Frequently Asked Questions
FLEXISEQ™ is a topically applied drug-free gel which is clinically proven to safely relieve the pain and improve the joint stiffness associated with osteoarthritis (OA). There is extensive clinical data available from several randomised, double-blind clinical trials and FLEXISEQ™ is approved as a medical device for the treatment of all joints affected by OA.
In the UK, a charity launch of FLEXISEQ™ will take place on 3rd December with PBB granting Arthritis Research UK a period of exclusivity to sell FLEXISEQ™ through its website with a significant proportion of proceeds going to the charity (http://www.arthritisresearchuk.org/shop/products/health/13702-flexiseq.aspx). For those patients who cannot access FLEXISEQ™ through the Arthritis Research UK website, FLEXISEQ™ can be purchased through 500 branches of Lloyds pharmacies. Lloyds will make a donation of £1 to Arthritis Research UK for each tube of FLEXISEQ™ it sells during this exclusive period.
For your nearest branch of Lloyds that is stocking FLEXISEQ™ during this period, please go to www.lloydspharmacy.com/en/info/flexiseq or call our helpline on 0800 098 7011.
From the end of January in the UK and in all other markets where it is available, FLEXISEQ™ can be purchased without prescription at your local pharmacy or online at www.flexiseq.com or call our helpline on 0800 098 7011.
The price of FLEXISEQ™ will vary in different countries so please contact your local pharmacy or online pharmacy.
FLEXISEQ™ contains tiny lipid spheres called Sequessome™ vesicles suspended in the gel which are capable of passing through the skin. Please see question 28 for further information about what Sequessome™ vesicles are made of.
There have been 5 clinical studies evaluating the safety and efficacy of FLEXISEQ™, and these consistently demonstrated reductions in pain of around 50% and improvements in physical function of around 40% 1,2,3
One of the key studies in this extensive clinical programme also demonstrated that FLEXISEQ™ is as effective at alleviating joint pain as a leading oral prescription drug which, unlike FLEXISEQ™, but in common with other treatments in this same class of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), has well recognised systemic side effects (problems resulting from the drug being spread throughout the body). In this comparison study, patients treated with FLEXISEQ™ reported a reduction in joint pain and stiffness that was equivalent to that reported by the patients taking oral celecoxib.2
These same studies have also demonstrated the safety of FLEXISEQ™: the most commonly reported side effects were mild/moderate skin irritations. In addition, there have now been over 6 million applications of the product in early markets and, unlike other oral and topical treatments, there have been no reported incidences of systemic side effects (such as heart attacks, strokes and gastro-intestinal problems linked to NSAIDs) related to the use of FLEXISEQ. This lack of systemic exposure also makes FLEXISEQ™ safe to use alongside any other therapy.
FLEXISEQ™ is a drug-free, topical treatment with excellent safety and tolerability. The extensive clinical programme and market experience demonstrates this safety. There have been over 6 million applications of the product in early markets and, unlike other routinely used oral and topical treatments, there have been no reported incidences of systemic side effects (such as heart attacks, strokes and gastro-intestinal problems linked to NSAIDs) related to the use of FLEXISEQ™. The absence of drug also makes FLEXISEQ™ safe to use alongside any other therapy.
The majority of Adverse Events (AEs) reported have been skin and subcutaneous tissue complaints, mild to moderate in intensity and will resolve over time without stopping treatment 1,2,3.
FLEXISEQ™ is a drug-free topical treatment and the side effects most commonly reported for FLEXISEQ™ are mild or moderate skin irritations with rash, dry skin and erythema (redness) being the most commonly reported events1,2,3. The majority of the skin irritations reported were temporary and minor and will resolve over time without stopping treatment (see question 8).
The extensive clinical programme and market experience demonstrates the safety of FLEXISEQ™. There have been over 6 million applications of the product in early markets and, unlike other routinely used oral and topical treatments, there have been no reported incidences of systemic side effects (such as heart attacks, strokes and gastro-intestinal problems linked to NSAIDs) related to the use of FLEXISEQ™.
