Forteo

Parathyroid Hormone Analogs and Modifiers

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Teriparatide solution should be clear and colorless.
Use of the Forteo formulation for more than 2 years during a patient's lifetime should only be considered if a patient remains at or has returned to having a high risk for fracture.
Use of the Bonsity formulation for more than 2 years during a patient's lifetime is not recommended.

Administer subcutaneously only. Do not inject intramuscularly or intravenously.
Administer the first dose under circumstances where the patient can sit or lie down if symptoms of orthostatic hypotension occur.
Patients and/or caregivers who administer teriparatide should receive appropriate training and instruction on the proper use of the prefilled delivery device (pen) from a qualified health care professional.
 
Subcutaneous Administration (Forteo or Bonsity Pen)
Inject subcutaneously into the thigh or abdomen.
Lightly pinch a fold of skin; insert the needle at a 90-degree angle. Push in the pen injection button until it stops. Hold it in and count to 5 slowly. Wait until the count of 5 to make sure the correct dose is administered. Then pull the needle from skin.
Properly dispose of used pen needles.
Rotate administration sites with each injection to prevent lipodystrophy.
The pen should never be shared among patients. Even if the disposable needle is changed, sharing may result in transmission of hepatitis viruses, HIV, or other blood-borne pathogens. Do not share pens among multiple patients; reserve the use of any pen for 1 patient only.
Storage: Store the pen under refrigeration at 2 to 8 degrees C (36 to 46 degrees F) at all times except when administering the product. Do not freeze. Do not use if the device has been frozen. Do not store the pen with the needle on, as the medication may leak out or air bubbles may form in the cartridge. Recap the delivery device when not in use to protect the cartridge from physical damage and light. During each use, time out of the refrigerator should be minimized; the dose may be delivered immediately following removal from the refrigerator. Each pen can be used for up to 28 days after the first injection. After 28 days, discard the pen, even if it still contains unused solution.

anaphylactic shock / Rapid / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
angioedema / Rapid / 0-1.0
calciphylaxis / Delayed / Incidence not known
osteogenic sarcoma / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known

hypercalcemia / Delayed / 1.0-10.0
hypertension / Early / 7.1-7.1
dyspnea / Early / 3.6-6.0
constipation / Delayed / 5.4-5.4
orthostatic hypotension / Delayed / 5.0-5.0
depression / Delayed / 4.1-4.1
antibody formation / Delayed / 2.2-3.0
angina / Early / 2.5-2.5
phosphaturia / Early / Incidence not known
hypercalciuria / Delayed / Incidence not known
hypomagnesemia / Delayed / Incidence not known

nausea / Early / 8.5-14.0
arthralgia / Delayed / 10.1-10.1
muscle cramps / Delayed / 1.0-10.0
rhinitis / Early / 9.6-9.6
asthenia / Delayed / 8.7-8.7
dizziness / Early / 8.0-8.0
headache / Early / 7.5-7.5
cough / Delayed / 6.4-6.4
pharyngitis / Delayed / 5.5-5.5
dyspepsia / Early / 5.2-5.2
diarrhea / Early / 5.1-5.1
rash / Early / 4.9-4.9
insomnia / Early / 4.3-4.3
vertigo / Early / 3.8-3.8
vomiting / Early / 3.0-3.0
syncope / Early / 2.6-2.6
diaphoresis / Early / 2.2-2.2
urticaria / Rapid / 0-1.0
injection site reaction / Rapid / Incidence not known

FORTEO

Rx

Recombinant human parathyroid hormone
Used for the treatment of osteoporosis in patients with high risk of fracture
Boxed warning regarding the risk of osteosarcoma; not recommended for use in patients at risk for osteosarcoma

20 mcg subcutaneously once daily. Patients at high risk of fracture are defined as those with history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. Supplement calcium and vitamin D if dietary intake is inadequate. Follow teriparatide treatment with a bisphosphonate or denosumab to prevent decline in bone density and loss of efficacy against fracture. Use of the Forteo formulation for more than 2 years during a patient's lifetime should only be considered if a patient remains at or has returned to having a high risk for fracture. Use of the Bonsity formulation for more than 2 years during a patient's lifetime is not recommended. The North American Menopause Society (NAMS) recommends that use of parathyroid analogs in postmenopausal women be reserved for those patients with a high risk of fracture who do not have hypercalcemia, bone metastases, any bone tumor-predisposing disorder, or a history of skeletal irradiation.

20 mcg subcutaneously once daily. Use of the Forteo formulation for more than 2 years during a patient's lifetime should only be considered if a patient remains at or has returned to having a high risk for fracture. Use of the Bonsity formulation for more than 2 years during a patient's lifetime is not recommended. Patients at high risk of fracture are defined as those with history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. Supplement calcium and vitamin D if dietary intake is inadequate.

Teriparatide has been investigated off-label for hypoparathyroidism, but the role of the drug for treatment of these patients is not established. Typical dosage used in open-label trials is 20 mcg subcutaneously once or twice daily. More study is needed to determine if teriparatide has a role in the treatment of these patients.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are necessary.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are necessary.

