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1. NEPHROLOGY NEWSLETTER
CHRONIC KIDNEY
DISEASE (CKD)
NOMENCLATURE
CKD is defined as abnormalities of kidney
structure or function, present for > 3
months, with implications for health. CKD
is classified based on Cause, GFR category
(G1-G5), andAlbuminuria category (A1-
A3), abbreviated as CGA.
LUPUS
NEPHRITIS
Approach to the diagnosis of kidney
involvement in systemic lupus
erythematosus (SLE)
Diagnosis of kidney involvement in systemic
lupus erythematosus. anti-dsDNA, anti-double-
stranded deoxyribonucleic acid; eGFR,
estimated glomerular filtration rate
Disease Or Its Treatments Should
Be Considered For All Patients
This Figure Measures to minimize
the risk of complications related to
lupus nephritis or its treatment.
HBV, hepatitis B virus; HCV,
hepatitis C virus; HIV, human
immunodeficiency virus;RAS, renin–
angiotensin system.
Severity Of Kidney
Involvement, A Kidney
Biopsy Is Useful To
Confirm The Diagnosis
And For The Assessment
Of Activity And
Chronicity Features That
Inform Treatment
Decisions And Prognosis
Activity and chronicity
items included in lupus
nephritis kidney biopsy
report. NIH,National
Institutes of Health, USA.

2. N e p h r o l o g y
n e w s l e t t e r
Class I or Class
II lupus
nephritis
Approach to immunosuppressive
treatment for patients with Class I or
Class II LN
Immunosuppressive
treatment for patients with
Class I or Class II lupus
nephritis
these patients are similar to
those with minimal change
disease (MCD) or focal
segmental glomerulosclerosis
(FSGS), often showing a good
response to glucocorticoid
treatment.81-83
Although there
have been no RCTs,
observational data showed that
over 90% of patients given
glucocorticoid monotherapy
achieved remission within a
median time of 4 weeks.81, 84-88
Data on relapse are even more
limited, but there appears to be
a significant risk of relapse
after glucocorticoids are
tapered.89
Although optimal
duration is not known,
maintenance with low-dose
glucocorticoid plus an
additional agent such as
mycophenolic acid analogues
(MPAA), azathioprine, or a
CNI is suggested, especially in
patients with a history of
relapse.
Class III or Class IV lupus
nephritis ,Initial therapy of active
Class III/IV lupus nephritis
recommend that patients with
active Class III or IV LN, with
or without a membranous
component, be treated initially
with glucocorticoids plus
either one of the following:
i. mycophenolic acid analogues
(MPAA) (1X); or
ii. low-dose intravenous
cyclophosphamide (1X)
iii. belimumab and either MPAA or low-
dose intravenous cyclophosphamide (X);
or
iv. MPAA and a calcineurin inhibitor
(CNI) when kidney function is not
severely impaired (for example
estimated glomerular filtration rate
[eGFR] ≤45 ml/min per 1.73 m2) (1X).
A regimen of reduced-dose
glucocorticoids following a short
course of methylprednisolone pulses
may be considered during the initial
treatment of active LN when both the
kidney and extrarenal disease
manifestations show satisfactory
improvement.
Example of glucocorticoid
regimens for lupus
nephritis.

3. N e p h r o l o g y
n e w s l e t t e r
Class V lupus
nephritis
the management of patients with pure ClassV LN
Assessing Treatment
Response In LN
Definitions of response to
therapy in LN are provided in
Figure 11. ∗For children <18
years old, complete response is
defined as proteinuria <0.5
g/1.73 m2
/d or <300 mg/m2
/d
based on a 24-h urine
specimen. PCR, protein–
creatinine ratio.

4. N e p h r o l o g y
n e w s l e t t e r
 A triple
immunosuppressive
regimen of belimumab
with glucocorticoids and
either MPAA or reduced-
dose cyclophosphamide
may be considered in
patients with repeated
renal flares or at high-risk
for progression to kidney
failure.
 Other therapies, such as
azathioprine or
leflunomide combined
with glucocorticoids, may
be considered in lieu of
the recommended initial
drugs for proliferative LN
in situations of patient
intolerance, lack of
availability, and/or
excessive cost of standard
drugs, but these
alternatives may be
associated with inferior
efficacy, including
increased rate of disease
flares and/or increased
incidence of drug
toxicities.
 Intravenous
cyclophosphamide should
be used as the initial
therapy for active Class III
and Class IV LN in patients
who may have difficulty
adhering to an oral
regimen.
 An MPAA-based regimen
is the preferred initial
therapy of proliferative LN
for patients at high risk of
infertility, patients who
have a moderate to high
prior cyclophosphamide
exposure.
 Newer biologic and non-
biologic therapies are under
development and may offer
future options for the
treatment of active LN.
Rituximab may be
considered for patients with
persistent disease activity or
inadequate response to
initial standard-of-care
therapy.
 Initial therapy with an
immunosuppressive
regimen that includes a
CNI (voclosporin,
tacrolimus, or
cyclosporine) may be
preferred in patients with
relatively preserved kidney
function and nephrotic-
range proteinuria likely
due to extensive podocyte
injury, as well as patients
who cannot tolerate
standard-dose MPAA or
are unfit for or will not use
cyclophosphamide-based
regimens.
Practice Points
Recommendation
Summary

