Teriparatide

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using teriparatide and call your doctor at once if you have any of these serious side effects:

• feeling light-headed or fainting every time you inject this medicine;
• fast or pounding heartbeats every time you inject this medicine; or
• nausea, vomiting, constipation, and muscle weakness.

Less serious side effects may include:

• mild dizziness;
• pain, redness, bruising, itching, or swelling where the medicine was injected;
• leg cramps;
• joint pain;
• cough, sore throat, runny nose;
• headache or neck pain; or
• nausea, constipation, diarrhea.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Teriparatide can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Avoid smoking cigarettes, or try to quit smoking altogether. Smoking can reduce your bone mineral density, making fractures more likely.

Avoid drinking alcohol, which also may affect your bone mineral density.

Before using teriparatide, tell your doctor if you are taking digoxin (digitalis, Lanoxin, Lanoxicaps). You may need a dose adjustment or special tests to safely use teriparatide.

There may be other drugs not listed that can interact with teriparatide. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Mechanism Of Action

Endogenous 84-amino acid parathyroid hormone (PTH) is the primary regulator of calcium and phosphate metabolism in bone and kidney. Physiological actions of PTH include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption. The biological actions of PTH and teriparatide are mediated through binding to specific high-affinity cellsurface receptors. Teriparatide and the 34 N-terminal amino acids of PTH bind to these receptors with the same affinity and have the same physiological actions on bone and kidney. Teriparatide is not expected to accumulate in bone or other tissues.

The skeletal effects of teriparatide depend upon the pattern of systemic exposure. Once-daily administration of teriparatide stimulates new bone formation on trabecular and cortical (periosteal and/or endosteal) bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity. In monkey studies, teriparatide improved trabecular microarchitecture and increased bone mass and strength by stimulating new bone formation in both cancellous and cortical bone. In humans, the anabolic effects of teriparatide manifest as an increase in skeletal mass, an increase in markers of bone formation and resorption, and an increase in bone strength. By contrast, continuous excess of endogenous PTH, as occurs in hyperparathyroidism, may be detrimental to the skeleton because bone resorption may be stimulated more than bone formation.

Pharmacodynamics

Effects on Mineral Metabolism - Teriparatide affects calcium and phosphorus metabolism in a pattern consistent with the known actions of endogenous PTH (e.g., increases serum calcium and decreases serum phosphorus).

Serum Calcium Concentrations - When teriparatide 20 mcg is administered once daily, the serum calcium concentration increases transiently, beginning approximately 2 hours after dosing and reaching a maximum concentration between 4 and 6 hours (median increase, 0.4 mg/dL). The serum calcium concentration begins to decline approximately 6 hours after dosing and returns to baseline by 16 to 24 hours after each dose.

In a clinical study of postmenopausal women with osteoporosis, the median peak serum calcium concentration measured 4 to 6 hours after dosing with FORTEO (teriparatide 20 mcg) was 2.42 mmol/L (9.68 mg/dL) at 12 months. The peak serum calcium remained below 2.76 mmol/L (11.0 mg/dL) in > 99% of women at each visit. Sustained hypercalcemia was not observed.

In this study, 11.1% of women treated with FORTEO had at least 1 serum calcium value above the upper limit of normal [2.64 mmol/L (10.6 mg/dL)] compared with 1.5% of women treated with placebo. The percentage of women treated with FORTEO whose serum calcium was above the upper limit of normal on consecutive 4- to 6-hour post-dose measurements was 3.0% compared with 0.2% of women treated with placebo. In these women, calcium supplements and/or FORTEO doses were reduced. The timing of these dose reductions was at the discretion of the investigator. FORTEO dose adjustments were made at varying intervals after the first observation of increased serum calcium (median 21 weeks). During these intervals, there was no evidence of progressive increases in serum calcium.

In a clinical study of men with either primary or hypogonadal osteoporosis, the effects on serum calcium were similar to those observed in postmenopausal women. The median peak serum calcium concentration measured 4 to 6 hours after dosing with FORTEO was 2.35 mmol/L (9.44 mg/dL) at 12 months. The peak serum calcium remained below 2.76 mmol/L (11.0 mg/dL) in 98% of men at each visit. Sustained hypercalcemia was not observed.

In this study, 6.0% of men treated with FORTEO daily had at least 1 serum calcium value above the upper limit of normal [2.64 mmol/L (10.6 mg/dL)] compared with none of the men treated with placebo. The percentage of men treated with FORTEO whose serum calcium was above the upper limit of normal on consecutive measurements was 1.3% (2 men) compared with none of the men treated with placebo. Although calcium supplements and/or FORTEO doses could have been reduced in these men, only calcium supplementation was reduced [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].

