Teriparatide injection

Pharmacological action Endogenous parathyroid hormone (PTH) consists of 84 amino acids and is the main regulator of calcium and phosphate metabolism in the bone and kidney. Forteo (rhPTH (1-34)) is the active fragment (1-34) of endogenous human parathyroid hormone. The physiological effects of PTH include direct action on osteoblasts to stimulate bone formation, indirect increase in intestinal calcium absorption, increase tubular calcium reabsorption and enhance renal excretion of phosphate. Forteo is a bone forming agent used to treat osteoporosis. The effect of Forteo on bone depends on the systemic exposure mode. Once-daily injection of Forteo can increase the accumulation of new bone on the surface of cancellous and cortical bones by preferentially stimulating osteoblast activity (relative to osteoclast activity). Toxicity studies Genotoxicity: Forteo did not show genotoxicity in standard combination tests. Reproductive toxicity: Forteo did not show teratogenic effects in rats, mice and rabbits. No serious reactions were found when pregnant rats or mice were given 30 to 1000 μg/kg of teriparatide daily. However, daily administration of 3 to 100 μg/kg of Forteo to pregnant rabbits resulted in embryo resorption and reduced litter size. The embryotoxicity observed in rabbits may be due to the fact that rabbits are more sensitive to the effects of PTH on serum calcium ions than rodents. Carcinogenicity: Two carcinogenicity bioassays were conducted in 344 Fischer rats. In the first study, male and female rats were given teriparatide 5, 30, or 75 mg/kg/day subcutaneously daily for 24 months starting at 2 months of age. These doses resulted in systemic exposures that were 3, 20, and 60 times higher than those observed in humans at a dose of 20 mg/kg/day, respectively (based on AUC comparisons). Teriparatide treatment resulted in a dose-related increase in the incidence of osteosarcoma, a rare malignant bone tumor, in male and female rats. Osteosarcoma was observed at all doses, with a morbidity rate of 40%-50% in the high-dose group. Teriparatide also caused a dose-related increase in the incidence of osteoblastomas and osteomas in both male and female rats. No osteosarcomas, osteoblastomas, or osteomas were observed in the untreated control group. Bone tumor development in rats was associated with bone mass and localized osteoblast hyperplasia. A second study was conducted over 2 years to determine the effects of treatment duration and age of the animals on the development of bone tumors. Female rats aged 2 to 26 months were treated subcutaneously with 5 mg/kg and 30 mg/kg (doses corresponding to 3-20 times the human exposure at the 20 mg dose based on AUC comparisons). This study showed that the development of osteosarcomas, osteoblastomas, and osteomas was dose- and exposure-dependent. Bone tumors were observed in immature rats aged 2 months treated with 30 mg/kg/day for 24 months and in rats treated with either 5 mg/kg/day or 30 mg/kg/day for 6 months. Bone tumors were also observed in mature rats aged 6 months who were treated with 30 mg/kg/day for 6 or 20 months. No tumors were detected in mature rats aged 6 months who were treated with 5 mg/kg/day for 6 or 20 months. The results did not show a difference in susceptibility to bone tumor formation associated with teriparatide treatment between mature and immature rats. The relevance of these animal studies to humans has not been determined. Other: Animal studies have shown that severely reduced hepatic blood flow reduces PTH exposure to the major clearance system (Kupffer cells), resulting in a corresponding reduction in the clearance of PTH (1-84).

The main ingredient is teriparatide. Excipients: glacial acetic acid, sodium acetate (anhydrous), mannitol, m-cresol (2.4mg/ml-3.3mg/ml), hydrochloric acid, sodium hydroxide, water for injection, hydrochloric acid and/or sodium hydroxide can be added to adjust the pH value.

Colorless clear liquid.