5. RECOMMENDED
APPROACH FOR
INITIAL THERAPY OF
ACTIVE CLASS III/IV
LUPUS NEPHRITIS.
Caution is warranted when CNI is
used in patients with significantly
impaired kidney function, in view of
increased susceptibility for severe
consequences due to CNI
nephrotoxicity. The eGFR and
serum creatinine levels stated in the
figure were patient selection criteria
adopted in the respective clinical
trials. †Refer to Figure 6 for
examples of corticosteroid treatment
regimen. ‡Refer to Figure 9 for
durations of CNI or belimumab
treatment in clinical trials. §Refer to
Figure 7 for comments on
cyclophosphamide regimens. b.i.d.,
twice daily. CNI, calcineurin
inhibitors; eGFR, estimated
glomerular filtration rate; i.v.,
intravenous; MMF, mycophenolate
mofetil; p.o., oral; q2wk, every 2
weeks; q4wk, every 4 weeks; s.c.,
subcutaneous; SCr, serum
creatinine.
-The dose of mycophenolate
mofetil (MMF) in the early
maintenance phase is
approximately 750–1000 mg
twice daily, and for mycophelolic
acid (MPA), approximately 540–
720 mg twice daily.
- The total duration of initial
immunosuppression plus
combination maintenance
immunosuppression for
proliferative LN should be ≥36
months.
- Patients treated with triple
immunosuppressive regimens
that include belimumab or a CNI
in addition to standard
immunosuppressive therapy can
continue with triple
immunosuppressive regimen as
maintenance therapy (Figure 9).
-If MPAA and azathioprine
cannot be used for maintenance,
CNIs or mizoribine or
leflunomide can be considered
(Figure 9).
-Glucocorticoids should be
tapered to the lowest possible
dose during maintenance, except
when glucocorticoids are
required for extrarenal lupus
manifestations; discontinuation
of glucocorticoids can be
considered after patients have
maintained a complete clinical
renal response for ≥12 months
MAINTENANCE
THERAPY FOR CLASS
III AND CLASS IV
LUPUS NEPHRITIS
-Azathioprine is an alternative to
MPAA after completion of initial
therapy in patients who do not tolerate
MPAA, who do not have access to
MPAA, or who are considering
pregnancy.
Figure 9 | Maintenance
immunosuppressive regimens in
patients with lupus nephritis.
AURORA, Aurinia Renal Response
in Active Lupus with Voclosporin;
AZA, azathioprine; BLISS-LN,
Efficacy and Safety of Belimumab in
Patients with Active Lupus Nephritis;
CNI, calcineurin inhibitor; LN, lupus
nephritis; MPAA, mycophenolate
acid analogs.
N e p h r o l o g y n e w s l e t t e r