In a clinical study of women previously treated for 18 to 39 months with raloxifene (n=26) or alendronate (n=33), mean serum calcium > 12 hours after FORTEO injection was increased by 0.09 to 0.14 mmol/L (0.36 to 0.56 mg/dL), after 1 to 6 months of FORTEO treatment compared with baseline. Of the women pretreated with raloxifene, 3 (11.5%) had a serum calcium > 2.76 mmol/L (11.0 mg/dL), and of those pretreated with alendronate, 3 (9.1%) had a serum calcium > 2.76 mmol/L (11.0 mg/dL). The highest serum calcium reported was 3.12 mmol/L (12.5 mg/dL). None of the women had symptoms of hypercalcemia. There were no placebo controls in this study.

In the study of patients with glucocorticoid-induced osteoporosis, the effects of FORTEO on serum calcium were similar to those observed in postmenopausal women with osteoporosis not taking glucocorticoids.

Urinary Calcium Excretion - In a clinical study of postmenopausal women with osteoporosis who received 1000 mg of supplemental calcium and at least 400 IU of vitamin D, daily FORTEO increased urinary calcium excretion. The median urinary excretion of calcium was 4.8 mmol/day (190 mg/day) at 6 months and 4.2 mmol/day (170 mg/day) at 12 months. These levels were 0.76 mmol/day (30 mg/day) and 0.3 mmol/day (12 mg/day) higher, respectively, than in women treated with placebo. The incidence of hypercalciuria ( > 7.5 mmol Ca/day or 300 mg/day) was similar in the women treated with FORTEO or placebo.

In a clinical study of men with either primary or hypogonadal osteoporosis who received 1000 mg of supplemental calcium and at least 400 IU of vitamin D, daily FORTEO had inconsistent effects on urinary calcium excretion. The median urinary excretion of calcium was 5.6 mmol/day (220 mg/day) at 1 month and 5.3 mmol/day (210 mg/day) at 6 months. These levels were 0.5 mmol/day (20 mg/day) higher and 0.2 mmol/day (8.0 mg/day) lower, respectively, than in men treated with placebo. The incidence of hypercalciuria ( > 7.5 mmol Ca/day or 300 mg/day) was similar in the men treated with FORTEO or placebo.

Phosphorus and Vitamin D - In single-dose studies, teriparatide produced transient phosphaturia and mild transient reductions in serum phosphorus concentration. However, hypophosphatemia ( < 0.74 mmol/L or 2.4 mg/dL) was not observed in clinical trials with FORTEO.

In clinical trials of daily FORTEO, the median serum concentration of 1,25-dihydroxyvitamin D was increased at 12 months by 19% in women and 14% in men, compared with baseline. In the placebo group, this concentration decreased by 2% in women and increased by 5% in men. The median serum 25- hydroxyvitamin D concentration at 12 months was decreased by 19% in women and 10% in men compared with baseline. In the placebo group, this concentration was unchanged in women and increased by 1% in men.

In the study of patients with glucocorticoid-induced osteoporosis, the effects of FORTEO on serum phosphorus were similar to those observed in postmenopausal women with osteoporosis not taking glucocorticoids.

Effects on Markers of Bone Turnover - Daily administration of FORTEO to men and postmenopausal women with osteoporosis in clinical studies stimulated bone formation, as shown by increases in the formation markers serum bone-specific alkaline phosphatase (BSAP) and procollagen I carboxyterminal propeptide (PICP). Data on biochemical markers of bone turnover were available for the first 12 months of treatment. Peak concentrations of PICP at 1 month of treatment were approximately 41% above baseline, followed by a decline to near-baseline values by 12 months. BSAP concentrations increased by 1 month of treatment and continued to rise more slowly from 6 through 12 months. The maximum increases of BSAP were 45% above baseline in women and 23% in men. After discontinuation of therapy, BSAP concentrations returned toward baseline. The increases in formation markers were accompanied by secondary increases in the markers of bone resorption: urinary N-telopeptide (NTX) and urinary deoxypyridinoline (DPD), consistent with the physiological coupling of bone formation and resorption in skeletal remodeling. Changes in BSAP, NTX, and DPD were lower in men than in women, possibly because of lower systemic exposure to teriparatide in men.

In the study of patients with glucocorticoid-induced osteoporosis, the effects of FORTEO on serum markers of bone turnover were similar to those observed in postmenopausal women with osteoporosis not taking glucocorticoids.

Pharmacokinetics

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.

Systemic clearance of teriparatide (approximately 62 L/hr in women and 94 L/hr in men) 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 the time required for absorption from the injection site.

No metabolism or excretion studies have been performed with teriparatide. However, the mechanisms of metabolism and elimination of PTH(1-34) and intact PTH have been extensively described in published literature. Peripheral metabolism of PTH is believed to occur by non-specific enzymatic mechanisms in the liver followed by excretion via the kidneys.

