For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only

Panimun Bioral
Cyclosporine USP

Panimun Bioral Solution

(Cyclosporine Oral Solution USP-100 mg/ml)

Description
Pale yellow coloured, clear liquid.

Composition
Each ml of solution contains:
Cyclosporine USP........100 mg.

Panimun Bioral 25 mg
(Cyclosporine Capsules USP-25 mg)

Description
Reddish brown coloured, oval shaped, soft gelatin capsules containing pale
yellow coloured, clear liquid.

Composition
Each soft gelatin capsule contains:
cyclosporine USP....... 25 mg
Approved colours used in capsule shells

Panimun Bioral 50 mg
(Cyclosporine Capsules USP-50 mg)

Description
Coffee browm coloured, oblong shaped, soft gelatin capsules containing pale
yellow coloured, cleared liquid.

Composition
Each soft gelatin capsule contains:
cyclosporine USP....... 50 mg
Approved colours used in capsule shells

Panimun Bioral 100 mg

(Cyclosporine Capsules USP-100 mg)

Description
Reddish brown coloured, oblong shaped, soft gelatin capsules containing pale
yellow coloured, clear liquid.
 Composition
Each soft gelatin capsule contains:
cyclosporine USP....... 100 mg
Approved colours used in capsule shells

PROPERTIES
The cyclosporine (also known as cyclosporine A) is a lipophillic cyclic polypeptide composed of
11 amino acids1. It is a potential immunosuppressor which has shown to be able to prolong in
animals, the survival of transplants such as skin, heart, kidneys, pancreas, bone marrow, small
intestine and lungs.
Various studies on animals have proved that cyclosporine inhibits the development of cell
mediated immunity including allograft immunity, delayed cutaneous hypersensitivity, experimental
allergic encephalomyelitis, Freund's adjuvant arthritis, reaction from transplantation towards host
(graft versus host disease, GVHD) and the production of T cell dependent antibodies.
Cyclosporine inhibits the production as well as the release of lymphokines such as interleukin
22(T cell growth factor, TCGF). From experimental data it can be noticed that cyclosporine blocks
the quiescent lymphocytes in phase G or at the beginning of phase G1 of the cellular cycle.
All the available data indicates that cyclosporine acts on the lymphocytes in a specific and
reversible manner. Cyclosporine does not depress hemopoiesis and does not alter the function of
phagocytes. Patients treated with cyclosporine are less susceptible to infections as compared to
those that receive another immunosuppressive treatment.
In human beings cyclosporine has given positive results in kidney transplants, bone marrow
transplants to prevent and treat rejection and GVHD, and in a series of diseases of autoimmune
origin.

PHARMACOKINETICS
After oral administration (oral solution and capsules) the peak plasma blood concentration is
reached between the first and third hour. Absolute bio-availability of oral preparation in stationery
state is 20-50% (average 34%).
The Cmax, Tmax and AUC0-24hrs of Panimun Bioral solution was 858.06 + 54.22 ng/ml, 1.42 + 0.11
hrs and 2995.78 + 139.32 ng hr ml-1 respectively, after a single dose of 1.8 ml solution equivalent
to 180 mg cyclosporine3. The Cmax, Tmax and AUC0-12hrs of Panimun Bioral Capsule was 792.94 +
54.07 ng/ml, 2.09 + 0.08 hrs and 3266.71 + 197.12 ng hr ml-1 respectively, after single oral dose
of 175 mg capsule.4 Assay employed was Radio Immuno Assay. The mean elimination half life
(t½) of single oral dose of solution and capsule was 4.87 + 1.73 hrs and 4.80 + 1.58 hrs
respectively.
Cyclosporine is distributed in large part outside the blood volume. In blood, distribution is
saturation dependent. Approximately 33-47% is found in the plasma, 4-9% in lymphocytes, 5-
12% in granulocytes, 41-58% in erythrocytes. In plasma approximately 90% is bound to proteins
primarily lipoproteins. Disposition of cyclosporine from blood is biphasic. Elimination is mainly
biliary and only 6% of dose is excreted in urine. Cyclosporine is extensively metabolised with no
major metabolic pathway. Only 0.1% of unchanged drug is excreted in urine.

