Viracept (nelfinavir mesylate)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Nelfinavir mesylate, an antiretroviral agent, is a human immunodeficiency virus (HIV) protease inhibitor (PI).
While the complete mechanism(s) of antiviral activity of nelfinavir has not been fully elucidated, nelfinavir appears to inhibit replication of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) by interfering with HIV protease. The drug, therefore, exerts a virustatic effect against retroviruses by acting as an HIV protease inhibitor.
Nelfinavir is a selective, competitive, reversible inhibitor of HIV protease. HIV protease, an aspartic endopeptidase that functions as a homodimer, plays an essential role in the HIV replication cycle and the formation of infectious virus. During HIV replication, HIV protease cleaves viral polypeptide products of the gag and gag-pol genes (i.e., p55 and p160) to form structural proteins of the virion core (i.e., p17, p24, p9, and p7) and essential viral enzymes (i.e., reverse transcriptase, integrase, and protease).
By interfering with the formation of these essential proteins and enzymes, nelfinavir blocks maturation of the virus and causes the formation of nonfunctional, immature, noninfectious virions. Nelfinavir is active in both acutely and chronically infected cells since it targets the HIV replication cycle after translation and before assembly.
Unlike nucleoside reverse transcriptase inhibitors, the antiretroviral activity of nelfinavir does not depend on intracellular conversion to an active metabolite. Nelfinavir and other HIV protease inhibitors (e.g., atazanavir, amprenavir (commercially available as fosamprenavir), lopinavir, ritonavir) act at a different stage of the HIV replication cycle than other available antiretroviral agents, including nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors. Results of in vitro studies indicate that the antiretroviral effects of nelfinavir and nucleoside or nucleotide reverse transcriptase inhibitors may be additive (didanosine) or synergistic (abacavir, emtricitabine, lamivudine, tenofovir disoproxil fumarate, zidovudine).
In vitro studies also indicate that the antiretroviral effects of nelfinavir and nonnucleoside reverse transcriptase inhibitors (efavirenz, nevirapine) are synergistic against HIV-1. In vitro studies evaluating the antiretroviral effects of nelfinavir used with other HIV protease inhibitors (amprenavir, lopinavir, ritonavir) have resulted in variable results ranging from antagonism to synergism.
A study in healthy individuals who received a single 750-mg dose of nelfinavir with food indicated that nelfinavir pharmacokinetics are similar following administration of 250-mg tablets or the oral powder (no longer commercially available in the US). Results of a multiple-dose study in HIV-infected individuals who received nelfinavir 1.25 g twice daily with food indicate that the commercially available 250-mg and 625-mg film-coated tablets are bioequivalent. Presence of food in the GI tract substantially increases the absorption of oral nelfinavir and decreases the pharmacokinetic variability of the drug relative to the fasting state.
In a study in healthy individuals who received a single 1.25-g dose of nelfinavir as 250-mg tablets, peak plasma concentration and AUC were 2-5 times greater when the dose was administered with a meal (125-1000 kCal with 20-50% fat) rather than under fasting conditions. Preliminary data indicate that food has a similar effect when the drug is administered as 625-mg tablets.
Following oral administration of a single 1.25-g dose of nelfinavir as two 625-mg tablets in fasting healthy individuals, the AUC of nelfinavir was 34% higher and peak plasma concentrations were 24% higher than values obtained when the dose was administered as five 250-mg tablets. When the same dose was given with food, AUC values were 24% higher with the 625-mg tablets but peak plasma concentrations were similar to values obtained with the 250-mg tablets. Following oral administration of multiple doses of nelfinavir 1.25 g twice daily with food, nelfinavir exposure (peak plasma concentration, AUC) at steady state in HIV-infected patients receiving two 625-mg tablets twice daily was similar to that in patients receiving five 250-mg tablets twice daily.
Nelfinavir is more than 98% bound to plasma protein. The drug is distributed into human milk.
The metabolic fate of nelfinavir has not been fully determined, but the drug is metabolized in the liver to many oxidative metabolites. In vitro studies indicate that metabolism of nelfinavir is mediated by several cytochrome P-450 isoenzymes, including CYP3A and CYP2C19. The plasma elimination half-life of nelfinavir is 3.5-5 hours.
Nelfinavir is excreted principally in the feces, both as unchanged drug and metabolites. Following oral administration of a 750-mg dose of radiolabeled nelfinavir, 87% of the dose is recovered in feces (22% as unchanged drug) and 1-2% is recovered in urine (principally as unchanged drug). Pharmacokinetic studies have not revealed gender-related differences in the pharmacokinetics of nelfinavir; further study is needed to determine if there are race-related differences.
USES: This drug is used with other HIV medications to help control HIV infection. It helps to decrease the amount of HIV in your body so your immune system can work better. This lowers your chance of getting HIV complications (such as new infections, cancer) and improves your quality of life.
Nelfinavir belongs to a class of drugs known as protease inhibitors. Nelfinavir is not a cure for HIV infection. To decrease your risk of spreading HIV disease to others, continue to take all HIV medications exactly as prescribed by your doctor.