Pharmacokinetic data in pediatric patients are not available [see WARNINGS AND PRECAUTIONS].

No age-related differences in teriparatide pharmacokinetics were detected (range 31 to 85 years).

Although systemic exposure to teriparatide was approximately 20% to 30% lower in men than women, the recommended dose for both genders is 20 mcg/day.

The populations included in the pharmacokinetic analyses were 98.5% Caucasian. The influence of race has not been determined.

No pharmacokinetic differences were identified in 11 patients with mild or moderate renal impairment [creatinine clearance (CrCl) 30 to 72 mL/min] administered a single dose of teriparatide. In 5 patients with severe renal impairment (CrCl < 30 mL/min), the AUC and T1/2 of teriparatide were increased by 73% and 77%, respectively. Maximum serum concentration of teriparatide was not increased. No studies have been performed in patients undergoing dialysis for chronic renal failure [see Use in Specific Populations].

No studies have been performed in patients with hepatic impairment. Nonspecific proteolytic enzymes in the liver (possibly Kupffer cells) cleave PTH(1-34) and PTH(1-84) into fragments that are cleared from the circulation mainly by the kidney [see Use in Specific Populations].

Drug Interactions

Digoxin - In a study of 15 healthy people administered digoxin daily to steady state, a single FORTEO dose did not alter the effect of digoxin on the systolic time interval (from electrocardiographic Q-wave onset to aortic valve closure, a measure of digoxin's calcium-mediated cardiac effect). However, sporadic case reports have suggested that hypercalcemia may predispose patients to digitalis toxicity. Because FORTEO may transiently increase serum calcium, FORTEO should be used with caution in patients taking digoxin [see DRUG INTERACTIONS].

Hydrochlorothiazide - In a study of 20 healthy people, the coadministration of hydrochlorothiazide 25 mg with teriparatide did not affect the serum calcium response to teriparatide 40 mcg. The 24-hour urine excretion of calcium was reduced by a clinically unimportant amount (15%). The effect of coadministration of a higher dose of hydrochlorothiazide with teriparatide on serum calcium levels has not been studied [see DRUG INTERACTIONS].

Furosemide - In a study of 9 healthy people and 17 patients with mild, moderate, or severe renal impairment (CrCl 13 to 72 mL/min), coadministration of intravenous furosemide (20 to 100 mg) with teriparatide 40 mcg resulted in small increases in the serum calcium (2%) and 24-hour urine calcium (37%) responses to teriparatide that did not appear to be clinically important [see DRUG INTERACTIONS].

Animal Toxicology

In single-dose rodent studies using subcutaneous injection of teriparatide, no mortality was seen in rats given doses of 1000 mcg/kg (540 times the human dose based on surface area, mcg/m²) or in mice given 10,000 mcg/kg (2700 times the human dose based on surface area, mcg/m²).

In a long-term study, skeletally mature ovariectomized female monkeys (N=30 per treatment group) were given either daily subcutaneous teriparatide injections of 5 mcg/kg or vehicle. Following the 18-month treatment period, the monkeys were removed from teriparatide treatment and were observed for an additional 3 years. The 5 mcg/kg dose resulted in systemic exposures that were approximately 6 times higher than the systemic exposure observed in humans following a subcutaneous dose of 20 mcg (based on AUC comparison). Bone tumors were not detected by radiographic or histologic evaluation in any monkey in the study.

Clinical Studies

Treatment Of Osteoporosis In Postmenopausal Women

The safety and efficacy of once-daily FORTEO, median exposure of 19 months, were examined in a double-blind, multicenter, placebo-controlled clinical study of 1637 postmenopausal women with osteoporosis (FORTEO 20 mcg, n=541).

All women received 1000 mg of calcium and at least 400 IU of vitamin D per day. Baseline and endpoint spinal radiographs were evaluated using the semiquantitative scoring. Ninety percent of the women in the study had 1 or more radiographically diagnosed vertebral fractures at baseline. The primary efficacy endpoint was the occurrence of new radiographically diagnosed vertebral fractures defined as changes in the height of previously undeformed vertebrae. Such fractures are not necessarily symptomatic.

New Vertebral Fractures - FORTEO, when taken with calcium and vitamin D and compared with calcium and vitamin D alone, reduced the risk of 1 or more new vertebral fractures from 14.3% of women in the placebo group to 5.0% in the FORTEO group. This difference was statistically significant (p < 0.001); the absolute reduction in risk was 9.3% and the relative reduction was 65%. FORTEO was effective in reducing the risk for vertebral fractures regardless of age, baseline rate of bone turnover, or baseline BMD (see Table 2).