THERAPEUTIC INDICATIONS
a) Organ transplantation
Cyclosporine is indicated as immunosuppressor for the prevention of refusal (or rejection) of
allogenic transplantation of kidney, liver, heart, lung and pancreas. It may be used alone or in
association with other immunosuppressants with low doses of corticosteroids. Cyclosporine may
also be used in the treatment for rejection of transplantation in patients who have received
previously other immunosuppressants.
b) Bone-marrow transplantation & Aplastic Anaemia
Cyclosporine is indicated as immunosuppressor in the prevention of rejection of bone marrow
transplantation and or in the prevention and in the therapy of the graft versus host disease
(GVHD) alone or in combination with other drugs.
c) Endogenous uveitis
Cyclosporine is indicated for treatment of posterior or intermediate uveitis of non infectious origin
in active phase, with grave risk of loss of visual function, when the other conventional therapies
have not proven to be effective or when they provoke unacceptable side effects. Cyclosporine is
also indicated for treatment of uveitis in the Behcet's Syndrome, with repeated inflammatory
attacks of the retina.
d) Psoriasis
Cyclosporine is indicated for patients with serious psoriasis, in whom the conventional therapies
have proved to be ineffective or inappropriate.
e) Rheumatoid arthritis
Cyclosporine is indicated for the treatment of severe rheumatoid arthritis in active phase, in whom
the classic antirheumatic medicines are inefficient and inappropriate.
f) Nephrotic syndrome
Cyclosporine can be used to induce remissions and to maintain the patients of steroid-dependent
and steroid resistant nephrotic syndrome due to glomerular diseases such as minimal change
nephropathy, focal and segmental glomerulosclerosis or membranous glomerulonephritis.
g) Unlabelled indications
Other conditions where cyclosporine can be used are primary biliary cirrhosis, atopic dermatitis,
lichen planus, pyoderma gangrenosum, alopecia areata, bullous disorders, psoriasis vulgaris,
ulcerative colitis, crohn's disease, chronic viral active hepatitis, auto immune chronic active
hepatitis, nephrotic syndrome, type I (Insulin dependent) diabetes mellitus and to a limited extent
in myasthenia gravis and multiple sclerosis.

CONTRAINDICATIONS
Hypersensitivity is known for cyclosporine.

PRECAUTIONS
Cyclosporine must be used only by medical specialists who have experience of
immunosuppressive therapy and/or of treatment of organ transplantation or transplantation of
bone marrow. Patients receiving cyclosporine must be followed by centres equipped with
appropriate laboratory facilities and adequate support of medical personnel.
Patients with malabsorption syndrome may have difficulty in achieving therapeutic levels.
Hypertension is a common side effect of cyclosporine therapy. Generally mild to moderate
hypertension is seen. However, on continuous administration incidence decreases with time.
Antihypertensives are generally recommended for this. Since hyperkalaemia may be seen with
cyclosporine therapy, potassium sparing diuretics are not recommended for treating this
condition. In such patients calcium antagonists can be effective agents for treating such
hypertension. Due to alterations in metabolism of cyclosporine by some calcium antagonists,
dosage adjustments of cyclosporine may be required.
During treatment with cyclosporine, vaccination may be less effective. Use of live attenuated
vaccines should be avoided
Repeated laboratory tests for renal, liver functions should be done to know the status of kidney
and liver. Since cyclosporine has tendency to alter lipid profile, it is advisable to evaluate the lipid
profile before and after treatment and after first month of therapy. In case of significant increase, it
is advisable to restrict dietary fats and if necessary reduce cyclosporine dosage.
Use cautiously in the treatment of patients with hyperuricemia. The dosage must be inspected
rigorously. Laboratory checks should be done periodically.
In case of infections, even trivial ones (cold, influenza etc.) the doctor must be immediately
informed.
For monitoring of the serum level of cyclosporine in whole blood, use of methods based on
specific monoclonal antibodies (RIA methods) or by HPLC are preferred. A standard separation
protocol (time and temperature) should be followed. It is necessary to keep in mind that the
concentration of cyclosporine in the blood, is only one of the many factors that contribute to the
clinical state of the patient. The repeated serum levels must therefore, be utilised as a guideline
for determining the dosage in the context of the other clinical or laboratory parameters.
SPECIAL WARNINGS
Cyclospoprine has not been shown to be teratogenic in animals. Experience with cyclosporine in
pregnant females is still limited. Data relative to women subjected to organ transplantation
indicate that, in comparison with the traditional immunosuppressive therapy, cyclosporine does
not provoke any additional risk on the course and outcome of pregnancy. However, there are no
adequate well controlled studies in pregnancy and hence cyclosporine should be used during
pregnancy only if potential benefits outweigh the risk to foetus.
Safety during lactation:
Infants of women receiving cyclosporine should not be breast-fed as the drug passes into breast
milk.
Cyclosporine in children:
Experience with cyclosporine in children is still limited. However, children of the age of 1 year and
above have received cyclosporine in standard dose with no particular problems. In many studies
pediatric patients have required and tolerated higher doses of cyclosporine per kg of body weight,
in comparison with those used in adults.

