Forteo

• Teriparatide (Forteo) is a prescription medicine used to treat osteoporosis, a bone disease that over time causes bones to become fragile and more likely to break. Teriparatide is similar to human parathyroid hormone (PTH) and is made using recombinant DNA (rDNA) technology. PTH is naturally produced by the body and is the key regulator of calcium and phosphate metabolism in the bone and kidney. Calcium and phosphate are the main minerals necessary for bone health. PTH also increases the absorption of calcium in the intestines. Teriparatide binds to the same receptors as natural PTH and mimics the favorable effects of PTH on bone health. Beneficial effects of teriparatide in osteoporosis treatment include reduced bone turnover, formation of new bone, and increased bone mineral density and bone strength.
• Teriparatide was first approved by the FDA in 2002.

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• Forteo injection should be used cautiously in patients taking digoxin (Lanoxin), a medication used to treat irregular heart rhythms. Forteo increases calcium in the blood and high levels of calcium may increase the risk for digoxin associated side effects.
• Forteo injection should be used cautiously with other medicines that may increase calcium in the blood.

Use this medication exactly as it was prescribed for you. Do not use the medication in larger amounts, or use it for longer than recommended by your doctor. Follow the instructions on your prescription label.

Teriparatide is given as an injection under the skin of the thigh or stomach. Your doctor, nurse, or other healthcare provider will give you this injection. You may be shown how to inject your medicine at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Use each disposable needle only one time. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

Teriparatide can cause you to feel dizzy or light-headed. It may help to sit or lie down for a short time after injecting the medication.

Do not use teriparatide for longer than 2 years unless your doctor tells you to.

Teriparatide is only part of a complete program of treatment that also includes diet, exercise, vitamins or mineral supplements, and changing certain behaviors. Follow your diet and exercise routines very closely.

It is important to use teriparatide regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Teriparatide can be injected at any time of the day. It may be easier to remember to use teriparatide if it is used at about the same time each day.

Do not teriparatide that is discolored or cloudy or that has particles in it. It should be clear and colorless. Do not use teriparatide after the expiration date printed on the pen or pen packaging.

Store the teriparatide injection pen in the refrigerator but do not allow it to freeze. Take the pen out of the refrigerator only long enough to use it. After use, recap the pen and put it back into the refrigerator.

Throw away the injection pen after 28 days of use, even if it still has medicine in it.

Seek medical attention if you think you have used too much of this medicine.

Overdose symptoms may include nausea, vomiting, dizziness, headache, feeling light-headed, or fainting.

Use the medication as soon as you remember the missed dose. If it is almost time for your next dose, skip the missed dose and use the medicine at your next regularly scheduled time. Do not use extra medicine to make up the missed dose.

Forteo is part of the drug class:

• PARATHYROID HORMONES AND ANALOGUES

Forteo can cause serious side effects including:

• 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 about all the medicines you take including prescription and non-prescription 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).

Tell your doctor if you are allergic to any of the ingredients in Forteo.

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

• 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 breastfeeding or plan to breastfeed. It is not known if Forteo passes into your breast milk. You and your doctor should decide if you will take Forteo or breastfeed. You should not do both.

Tell your healthcare provider about all the medicines you take including prescription and non-prescription 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).

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

• 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.
• 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 can not 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.

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.

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Treatment of Osteoporosis in Men and Postmenopausal Women

The safety of Forteo in the treatment of osteoporosis in men and postmenopausal women was assessed in two randomized, double-blind, placebo-controlled trials of 1382 patients (21% men, 79% women) aged 28 to 86 years (mean 67 years). The median durations of the trials were 11 months for men and 19 months for women, with 691 patients exposed to Forteo and 691 patients to placebo. All patients received 1000 mg of calcium plus at least 400 IU of vitamin D supplementation per day.

The incidence of all cause mortality was 1% in the Forteo group and 1% in the placebo group. The incidence of serious adverse events was 16% in Forteo patients and 19% in placebo patients. Early discontinuation due to adverse events occurred in 7% of Forteo patients and 6% of placebo patients.

Table 1 lists adverse events from the two principal osteoporosis trials in men and postmenopausal women that occurred in ≥2% of Forteo-treated and more frequently than placebo-treated patients.