Table 2: Effect of FORTEO on Risk of Vertebral Fractures in Postmenopaus al Women with Osteoporosis

New Nonvertebral Osteoporotic Fractures - FORTEO significantly reduced the risk of any nonvertebral fracture from 5.5% in the placebo group to 2.6% in the FORTEO group (p < 0.05). The absolute reduction in risk was 2.9% and the relative reduction was 53%. The incidence of new nonvertebral fractures in the FORTEO group compared with the placebo group was ankle/foot (0.2%, 0.7%), hip (0.2%, 0.7%), humerus (0.4%, 0.4%), pelvis (0%, 0.6%), ribs (0.6%, 0.9%), wrist (0.4%, 1.3%), and other sites (1.1%, 1.5%), respectively.

The cumulative percentage of postmenopausal women with osteoporosis who sustained new nonvertebral fractures was lower in women treated with FORTEO than in women treated with placebo (see Figure 1).

Figure 1: Cumulative Percentage of Postmenopausal Women with Osteoporosis Sustaining New Nonvertebral Osteoporotic Fractures

Effect on Bone Mineral Density (BMD)

FORTEO increased lumbar spine BMD in postmenopausal women with osteoporosis. Statistically significant increases were seen at 3 months and continued throughout the treatment period. Postmenopausal women with osteoporosis who were treated with FORTEO had statistically significant increases in BMD from baseline to endpoint at the lumbar spine, femoral neck, total hip, and total body (see Table 3).

Table 3: Mean Percent Change in BMD from Baseline to Endpoint in Postmenopausal Women with Osteoporosis, Treated with FORTEO or Placebo for a Median of 19 Months

FORTEO treatment increased lumbar spine BMD from baseline in 96% of postmenopausal women treated. Seventy-two percent of patients treated with FORTEO achieved at least a 5% increase in spine BMD, and 44% gained 10% or more.

Both treatment groups lost height during the trial. The mean decreases were 3.61 and 2.81 mm in the placebo and FORTEO groups, respectively.

The effects of teriparatide on bone histology were evaluated in iliac crest biopsies of 35 postmenopausal women treated for 12 to 24 months with calcium and vitamin D and teriparatide 20 or 40 mcg/day. Normal mineralization was observed with no evidence of cellular toxicity. The new bone formed with teriparatide was of normal quality (as evidenced by the absence of woven bone and marrow fibrosis).

Treatment To Increase Bone Mass In Men With Primary Or Hypogonadal Osteoporosis

The safety and efficacy of once-daily FORTEO, median exposure of 10 months, were examined in a double-blind, multicenter, placebo-controlled clinical study of 437 men with either primary (idiopathic) or hypogonadal osteoporosis (FORTEO 20 mcg, n=151). All men received 1000 mg of calcium and at least 400 IU of vitamin D per day. The primary efficacy endpoint was change in lumbar spine BMD.

FORTEO increased lumbar spine BMD in men with primary or hypogonadal osteoporosis. Statistically significant increases were seen at 3 months and continued throughout the treatment period. FORTEO was effective in increasing lumbar spine BMD regardless of age, baseline rate of bone turnover, and baseline BMD. The effects of FORTEO at additional skeletal sites are shown in Table 4.

FORTEO treatment for a median of 10 months increased lumbar spine BMD from baseline in 94% of men treated. Fifty-three percent of patients treated with FORTEO achieved at least a 5% increase in spine BMD, and 14% gained 10% or more.

Table 4: Mean Percent Change in BMD from Baseline to Endpointa in Men with Primary or Hypogonadal Osteoporosis, Treated with FORTEO or Placebo for a Median of 10 Months

Treatment Of Men And Women With Glucocorticoid-Induced Osteoporosis

The efficacy of FORTEO for treating glucocorticoid-induced osteoporosis was assessed in a randomized, double-blind, active-controlled trial of 428 patients (19% men, 81% women) aged 22 to 89 years (mean 57 years) treated with ≥ 5 mg/day prednisone or equivalent for a minimum of 3 months. The duration of the trial was 18 months with 214 patients exposed to FORTEO. In the FORTEO group, the baseline median glucocorticoid dose was 7.5 mg/day and the median duration of glucocorticoid use was 1.5 years. The mean (SD) baseline lumbar spine BMD was 0.85 ± 0.13 g/cm² and lumbar spine BMD Tscore was -2.5 ± 1 (number of standard deviations below the mean BMD value for healthy adults). A total of 30% of patients had prevalent vertebral fracture(s) and 43% had prior non-vertebral fracture(s).  The patients had chronic rheumatologic, respiratory or other diseases that required sustained glucocorticoid therapy. All patients received 1000 mg of calcium plus 800 IU of vitamin D supplementation per day.

Because of differences in mechanism of action (anabolic vs. anti-resorptive) and lack of clarity regarding differences in BMD as an adequate predictor of fracture efficacy, data on the active comparator are not presented.

