Everolimus Ethypharm: Uses, Dosage & Side Effects
An mTOR inhibitor used to prevent organ rejection following kidney or heart transplantation, taken in combination with ciclosporin and corticosteroids
Everolimus Ethypharm is an immunosuppressant medication containing the active substance everolimus, a selective inhibitor of the mammalian target of rapamycin (mTOR). It is prescribed to prevent organ rejection in adult patients who have received a kidney or heart transplant. Everolimus Ethypharm is always used as part of a combination immunosuppressive regimen, typically alongside ciclosporin (a calcineurin inhibitor) and corticosteroids. By inhibiting the mTOR signaling pathway, everolimus suppresses T-cell activation and proliferation, thereby preventing the immune system from attacking the transplanted organ. This medication requires careful therapeutic drug monitoring and is initiated and supervised exclusively by transplant specialists.
Quick Facts: Everolimus Ethypharm
Key Takeaways
- Everolimus Ethypharm is an mTOR inhibitor immunosuppressant used to prevent rejection of kidney or heart transplants in adult patients, always in combination with ciclosporin and corticosteroids.
- The medication has a narrow therapeutic index, requiring regular blood level monitoring (therapeutic drug monitoring) to ensure the dose remains within the target range and to minimize the risk of rejection or toxicity.
- Common side effects include increased susceptibility to infections, elevated cholesterol and blood sugar levels, anemia, and impaired wound healing; regular blood tests are essential throughout treatment.
- Strong CYP3A4 inhibitors (such as ketoconazole) and inducers (such as rifampicin) significantly alter everolimus blood levels; grapefruit and St. John's wort must also be avoided.
- Everolimus Ethypharm must not be used during pregnancy due to reproductive toxicity; effective contraception is required during treatment and for at least 8 weeks after the last dose.
What Is Everolimus Ethypharm and What Is It Used For?
Everolimus Ethypharm contains the active substance everolimus, a potent and selective inhibitor of the mammalian target of rapamycin (mTOR). mTOR is a serine-threonine kinase that plays a central role in regulating cell growth, proliferation, metabolism, and survival. In the context of transplantation, mTOR signaling is critical for the activation and clonal expansion of T lymphocytes – the immune cells primarily responsible for recognizing and attacking foreign tissue, including transplanted organs. By inhibiting this pathway, everolimus provides immunosuppression that helps prevent the body from rejecting the transplanted organ.
The mechanism of action of everolimus involves binding to the intracellular protein FKBP-12 (FK506-binding protein 12). The resulting everolimus-FKBP-12 complex then binds to and inhibits mTOR complex 1 (mTORC1), a key regulatory kinase downstream of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Inhibition of mTORC1 blocks the signaling driven by interleukin-2 (IL-2) and other T-cell growth factors, effectively preventing T-cell progression from the G1 to the S phase of the cell cycle. This results in selective suppression of the adaptive immune response, reducing the risk of acute and chronic organ rejection without completely ablating immune function.
Everolimus also has antiproliferative effects on non-immune cells, including vascular smooth muscle cells. This property is of particular clinical interest in transplantation because chronic allograft vasculopathy (a progressive narrowing of the blood vessels within the transplanted organ) is a major cause of late graft failure. By inhibiting smooth muscle cell proliferation, everolimus may help slow the development of this condition, potentially improving long-term graft survival.
Everolimus Ethypharm is approved for the prevention of organ rejection in the following transplant settings:
- Kidney transplantation: Everolimus Ethypharm is used in combination with ciclosporin microemulsion and corticosteroids in adult patients at low to moderate immunological risk who have received a kidney transplant. This combination allows for reduced ciclosporin exposure, which may help preserve kidney function over the long term, since ciclosporin itself can be toxic to the kidneys (nephrotoxicity).
- Heart transplantation: Everolimus Ethypharm is used in combination with ciclosporin and corticosteroids in adult heart transplant recipients to prevent organ rejection. In heart transplantation, the additional benefit of everolimus's antiproliferative effects on vascular smooth muscle may help reduce the incidence and severity of cardiac allograft vasculopathy.
Organ transplantation is a life-saving procedure for patients with end-stage organ failure. However, the recipient's immune system naturally recognizes the transplanted organ as foreign and mounts an immune response to destroy it. Without immunosuppressive therapy, virtually all transplanted organs would be rejected. Modern transplant medicine relies on combination immunosuppressive regimens that target different components of the immune response, allowing for effective rejection prevention while minimizing the toxicity associated with any single agent.
