A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Viracept Side Effects, and Drug Interactions - Nelfinavir mesylate
Viracept Side Effects, and Drug Interactions - Nelfinavir mesylate
SIDE EFFECTS
The safety of VIRACEPT was studied in over 1500 patients who received
drug either alone or in combination with nucleoside
analogues (d4T or ZDV/3TC). The majority of adverse events were
of mild intensity. The most frequently reported adverse event among
patients receiving VIRACEPT was diarrhea, which was generally of
mild to moderate intensity.
Drug-related clinical
adverse experiences of moderate or severe intensity in 2% or more
of patients treated with VIRACEPT coadministered with ZDV plus 3TC
(Study 511) or in combination with d4T (Study 506) for up to 24
weeks are presented in Table 3.
Table 3
Percentage of Patients with Treatment-Emergent1 Adverse
Events of Moderate or Severe Intensity Reported in 2% or more of
Patients
| Adverse Events |
Study 511
Naive Patients |
Study 506
Experienced Patients |
Placebo + ZDV/3TC
(n=101) |
500 mg
TID VIRACEPT + ZDV/3TC
(n=97) |
750 mg
TID VIRACEPT + ZDV/3TC
(n=100) |
Placebo + d4T
(n=109) |
500 mg
TID VIRACEPT + d4T
(n=98) |
750 mg
TID VIRACEPT + d4T
(n=101) |
|
Body as a Whole
|
| Abdominal Pain |
1% |
0 |
0 |
3% |
2% |
4% |
| Asthenia |
2% |
1% |
1% |
4% |
3% |
1% |
|
Digestive System
|
| Diarrhea |
3% |
14% |
20% |
10% |
28% |
32% |
| Nausea |
4% |
3% |
7% |
1% |
3% |
2% |
| Flatulence |
0 |
5% |
2% |
4% |
8% |
3% |
|
Skin/Appendages
|
| Rash |
1% |
1% |
3% |
0 |
4% |
3% |
1Includes those adverse events at least possibly related
to study drug or of unknown
relationship and excludes concurrent HIV
conditions
Adverse events occurring in less than 2% of patients receiving
VIRACEPT in all phase
II/III clinical trials
and considered at least possibly related or of unknown relationship
to treatment and of
at least moderate severity are listed below.
Body as a Whole: accidental injury,
allergic reaction,
back pain, fever, headache,
malaise, and pain.
Digestive System: anorexia,
dyspepsia, epigastric
pain, gastrointestinal
bleeding, hepatitis,
mouth ulceration, pancreatitis
and vomiting.
Hemic/Lymphatic System: anemia,
leukopenia and thrombocytopenia.
Metabolic/Nutritional System: increases in alkaline
phosphate, amylase, creatine
phosphokinase, lactic
dehydrogenase, SGOT, SGPT
and gamma glutamyl transpeptidase; hyperlipemia, hyperuricemia,
hyperglycemia,
hypoglycemia, dehydration, and liver
function tests abnormal.
Musculoskeletal System: arthralgia,
arthritis, cramps,
myalgia, myasthenia and myopathy.
Nervous System: anxiety,
depression, dizziness,
emotional lability, hyperkinesia, insomnia,
migraine, paresthesia,
seizures, sleep disorder,
somnolence and suicide
ideation.
Respiratory System: dyspnea,
pharyngitis, rhinitis,
and sinusitis.
Skin/Appendages: dermatitis,
folliculitis, fungal
dermatitis, maculopapular rash,
pruritus, sweating,
and urticaria.
Special Senses: acute
iritis and eye
disorder.
Urogenital System: kidney
calculus, sexual dysfunction
and urine abnormality.
Laboratory Abnormalities
Few patients experienced significant
laboratory abnormalities
while receiving VIRACEPT. The percentage of patients with marked
laboratory abnormalities
in Studies 511 and 506 are presented in Table 4. Marked laboratory
abnormalities are defined as a Grade 3 or 4 abnormality
in a patient with a
normal baseline value
or a Grade 4 abnormality
in a patient with a
Grade 1 abnormality at baseline.
Table 4
Percentage of Patients by Treatment Group With Marked Laboratory
Abnormalities1 in >2% of Patients
|
Study 511
Naive Patients |
Study 506
Experienced Patients |
Placebo + ZDV/3TC
(n=101) |
500 mg
TID VIRACEPT + ZDV/3TC
(n=97) |
750 mg
TID VIRACEPT + ZDV/3TC
(n=100) |
Placebo + d4T
(n=109) |
500 mg
TID VIRACEPT + d4T
(n=98) |
750 mg
TID VIRACEPT + d4T
(n=101) |
|
Hematology
|
| Hemoglobin |
6% |
3% |
2% |
0 |
0 |
0 |
| Neutrophils |
4% |
3% |
5% |
1% |
1% |
4% |
| Lymphocytes |
1% |
6% |
1% |
1% |
1% |
0 |
|
Chemistry
|
| ALT (SGPT) |
6% |
1% |
1% |
1% |
3% |
2% |
| AST (SGOT) |
4% |
1% |
0 |
0 |
3% |
3% |
| Creatine Kinase |
7% |
2% |
2% |
4% |
5% |
6% |
1Marked laboratory
abnormalities are defined as a shift
from Grade 0 at baseline
to at least Grade 3 or from Grade 1 to Grade 4
DRUG INTERACTIONS
Nelfinavir is an inhibitor
of CYP3A (cytochrome P450 3A). Coadministration of VIRACEPT and
drugs primarily metabolized by CYP3A (e.g., dihydropyridine calcium
channel blockers) may
result in increased plasma
concentrations of the other drug
that could increase or prolong both its therapeutic
and adverse effects. Nelfinavir is metabolized in proof
by C.P.A. Coadministration
of VIRACEPT and drugs that induce CYP3A may decrease nelfinavir
plasma concentrations and reduce
its therapeutic
effect. Coadministration of VIRACEPT and drugs that inhibit CYP3A
may increase nelfinavir
plasma concentrations.
