Active ingredients: Teriparatide
FORSTEO 20 micrograms / 80 microliters solution for injection in pre-filled pen
Indications Why is Forsteo used? What is it for?
FORSTEO contains the active ingredient teriparatide which is used to make bones stronger and reduce the risk of fractures by stimulating bone rebuilding.
FORSTEO is used to treat osteoporosis in adults. Osteoporosis is a disease that causes bones to become thin and brittle. This disease is particularly common in women after menopause, but it can also occur in men. Osteoporosis is also common in patients being treated with corticosteroids.
Contraindications When Forsteo should not be used
Do not take FORSTEO
- If you are allergic to teriparatide or any of the other ingredients of this medicine
- If you have high calcium levels (pre-existing hypercalcaemia).
- If you have severe kidney problems.
- If you have ever been diagnosed with bone cancer or other cancers that have spread (metastasized) to your bone.
- If you have other bone diseases. If you have bone disease, please tell your doctor.
- If you have high levels of alkaline phosphatase of unknown nature in your blood, this means you may have Paget's disease of bone (a disease with abnormal bone changes). If you are not sure, ask your doctor.
- If you have had radiation therapy that involved your bones.
- If you are pregnant or breastfeeding.
Precautions for use What you need to know before you take Forsteo
Forsteo can cause an increase in the amount of calcium in the blood or urine.
Talk to your doctor or pharmacist before or while taking FORSTEO:
- if you continually have nausea, vomiting, constipation, low energy or muscle weakness. These may be signs that there is too much calcium in the blood.
- if you suffer from kidney stones or if you have experienced kidney stones.
- if you have kidney problems (moderate renal impairment).
Some patients experience dizziness or a rapid heartbeat after taking the first few doses. When taking the first few doses, if you feel dizzy, inject FORSTEO in a place where you can sit or lie down.
The recommended treatment period of 24 months should not be exceeded.
FORSTEO should not be used in growing adults.
Children and adolescents
FORSTEO should not be used in children and adolescents (under 18 years of age).
Interactions Which drugs or foods can modify the effect of Forsteo
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, as they may occasionally interact (e.g. digoxin / digitalis, a medicine used to treat heart disease).
Warnings It is important to know that:
Pregnancy and breastfeeding
Do not take FORSTEO if you are pregnant or if you are breast-feeding. If you are a woman of childbearing potential, you must use effective methods of contraception while using FORSTEO. If you are pregnant, FORSTEO should be discontinued. Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
Some patients may feel dizzy after injecting FORSTEO. If you feel dizzy, do not drive or operate machinery until you feel better.
Important information about some of the ingredients of FORSTEO
This medicinal product contains less than 1 mmol sodium (23 mg) per dose. This means it is basically "sodium free".
Dose, Method and Time of Administration How to use Forsteo: Posology
Always take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
The recommended dose is 20 micrograms given once a day by injection under the skin (subcutaneous injection) in the thigh or abdomen. To help you remember to take your medicine, you inject it at the same time each day.
Inject FORSTEO every day for as long as your doctor has prescribed. The total duration of treatment with FORSTEO should not exceed 24 months. You must not receive more than 24 months of treatment for the rest of your life.
FORSTEO can be injected at mealtimes.
Read the user manual, which is included in the carton, for instructions on how to use the pen containing FORSTEO.
Injection needles are not included in the pen package. It can use Becton, Dickinson and Company injection pen needles 29 to 31 gauge (0.25 to 0.33mm in diameter) and 5, 8 and 12.7mm in length.
You must inject FORSTEO within a short time after taking the pen from the refrigerator as described in the user manual. After use, immediately return the pen to the refrigerator. Use a new needle for each injection and discard it each time after use. Never store your pen with the needle inserted. Never share your FORSTEO pen with other people.
Your doctor may advise you to take FORSTEO with calcium and vitamin D. Your doctor will tell you how much calcium and vitamin D to take each day.
