluation and management are necessary.