Rapamycin (Sirolimus) — Informed Consent (Off‑label Longevity Use)

INFORMED CONSENT FOR RAPAMYCIN (SIROLIMUS) — OFF‑LABEL LONGEVITY USE

§1 PURPOSE, CONTEXT, AND SCOPE

§1.1 This document constitutes an informed consent agreement between the Patient identified herein (the "Patient") and the Prescribing Physician acting on behalf of the Clinic. It is intended to document that the Patient has received, understood, and accepted comprehensive information regarding the proposed pharmacological use of rapamycin (sirolimus) for off‑label longevity/healthspan purposes.

§1.3 Health optimization context: The Patient understands that the Clinic operates as a proactive health optimization / longevity practice. The Clinic is not an emergency provider. The Patient is responsible for maintaining an appropriate relationship with a primary care physician and/or relevant specialist(s) for diagnosis and management of disease, acute care, and emergencies.

§1.4 This consent is governed by the laws of Denmark and the European Union, including but not limited to the Danish Health Act (Sundhedsloven) and Regulation (EU) 2016/679 (General Data Protection Regulation).

§1.5 By signing this document, the Patient confirms they have had adequate time to read, consider, and ask questions, and that their questions have been answered to their satisfaction.

§3 MEDICATION, CLASS, AND DESCRIPTION OF TREATMENT

§3.1 Rapamycin (also known as sirolimus) is an immunosuppressive medication that inhibits the mammalian target of rapamycin (mTOR) pathway, a key regulator of cell growth, proliferation, and metabolism.

§3.3 Intended use in this Clinic: The Patient understands that rapamycin is being prescribed for off‑label use related to longevity/healthspan optimization. The Patient understands that this intended use is not an EMA‑authorised indication and is based on preclinical research and emerging clinical evidence suggesting potential benefits in aging biology.

§3.4 Off‑label status: The Patient understands that:

  • Rapamycin is EMA‑authorised for specific medical indications (e.g., organ transplantation, certain lymphangioleiomyomatosis cases)
  • Use for "longevity," "healthspan," or "geroprotection" is off‑label
  • Clinical benefit for longevity/healthspan extension in humans is not proven
  • Evidence supporting longevity use is primarily from preclinical studies (animal models) and limited human observational data

§3.5 The treatment will be administered orally, typically at a low dose (often weekly or intermittent dosing), at a regimen determined by the Prescribing Physician based on the Patient's clinical status and treatment goals.

§4 REGULATORY STATUS AND APPROVED INDICATIONS

§4.1 Rapamycin (sirolimus) has been authorised by the European Medicines Agency (EMA) for specific medical indications, including:

  • Prevention of organ rejection in kidney transplantation
  • Treatment of lymphangioleiomyomatosis (LAM) in selected patients

§4.2 Off‑label longevity use: The Patient understands that prescribing rapamycin primarily for "longevity," "healthspan," "geroprotection," or proactive aging intervention is off‑label and is not an EMA‑approved indication.

§4.3 The Patient understands that evidence supporting off‑label longevity use is derived from:

  • Preclinical research in model organisms (yeast, worms, flies, mice) showing lifespan extension
  • Mechanistic studies suggesting mTOR inhibition may influence aging pathways
  • Limited human observational data and small clinical studies
  • Ongoing research in the field of geroprotection

§4.4 The Patient understands that results observed in preclinical models and limited human studies may not translate to comparable magnitude of benefit in healthy individuals, and that prevention of age‑related disease and extension of lifespan in an individual patient cannot be guaranteed.

§4.5 The Patient has been informed that the intended use in this Clinic is off‑label and accepts this information.

§5 PROPOSED BENEFITS OF TREATMENT

§5.1 The Patient understands that the potential benefits of rapamycin in the context of off‑label longevity use are hypothetical and not proven in humans. Proposed benefits may include, but are not limited to:

§5.1.1 Hypothetical longevity/healthspan effects: Based on preclinical research, some authors propose that mTOR inhibition may:

  • Influence cellular maintenance pathways (e.g., autophagy)
  • Reduce age‑related inflammation
  • Improve metabolic function
  • Potentially delay age‑related diseases

§5.1.2 The Patient understands that these proposed benefits are based on mechanistic hypotheses and preclinical data, and that clinical benefit for longevity/healthspan in humans is not established.

§5.2 No guarantee of benefit: The Patient acknowledges that:

  • No clinical benefit for longevity/healthspan extension in humans has been proven
  • Individual responses vary, and some patients may not experience any benefit
  • Rapamycin does not guarantee prevention of age‑related decline, extension of lifespan, or improvement in healthspan
  • Long‑term safety and efficacy for longevity use in healthy individuals are not established

§6 MATERIAL RISKS AND ADVERSE EFFECTS

§6.1 The Patient has been informed of the following risks and adverse effects associated with rapamycin therapy. The Patient understands that this list is not exhaustive and that other adverse effects may occur.