Immunogenicity In the clinical trial, antibodies that cross-reacted with teriparatide were detected in 3% of women (15/541) receiving Forteo. Generally, antibodies were first detected following 12 months of treatment and diminished after withdrawal of therapy. There was no evidence of hypersensitivity reactions or allergic reactions among these patients. Antibody formation did not appear to have effects on serum calcium, or on bone mineral density (BMD) response.

Laboratory Findings

Serum Calcium Forteo transiently increased serum calcium, with the maximal effect observed at approximately 4 to 6 hours post-dose. Serum calcium measured at least 16 hours post-dose was not different from pretreatment levels. In clinical trials, the frequency of at least 1 episode of transient hypercalcemia in the 4 to 6 hours after Forteo administration was increased from 2% of women and none of the men treated with placebo to 11% of women and 6% of men treated with Forteo. The number of patients treated with Forteo whose transient hypercalcemia was verified on consecutive measurements was 3% of women and 1% of men.

Urinary Calcium Forteo increased urinary calcium excretion, but the frequency of hypercalciuria in clinical trials was similar for patients treated with Forteo and placebo [see Clinical Pharmacology (12.2)].

Serum Uric Acid Forteo increased serum uric acid concentrations. In clinical trials, 3% of Forteo patients had serum uric acid concentrations above the upper limit of normal compared with 1% of placebo patients. However, the hyperuricemia did not result in an increase in gout, arthralgia, or urolithiasis.

Renal Function No clinically important adverse renal effects were observed in clinical studies. Assessments included creatinine clearance; measurements of blood urea nitrogen (BUN), creatinine, and electrolytes in serum; urine specific gravity and pH; and examination of urine sediment.

Studies in Men and Women with Glucocorticoid-Induced Osteoporosis

The safety of Forteo in the treatment of men and women with 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 ≥ 5mg per day prednisone or equivalent for a minimum of 3 months. The duration of the trial was 18 months with 214 patients exposed to Forteo and 214 patients exposed to oral daily bisphosphonate (active control). All patients received 1000 mg of calcium plus 800 IU of vitamin D supplementation per day.

The incidence of all cause mortality was 4% in the Forteo group and 6% in the active control group. The incidence of serious adverse events was 21% in Forteo patients and 18% in active control patients, and included pneumonia (3% Forteo, 1% active control). Early discontinuation because of adverse events occurred in 15% of Forteo patients and 12% of active control patients, and included dizziness (2% Forteo, 0% active control).

Adverse events reported at a higher incidence in the Forteo group and with at least a 2% difference in Forteo-treated patients compared with active control-treated patients were: nausea (14%, 7%), gastritis (7%, 3%), pneumonia (6%, 3%), dyspnea (6%, 3%), insomnia (5%, 1%), anxiety (4%, 1%), and herpes zoster (3%, 1%), respectively.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Forteo. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Osteosarcoma: Cases of bone tumor and osteosarcoma have been reported rarely in the postmarketing period. The causality to Forteo use is unclear. Long term osteosarcoma surveillance studies are ongoing [see Warnings and Precautions (5.1)]
• Hypercalcemia: Hypercalcemia greater than 13.0 mg/dL has been reported with Forteo use.

Adverse events reported since market introduction that were temporally (but not necessarily causally) related to Forteo therapy include the following:

• Allergic Reactions: Anaphylactic reactions, drug hypersensitivity, angioedema, urticaria
• Investigations: Hyperuricemia
• Respiratory System: Acute dyspnea, chest pain
• Musculoskeletal: Muscle spasms of the leg or back
• Other: Injection site reactions including injection site pain, swelling and bruising; oro-facial edema

Pregnancy

Pregnancy Category C There are no adequate and well-controlled studies of Forteo in pregnant women. In animal studies, teriparatide increased skeletal deviations and variations in mouse offspring at doses more than 60 times the equivalent human dose and produced mild growth retardation and reduced motor activity in rat offspring at doses more than 120 times the equivalent human dose. Forteo should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In animal studies, pregnant mice received teriparatide during organogenesis at subcutaneous doses 8 to 267 times the human dose. At doses ≥ 60 times the human dose, the fetuses showed an increased incidence of skeletal deviations or variations (interrupted rib, extra vertebra or rib). When pregnant rats received subcutaneous teriparatide during organogenesis at doses 16 to 540 times the human dose, the fetuses showed no abnormal findings.