The use of everolimus as part of a ciclosporin-based regimen represents an important therapeutic strategy in transplant medicine. Clinical trials, including the landmark A2309 study in kidney transplantation and the A2310 study in heart transplantation, have demonstrated that everolimus-based regimens can effectively prevent acute rejection episodes while enabling reduced ciclosporin dosing. This calcineurin inhibitor (CNI)-sparing approach is particularly valuable because long-term high-dose ciclosporin use is associated with progressive nephrotoxicity, a leading cause of kidney function decline in transplant recipients.
Everolimus Ethypharm must only be prescribed and supervised by physicians experienced in transplant medicine. This medication requires regular blood level monitoring and dose adjustments based on trough blood concentrations. It is never used alone but always as part of a combination immunosuppressive regimen. Do not adjust your dose or stop taking this medication without your transplant team's guidance, as doing so could result in organ rejection.
What Should You Know Before Taking Everolimus Ethypharm?
Contraindications
There are specific situations in which Everolimus Ethypharm must not be used. Understanding these absolute contraindications is essential before treatment begins.
- Hypersensitivity: Do not take Everolimus Ethypharm if you are allergic to everolimus, to other rapamycin derivatives (such as sirolimus or temsirolimus), or to any of the excipients in the formulation. Allergic reactions may include rash, itching, swelling, dizziness, or difficulty breathing.
- Concurrent use with strong CYP3A4 inhibitors or inducers: While not an absolute contraindication, concomitant use of strong CYP3A4 inhibitors (such as ketoconazole, itraconazole, voriconazole, or clarithromycin) or strong CYP3A4 inducers (such as rifampicin or phenytoin) is generally not recommended unless the benefit clearly outweighs the risk, due to significant alterations in everolimus blood levels.
Warnings and Precautions
Like all immunosuppressants, Everolimus Ethypharm increases the risk of developing infections (including opportunistic infections) and certain cancers (particularly lymphomas and skin cancers). The risk increases with the intensity and duration of immunosuppression. Minimize sun exposure and use protective clothing and high-SPF sunscreen. Report any unusual lumps, skin changes, fever, or persistent symptoms to your transplant team promptly.
Before and during treatment with Everolimus Ethypharm, you should discuss the following with your doctor:
- Infections: Immunosuppression increases susceptibility to bacterial, viral, fungal, and protozoal infections. Serious infections, including opportunistic infections such as BK virus-associated nephropathy (particularly in kidney transplant recipients), cytomegalovirus (CMV) infection, and Pneumocystis jirovecii pneumonia (PCP), have been reported. Prophylactic antimicrobial therapy may be recommended, particularly in the early post-transplant period.
- Non-infectious pneumonitis: Everolimus has been associated with cases of non-infectious pneumonitis, including interstitial lung disease. Symptoms include cough, shortness of breath, and fever. If you develop unexplained respiratory symptoms, contact your doctor immediately. The condition is usually reversible upon dose reduction or discontinuation.
- Hyperlipidemia: Everolimus commonly causes elevated blood cholesterol (hypercholesterolemia) and triglycerides (hypertriglyceridemia). Regular lipid monitoring is necessary, and treatment with lipid-lowering medications (statins or fibrates) may be required. When statins are used with ciclosporin, monitor for signs of rhabdomyolysis (muscle breakdown).
- Hyperglycemia and new-onset diabetes: Elevated blood sugar levels and new-onset diabetes mellitus after transplant (NODAT) have been observed with everolimus. Blood glucose levels should be monitored regularly. Patients with pre-existing diabetes may need adjustments to their diabetic medication.
- Impaired wound healing: mTOR inhibitors are known to impair wound healing. This is particularly relevant in the early post-transplant period. Some transplant centers prefer to delay everolimus initiation until adequate wound healing has occurred. Discuss any planned surgical or dental procedures with your doctor.
- Angioedema: The risk of angioedema (swelling of the face, lips, tongue, or throat) is increased when everolimus is used with ACE inhibitors (such as ramipril, enalapril, or lisinopril). Inform your doctor if you experience swelling, especially of the face or airways.
- Proteinuria: Urinary protein excretion may increase during treatment with everolimus. Regular monitoring of urine protein levels is recommended, particularly in kidney transplant recipients.
