preloder

Adefovir Dipivoxil


Adefovir Dipivoxil

is a prescription

medicine

used

to treat (chronic)

infections

with

hepatitis B

virus

.
Dosing
Adult dosing:
Hepatitis B; Prophylaxis – Transplantation of liver:
5 to

10 mg

orally

daily (off-label dosage)

HIV infection – Type B

viral hepatitis

, chronic:

10 mg

orally

once daily (off-label dosage) in combination with

lamivudine

or

emtricitabine

(guideline dosage)

Type B

viral hepatitis

, chronic:

10 mg

orally

once daily; in patients with

lamivudine

-resistant

hepatitis B

virus

infection

,

use

in combination with

lamivudine

to reduce the risk of resistance

Pediatric dosing:
General Dosage Information:
Not recommended in children less than 12 years of age

Type B

viral hepatitis

, chronic:

12 years or older:

10 mg

orally

once daily; in patients with

lamivudine

-resistant

virus

infection

,

use

in combination with

lamivudine

to reduce the risk of resistance

Indications
FDA-Labeled Indications:
Type B

viral

hepatitis

, chronic

Non-FDA Labeled Indications:

hepatitis B

; Prophylaxis –

Transplantation of liver


HIV

infection

– Type B

viral

hepatitis

, chronic

Mechanism of Action

Adefovir

is an acyclic nucleotide analog of

adenosine monophosphate

which is phosphorylated to the active

metabolite

Adefovir

diphosphate by

cellular

kinases

.

Adefovir

diphosphate inhibits HBV

DNA

polymerase

(reverse transcriptase) by competing with the natural substrate deoxyadenosine triphosphate and by causing

DNA

chain termination after its incorporation into

viral

DNA

. The inhibition constant (Ki) for

Adefovir

diphosphate for HBV

DNA

polymerase

was 0.1 µM.

Adefovir

diphosphate is a weak inhibitor of human

DNA

polymerases

α and γ with Ki values of 1.18 µM and 0.97 µM, respectively
Adverse Effect
Common:
Neurologic:

Asthenia

(13%)

Renal:

Serum

creatinine raised

Serious:
Dermatologic:

Stevens-Johnson syndrome


Toxic epidermal necrolysis



Endocrine metabolic:

Hypophosphatemia


Lactic acidosis



Gastrointestinal:

Pancreatitis



Hepatic:
ALT/SGPT level raised (up to 25%)

Hepatitis

(up to 25%)

Hepatomegaly

, with steatosis

Renal:

Nephrotoxicity


Renal failure



Contraindication

Hypersensitivity

to

Adefovir Dipivoxil

or any other component of the product
Interaction
Since

Adefovir

is eliminated by the kidney, co-administration of

Adefovir Dipivoxil

with drugs that reduce

renal function

or compete for active

tubular secretion

may increase

serum concentrations

of either

Adefovir

and/or these co-administered drugs .Patients should be monitored closely for adverse events when

Adefovir

Dipivoxil is co-administered with drugs that are excreted renally or with other drugs known to affect

renal function

.

Adefovir Dipivoxil

should not be administered in combination with
tenofovir
disoproxil
fumarate
.
Phamacokinetics
Absorption:
Time for Maximum Plasma Concentration (Tmax):
Mild

renal impairment

: 1.5 hours
Moderate

renal impairment

: 3.3 hours

Bioavailability
:
Adults: 59%

Effect of food
: None
Distribution:
Plasma Protein binding
: less than or equal to 4%
Volume of Distribution
(Vd): 352 +/- 75 to 352 +/- 9 mL/kg

Metabolism:
Active metabolite:

Adefovir



Excretion:
Renal: 45%

Adefovir

recovered in urine
Dialyzable: Yes (hemodialysis) 70% to 90%

Total body clearance:
Mild

renal impairment

: 251 mL/minute
Moderate

renal impairment

: 163.8 mL/minute

Elimination:
7.48 +/- 1.65 hours
Mild

renal impairment

: 5.9 hours
Moderate

renal impairment

: 8.9 hours

Precaution
Concomitant

use

:

Concomitant

use

with tenofovir disoproxil fumarate, or products containing tenofovir disoproxil fumarate, is not recommended.

Endocrine and metabolic:

Lactic acidosis

, with some cases fatal, has been reported, with an increased risk in women, obese patients, and prolonged

use

; discontinue

Hepatic:
Severe hepatomegaly with steatosis, with some cases fatal, has been reported, with an increased risk in women, obese patients, and prolonged

use

; discontinue
Hepatic decompensation, some cases fatal, may occur, especially in patients with cirrhosis or advanced

liver disease

; monitoring recommended.
Clinical resistance may occur leading to

viral

load rebound,

hepatitis B

virus

(HBV) exacerbation, and subsequent

hepatic decompensation

; monitoring of HBV

DNA

recommended.

Renal:

Nephrotoxicity

may occur, especially in patients at risk for or with underlying

renal dysfunction

(CrCl less than 50 mL/minute) and in those taking concomitant nephrotoxic agents; monitoring and dose adjustments recommended

Pregnancy Category
C (FDA)
Breast Feeding
Infant risk cannot be ruled out.
Monitoring
AST/ALT,

hepatitis B

envelope antigen,

hepatitis B

surface antigen, and HBV

DNA

levels every three months for first year of therapy and annually thereafter during
treatment
; following
treatment
discontinuation monitor every 3 months for 1 year then annually thereafter; increased frequency may be required in patients with advanced or decompensated cirrhosis, HIV co-

infection

, or where
treatment
adherence is a concern
Non-invasive liver testing; annually in patients without cirrhosis at baseline for the presence of cirrhosis
Clinical response in patients with renal insufficiency
HIV

antibody

testing in all patients prior to therapy
Renal function; prior to initiation and during therapy; particularly in or patients with pre-existing

renal impairment

or at risk for renal toxicity

Hepatic function

; closely for clinical and laboratory signs of hepatitis exacerbation at repeated intervals for at least several months in patients who discontinue therapy
Signs and symptoms of adverse events when concomitantly administered with drugs that are renally excreted or known to affect renal function
How to Take or Administration
Oral:
Take with or without food

Dosage Form
Oral Tablet:

10 mg



Patient Counselling or Clinical Teaching
Counsel patient to practice safe sex Drug does not prevent disease transmission.
Warn patient to not abruptly discontinue

medications

, as severe acute exacerbation of hepatitis may occur
This drug may cause

abdominal pain

,

diarrhea

,

dyspepsia

,

flatulence

,

nausea

,

asthenia

, or

headache


Instruct patient to report signs/symptoms of nephrotoxicity,

lactic acidosis

(

nausea

,

vomiting

,

abdominal pain

, and

tachypnea

) or hepatotoxicity (

severe abdominal pain

,

muscle pain

,

yellowing of the eyes

,

dark urine,

pale stools, and

loss of appetite

)
Advise patient there are multiple significant drug-drug interactions for this drug. Consult healthcare professional prior to new drug

use

(including over-the-counter and herbal drugs such as St. John’s Wort)
Advise patient to call healthcare professional if a dose is missed, as drug should be given on a regular schedule












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