INTERACTIONS
Particular attention must be paid in administering cyclosporine in association with medicines with
noted nephrotoxic effects, for example aminoglycosides, amphotericin B, ciprofloxacin, digoxin,
melfalan, colchicine and trimethoprim.
Since nonsteroidal antiinflammatory drugs (NSAIDs) may alter the renal function, association of
these with cyclosporine or an increase of their dosage, must be accompanied in the initial phase
by an attentive monitoring of the renal function.
Cyclosporine can increase the risk of muscular toxicity, including pain and weakness of muscles
which may be noticed in the course of treatment with lovastatine. Hence, use of such medicines
along with cyclosporine must be attentively and carefully considered. It is known that various
medicines are capable of increasing or decreasing serum concentration of cyclosporine acting
through competitive inhibition or induction of hepatic enzymes (in particular cytochrome P450)
involved in the metabolism and excretion of cyclosporine. The following medicines can increase
the serum levels of cyclosporine, e.g. ketoconazole, some macrolide antibiotics including
erythromycin and josamycine, methyl prednisolone, metoclopramide, ranitidine, amiodarone,
itraconazole, danazol, metronidazole, norfloxacin, and some calcium channel antagonists such as
diltiazem, nicardipine and verapamil. Avoid taking nifedipine for patients who have developed
gingival hypertrophy. Among the medicines that decrease the concentration of cyclosporine in
plasma or in the whole blood, following have been indicated; barbiturates, carbamazepine,
phenytoin and rifampicin. Hence, it is recommended that administration of cyclosporine along with
these medicines must be avoided. If the concomitant administration of cyclosporine and one of
these medicines is inevitable, blood concentration of cyclosporine must be monitored and
appropriate modifications of dosage of cyclosporine must be brought about.

SIDE EFFECTS
The side effects are dose dependent and regress with the reduction of the dose. Those observed
more frequently include hypertrichosis, tremors, renal dysfunction, hypertension, hepatic
dysfunction, fatigue, gingival hypertrophy, gastrointestinal disturbances (anorexia, nausea,
vomiting, diarrhoea) and sensation of burning of the hands and feet (usually during -the first week
of the treatment). Occasionally headache and rashes, possibly of allergic origin are observed,
besides slight anaemia, hyperkalemia, hyperuricemia, hypomagnesemia, increase in weight,
oedema, pancreatitis, paresthesia and convulsions. In rare cases muscular cramps, muscular
weakness and myopathy have been observed.
Especially in patients who have undergone liver transplantation, signs of encephalopathy,
disturbances of vision and movement and altered consciousness have been observed. It has not
yet been established if such alterations are caused by cyclosporine, by the underlying pathology
itself, or by other conditions. Rarely a syndrome of thrombocytopenia and microangiopathic
hemolytic anaemia and renal failure (hemolytic uremic syndrome) has been observed. In some
patients neoplasms or lymphoproliferative disorders have been observed but their incidence and
distribution is similar to those in patients who have undergone conventional immunosuppressive
therapy.