Based on known metabolic profiles, clinically significant drug interactions
are not expected between VIRACEPT and dapsone, trimethoprim/sulfamethoxazole,
clarithromycin, erythromycin, itraconazole or fluconazole.
| Drugs That Should Not Be
Coadministered With VIRACEPT |
| Drug Class |
Drugs Within Class Not To Be
Coadministered With VIRACEPT |
| Antiarrhythmics |
amiodarone, quinidine |
| Antihistamines |
astemizole, terfenadine |
| Antimigraine |
ergot derivatives |
| Antimycobacterial agents |
rifampin |
| Benzodiazepines |
midazolam, triazolam |
| GI motility
agents |
cisapride |
| Drugs Which Require a Dose Reduction When Coadminstered
With VIRACEPT |
| Drug Class |
Drugs Within Class Which Require Dose Reduction |
| Antimycobacterial agents |
rifabutin |
| Other Potentially Clinically Significant Drug
Interactions With VIRACEPT* |
| Anticonvulsants: carbamazepine, phenobarbital,
phenytoin |
May decrease nelfinavir
plasma concentrations** |
| Anti-HIV protease inhibitors: indinavir, ritonavir |
May increase nelfinavir
plasma concentrations |
| Oral contraceptives: ethinyl estradiol, norethindrone |
Plasma concentrations may be decreased by VIRACEPT |
* This table is not all
inclusive
** VIRACEPT may not be effective due to decreased nelfinavir
plasma concentrations
in patients taking these agents concomitantly
Antihistamines
Terfenadine: Administration of terfenadine with VIRACEPT
resulted in the appearance
of unchanged terfenadine in plasma; therefore, VIRACEPT should not
be administered concurrently with terfenadine because of the potential
for serious and/or life-threatening cardiac
arrhythmias. Because a similar interaction is likely, VIRACEPT should
also not be administered concurrently with astemizole.
Anti-HIV Protease Inhibitors
Indinavir: Coadministration of indinavir
with VIRACEPT resulted in an 83% increase in nelfinavir
plasma AUC
and a 51% increase in indinavir plasma A.C.
Currently, there are no safety
and efficacy data available
from the use of this combination.
Ritonavir: Coadministration of ritonavir with VIRACEPT
resulted in a 152% increase in nelfinavir
plasma AUC
and very little change in ritonavir plasma A.C.
Currently, there are no safety
and efficacy data available
from the use of this combination.
Saquinavir: Coadministration of saquinavir
(using an experimental soft-gelatin capsule
formulation of saquinavir
1200mg) with VIRACEPT resulted in an 18% increase in nelfinavir
plasma AUC
and a 4-fold increase in saquinavir plasma A.C.
If used in combination with saquinavir
hard gelatin capsules
at the recommended dose
of 600 mg tid, no
dose adjustments are needed.
Currently, there are no safety
and efficacy data available
from the use of this combination.
Antifungal Agents
Ketoconazole: Coadministration of ketoconazole with
VIRACEPT resulted in a 35% increase in nelfinavir
plasma A.C.
This change was not considered clinically significant
and no dose
adjustment is needed
when ketoconazole and VIRACEPT are coadministered.
Anti-HIV Reverse Transcriptase
Inhibitors
Didanosine: It is recommended that didanosine
be administered on an empty stomach; therefore, nelfinavir
should be administered (with food) one hour after or more than two
hours before didanosine.
Zidovudine: Coadministration of zidovudine
and lamivudine with
VIRACEPT resulted in a 35% decrease in zidovudine
plasma A.C.
A dose adjustment is not
needed when zidovudine
is administered with VIRACEPT.
Little or no change in the
pharmacokinetics
of either drug was observed
when VIRACEPT was coadministered with lamivudine or stavudine.
Antimycobacterial Agents
Rifabutin: Coadministration of rifabutin and VIRACEPT
resulted in a 32% decrease in nelfinavir
plasma AUC
and a 207% increase in rifabutin plasma A.C.
It is recommended that the dose
of rifabutin be reduced to one-half the usual dose
when administered with VIRACEPT.
Rifampin: Coadministration of rifampin
and VIRACEPT resulted in an 82% decrease in nelfinavir
plasma A.C.
VIRACEPT and rifampin
should not be coadministered.
Oral Contraceptives
Ethinyl Estradiol
and Norethindrone: Coadministration of VIRACEPT with
OVCON-35 resulted in a 47% decrease in ethinyl estradiol
and an 18% decrease in norethindrone
plasma concentrations.
Alternate or additional contraceptive measures should be used during
therapy with VIRACEPT.
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