6. TREATMENT OF RELAPSE
After a complete or partial remission has been achieved, LN relapse
should be treated with the same initial therapy used to achieve the
original response, or an alternative recommended first-line therapy.
lupus nephritis and thrombotic microangiopathy
Patients with LN and thrombotic microangiopathy (TMA) should be
managed according to the underlying etiology of TMA, as shown in
Figure 13
TMA Due To Lupus-
Associated TTP
The diagnosis of TTP is
mainly reserved for
patients with TMA and low
ADAMST13 activity
(≤10%).282, 287 The
treatment of confirmed
TTP in LN is extrapolated
from that of acquired TTP
and includes plasma
exchange,288, 289 high-dose
glucocorticoids,290, 291
rituximab,292-295 and/or
caplacizumab
Pregnancy &
contraception in
patients with lupus
nephritis
Counseling with regard to
contraception and pregnancy
should be done early in patients
of childbearing age. Patients
should be seen by a
gynecologist to discuss the
choice of methods for
contraception. For patients who
prefer oral hormonal
contraception, estrogen–
progestin contraceptives with
ethinyl estradiol dose at not
higher than 30 μg may be used
in patients who are negative for
antiphospholipid antibodies and
with stable low disease activity,
whereas progestin-only
contraceptives are preferable in
patients with a moderate or
high level of disease activity.
Estrogen-containing
contraceptives should be
avoided in patients with
antiphospholipid antibodies or a
history of thrombosis, in view
of the risk of thromboembolism
Patients with active LN
should be counseled to
avoid pregnancy while
the disease is active or
when treatment with
potentially teratogenic
drugs is ongoing, and for
≥6 months after LN
becomes inactive
To reduce the risk of pregnancy
complications,
hydroxychloroquine should be
continued during pregnancy, and
low-dose aspirin should be started
before 16 weeks of gestation.
Only glucocorticoids,
hydroxychloroquine, azathioprine,
tacrolimus, and cyclosporin are
considered safe
immunosuppressive treatments
during pregnancy.
N e p h r o l o g y n e w s l e t t e r

7. INFECTIONS IN PATIENTS
WITH LN
Infection is a leading cause of death in
patients with LN, and infection-related deaths are
more common during the initial phase of
management following exposure to intensive
immunosuppressive therapy.
trimethoprim/sulfamethoxazole (TMP-SMX) was
effective in preventing pneumocystis pneumonia.
Herpes zoster is 2–10 times higher in patients with
SLE than in healthy controls, but the role of
antiviral prophylaxis is uncertain. Available zoster
vaccine preparations include the live-attenuated
vaccine Zostavax® and the adjuvanted
recombinant vaccine Shingrix. In general, live
vaccines should be avoided in immunosuppressed
subjects
. There is also concern that the polio vaccination
has been associated with lupus flares, whereas the
data on influenza vaccination are conflicting.
Response to vaccination is reduced following
exposure to high-dose immunosuppression
CARDIOVASCULAR COMPLICATIONS
IN PATIENTS WITH LN
Patients with SLE have both traditional
(dyslipidemia, smoking, obesity,
etc.) and non-traditional
(proteinuria, inflammation, etc.) CV
risk factors. A patient often has
multiple risk factors, which can be
secondary to disease-related organ damage
(especially CKD, hypertension, proteinuria) or
treatment (such as glucocorticoids and calcineurin
inhibitors [CNIs]). Regular evaluation of various
risk factors and timely treatment are essential to
prevent premature CV complications.
TREATMENT OF LUPUS NEPHRITIS IN
CHILDREN
Treat pediatric patients with LN using
immunosuppression regimens similar to those used
in adults, but consider issues relevant to
this population, such as dose
adjustment, growth, fertility, and
psychosocial factors, when devising
the therapy plan.
BONE HEALTH
Glucocorticoid therapy,
especially when high
doses are used
for long
durations,
increases bone
loss
glucocorticoid dose, and
the Fracture Risk
Assessment Tool (FRAX)
score.Calcium (optimal
intake 1000–1200 mg/d)
and vitamin D
supplementation are
recommended for patients
with LN, as well as
consideration for oral
bisphosphonates according
to individual risk
assessment
Malignancies in patients
with LN
Patients with SLE have
increased risk of malignant
tumors, including non-
Hodgkin’s lymphoma,
lung, liver, vulvar/vaginal,
thyroid, nonmelanoma
skin cancer, and the risk
(especially with bladder
cancer) is increased in
patients with a history of
exposure to
cyclophosphamide.
LUPUS PATIENTS
WITH KIDNEY
FAILURE
Patients with LN who
develop kidney failure
may be treated with
hemodialysis, peritoneal
dialysis, or kidney
transplantation; and
kidney transplantation is
preferred to
long-term
dialysis.
SPECIAL
POPULATIONS
N e p h r o l o g y n e w s l e t t e r