POSOLOGY AND FREQUENCY OF ADMINISTRATION

The intervals of dosage specified successively must be understood as per indications and
references. Regular monitoring of the cyclosporine blood levels is advised.
a) Solid Organ Transplantation
The initial dose of cyclosporine equal to 10-15 mg/kg of cyclosporine5 must be administered
within 12 hours before the operation in one intake. As a general rule, the same daily dose must
be administered even after the operation for one or two weeks; then reduce the daily dose by five
percent per week in accordance with the blood levels, till a maintenance dose of 2-6 mg/kg/day in
divided doses. Cyclosporine concentrate for intravenous infusion can be used in case of
gastroenteric intolerance so as to compromise the absorption of the oral preparations of the
medicine. It is advised to change to oral preparations as soon as possible.
If cyclosporine is utilised in association with other immunosuppressive medicines (e.g. with
corticosteroids or when triple or quadruple immunosuppressive therapy is necessary), lesser
doses may be used (e.g. 3 to 6 mg/Kg/day given in two divided doses for initial treatment).
b) Bone Marrow Transplantation
The initial dose of cyclosporine must be administered the day preceeding that of transplantation.
In majority of the cases one prefers to use the concentrate for intravenous infusion at a dose of
2.5-5 mg/kg/day as initial dose and in the period following immediately the transplantation for a
duration of not more than 2 weeks to pass on to the maintenance therapy by oral method at a
dose of 12.5 mg/kg/day.6
In case of gastrointestinal complications that may reduce the absorption of medicine, a higher
oral or intravenous dosage may be necessary. Cyclosporine may be given to initiate the
treatment. In this case the advised dose is of 12.5-15 mg/kg/day in two divided doses from the
first day of transplantation.
The maintenance therapy must be prolonged for at least 3-6 months (preferably 6 months) before
reducing gradually to zero after one year.
In some patients, discontinuation of cyclosporine may result in GVHD. In this case generally a
positive response is obtained with the resumption of administration of cyclosporine. Low dose
cyclosporine should be used to treat mild chronic GVHD. Intravenous cyclosporine is advised to
be used in the treatment at a dose of 3.5 mg/kg/day, till the time the medicine cannot be taken
orally. If possible oral administration at a dose of 12.5-15 mg/kg/day may be utilised right from the
beginning. Initial posology must be maintained for about 2 months, reducing then gradually the
dose (5% every week) till reaching 2 mg/kg/day. At such dosage the treatment can be
suspended.
c) Aplastic Anaemia
The exact cyclosporine dosage has not yet been formalised in patients of aplastic anaemia
However, cyclosporine in initial dosage should be given in range of 3 to 7 mg/kg/day2 adjusted
according to the response and serum creatinine levels. Cyclosporine should be continued for at
least 3 months and until peripheral blood count has stabilized for at least one month and then
drug is tapered off slowly.
d) Endogenous Uveitis (including Behcet's syndrome)
It is recommended to start with an oral dose of 5 mg/kg/day in two divided doses2 till remission of
the active inflammation of the uvea and improvement of vision is achieved. In refractory cases,
dose can be increased to 7 mg/kg/day for a limited period, on condition that cyclosporine is
tolerated and that alterations of biochemical parameters (creatininemia) or of blood pressure are
not present.
For obtaining the initial remission or for controlling repeated inflammatory ocular attacks,
cyclosporine is administered in concomitance with systemic corticosteroids if cyclosporine alone
provides insufficient control (0.2-0.6 mg/kg/day equivalent to prednisone or equivalent doses of
other corticosteroids).
In the maintenance therapy, the posology must be decreased gradually to the minimum effective
dose so that during the phase of remission it should not surpass 5 mg/kg/day.
Warning
Since cyclosporine may alter the renal function, only patients with normal renal function must be
treated. It is necessary to frequently evaluate the renal function and reduce the dose by 25-50% if
the serum creatinine increases beyond 30% of the value recorded before starting the therapy
even if such value is in the normal range. If an improvement of the intraocular inflammation is not
obtained after 3 months of treatment with cyclosporine at adequate doses and in association with
steroids, the possibility of adopting alternative therapies must be looked into.
e) Psoriasis
For inducing remission, it is recommended to start with 2.5 mg/kg/day orally in two divided2
doses. If no improvement is noted within a month gradually increase the posology without
surpassing 5mg/kg/day. In patients who do not show adequate response after 6 months of the
therapy at a dose of 5 mg/kg/day, it is better to discontinue the administration; it is also better to
discontinue it in patients in whom the minimum effective dose is not compatible with the norms
given later (see warnings) for ensuring the treatment. It is possible to begin the therapy with 5
mg/kg/day in patients in whom rapid improvement is required due to seriousness of the disease.
For every patient the minimum effective dose of maintenance must be established, such dose
should not exceed 5 mg/kg/day.
Warning
Patients with altered renal function, uncontrolled hypertension, clinically relevant infections or any
