HM Medical Clinic

Some reviews of clomid noted that the drug can also cause weight gain, hair loss and vision impairment clomid cost The information is provided for informational purposes only and is not a guide for self .

Cialis ne doit pas être prise à tous. Il est important que cialis en ligne est prescrit par un médecin, bien se familiariser avec les antécédents médicaux du patient. Ich habe Probleme mit schnellen Montage. Lesen Sie Testberichte Nahm wie cialis rezeptfrei 30 Minuten vor dem Sex, ohne Erfolg. Beginn der Arbeiten nach 4 Stunden, links ein Freund ein trauriges Ja, und Schwanz in sich selbst nicht ausstehen, wenn es keinen Wunsch ist.

Oxford myeloma group


Myeloma group
CYCLOPHOSPHAMIDE / BORTEZOMIB (/
DEXAMETHASONE (CyBorDex) Amyloidosis
protocol


INDICATION
Bortezomib is routinely commissioned by NHSE (baseline commissioning) for the the 1st line
treatment of patients with multi-system Amyloidosis following National Amyloidosis Centre review
Note: Mayo-stage III patients have a mortality risk of 50% in the first year.
GENERAL PRE-ASSESSMENT

1. Ensure all the following staging investigations are done: o FBC & film o Clotting screen o U&Es o LFTs o Calcium o Uric acid o CRP o Virology : HIV, Hepatitis B (including core antibody), and Hepatitis C o Calculated creatinine clearance (CrCl), urine/ creatinine ratio, light chain (Bence Jones) o Electrophoresis and immunofixation for quantitation of serum paraprotein and o Serum free light chain assay (Freelite) o Hevylite analysis (if paraprotein level difficult to quantify) o Albumin & β2 microglobulin for ISS staging o Myeloma FISH should be performed in all patients at diagnosis, and in selected patients at relapse/progression to help guide treatment decisions Samples should be sent to Wessex Regional Genetics Laboratory (address below) o Urine pregnancy testing for pre-menopausal women younger than 55 before each cycle. o Group and save o Imaging as per NICE/network guidance and clinical presentation o Bone marrow aspirate and trephine (with immunophenotyping for kappa/lambda if
Wessex regional genetic labolatory
Salisbury NHS Foundation Trust
Salisbury Disctrict hospital
Salisbury
Wilts
SP2 8BJ

This is a controlled document and therefore must not be changed
Authorised by Myeloma lead Dr. Karthik Ramasamy CyBorDex- Amyloidosis


Myeloma group
2. Consent - ensure patient has received adequate verbal and written information regarding their disease, treatment and potential side effects. Document in medical notes all information that has been given. 3. Fertility - all relevant patients should be offered fertility advice. 4. Document patient's height and weight
REGIMEN SPECIFIC PRE- ASSESSMENT

Evaluate for presence of neuropathy. This is usually done by clinical assessment although nerve
conduction studies may be useful in occasional patients to document the extent of neurological
damage prior to treatment with Bortezomib. Baseline clinical assessment must be documented in
the notes before the first dose of bortezomib is prescribed.
Baseline lying and standing blood pressure should be recorded prior to administration of cycle #1.
Echocardiogram/ cardiac MRI as appropriate
Patients with suspected/proven cardiac amyloid should be managed as an inpatient on a
cardiology ward for at least the first cycle, joint care with cardiologist
Refer for a specialist review at the national amyloidosis centre.
Serum NT-Pro BNP, cardiac troponin

DRUG REGIMEN

Bortezomib
1.3 mg/m2 given as SC Days 1, 8, 15 and 22. bolus as standard. In certain situations, in the first cycle, bortezomib can be administered intravenously 10 mg PO once daily On days of bortezomib only. increased to 20mg once daily if tolerated Cyclophosphamide 500 mg PO or IV weekly or, Days 1, 8, 15, 22 and 29 for weekly dosing

In patients with suspected/proven cardiac amyloid, add Doxycycline 100mg BD
CYCLE FREQUENCY

This is a controlled document and therefore must not be changed
Authorised by Myeloma lead Dr. Karthik Ramasamy CyBorDex- Amyloidosis


Myeloma group
Repeat every 35 days, for typically between 4-6 cycles. Consider reduction of dexamethasone
dose in elderly patients and watch fluid balance closely.

