Gemtide

Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture

Gemtide is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, Gemtide reduces the risk of vertebral and nonvertebral fractures.

Increase of Bone Mass in Men with Primary or Hypogonadal Osteoporosis at High Risk for Fracture

Gemtide is indicated to increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy.

Treatment of Men and Women with Glucocorticoid-Induced Osteoporosis at High Risk for Fracture

Gemtide is indicated for the treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy.

Gemtide is a synthetic form of the natural human parathyroid hormone and is used by injection to treat osteoporosis. Gemtide forms new bone, increases bone mineral density and bone strength, and as a result reduces the chance of getting a fracture (broken bone). Gemtide can be used by men or postmenopausal women with osteoporosis who are at high risk for having fractures. Gemtide can be used by people who have had a fracture related to osteoporosis, or who have multiple risk factors for fracture, or who cannot use other osteoporosis treatments.

Gemtide has been used by injection into a vein as a test to help diagnose problems of the parathyroid gland. This test determines whether you have hypoparathyroidism or a type of pseudohypoparathyroidism.

This product, for use as a test to help diagnose problems of the parathyroid gland, was withdrawn from the U.S. market in January 1997.

Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture

The recommended dose is 20 mcg subcutaneously once a day.

Increase of Bone Mass in Men with Primary or Hypogonadal Osteoporosis at High Risk for Fracture

The recommended dose is 20 mcg subcutaneously once a day.

Treatment of Men and Women with Glucocorticoid-Induced Osteoporosis at High Risk for Fracture

The recommended dose is 20 mcg subcutaneously once a day.

Administration

• Gemtide should be administered as a subcutaneous injection into the thigh or abdominal wall. There are no data available on the safety or efficacy of intravenous or intramuscular injection of Gemtide.
• Gemtide should be administered initially under circumstances in which the patient can sit or lie down if symptoms of orthostatic hypotension occur.

• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Gemtide is a clear and colorless liquid. Do not use if solid particles appear or if the solution is cloudy or colored.

• Patients and caregivers who administer Gemtide should receive appropriate training and instruction on the proper use of the Gemtide delivery device from a qualified health professional.

Treatment Duration

The safety and efficacy of Gemtide have not been evaluated beyond 2 years of treatment. Consequently, use of the drug for more than 2 years during a patient's lifetime is not recommended.

How supplied

Dosage Forms And Strengths

Multi-dose prefilled delivery device (pen) for subcutaneous injection containing 28 daily doses of 20 mcg.

The Gemtide delivery device (pen) is available in the following package size:

2.4 mL prefilled delivery device NDC 0002-8400-01 (MS8400).

Storage and Handling

• The Gemtide delivery device should be stored under refrigeration at 2° to 8°C (36° to 46°F) at all times.
• Recap the delivery device when not in use to protect the cartridge from physical damage and light.
• During the use period, time out of the refrigerator should be minimized; the dose may be delivered immediately following removal from the refrigerator.
• Do not freeze. Do not use Gemtide if it has been frozen.

Revised: March 13, 2012. Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA

See also:
What is the most important information I should know about Gemtide?

Hypersensitivity to Gemtide or any of the excipients of Gemtide.

Preexisting hypercalcemia; metabolic bone diseases other than primary osteoporosis (including hyperparathyroidism and Paget's disease of the bone), unexplained elevations of alkaline phosphatase, prior external beam or implant radiation therapy to the skeleton, and patients with skeletal malignancies or bone metastases should be excluded from treatment with Gemtide.

Renal Impairment: Gemtide should not be used in patients with severe renal impairment. In patients with moderate renal impairment, Gemtide should be used with caution.

Use in pregnancy & lactation: Studies in rabbits have shown reproductive toxicity. The potential risk for humans is unknown. Gemtide should not be used during pregnancy or by breastfeeding women.

Gemtide is contraindicated for use during pregnancy or breastfeeding.

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.

Gemtide 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.

Gemtide 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 Gemtide for longer than 2 years unless your doctor tells you to.