In a perinatal/postnatal study, pregnant rats received subcutaneous teriparatide from organogenesis through lactation. Mild growth retardation in female offspring at doses ≥120 times the human dose (based on surface area, mcg/m2). Mild growth retardation in male offspring and reduced motor activity in both male and female offspring occurred at maternal doses 540 times the human dose. There were no developmental or reproductive effects in mice or rats at doses 8 or 16 times the human dose, respectively.

Exposure multiples were normalized based on body surface area (mcg/m2). Actual animal doses: mice (30 to 1000 mcg/kg/day); rats (30 to 1000 mcg/kg/day).

Nursing Mothers

It is not known whether teriparatide is excreted in human milk. Because of the potential for tumorigenicity shown for teriparatide in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and efficacy of Forteo have not been established in any pediatric population. Forteo should not be prescribed in patients at an increased baseline risk of osteosarcoma which include pediatric and young adult patients with open epiphyses. Therefore, Forteo is not indicated for use in pediatric or young adult patients with open epiphyses [see Warnings and Precautions (5.1)].

Geriatric Use

Of the patients receiving Forteo in the osteoporosis trial of 1637 postmenopausal women, 75% were 65 years of age and over and 23% were 75 years of age and over. Of the patients receiving Forteo in the osteoporosis trial of 437 men, 39% were 65 years of age and over and 13% were 75 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Hepatic Impairment

No studies have been performed in patients with hepatic impairment. [see Clinical Pharmacology (12.3)].

Renal Impairment

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 [see Clinical Pharmacology (12.3)].

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 cell-surface 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

Pharmacodynamics in Men and Postmenopausal Women with Osteoporosis

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 (5.5) and Adverse Reactions (6.1)].

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 carboxy-terminal 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

Absorption 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.

Distribution 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.

Metabolism and Excretion 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.

Pediatric Patients Pharmacokinetic data in pediatric patients are not available [see Warnings and Precautions (5.1)].

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

Gender 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.

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

Renal Impairment 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 (8.7)].

Hepatic Impairment No studies have been performed in patients with hepatic impairment. Non-specific 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 (8.6)].

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 (7.1)].

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 (7.2)].

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 (7.3)].

Before using Forteo, tell your doctor if you are allergic to any drugs, or if you have:

• Paget's disease or other bone disorders (besides osteoporosis);

• high levels of calcium or alkaline phosphatase in your blood;

• a condition called hyperparathyroidism;

• a bone disease other than osteoporosis;

• a history of bone cancer or radiation treatment involving your bones; or

• if you have ever had kidney stones.

If you have any of these conditions, you may need a dose adjustment or special tests to safely use Forteo.

This medication has been found to cause an increased risk of bone cancer in animal studies. It is not known if this risk is also increased in humans treated with Forteo. Talk with your doctor about your individual risk.

Use this medication exactly as it was prescribed for you. Do not use the medication in larger amounts, or use it for longer than recommended by your doctor. Follow the instructions on your prescription label.

Forteo is given as an injection under the skin of the thigh or stomach. Your doctor, nurse, or other healthcare provider will give you this injection. You may be shown how to inject your medicine at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Use each disposable needle only one time. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

Do not use Forteo for longer than 2 years unless your doctor tells you to.

Forteo is only part of a complete program of treatment that also includes diet, exercise, vitamins or mineral supplements, and changing certain behaviors. Follow your diet and exercise routines very closely.

It is important to use Forteo regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Forteo can be injected at any time of the day. It may be easier to remember to use Forteo if it is used at about the same time each day.

Throw away the injection pen after 28 days of use, even if it still has medicine in it.

Teriparatide is a man-made form of parathyroid hormone that exists naturally in the body. Teriparatide increases bone mineral density and bone strength, which may prevent fractures.

Teriparatide is used to treat osteoporosis caused by menopause, steroid use, or gonadal failure. This medicine is for use when you have a high risk of bone fracture due to osteoporosis.

Teriparatide may also be used for purposes not listed in this medication guide.