- Thrombotic microangiopathy (TMA): Thrombotic microangiopathy, thrombotic thrombocytopenic purpura (TTP), and hemolytic uremic syndrome (HUS) have been reported. Symptoms may include low platelet counts, reduced red blood cell counts, fatigue, kidney dysfunction, and neurological changes.
- Hepatic impairment: If you have liver problems, dose adjustments may be necessary, as everolimus is extensively metabolized by the liver. Blood levels should be monitored more frequently in patients with hepatic impairment.
- Renal function: In combination with ciclosporin, everolimus may contribute to impaired kidney function. Close monitoring of serum creatinine and estimated glomerular filtration rate (eGFR) is essential. Ciclosporin dose reductions guided by blood levels are an important part of the regimen to protect kidney function.
- Vaccinations: Live vaccines must be avoided during treatment. Inactivated vaccines may have reduced effectiveness due to immunosuppression. Discuss your vaccination schedule with your transplant team, ideally completing all necessary vaccinations before transplantation.
- Male fertility: Everolimus may affect sperm count and quality. Male patients should discuss fertility concerns with their doctor before starting treatment.
Pregnancy and Breastfeeding
Everolimus Ethypharm should not be used during pregnancy. Animal reproductive toxicity studies have demonstrated embryotoxicity and fetotoxicity, including increased resorptions, reduced fetal weight, and skeletal malformations at doses that were below the human therapeutic exposure. Although there are limited data in pregnant women, the potential risk to the fetus is considered significant based on the mechanism of action and animal data.
Women of childbearing potential must use highly effective contraception during treatment with Everolimus Ethypharm and for at least 8 weeks after the last dose. If you become pregnant or suspect you may be pregnant during treatment, contact your doctor immediately. A careful assessment of the risks and benefits will be needed, and alternative immunosuppressive regimens with a better-established safety profile in pregnancy may be considered.
It is not known whether everolimus is excreted in human breast milk. In animal studies, everolimus and its metabolites were detected in the milk of lactating rats. Given the potential for serious adverse effects in the breastfed infant, breastfeeding is not recommended during treatment with Everolimus Ethypharm and for at least 2 weeks after the last dose.
Male patients should be aware that everolimus may impair fertility. Reduced sperm counts and sperm motility have been reported. These effects are generally considered reversible after stopping treatment, but the time to recovery may vary. Men should discuss sperm cryopreservation with their doctor if future fertility is a concern.
Driving and Operating Machinery
The effect of Everolimus Ethypharm on the ability to drive and operate machinery has not been systematically studied. However, if you experience side effects such as fatigue, dizziness, or visual disturbances while taking this medication, you should exercise caution when driving or operating machinery. Discuss any concerns with your healthcare provider.
How Does Everolimus Ethypharm Interact with Other Drugs?
Drug interactions with Everolimus Ethypharm are of critical clinical importance because everolimus has a narrow therapeutic index. Even modest changes in blood levels can result in either organ rejection (if levels are too low) or increased toxicity (if levels are too high). Everolimus is primarily metabolized by cytochrome P450 3A4 (CYP3A4) in the liver and gut, and is also a substrate of the efflux transporter P-glycoprotein (P-gp). Medications that affect CYP3A4 or P-gp activity can therefore significantly alter everolimus blood concentrations.
It is essential to inform your transplant team about all medications you are taking, including prescription drugs, over-the-counter medicines, herbal supplements, and dietary products. Any change in medication during everolimus treatment should be accompanied by additional blood level monitoring.
