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VIRACEPT® (nelfinavir mesylate) is an inhibitor of the human immunodeficiency virus (HIV) protease. VIRACEPT Tablets are available for oral administration as a light blue, capsule-shaped tablet with a clear film coating in a 250 mg strength (as nelfinavir free base). Each tablet also contains the following inactive ingredients: calcium silicate, crospovidone, magnesium stearate, FD&C blue #2 powder, hydroxypropyl methylcellulose and triacetin. VIRACEPT Oral Powder is available for oral administration in a 50 mg/g strength (as nelfinavir free base) in bottles. The oral powder also contains the following inactive ingredients: microcrystalline cellulose, maltodextrin, dibasic potassium phosphate, crospovidone, hydroxypropyl methylcellulose, aspartame, sucrose palmitate, and natural and artificial flavor. The chemical name for nelfinavir mesylate is [3 S -[2(2 S *, 3 S *), 3(alpha),4a(beta),8a(beta)]]- N -(1,1-dimethylethyl)decahydro-2-[2-hydroxy-3-[(3-hydroxy-2- methylbenzoyl)amino]-4-(phenylthio)butyl]-3-isoquinolinecarboxamide mono-methanesulfonate (salt) and the molecular weight is 663.90 (567.79 as the free base). Nelfinavir mesylate has the following structural formula:
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Nelfinavir mesylate is a white to off-white amorphous powder, slightly soluble in water at pH </=4 and freely soluble in methanol, ethanol, isopropanol and propylene glycol.
Mechanism of Action: Nelfinavir is an inhibitor of the HIV-1 protease. Inhibition of the viral protease prevents cleavage of the gag-pol polyprotein resulting in the production of immature, non-infectious virus.
Antiviral Activity In Vitro: The antiviral activity of nelfinavir in vitro has been demonstrated in both acute and/or chronic HIV infections in lymphoblastoid cell lines, peripheral blood lymphocytes and monocytes/macrophages. Nelfinavir was found to be active against several laboratory strains of HIV-1 and several clinical isolates of HIV-1 and the HIV-2 strain ROD. The EC 95 (95% effective concentration) of nelfinavir ranged from 7 to 196 nM. In combination with reverse transcriptase inhibitors, nelfinavir demonstrated additive (didanosine or stavudine) to synergistic (zidovudine, lamivudine or zalcitabine) antiviral activity in vitro without enhanced cytotoxicity. Drug combination studies with protease inhibitors (ritonavir, saquinavir or indinavir) showed variable results ranging from antagonistic to synergistic.
Drug Resistance: HIV-1 isolates with reduced susceptibility to nelfinavir have been selected in vitro . HIV isolates from selected patients treated with nelfinavir alone or in combination with reverse transcriptase inhibitors were monitored for phenotypic (n=19) and genotypic (n=195, 157 of which were evaluable) changes in clinical trials over a period of 2 to 82 weeks. One or more virus protease mutations at amino acid positions 30, 35, 36, 46, 71, 77 and 88 were detected in >10% of patients with evaluable isolates. Of 19 patients for which both phenotypic and genotypic analyses were performed on clinical isolates, 9 showed reduced susceptibility (5- to 93-fold) to nelfinavir in vitro . All 9 patients possessed one or more mutations in the virus protease gene. Amino acid position 30 appeared to be the most frequent mutation site.
The overall incidence of the D30N mutation in the virus protease of evaluable patients (n=157) receiving nelfinavir monotherapy or nelfinavir in combination with zidovudine and lamivudine or stavudine was 54.8%. The overall incidence of other mutations associated with primary protease inhibitor resistance was 9.6% for the L90M substitution whereas substitutions at 48, 82, or 84 were not observed.
Cross-resistance: Preclinical Studies - HIV isolates obtained from 5 patients during nelfinavir therapy showed a 5- to 93-fold decrease in nelfinavir susceptibility in vitro when compared to matched baseline isolates, but did not demonstrate a concordant decrease in susceptibility to indinavir, ritonavir, saquinavir or amprenavir, in vitro . Conversely, following ritonavir therapy 6 of 7 clinical isolates with decreased ritonavir susceptibility (8- to 113-fold) in vitro compared to baseline also exhibited decreased susceptibility to nelfinavir in vitro (5- to 40-fold). An HIV isolate obtained from a patient receiving saquinavir therapy showed decreased susceptibility to saquinavir (7-fold), but did not demonstrate a concordant decrease in susceptibility to nelfinavir. Cross-resistance between nelfinavir and reverse transcriptase inhibitors is unlikely because different enzyme targets are involved. Clinical isolates (n=5) with decreased susceptibility to zidovudine, lamivudine, or nevirapine remain fully susceptible to nelfinavir in vitro .