DOSE MODIFICATIONS

Haematological toxicity
Prior to initiating a new cycle of therapy:
• Platelets ≥ 70 x 109/L and ANC ≥ 1.0 x 109/L
• Non-haem toxicities should resolve to G1 or baseline

Toxicity
Posology modification or delay
Haematological toxicity during a cycle
• If prolonged G4 neutropenia or Omit cyclophosphamide 1 week (continue thrombocytopenia, or thrombocytopenia with dexamethasone). Restart at same dose when bleeding is observed in the previous cycle neutrophils and platelets recovered as above. If recurrent, i.e. if neutrophils < 1.0 x 109/L and platelets < 50 x 109/L on day 1 of subsequent cycles (when previously > than these levels), omit cyclophosphamide and consider dose reduction of cyclophosphamide for subsequent doses. If the patient was receiving 500 mg weekly, reduce to 400 mg, if 400 mg reduce to 300 mg, if 300 mg reduce to 200 mg. If patients receiving 50mg daily omit for a week and consider reduced frequency. • If platelet ≤ 30 x 109/L or ANC ≤ 0.75 x 109/l Withhold VELCADE on a VELCADE dosing day (other than Day 1) • If several VELCADE doses in a cycle are VELCADE reduced by 1 dose level (from 1.3 withheld (≥ 3 doses during twice weekly mg/m2 to 1 mg/m2, or from 1 mg/m2 to 0.7 administration or ≥ 2 doses during weekly administration) G ≥ 3 non-haem toxicities VELCADE withheld until symptoms resolved to G1 or baseline. VELCADE reinitiated with one (see above for neuropathic pain and/or dose level reduction (from 1.3 mg/m2 to 1 peripheral neuropathy) mg/m2, or from 1 mg/m2 to 0.7 mg/m2) Bortezomib-related neuropathy:
Severity of neuropathy
Posology modification
G1 with no pain or loss of function G1 with pain or G2 Reduce to 1.0 mg/m2 G2 with pain or G3 Withhold treatment until symptoms of toxicity have resolved. When toxicity resolves re-initiate treatment at 0.7 mg/m2 once per week. G4 and/or severe autonomic neuropathy Renal/Hepatic Impairment:
This is a controlled document and therefore must not be changed
Authorised by Myeloma lead Dr. Karthik Ramasamy CyBorDex- Amyloidosis


Myeloma group


Bortezomib:
Clinical decision if GFR < 20ml/min Bili > 1.5x ULN: reduce to 0.7 mg/m2 in the first treatment cycle. Consider dose escalation to 1.0 mg/m2 or further dose reduction to 0.5 mg/m2 in subsequent cycles based on patient tolerability.
Cyclophosphamide:
Clinical decision Exposure to active metabolites may not be increased, GFR > 20ml/min 100% dose suggesting that dose reduction may not be necessary. GFR 10 – 20ml/min 75% dose Clinical decision. GFR < 10ml/min 50% dose
Cyclophosphamide related toxicities include: leucopenia, amenorrhoea, haematuria, hair loss,
mucosal ulceration, anorexia, nausea and vomiting, pigmentation (typically affecting the palms and
nails of the palms and the soles of the feet) and interstitial pulmonary fibrosis. Dexamethasone
related toxicities include: mood changes, restlessness, withdrawal effects, glucose intolerance.

INVESTIGATIONS (at the beginning of each cycle unless otherwise noted)

• Urine pregnancy testing for pre-menopausal women younger than 55 before each cycle.
• FBC (weekly) • U&E, LFTs, Ca++ • Clinical assessment of neuropathy should be undertaken and documented prior to each cycle • Blood pressure (consider checking for postural drop if symptomatic). • Ig's, paraprotein, Freelite assay. • Consider bone marrow assessment after four cycles for non-secretory Myeloma.

CONCURRENT MEDICATIONS

• Allopurinol 300 mg daily for 7 days for cycle 1 only.
• Prophylactic aciclovir 200 mg bd to tid (depending on renal function) for the duration of treatment and 3 months post therapy. • Bisphosphonates as per protocol. • Proton Pump Inhibitor or H2 antagonist at clinician's discretion. • Consider prophylactic co-trimoxazole if heavily pre-treated or previous autograft. • Prescribe loperamide if needed for diarrhoea. • In patients with suspected/proven cardiac amyloid, add Doxycycline 100mg BD • Patients should be cautioned about the use of concomitant medications that may be associated with peripheral neuropathy (such as amiodarone, antivirals, isoniazid, nitrofurantoin or statins), or with a decrease in blood pressure. This is a controlled document and therefore must not be changed
Authorised by Myeloma lead Dr. Karthik Ramasamy CyBorDex- Amyloidosis


Myeloma group
Patients on bortezomib should be closely monitored if on CYP3A4-inhibitors (e.g. ketoconazole, ritonavir), or CYP3A4-inducers (rifampicin, carabamazepine, phenytoin, phenobarbital, and St John's wort). Patients on oral hypoglycaemic may require close monitoring of blood sugar levels. Emetic Risk:
Moderate emetic risk on weekly cyclophosphamide days, otherwise low risk.