Major Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Ketoconazole (strong CYP3A4 inhibitor) | Increases everolimus Cmax by 3.9-fold and AUC by 15-fold | Avoid combination; if unavoidable, major dose reduction and close monitoring required |
| Itraconazole, voriconazole, posaconazole | Significant increase in everolimus blood levels due to CYP3A4 inhibition | Avoid if possible; substantial dose reduction and frequent level monitoring needed |
| Rifampicin (strong CYP3A4 inducer) | Decreases everolimus Cmax by 58% and AUC by 63% | Avoid combination; risk of subtherapeutic levels and organ rejection |
| Ciclosporin (calcineurin inhibitor) | Increases everolimus AUC by approximately 2-fold via CYP3A4 and P-gp inhibition | Essential co-medication; everolimus dosing accounts for this interaction; monitor both drug levels |
| Live vaccines (e.g., MMR, varicella, BCG, yellow fever) | Risk of vaccine-strain infection due to immunosuppression | Contraindicated during treatment; inactivated vaccines may have reduced efficacy |
Minor Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Erythromycin, clarithromycin (moderate CYP3A4 inhibitors) | Moderate increase in everolimus levels | Monitor everolimus blood levels; dose adjustment may be needed |
| Grapefruit and grapefruit juice | CYP3A4 inhibition in gut wall, increased everolimus absorption | Avoid completely during treatment |
| St. John's wort (Hypericum perforatum) | CYP3A4 induction; may decrease everolimus levels unpredictably | Avoid completely; risk of rejection |
| ACE inhibitors (ramipril, enalapril, lisinopril) | Increased risk of angioedema when combined with mTOR inhibitors | Use with caution; monitor for facial or airway swelling |
| Statins (atorvastatin, simvastatin) | Ciclosporin (co-administered) increases statin levels; combined risk of myopathy | Use lowest effective statin dose; monitor for muscle pain and creatine kinase |
| Phenytoin, carbamazepine, phenobarbital | CYP3A4 induction; decreased everolimus levels | Avoid if possible; if used, increase monitoring frequency |
Because of the numerous potential drug interactions affecting everolimus blood levels, therapeutic drug monitoring (TDM) is mandatory. Any time a new medication is started, stopped, or has its dose changed, additional everolimus trough level measurements should be performed within a few days to ensure concentrations remain within the target range.
What Is the Correct Dosage of Everolimus Ethypharm?
Dosing of Everolimus Ethypharm is always individualized and guided by therapeutic drug monitoring (TDM). The target blood trough concentration depends on the type of transplant, the time since transplantation, and the specific immunosuppressive regimen used. Your transplant specialist will determine the appropriate dose based on your blood levels, kidney function, and clinical status. Never change your dose without specific instructions from your transplant team.
Adults – Kidney Transplantation
Kidney Transplant Recipients
Starting dose: 0.75 mg twice daily (total daily dose 1.5 mg), initiated as soon as possible after transplantation.
Target trough level: 3–8 ng/mL (whole blood trough concentration, measured using a validated immunoassay).
Ciclosporin co-administration: Everolimus should be taken at the same time as ciclosporin. The ciclosporin dose should be gradually reduced starting from month 1 post-transplant, targeting lower ciclosporin trough levels (C0) to protect kidney function. Typical ciclosporin target ranges decrease over time as guided by your transplant center's protocol.
Dose adjustments: Based on blood trough levels measured at steady state (at least 4–5 days after a dose change). Adjustments are typically made in 0.25 mg increments.
Adults – Heart Transplantation
Heart Transplant Recipients
Starting dose: 0.75 mg twice daily (total daily dose 1.5 mg), initiated as soon as clinically possible after transplantation.
Target trough level: 3–8 ng/mL (whole blood trough concentration).
Ciclosporin co-administration: As with kidney transplantation, everolimus is taken concurrently with ciclosporin. Ciclosporin trough levels should be maintained within the transplant center's recommended range, which may be adjusted over time.
Dose adjustments: Guided by blood trough level monitoring. Additional measurements should be performed after any change in everolimus dose, ciclosporin dose, or whenever CYP3A4 inhibitors or inducers are started or stopped.
Children and Adolescents
Everolimus Ethypharm is not recommended for use in children and adolescents under 18 years of age for transplant rejection prevention. There is insufficient data on the safety and efficacy of everolimus in the pediatric transplant population for this specific indication. If a pediatric patient requires immunosuppression, the treating physician will select an appropriate alternative regimen.
Elderly Patients
Limited clinical data are available for patients aged 65 years and older. No specific dose adjustment is recommended based on age alone. However, elderly patients may have reduced hepatic and renal function and are more likely to be taking multiple medications that could interact with everolimus. More frequent blood level monitoring and careful assessment of kidney and liver function are advisable. Dose adjustments should be made based on therapeutic drug monitoring rather than age per se.