In patients with glucocorticoid-induced osteoporosis, FORTEO increased lumbar spine BMD compared with baseline at 3 months through 18 months of treatment. In patients treated with FORTEO, the mean percent change in BMD from baseline to endpoint was 7.2% at the lumbar spine, 3.6% at the total hip, and 3.7% at the femoral neck (p < 0.001 all sites). The relative treatment effects of FORTEO were consistent in subgroups defined by gender, age, geographic region, body mass index, underlying disease, prevalent vertebral fracture, baseline glucocorticoid dose, prior bisphosphonate use, and glucocorticoid discontinuation during trial.

FORTEO®
(for-TAY-o) teriparatide (rDNA origin) Injection

Read this Medication Guide before you start taking FORTEO® and each time you get a refill. There may be new information. Also, read the User Manual that comes with the FORTEO delivery device (pen) for information on how to use the device to inject your medicine the right way. This Medication Guide does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about FORTEO?

1. Possible bone cancer. During drug testing, the medicine in FORTEO caused some rats to develop a bone cancer called osteosarcoma. In people, osteosarcoma is a serious but rare cancer. Osteosarcoma has rarely been reported in people who took FORTEO. It is not known if people who take FORTEO have a higher chance of getting osteosarcoma.

2. You should not take FORTEO for more than 2 years over your lifetime.

3. There is a voluntary Patient Registry for people who take FORTEO. The purpose of the registry is to collect information about the possible risk of osteosarcoma in people who take FORTEO. For information about how to sign up for this patient registry, call 1-866-382-6813 or go to www.forteoregistry.rti.org.

What is FORTEO?

• FORTEO is a prescription medicine that is like a hormone made by the body called parathyroid hormone or PTH. FORTEO may help to form new bone, increase bone mineral density and bone strength.
• FORTEO can lessen the number of fractures of the spine and other bones in postmenopausal women with osteoporosis.
• The effect on fractures has not been studied in men.
• FORTEO is used in both men and postmenopausal women with osteoporosis who are at high risk for having fractures. FORTEO can be used by people who have had a fracture related to osteoporosis, or who have several risk factors for fracture, or who can not use other osteoporosis treatments.
• FORTEO is used in both men and women with osteoporosis due to use of glucocorticoid medicines, such as prednisone, for several months, who are at high risk for having broken bones (fractures). These include men and women with either a history of broken bones, who have several risk factors for fracture, or who can not use other osteoporosis treatments.

It is not known if FORTEO is safe and effective in children.

FORTEO should not be used in children and young adults whose bones are still growing.

Who should not use FORTEO?

Do not use FORTEO if you:

• are allergic to any of the ingredients in FORTEO. See the end of this Medication Guide for a complete list of the ingredients in FORTEO.

What should I tell my healthcare provider before taking FORTEO?

Before you take FORTEO, tell your healthcare provider if you:

• have the condition listed in the section “Who should not use FORTEO?”
• have Paget's disease or other bone disease
• have cancer in your bones
• have trouble injecting yourself and do not have someone who can help you
• are a child or young adult whose bones are still growing
• have or have had kidney stones
• have had radiation therapy
• have or had too much calcium in your blood
• have any other medical conditions
• are pregnant or thinking about becoming pregnant. It is not known if FORTEO will harm your unborn baby.
• are breast-feeding or plan to breast-feed. It is not known if FORTEO passes into your breast milk. You and your doctor should decide if you will take FORTEO or breast feed. You should not do both.

Tell your healthcare provider about all the medicines you take including prescription and nonprescription medicines, vitamins, and herbal supplements. Your healthcare provider needs this information to help keep you from taking FORTEO with other medicines that may harm you.

• Especially tell your doctor if you take medicines that contain digoxin (Digoxin®, Lanoxicaps®, Lanoxin®).

How should I use FORTEO?

• Inject FORTEO one time each day in your thigh or abdomen (lower stomach area). Talk to a healthcare provider about how to rotate injection sites.
• Before you try to inject FORTEO yourself, a healthcare provider should teach you how to use the FORTEO delivery device to give your injection the right way.
• Read the detailed User Manual at the end of this Medication Guide.
• You can take FORTEO with or without food or drink.
• The FORTEO delivery device has enough medicine for 28 days. It is set to give a 20 microgram dose of medicine each day. Do not inject all the medicine in the FORTEO delivery device at any one time.
• Do not transfer the medicine from the FORTEO delivery device to a syringe. This can result in taking the wrong dose of FORTEO. If you do not have pen needles to use with your FORTEO delivery device, talk with your healthcare provider.
• FORTEO should look clear and colorless. Do not use FORTEO if it has particles in it, or if it is cloudy or colored.
• Inject FORTEO right away after you take the delivery device out of the refrigerator.
• After each use, safely remove the needle, recap the delivery device, and put it back in the refrigerator right away.
• You can take FORTEO at any time of the day. To help you remember to take FORTEO, take it at about the same time each day.
• If you forget or cannot take FORTEO at your usual time, take it as soon as you can on that day. Do not take more than one injection in the same day.
• If you take more FORTEO than prescribed, call your healthcare provider. If you take too much FORTEO, you may have nausea, vomiting, weakness, or dizziness.