FORSTEO can be taken with or without meals.
Overdose What to do if you have taken too much Forsteo
If you take more FORSTEO than you should
If, by mistake, you have taken more FORSTEO than you should, contact your doctor or pharmacist.
Effects of an overdose that might be expected include nausea, vomiting, dizziness and headache.
If you forget or cannot take FORSTEO when you usually do, take it during the day as soon as possible. Do not take a double dose to make up for a forgotten dose. Do not take more than one injection on the same day. Do not try to make up for a missed dose.
If you stop taking FORSTEO
If you are considering stopping FORSTEO treatment, please discuss this with your doctor. Your doctor will advise you and decide how long FORSTEO should be treated.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Forsteo
Like all medicines, this medicine can cause side effects, although not everybody gets them. The most common side effects are pain in the limbs (frequency is very common, may affect more than 1 in 10 people) and feelings of nausea, headache and dizziness (frequency is common).
If you feel dizzy after the injection, you should sit or lie down until you feel better. If you do not feel better, you should call a doctor before continuing treatment. Cases of fainting have been reported in association with treatment. use of teriparatide.
If you experience discomfort such as skin redness, pain, swelling, itching, a small localized hematoma or minimal bleeding around the injection site (frequency is common), this should resolve within a few days or weeks. Otherwise, tell your doctor as soon as possible.
Some patients have experienced allergic reactions within a short time after injection, including breathlessness, facial swelling, rash and chest pain (frequency is rare). In rare cases, serious and potentially life-threatening allergic reactions may occur including the anaphylaxis.
Other side effects include:
Common: may affect up to 1 in 10 people
- increased blood cholesterol levels
- depression
- neuralgic pain in the legs
- feeling of weakness
- irregular heartbeats
- breathlessness
- increased sweating
- muscle cramps
- loss of energy
- tiredness
- chest pain
- decrease in blood pressure
- heartburn (painful or burning sensation felt just below the breastbone)
- generally feeling unwell (vomiting)
- the presence of a herniated duct that carries food into the stomach
- decrease in hemoglobin or in the number of red blood cells (anemia)
Uncommon: may affect up to 1 in 100 people
- increased heart rate
- abnormal heart sounds
- wheezing
- hemorrhoids
- involuntary loss or leakage of urine
- increased need to eliminate fluids
- weight gain
- kidney stones
- pain in the muscles and pain in the joints. Some patients have experienced severe cramping or back pain that required hospitalization.
- increase in blood calcium levels
- increased levels of uric acid in the blood
- increase in an enzyme called alkaline phosphatase
Rare: may affect up to 1 in 1,000 people
- reduced renal function, including renal impairment
- swelling, especially in the hands, feet and legs
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V * By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and pen after EXP. The expiry date refers to the last day of that month.
FORSTEO must always be stored in the refrigerator (2 ° C to 8 ° C).
You can use FORSTEO for up to 28 days after the first injection, during which time the pen is stored in the refrigerator (2 ° C - 8 ° C). Do not freeze FORSTEO. Avoid placing pens near the ice compartment in the refrigerator to prevent freezing. Do not use FORSTEO if it is or has been frozen.
After 28 days, each pen should be discarded properly, even if it is not completely empty.
FORSTEO contains a colorless and clear solution. Do not use FORSTEO if you notice solid particles or if the solution appears cloudy or colored.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What FORSTEO contains
- The active ingredient is teriparatide. Each milliliter of solution for injection contains 250 micrograms of teriparatide.
- The other ingredients are glacial acetic acid, sodium acetate (anhydrous), mannitol, metacresol and water for injections. Additionally, hydrochloric acid solution and / or sodium hydroxide solution may have been added for pH adjustment.