type of malignancy (excluding the cutaneous ones, see later), should not be treated with
cyclosporine. In patients with hyperuricemia or hyperkalemia, caution is necessary. Since
cyclosporine may worsen the renal function, it is advisable to measure the serum creatinine levels
every two weeks for the first three months of the therapy; subsequently in patients treated with
2.5 mg/kg/day, if serum creatinine remains stable, carry out a check every 2 months and monthly
in those treated with higher doses. It is necessary to reduce the dose by 25-50% if the
creatininemia increases beyond 30% with respect to base value, even if the values are in the
normal range. If such reduction does not bring about the desired corrections of the parameter
within one month, interrupt the treatment with cyclosporine. If in the course of the treatment an
uncontrollable hypertension is set up even with an appropriate antihypertensive therapy, it is
better to interrupt the treatment.
In patients with psoriasis, treated with cyclosporine or with other therapies, appearance of
neoplasm, particularly of skin is reported. Cutaneous lesions, not typical of psoriasis which could
make one think to be neoplastic or preneoplastic lesions, must be subjected to biopsy before
initiating the treatment with cyclosporine. The patients who show cutaneous preneoplastic or
neoplastic alterations can initiate the treatment with cyclosporine only after an adequate
treatment of such lesions, and only if successful alternative therapy does not exist. Rarely
appearance of lymphoproliferative disorders is observed in patients of psoriasis treated with
cyclosporine which is readily reversible on suspension of the treatment.
f) Rheumatoid arthritis
The initial cyclosporine dose should range from 2.5 to 3.5 mg/kg/day2 with a maximum dosage of
5 mg/kg/day increased at 1-2 month interval by 0.5 mg/kg/day if clinical response is not seen. In
responders cyclosporine dosage should be slowly reduced by 0.5 mg/kg/day, decrements every
1-2 months to lowest effective dosage.
In the subsequent maintenance therapy the dose must be adapted for individual patients in
accordance with tolerability. Cyclosporine can be administered in combination with low doses of
corticosteroids and/or non steroidal anti-inflammatory drugs.
Warning
Patients with reduced renal function, with uncontrollable hypertension or with malignant
neoplasms of any type must not take cyclosporine. Since cyclosporine can alter renal function, it
is necessary to determine the pretreatment value of serum creatinine carefully through at least
two determinations. During the first three months of the therapy, it is advisable to monitor the
levels of serum creatinine at intervals of two weeks, subsequently the determinations may be
made every 4 week but a more frequent monitoring is necessary in case where the dose of
cyclosporine is increased or concomitant treatment with a non steroidal anti-inflammatory drug is
started. If serum creatinine reaches values exceeding 30% with respect to the base value in more
than one measurement, it is necessary to reduce the dosage of cyclosporine. If the reduction of
the dosage is not sufficient to decrease the values within a month, it is necessary to interrupt the
treatment with cyclosporine. Interruption of the therapy may also be necessary if during the
course of the treatment, uncontrollable hypertension even with appropriate antihypertensive
therapy has developed. As with other immunosuppressive medicines one must keep in mind the
possibility of increase of the risk of occurrence of the lymphoproliferative disorders.
g) Nephrotic syndrome2
For inducing remission, the recommended daily dose given in two divided oral doses is 5 mg/kg
for adults and 6 mg/kg for children, if, except for proteinuria, renal function is normal. In patients
with impaired renal function the initial dose should not exceed 2.5 mg/kg a day. The combination
of cyclosporine with low doses of oral corticosteroids is recommended if the effect of cyclosporine
alone is not satisfactory, especially in steroid resistant patients. If no improvement has been
observed after 3 months treatment, cyclosporine therapy should be discontinued. The doses
need to be adjusted individually according to efficacy (proteinuria) and safety (primarily serum
creatinine) but should not exceed 5 mg/kg a day in adults and 6 mg/kg a day in children. For
maintenance treatment the dose should be slowly reduced to the lowest effective level.
Warning
Since cyclosporine can impair renal function it is necessary to assess renal function frequently. If
serum creatinine remains increased to more than 30% above creatinine levels recorded before
starting cyclosporine therapy at more than one measurement, reduce the dosage of cyclosporine
by 25 to 50%. Patients with abnormal baseline renal function should initially be treated with 2.5
mg/kg a day and must be monitored very carefully. In some patients it may be difficult to detect
cyclosporine induced renal dysfunction because of changes in renal function related to the
nephrotic syndrome itself. This explains why, in rare cases, cyclosporine associated structural
kidney alterations have been observed without increases in serum creatinine. Renal biopsy
should be considered for patients with steroid dependent minimal change nephropathy in whom
cyclosporine therapy has been maintained for more than one year. In patients with nephrotic
syndrome treated with immunosuppressants (including cyclosporine), the occurrance of
malignancies (including Hodgkin's lymphoma) has occasionally been reported.