Follow your healthcare provider's instructions about other ways you can help your osteoporosis, such as exercise, diet, and reducing or stopping your use of tobacco and alcohol. If your healthcare provider recommends calcium and vitamin D supplements, you can take them at the same time you take FORTEO.

What are the possible side effects of FORTEO?

FORTEO can cause serious side effects including:

• See “What is the most important information I should know about FORTEO?”
• Decrease in blood pressure when you change positions. Some people feel dizzy, get a fast heartbeat, or feel faint right after the first few doses. This usually happens within 4 hours of taking FORTEO and goes away within a few hours. For the first few doses, take your injections of FORTEO in a place where you can sit or lie down right away if you get these symptoms. If your symptoms get worse or do not go away, stop taking FORTEO and call your healthcare provider.
• Increased calcium in your blood. Tell your healthcare provider if you have nausea, vomiting, constipation, low energy, or muscle weakness. These may be signs there is too much calcium in your blood.

Common side effects of FORTEO include:

• nausea
• joint aches
• pain

Your healthcare provider may take samples of blood and urine during treatment to check your response to FORTEO. Also, your healthcare provider may ask you to have follow-up tests of bone mineral density.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of FORTEO. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800- FDA-1088.

How should I store FORTEO?

• Keep your FORTEO delivery device in the refrigerator between 36° to 46°F (2° to 8°C).
• Do not freeze the FORTEO delivery device. Do not use FORTEO if it has been frozen.
• Do not use FORTEO after the expiration date printed on the delivery device and packaging.
• Throw away the FORTEO delivery device after 28 days even if it has medicine in it (see the User Manual).

Keep FORTEO and all medicines out of the reach of children.

General information about FORTEO

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use FORTEO for a condition for which it was not prescribed. Do not give FORTEO to other people, even if they have the same condition you have.

This Medication Guide summarizes the most important information about FORTEO. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about FORTEO that is written for healthcare professionals. For more information, go to www.FORTEO.com or call Lilly at 1-866-436-7836.

What are the ingredients in FORTEO?

Active ingredient: teriparatide

Inactive ingredients: glacial acetic acid, sodium acetate (anhydrous), mannitol, metacresol, and water for injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.

What is Osteoporosis?

Osteoporosis is a disease in which the bones become thin and weak, increasing the chance of having a broken bone. Osteoporosis usually causes no symptoms until a fracture happens. The most common fractures are in the spine (backbone). They can shorten height, even without causing pain. Over time, the spine can become curved or deformed and the body bent over. Fractures from osteoporosis can also happen in almost any bone in the body, for example, the wrist, rib, or hip. Once you have had a fracture, the chance for more fractures greatly increases.

The following risk factors increase your chance of getting fractures from osteoporosis:

• past broken bones from osteoporosis
• very low bone mineral density (BMD)
• frequent falls
• limited movement, such as using a wheelchair
• medical conditions likely to cause bone loss, such as some kinds of arthritis
• taking steroid medicines called glucocorticoids, such as prednisone
• other medicines that may cause bone loss, for example: seizure medicines (such as phenytoin), blood
• thinners (such as heparin), and high doses of vitamin A

This Medication Guide has been approved by the U.S. Food and Drug Administration.

*The brands listed are trademarks of their respective owners and are not trademarks * of Eli Lilly and Company.

Marketed by: Lilly USA, LLC, Indianapolis , IN 46285, USA. Medication Guide revised: August 30, 2013

FORTEO®
(for-TAY-o) teriparatide (rDNA origin) Injection

User Manual

Important: First read the Medication Guide that comes inside your FORTEO carton.

Before you use your new FORTEO delivery device, please read the entire front and back of this User Manual completely. Follow the directions carefully when using the FORTEO delivery device

Do not share your delivery device or needles because infection or disease can be spread from one person to another.

The FORTEO delivery device contains 28 days of medicine. Throw away the FORTEO delivery device after 28 days, even if it is not completely empty. Do not inject more than one dose of FORTEO in the same day.

Do not transfer FORTEO to a syringe.

Wash your hands before every injection. Prepare the injection site as your healthcare provider instructed.

1. Pull off white cap

Check the FORTEO delivery device label to make sure you have the right medicine and that it has not expired.