Description of the appearance of FORSTEO and contents of the pack
FORSTEO is a colorless and clear solution. FORSTEO is supplied in a cartridge contained in a pre-filled pen. Each pen contains 2.4 mL of solution sufficient for 28 doses. The pens are available in cases containing one or three pens. Not all pack sizes may be available.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
FORSTEO 20 mcg / 80 MICROLITERS SOLUTION FOR INJECTION IN A PRE-FILLED PEN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 80 microlitre dose contains 20 mcg of teriparatide *.
One 2.4 mL pre-filled pen contains 600 mcg of teriparatide (corresponding to a concentration of 250 mcg per milliliter).
* Teriparatide, rhPTH (1-34), produced in E. coli using recombinant DNA technology, is identical to the 34 N-terminal amino acid sequence of endogenous human parathyroid hormone.
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Injectable solution.
Colorless, clear solution.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
FORSTEO is indicated in adults.
Treatment of osteoporosis in postmenopausal women and men at increased risk of fracture (see section 5.1). In postmenopausal women, a significant reduction in the incidence of vertebral and non-vertebral fractures has been demonstrated, but not femoral fractures.
Treatment of osteoporosis induced by prolonged systemic glucocorticoid therapy in women and men at increased risk of fracture (see section 5.1).
04.2 Posology and method of administration
Dosage
The recommended dose of FORSTEO is 20 micrograms administered once daily.
The maximum total duration of FORSTEO treatment should be 24 months (see section 4.4). The treatment with FORSTEO lasting 24 months must not be repeated over the patient's life span.
Supplementation with calcium and vitamin D is recommended in patients whose dietary intake of these substances is inadequate.
After the conclusion of FORSTEO therapy, patients can continue with other therapies for osteoporosis.
Special populations
Patients with renal impairment
In patients with severe renal impairment, FORSTEO must not be used (see section 4.3).In patients with moderate renal impairment, FORSTEO should be used with caution. In patients with mild renal impairment, no special caution is required.
Patients with hepatic impairment
There are no data available in patients with hepatic impairment (see section 5.3). Therefore, FORSTEO should be used with caution.
Pediatric population and young adults with unsealed epiphyses
The safety and efficacy of FORSTEO in children and adolescents under the age of 18 has not been established. FORSTEO should not be used in pediatric patients (below 18 years), or in young adults with unsealed epiphyses.
Elderly patients
No dose adjustment is required based on age (see section 5.2).
Method of administration
FORSTEO should be administered once daily by subcutaneous injection in the thigh or abdomen.
Patients should be instructed to follow appropriate injection techniques (see section 6.6). A User Manual is also available to instruct patients in the correct use of the pen.
04.3 Contraindications
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
• Pregnancy and lactation (see sections 4.4 and 4.6).
• Pre-existing hypercalcemia.
• Severe renal insufficiency.
• Metabolic bone diseases (including hyperparathyroidism and Paget's disease of the bone)
other than primary osteoporosis and glucocorticoid-induced osteoporosis.
• Unjustified increases in alkaline phosphatase.
• Previous radiation therapy of the skeleton from an external source or an internal source (implant).
• Patients with skeletal malignancies or bone metastases should be excluded from treatment with teriparatide.
04.4 Special warnings and appropriate precautions for use
Calcemia and calcuria
In patients with normal calcium levels, transient and mild increases in serum calcium concentrations have been observed after teriparatide injection. After each dose of teriparatide, serum calcium concentrations peak between 4 and 6 hours and then return to baseline within 16 to 24 hours. Therefore, if blood samples are taken for calcium measurements, this should be done at least 16 hours after the most recent FORSTEO injection. Routine calcium monitoring is not required during therapy.
FORSTEO may cause small increases in urinary calcium elimination, but the incidence of hypercalciuria was not different from that seen in patients treated with placebo in clinical trials.
Urolithiasis
FORSTEO has not been studied in patients with active urolithiasis. FORSTEO should be used with caution in patients with active or recent urolithiasis as it can potentially worsen this condition.