8. Glucocorticoids are used in all
current treatment regimens of
LN. These drugs have both
immunosuppressive and anti-
inflammatory effects and
provide immediate treatment for
the often extensive intrarenal
inflammation that is seen in
patients with Class III and Class
IV LN. This regimen is
necessary because there is a lag
before the immunosuppressive
effects of cyclophosphamide,
MPAA, CNIs, or B cell–
directed therapies are seen. The
dose, tapering regimen, and
duration of glucocorticoid
schemes vary considerably
among clinicians and are largely
opinion-based.
To minimize the side effects due
to high cumulative exposure to
glucocorticoids, there is
increasing use of initial i.v.
glucocorticoid pulses followed
by a lower starting dose and/or
more-rapid taper of oral
glucocorticoid in recent clinical
trials.
A Regimen Of Reduced-Dose
Glucocorticoids Following A
Short Course Of
Methylprednisolone Pulses May
Be Considered During The Initial
Treatment Of Active LN When
Both The Kidney And Extrarenal
Disease Manifestations Show
Satisfactory Improvement
Results from a retrospective
propensity analysis of data from 63
patients enrolled in the Aspreva Lupus
Management Study (ALMS) and the
phase 2 AURA-LV trialsuggested that
doses of glucocorticoids and MPAA
lower than those adopted in ALMS
may result in better long-term safety,
including a reduction in
lymphoproliferative disorders, skin
cancers, and glucocorticoid-related side
effects. In children, the avoidance of
excessive glucocorticoid exposure also
has implications for growth,
psychosocial issues, and drug
adherence.With accumulating data on
the efficacy and glucocorticoid-sparing
role of immunosuppressive medications
such ascyclophosphamide, MPAA, and
triple immunosuppressive drug
combinations, there is a move toward
reducing exposure to glucocorticoids
(Supplementary Table S12. Examples
of dosing and tapering regimens in
initial treatment of LN, based on
published literature and recent clinical
trials that investigate the efficacy and
safety of new therapeutic agents. They
serve to illustrate variations in
exposure to glucocorticoids, but it is
premature to recommend one over the
other,as the evidence supporting these
regimens is low as they have only been
compared in relatively small clinical
trialsand observational studies.The use
of reduced-dose glucocorticoids may
decrease the incidence of major
infections
The role of i.v.
methylprednisolone
pulses at the start of
treatment is not
well-studied but is
commonly given as
up to 3 daily doses
of 500 mg each
(range 250–1000
mg/d), especially in
patients who
present with a
clinical syndrome
of rapidly
progressive
glomerulonephritis
(RPGN)—acute
and severe
deterioration of
kidney function
often accompanied
by a high
proportion of
crescents or
vascularlesions in
the kidney biopsy,
or when there are
severe extrarenal
manifestations,
such as central
nervoussystem or
lung involvement.
Methyl
prednisolone in
L.N
N e p h r o l o g y n e w s l e t t e r

9. Figure 7 |
Cyclophosphamide
dosing regimens,
combined with
glucocorticoids, in
initial treatment
for active Class
III/IV lupus
nephritis. i.v.,
intravenous; max,
maximum; NIH,
NationalInstitutes
of Health
Cyclophosphamide
may be given orally
or intravenously,
and in a standard-
dose (also known as
themodified
National Institutes
of Health (NIH)
regimen or high-
dose regimen) or
low-dose (also
known as the Euro-
Lupus regimen).
The dosing and
duration for these
regimens are given
The Choice Of Which
Regimen To Use
Depends On Several
Factors And Can Be
Individualized
Efficacy: Oral and standard-dose i.v. cyclophosphamide regimens
have been used in diverse ethnic populations and for all levels of
disease severity, and show equivalent efficacy.18, 143-146
Reduced-
dose cyclophosphamide (Euro-Lupus regimen) shows equivalent
efficacy to standard-dose cyclophosphamide but was tested mainly in
White patients. Emerging data suggest low-dose cyclophosphamide
is effective in Asians, Hispanics, and Black patients, but these studies
did not make direct comparisons to standard-dose i.v.
cyclophosphamide.
Cost: Intravenous cyclophosphamide is more expensive than oral and
requires the availabilityof an infusion suite and experienced staff.
Convenience: Oral cyclophosphamide does not require patients to
stop work or familyactivities.
Toxicity: The toxicities of cyclophosphamide may be considered
immediate (e.g., gastrointestinal, susceptibility to infection) or
delayed (e.g., loss of fertility, futuremalignancies).
Standard-dose i.v. cyclophosphamide was shown to be less toxic than
oral cyclophosphamide, but the dose and duration of oral treatment in
these reports were substantially higher and longerthan those currently
recommended (Supplementary Table S1313, 148
). The incidence of
bladder toxicity is also felt to be lower with i.v. cyclophosphamide.
Reduced-dose i.v. cyclophosphamide has the most favorable
immediate toxicity profile among the 3 cyclophosphamide regimens.
The risk of future hematologic malignancy is related to total
lifetime exposure (>36 g), as ismyelofibrosis (>80 g). Total lifetime
exposure plus age constitutes a significant risk factor for premature
ovarian failure (>7.5–15 g/m2
for young to older pediatric patients,
respectively; 300 mg/kg for adults)
Cyclophosphamide
in L.N
N e p h r o l o g y n e w s l e t t e r