Gemtide 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 Gemtide regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

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

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

Store the Gemtide 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.

Use: Labeled Indications

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

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

See also:
What other drugs will affect Gemtide?

Digoxin: A single Gemtide (rDNA origin) injection 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, because Gemtide (rDNA origin) injection may transiently increase serum calcium, Gemtide (rDNA origin) injection should be used with caution in patients taking digoxin.

Hydrochlorothiazide: The coadministration of hydrochlorothiazide 25 mg with Gemtide did not affect the serum calcium response to Gemtide 40 mcg. The effect of coadministration of a higher dose of hydrochlorothiazide with Gemtide on serum calcium levels has not been studied.

Furosemide: Coadministration of intravenous furosemide (20 to 100 mg) with Gemtide 40 mcg in healthy people and patients with mild, moderate or severe renal impairment (CrCl 13 to 72 mL/min) resulted in small increases in the serum calcium (2%) and 24-hour urine calcium (37%) responses to Gemtide that did not appear to be clinically important.

See also:
What are the possible side effects of Gemtide?

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 Gemtide 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 Gemtide 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 Gemtide group and 1% in the placebo group. The incidence of serious adverse events was 16% in Gemtide patients and 19% in placebo patients. Early discontinuation due to adverse events occurred in 7% of Gemtide 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 Gemtide-treated and more frequently than placebo-treated patients.

Table 1: Percentage of Patients with Adverse Events Reported by at Least 2% of Gemtide-Treated Patients and in More Gemtide-Treated Patients than Placebo-Treated Patients from the Two Principal Osteoporosis Trials in Women and Men Adverse Events are Shown Without Attribution of Causality

Immunogenicity — In the clinical trial, antibodies that cross-reacted with Gemtide were detected in 3% of women (15/541) receiving Gemtide. 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 — Gemtide 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 Gemtide 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 Gemtide. The number of patients treated with Gemtide whose transient hypercalcemia was verified on consecutive measurements was 3% of women and 1% of men.

Urinary Calcium — Gemtide increased urinary calcium excretion, but the frequency of hypercalciuria in clinical trials was similar for patients treated with Gemtide and placebo.

Serum Uric Acid — Gemtide increased serum uric acid concentrations. In clinical trials, 3% of Gemtide 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 Gemtide 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 Gemtide 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 Gemtide group and 6% in the active control group. The incidence of serious adverse events was 21% in Gemtide patients and 18% in active control patients, and included pneumonia (3% Gemtide, 1% active control). Early discontinuation because of adverse events occurred in 15% of Gemtide patients and 12% of active control patients, and included dizziness (2% Gemtide, 0% active control).

Adverse events reported at a higher incidence in the Gemtide group and with at least a 2% difference in Gemtide-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 Gemtide. 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 Gemtide use is unclear. Long term osteosarcoma surveillance studies are ongoing
• Hypercalcemia: Hypercalcemia greater than 13.0 mg/dL has been reported with Gemtide use.

Adverse events reported since market introduction that were temporally (but not necessarily causally) related to Gemtide 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

Each mL of Gemtide [recombinant-human parathyroid hormone (1-34)] injection contains: Recombinant human parathyroid hormone (1-34) 250 mcg, succinic acid USP/NF 0.29 mg, sodium hydroxide USP/NF 0/05 mg, glycerol USP/NF 50 mg, m-cresol USP/NF 3 mg, and water for injection USP/NF.

Gemtide (rDNA origin) contains recombinant human parathyroid hormone (1-34), and is also called rhPTH (1-34). It has an identical sequence to the 34 N-terminal amino acids (the biologically active region) of the 84-amino acid human parathyroid hormone. Gemtide has a molecular weight of 4117.8 daltons.

Gemtide (rDNA origin) is manufactured using a strain of Escherichia coli modified by recombinant DNA technology. Gemtide injection is available as a clear and colorless solution.

Excipients/Inactive ingredients: Succinic acid, USP/NF, sodium hydroxide USP/NF, glycerol USP/NF, m-cresol USP/NF, water for injection USP/NF.