Teriparatide Injection 20mg is a recombinant human parathyroid hormone analogue (PTH 1-34), and its active ingredient has the same sequence as the 34th N-terminal amino acid (bioactive region) of the 84-amino acid human parathyroid hormone. This drug stimulates bone formation and reduces bone resorption by mimicking the action of endogenous parathyroid hormone, thereby increasing bone density and reducing the risk of fractures. The common specifications currently available on the market are 20μg:80μl, 2.4ml per vial, meaning each injection contains 20μg of teriparatide.
In the clinical trial of teriparatide, 82.8% and 84.5% of the patients in the placebo group reported at least one adverse reaction, respectively. The most commonly reported adverse reactions among patients treated with this product are nausea, limb pain, headache and dizziness. Besides, Palpitations, weight gain, anemia, sciatica, shortness of breath, vomiting, hemorrhoids, urinary incontinence, polyuria, increased sweating, painful muscle spasms, joint pain, back spasms/pain, hypercholesterolemia, elevated blood calcium levels, hypotension, fatigue, chest pain, weakness, injection site reactions (such as pain, swelling, erythema, local abrasions, itching and mildness) may also occur Microbleeds, etc.
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Teriparatide Powder COA
Basic Information of the Drug
Teriparatide Injection 20mg is a recombinant human parathyroid hormone analogue (PTH 1-34), and its amino acid sequence has the same sequence as the 34th N-terminal amino acid (bioactive region) of the 84-amino acid human parathyroid hormone. This drug was first developed by Eli Lilly Nederland B.V. and was approved for marketing in the United States in November 2002. It is the world's first bone formation promoting drug to be marketed. Its original research product was approved for marketing in China in March 2011, with the trade name Forsteo® /Forsteo®, and the specification is 20μg:80μl, 2.4ml per vial.
Manufacturing Process
Expression System
Teriparatide injection was prepared using the Escherichia coli expression system. The Escherichia coli expression system has the advantages of clear genetic background, simple culture operation, high transformation and transduction efficiency, fast growth and reproduction, and low cost, and can efficiently express recombinant human parathyroid hormone (1-34).
Production process flow
Strain construction and fermentation
Introduce the gene encoding teriparatide into Escherichia coli to construct an engineered strain. Then, the engineered strain was subjected to fermentation culture to enable it to express teriparatide in large quantities.
01
Separation and purification
Through a series of separation and purification steps, such as centrifugation, filtration, chromatography, etc., teriparatide is separated from the fermentation broth, and impurities are removed to obtain high-purity teriparatide.
02
Preparation
Mix the purified teriparatide with excipients (such as glacial acetic acid, sodium acetate (anhydrous), mannitol, m-cresol, hydrochloric acid, sodium hydroxide, water for injection, etc.) to prepare an injection solution. During the preparation of the formulation, parameters such as pH value and osmotic pressure need to be strictly controlled to ensure the stability and safety of the drug.
03
Filling and packaging
The prepared injection solution is filled into pre-filled injection pens and then packaged. The use of pre-filled injection pens facilitates patients' self-injection and improves their compliance.
04
Quality Control
Quality control of active pharmaceutical ingredients
Strict quality control is carried out on the raw material of teriparatide, including the detection of its purity, molecular weight, amino acid sequence, biological activity and other indicators. Only active pharmaceutical ingredients that meet quality standards can be used in the production of preparations.
Quality Control of preparations
Comprehensive quality control is carried out on teriparatide injection, including tests on appearance, pH value, osmotic pressure, content, related substances, bacterial endotoxin, sterility and other items. Ensure that each injection meets the quality standards to guarantee the medication safety of patients.
Stability study
The stability study of teriparatide injection was conducted to investigate its stability under different conditions such as temperature and humidity. Based on the results of the stability study, determine the validity period and storage conditions of the drug.
Research and Development and Market Launch of Generic Drugs
Research and Development Progress
At present, many domestic enterprises have carried out the research and development work of generic teriparatide injection. For instance, Xinlitai (Suzhou) Pharmaceutical's teriparatide injection was successfully approved for marketing in April 2022, becoming the first domestic teriparatide injection to be approved. In addition, several enterprises have submitted marketing applications for this project under the category of therapeutic biological products of Class 3.3 or chemical drugs of Class 4.
Bioequivalence studies
For the research and development of generic drugs, bioequivalence studies need to be conducted to prove that there are no clinically significant differences in safety and efficacy between generic drugs and the original drugs. For a small molecule polypeptide product of recombinant origin like teriparatide injection, which has a simple structure and low immunogenicity risk, if more precise pharmaceutical analysis and characterization have proved to be similar to the original research product, a "head-to-head" PK equivalence study with the reference drug can support its marketing as a biosimilar.
Post-listing supervision
After generic drugs are launched on the market, it is necessary to strengthen supervision to ensure that their quality and efficacy are consistent with those of the original research drugs. Drug regulatory authorities will conduct regular spot checks on generic drugs and deal with products that do not meet quality standards seriously.
Storage and Transportation
Teriparatide injection 20mg should be stored in a refrigerator at 2℃ to 8℃, avoiding freezing. During transportation, it is also necessary to maintain appropriate temperature conditions to ensure the quality and stability of the drugs. After each injection, the patient should store this product in the refrigerator. If the solution is turbid, colored or has particles, it must not be used.
