Side Effects of Viracept (nelfinavir)

Viracept (nelfinavir) is a protease inhibitor used to treat infections with the human immunodeficiency virus (HIV). 

During infection with HIV, the HIV virus multiplies within the body's cells. Viruses are released from the cells and spread throughout the body where they infect other cells. In this manner, HIV infection is perpetuated among new cells that the body continually produces. 

During the production of the viruses, new proteins are made. Some of the proteins are structural proteins that form the body of the virus. Other proteins are enzymes which manufacture DNA and other components for the new viruses. 

Protease is the enzyme that forms the new structural proteins and enzymes. Viracept blocks the activity of protease and results in the formation of defective viruses that are unable to infect the body's cells. 

As a result, the number of viruses in the body (the viral load) decreases. Viracept does not prevent the transmission of HIV among individuals, and it does not cure HIV infections or AIDS.

Common side effects of Viracept include

• nausea,
• diarrhea,
• gas (flatulence),
• allergic reactions,
• rash, and
• redistribution or accumulation of body fat.

Serious side effects of Viracept include

• yellowing skin and eyes (jaundice),
• metabolic disturbance,
• liver failure,
• failure of the pancreas (pancreatitis),
• increased cholesterol,
• worsening of diabetes,
• immune reconstitution syndrome (an inflammatory response to infection), and
• spontaneous bleeding in patients with hemophilia.

Drug interactions of Viracept include

• fluticasone,
• itraconazole,
• ketoconazole,
• lopinavir/ritonavir,
• methadone,
• omeprazole,
• rifabutin,
• St. John's wort,
• antidepressants,
• calcium channel blockers,
• cholesterol-lowering medicines,
• drugs that weaken the immune system,
• insulin or oral diabetes medications,
• medicines to treat erectile dysfunction, and
• seizure medications. 

Viracept is not expected to be harmful to an unborn baby, but HIV can be passed to a baby if the mother is not properly treated during pregnancy. Tell your doctor if you are pregnant or plan to become pregnant. 

It is unknown if Viracept is secreted in breast milk. Nevertheless, HIV-infected mothers should not breastfeed because of the potential risk of transmitting HIV to an infant that is not infected.

The most common side effects are

• nausea,
• diarrhea,
• flatulence,
• allergic reactions, and
• rash.

Other important side effects Nelfinavir include:

• jaundice,
• metabolic disturbance,
• liver failure and
• failure of the pancreas (pancreatitis).

Nelfinavir oral powder contains phenylalanine and should be avoided by individuals with phenylketonuria. Like other protease inhibitors, use of nelfinavir may be associated with redistribution or accumulation of body fat, increased cholesterol and worsening of diabetes.

Immune reconstitution syndrome, an inflammatory response to infection, may occur in patients treated with combinations of drugs for the treatment of HIV infection. There have been reports of spontaneous bleeding in patients with hemophilia treated with protease inhibitors.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials Experience: Adults And Adolescents (13 Years and Older)

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 4.

Table 4: Percentage of Patients with Treatment-Emergent* Adverse Events of Moderate or Severe Intensity Reported in ≥ 2% of Adult and Adolescent Patients

Adverse events occurring in less than 2% of patients receiving Viracept in all phase 2 and 3 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.

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 phosphatase, 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

The percentage of patients with marked laboratory abnormalities in Studies 542 and 511 are presented in Table 5. 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 5: Percentage of Patients by Treatment Group with Marked Laboratory Abnormalities* in > 2% of Patients

Clinical Trials Experience: Pediatrics (2 to Less than 13 Years of Age)

Viracept has been studied in approximately 400 pediatric patients in clinical trials from birth to 13 years of age. The adverse event profile seen during pediatric clinical trials was similar to that for adults.

The most commonly reported drug-related, treatment-emergent adverse events reported in the pediatric studies included:

• diarrhea,
• leukopenia/neutropenia,
• rash,
• anorexia, and
• abdominal pain.

Diarrhea, regardless of assigned relationship to study drug, was reported in 39% to 47% of pediatric patients receiving Viracept in 2 of the larger treatment trials. Leukopenia/neutropenia was the laboratory abnormality most commonly reported as a significant event across the pediatric studies.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Viracept. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole: hypersensitivity reactions (including bronchospasm, moderate to severe rash, fever, and edema).

Cardiovascular System: QTc prolongation, torsades de pointes.

Digestive System: jaundice.

Metabolic/Nutritional System: bilirubinemia, metabolic acidosis.

Potential For Viracept To Affect Other Drugs

Nelfinavir is an inhibitor of CYP3A. Coadministration of Viracept and drugs primarily metabolized by CYP3A (e.g., dihydropyridine calcium channel blockers, HMG-CoA reductase inhibitors, immunosuppressants, and PDE5 inhibitors) may result in increased plasma concentrations of such drugs that could increase or prolong both its therapeutic and adverse effects (see Tables 3 and 6).

Potential For Other Drugs To Affect Viracept

Nelfinavir is metabolized by CYP3A and CYP2C19. Coadministration of Viracept and drugs that induce CYP3A or CYP2C19, such as rifampin, may decrease nelfinavir plasma concentrations and reduce its therapeutic effect. Coadministration of Viracept and drugs that inhibit CYP3A or CYP2C19 may increase nelfinavir plasma concentrations.

Established And Other Potentially Significant Drug Interactions

Table 6 provides the effect on concentrations of Viracept or concomitant drug as a result of coadministration with Viracept. These recommendations are based on either drug interaction studies or predicted interactions due to the expected magnitude of interaction and potential for serious adverse events or loss of efficacy.

Table 6: Established and Other Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies [see (Tables 12 and 13) for magnitude of interaction]