Cyclosporine a very strong immunosuppressant drug.
For many years I worked in National Serum and Vaccination Plant in
managerial capacity with hands on production duties of all human and animal
immunoglobulin, serums and many vaccines, so I become very alarmed / shocked
while Apotex announced, that Cyclosporine's
(avery strong immunosuppressant drug widely used in post-allogeneic organ
transplant to reduce the activity of the patient's immune system, and
therefore the risk of organ rejection. It has been studied in transplants of
skin, heart, kidney, liver, lung, pancreas, bone marrow, and small
intestine. Ciclosporin is a cyclic nonribosomal peptide of 11 amino acids
and contains a single D-amino acid. Apart from in transplant medicine,
ciclosporin is also used in psoriasis, severe atopic dermatitis, pyoderma
gangrenosum, chronic autoimmune urticaria, and, infrequently, in rheumatoid
arthritis and related diseases.) classification was changed and apparently
Authorities allowed production of it with out any restrictions/ protection
in common Manufacturing area / next to production of other products.
Treatment / exposure to Cyclosporine may be associated with a number of
potentially serious adverse drug reactions (ADRs).
ADRs can include gingival hyperplasia, convulsions, peptic ulcers,
pancreatitis, fever, vomiting, diarrhea, confusion, hypercholesterolemia,
dyspnea, numbness and tingling particularly of the lips, pruritus, high
blood pressure, potassium retention, and possibly hyperkalemia, kidney and
liver dysfunction (nephrotoxicity& hepatotoxicity), burning sensation at
finger tips and an increased vulnerability to opportunistic fungal and viral
I request from Apotex a Carbon Copy of Original industrial manufacturing
classification for Cyclosporine, which demanded processing of this substance
in isolated area (with Air Locks in entrances to the Process Rooms, on
dedicated equipment, with special Air Handling Systems, with special
protective equipment for Personnel etc.)
During production of Validation Batches in not compliant manner and due to
massive discharges of this material on the floors it was discovered, that
product does heavily end up all over the plant including Offices (all over
the desks of Offices employees) and Personnel had to be evacuated from the
Apotex in stead of getting its infrastructure modernized and up to
regulatory compliance announced that apparently did manage to change product's
classification which apparently removed ALL restrictions / Regulations and
allowed Apotex to process it with out any considerations for contamination
of the Personnel and cross contamination of the products. I request Carbon
Copy of Regulatory Agency's Report (Health Canada? etc.) changing
classification of the Cyclosporine which permitted Apotex to proceed with
production of this substance in not controlled / regulated manner.
Cyclosporine Side Effects
Autonomic Nervous System:
Dry mouth, increased sweating
Body as a Whole:
Allergy, asthenia, hot flushes, malaise, overdose, procedure NOS*, tumor
NOS*, weight decrease, weight increase
Abnormal heart sounds, cardiac failure, myocardial infarction, peripheral
Central and Peripheral Nervous System :
Hypoesthesia, neuropathy, vertigo
Constipation, dysphagia, enanthema, eructation, esophagitis, gastric ulcer,
gastritis, gastroenteritis, gingival bleeding, glossitis, peptic ulcer,
salivary gland enlargement, tongue disorder, tooth disorder
Abscess, bacterial infection, cellulitis, folliculitis, fungal infection,
herpes simplex, herpes zoster, renal abscess, moniliasis, tonsillitis, viral
Anemia, epistaxis, leukopenia, lymphadenopathy
Liver and Biliary System:
Metabolic and Nutritional:
Diabetes mellitus, hyperkalemia, hyperuricemia, hypoglycemia
Arthralgia, bone fracture, bursitis, joint dislocation, myalgia, stiffness,
synovial cyst, tendon disorder
Breast fibroadenosis, carcinoma
Anxiety, confusion, decreased libido, emotional lability, impaired
concentration, increased libido, nervousness, paroniria, somnolence etc.
Reproductive (Female) :
Breast pain, uterine hemorrhage
Respiratory System :
Abnormal chest sounds, bronchospasm
Skin and Appendages :
Abnormal pigmentation, angioedema, dermatitis, dry skin, eczema, nail
disorder, pruritus, skin disorder, urticaria
Abnormal vision, cataract, conjunctivitis, deafness, eye pain, taste
perversion, tinnitus, vestibular disorder
Urinary System :
Abnormal urine, hematuria, increased BUN, micturition urgency, nocturia,
polyuria, pyelonephritis, urinary incontinence
Body as a Whole:
Fever, flushes, hot flushes
Central and Peripheral Nervous System :
Appetite increased, insomnia, dizziness, nervousness, vertigo
Abdominal distention, constipation, gingival bleeding
Liver and Biliary System:
Skin malignancies (squamous cell and basal cell carcinomas)
Platelet, bleeding, and clotting disorders, red blood cell disorder
Infection, viral and other infection
Skin and Appendages :
Acne, folliculitis, keratosis, pruritus, rash, dry skin
Mild hypomagnesemia and hyperkalemia may occur but are asymptomatic.