Safety and tolerance
Common Adverse Reactions
Injection site reaction
The patient may experience redness, swelling, pain or itching at the injection site. These reactions are usually mild and in most cases do not require special treatment. As the treatment time extends, the symptoms may gradually ease.
Systemic adverse reactions
Nausea, headache and dizziness: These are relatively common systemic adverse reactions, usually mild in severity, and most patients can tolerate them.
Limb pain: Some patients may experience limb pain, which may be related to the changes in bone metabolism during the process of bone formation promoted by drugs.
Leg cramps: A small number of patients may experience leg cramps, which may have a certain impact on their daily life.
Hypercalcemia
Excessive calcium content in the blood is a manifestation of hypercalcemia. Teriparatide can stimulate the release of bone calcium into the blood, resulting in a transient increase in blood calcium concentration. In clinical trials, the incidence of hypercalcemia is approximately 11%, and it is more common in patients with stage 3-4 chronic kidney disease, especially those who use calcium supplements in combination with a daily dose of more than 1000mg. The treatment approach was to suspend the administration until the blood calcium level was <2.6mmol/L, and then reduce the dosage to 10μg/ day.
Other rare adverse reactions
Including transient orthostatic hypotension, cramps, joint pain, painful abdominal cramps, urge to defecate, diarrhea, etc. In very rare cases, patients may experience serious side effects such as high fever, chills and severe rashes.
Safety of Special Groups
Patients with renal insufficiency
Patients with severe renal insufficiency: Teriparatide injection 20mg is contraindicated. Because the metabolism and excretion of drugs in the body may be affected, leading to the accumulation of drugs in the body and increasing the risk of adverse reactions.
Patients with moderate renal insufficiency: This product should be used with caution. During the usage, it is necessary to closely monitor renal function and blood calcium levels, and adjust the treatment plan based on the monitoring results.
Patients with impaired liver function
At present, no relevant research has been conducted in patients with liver dysfunction. It should be used with caution under the guidance of a doctor. Since the liver plays a significant role in drug metabolism, liver dysfunction may affect the metabolic process of drugs, thereby influencing the safety and efficacy of the drugs.
Children and adolescents with open epiphyses
There is no experience of application in children and adolescents under the age of 18, and it should not be used in children and adolescents under the age of 18 and young people with open epiphyses. The bone development of children and adolescents is not yet mature. The effect of teriparatide on their bone development is not clear, and its use may have adverse effects on bone growth.
Elderly patients
There is no need to adjust the dosage according to age. However, elderly patients may have multiple chronic diseases, their physical functions may decline, and their tolerance to drugs may be poor. During the medication process, the occurrence of adverse reactions needs to be closely observed.
Long-term Safety
Osteosarcoma risk
Animal experiments have shown that long-term high-dose (≥60μg/kg/ day) injection of teriparatide poses a risk of osteosarcoma. However, in human experiments, after a 20-year follow-up, no increase in risk has been found so far. Nevertheless, caution is still needed when using teriparatide, especially for patients with a family history of bone tumors or other potential risk factors.
Cardiovascular safety
In most clinical studies, teriparatide has no significant association with cardiovascular events. However, some studies have reported that patients may experience a brief increase in heart rate after using teriparatide. Therefore, for patients with a previous history of cardiovascular diseases, high caution must be exercised when using it. Doctors should formulate appropriate treatment plans based on the individual conditions of patients and assess and manage possible risk factors.
Safety of Drug Interactions
It interacts with the efficacy of dihydrochlorothiazide
Relevant studies have been conducted and no clinically significant interactions have been found. This means that when teriparatide is used in combination with dihydrochlorothiazide, there is no need to adjust the drug dosage, but the patient's response still needs to be closely monitored.
It is used in combination with raloxifen or hormone replacement therapy
It does not change the effect of teriparatide on blood calcium or urinary calcium, nor does it change its clinical adverse reactions. This provides a certain level of safety guarantee for patients who need to use these drugs in combination, but they still need to follow the doctor's advice when using them in combination.
Safety Monitoring and Management
Blood calcium and urine calcium monitoring
Since teriparatide may cause an increase in blood calcium concentration, it is necessary to monitor the levels of calcium and phosphorus in the blood regularly during the treatment period. When monitoring blood calcium, if blood samples are collected for the purpose of monitoring blood calcium, it should be done between 4 and 6 hours after the most recent injection of this product, as the blood calcium concentration reaches its peak at this time, which can more accurately reflect the effect of the drug on blood calcium.
Adverse reaction monitoring and management
During the treatment period, patients should pay close attention to their physical reactions and report any abnormal conditions to the doctor. Doctors should decide whether to adjust the drug dosage or suspend treatment based on the severity of adverse reactions. For serious adverse reactions, corresponding treatment measures should be taken in a timely manner.
Individualized treatment plan
Doctors should formulate appropriate treatment plans based on the individual conditions of patients, such as age, gender, medical history, and concurrent medications, and assess and manage possible risk factors. During the treatment process, the treatment plan should be adjusted in a timely manner based on the patient's response and monitoring results to ensure the patient's safety.
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