FAQ

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.

The Intended Use of FLEXISEQ® is: FLEXISEQ® lubricates the cartilage in joints to relieve pain and stiffness and improve impaired joint function associated with all stages of osteoarthritis.

FLEXISEQ® is available as three products: the original FLEXISEQ® Osteoarthritis (OA) is in a white and blue box and is intended for patients who need to treat the pain and stiffness associated with OA. Patients seeking maximum strength treatment for their symptoms should choose FLEXISEQ® (OA). FLEXISEQ® Active is available in a black and blue carton and is a lighter formulation specially developed to serve as an introduction to Joint Lubrication Therapy for the daily needs of joint pain and early-stage arthritis sufferers. 

All FLEXISEQ® products contain Sequessome™ vesicles – the tiny lipid spheres that pass through the skin when the gel is applied topically. FLEXISEQ® (OA) contains the maximum concentration of these vesicles. FLEXISEQ® Active contains a lower concentration of the vesicles, making it lighter and therefore suitable for the daily needs of joint pain and early stage arthritis sufferers, seeking a sustainable drug-free solution.

All FLEXISEQ® products contain Sequessome™ vesicles – the tiny lipid spheres that pass through the skin when the gel is applied topically. Fully concentrated FLEXISEQ® Osteoarthritis (the original product) is clinically proven to be as effective as a prescription oral painkiller (celecoxib) for the pain and stiffness associated with osteoarthritis and is the gold standard product we offer. Patients seeking max strength treatment for their condition should choose this formulation.

FLEXISEQ® Active contains a lower concentration of the Sequessome™ vesicles, making it lighter and therefore suitable for the daily needs of joint pain and early stage arthritis sufferers.

Both products offer a drug-free alternative for treatment of joint pain and stiffness which means patients can avoid drug-based side effects that can be caused by traditional painkillers such as diclofenac and ibuprofen. In addition, FLEXISEQ® products can be used alongside medications and by patients with co-morbidities without exacerbating other conditions.

All FLEXISEQ® products are widely available without prescription at pharmacies and other stores including Boots, Lloyds Pharmacy, Tesco, Superdrug and Well Pharmacy. They are also available online from numerous suppliers including Treatments Direct and Amazon.

The price of the FLEXISEQ® products will vary in different countries so please contact your local pharmacy or online pharmacy.

FLEXISEQ® Active contains a lower concentration of Sequessome™ vesicles, the product from the cost intensive part of the manufacturing process, and therefore costs less.

At the moment, whilst many doctors are recommending FLEXISEQ® to their patients, it is not possible for them to prescribe FLEXISEQ® on the NHS. The company is going through the reimbursement process to try and get the product available on prescription for certain patient groups.

All products contain tiny lipid spheres (Sequessome™ vesicles) in a watery gel. These spheres can pass through the skin into the joint below.

FLEXISEQ® (OA) and FLEXISEQ® Active composition: Aqua, Phosphatidylcholine, Alcohol, Glycerin, Carbomer, Polysorbate 80, Disodium Phosphate, Sodium Hydroxide, Benzyl Alcohol, Methylparaben, Ethylparaben, Linalool, Disodium EDTA, Sodium Phosphate, Sodium Metabisulphite, BHT

There have been 5 clinical studies evaluating the safety and efficacy of FLEXISEQ® across a range of doses representative of the three products, and these consistently demonstrated reductions in pain of around 50% and improvements in physical function of around 40%^{i, ii, iii}

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.ⁱⁱ

These same studies have also demonstrated the safety of FLEXISEQ® products: the most commonly reported side effects were mild/moderate skin irritations. In addition, there have now been over 50 million applications of the product 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 these products safe to use alongside any other therapy.

As with all treatments, if you have any concerns, please consult a doctor or pharmacist.

FLEXISEQ® are drug-free topical treatments and the side effects most commonly reported are mild or moderate skin irritations with rash, dry skin and erythema (redness) being the most commonly reported events.^{i, ii, iii} The majority of the skin irritations reported were temporary, minor and resolved over time without stopping treatment. The extensive clinical programme and market experience demonstrate the safety of FLEXISEQ® products. There have been over 50 million applications 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® products safe to use alongside any other therapy.^{i, ii, iii}

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. If you have to stop treatment, once the condition is resolved, usually within a few days, you may then be able to restart administration if there is no evidence of an allergic reaction as a result of skin contact.

If you are at all worried, please consult a doctor or a pharmacist.