10. MAINTENANCE THERAPY FOR CLASS III AND CLASS IV LUPUS NEPHRITIS
This Recommendation Places A High Value On The Data Demonstrating That
Long-Term, Reduced-Dose MPAA Decrease The Risk Of LN Relapse Compared
To Azathioprine Or No Treatment And That MPAA HaveEffectiveness
Comparable To That Of Cyclophosphamide But With A Lower Risk Of Adverse
Events. The Recommendation Places A Lower Value On The Risk Of Adverse
Events Associated With Long-Term MPAA Treatment As Compared To No
Treatment (Figure 8).
MAINTENANCE IMMUNOSUPPRESSIVE REGIMENS IN
PATIENTS WITH LUPUS NEPHRITIS.
Renal Response in Active Lupus with Voclosporin; AZA,
azathioprine; BLISS-LN,Efficacy and Safety of Belimumab in
Patients with Active Lupus Nephritis; CNI, calcineurin
inhibitor; LN, lupus nephritis; MPAA, mycophenolate acid
analogs.
N e p h r o l o g y n e w s l e t t e r

11. N e p h r o l o g y n e w s l e t t e r
Tacrolimus
Trade name prograf
Dose 2-3mg/day
Administration
& dilution
Oral
Side effects Prolonged QT interval
Ventricular fibrillation
Hyperkalemia
Development of malignancy
( BLACK BOX
WARNING)
Increase risk of infection (
BLACK BOX WARNING)
Hyperpigmentation
Stevens -Johnson syndrome
Weight loss
Gastric ulcer
Pancreatitis
Biliary obstruction
Febrile neutropenia
Hepatic cirrhosis
Hemorrhagic cystitis
Respiratory failure
Pulmonary hypertension
Rhabdomyolysis
Contraindication Hypersensitivity
Dose adjustment No dose adjustment in renal
impairment
Not dialyzable
pk Should maintain trough
blood levels 4-10 ng/ml
Half life elimination 23-46
hours
Time to peak 0.5-6 hours
Excretion : feces 93%
Stability Store at room temp
Eculizumab
Trade name Soliris
Elizaria
Dose 900 mg weekly for 4 doses as LD
Then
1200 mg at week 5 then 1200 mg
every 2 week
Administration
& dilution
IV infusion over 35 min
Not IV push or bolus
Side effects Life threating meningococcal
infections ( black box warning)
Sever hypertension
High fever
Respiratory tract infection
Hypokalemia
Vomiting , diarrhea
Urinary tract infection
Anemia , leukopenia
Contraindication Hypersensitivity
Unresolved Neisseria meningitidis
Dose adjustment No dose adjustment in hepatic or
renal impairment
pk Half life 272 to 291 hours
Excretion in urine or bile
Stability Store intact vials at 2 to 8 C
Do not freeze
Can store at room temp in the
original cartoon up to 3 days
Protect from light
Do not shake
Following dilution , use within 24
hour

12. N e p h r o l o g y n e w s l e t t e r
Mizoribine
Trade name Bredinin
Dose 50 mg 3 times daily
Administration &
dilution
Oral form
Side effects Cardiovascular : edema
Alopecia
Toxic epidermal
necrolysis
Stevenes johnson
syndrome
Hyperglycemia
Gout
Proteinuria
Bone marrow
suppression
Increase
ALT,AST,bilirubin
Increase BUN,creat
Fever
Upper airway symptoms
inflammation
Contraindication Hypersensitivity
Pregnancy or those who
become pregnant
Breastfeeding
Leukocyte count less
than 3000/mm
Dose adjustment No dose adjustment in
hepatic or renal failure
pk Half life 3 hours
Excretion in urine
,unchanged 65%
Stability Store in an airtight
container at room
temperature
Azathioprine
Trade name Imuran
Dose 2 mg/kg/day oral
Administration &
dilution
Oral form
Side effects Leukopenia
Infection
Lymphoma (HSTCL)
Bone marrow
suppression
Hepatotoxicity
Thrombocytopenia
Rash
Macrocytic anemia
Fever
Contraindication Hypersenstivity
Pregnancy
Lactation
Rheumatoid arthritis:
patients previously
treating with alkylating
agents
Dose adjustment In renal impairment:
-GFR 10-20 ml/min :
75% of normal dose
- GFR less than 10 ml/
min: 50% of normal dose
pk Oral form well absorbed
with peak serum conc
attained within 1-2 hours
Half life : 5 hours
Excreted in urine
Stability Store at room temp
Protect from light