Patients with Hepatic Impairment
| Hepatic Function | Dose Adjustment | Monitoring |
|---|---|---|
| Mild (Child-Pugh A) | Reduce to approximately two-thirds of normal dose | Frequent trough level monitoring |
| Moderate (Child-Pugh B) | Reduce to approximately half of normal dose | Close monitoring; adjust based on trough levels |
| Severe (Child-Pugh C) | Reduce to approximately one-third of normal dose; use only if benefit outweighs risk | Very frequent monitoring; consider alternative agents |
Missed Dose
If you miss a dose of Everolimus Ethypharm, take it as soon as you remember, provided it is within 6 hours of the scheduled time. If more than 6 hours have passed since the missed dose, skip it and take the next dose at the usual scheduled time. Do not take a double dose to make up for a forgotten dose, as this could increase the risk of side effects without providing additional benefit. If you repeatedly miss doses, contact your transplant team, as inconsistent dosing increases the risk of organ rejection.
Maintaining consistent dosing is critically important for transplant recipients. Consider using a pill organizer, smartphone alarm, or other reminder system to help ensure doses are taken on time every day. Your transplant team may also be able to suggest strategies for medication adherence.
Overdose
There is limited clinical experience with everolimus overdose in transplant recipients. In the event of suspected overdose, contact your doctor, go to the nearest emergency department, or call your local poison control center immediately. Symptoms of overdose may mirror and intensify the known side effects of everolimus, including increased susceptibility to infections, worsening of blood count abnormalities, and metabolic disturbances.
There is no specific antidote for everolimus overdose. Due to its high protein binding (approximately 74%) and extensive distribution into blood cells, everolimus is unlikely to be effectively removed by dialysis. Treatment is supportive and symptomatic. Activated charcoal may be considered if the overdose is recent and the patient is alert, but its effectiveness has not been established for everolimus specifically. Blood levels should be monitored closely, and supportive care should be provided as needed.
What Are the Side Effects of Everolimus Ethypharm?
Like all immunosuppressive medications, Everolimus Ethypharm can cause side effects, although not everybody gets them. The side effects listed below are based on clinical trial data and post-marketing surveillance. Some side effects are directly related to everolimus, while others may be influenced by the combination with ciclosporin and corticosteroids. Your transplant team will monitor you regularly with blood tests and clinical assessments to detect side effects early and manage them appropriately.
The frequency categories below follow the standard medical classification used by the European Medicines Agency (EMA) and the World Health Organization (WHO). If you experience any of the symptoms listed below, or any other unusual symptoms, discuss them with your transplant team. Do not stop taking Everolimus Ethypharm without medical advice, as stopping immunosuppression carries a risk of organ rejection that is typically more dangerous than the side effects themselves.
Very Common
Affects more than 1 in 10 patients
- Infections (viral, bacterial, and fungal, including urinary tract infections, upper respiratory infections, and CMV infection)
- Anemia (low red blood cell count)
- Leukopenia (low white blood cell count)
- Thrombocytopenia (low platelet count)
- Hypercholesterolemia (high cholesterol)
- Hyperlipidemia (high blood fats)
- New-onset diabetes or hyperglycemia (high blood sugar)
- Hypertension (high blood pressure)
- Peripheral edema (swelling of legs and ankles)
- Abdominal pain, diarrhea, nausea
- Impaired wound healing
- Elevated serum creatinine (indicating kidney stress)
- Proteinuria (protein in urine)
Common
Affects 1 in 10 to 1 in 100 patients
- Sepsis (blood infection)
- Wound infections
- Pneumonia
- Hypertriglyceridemia (high triglycerides)
- Hypokalemia (low potassium)
- Venous thromboembolism (blood clots)
- Pericardial effusion (fluid around the heart)
- Pleural effusion (fluid around the lungs)
- Mouth ulcers (stomatitis)
- Vomiting
- Elevated liver enzymes
- Rash, acne
- Arthralgia (joint pain)
- Headache, tremor
- Insomnia
- Urinary tract infections
- Male hypogonadism or erectile dysfunction
Uncommon
Affects 1 in 100 to 1 in 1,000 patients
- Lymphoma and post-transplant lymphoproliferative disorder (PTLD)
- Thrombotic microangiopathy (TMA/TTP/HUS)
- Non-infectious pneumonitis / interstitial lung disease
- Angioedema (swelling of face, lips, or throat)
- Pancreatitis
- Hepatitis
- Myalgia (muscle pain)
- Azoospermia (absence of sperm)
Rare
Affects fewer than 1 in 1,000 patients
- Pulmonary alveolar proteinosis
- BK virus-associated nephropathy with graft loss
- Hepatic necrosis
- Posterior reversible encephalopathy syndrome (PRES)
- Severe skin reactions (erythema multiforme)
Contact your transplant team or go to the nearest emergency department immediately if you experience: sudden shortness of breath or difficulty breathing; severe headache with visual disturbances or confusion; persistent high fever, chills, or signs of serious infection; chest pain or irregular heartbeat; facial swelling or difficulty swallowing; bloody or dark stools; significantly reduced urine output; or any other sudden or severe symptom.