Do not use if the FORTEO delivery device looks damaged, if the medicine in the cartridge is not clear and colorless, or if it has particles in it.

2 Attach new Needle

Pull off paper tab.

Push needle straight onto medicine cartridge.

Screw on needle clockwise until firmly attached.

Pull off large needle cover and save it.

3. Set dose

Pull out black injection button until it stops.

If you cannot pull out the black injection button see Troubleshooting, Problem E, on back page.

Check to make sure red stripe shows.

Pull off small needle protector and throw away.

4. Inject dose

Gently hold a fold of skin on your thigh or abdomen and insert needle straight into skin.

Push in black injection button until it stops. Hold it in and count to 5 slowly. You must wait until the count of 5 to make sure you receive the correct dose. Then pull the needle from skin.

IMPORTANT

5. Confirm dose

After completing the injection: Once the needle is removed from the skin, take your thumb off the black injection button. Check to make sure the black injection button is all the way in. If the yellow shaft does not show, you have finished the injection steps the right way.

You should NOT see any of the yellow shaft. If you do and have already injected the medicine, do not inject yourself a second time on the same day. Instead, you MUST reset the FORTEO delivery device (see Troubleshooting, Problem A, on back page).

6. Remove needle

Put large needle cover on needle. Do not try to put the needle cover back on with your hands.

Unscrew the covered needle all the way by giving the large needle cover 3 to 5 counterclockwise turns.

Pull off needle and throw away in a puncture-resistant container.

Push white cap back on. Right after use, place FORTEO delivery device in the refrigerator.

For more information, or if you have any questions , turn to the back of this page.

FORTEO®
(for-TAY-o) teriparatide (rDNA origin) Injection

Troubles hooting

Problem

A. The yellow shaft is still showing after I push in the black injection button. How do I reset my FORTEO delivery device?

Solution

To reset the FORTEO delivery device, follow the steps below.

1. If you have already injected, DO NOT inject yourself a second time on the same day.
2. Remove the needle.
3. Attach a new needle, pull off the large needle cover and save it.
4. Pull out the black injection button until it stops. Check to make sure the red stripe shows.
5. Pull off the small needle protector and throw away.
6. Point the needle down into an empty container. Push in the black injection button until it stops. Hold it in and slowly count to five. You may see a small stream or drop of fluid. When you have finished, the black injection button should be all the way in.
7. If you still see the yellow shaft showing, contact Eli Lilly and Company (see Contact Information below) or your healthcare provider.
8. Put the large needle cover on needle. Unscrew the needle all the way by giving the needle cover 3 to 5 counter-clockwise turns. Pull off the covered needle and throw away as instructed by your healthcare provider. Push the white cap back on, and put your FORTEO delivery device in the refrigerator.

You can prevent this problem by always using a NEW needle for each injection, and by pushing the black injection button all the way in and slowly counting to five.

B. How can I tell if my FORTEO delivery device works ?

The black injection button should be all the way in to show that the full dose of medicine has been injected from the FORTEO delivery device.

Use a new needle every time you inject to be sure your FORTEO delivery device will work properly.

C. I see an air bubble in my FORTEO delivery device.

A small air bubble will not affect your dose and it will not harm you. You can continue to take your dose as usual.

D. I cannot get the needle off.

1. Put the large needle cover on the needle.
2. Use the large needle cover to unscrew the needle.
3. Unscrew the needle all the way by giving the large needle cover 3 to 5 counter-clockwise turns.
4. If you still cannot get the needle off, ask someone to help you.

E. What should I do if I have difficulty pulling out the black injection button?

Change to a new FORTEO delivery device to take your dose as instructed by your healthcare provider.

When the black injection button becomes hard to pull out, this means there is not enough medicine in your FORTEO delivery device for another dose. You may still see some medicine left in the cartridge.

Cleaning and Storage

Cleaning Your FORTEO Delivery Device

• Wipe the outside of the FORTEO delivery device with a damp cloth.
• Do not place the FORTEO delivery device in water, or wash or clean it with any liquid.

Storing Your FORTEO Delivery Device

• After each use, refrigerate the FORTEO delivery device right away. Read and follow the instructions in the Medication Guide section “How should I store FORTEO?”.
• Do not store the FORTEO delivery device with a needle attached. Doing this may cause air bubbles to form in the medicine cartridge.
• Store the FORTEO delivery device with the white cap on.
• Do not freeze FORTEO. If the FORTEO delivery device has been frozen, throw the device away and use a new FORTEO delivery device.
• If the FORTEO delivery device has been left out of the refrigerator, do not throw the delivery device away. Place the delivery device back in the refrigerator and call Eli Lilly and Company at 1- 866-4FORTEO (1-866-436-7836).