Use an effective barrier method (latex or polyurethane condoms/dental dams) during sexual activity as directed by your doctor. Do not share personal items (such as needles/syringes, toothbrushes, and razors) that may have contacted blood or other body fluids. Consult your doctor or pharmacist for more details.
Generic name: nelfinavir mesylate
Pronunciation: (nell-FIN-uh-veer)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Viracept
Indications
The following indications are listed for Viracept:
- Hiv Infection
Also known as: Human Immunodeficiency Virus Disease, Human Immunodeficiency Virus Infection.
Dosing
Dosage of nelfinavir mesylate is expressed in terms of nelfinavir.
Nelfinavir is administered orally 2 or 3 times daily.
Nelfinavir should be taken with a meal; presence of food in the GI tract can increase bioavailability of the drug.
Nelfinavir is commercially available as tablets (an oral powder for solution was discontinued).
For patients unable to swallow tablets, the appropriate dose of tablets may be placed in a small amount of water and allowed to disperse. After the tablets dissolve, the cloudy liquid should be mixed well and immediately consumed. To ensure that the entire dose is consumed, the glass should be rinsed with water and the rinse swallowed.
Nelfinavir tablets should not be mixed with acidic food or juice (e.g., apple juice, applesauce, orange juice) since the resulting mixture may have a bitter taste.
If a dose of nelfinavir is missed, it should be taken as soon as it is remembered and the next dose taken at the regularly scheduled time. If a dose is skipped, do not administer a double dose to make up for the missed dose.
Store nelfinavir tablets at 15-30oC in the original container.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Metabolism of nelfinavir is mediated in part by the cytochrome P-450 isoenzymes CYP3A and CYP2C19 and the possibility exists that drugs that induce these isoenzymes may reduce nelfinavir plasma concentrations. Conversely, concomitant use of nelfinavir with drugs that inhibit CYP3A or CYP2C19 may increase nelfinavir plasma concentrations. In addition, nelfinavir is an inhibitor of CYP3A and the possibility exists that the drug may alter the pharmacokinetics of drugs metabolized by this isoenzyme. However, nelfinavir does not appear to have any appreciable inhibitory effect on CYP2D6, 2C9, 2C19, 2C8, 1A2, or 2E1 at clinically relevant concentrations The fact that dosage adjustments of nelfinavir and/or other drugs may be necessary in patients receiving concurrent therapy with drugs that are extensively metabolized by, or that induce or inhibit, CYP3A or CYP2C19 isoenzymes should be considered.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Concomitant use with drugs highly dependent on cytochrome P-450 (CYP) isoenzyme 3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening adverse events (e.g., alfuzosin, amiodarone, cisapride, ergot alkaloids, lovastatin, lurasidone, oral midazolam, pimozide, quinidine, sildenafil used for treatment of pulmonary arterial hypertension (PAH), simvastatin, triazolam).
*Concomitant use with drugs that are CYP3A inducers where significantly reduced nelfinavir plasma concentrations may be associated with a potential loss of virologic response, and possible development of resistance or cross-resistance to other antiretrovirals (e.g., rifampin, St. John's Wort (Hypericum perforatum)).
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in at least 2% of adult and adolescent patients >=13 years of age receiving nelfinavir include diarrhea, nausea, rash, and flatulence.
The most commonly reported adverse effects in pediatric patients 2 to <13 years of age receiving nelfinavir include diarrhea, leukopenia/neutropenia, rash, anorexia, and abdominal pain.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of nelfinavir in pediatric patients younger than 2 years of age have not been established. The manufacturer states that while nelfinavir has been found to be safe at doses studied in pediatric patients younger than 2 years of age, a reliably effective dosage has not been established for this age group. In some studies, the response rate was lower in pediatric patients younger than 2 years of age than in those 2 years of age or older.
Safety and efficacy of nelfinavir for treatment of HIV-1 infection in pediatric patients 2-13 years of age were evaluated in randomized, placebo-controlled trials in antiretroviral-naive and antiretroviral-experienced pediatric patients. Safety and efficacy in adolescents 13 years of age and older is supported by controlled studies in adults.
Use of nelfinavir in pediatric patients is associated with highly variable drug exposure. Unpredictable drug exposure may be exacerbated since pediatric patients clear nelfinavir more rapidly than adults. In addition, these patients may have difficulty with compliance and there may be inconsistent food intake with dosing.
The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to nelfinavir during pregnancy. Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting https://www.apregistry.com/.
Hepatic adverse events, including hepatic enzyme elevations and hepatic failure, have been reported in pregnant patients exposed to nelfinavir. Based on the adverse event profile of nelfinavir, including hepatic adverse events, and literature reports of decreased drug exposure in the second and third trimesters, consider using alternative antiretroviral agents during pregnancy.
Limited data indicate that nelfinavir is present in breastmilk, and adverse effects from infant exposure to nelfinavir have been reported.
The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.
The manufacturer makes no specific dosage recommendations for geriatric patients. Clinical trials did not include a sufficient number of patients >=65 years of age to determine whether there are differences in response compared to younger adults.
Clinical studies of nelfinavir to date have not included sufficient numbers of adults >=65 years of age to determine whether geriatric patients respond differently to the drug than younger adults.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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