FLEXISEQ™ has an excellent safety and tolerability profile. Unlike many pain killers taken by patients, the majority of the side effects seen in clinical trials were mild-to-moderate skin irritations. Most patients in the clinical trials continued using the product, even if skin reactions were experienced. The majority of these irritations will resolve over time without stopping treatment. In the case of continuing side effects, you may first reduce the dose (e.g. from twice daily to once daily) and only if this does not improve the condition should you consider interrupting or stopping treatment.
In you are at all worried, please consult a doctor or a pharmacist.
FLEXISEQ™ should be applied twice daily to the affected joint, usually in the morning and the evening. Use enough gel to evenly cover the soft tissue around the joint.
For the knee: a twice daily dose of 2.2 g corresponding to approximately 7 cm line of gel as squeezed from the tube is recommended. The gel should not be applied to the patella (knee cap) and should include the area at the back of the knee. FLEXISEQ™ must be allowed to dry before covering; drying should take no longer than 10 minutes if the product is applied to clean, dry skin. If drying takes longer than this, ensure that the skin is dry (for example if applying after a bath or shower) and try using a little less gel. Alternatively a hair dryer [on a low / cool setting] can be used to speed up the drying time. If the drying time is considerably less than 10 minutes then a little more gel can be used next time. Please wash your hands after applying the gel.
For the hip: Locate the edge of your pelvis (or hipbone) at your side and apply the gel approximately two inches below where you can no longer feel bone but soft tissue. Do not spread towards the buttocks but instead towards your centre line. It is difficult to give precise dosing amounts for the hip as the size of this joint can vary widely from patient to patient. If you consider yourself to be of average weight, use approximately 3 g (approximately 10 cm line of gel as squeezed from the tube) to cover an area of approximately the size of your hand. If you believe you are above average size, you may need to apply a little more. You will know if you have applied the correct amount as it should take around 10 minutes to dry. For the first few applications the amount applied may need to be increased or decreased to achieve a 10 minute drying time. Alternatively a hair dryer [on a low / cool setting] may be used gently to dry the area. In order to achieve optimum effect, FLEXISEQ™ gel should be applied twice daily to the whole affected joint, not rubbed in but left to dry. The joint should not be covered until the gel has completely dried. Please wash your hands after applying the gel.
For the shoulder: It is difficult to give precise dosing amounts for the shoulder as the size of this joint and location of the pain varies from patient to patient. If you consider yourself to be of average weight, use approximately 2.2 g corresponding to approximately 7 cm line of gel as squeezed from the tube to cover the area corresponding to the location of your pain. If you believe you are above average size, you may need to apply a little more. You will know if you have applied the correct amount as it should take around 10 minutes to dry (although may remain tacky after this time). Alternatively a hair dryer [on a low / cool setting] may be used gently to dry the area. For the first few applications the amount applied may need to be increased or decreased to achieve a 10 minute drying time. In order to achieve optimum effect, FLEXISEQ™ gel should be applied twice daily to the whole affected joint, not rubbed in but left to dry. The joint should not be covered until the gel has completely dried. Please wash your hands after applying the gel.
FLEXISEQ™ has an excellent tolerability and safety profile.
- a. If too much gel has been applied – there are no safety issues with applying too much gel. It will simply take longer for all of the gel to dry off. You can wipe off excess gel and apply less the next time. As a general guidance it should not take longer than 10 minutes for the gel to dry off completely.
- b. If gel has entered the eyes – as with most topical treatments, you should avoid allowing the gel to enter the eyes. If gel does enter the eyes, they should be rinsed with plenty of cold water. If excessive stinging/symptoms occur, please consult a pharmacist or doctor.
- c. If gel has been eaten –the gel should not be taken orally, but if it has been ingested, it should not cause major problems. As with other medical products, care should be taken to store it out of reach of children. If symptoms occur, please consult a pharmacist or doctor.
As with all treatments, if you have any concerns, please consult a doctor or pharmacist.