Clinical Studies - There have been no controlled or comparative studies evaluating the virologic response to subsequent protease inhibitor-containing regimens in patients who have demonstrated loss of virologic response to a nelfinavir-containing regimen. However, virologic response was evaluated in a single-arm prospective study of 26 patients with extensive prior antiretroviral experience with reverse transcriptase inhibitors (mean 2.9) who had received VIRACEPT for a mean duration of 59.7 weeks and were switched to a ritonavir (400 mg BID)/saquinavir hard-gel (400 mg BID) containing regimen after a prolonged period of VIRACEPT failure (median 48 weeks). Sequence analysis of HIV-1 isolates prior to switch demonstrated a D30N or an L90M substitution in 18 and 6 patients, respectively. Subjects remained on therapy for a mean of 48 weeks (range 40 to 56 weeks) where 17 of 26 (65%) subjects and 13 of 26 (50%) subjects were treatment responders with HIV RNA below the assay limit of detection (Chiron bDNA) at 24 and 48 weeks, respectively.
The pharmacokinetic properties of nelfinavir were evaluated in healthy volunteers and HIV-infected patients; no substantial differences were observed between the two groups.
Absorption In a pharmacokinetic study in HIV-positive patients, multiple dosing with 750 mg (three 250 mg tablets) three times daily (TID) for 28 days (11 patients) achieved peak plasma concentrations (C max ) of 3.0 +/- 1.6 mg/L and morning and afternoon trough concentrations of 1.4 +/- 0.6 mg/L and 1.0 +/- 0.5 mg/L, respectively. In the same study, multiple dosing with 1250 mg (five 250 mg tablets) twice daily (BID) for 28 days (10 patients) achieved C max of 4.0 +/- 0.8 mg/L and morning and evening trough concentrations of 2.2 +/- 1.3 mg/L and 0.7 +/- 0.4 mg/L, respectively. The difference between morning and afternoon or evening trough concentrations for the TID and BID regimens was also observed in healthy volunteers who were dosed at precise 8- or 12-hour intervals.
Effect of Food on Oral Absorption: Maximum plasma concentrations and area under the plasma concentration-time curve (AUC) were 2 to 3-fold higher under fed conditions compared to fasting. The effect of food on nelfinavir absorption was evaluated in two studies (n=14, total). The meals evaluated contained 517 to 759 Kcal, with 153 to 313 Kcal derived from fat.
Distribution The apparent volume of distribution following oral administration of nelfinavir was 2-7 L/kg. Nelfinavir in serum is extensively protein-bound (>98%).
Metabolism Unchanged nelfinavir comprised 82-86% of the total plasma radioactivity after a single oral 750 mg dose of 14 C-nelfinavir. In vitro , multiple cytochrome P-450 isoforms including CYP3A are responsible for metabolism of nelfinavir. One major and several minor oxidative metabolites were found in plasma. The major oxidative metabolite has in vitro antiviral activity comparable to the parent drug.
Elimination: The terminal half-life in plasma was typically 3.5 to 5 hours. The majority (87%) of an oral 750 mg dose containing 14 C-nelfinavir was recovered in the feces; fecal radioactivity consisted of numerous oxidative metabolites (78%) and unchanged nelfinavir (22%). Only 1-2% of the dose was recovered in urine, of which unchanged nelfinavir was the major component.
Hepatic or Renal Insufficiency: The pharmacokinetics of nelfinavir have not been studied in patients with hepatic or renal insufficiency; however, less than 2% of nelfinavir is excreted in the urine, so the impact of renal impairment on nelfinavir elimination should be minimal.
Gender and Race: No significant pharmacokinetic differences have been detected between males and females. Pharmacokinetic differences due to race have not been evaluated.
Pediatrics see PRECAUTIONS : Pediatric Use
Geriatric Patients: The pharmacokinetics of nelfinavir have not been studied in patients over 65 years of age.