13. Leflunamide
Trade name Avara
Dose 20-40 mg daily
Administration
& dilution
oral
Side effects Diarrhea
Increase serum ALT/AST
conc
Respiratory infection
Interstitial lung disease
Opportunistic infections
including sepsis
Thrombocytopenia ,
leukopenia
,neutropenia,pancytopenia
Angioedema
peripheral neuropathy
stevens- johnson syndrome
Toxic epidermal necrolysis
Hypertension
Alopecia
Contraindication pregnancy
Sever liver impairment
Hypersentivity
Current treatment with
teriflunomide
Influenza vaccine
Hepatitis A , B vaccines
Any live vaccine (MMR)
Dose adjustment No dose adjustment in renal
impairment
Not recommended in hepatic
impairment , contraindicated
in sever hepatic impairment
pk Bioavailability 80%
Half life :14-18 days
Clearance : 31 ml/hr
Renal elimination during first
96 hr
Stability Tablets at room temp
Protect from light
Belimumab
Trade name Benlysta
Dose LD : 10 mg/kg IV 3 doses every 2 weeks
then MD: 10 mg/kg IV every 4 weeks
Or
SC LD 400 mg weekly 4 doses then MD
200 mg weekly
Transition from IV to SC any time after
completing the first 2 IV doses
If transitioning , administer first SC dose
of 200 mg 1-2 weeks after the last IV dose
Administration &
dilution
NOT Adminster by rapid IV push or bolus
Infuse over 1 hour
Diluted with normal saline , 0.45% sodium
chloride or lactated ringer
SC form : administer into abdomen or
thigh, rotate injections sites
Side effects SC form :
Nausea
Diarrhea
Serious infections
Depression
Suicidal ideation
IV form:
Nasopharyngitis
Bronchitis
Leukopenia
Pain in extremity
Migraine
Insomnia
Cystitis
pyrexia
Contraindication History of anaphylaxis
Dose adjustment Renal or hepatic impairment : no dose
adjustment needed
pk Bioavailability :74% SC
Half life
IV: 19.4 days
SC: 18.3 days
Stability Vial store at room temp
SC form : allow syringe to sit at room
temp for at least 30 min prior to
adminstration

14. Hydroxychloroquine
Indication &
Dose
200 – 400 mg daily as a single
dose .or in divided 2 doses.
Don’t receive more than
5mg/kg/day
Administration
route:
Oral Tab: administer with food
or milk . can be crushed
Tablets have a bitter taste.
PK Absorption : incomplete &
variable ( 25% - 100 % )
Storage/ stability  Store up to 30C.
 Protect from light
Contraindication Preexisting retinopathy
SE  Retinopathy
 Ventricular arrhythmia
& QTprolongation
 Hypoglycemia , acute
hepatic failure & renal
insufficiency,bronchos
pasm , myopathy .
Voclosporin
indication Lupus nephritis: 23.7mg twice daily
In combination with cs &
mycophenolate
Dose  Renal impairment:
* before ttt initiation ( Cockroft-
Gault Formula):
-crcl > 30 ml/min : no dose
adjustment.
- crcl< 30 ml/min : 15.8 twice
daily
* during ttt ( eGFR):
-eGFR < 60 ml/min/1.73m2
:
reduced from baseline by > 20% -
<30% decrease dose by 7.9 mg
twice daily; reassess eGFR within
2 weeks & if still reduced by
20% reduce dose to 7.9 mg twice
daily.
-eGFR < 60 ml/min/1.73m2
:
reduced from baseline by >30%
discontinue therapy; reassess
within 2 weeks if returned to >
80% of baseline, reinitiate at a
lower dose ( 7.9 mg twice daily )
 Hepatic impairment:
- Child -Pugh class
Aor B:15.8 mg twice
daily.
- Child – Pugh class C:
not recommended
Administration route: Oral capsule( on empty stomach
every 12 hr )
Storage Store in original container 20C -25C
PK  Food decrease rate & extent
of absorption
Contraindication  Use with CYP3A4 inhibitor (
ketoconazole, itraconazole ,
clarithromycin)
SE HTN, hyperkalemia diarrhea, prolong
QT interval ,AKI, Tremor headache,
cough.