Unlike most other pain medication, FLEXISEQ™ is drug-free and therefore has an excellent safety profile and can be used in patients with other conditions and who take medication. It has been shown to be as effective at alleviating joint pain as the oral prescription drug, celecoxib (an oral NSAID)2.
FLEXISEQ™ has a physical mode of action, while NSAIDs have a pharmacological effect and alter physiological pathways in the body. NSAID use is often associated with gastrointestinal (GI) side effects such as ulcers,4,5 and cardiovascular effects such as increased risk of a heart attack and these side effects can be very serious6,7. In contrast, the side effects most commonly reported for FLEXISEQ™ are mild or moderate skin irritations1,2,3 that are temporary and will resolve over time without stopping treatment.
There is increasing awareness that oral NSAIDs are not suitable for patients with certain other conditions (such as heart disease, asthma and stomach ulcers), who are on specific medications or are elderly. These patients will therefore benefit from the availability of a new topical treatment, FLEXISEQ™, which is not an NSAID. Patients already taking NSAIDs may also use FLEXISEQ™ in combination if additional pain relief is required, whereas topical NSAIDs cannot be used alongside oral NSAIDs at the same time. More details can be found at the National Institute for Health and Care at http://cks.nice.org.uk/nsaids-prescribing-issues.
No trials have been conducted comparing FLEXISEQ™ with other topical treatments for pain associated with OA, but FLEXISEQ™ has been studied compared to a commonly prescribed oral NSAID (celecoxib), and has been shown to have equivalent efficacy, while avoiding the well-documented side effects (such as heart attacks, stroke and ulcers) associated with oral NSAID treatments2.
One of the most commonly used class of topical for pain is topical NSAIDs. Depending on the amount applied, these products can still result in absorption of the NSAID into the blood (systemic exposure) and hence can cause the same side effects, potentially serious, commonly seen with the oral NSAIDs. Many topical NSAIDs carry the same warnings as the oral NSAIDs and cannot be used alongside oral NSAIDs.
FLEXISEQ™ is a drug-free gel that relieves pain and stiffness associated with osteoarthritis. FLEXISEQ™ exerts its pain-relieving effect via lubrication of the joint which is a physical mode of action. It has no pharmacological, metabolic or immunological activity.
FLEXISEQ™ is a gel containing Sequessome™ vesicles, which are tiny phospholipid spheres. As the gel dries on the skin, these spheres change their shape and pass through the skin, then on into the joint where they lubricate the surface of the cartilage to provide relief from pain and stiffness.
Phospholipids are naturally occurring substances in the body and are known to have numerous functions, including lubrication of articulating cartilage8. Patients with joint disorders such as OA have been found to have reduced levels of phospholipids in their synovial fluid9 and this is one of the factors contributing to the pain and loss of joint function in patients with OA8. There is also strong evidence in published literature that liposomes (phospholipids) act as a bio-lubricant in the knee joint, and hence can reduce pain and improve mobility8.
Research has shown that following topical application of FLEXISEQ™, the Sequessome™ vesicles pass through the skin and penetrate the synovial fluid within the joint where they collect on cartilage surfaces10. The physical properties of the Sequessome™ vesicles make them particularly efficient at lubricating.
A study using fluorescent labelled Sequessome™ vesicles demonstrated that following topical application of FLEXISEQ™, they pass through the skin, penetrate the synovial fluid within the joint and collect on cartilage surfaces10.
Twice-daily treatment with FLEXISEQ™ provides pain relief after as little as 2 days (the earliest measured timepoint in clinical trials), which is comparable with the onset of sustainable pain relief to other OA therapies, including oral celecoxib. It may take up to 14 days for the full effect to be seen2.
The clinical evidence is from studies ranging from 6 to 52 weeks and showed excellent safety and tolerability throughout these periods. Given the physical action of FLEXISEQ™ and the excellent safety and tolerability data, there is no reason to advise a maximum duration of treatment. In addition, since the launch of FLEXISEQ™ over 12 months ago there have now been over 6 million applications of the product in early markets and, unlike other oral and topical treatments, there have been no reported incidences of systemic side effects related to the use of FLEXISEQ™. This lack of systemic exposure also makes FLEXISEQ™ safe to use alongside any other therapy.