Drug Interactions (also see CONTRAINDICATIONS , , PRECAUTIONS : Drug Interactions )
The potential ability of nelfinavir to inhibit the major human cytochrome P450 isoforms (CYP3A, CYP2C19, CYP2D6, CYP2C9, CYP1A2 and CYP2E1) has been investigated in vitro . Only CYP3A was inhibited at concentrations in the therapeutic range.
Specific drug interaction studies were performed with nelfinavir and a number of drugs. Table 1 summarizes the effects of nelfinavir on the geometric mean AUC and C max of coadministered drugs. Table 2 shows the effects of coadministered drugs on the geometric mean AUC and C max of nelfinavir.
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For information regarding clinical recommendations, see CONTRAINDICATIONS , , PRECAUTIONS : Drug Interactions .
VIRACEPT in combination with other antiretroviral agents is indicated for the treatment of HIV infection.
In the clinical studies described below, efficacy was evaluated by the percent of patients with plasma HIV RNA < 400 copies/mL (Studies 511 and 542) or < 500 copies/mL (Study ACTG 364), using the Roche RT-PCR (Amplicor) HIV-1 Monitor or < 50 copies/mL, using the Roche HIV-1 Ultrasensitive assay (Study Avanti 3). In the analysis presented in each figure, patients who terminated the study early for any reason, switched therapy due to inadequate efficacy or who had a missing HIV-RNA measurement that was either preceded or followed by a measurement above the limit of assay quantification were considered to have HIV-RNA above 400 copies/mL, above 500 copies/mL, or above 50 copies/mL at subsequent time points, depending on the assay that was used.
a. Studies in Antiretroviral Treatment Naive Patients
Study 511: VIRACEPT + zidovudine + lamivudine versus zidovudine + lamivudine
Study 511 was a double-blind, randomized, placebo controlled trial comparing treatment with zidovudine (ZDV; 200mg TID) and lamivudine (3TC; 150mg BID) plus 2 doses of VIRACEPT (750mg and 500mg TID) to zidovudine (200mg TID) and lamivudine (150mg BID) alone in 297 antiretroviral naive HIV-1 infected patients (median age 35 years [range 21 to 63], 89% male and 78% Caucasian). Mean baseline CD 4 cell count was 288 cells/mm 3 and mean baseline plasma HIV RNA was 5.21 log 10 copies/mL (160,394 copies/mL). The percent of patients with plasma HIV RNA < 400 copies/mL and mean changes in CD 4 cell count are summarized in Figures 1 and 2, respectively.
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Study 542: VIRACEPT BID + stavudine + lamivudine compared to VIRACEPT TID + stavudine + lamivudine
Study 542 is an ongoing, randomized, open-label trial comparing the HIV RNA suppression achieved by VIRACEPT 1250 mg BID versus VIRACEPT 750 mg TID in patients also receiving stavudine (d4T; 30-40mg BID) and lamivudine (3TC; 150mg BID). Patients had a median age of 36 years (range 18 to 83), were 84% male, and were 91% Caucasian. Patients had received less than 6 months of therapy with nucleoside transcriptase inhibitors and were naive to protease inhibitors. Mean baseline CD4 cell count was 296 cells/mm 3 and mean baseline plasma HIV RNA was 5.0 log 10 copies/mL (100,706 copies/mL).
Results showed that there was no significant difference in mean CD4 count among treatment groups; the mean increases from baseline for the BID and TID arms were 150 cells/mm 3 at 24 weeks and approximately 200 cells/mm 3 at 48 weeks.
The percent of patients with HIV RNA <400 copies/mL is summarized in Figure 3. The outcomes of patients through 48 weeks of treatment are summarized in Table 3.
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Study Avanti 3: VIRACEPT TID + zidovudine + lamivudine compared to zidovudine + lamivudine.