FLEXISEQ® products 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. If the drying time is considerably less than 10 minutes then a little more gel should 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. 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 hand: It is difficult to give precise dosing amounts for the hand as the actual joints affected vary from patient to patient. As a guide, approximately 1 g (3 cm line of gel as squeezed from the tube) would be adequate to treat the knuckles across one hand. You should apply the gel to the entire affected area and 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). 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 skin around the joint, not rubbed in but left to dry. The joint should not be covered until the gel has completely dried. Please avoid washing the affected hand for 30 minutes after application.

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). 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.

• 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.
• 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.
• 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.

All the FLEXISEQ® products should be applied twice a day, usually morning and evening. Please see Question 12 for more information.

The proven clinical efficacy is based on twice daily dosing and we have no data to recommend reducing your dose.

Unlike most pain treatments, FLEXISEQ® treatments are drug-free and therefore have an excellent safety profile. They can be used in patients with other conditions and who take medication. FLEXISEQ® has been shown to be as effective at alleviating joint pain as the oral prescription drug, celecoxib (an oral NSAID).ⁱⁱ

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,^{iv, v} and cardiovascular effects such as increased risk of a heart attack and these side effects can be very serious.^{vi, vii} In contrast, the side effects most commonly reported for FLEXISEQ® are mild or moderate skin irritations ^{i, ii, iii} that are temporary and usually 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), or those who are on specific medications or are elderly. These patients will therefore benefit from the availability of this drug free, effective 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 about the concerns with NSAIDs 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® products 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 treatments.ⁱⁱ

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® treatments are drug-free and relieve the 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 lipid spheres. As the gel dries on the skin, these spheres change their shape and pass through the skin, then into the joint where they lubricate the surface of the cartilage to provide relief from pain and stiffness. They are compressible and deformable, yet stable.

Patients with joint disorders such as OA have been found to have reduced levels of lubricants in their synovial fluid^viii and this is one of the factors contributing to the pain and loss of joint function in patients with OA.^ix There is also strong evidence in published literature that liposome vesicles can act as a bio-lubricant in the knee joint, and hence can reduce pain and improve mobility.^ix

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 surfaces.^x 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 surfaces.^x

All FLEXISEQ® presentations have exactly the same physical mode of action and work by lubricating the affected joint to improve pain and joint function.

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 seen.ⁱⁱ

FLEXISEQ® products are approved for long-term use and there is no maximum treatment duration.

FLEXISEQ® products are approved for long-term use and there is no maximum treatment duration. We have data from a 52 week study that shows that FLEXISEQ® is extremely well tolerated for a year and that treatment effects are maintained.^xi In addition, since the launch of FLEXISEQ® over 12 months ago there have now been over 50 million applications of the product and, unlike other oral and topical treatments, there have been no reported incidences of systemic side effects related to the use of FLEXISEQ®.

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.

Any patients with joint pain and pain or stiffness associated with OA can use the FLEXISEQ® products. They are of 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 question on pregnancy).

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® alone^{i, ii, iii} whilst others received FLEXISEQ® in combination with other treatments.^xii

Since the first launch in 2012, there have been 50 million doses of FLEXISEQ® used. In all this time, we have only had 20 spontaneously reported related 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 profile.^{i, ii, iii}

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 consistently 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® products are 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.^xiii 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^xiv.

Yes – FLEXISEQ® is registered for the treatment of joints affected by OA, including the knee, hip, hand, shoulder etc.

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:

• You are applying the treatment correctly (see Question 12) – the product will not be effective if under-dosed or if you are covering the treated area too soon
• 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)

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 use of FLEXISEQ® products during pregnancy is not advised unless deemed appropriate by your doctor or physician. Likewise, 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 Austria, Germany, Ireland, Italy, Latvia, Lithuania, Malta, Estonia , and the United Kingdom. It is also available in Hong Kong, Malaysia, Singapore, Australia, New Zealand, Turkey, Jordan and South Africa.

The FLEXISEQ® products have been classified by the UK, European and other Regulatory Agencies as medical devices and not a pharmaceutical drug, as these gels have a physical mode of action and do not contain any pharmaceutically active ingredients.

FLEXISEQ® products are sold under global licence by Pro Bono Group plc and its affiliates.

FLEXISEQ® products are manufactured in Germany and Italy.

Any questions or concerns relating to the product or use of FLEXISEQ® should be addressed preferably via email to enquiries@flexiseq.com. If you prefer, you can write to PBB Devices:

PBB Devices Limited, Liverpool Science Park, 131 Mount Pleasant, Liverpool, L3 5TF, UK.

As FLEXISEQ® is a Medical Device rather than a medicine there is no Summary of Product Characteristics. The Patient Information Leaflet (IFU) provides relevant information on FLEXISEQ® and can be downloaded from www.flexiseq.com.