Euflexxa
- Generic Name: sodium hyaluronate intra-articular injection, 1%
- Brand Name: Euflexxa
- Drug Class: Sodium hyaluronate
Euflexxa (Sodium Hyaluronate Intra-articular Injection, 1%) side effects drug center
Euflexxa Side Effects Center
What Is Euflexxa?
Euflexxa (1% sodium hyaluronate) is a cartilaginous defect repair agent indicated for the treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to respond adequately to conservative non-pharmacologic therapy and simple analgesics (e.g., acetaminophen).
What Are Side Effects of Euflexxa?
Common side effects of Euflexxa include:
- joint pain,
- back pain,
- pain in extremities,
- musculoskeletal pain,
- joint swelling,
- fluid accumulation around the joints,
- injection site pain,
- arthritis,
- nausea,
- fatigue,
- bronchitis,
- infection,
- increased blood pressure,
- tendonitis,
- headache,
- numbness and tingling,
- runny or stuffy nose,
- skin redness, and
- itching.
Dosage for Euflexxa
A dose of 2 mL of Euflexxa is injected intra-articularly into the affected knee at weekly intervals for three weeks, for a total of three injections.
What Drugs, Substances, or Supplements Interact with Euflexxa?
Euflexxa may interact with other drugs. Tell your doctor all medications and supplements you use.
Euflexxa During Pregnancy and Breastfeeding
During pregnancy, Euflexxa should be used only if prescribed. It is unknown if Euflexxa passes into breast milk. Consult your doctor before breastfeeding.
Additional Information
Our Euflexxa (1% sodium hyaluronate) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
Euflexxa Consumer Information
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have:
- severe pain or swelling around the knee after the injection.
Common side effects may include:
- warmth, pain, redness, stiffness, bruising, or puffiness where the medicine was injected;
- nausea, stomach pain;
- trouble walking;
- swelling in your hands or feet;
- back pain, joint pain, muscle pain;
- numbness or tingly feeling;
- headache, dizziness; or
- runny or stuffy nose, sneezing, sore throat.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for Euflexxa (Sodium Hyaluronate Intra-articular Injection, 1%)
Euflexxa Professional Information
SIDE EFFECTS
Adverse event information regarding the use of EUFLEXXA as a treatment for pain in OA of the knee was available from two sources; a 12 week multicenter clinical trial conducted in Germany, and a 26 week multicenter clinical trial conducted in the US.
Reported Device-Related Adverse Events
The most common adverse event related to EUFLEXXA injections reported in the clinical studies are the following:
- Arthralgia
- Back pain
- Pain in extremity
- Musculoskeletal pain
- Joint swelling
All adverse events related to EUFLEXXA injections reported in Tables 1, 2, 3 and 4.
Potential Adverse Events
The following adverse events are among those that may occur in association with intra-articular injections
12 Week Multicenter Clinical Study
This clinical investigation was a prospective randomized, double-blinded, active control (commercially available hyaluronan product) study conducted at 10 centers. Three hundred twenty-one patients were randomized into groups of equal size to receive either EUFLEXXA (n=160) or the active control (n=161).
A total of 119 patients reported 196 adverse events; this number represents 54 (33.8%) of the EUFLEXXA group and 65 (44.4%) of the active control group. There were no deaths reported during the study. Incidences of each event were similar for both groups, except for knee joint effusion, which was reported by 9 patients in the active control group and one patient in the EUFLEXXA treatment group. Fifty-two adverse events were considered device-related. Table 1 lists the adverse events reported during this investigation.
Table 1: Incidence of Adverse Events Reported by
> 1% of Patients
| Body System | ADE | Patients, n (%) | |
| EUFLEXXA (n = 160) |
Active Control (n = 161) |
||
| Gastrointestinal disorders | Nausea | 3 (1.88) | 0 |
| General disorders and administration site | Fatigue | 2 (1.25) | 0 |
| Infections and infestations | Bronchitis | 1 (0.63) | 2 (1.24) |
| Infection | 2 (1.25) | 0 | |
| Investigations | Blood pressure increased | 6 (3.75) | 1 (0.62) |
| Musculoskeletal, connective tissue and bone | Arthralgia | 14 (8.75) | 17 (10.6) |
| Arthrosis | 2 (1.25) | 0 | |
| Back pain | 8 (5.00) | 11 (6.83) | |
| Joint disorder | 2 (1.25) | 2 (1.24) | |
| Joint effusion | 1 (0.63) | 13 (8.07) | |
| Joint swelling | 3 (1.88) | 3 (1.86) | |
| Pain in limb | 2 (1.25) | 0 | |
| Tendonitis | 3 (1.88) | 2 (1.24) | |
| Nervous system disorders | Headache | 1 (0.63) | 3 (1.86) |
| Paresthesia | 2 (1.25) | 1 (0.62) | |
| Respiratory, thoracic and mediastinal | Rhinitis | 5 (3.13) | 7 (4.35) |
| Skin and subcutaneous tissue disorders | Erythema | 0 | 2 (1.24) |
| Pruritus | 0 | 3 (1.86) | |
| Vascular disorders | Phlebitis | 0 | 2 (1.24) |
A total of 160 patients received 478 injections of EUFLEXXA. There were 27 reported adverse events considered to be related to EUFLEXXA injections: arthralgia - 11 (6.9%); back pain - 1 (0.63%); blood pressure increase - 3 (1.88%); joint effusion - 1 (0.63%); joint swelling - 3 (1.88%); nausea - 1 (0.63%); paresthesia - 2 (1.25%); feeling of sickness of injection - 3 (1.88%); skin irritation - 1 (0.63%); tenderness in study knee - 1 (0.63%). Four adverse events were reported for the EUFLEXXA group that the relationship to treatment was considered to be unknown: fatigue - 3 (1.88%); nausea - 1 (0.63%).