Study Avanti 3 was a placebo-controlled, randomized, double-blind study designed to evaluate the safety and efficacy of VIRACEPT (750 mg TID) in combination with zidovudine (ZDV; 300 mg BID) and lamivudine (3TC; 150 mg BID) versus placebo in combination with ZDV and 3TC administered to antiretroviral-naive patients with HIV infection and a CD4 lymphocyte count between 150 and 500 cells/µL. Patients had a mean age of 35 (range 22-59) were 89% male and 88% Caucasian. Mean baseline CD4 cell count was 304 cells/mm 3 and mean baseline plasma HIV RNA was 4.8 log 10 copies/mL (57,887 copies/mL). The percent of patients with plasma HIV RNA <50 copies/mL at 52 weeks was 54% for the VIRACEPT + ZDV + 3TC treatment group and 13% for the ZDV + 3TC treatment group.
b. Studies in Antiretroviral Treatment Experienced Patients
Study ACTG 364: VIRACEPT TID + 2NRTIs compared to efavirenz + 2NRTIs compared to VIRACEPT + efavirenz + 2NRTIs
Study ACTG 364 was a randomized, double-blind study that evaluated the combination of VIRACEPT 750 mg TID and/or efavirenz 600 mg QD with 2 NRTIs (either didanosine [ddI]+ d4T, ddI + 3TC, or d4T + 3TC) in patients with prolonged prior nucleoside exposure who had completed 2 previous ACTG studies. Patients had a mean age of 41 years (range 18 to 75), were 88% male, and were 74% Caucasian. Mean baseline CD4 cell count was 389 cells/mm 3 and mean baseline plasma HIV RNA was 3.9 log 10 copies/mL (7,954 copies/mL).
The percent of patients with plasma HIV RNA < 500 copies/mL at 48 weeks was 42%, 62%, and 72% for the VIRACEPT, EFV, and VIRACEPT+EFV treatment groups, respectively. The 4-drug combination of VIRACEPT + EFV + 2 NRTIs was more effective in suppressing plasma HIV RNA in these patients than either 3-drug regimen.
VIRACEPT is contraindicated in patients with clinically significant hypersensitivity to any of its components.
VIRACEPT should not be administered concurrently with cisapride, triazolam, midazolam, ergot derivatives, amiodarone or quinidine because VIRACEPT may affect the hepatic metabolism of these drugs and create the potential for serious and/or life-threatening adverse events.
Patients with Phenylketonuria: VIRACEPT Oral Powder contains 11.2 mg phenylalanine per gram of powder.
New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus and hyperglycemia have been reported during post-marketing surveillance in HIV-infected patients receiving protease inhibitor therapy. Some patients required either initiation or dose adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases diabetic ketoacidosis has occurred. In those patients who discontinued protease inhibitor therapy, hyperglycemia persisted in some cases. Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made and a causal relationship between protease inhibitor therapy and these events has not been established.
Concomitant use of VIRACEPT with lovastatin or simvastatin is not recommended. Caution should be exercised if HIV protease inhibitors, including VIRACEPT, are used concurrently with other HMG-CoA reductase inhibitors that are also metabolized by the CYP3A4 pathway (e.g., atorvastatin or cerivastatin). The risk of myopathy including rhabdomyolysis may be increased when protease inhibitors, including VIRACEPT, are used in combination with these drugs.
Particular caution should be used when prescribing sildenafil in patients receiving protease inhibitors, including VIRACEPT. Coadministration of a protease inhibitor with sildenafil is expected to substantially increase sildenafil concentrations and may result in an increase in sildenafil-associated adverse events, including hypotension, visual changes, and priapism. (see PRECAUTIONS , Drug Interactions and Information for Patients , and the complete prescribing information for sildenafil)
Concomitant use of St. John's wort (hypericum perforatum) or St. John's wort containing products and VIRACEPT is not recommended. Coadministration of St. John's wort with protease inhibitors, including VIRACEPT, is expected to substantially decrease protease inhibitor concentrations and may result in sub-optimal levels of VIRACEPT and lead to loss of virologic response and possible resistance to VIRACEPT or to the class of protease inhibitors.
Nelfinavir is principally metabolized by the liver. Therefore, caution should be exercised when administering this drug to patients with hepatic impairment.
HIV cross-resistance between protease inhibitors has been observed. (see Microbiology )
There have been reports of increased bleeding, including spontaneous skin hematomas and hemarthrosis, in patients with hemophilia type A and B treated with protease inhibitors. In some patients, additional factor VIII was given. In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced. A causal relationship has not been established.
Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.
For optimal absorption, patients should be advised to take VIRACEPT with food (See : and DOSAGE AND ADMINISTRATION ).