15. MABTHERA
drug name rituximab
Indication and dose Consider for use in patients who are resistant to initial
therapy
IV: 1 g on days 0 and 15 or 375 mg/m2 once weekly for
4 doses .
Administration Route
For IV administration only. Do not administer IV push
or bolus. Do not administer IV rituximab
subcutaneously.
nitial infusion: Start an infusion rate of 50 mg/hour; if
there is no infusion-related reaction, increase the rate by
50 mg/hour increments every 30 minutes, to a
maximum rate of 400 mg/hour.
Diluent
dilute to a final concentration of 1 to 4 mg/mL with NS
or D5W.
Do not shake. Do not mix or dilute with other
medications. Compatible in polyvinyl chloride and
polyethylene bags .
Stability
Store intact vials at 2°C to 8°C ,do not freeze. Do not
shake. Protect vials from direct sunlight.
Solutions diluted for infusion in NS or D5W may be
stored at 2°C to 8°C for 24 hours.
PK
Contraindication
hypersensitivity or anaphylactic reaction to murine
proteins,
Common S.E
Hepatitis B virus reactivation
Hypogammaglobulinemia and Infection
Infusion-related reactions
Progressive multifocal leukoencephalopathy (PML

16. CELLCEPT
drug name MYCOPHENOLATE MOFETIL
Indication and dose
Lupus nephritis, focal or diffuse:
Note: Give as part of an appropriate combination regimen.
Initial therapy:
Mycophenolate mofetil: Oral: 1 to 1.5 g twice daily or 500 mg twice
daily for 1 week, then 1 g twice daily for 1 week, then 1.5 g twice daily
.
Mycophenolate sodium, delayed release: Oral: 720 mg twice daily .
Duration: Variable, ~6 months .
Subsequent therapy:
Mycophenolate mofetil: Oral: 1 g twice daily (range: 500 mg to 3
g/day) . Duration is typically ≥2 years .
Mycophenolate sodium, delayed release: Oral: 360 mg twice daily.
Administration Route
May be administered with or without food as effects of food on
bioavailability are minor.
Oral suspension may be administered via a nasogastric tube .
Delayed-release mycophenolate sodium tablets (Myfortic) should be
swallowed whole and should not be crushed, cut, or chewed.
Diluent
Oral suspension: Should be constituted prior to dispensing to the
patient and not mixed with any other medication. Add 47 mL of water
to the bottle and shake well for ~1 minute. Add another 47 mL of
water to the bottle and shake well for an additional minute. Final
concentration is 200 mg/mL of mycophenolate mofetil
Stability
Capsules: Store at 25°C
Tablets: Store at 25°C. Protect from light.
Oral suspension: Store powder for oral suspension at 25°C. Once
reconstituted, the oral solution may be stored at 2°C to 8°. Do not
freeze. The mixed suspension is stable for 60 days.
PK
Metabolism: Hepatic and via GI tract
Bioavailability: Oral: Mycophenolate mofetil: 94%
Half-life elimination:
Mycophenolate mofetil: MPA: Oral: 17.9 ± 6.5 hours
Contraindication
Hypersensitivity to mycophenolate mofetil, mycophenolic acid,
mycophenolate sodium, or any component of the formulation.
Canadian labeling:Pregnancy; women of childbearing potential and not
using highly effective contraceptive methods; women of childbearing
potential not providing a pregnancy test result; breastfeeding.
Common S.E Acute inflammatory syndrome
Bone marrow suppression
GI effects
Infection
Lymphoproliferative disorders
Pure red cell aplasia