Orthostatic hypotension
In short-term clinical trials with FORSTEO, isolated episodes of transient orthostatic hypotension have been observed. These events generally began within 4 hours of dose administration and resolved spontaneously within minutes to a few hours. In the case of transient orthostatic hypotension, this occurred following the first administrations, was attenuated by making the subjects assume a lying position and did not preclude the continuation of treatment.
Renal impairment
Caution should be observed in patients with moderate renal impairment.
Younger adult population
In the younger adult population, including premenopausal women, experience is limited (see section 5.1). In this population group, treatment should only be started if the benefit clearly outweighs the risks.
Women of childbearing potential should use effective contraception while using FORSTEO. If pregnancy occurs, the use of FORSTEO should be discontinued.
Duration of treatment
Studies in rats with long-term administration of teriparatide indicate a higher incidence of osteosarcoma (see section 5.3). Until further clinical data are available, the recommended treatment duration of 24 months should not be exceeded.
04.5 Interactions with other medicinal products and other forms of interaction
In a study of 15 healthy subjects administered digoxin daily until steady-state was reached, a single dose of FORSTEO did not alter the cardiac effect of digoxin. However, sporadic case reports have suggested that hypercalcaemia may predispose patients to a digitalis toxicity. Since FORSTEO causes transient increases in calcium, FORSTEO should be used with caution in patients taking digitalis.
FORSTEO has been evaluated in pharmacodynamic interaction studies with hydrochlorothiazide. No clinically significant interactions were observed.
Co-administration of raloxifene or hormone replacement therapy with FORSTEO did not change the effects of FORSTEO on serum or urinary calcium or adverse clinical events.
04.6 Pregnancy and lactation
Women of childbearing age / Contraception in women
Women of childbearing potential should use effective contraception while using FORSTEO. If pregnancy occurs, the use of FORSTEO should be discontinued.
Pregnancy
The use of FORSTEO is contraindicated during pregnancy (see section 4.3).
Feeding time
The use of FORSTEO is contraindicated during breastfeeding. It is unknown whether teriparatide is excreted in human milk.
Fertility
Studies in rabbits have shown reproductive toxicity (see section 5.3). The effect of teriparatide on human fetal development has not been studied. The potential risk to humans is unknown.
04.7 Effects on ability to drive and use machines
FORSTEO has no or negligible influence on the ability to drive or use machines. Transiently, orthostatic hypotension or dizziness has been observed in some patients. These patients should refrain from driving or using machines until symptoms have disappeared.
04.8 Undesirable effects
Summary of the safety profile
The most commonly reported adverse reactions in patients treated with FORSTEO are nausea, pain in limb, headache and dizziness.
Table of adverse reactions
In clinical trials with teriparatide, 82.8% of FORSTEO-treated patients and 84.5% of placebo-treated patients reported at least 1 adverse event.
Adverse reactions associated with the use of teriparatide in clinical trials for osteoporosis and post-marketing are summarized in the table below. The following convention has been used for the classification of adverse reactions: very common (≥ 1/10), common (≥ 1/100 and
* Severe cases of back cramp or pain have been reported within minutes after injection.
Description of selected adverse reactions
In clinical trials the following reactions were reported with a ≥ 1% difference in frequency compared to placebo: vertigo, nausea, pain in limb, dizziness, depression, dyspnoea.
FORSTEO increases serum concentrations of uric acid. In clinical trials, 2.8% of FORSTEO-treated patients had serum uric acid concentrations above the upper limit of normal compared with 0.7% of placebo-treated patients. However, hyperuricaemia did not lead to an increase in cases of gout, arthralgia, or urolithiasis.
In a large clinical study, antibodies cross-reacting with teriparatide were found in 2.8% of women who received FORSTEO. Usually, antibodies were initially detected after 12 months of treatment and decreased after cessation of therapy. There was no evidence of hypersensitivity reactions, allergic reactions, effects on calcium levels or effects on bone mineral density response (Bone Mineral Density, BMD).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.