Patients should be informed that VIRACEPT is not a cure for HIV infection and that they may continue to acquire illnesses associated with advanced HIV infection, including opportunistic infections.
Patients should be told that there is currently no data demonstrating that VIRACEPT therapy can reduce the risk of transmitting HIV to others through sexual contact or blood contamination.
Patients should be told that sustained decreases in plasma HIV RNA have been associated with a reduced risk of progression to AIDS and death. Patients should be advised to take VIRACEPT and other concomitant antiretroviral therapy every day as prescribed. Patients should not alter the dose or discontinue therapy without consulting with their doctor. If a dose of VIRACEPT is missed, patients should take the dose as soon as possible and then return to their normal schedule. However, if a dose is skipped, the patient should not double the next dose.
Patients should be informed that VIRACEPT Tablets are film-coated and that this film-coating is intended to make the tablets easier to swallow.
The most frequent adverse event associated with VIRACEPT is diarrhea, which can usually be controlled with non-prescription drugs, such as loperamide, which slow gastrointestinal motility.
Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy including protease inhibitors and that the cause and long term health effects of these conditions are not known at this time.
VIRACEPT may interact with some drugs, therefore, patients should be advised to report to their doctor the use of any other prescription, non-prescription medication or herbal products, particularly St. John's wort.
Patients receiving oral contraceptives should be instructed that alternate or additional contraceptive measures should be used during therapy with VIRACEPT.
Patients receiving sildenafil and nelfinavir should be advised that they may be at an increased risk of sildenafil-associated adverse events including hypotension, visual changes, and prolonged penile erection, and should promptly report any symptoms to their doctor.
Drug Interactions (Also see CONTRAINDICATIONS , , : 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, HMG-CoA reductase inhibitors, immunosuppressants and sildenafil) may result in increased plasma concentrations of the other drug that could increase or prolong both its therapeutic and adverse effects, see Tables 4, 5 and 6. Nelfinavir is metabolized in part by CYP3A. Coadministration of VIRACEPT and drugs that induce CYP3A, such as rifampin, may decrease nelfinavir plasma concentrations and reduce its therapeutic effect. Coadministration of VIRACEPT and drugs that inhibit CYP3A may increase nelfinavir plasma concentrations.
Drug interaction studies reveal no clinically significant drug interactions between nelfinavir and didanosine, lamivudine, stavudine, zidovudine, efavirenz or ketoconazole and no dose adjustments are needed. In the case of 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 2 hours before didanosine.
Based on known metabolic profiles, clinically significant drug interactions are not expected between VIRACEPT and dapsone, trimethoprim/sulfamethoxazole, clarithromycin, azithromycin, erythromycin, itraconazole or fluconazole.
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Carcinogenicity studies in animals have not yet been completed. Nelfinavir was not, however, mutagenic or clastogenic in a battery of in vitro and in vivo tests including microbial mutagenesis (Ames), mouse lymphoma, chromosome aberrations in human lymphocytes, and an in vivo rat micronucleus assay.
Comparisons of systemic exposure are based on the steady-state area under the plasma concentration time curve (AUC) observed in humans receiving the recommended therapeutic dose. Nelfinavir produced no effects on either male or female mating and fertility or embryo survival in rat studies at exposures comparable to human therapeutic exposure. There were also no effects on fetal development or maternal toxicity when nelfinavir was administered to pregnant rats at systemic exposures comparable to human exposure. Administration of nelfinavir to pregnant rabbits resulted in no fetal development effects up to a dose at which a slight decrease in maternal body weight was observed; however, even at the highest dose evaluated, systemic exposure in rabbits was significantly lower than human exposure. Additional studies in rats indicated that exposure to nelfinavir in females from mid-pregnancy through lactation had no effect on the survival, growth, and development of the offspring to weaning. Subsequent reproductive performance of these offspring was also not affected by maternal exposure to nelfinavir. However, there are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, VIRACEPT should be used during pregnancy only if clearly needed.
Antiretroviral Pregnancy Registry: To monitor maternal-fetal outcomes of pregnant women exposed to VIRACEPT and other antiretroviral agents, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling (800) 258-4263.
The Centers for Disease Control and Prevention recommends that HIV-infected mothers not breast-feed their infants to avoid risking postnatal transmission of HIV. Studies in lactating rats have demonstrated that nelfinavir is excreted in milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breast-feed if they are receiving VIRACEPT.