17. Endoxan
Indication and dose Lupus nephritis, focal or diffuse :
IV (shorter, low-dose regimen; preferred regimen): 500 mg once every 2 weeks for 6
doses, then transition to an alternative immunosuppressive agent.
IV (longer, high-dose regimen): 500 to 1,000 mg/m2 once every month for 6 doses,
then transition to an alternative immunosuppressive agent . Maximum dose has not
been established; some experts do not exceed 1,000 mg/dose .
Oral: Initial: 1 to 1.5 mg/kg once daily; some experts increase by 0.5 mg/kg/day every
week up to 2 mg/kg once daily if needed based on response, and do not exceed 150
mg/day .Continue therapy for 2 to 4 months once the dose is stabilized, then transition
to an alternative immunosuppressive agent .
Administration Route Administer by direct IV injection, IVPB, or continuous IV infusion.
Oral: swallow whole; do not crush or chew; do not open capsules.
Diluent NS or SWFI.
1/2 NS, D5W,
Stability
. Powder for reconstitution: Store intact vials of powder at ≤25°C (77°F). According
to the manufacturer, reconstituted solutions in NS are stable for 24 hours at room
temperature and for 6 days refrigerated at 2°C to 8°C (36°F to 46°F). Solutions
diluted for infusion in 1/2NS are stable for 24 hours at room temperature and for 6
days refrigerated and solutions diluted in D5W or D5NS are stable for 24 hours at
room temperature and for 36 hours refrigerated (according to product labeling).
Multi-dose solution: Store intact vials at 2°C to 8°C (36°F to 46°F). Solutions diluted
for infusion (20 mg/mL or 2 mg/mL concentration) may be stored for up to 24 hours at
room temperature or for up to 6 days at 2°C to 8°C (36°F to 46°F). After first use,
partially used vials should be stored at 2°C to 8°C (36°F to 46°F) in the original
carton and used within 28 days.
Single-dose solution: Store intact vials at 2°C to 8°C (36°F to 46°F). Vials diluted
with SWFI may be stored at room temperature or in the refrigerator for up to 24
hours. Infusion solutions diluted in ½NS are stable for up to 24 hours at room
temperature or for up to 6 days refrigerated. Infusion solutions diluted in D5W or
D5NS are stable for up to 24 hours at room temperature or for up to 36 hours
refrigerated.
Oral:
Capsules, tablets: Store at 20°C to 25°C (68°F to 77°F); excursions are permitted
between 15°C and 30°C (59°F and 86°F).
PK
Absorption: Oral: Well absorbed
Distribution: Vd: 30 to 50 L , crosses into CSF
Protein binding: ~20%; some metabolites are bound at >60%
Metabolism: Hepatic to active metabolites acrolein, 4-aldophosphamide, 4-
hydroperoxycyclophosphamide, and nor-nitrogen mustard
Bioavailability: >75%
Half-life elimination: IV: 3 to 12 hours; Children: 4 hours; Adults: 6 to 8 hours
Time to peak: Oral: ~1 hour; IV: Metabolites: 2 to 3 hours
Excretion: Urine (10 to 20% as unchanged drug); feces (4%)
Contraindication
History of severe hypersensitivity to cyclophosphamide.
Severe myelosuppression, severe renal or hepatic impairment, active infection
(especially varicella zoster), severe immunosuppression.
Common S.E
Bone marrow suppression and infection
Cardiotoxicity
Hemorrhagic cystitis
Hepatotoxicity
Pulmonary toxicity
Second primary malignancy

18. SOLUMEDROL
INDICATION AND DOSE
ADMINISTRATION ROUTE IV (SUCCINATE):
-IV PUSH: MAY ADMINISTER AS A SLOW IV
INJECTION.
-INTERMITTENT IV INFUSION: RATE DEPENDENT
UPON DOSE AND SEVERITY OF CONDITION;
TYPICALLY ADMINISTERED AS AN INTERMITTENT
INFUSION OVER 15 TO 60 MINUTES. ADMINISTER
DOSES >250 MG OVER AT LEAST 30 TO 60 MINUTES
DILUENT
METHYLPREDNISOLONE SODIUM SUCCINATE
INJECTION: RECONSTITUTE VIALS ONLY WITH
PROVIDED DILUENT OR BACTERIOSTATIC WATER
WITH BENZYL ALCOHOL . FOR IV INFUSION, DILUTE
RECONSTITUTED DOSE IN D5W, NS, OR D5NS.
STABILITY
METHYLPREDNISOLONE ACETATE INJECTION AND
TABLETS: STORE AT 20°C TO 25°C .DO NOT
AUTOCLAVE VIALS.
METHYLPREDNISOLONE SODIUM SUCCINATE
INJECTION: STORE INTACT VIALS AT 20°C TO 25°C
.PROTECT FROM LIGHT. DO NOT AUTOCLAVE.
STORE RECONSTITUTED VIALS AT 20°C TO 25°C
AND USE WITHIN 48 HOURS.
PK
METABOLISM: HEPATIC TO METABOLITES
HALF-LIFE ELIMINATION:
ADOLESCENTS: IV: 1.9 ± 0.7 HOURS
EXCRETION: URINE
CONTRAINDICATION
HYPERSENSITIVITY TO METHYLPREDNISOLONE OR
ANY COMPONENT OF THE FORMULATION.
COMMON S.E
ADRENAL SUPPRESSION (TERTIARY ADRENAL
INSUFFICIENCY)
CNS AND PSYCHIATRIC/BEHAVIORAL EFFECTS
CUSHINGOID FEATURES/CUSHING SYNDROME
GI EFFECTS
HYPERGLYCEMIA
INFECTION
NEUROMUSCULAR AND SKELETAL EFFECTS
OCULAR EFFECTS