The recommended dose of this product is 20 micrograms per day for subcutaneous injection. The injection site should be the thigh or abdomen. Patients should be instructed to use the correct injection method. Patients can also refer to the user manual attached to this product to use the injection pen correctly. The maximum total treatment time of this product is 24 months. Patients can only receive a 24-month treatment once in their lifetime. If the diet cannot meet the needs, patients should supplement calcium and vitamin D. After stopping the treatment of this product, patients can continue other osteoporosis treatments. Patients with renal insufficiency: This product should not be used in patients with severe renal insufficiency. This product should be used with caution in patients with moderate renal insufficiency. Patients with hepatic insufficiency: No studies have been conducted in patients with hepatic insufficiency, and it should be used with caution under the guidance of a doctor. Children and adolescents with open epiphyses: There is no experience of using this product in adolescents under 18 years of age. This product should not be used in adolescents under 18 years of age and young people with open epiphyses. Elderly medication: No dosage adjustment is required according to age. Injection pen use guide For detailed operation diagrams and injection instructions for the injection pen, please refer to the "Injection Pen Use Manual" attached to the packaging box of this product. Important Note: Please read the "Injection Pen User Manual" carefully before using this injection pen. If you do not follow the instructions in full, incorrect dosage, damage to the injection pen or infection may occur. This product is a pre-filled pen syringe, and each pen is for use by one patient only. A new sterile injection needle must be used for each injection. The injection pen user manual is included in the package. This product does not contain a needle. You can use an insulin injection pen needle. After each injection, this product should be returned to the refrigerator for storage. If the solution is cloudy, colored or has particles, it must not be used. Please refer to the injection pen user manual for the use of the injection pen. Please follow local regulations for the disposal of unused products and waste.

In clinical trials of teriparatide, 82.8% and 84.5% of patients in the Forteo and placebo groups, respectively, reported at least one adverse reaction. The most commonly reported adverse reactions in patients treated with Forteo were nausea, limb pain, dizziness, and vertigo. The following table lists the adverse reactions associated with the use of teriparatide in clinical studies for the treatment of osteoporosis and after the product is marketed. The frequency of adverse reactions is defined as follows: Very common (≥1/10), Common (≥1/100 and examination Uncommon: weight gain, heart murmur, increased alkaline phosphatase Cardiac abnormalities Common: palpitations Uncommon: tachycardia Blood and lymphatic system abnormalities Common: anemia Nervous system abnormalities Common: dizziness, headache, sciatica Unknown: syncope Ear and vagus nerve abnormalities Common: dizziness, breathing Thoracic and mediastinal abnormalities Common: dyspnea Uncommon: emphysema Gastrointestinal abnormalities Common: nausea, vomiting, hiatal hernia Gastroesophageal reflux disease Uncommon: hemorrhoids Kidney and urinary system abnormalities Uncommon: incontinence, polyuria, frequent urination, urgency Unknown: renal failure/renal damage Skin and subcutaneous tissue abnormalities Common: Increased sweating Musculoskeletal and connective tissue disorders Very common: Limb pain Common: Muscle cramps Uncommon: Myalgia, arthralgia Unknown: Back spasm/pain* Metabolic and nutritional disorders Common: Hypercholesterolemia Uncommon: Blood calcium higher than 2.76mmol/L, hyperuricemia Rare: Blood calcium higher than 3.25mmol/L Vascular disorders Common: Hypotension Systemic and injection site abnormalities Common: Fatigue, chest pain, weakness, transient mild reactions at the injection site, including: pain, swelling, erythema, local abrasions, itching and mild bleeding at the injection site. Uncommon: Injection site erythema, injection site reactions Rare: Allergic reactions that may occur within a period of time after injection: Acute dyspnea/facial edema, Generalized urticaria, chest pain, edema (primarily peripheral) Nervous system abnormalities Common: Depression* Severe back spasms or pain have been reported within minutes of injection. In clinical trials, the following reactions were reported at ≥1% compared to placebo: dizziness, nausea, pain in limb, lightheadedness, depression, dyspnea. Forteo increases serum uric acid concentrations. In clinical trials, 2.8% of patients in the Forteo group had serum uric acid concentrations above the upper limit of normal, while 0.7% of patients in the placebo group had serum uric acid concentrations above the upper limit. However, hyperuricemia did not lead to an increased incidence of gout, arthralgia, or urolithiasis. In a large clinical trial, hyperuricemia was detected in 2.8% of women treated with Forteo. Teriparatide has cross-reactive antibodies. Usually, antibodies are first detected after 12 months of treatment with Forteo and disappear after treatment is stopped. There is no evidence of hypersensitivity and allergic reactions, and there is no effect on the response to blood calcium and bone mineral density (BMD). The clinical trial study conducted in China was a Phase III open-label, multicenter, active-controlled, randomized non-hospitalized clinical study that compared teriparatide (20 μg/day) and calcitonin (200 IU/day) in the treatment of osteoporosis in men and postmenopausal women during a 24-week treatment period. A total of 364 patients (329 women and 35 men) were enrolled. One case of myocardial infarction that was possibly related to the drug occurred.