We have data from a 52 week study that shows that FLEXISEQ™ is extremely well tolerated for a year and that treatment effects are maintained11. In addition, since the launch of FLEXISEQ™ over 12 months ago there have now been over 6 million applications of the product in early markets and, unlike other oral and topical treatments, there have been no reported incidences of systemic side effects related to the use of FLEXISEQ™.
As above. FLEXISEQ™ works by delivery of lubricating vesicles into the joint. These vesicles are made of naturally occurring phospholipids and will be broken down over time and will need replacing. Therefore patients will need to continue to use FLEXISEQ™ in order to maintain efficacy.
We have no clinical data on any other treatment regimen other than twice daily.
Any patients with pain associated with OA can use FLEXISEQ™. It is particular interest to
- Patients for whom other treatment options (NSAIDs, COX-II inhibitors and paracetamol) should be avoided or used as little as possible, either because of their other medical conditions, their age or their concomitant medications. This includes patients with cardio-vascular or gastro-intestinal risk factors and problems.
- Patients who are not receiving adequate symptomatic relief from their current treatment and want to add another option.
- Cautions: Patients with known sensitivity to any of the ingredients listed on the box should not use FLEXISEQ™. Pregnant women should consult their doctor (see Q32).
There is no evidence from the extensive and growing market experience and the study programme that FLEXISEQ™ in any way influences other underlying conditions or interacts with treatments for other conditions. This therefore reassures you that using FLEXISEQ™ will not compromise your existing oral medication. As with any treatment, if you have specific concerns, please consult your pharmacist or doctor.
FLEXISEQ™ does not contain any active pharmaceutical ingredients and therefore cannot compromise any existing oral medications, such as low-dose aspirin, paracetamol, diuretics. If you have any specific concerns, a pharmacist or doctor should be consulted.
In the clinical programme, 1675 patients were treated with FLEXISEQ™; the duration of treatment lasted from 6 to 52 weeks. Some of these patients received FLEXISEQ™ alone1,2,3, whilst others received FLEXISEQ™ in combination with other treatments12.
Since the first launch in 2012, there have been 6 million doses of FLEXISEQ™ used. In all this time, we have only had 5 spontaneously reported adverse events – all minor skin irritations. In addition, during this time and unlike other routinely used oral and topical treatments, there have been no reported incidences of systemic side effects related to the use of FLEXISEQ™.
Unlike many medical devices, the safety and efficacy of FLEXISEQ™ have been demonstrated in an extensive trial programme where 1,675 patients have been treated with FLEXISEQ™ for up to 52 weeks. The three key studies have demonstrated that FLEXISEQ™ reduces pain associated with OA of the knee, improves joint stiffness and physical function and has an excellent safety and tolerability profile1,2,3.
OA of the knee is extremely common and difficult to treat because it is a weight-bearing joint that is difficult to rest. While other joints are also commonly affected by OA, they are not always symptomatic whereas OA of the knees is almost always symptomatic and has a significant impact on patients' lives. Hence, as for the studies done on most pain interventions, the primary focus for studies of FLEXISEQ™ has been patients experiencing pain associated with OA of the knee. Showing such good effect on this challenging target is recognised as what is needed to show that FLEXISEQ™ will work on joints of the hand or other joints. FLEXISEQ™ is registered as a device for use on all joints affected by OA.
FLEXISEQ™ is registered for treatment of all joints affected by OA. The joints affected by OA, such as the knee, the hip, the hand, the elbow, etc., are all synovial joints and it is understood that any pain-reducing treatment would benefit a joint with OA, regardless of its location.13 In addition, a study of a gel containing a similar phospholipid vesicle found that the gel was effective for reducing OA pain in several different types of joints, including the knee, hand, hip and shoulder, and there were no differences in effectiveness between the indications.14
Yes - FLEXISEQ™ is registered for the treatment of joints affected by OA, including the knee, hip, hand, shoulder etc.
