Atri III

Atri III

sodium hyaluronate

Manufacturer:

Yoo Young Pharm

Distributor:

Cosma Medical

Marketer:

Cosma Medical
Full Prescribing Info
Contents
Sodium hyaluronate.
Description
Each syringe (2 mL) contains sodium hyaluronate (EP) 20 mg and isotonic agent sodium chloride 17 mg.
Action
Pharmacology: Pharmacodynamics: Clinical study: A randomized, multiple dose (3 injections) clinical trial of highly purified, HMW Sod. Hyalmonate (ATRI-III) was carried out at 3 sites in South Korea during the period Aug 2008 to Oct 2008.
Study design: Patient eligibility was evaluated during a screening visit before entry into the study.
To ensure patients were blinded to their treatment group assignment, each patient in each treatment group received 3 injections.
Patients received 3 weekly injections of HMW Sod. Hyaluronate followed by one arthrocentesis procedure; Multiple arthrocentesis are not used as a standard treatment for OA. The protocol was approved by the appropriate institutional review boards of each institution. Informed consent was obtained from all subjects prior to participation in the study. HMW Sod. Hyaluronate (molecular weight 3 million Dalton) were administered by IA injection. The Hyaluronate was purified from bacterial fermentation and manufactured under current Good Manufacturing Practices.
Study protocol: The study protocol required 10 patient visits, including the screening visit. Potential study participants returned for a baseline visit after washout of NSAID and analgesics (Week 0). At the baseline visit, patients who met the enrollment criteria were randomly assigned to one of the 3 treatment group and received the first of the series of the IA study treatments. Participant enrollment the radiographic eligibility of the patient was assessed using the K-L grading criteria Assessment included a history, physical examination (range of motion, presence and for synovitis or effusion), and a standing anterior-posterior radiograph. All patients were ≥40 years of age and were willing to discontinue all analgesics and NSAID 7 days before the injection and for the duration of the study. All patients had a diagnosis of knee OA according to the radiographic evidence of knee OA. (See Tables 1 and 2.)

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Study Result: Total 26 patients were in the age from 39 to 78 and female is roughly twice than male.
Patient demographics and baseline disease characteristics. The 26 patients (ATRI-III shows good improvement). (See Table 3.)

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Effect of HMW Sod. Hyaluronate on knee pain, stiffness, and function within treatment evaluable population (n=26), a statistically significant improvement from baseline was observed. Among treatment groups, all endpoints indicated clinical improvements in patients receiving HMW Sod. Hyaluronate.
The changes from baseline scores for all endpoints compared are shown in Table 8. (See Table 4.)

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Degenerative Osteoarthritis: According to Kellegren's radiation classification 18 cases on stage III, 6 cases on stage II, 2 cases on stage I. (See Table 5.)

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Changes by time passing: We evaluate the changes of Subject finding, Objective finding and routine monitoring  for 4 weeks. As a result, showed  significant  improvement after injection. (See Table 6.)

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Adverse reaction: There were none findings of unwanted reaction during the 4 weeks of observation periods. (See Table 7.)

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Discussion and Conclusion: The study in short term periods showed that HMW Sod. Hyaluronate (3 million dalton) intraartricular injection on knee joint was beneficial to improve patients' subjective symptoms and relief of pain. It is recommended to follow up study which will be required to increase number of patients with long periods. (See Table 8.)

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Intraarticular HMW Sod. Hyaluronate injection is an alternative therapeutic option for OA of the knee. This may provide clinical benefit to patients over the long tern by improving joint function and avoiding the potential GI, cardiovascular and renal side effects associated with chronic NSAID therapy and evaluation of the efficacy and safety of High Molecular Weight Sod. Hyaluronate in patients with OA of the knee in a randomized, multicenter trial.
The effectiveness of the 3 week injection regimen was masked by the high rate of response in the arthrocentesis group. A similar placebo effect was also observed in a previous study with the 3-injection regimen of saline in injection as the control been reported. Brandt, et al reported clinical improvement in WOMAC Pain, Patient Global assessments, Investigator Global assessments, and Pain on Standing compared to saline (control) injections.
In summary, the data demonstrate that high molecular weight Sod. Hhyaluronate (ATRI-III) is a safe product for treatment of knee osteoarthritis. These data indicate that ATRI-III seems to be effective in reducing the pain and symptoms associated with OA of the knee using a series of 3 week injections. The potential benefit for clinically significant pain reduction using ATRI-III outweighs the potential risk of a low rate of minor adverse effects.
Indications/Uses
Relieve pain associated with osteoarthritis of the knee; deforming gonarthrocace.
Dosage/Direction for Use
Adults: The contents of one pre-filled syringe (20 mg) to be injected into the affected joint once a week for 3 weeks using a standard technique. Strict aseptic administration technique must be followed.
Contraindications
Patients with hypersensitivity to any components in this material; in cases of infections or skin diseases in the area of the injection site; patient with hepatic failure or history thereof. (Abnormal value of AST and ALT have been reported in patients with a history of hepatic failure.)
Special Precautions
In case that joint inflammation is severe due to deforming gonitis, local inflammation may become worse with this drug. It is recommended to get ride of inflammation symptom prior to injection of ATRI-III INJ.
Because transient pain the injected joint may occur after intra-articular injection of ATRI-III INJ, treatment such as local stabilization is exercised.
Leaked drug beyond articular cavity may cause pain. Therefore, this injection should be correctly injected by intra-atricular injection.
Use in Children: The safety and effectiveness of ATRI-III Inj. have not been established in children.
Use in Elderly: Generally elderly is in the status of low biological function. Therefore careful observation is required.
Use In Pregnancy & Lactation
Pregnancy: Animal reproduction studies have revealed no evidence of impaired fertility. However, safety and efficacy have not been determined during pregnancy. Women who are pregnant or considering pregnancy should be administered only if the therapeutic benefits justifies the potential risks.
Lactation:
In animal studies, it was excreted in milk. Therefore nursing is discontinued during the therapy.
Adverse Reactions
Shock: Since shock may occur, careful observation is required. In the occurrence of adverse reaction, the drug is discontinued and appropriate measures are taken.
Hypersensitivity: Edema (facial edema, palpebral edema), facial flare, rare rash, urticaria and itching may occur. In the occurrence of adverse reaction, the drug is discontinued and appropriate measures are taken.
Injection site: Occasional pain (transient pain after administration), swelling, rare hydrops, flare, warmth, severe compressing sense on local site and ecchymosis may occur.
Others: Nausea, vomiting, fever and headache may occur.
Caution For Usage
Cautions on application: Cautions on injection: Strict aseptic administration technique must be followed.
If symptom is not improved after 3 injections, therapy should be discontinued.
Joint effusion, if present, should be aspirated by arthrocentesis prior to injection of ATRI-III.
Others: This preparation should not be administered by intravenous injection.
This preparation should not be used for ophthalmic.
Caution is required because disinfectants containing quaternary ammonium salts because hyaluronic acid such as benzalkonium chloride or chlorhexidine can precipitate in their presence.
Storage
Place in a light-resistant, hermetic container and store in a cold place (1-15°C).
Shelf-Life: 36 months from manufacturing date.
ATC Classification
M09AX01 - hyaluronic acid ; Belongs to the class of other drugs for disorders of the musculo-skeletal system.
Presentation/Packing
Inj (pre-filled syringe) (clear, colorless, viscous fluid) 20 mg/2 mL x 3's.
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