§6.2 Common adverse effects (occurring in ≥1% of patients):

  • Mouth ulcers (stomatitis, aphthous ulcers)
  • Elevated cholesterol and triglycerides
  • Acne or rash
  • Gastrointestinal upset (nausea, diarrhoea, abdominal discomfort)
  • Headache
  • Fatigue
  • Oedema (fluid retention)
  • Joint pain

§6.3 Uncommon adverse effects (occurring in 0.1–1% of patients):

  • Elevated blood glucose or worsening glucose tolerance
  • Anaemia or thrombocytopenia (low blood cell counts)
  • Elevated liver enzymes
  • Elevated creatinine (kidney function markers)
  • Pneumonitis (lung inflammation)
  • Wound healing complications

§6.4 Rare but serious adverse effects (occurring in <0.1% of patients or reported post‑marketing):

§6.4.1 Immunosuppression and infection risk: Rapamycin suppresses the immune system, increasing the risk of infections, including:

  • Bacterial infections
  • Viral infections (including reactivation of latent viruses)
  • Fungal infections
  • Opportunistic infections

The Patient must seek urgent medical care for signs of infection, including fever, chills, persistent cough, or other symptoms of infection.

§6.4.2 Impaired wound healing: Rapamycin can delay wound healing and increase the risk of wound complications. The Patient must inform the Clinic before any planned surgery or procedures, and may need to temporarily discontinue rapamycin.

§6.4.3 Pneumonitis: Rare but serious lung inflammation can occur. The Patient must seek urgent care for persistent cough, shortness of breath, or chest discomfort.

§6.4.4 Metabolic effects: Rapamycin can cause:

  • Hyperlipidaemia (elevated cholesterol/triglycerides)
  • Hyperglycaemia (elevated blood glucose)
  • The Patient understands that regular monitoring of lipids and glucose is required

§6.4.5 Renal effects: Rapamycin may affect kidney function. The Patient understands that regular monitoring of renal function is required.

§6.4.6 Hematological effects: Rapamycin can cause anaemia, thrombocytopenia, or leukopenia. The Patient understands that regular monitoring of blood counts is required.

§6.4.7 Allergic reactions: Rare allergic reactions can occur. The Patient must seek urgent care for swelling of face/tongue/throat, difficulty breathing, or widespread rash.

§7 CONTRAINDICATIONS AND PRECAUTIONS

§7.1 The Patient confirms that they have disclosed all relevant medical history to the Prescribing Physician. Rapamycin is generally contraindicated or requires special caution in the following circumstances:

§7.2 Absolute contraindications:

  • Known hypersensitivity or allergy to rapamycin or any excipients
  • Active infection (relative contraindication; requires assessment)
  • Severe liver impairment
  • Severe renal impairment

§7.3 Relative contraindications and precautions:

  • History of recurrent infections or immunodeficiency
  • Active or recent malignancy (requires specialist assessment)
  • Uncontrolled diabetes or severe hyperglycaemia
  • Severe hyperlipidaemia
  • History of pneumonitis or interstitial lung disease
  • Planned surgery or procedures (requires temporary discontinuation)
  • Use in children or adolescents (except under specialist supervision)

§8 DRUG INTERACTIONS

§8.1 The Patient has disclosed all current medications, including prescription drugs, over‑the‑counter medications, supplements, and herbal products. Rapamycin has numerous and potentially serious drug interactions. The following are of particular clinical significance:

§8.2 CYP3A4 inhibitors (increase rapamycin levels, increasing risk of toxicity):

  • Certain antibiotics (e.g., clarithromycin, erythromycin)
  • Antifungals (e.g., ketoconazole, itraconazole)
  • Certain antivirals
  • Grapefruit and grapefruit juice
  • Certain calcium channel blockers

§8.3 CYP3A4 inducers (decrease rapamycin levels, reducing efficacy):

  • Certain anticonvulsants (e.g., carbamazepine, phenytoin)
  • Rifampin
  • St. John's wort

§8.4 Other significant interactions:

  • Other immunosuppressive medications (increased infection risk)
  • Live vaccines (contraindicated due to immunosuppression)
  • Certain anticoagulants

§8.5 The Patient agrees to inform the Clinic before starting any new medication, supplement, or herbal product, and to avoid grapefruit and grapefruit juice while taking rapamycin.