How Should You Store Everolimus Ethypharm?
Proper storage of Everolimus Ethypharm is essential to maintain the medication's effectiveness and safety throughout its shelf life. Everolimus is sensitive to moisture and light, so careful handling and storage conditions must be maintained at all times.
- Temperature: Store at or below 25°C (77°F). Do not refrigerate or freeze the tablets unless specifically instructed by the pharmacist. Brief excursions to temperatures up to 30°C are generally acceptable, but prolonged exposure to high temperatures should be avoided.
- Light and moisture protection: Keep the tablets in their original blister packaging until the time of use. The blister packaging provides protection from moisture and light. Do not transfer the tablets to a pill organizer for long periods, as this removes the protective packaging.
- Keep out of reach of children: Store this medication in a secure location where children and pets cannot access it. Everolimus is a potent immunosuppressant and can be harmful if ingested by someone for whom it is not prescribed.
- Expiry date: Do not use this medication after the expiry date stated on the blister and carton (marked "EXP"). The expiry date refers to the last day of that month. If you notice that tablets have passed their expiry date, return them to a pharmacy for safe disposal.
- Disposal: Do not dispose of unused or expired medications via household waste or wastewater. Return unused medications to a pharmacy or use your local medication take-back program. This helps protect the environment and prevents accidental ingestion by others.
If you have any questions about the storage or handling of your medication, consult your pharmacist or transplant team. They can provide guidance specific to your local climate and storage conditions.
What Does Everolimus Ethypharm Contain?
Understanding the full composition of your medication is important, particularly if you have known allergies or intolerances to specific excipients. Below is a detailed breakdown of what each Everolimus Ethypharm 2.5 mg tablet contains.
Active Substance
Each tablet contains 2.5 mg of everolimus. Everolimus is a semi-synthetic derivative of sirolimus (rapamycin), a natural macrolide compound originally isolated from Streptomyces hygroscopicus in a soil sample from Easter Island (Rapa Nui). The chemical modification at the C-40 position of the sirolimus molecule gives everolimus improved oral bioavailability and pharmacokinetic properties compared to its parent compound.
Inactive Ingredients (Excipients)
The excipients in Everolimus Ethypharm tablets serve various pharmaceutical functions including binding, disintegration, lubrication, and stability. The typical excipients include:
- Lactose monohydrate: Used as a filler/diluent. Patients with rare hereditary galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medication.
- Hypromellose (HPMC): Used as a binder and film-coating agent to ensure tablet integrity and facilitate swallowing.
- Crospovidone: Functions as a disintegrant, helping the tablet break apart in the gastrointestinal tract for proper absorption of the active substance.
- Magnesium stearate: Used as a lubricant in the manufacturing process to prevent the tablet material from sticking to machinery during production.
- Butylated hydroxytoluene (BHT): An antioxidant added to protect everolimus from oxidative degradation, helping to maintain the potency and stability of the active substance throughout the product's shelf life.
- Lactose anhydrous: Additional filler used in the tablet formulation.
Everolimus Ethypharm tablets contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, speak to your doctor or pharmacist before taking this medicine. The amount of lactose per tablet is generally small, but patients with severe lactose intolerance should discuss this with their healthcare provider.
Appearance
Everolimus Ethypharm 2.5 mg tablets are white to slightly yellowish, round, flat tablets. They are supplied in blister packs within a carton. Each blister strip is sealed in an aluminum foil pouch to provide additional protection from moisture. Always check that the tablets match the description provided in the patient information leaflet. If you notice any unusual appearance (discoloration, crumbling, or unusual odor), do not take the tablets and consult your pharmacist.