Increases in uric acid may occur and attacks of gout have been rarely
reported. A minor and dose related hyperbilirubinemia has been observed in
the absence of hepatocellular damage. Cyclosporine therapy may be associated
with a modest increase of serum triglycerides or cholesterol.
Side Effects by Body System
BK virus associated nephropathy has been associated with serious outcomes,
including deteriorating renal function and renal graft loss.
Elevations in serum creatinine and BUN are common during cyclosporine
therapy and do not necessarily indicate allograft rejection.
In addition, cyclosporine-induced hyperuricemia may predispose the patient
to renal calculi.
Renal insufficiency is dose-related. It is often accompanied by
hypertension. Cyclosporine causes a reversible reduction in renal blood flow
and glomerular filtration rate. The mechanism of cyclosporine-induced
nephrotoxicity is now considered to be vasoconstriction of the afferent
arterioles. ET1 is also considered to be a key substance of
cyclosporine-induced nephrotoxicity. Mild nephrotoxicity generally responds
to reductions in cyclosporine doses. A chronic, progressive nephrotoxicity
may also occur in which discontinuation of cyclosporine fails to alleviate
the renal insufficiency. Renal biopsies from these patients may demonstrate
interstitial fibrosis, tubular atrophy, global or segmental
glomerulosclerosis, or smooth vascular muscle damage. It has been suggested
that higher cumulative doses or high cyclosporine trough levels may be
associated with the development of interstitial fibrosis.
Renal function should be closely monitored. Differentiation between
cyclosporine-induced nephrotoxicity, allograft rejection, and other causes
of impaired renal function should be made before considering cyclosporine
The use of nonsteroidal anti-inflammatory agents in combination with
cyclosporine may increase the risk of renal toxicity, especially in
rheumatoid arthritis patients. Intact renal prostaglandins are necessary for
maintaining adequate renal blood flow in patients treated with cyclosporine.
Renal deterioration may occur independent of changes in cyclosporine levels.
Renal side effects including renal insufficiency (up to 38%) and BK virus
associated nephropathy have been reported. A chronic, progressive,
irreversible nephrotoxicity has also been reported. Elevations in serum
creatinine and BUN are common during cyclosporine therapy and do not
necessarily indicate allograft rejection. A case of hemolytic uremic
syndrome (HUS) associated with cyclosporine therapy has been reported. A
fatal case of acute tubular necrosis has been reported. In addition,
cyclosporine-induced hyperuricemia may predispose the patient to renal
Seizures in patients on cyclosporine therapy may be associated with
hypomagnesemia or concomitant high-dose corticosteroids. In addition,
hypercholesterolemia and hypertension may contribute to cyclosporine
neurotoxicity. Hypomagnesemia and hypercholesterolemia allow easier
diffusion of cyclosporine across the blood-brain barrier potentiating
A review of cyclosporine-induced neurotoxicity revealed incidence after
liver transplantation. Intravenous administration of cyclosporine was
associated with more severe reactions such as psychosis, however severe
reactions occurred rarely. MRI abnormalities were seldom found. Only 61% of
patients that experienced neurotoxicity had cyclosporine trough levels
suggestive of toxicity.
The speech disorder leading to mutism which has been associated with
cyclosporine therapy was reversible.
The permanent blindness which was reported in patients was suspected to be
due to neurotoxicity associated with elevated cyclosporine levels.
Dechallenge with cyclosporine did not reverse the blindness . The blindness
occurred over a 36 hour period 3 weeks following a kidney-pancreas
transplant. The cyclosporine trough level was at its highest on the day of
complete blindness (495 ng/mL). The mechanism by which cyclosporine induces
neurologic blindness is unknown.
Nervous system side effects of cyclosporine have included tremors (to 55%)
and headache (to 15%). Depression, somnolence, decreased visual acuity,
confusion, paresthesias, seizures, and a reversible speech disorder leading
to mutism have also been associated with cyclosporine therapy. Three cases
of leukoencephalopathy have also been reported.
Dermatologic side effects of cyclosporine have included hypertrichosis acne
and pruritus. Cyclosporine has been associated with pilosebaceous lesions,
including hypertrichosis, epidermal cysts, keratosis pilaris, acne,
folliculitis, sebaceous gland hyperplasia, and cutaneous malignancies. A
case of erythroderma resembling Sezary syndrome with lymphocytic infiltrates
of the skin has been reported. Cases of folliculodystrophy and
pseudoporphyria have also been reported.
Hepatic side effects have been common, occurring in up to 50% of patients,
generally mild and self-limited, and manifest as elevated bilirubin, serum
transaminases, and alkaline phosphatase values. In addition, cholestatic
jaundice has been reported.