ADVERSE EFFECTS/REGIEMN SPECIFIC COMPLICATIONS
Sudden Cardiac Death: patients with proven/suspected cardiac amyloid have a risk of fatal
arrhythmias in the early days/weeks of treatment. Patients should be counselled
appropriately for this
Painful neuropathy: Patients should be advised to report pain hypersensitivity prickling,
numbness and paraesthesia, if these occur see above dose reductions and consider use of Amitriptyline, Gabapentin and Pain Team referral. Neuropathy assessment tools are available in DTU. Caution in patients with existing peripheral neuropathy ( > Grade 2). • Dizziness and orthostatic hypotension: Patients should be advised that Bortezomib may
cause orthostatic hypotension and that they should sit upright for a few minutes prior to standing up from a recumbent position. Caution in patients with history of syncope, receiving medications associated with hypotension and patients who are dehydrated. Patients who experience dizziness or low blood pressure may benefit from 500ml intravenous 0.9% sodium chloride with each dose of bortezomib. • Gastrointestinal: Nausea, diarrhoea, vomiting and constipation are very common and ileus
has been reported. • Cyclophosphamide related toxicities include: leucopenia, amenorrhoea, haemorrhagic
cystitis, haematuria, hair loss, mucosal ulceration, anorexia, nausea and vomiting, pigmentation (typically affecting the palms and nails of the palms and the soles of the feet) pneumonitis and interstitial pulmonary fibrosis. • Dexamethasone related toxicities include: mood changes, restlessness, withdrawal effects,
glucose intolerance. • Herpes zoster virus reactivation, progressive multifocal leukoencephalopathy (PML)
REGIMEN SPECIFIC MORTALITY

• Patients with Mayo Stage III amyloid have an approximate 50% mortality in the first year. Patients should be carefully counselled about this very high risk.
REFERENCES
1. Richardson PG, Sonneveld P, Schuster MW et al. for the Assessment of Proteasome Inhibition
for Extending Remissions (APEX) Investigators. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005 Jun 16;352(24):2487-98. This is a controlled document and therefore must not be changed
Authorised by Myeloma lead Dr. Karthik Ramasamy CyBorDex- Amyloidosis


Myeloma group
2. Ailawadhi S, Mashtare TL, Coignet MV et al. Renal dysfunction does not affect clinical response in multiple myeloma (MM) patients treated with Bortezomib-based regimens. Blood. 2007; 110:Abstract 1477. 3. NICE guidance. TA129, October 2007, and TA228, July 2011. 4. Richardson P, Mitsiades C, Schlossman R et al. The treatment of relapsed and refractory multiple myeloma. Hematology Am Soc Hematol Educ Program. 2007:317-23. 5. Davies FE, Wu P, Jenner M, Srikanth M, Saso R, Morgan GJ. The combination of cyclophosphamide, velcade and dexamethasone induces high response rates with comparable toxicity to velcade alone and velcade plus dexamethasone. Haematologica 2007 Aug;92(8):1149-50. 6. eMC UK Summary of Product Characteristics for Velcade, Janssen, January 2016 Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma.2005 Dec 1;106(12):3777-84. 8. Wechalekar A D, Gillmore J D, Bird J, et all. 2014. Internet. Guidelines on the management of AL Amyloidosis. Online. Available at: (last accessed on 27/6/16). 9. Wechalekar AD, Schonland SO, Kastritis E, Gillmore JD, Dimopoulos MA, Lane T, Foli A, Foard D, Milani P, Rannigan L, Hegenbart U, Hawkins PN, Merlini G, Palladini G: A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood 2013;121:3420-3427. 9. eMC UK Summary of Product Characteristics for cyclophosphamide 50 mg tablets, Pharmacia, Revision
Review date
Formatting, drug regime, contraindication section removed This is a controlled document and therefore must not be changed
Authorised by Myeloma lead Dr. Karthik Ramasamy CyBorDex- Amyloidosis

Source: http://nssg.oxford-haematology.org.uk/myeloma/pdf-protocols/mm-11-cy-bor-dex-amyloidosis.pdf

Microsoft word - e-fps-1p _gb_.doc

Enzymatic Immunoassay for the quantitative determination of free Prostata Specific Antigen (PSA) in human serum The standards are calibrated against NIBSC (WHO) Prostate cancer is the most frequent type of cancer found in the man and the second cause of death due to the cancer in man, Until recently, digital rectal examination was the most accepted Zero Standard/Diluent:

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TRIBUNAL SPORTIF AUDIENCE PUBLIQUE DU 12 DECEMBRE 2014 Le Tribunal Sportif prononce le jugement suivant, en cause de : M. Eric CUNIN, titulaire de la licence pilote RACB SPORT n°698155 (Nationale, C-Rally). ENTENDU : - Me Gérard MARTIN, en sa qualité de Rapporteur judiciaire; - M. Eric CUNIN, licencié poursuivi ; - Le docteur Jean-Claude TELLINGS, secrétaire de la Commission