Other Important Notes

• The FORTEO delivery device contains 28 days of medicine.
• Do not transfer FORTEO to a syringe. This may result in you taking the wrong dose of medicine.
• Read and follow the instructions in the User Manual so that you use your FORTEO delivery device the right way.
• Check the FORTEO delivery device label to make sure you have the right medicine and that it has not expired.
• Do not use the FORTEO delivery device if it looks damaged. Look at the FORTEO medicine in the cartridge. If the medicine is not clear and colorless, or if it has particles, do not use it. Call Eli Lilly and Company if you notice any of these (see Contact Information).
• Use a new needle for each injection.
• During injection, you may hear one or more clicks - this is normal.
• The FORTEO delivery device is not recommended for use by the blind or by those who have vision problems without help from a person trained in the proper use of the device.
• Keep your FORTEO delivery device and needles out of the reach of children.

Disposal of Pen Needles and Delivery Device

Disposal of Pen Needles and the FORTEO Delivery Device

• Before throwing away the FORTEO delivery device, be sure to remove the pen needle.
• Throw away your FORTEO delivery device and used needles as instructed by your healthcare provider, local or state laws, or institutional policies.

Dis pose of the FORTEO delivery device 28 days after first use.

1 use date ______ / ______ / ______ Throw away after ______ / ______ / ______

Contact Information

If you have questions or need help with your FORTEO delivery device, contact Eli Lilly and Company at 1-866-4FORTEO (1-866-436-7836) or your healthcare provider.

For more information about FORTEO, go to www.FORTEO.com

Tell your doctor if you are breastfeeding or planning to breastfeed. It is not known if teriparatide is excreted in human breast milk or if it will harm your nursing baby.

• Inject teriparatide one time each day in your thigh or abdomen (lower stomach area). Talk to a healthcare provider about how to rotate injection sites.
• Before you try to inject teriparatide yourself, a healthcare provider should teach you how to use the teriparatide delivery device to give your injection the right way.
• You can take teriparatide with or without food or drink.
• The teriparatide delivery device has enough medicine for 28 days. It is set to give a 20 microgram dose of medicine each day. Do not inject all the medicine in the teriparatide delivery device at any one time.
• Do not transfer the medicine from the teriparatide delivery device to a syringe. This can result in taking the wrong dose of teriparatide. If you do not have pen needles to use with your teriparatide delivery device, talk with your healthcare provider.
• Teriparatide should look clear and colorless. Do not use teriparatide if it has particles in it, or if it is cloudy or colored.
• Inject teriparatide right away after you take the delivery device out of the refrigerator.
• After each use, safely remove the needle, recap the delivery device, and put it back in the refrigerator right away.
• You can take teriparatide at any time of the day. To help you remember to take teriparatide, take it at about the same time each day.
• If you forget or can not take teriparatide at your usual time, take it as soon as you can on that day. Do not take more than one injection in the same day.
• If you take more teriparatide than prescribed, call your healthcare provider. If you take too much teriparatide, you may have nausea, vomiting, weakness or dizziness.
• Follow your healthcare provider's instructions about other ways you can help your osteoporosis, such as exercise, diet, and reducing or stopping your use of tobacco and alcohol. If your healthcare provider recommends calcium and vitamin D supplements, you can take them at the same time you take teriparatide.

The recommended teriparatide dose is 20 mcg given subcutaneously once a day. Your doctor will determine the best dose for you. Take teriparatide exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

If you take too much teriparatide, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If teriparatide is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Storage

Parenteral

2–8°C; do not freeze.1

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of high or low blood pressure like very bad headache or dizziness, passing out, change in eyesight.
• Signs of high calcium levels like weakness, confusion, feeling tired, headache, upset stomach and throwing up, hard stools (constipation), or bone pain.
• Back pain, belly pain, or blood in the urine. May be signs of a kidney stone.
• Feeling very tired or weak.
• Muscle weakness.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time teriparatide is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take teriparatide 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 teriparatide. 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.

Review Date: October 4, 2017

(ter i PAR a tide)

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

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

Administration advice:
-The use of this drug for more than 2 years has not been evaluated and is not recommended.
-This drug should be administered initially under circumstances in which the patient can sit or lie down if symptoms of orthostatic hypotension occur.

General:
-Adequate intake of calcium and vitamin D should be ensured. When therapy has been ceased, patients may be continued on other osteoporosis therapies.
-Patients should receive education on the proper injection techniques of this drug.
-Data are not available on the safety or efficacy of IV or IM administration of this drug.

Storage requirements:
-The pens for subcutaneous administration should be stored between 2 to 8 degrees C (36 to 46 degrees F), and should be administered as soon as possible after removal from the refrigerator.
-Each pen should be used within 28 days after the first injection.
-This drug should not be frozen.
-The delivery device should be recapped when not in use to protect the cartridge from physical damage and light.