Frequently Asked Questions About Everolimus Ethypharm
Everolimus Ethypharm is a generic formulation of everolimus manufactured by Ethypharm. Other branded versions of everolimus include Certican and Votubia (by Novartis). All contain the same active substance (everolimus) and work in the same way. However, it is important not to switch between different brands or formulations of everolimus without your transplant team's knowledge and approval, as slight differences in bioavailability between formulations could affect blood levels. Your transplant center will typically specify which brand should be dispensed, and any switch requires blood level monitoring.
No, you should avoid grapefruit and grapefruit juice entirely while taking Everolimus Ethypharm. Grapefruit contains compounds called furanocoumarins that inhibit the CYP3A4 enzyme in the intestinal wall. Since everolimus is metabolized by CYP3A4, consuming grapefruit can significantly increase the amount of everolimus absorbed into your bloodstream, leading to higher-than-intended blood levels and an increased risk of side effects. Other citrus fruits such as oranges, lemons, and limes do not have the same effect and are generally safe to consume.
Blood tests are performed frequently, especially in the early post-transplant period. Typically, everolimus trough levels, kidney function (creatinine, eGFR), liver function, complete blood count, cholesterol, triglycerides, and blood sugar are monitored. In the first few months after transplantation, blood level monitoring may be performed weekly or every 1–2 weeks. As your dose stabilizes, the frequency may decrease to monthly or every few months. However, additional blood tests are needed whenever your dose is changed, when other medications are started or stopped, or if you develop symptoms suggestive of side effects. Always attend your scheduled monitoring appointments.
Everolimus Ethypharm can be taken either with or without food, but it is important to be consistent. Food affects the rate and extent of absorption of everolimus. Taking it with a high-fat meal can reduce peak blood levels compared to taking it on an empty stomach. To minimize variability in blood levels and ensure consistent therapeutic effect, always take your tablets the same way – either always with food or always without food – and at the same time each day. Discuss with your transplant team which approach they recommend for your specific situation.
Live vaccines (such as MMR, varicella, BCG, yellow fever, and live influenza nasal spray) must not be given while you are taking Everolimus Ethypharm, as the immunosuppression could allow the weakened vaccine viruses to cause actual infection. Inactivated vaccines (such as the flu shot, COVID-19 mRNA vaccines, and pneumococcal vaccine) are generally safe to receive, but their effectiveness may be reduced due to your suppressed immune system. Your transplant team will advise you on which vaccines are recommended and when. Ideally, all vaccinations should be completed before transplantation when possible.
Stopping Everolimus Ethypharm suddenly without medical supervision can lead to acute organ rejection, which is a medical emergency. When immunosuppression is discontinued or significantly reduced, the immune system can rapidly recognize and attack the transplanted organ. This can result in irreversible damage to the graft and potential graft loss, which may necessitate a return to dialysis (for kidney transplant recipients) or could be life-threatening (for heart transplant recipients). Never stop or reduce your immunosuppressive medications without explicit instructions from your transplant team. If you are experiencing side effects that make it difficult to continue, discuss alternatives with your doctor.
References
- European Medicines Agency (EMA). Everolimus – Summary of Product Characteristics. Available from: ema.europa.eu. Last updated 2025.
- Kidney Disease: Improving Global Outcomes (KDIGO). Clinical Practice Guideline for the Care of Kidney Transplant Recipients. Am J Transplant. 2024.
- International Society for Heart and Lung Transplantation (ISHLT). Guidelines for the Care of Heart Transplant Recipients. J Heart Lung Transplant. 2024.
- European Society for Organ Transplantation (ESOT). Consensus Statement on Immunosuppression in Solid Organ Transplantation. 2024.
- Vitko S, et al. Everolimus with optimized cyclosporine dosing in renal transplant recipients: 6-month safety and efficacy results of two randomized studies. Am J Transplant. 2004;4(4):626–635.
- Eisen HJ, et al. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med. 2003;349(9):847–858.
- Tedesco-Silva H, et al. Everolimus plus reduced-exposure CsA versus mycophenolic acid plus standard-exposure CsA in renal-transplant recipients. Am J Transplant. 2010;10(6):1401–1413.
- World Health Organization (WHO). ATC/DDD Index – L04AA18 Everolimus. WHO Collaborating Centre for Drug Statistics Methodology. 2025.
- Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med. 2004;351(26):2715–2729.
- British National Formulary (BNF). Everolimus. National Institute for Health and Care Excellence (NICE). 2025.
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