04.9 Overdose
Signs and symptoms
FORSTEO was administered in single doses up to 100 mcg and in repeated doses up to 60 mcg / day for 6 weeks.
Effects of overdose that might be expected include delayed hypercalcaemia and the risk of orthostatic hypotension. Nausea, vomiting, dizziness and headache may also occur.
Overdose experience based on post-marketing spontaneous reports Among the post-marketing spontaneous reports, there have been cases of medication errors in which the entire contents of the teriparatide pen (up to 800 mcg) had been administered as a single dose. Transient events reported included nausea, weakness / lethargy and hypotension In some cases, no adverse events occurred following overdose No fatalities associated with overdose have been reported.
Treatment of overdose
There is no specific antidote for FORSTEO. Treatment of a suspected overdose should include transient discontinuation of FORSTEO, monitoring of calcium, and the implementation of appropriate supportive measures, such as hydration.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Calcium-homeostatic, parathyroid hormones and analogues, ATC code: H05 AA02.
Mechanism of action
Endogenous parathyroid hormone (PTH) with 84 amino acids is the main regulator of calcium and phosphate metabolism in bones and kidneys. FORSTEO (rhPTH (1-34)) is the active (1-34) fragment of parathyroid hormone endogenous human. The physiological actions of PTH include the stimulation of osteogenesis by direct effects on the cells responsible for the formation of bone (osteoblasts) indirectly increasing the intestinal absorption of calcium and increasing the tubular reabsorption of calcium and the renal elimination of phosphate.
Pharmacodynamic effects
FORSTEO is a bone-replenishing substance for the treatment of osteoporosis. The effects of FORSTEO on the skeleton depend on the type of systemic exposure. Administration of FORSTEO once daily increases the apposition of new bone on the trabecular and cortical surfaces of the body. bone by preferential stimulation of the osteoblastic activity compared to the osteoclastic one.
Clinical efficacy
Risk factors
Independent risk factors, such as low BMD, age, existence of a previous fracture, family history of proximal femoral extremity fractures, high bone turnover and low body mass index should be considered in order to identify women and men at increased risk of osteoporotic fractures who could benefit from treatment.
Premenopausal women with glucocorticoid-induced osteoporosis should be considered at high risk of fracture if they have a prevalent fracture or a combination of risk factors that place them at high risk of fracture (e.g., low bone density [e.g., T-score ≤ -2]), prolonged high-dose glucocorticoid therapy [eg, ≥ 7.5 mg / day for at least 6 months], marked underlying disease activity, low levels of sex steroids).
Postmenopausal osteoporosis
The main study included 1,637 postmenopausal women (with a mean age of 69.5 years). At baseline, 90% of patients had one or more vertebral fractures and, on average, vertebral BMD was 0.82 g / cm2 (equivalent to a T-score = -2.6). Each day all patients received 1,000 mg of calcium and at least 400 IU of vitamin D. Results after a period of treatment with FORSTEO up to 24 months (mean: 19 months) demonstrate a statistically significant reduction in fracture (Table 1). To prevent one or more new vertebral fractures, 11 women had to be treated for an average of 19 months.
Table 1
Abbreviations: N = number of randomized patients assigned to each treatment group;
CI = Confidence Interval.
a The incidence of vertebral fractures was evaluated in 448 patients treated with placebo and in 444 patients treated with FORSTEO, who had x-rays of the spine at baseline and subsequently
bp ≤ 0.001 compared with placebo
c There has been no evidence of a significant reduction in the incidence of femoral fractures
dp ≤ 0.025 compared with placebo
After a treatment period (mean) of 19 months, bone mineral density (BMD) increased in the lumbar spine and the whole femur by 9% and 4%, respectively, compared to placebo (p
Post-treatment fracture efficacy: Following treatment with FORSTEO, 1,262 postmenopausal women from the pivotal study were enrolled in a post-treatment follow-up study. The primary objective of the study was to collect data on the safety of FORSTEO. During this observation period, other treatments for osteoporosis were allowed and additional evaluation of vertebral fractures was performed.