Table 2: Relationship of Adverse Effects to Treatment
Groups That Were Considered to Be Treatment Related
| Adverse Event | (EUFLEXXA) (Number of Reports) n = 160 |
Commercially Available Hyaluronan Product (Number of Reports) n = 161 |
| Arthralgia | 11 | 9 |
| Back pain | 1 | 0 |
| Baker's cyst | 0 | 1 |
| Blood pressure increase | 3 | 0 |
| Erythema | 0 | 1 |
| Inflammation localized | 0 | 1 |
| Joint effusion | 1 | 9 |
| Joint swelling | 3 | 2 |
| Nausea | 1 | 0 |
| Edema lower limb | 0 | 1 |
| Paresthesia | 2 | 0 |
| Pruritus | 0 | 1 |
| Sickness | 3 | 0 |
| Skin irritation | 1 | 0 |
| Tenderness | 1 | 0 |
| TOTAL | 27 | 25 |
26 Week Multicenter Study
This was a multicenter, randomized, double-blind trial evaluating the efficacy and safety of EUFLEXXA, as compared with saline, in subjects with chronic osteoarthritis of the knee followed by an open labeled safety extension study. The intervention consisted of three (3) weekly injections of study device into the target knee, with scheduled follow-up evaluations during the 26 weeks following the first injection. In the extension phase subjects received three (3) weekly injections of EUFLEXXA into the target knee with follow-up evaluation up to 52 weeks. Table 3 shows the treatmentemergent adverse events by preferred term with an incidence of ≥ 2% among treatment groups.
Table 3: Treatment-Emergent Adverse Events by
Preferred Term with an Incidence of ≥ 2% among the Treatment Groups (Safety
Population)
| System Organ Class Preferred Term |
26 Week FLEXX Study (Core) | Extension Study Repeat Injection for 52 Weeks* | ||
| All Treatments N = 588 n (%) |
Saline N = 295 n (%) |
EUFLEXXA N = 293 n (%) |
EUFLEXXA N = 219 n (%) |
|
| Any TEAE | 326 (55.4) | 169 (57.3) | 157 (53.6) | 96 (43.8) |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 62 (10.5) | 35 (11.9) | 27 (9.2) | 19 (8.7) |
| Back pain | 23 (3.9) | 11 (3.7) | 12 (4.1) | 6 (2.7) |
| Pain in extremity | 13 (2.2) | 10 (3.4) | 3 (1.0) | 3 (1.4) |
| Musculoskeletal pain | 10 (1.7) | 4 (1.4) | 6 (2.0) | 2 (0.9) |
| Osteoarthritis | 9 (1.5) | 7 (2.4) | 2 (0.7) | 0 |
| Joint swelling | 8 (1.4) | 4 (1.4) | 4 (1.4) | 6 (2.7) |
| Infections and infestations | ||||
| Upper respiratory tract infection | 23 (3.9) | 11 (3.7) | 12 (4.1) | 6 (2.7) |
| Nasopharyngitis | 17 (2.9) | 13 (4.4) | 4 (1.4) | 10 (4.6) |
| Sinusitis | 16 (2.7) | 10 (3.4) | 6 (2.0) | 5 (2.3) |
| Urinary tract infection | 12 (2.0) | 6 (2.0) | 6 (2.0) | 3 (1.4) |
| Injury, poisoning, and procedural complications | ||||
| Injury | 17 (2.9) | 9 (3.1) | 8 (2.7) | 9 (4.1) |
| Nervous system disorders | ||||
| Headache | 17 (2.9) | 11 (3.7) | 6 (2.0) | 3 (1.4) |
| Gastrointestinal disorders | ||||
| Diarrhea | 14 (2.4) | 2 (0.7) | 12 (4.1) | 3 (1.4) |
| Nausea | 12 (2.0) | 7 (2.4) | 5 (1.7) | 4 (1.8) |
| Respiratory, thoracic, and mediastinal disorders | ||||
| Cough | 10 (1.7) | 3 (1.0) | 7 (2.4) | 3 (1.4) |
| Vascular disorders | ||||
| Hypertension | 18 (3.1) | 5 (1.7) | 13 (4.4) | 1 (0.5) |
| *Treatment group for repeat study are for subjects who
received EUFLEXXA in both the core and extension (219 out of 433). N = number of subjects in a given treatment group for the population analyzed; n = number of subjects reporting at least one adverse event within system organ class/preferred term; (%) = percentage of subjects based on N; TEAE = treatment-emergent adverse event. Note: An adverse event was counted as a TEAE if it was either not present at baseline (prior to the first dose of double-blind study device) or present at baseline but increased in severity during the treatment period. |
||||
During the initial randomization/treatment phase, 326 (55.4%) subjects in the safety population experienced 742 TEAEs. The proportion of subjects reporting TEAEs was generally similar in the EUFLEXXA and saline groups (53.6% and 57.3%, respectively). The most common preferred term of TEAE was arthralgia (10.5% of all subjects). Thirty (5.1%) subjects experienced severe TEAEs, and the proportion with severe events was larger in the saline group (6.4%) than the EUFLEXXA group (3.8%). Overall, 10.4% of subjects had TEAEs considered related to study device, with comparable proportions in each treatment group (9.9% and 10.8% for EUFLEXXA and saline, respectively).