MODE OF ADMINISTRATION
Oral Solution
For making the solution of the medicine, the syringe enclosed in the wrapping must be used.
Procedure of making oral solution :

1. Lift the plastic protection of the metallic cap

2. Remove completely the metallic cap
3. Remove the rubber plug and throw it away
4. Introduce the cannula in the bottle pushing the white cap till the mouth of the bottle.
5. Insert the syringe in the white cap of the cannula
6. Draw the required volume of solution
7. In case big air bubbles are formed inside the syringe, push the piston towards the base
so that the bubbles escape from the cannula. Draw again the required volume of solution
slowly. Presence of a few minute bubbles does not effect the quantity of the required
dose.
8. After use, do not rinse the syringe, but clean only the external part with dry tissue paper
and place it in the case. The cannula must remain in the bottle. Close the bottle with the
black plastic cap provided separately.

Panimun Bioral should be diluted in a glass container (not of plastic), utilising preferably apple or
orange juice (avoid grape juice). Soft drinks can be added according to individual taste. Prepare
the solution immediately before taking. After having poured the medicine, mix well and drink
immediately; subsequently rinse the glass with a small quantity of the same drink and drink it for
ensuring that the full dose has been taken. The same drink should be continued for the entire
duration of the treatment. The syringe for measuring the medicine must not get in contact with the
drink. Cyclosporine solution should be used within 2 months of opening the bottle and be stored
between 25 and 35OC - preferably not below 25oC for prolonged periods as it contains oily
components of natural origin which tend to solidify at low temperatures. A jelly like formation may
occur below 25OC, which is however reversible at temperature up to 35OC. Minor flakes or a slight
sediment may still be observed. These phenomena do not affect the efficacy and safety of the
product, and the dosing by means of the syringe remains accurate.
Do not utilise the solution if the aluminium seal is broken or has been removed before use.
Capsules
Panimun Bioral capsules should not be removed from the blister pack till required. On opening
the blister pack one will notice a characteristic odour; it is normal and is not prejudicial to the
utilisation of the medicine. The capsules must be swallowed whole and stored at temperature not
exceeding 30OC protected from moisture and should be administered in two divided doses.

OVERDOSAGE
Only minimal experience with overdosage is available. However, because of slow absorption of
cyclosporine (capsules and solution) forced emesis would be of value up to 2 hours of
administration. Transient hepatotoxicity and nephrotoxicity may occur which resolve after drug
withdrawal. General supportive measures and symptomatic treatment should be followed in such
cases. Cyclosporine is not dialysable to large extent and neither is cleared by charcoal
hemoperfusion.
The oral LD50 is 2329 mg/kg in mice, 1480 mg/kg in rats and more than 1000 mg/kg in rabbits
while I.V. LD50 is 148 mg/kg in mice, 104 mg/kg in rats and 46 mg/kg in rabbits.

CAUTION
Do not utilise the medicine after the date of expiry as indicated.

REFERENCES

1. 1. Kahan BD. Cyclosporin.

N.England J. of Medicine 1989; 321:1725-1738.
2. Faulds H, Goa KL and Benfild P. Cyclosporin : a review of its pharmacodynamic and
pharmacokinetic properties and therapeutic use in immunoregulatory disorders.
Drugs 1993; 45(6):953-1040.
3. Kulkarni RD, Ramamurthy L and Chauhan B et al. Single dose, randomised two way
cross-over relative bioavailablity of cyclosporine in 18 volunteers. Panimun Bioral
Solution Vs Sandimmun Neoral solution. Data on file.
4. Kulkarni RD, Ramamurthy L and Chauhan B. Relative Bioavailability of two oral dosage
forms of cyclosporine A. Indian J. of Nephrology. 1999; 9(3): 84-86
5. Diasio RB and Lobuglio AF. Immunomodulators : Immunosuppressive agents and
immunostimulants, cited in , Goodman & Gillman's. The pharmacological basis of
therapeutics 1996; 9th ed.: 1269 - 1299.
6. Capone D, Demarino V, Fontana R. Effect of different routes of cyclosporine A
administration on blood levels in patients undergoing bone marrow transplantation.
Bone Marrow Transplantation 1997 Feb.; 19(4):369 - 372.