As well as the Sequessome™ vesicles, FLEXISEQ™ comprises standard excipients which are widely used in a variety of marketed pharmaceutical, foodstuff and cosmetic products. In addition, the constituents of the Sequessome™ vesicles that pass into the joints are all designated as GRAS (Generally Recognised As Safe) by the US FDA. A full listing can be found on the packaging and patient leaflet.
FLEXISEQ™ is easy to look after, and can be stored at room temperature (between 8°C and 25°C). It does not need to be refrigerated and should not be stored in the fridge. After first opening the tube, the product should be used within 3 months.
No treatment will work for all patients. However, before it is assumed that you are one of those for whom this treatment does not work, please check that:
- a) You are applying the treatment correctly (see question 9) – the product will not be effective if under-dosed or if you are covering the treated area too soon
- b) treatment has been ongoing for long enough for an effect to be seen (we recommend 4 weeks although an effect will usually be seen sooner; some patients may take longer)
- c) the pain or other symptom being treated is caused by OA and not another unrelated condition
If you are using the gel correctly and not receiving benefit, then unfortunately it may simply not be the treatment for you.
If body lotion is applied alongside FLEXISEQ™ or before the FLEXISEQ™ is dried, it may reduce its effectiveness. However, patients may apply a little body lotion or light cream, preferably unperfumed, when necessary to keep their skin moisturised once FLEXISEQ™ is fully dried off and absorbed into the skin.
FLEXISEQ™ has not been tested on pregnant women in clinical trials, and therefore its use during pregnancy is not advised unless deemed appropriate by your doctor or physician. It is unknown whether FLEXISEQ™ may be harmful to your child if you are breastfeeding. Please ask your doctor or pharmacist for advice before using the product.
FLEXISEQ™ is available in multiple European markets and also additional markets worldwide.
FLEXISEQ™ has been classified by the UK, European and other regulators as a medical device and not a pharmaceutical drug, as it has a physical mode of action and does not contain any pharmaceutically active ingredients which can interfere with other medication or treatment and cause systemic side-effects.
FLEXISEQ™ is under global license to and marketed by Pro Bono Bio, a healthcare company launched on 12 September 2011.
FLEXISEQ™ is manufactured in Germany.
- Kneer W, Seidel EJ, Mazgareanu S, Rother M. J Pain Res 2013;6:743-753
- Conaghan P, Dickson J, Bolten W, Cevc G, Rother M. Rheumatology 2013 Jul; 52(7):1303-12
- Rother M, Conaghan PG. J Rheumatology 2013 2013;40:1742-48
- NICE, 2008. Available at: www.nice.org.uk/CG059 (accessed 27 February 2012).
- McKenzie S, Torkington A. Aust Fam Physician 2010;39(9):622–625.
- Coxib and Traditional NSAID Trialists' (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013;pii: Q5 S0140-6736(13)60900-9
- Fosbøl EL, Gislason GH, Jacobsen S, et al. Risk of myocardial infarction and death associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) among healthy individuals: a nationwide cohort study. Clin Pharmacol Ther 2009;85:190-7
- Vecchio P, Thomas R, Hills BA. Surfactant treatment for osteoarthritis. Rheumatology 1999;38:1020−1021
- Hills BA, Monds MK. Br J Rheumatol 1998;37:143–147.
- Caliper Lifescience study, data on file
- Clinical study report (sponsor code CL-033-III-05). IDEA AG, Frankfurter Ring 197a, 80807 Munich, Germany. 15 December 2008
- Rother M, Yeoman G, Ekman E. Annual EULAR Congress 2012b Abstract no. EULAR12-3375
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 2010. Osteoarthritis. Available at: www.niams.nih.gov/health_info/osteoarthritis/ (accessed 27 February 2012).
- Kneer W, et al. Curr Drug Saf 2009;4:5–10.