Nelfinavir was studied in one open-label, uncontrolled trial in 38 pediatric patients ranging in age from 2 to 13 years. In order to achieve plasma concentrations in pediatric patients which approximate those observed in adults, the recommended pediatric dose is 20-30 mg/kg given three times daily with a meal or light snack, not to exceed 750 mg three times a day. (see DOSAGE AND ADMINISTRATION ).
A similar adverse event profile was seen during the pediatric clinical trial as in adult patients. The evaluation of the antiviral activity of nelfinavir in pediatric patients is ongoing. The evaluation of the safety, effectiveness and pharmacokinetics of nelfinavir in pediatric patients below the age of 2 years is ongoing.
Clinical studies of VIRACEPT did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
The safety of VIRACEPT was studied in over 5000 patients who received drug either alone or in combination with nucleoside analogues. 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% of patients treated with VIRACEPT coadministered with d4T and 3TC (Study 542) for up to 48 weeks or with ZDV plus 3TC (Study 511) for up to 24 weeks are presented in Table 7.
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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: abdominal pain, accidental injury, allergic reaction, asthenia, back pain, fever, headache, malaise, pain and redistribution/accumulation of body fat (see PRECAUTIONS , Fat Redistribution .)
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.
The following additional adverse experiences have been reported from postmarketing surveillance as at least possibly related or of unknown relationship to VIRACEPT:
Body as a Whole: Hypersensitivity reactions (including bronchospasm, moderate to severe rash, fever and edema).
Metabolic/Nutritional System: bilirubinemia, metabolic acidosis
The percentage of patients with marked laboratory abnormalities in Studies 542 and 511 are presented in Table 8. 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.
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Human experience of acute overdose with VIRACEPT is limited. There is no specific antidote for overdose with VIRACEPT. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage. Administration of activated charcoal may also be used to aid removal of unabsorbed drug. Since nelfinavir is highly protein bound, dialysis is unlikely to significantly remove drug from blood.
Adults: The recommended dose is 1250 mg (five 250 mg tablets) twice daily or 750 mg (three 250 mg tablets) three times daily. VIRACEPT should be taken with a meal or light snack. It is recommended that VIRACEPT be used in combination with nucleoside analogues. Patients unable to swallow tablets may place whole tablets or crushed tablets in a small amount of water to dissolve before ingestion or they may mix crushed tablets in a small amount food. Once mixed with food or dissolved in water, the entire contents must be consumed within 6 hours in order to obtain the full dose.
Pediatric Patients (2-13 years): The recommended oral dose of VIRACEPT for pediatric patients 2 to 13 years of age is 20-30 mg/kg per dose, three times daily with a meal or a light snack. The pharmacokinetics of twice daily dosing of VIRACEPT in pediatric patients has not been established. For children unable to take tablets, VIRACEPT Oral Powder may be administered. The oral powder may be mixed with a small amount of water, milk, formula, soy formula, soy milk or dietary supplements; once mixed, the entire contents must be consumed in order to obtain the full dose. The recommended use period for storage of the product in these media is 6 hours. Acidic food or juice (e.g., orange juice, apple juice or apple sauce) are not recommended to be used in combination with VIRACEPT, because the combination may result in a bitter taste. VIRACEPT Oral Powder should not be reconstituted with water in its original container. The recommended pediatric dose of VIRACEPT to be administered three times daily is described in Table 9.
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VIRACEPT (nelfinavir mesylate) Tablets, 250 mg, are light blue, capsule-shaped tablets with a clear film coating engraved with "VIRACEPT" on one side and "250 mg" on the other.
Available as:
NDC 63010-010-27, bottle containing 270 tablets
NDC 63010-010-30, bottle containing 300 tablets
VIRACEPT (nelfinavir mesylate) Oral Powder, 50 mg/g is an off-white powder containing 50 mg (as nelfinavir free base) in each level scoopful (1 gram).
Available as:
NDC 63010-011-90, multiple use bottle containing 144 grams of powder with scoop.
VIRACEPT Tablets and Oral Powder should be stored at 15 to 30 °C (59° to 86 °F).
Keep container tightly closed. Dispense in original container.
VIRACEPT is a registered trademark of Agouron Pharmaceuticals, Inc.
Issue 5/18/2000
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