During a mean of 18 months after cessation of FORSTEO treatment, there was a 41% (p = 0.004) reduction compared to placebo in the number of patients with a minimum of one new vertebral fracture.
In an open-label study, 503 postmenopausal women with severe osteoporosis and a fragility fracture in the previous 3 years (83% had received prior osteoporosis therapy) were treated with FORSTEO for up to 24 months. At 24 months, l "Mean increase from baseline in BMD in lumbar spine, total femur, and femoral neck was 10.5%, 2.6%, and 3.9%, respectively. From 18 to 24 months, the mean increase in BMD in the lumbar spine, the whole femur, and the femoral neck was 1.4%, 1.2%, and 1.6%, respectively.
Male osteoporosis
437 male patients (mean age 58.7 years) with hypogonadal osteoporosis (defined by low morning free testosterone levels or high FSH or LH) or idiopathic were enrolled in a clinical trial. The mean baseline BMD T-scores of the spine and femoral neck were -2.2 and -2.1, respectively. At baseline, 35% of patients had had a vertebral fracture and 59% had had a non-vertebral fracture.
All patients received 1,000 mg of calcium and at least 400 IU of vitamin D daily. Lumbar spine BMD increased significantly within 3 months. After 12 months, BMD had increased in the lumbar spine and the whole femur by 5% and 1%, respectively, compared to placebo. However, no significant effect on fracture frequencies was demonstrated. .
Glucocorticoid-induced osteoporosis
The efficacy of FORSTEO in men and women (N = 428) receiving prolonged systemic glucocorticoid therapy (equivalent to 5 or more mg prednisone for at least 3 months) was demonstrated in the initial 18 months of a study lasting 36-month total, double-blind, randomized, and active comparator-controlled (alendronate 10 mg / day). At baseline, 28% of patients had one or more radiographically confirmed vertebral fractures. All patients received 1,000 mg daily. calcium and 800 IU of vitamin D.
This study included postmenopausal women (N = 277), premenopausal women (N = 67), and men (N = 83). At baseline, postmenopausal women had a mean age of 61 years, lumbar spine BMD with a mean T-score of -2.7, mean an equivalent prednisone dose of 7.5 mg / day, and 34% had one or more radiographically confirmed vertebral fractures; premenopausal women had a mean age of 37 years, lumbar spine BMD with mean T-score of -2.5, on average one dose
prednisone equivalent of 10 mg / day, and 9% had one or more radiographically confirmed vertebral fractures; men had a mean age of 57 years, lumbar spine BMD with a mean T-score of -2.2, mean an equivalent dose of prednisone of 10 mg / day, and 24% had one or more radiographically confirmed vertebral fractures.
69% of patients completed the 18 months of the initial phase. At the end of 18 months, FORSTEO had significantly increased lumbar spine BMD (7.2%) compared to alendronate (3.4%) (p
Between 18 and 24 months in patients treated with teriparatide, BMD increased by an additional 1.7%, 0.9% and 0 respectively in the lumbar spine, the whole femur and the femoral neck. , 4%.
At 36 months, analysis of spine radiographs of 169 alendronate-treated patients and 173 FORSTEO-treated patients showed that 13 patients in the alendronate-treated group (7.7%) had experienced a new vertebral fracture compared with 3 patients in the FORSTEO group (1.7%) (p = 0.01). In addition, 15 of 214 patients in the alendronate group (7.0%) had a non-vertebral fracture compared with 16 of 214 patients in the alendronate group. FORSTEO (7.5%) (p = 0.84).
In premenopausal women, the increase in BMD from baseline to end during the 18 months of observation was significantly greater in the FORSTEO group than in the lumbar spine group (4.2% compared with alendronate). - 1.9%; p
05.2 "Pharmacokinetic properties
Distribution
The volume of distribution is approximately 1.7 L / kg. The half-life of FORSTEO is approximately 1 hour when administered subcutaneously, reflecting the time required for absorption from the injection site.