During the extension phase, 43.4% (188/433) of subjects reported 377 TEAEs. Of these 43.8% (96/219) subjects receiving repeated EUFLEXXA reported 199 TEAEs. The most frequently reported preferred term in subjects formerly assigned to the core study EUFLEXXA group were arthralgia (8.7%), nasopharyngitis (4.6%), injury (4.1%), upper respiratory tract infections (2.7%), joint swelling (2.7%), back pain (2.7%), and sinusitis (2.3%). Of these TEAEs 9 (4.1%) subjects had study device related AEs classified as “Certain,” “Probable,” “Possible” or “Un-assessable.” The most common related TEAEs were arthralgia (2.3%) and joint swelling (1.4%).Table 4 shows the Study Device Related Treatment-Emergent Adverse Events by Preferred Term with an Incidence of > 1 among Treatment Groups (Safety Population).
Table 4: Study Device Related Treatment-Emergent
Adverse Events (TEAEs) by Preferred Term with an Incidence of ≥ 1
among Treatment Groups (Safety Population)
| System Organ Class Preferred Term |
26 Week FLEXX Study (Core) | Extension Study Repeat Injection for 52 Weeks* | ||
| All Treatments N = 588 n (%) |
Saline N = 295 n (%) |
EUFLEXXA N = 293 n (%) |
EUFLEXXA N = 219 n (%) |
|
| Any related TEAEs | 61 (10.4) | 32 (10.8) | 29 (9.9) | 9 (4.1) |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 23 (3.9) | 13 (4.4) | 10 (3.4) | 5 (2.3) |
| Joint swelling | 3 (0.5) | 2(0.7) | 1 (0.3) | 3 (1.4) |
| Pain in extremity | 3 (0.5) | 3 (1) | 0 | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Erythema | 5 (0.9) | 3 (1) | 2 (0.7) | 0 |
| *TEAEs are for subjects who received EUFLEXXA in both the
core and extension (219 out of 433). N = number of subjects in a given treatment group for the population analyzed; n = number of subjects reporting at least 1 AE within system organ class/preferred term; (%) = percentage of subjects based on N; TEAE = treatment-emergent adverse event. Note: Related AEs are AEs with study device relationship classified as “Certain,” “Probable,” “Possible” or “Un-assessable.” |
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Twenty-three serious TEAEs were reported in 19 (3.2%) subjects during the study: 10 (3.4%) subjects in the EUFLEXXA group and 9 (3.1%) subjects in the saline group. One of these events was considered related to the study device (increased redness of the left knee joint in the EUFLEXXA group). Eight (1.4%) subjects had 9 TEAEs leading to discontinuation: 3 (1.0%) subjects in the EUFLEXXA group and 5 (1.7%) subjects in the saline group.
Twelve (2.8%) subjects reported 20 serious TEAEs during the extension phase. Six of these subjects had received EUFLEXXA during the core study. None of the serious TEAEs was considered related to study device, and all resolved. Two (0.5%) subjects had TEAEs leading to discontinuation from the study, one of whom received EUFLEXXA during the core study; both subjects had events that were considered unrelated to study device.
Two subjects on saline experienced joint effusion. There were no reports of joint effusion among subjects receiving EUFLEXXA during the core and extension phase.
Read the entire FDA prescribing information for Euflexxa (Sodium Hyaluronate Intra-articular Injection, 1%)
&Copy; Euflexxa Patient Information is supplied by Cerner Multum, Inc. and Euflexxa Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.