Patients who are allergic to teriparatide or any of the excipients of Forteo. Pregnant and lactating women. Patients with hypercalcemia. Patients with severe renal insufficiency. Other bone metabolic diseases other than primary osteoporosis and glucocorticoid-induced osteoporosis (including hyperparathyroidism and Paget's disease). Unexplained elevation of alkaline phosphatase. Patients who have previously received external irradiation or bone implant radiotherapy. Forteo's treatment scope should exclude patients with bone malignancies or bone metastases. View full text

Pediatric Precautions: The safety and efficacy of Forteo have not been established in any pediatric population. Forteo should not be used in patients with an increased risk of osteosarcoma at baseline, including children and young adults with unclosed epiphyses. Therefore, Forteo is not indicated for use in children and young adults with unclosed epiphyses. Precautions during pregnancy and lactation: General Advice Studies in rabbits have shown Forteo to be reproductively toxic. Studies on the effects of Forteo on human fetal development have not been conducted. The potential risk to humans is unknown. It is not known whether teriparatide is excreted in human milk. Forteo is contraindicated in pregnant and lactating women. Women of childbearing potential should use effective contraceptive measures while using Forteo. If pregnancy occurs, Forteo should be discontinued. Precautions for the Elderly: In a trial of 1,637 postmenopausal women with osteoporosis treated with Forteo, 75% were 65 years of age or older and 23% were 75 years of age or older. No overall differences in safety and effectiveness were observed between these subjects and younger subjects, and other clinical experience reports have not found different responses between elderly and younger patients, but it cannot be ruled out that some elderly people are more sensitive to the drug. No differences in the pharmacokinetics of Forteo were observed with age (31 to 85 years). No dose adjustment is required based on age.

A pharmacodynamic interaction study between Forteo and hydrochlorothiazide has been conducted and no clinically significant interaction was found. Co-administration of Forteo with raloxifene or hormone replacement therapy did not alter the effects of Forteo on serum or urinary calcium, nor did it change its clinical adverse reactions. In a study of 15 healthy subjects taking digoxin daily to steady-state levels, a single dose of Forteo did not alter the effects of digoxin on the heart. However, there are anecdotal case reports suggesting that hypercalcemia may lead to digitalis toxicity in patients. Because Forteo can transiently increase serum calcium levels, Forteo should be used with caution in patients taking digitalis.

The product should be stored in a refrigerated environment at 2°C to 8°C and away from light. The injection pen should be returned to the refrigerator immediately after use. Do not freeze. Do not store the injection pen with the needle installed.

20μg:80μl, 2.4ml/vial.

24 months. The data from the chemical, physical and microbiological stability tests of Futiao during its use period support a shelf life of 28 days when stored at 2-8°C. Once used, Futiao can be stored at 2-8°C for up to 28 days. If Futiao is used beyond the above storage time and storage conditions, it is the responsibility of the user.