Biotransformation
No metabolism and elimination studies have been performed with FORSTEO but peripheral parathyroid hormone metabolism is believed to occur primarily in the liver and kidneys.
Elimination
FORSTEO is eliminated by hepatic and extra-hepatic clearance (approximately 62 L / hour in women and
94 L / hour in men).
Elderly patients
There were no differences in the pharmacokinetics of FORSTEO with respect to age (range 31 to 85 years). No dose adjustment is required based on age.
05.3 Preclinical safety data
Teriparatide was not genotoxic in a standard series of tests, nor did it produce teratogenic effects in rats, mice or rabbits. No major effects were observed in pregnant rats and mice administered teriparatide at daily doses of 30 to 1,000 mcg / kg. However, in pregnant rabbits given daily doses of 3 to 100 mcg / kg there was fetal resorption and reduced offspring. The embryotoxicity observed in rabbits may be related to their greater sensitivity to the effects of PTH on blood ionized calcium compared to rodents.
Rats treated with daily injections for a period of time approximately equal to their lifespan had excessive dose-dependent bone reconstitution and an increased incidence of osteosarcoma most likely due to an epigenetic mechanism. Teriparatide did not increase the incidence of any other type of malignancy in rats. Due to differences in bone physiology between rats and humans, the clinical significance of these findings is likely to be minor. No bone tumors have been observed in the ovariectomized monkeys treated for 18 months or during a 3-year follow-up period after treatment discontinuation In addition, no osteosarcoma was observed in clinical trials or during the post-treatment follow-up study.
Animal studies have shown that markedly reduced hepatic blood flow decreases PTH exposure to the major cleavage system (liver Kupffer cells) and, consequently, PTH clearance (1-84).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Glacial acetic acid
Sodium acetate (anhydrous)
Mannitol
Metacresol
Hydrochloric acid (for pH adjustment)
Sodium hydroxide (for pH adjustment)
Water for injections
06.2 Incompatibility
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
06.3 Period of validity
2 years.
The chemical, physical and microbiological stability of the product in use has been demonstrated for 28 days at a temperature between 2 ° C and 8 ° C. After first use, the product can be stored for up to 28 days at a temperature between 2 ° C and 8 ° C. Other methods and storage times of the product in use are the responsibility of the user.
06.4 Special precautions for storage
Always store in the refrigerator (2 ° C-8 ° C). Immediately after use, the pen should be returned to the refrigerator. Do not freeze.
Do not store the injection device with the needle inserted.
06.5 Nature of the immediate packaging and contents of the package
2.4 mL of solution in cartridge (Type I siliconized glass), with a plunger (halobutyl rubber), disc closure (polyisoprene / bromobutyl rubber laminate) / aluminum assembled in a pen device.
FORSTEO is available in packs of 1 and 3 pens. Each pen contains 28 doses of
20 mcg (for 80 microliters).
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
FORSTEO is supplied with a pre-filled pen. Each pen is for use by one patient only. A new, sterile needle should be used for each injection. Each FORSTEO package is supplied with a user manual which fully describes how to use the pen. Needles are not included in the package. The device can be used with injection needles for the insulin pen. After each injection, the FORSTEO pen should be placed in the refrigerator.
FORSTEO should not be used if the solution appears cloudy, colored or contains particles. Also refer to the user manual for instructions on how to use the pen.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Eli Lilly Nederland B.V., Grootslag 1-5, NL-3991 RA Houten, The Netherlands.
08.0 MARKETING AUTHORIZATION NUMBER
EU / 1/03/247 / 001-002
035926017
035926029
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 10 June 2003. Date of most recent renewal: 10 June 2013.
10.0 DATE OF REVISION OF THE TEXT
D.CCE April 2015