A syndrome characterized by thrombocytopenia and microangiopathic anemia is
reported in some patients.
Hematologic side effects have included leukopenia anemia, and
Metabolic side effects of cyclosporine have included significant
hyperkalemia, which is sometimes associated with hyperchloremic metabolic
Gastrointestinal side effects have included gum hyperplasia , diarrhea ,
nausea and vomiting , anorexia, abdominal discomfort, and reports of upper
gastrointestinal bleeding. Pancreatitis has also been reported.
Study has reported that reduced basal and stimulated nitrous oxide
production in cyclosporine-treated renal transplant recipients. The authors
stated that this suggests endothelial dysfunction, and may explain the
increased risk of premature atherosclerosis and cardiovascular death. They
felt this might also provide, at least in part, a potential mechanism to
explain cyclosporine-induced hypertension.
Cardiovascular side effects have included hypertension induced by
cyclosporine. Myocardial infarction has also been reported rarely.
Endocrine side effects of cyclosporine have included hypertriglyceridemia,
increases in serum prolactin, decreases in serum testosterone, gynecomastia,
hyperglycemia, and hypertrichosis.
Other side effects including a significant risk of acute rejection and death
and/or graft loss have been reported. Cases of trichomegaly has been
reported. A cases of calcineurin inhibitor induced pain syndrome (CIPS) has
also been reported.
Hypersensitivity side effects to cyclosporine have occurred.
Anaphylaxis, manifest as acute dyspnea, tachypnea, pruritus, rash, and chest
discomfort has been reported in rare cases after intravenous administration
A manifestation of neurotoxicity induced by cyclosporine (which has occurred
in transplant patients more frequently than in other indications) is optic
disc edema including papilledema, with possible visual impairment, secondary
to benign intracranial hypertension.
Ocular side effects have included reports of pseudotumor cerebri, which
resolved rapidly upon discontinuation of cyclosporine, and optic disk edema.
Permanent blindness has been reported in one patient. A cases of
cyclosporine-induced retinal toxic blindness has also been reported.
Oncologic side effects including fatal cases of metastatic angiosarcoma
during cyclosporine and prednisone immunosuppression (after kidney
transplantation) have been reported.
The development of neoplasms, particularly lymphomas and skin malignancies,
is more likely in immunosuppressed patients.
In a large study, an increased incidence of lymphoma and Kaposi's sarcoma
was found in patients treated with cyclosporine relative to those treated
with a combination of azathioprine and prednisone. In some reported cases of
B-cell lymphoma, the Epstein-Barr virus genome was found in the malignant
cells, suggesting opportunistic infection during a cyclosporine-induced
Immunologic side effects have included an increased patient susceptibility
to opportunistic infections due to cyclosporine-induced immunosuppression.
Accelerated hepatitis B and C infections, sometimes resulting in hepatic
necrosis, Pneumocystis pneumoniae infections, as well as other viral,
fungal, and bacterial infections have been reported in patients treated with
cyclosporine. An in vitro study demonstrated enhanced intracellular
cytomegalovirus production and virus spread, indicating an increased risk of
CMV infection in cyclosporine-treated patients.
Local side effects including a cases of recurrent infusion phlebitis have
Respiratory side effects have included respiratory arrest and aspiration
pneumonia in one patient that lead to the death of that patient.
Apotex subjected me to the most horrifying experiences imaginable.
BEYOND ANY DOUBT I WAS EXPOSED TO VERY MANY (4000 +) DANGEROUS SUBSTANCES
WITH OUT ANY PROTECTION AND THAT THEY CAUSED THE ADVERSE EFFECTS AND
INJURIES I NOW SUFFER (Documented).
Apotex (my former employer) ravaged me (my system)! Apotex exposed me with
out any personal / collective protection to well over 4000 very potent
chemicals / actives. The human nervous system is particularly vulnerable to
toxic-chemical insults. Many chemicals can permanently disrupt nervous
Many of those side effects I do suffer includeing abnormal pigmentation,
skin disorder , skin malignancies (basal cell carcinomas), very painful a
soft-tissue mass (soft-tissue tumors/soft-tissue lumps etc.
DECIVED, ABONDONED BY Ontario Labour Board, Ontario Ombudsmen Office, FAIR
PRACTICES COMMISION, Ontario Worker Adviser, Ontario Human Rights
Commission, Ontario Human Rights Tribunal, WSiB, -GOVERNMENT of ONTARIO.
Unfortunately in my case many key Government Agencies turn out to be
dysfunctional and criminal.
I AM SUFFERING WITH OUT ANY HELP NOR CONSTITUTIONAL / LAW PROTECTION IN
The issue/problem becomes politically sensitive and concluding it in lawful
manner is in the best interest of General Public.