§9 MONITORING REQUIREMENTS

§9.1 The Patient agrees to undergo monitoring as recommended by the Prescribing Physician, which may include:

§9.2 Baseline assessments (before starting rapamycin):

  • Complete blood count (CBC)
  • Lipid profile (cholesterol, triglycerides)
  • Fasting glucose and HbA1c
  • Liver function tests
  • Renal function (creatinine, eGFR)
  • Blood pressure
  • Assessment of infection risk and vaccination status

§9.3 Ongoing monitoring (typically every 3–6 months, or more frequently as clinically indicated):

  • Complete blood count (to monitor for cytopenias)
  • Lipid profile (to monitor for hyperlipidaemia)
  • Fasting glucose and HbA1c (to monitor for hyperglycaemia)
  • Liver function tests
  • Renal function
  • Blood pressure
  • Clinical assessment of symptoms, adverse effects, and signs of infection

§9.4 Dose adjustment: The Patient understands that rapamycin dosing may be adjusted based on clinical response, laboratory values, and adverse effects. The Patient agrees to follow dosing instructions and not to self‑adjust the dose.

§9.5 Discontinuation considerations: The Patient understands that:

  • Rapamycin should be temporarily discontinued before planned surgery or procedures
  • The Patient must inform the Clinic before any planned procedures
  • The Patient agrees to consult with the Prescribing Physician before discontinuing treatment

§10 ALTERNATIVE TREATMENTS

§10.1 The Patient has been informed of the following alternatives to rapamycin for longevity/healthspan optimization:

§10.2 Lifestyle interventions: Evidence‑based lifestyle interventions, including:

  • Caloric restriction or intermittent fasting
  • Regular physical activity (aerobic and resistance training)
  • Adequate sleep
  • Stress management
  • Smoking cessation
  • Moderate alcohol consumption

§10.3 Other pharmacological interventions: Other medications or supplements that have been proposed for longevity/healthspan (e.g., metformin, SGLT2 inhibitors), understanding that evidence for longevity benefit in humans is also limited.

§10.4 No treatment: The Patient may choose not to receive pharmacological intervention for longevity/healthspan, understanding that this is a personal choice and that evidence for benefit is not established.

§10.5 The Patient confirms that these alternatives have been discussed and that they have chosen to proceed with rapamycin.

§12 LIMITATION OF LIABILITY / NO GUARANTEE

§12.1 The Patient understands that medicine is not an exact science and no outcomes can be guaranteed.

§12.2 The Patient understands that:

  • Clinical benefit for longevity/healthspan extension in humans is not proven
  • Rapamycin does not guarantee prevention of age‑related decline, extension of lifespan, or improvement in healthspan
  • Long‑term safety and efficacy for longevity use in healthy individuals are not established

§12.3 The Patient understands that adverse effects may occur despite appropriate prescribing and monitoring.

§12.4 Nothing in this consent excludes liability that cannot be excluded under applicable Danish law.

§13 WITHDRAWAL OF CONSENT

§13.1 The Patient may withdraw consent at any time by contacting the Clinic. The Prescribing Physician will provide guidance on safe discontinuation where applicable.

§14 DATA PROTECTION AND RECORDKEEPING

§14.1 The Patient's personal data and health information will be processed in accordance with GDPR and applicable Danish law.

§14.2 This consent may be retained as part of the Patient's medical record.

§15 ACKNOWLEDGMENTS AND DECLARATIONS

By consenting, the Patient confirms the following:

  • I have read this consent document in its entirety, or it has been read to me, and I understand its contents.
  • I understand that rapamycin is being prescribed for off‑label longevity/healthspan use and that clinical benefit for longevity in humans is not proven.
  • I understand the medication prescribed (the prescribed medication) and the purpose of off‑label rapamycin therapy.
  • I understand that benefits are hypothetical and not guaranteed.
  • I understand the material risks, including immunosuppression and infection risk, impaired wound healing, metabolic effects (hyperlipidaemia, hyperglycaemia), and drug interactions (especially CYP3A4 inhibitors/inducers and grapefruit).
  • I understand that regular monitoring (blood counts, lipids, glucose, liver/kidney function) is required.
  • I understand the contraindications and have disclosed all relevant medical history.
  • I understand that I must avoid grapefruit and grapefruit juice and inform the Clinic before starting any new medications.
  • I understand that I must inform the Clinic before any planned surgery or procedures.
  • I have disclosed all relevant medical history and current medications to the Clinic.
  • I understand I must seek urgent/emergency care for signs of infection or other severe symptoms and that the Clinic is not an emergency service.
  • I have had the opportunity to ask questions and my questions were answered.
  • I voluntarily consent to commence or continue treatment with the prescribed medication under the regimen agreed with my clinician.