Calcium: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Digoxin: (Minor) Sporadic case reports have suggested that hypercalcemia may predispose patients to digitalis toxicity. Because teriparatide increases serum calcium it should be used with caution in patients taking digoxin. Administering a single dose of teriparatide to patients with steady state digoxin levels did not alter the effect of digoxin on the systolic time interval.

Forteo/Teriparatide Subcutaneous Inj Sol: 1mL, 250mcg

20 mcg/day subcutaneously for osteoporosis.

20 mcg/day subcutaneously for osteoporosis.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Mechanism of Action: Teriparatide is a recombinant amino terminal fragment of parathyroid hormone (PTH), comprised of the first 34 amino acids of PTH which produce most of its chief biologic effects. Endogenous PTH is the primary regulator of calcium and phosphate metabolism in the bone and kidney; it acts directly on the bone and kidney and also acts indirectly on the intestine to increase serum calcium concentrations. Teriparatide affects calcium and phosphorus metabolism in a pattern consistent with the known actions of endogenous PTH (i.e., increases serum calcium and decreases serum phosphorous.) Teriparatide binds to the same receptors as PTH and is known to exert effects identical to that of PTH on the bone and the kidney. Studies have shown teriparatide to be an effective treatment for patients with hypoparathyroidism.PTH and teriparatide stimulate bone formation and resorption and can increase or decrease bone mass, depending on the level of exposure. Continuous infusions and intermittent subcutaneous injections of these agents stimulate bone formation similarly but have different effects on bone resorption and bone mass. Continuous infusions result in persistent elevation of serum PTH and teriparatide concentrations which lead to greater bone resorption, while intermittent (i.e. once or twice daily) injections provide a transient increase in serum concentrations and preferentially stimulate osteoblastic activity over osteoclastic activity, resulting in a net stimulation of new bone formation, particularly on the trabecular, endocortical, endosteal, and periosteal bone surfaces.Teriparatide's anabolic effects manifest as in increase in skeletal mass, increase in the number of osteoblasts and osteoclasts allowing for an increase in bone remodeling, and an increase in bone strength. Osteoblasts have PTH receptors where teriparatide binds and stimulates bone-forming effects. Osteoclasts do not have PTH receptors, but appear to be activated by cytokines and other biochemical precursors that are released by stimulated osteoblasts. Teriparatide binds to the plasma-membrane receptors on osteoblasts and increases intracellular production of cyclic adenosine monophosphate (cAMP) and adenyl cyclase (AC). The release of cAMP and AC triggers osteogenesis, and cAMP prompts the release of genes that drive the accumulation of osteoblasts and osteogenesis. The net result of increased number of osteoblasts and increased osteogenesis is increased bone mass and bone strength.

Teriparatide is administered as a subcutaneous injection. Systemic clearance (approximately 62 L/hour in women and 94 L/hour in men) of teriparatide exceeds the rate of normal liver plasma flow, consistent with both hepatic and extra-hepatic clearance. Volume of distribution following intravenous injection is approximately 0.12 L/kg. Intersubject variability in systemic clearance and volume of distribution is 25% to 50%. The half-life of teriparatide in serum is 5 minutes when administered by intravenous injection and approximately 1 hour when administered by subcutaneous injection. The longer half-life following subcutaneous administration reflects absorption from the injection site. Peripheral metabolism of intact PTH, the 34 N-terminal amino acids, and, presumably, teriparatide, is believed to occur by non-specific enzymatic mechanisms in the liver followed by excretion via the kidneys.
 
Affected cytochrome P450 isoenzymes and drug transporters: None

Teriparatide is absorbed after subcutaneous injection; the absolute bioavailability is approximately 95% based on pooled data from 20-, 40-, and 80-mcg doses. The rates of absorption and elimination are rapid. The peptide reaches peak serum concentrations about 30 minutes after subcutaneous injection of a 20-mcg dose and declines to non-quantifiable concentrations within 3 hours. Pharmacokinetic data from another brand of injection (20-mcg dose) results in a Cmax of 109.5 +/- 62.8 pg/mL (mean +/- SD) at a median Tmax of 0.25 hours (0.12 minimum, 1.08 maximum). Concentrations decline to non-quantifiable within 3 hours.

Consider discontinuing teriparatide when pregnancy is recognized. There are no available data regarding the use of teriparatide in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.  In animal reproduction studies, teriparatide increased skeletal deviations and variations in mouse offspring at subcutaneous doses equivalent to more than 60 times the recommended 20 mcg human daily dose (based on body surface area), and the drug produced mild growth retardation and reduced motor activity in rat offspring at subcutaneous doses equivalent to more than 120 times the human dose.

It is not known whether teriparatide is excreted in human milk, affects human milk production, or has effects on the breastfed infant. Because of the potential for osteosarcoma shown with teriparatide in animal studies, advise patients that breast-feeding is not recommended during treatment.