nelfinavir mesylate

Action

Inhibits action of human immunodeficiency virus (HIV) protease and prevents cleavage of viral polyproteins, resulting in production of immature, noninfectious virus

Availability

Oral powder: 50 mg/1 g powder (1 g powder/level scoopful)

Tablets: 250 mg, 625 mg

Indications and dosages

➣ HIV infection

Adults and children older than age 13: 750 mg P.O. t.i.d. or 1,250 mg b.i.d., given with other antiretrovirals

Children ages 2 to 13: 20 to 30 mg/kg P.O. t.i.d., given with a meal or light snack

Contraindications

• Hypersensitivity to drug or its components

• Concurrent use of amiodarone, dihydroergotamine, ergonovine, ergotamine, midazolam, pimozide, quinidine, rifampin, sildenafil (when used for pulmonary arterial hypertension), or triazolam

Precautions

Use cautiously in:

• moderate or severe hepatic impairment (avoid use)

• hemophilia, diabetes mellitus

• concurrent use of lovastatin, simvastatin, or St. John's wort (not recommended)

• concurrent use of other HMG-CoA reductase inhibitors also metabolized by the CYP3A pathway, proton pump inhibitors, and rifampin

• phenylketonuria (oral powder contains phenylalanine)

• breastfeeding patients.

Administration

• Give tablets with food.

• For adult who can't swallow tablets whole, crush and mix in food or dissolve in small amount of water. Have patient consume mixture immediately, or refrigerate for up to 6 hours.

• For child who can't swallow tablets, mix oral powder with small amount of water, formula, or milk. Have child consume mixture immediately, or refrigerate for up to 6 hours.

• Don't mix powder with water in its original container.

• Don't mix powder with acidic juice (combination produces bitter taste).

Don't give concurrently with amiodarone, astemizole, cisapride, dihydroergotamine, ergotamine, midazolam, quinidine, rifampin, terfenadine, or triazolam.

Adverse reactions

CNS: anxiety, depression, dizziness, drowsiness, emotional lability, headache, hyperkinesia, insomnia, malaise, migraine headache, sleep disorders, weakness, myasthenia, paresthesia, suicidal ideation, seizures

EENT: acute iritis, rhinitis, sinusitis, pharyngitis

GI: nausea, diarrhea, abdominal pain, flatulence

GU: nephrolithiasis, sexual dysfunction

Hematologic: anemia, leukopenia, thrombocytopenia

Metabolic: dehydration, hyperuricemia, hyperglycemia, hypoglycemia

Musculoskeletal: joint pain, arthritis, back pain, myalgia, myopathy

Respiratory: dyspnea, bronchospasm

Skin: pruritus, rash, sweating, fungal dermatitis, folliculitis, urticaria

Other: fever, body fat redistribution, allergic reactions, immune reconstitution syndrome

Interactions

Drug-drug. Amiodarone, dihydroergotamine, ergotamine, midazolam, quinidine, triazolam: excessive sedation, vasoconstriction, serious arrhythmias

Atorvastatin, rosuvastatin: increased statin concentration

Azithromycin, bosentan, colchicine, inhaled fluticasone, salmeterol: increased concentration of these drugs

Carbamazepine, phenobarbital, phenytoin, rifampin: decreased nelfinavir blood level and efficacy

Delavirdine: increased nelfinavir concentration, decreased delavirdine concentrations

HMG-CoA reductase inhibitors: increased risk of serious reactions, such as myopathy and rhabdomyolysis

Hormonal contraceptives: decreased contraceptive blood level and efficacy

Immunosuppressants (cyclosporine, sirolimus, tacrolimus): increased immunosuppressant concentration

Indinavir, saquinavir: increased indinavir or saquinavir concentration and increased nelfinavir concentration

Methadone, trazodone: decreased concentration of these drugs Nevirapine: decreased nelfinavir concentration

Rifabutin: decreased rifabutin metabolism and effects Ritonavir: increased nelfinavir concentration

Sildenafil, tadalafil, vardenafil: increased risk of adverse events

Warfarin: affected warfarin concentration

Drug-diagnostic tests. Alanine amino-transferase, alkaline phosphatase, amylase, aspartate aminotransferase, creatine kinase, gamma-glutamyl transpeptidase, lactic dehydrogenase lipids, uric acids: increased levels Blood glucose: increased or decreased level

Hemoglobin, platelets, white blood cells: decreased levels

Drug-food. Most foods: enhanced drug absorption

Drug-herbs. St. John's wort: decreased nelfinavir blood level and efficacy

Patient monitoring

Watch for signs and symptoms of depression and suicidal ideation.

• Evaluate neurologic status closely, particularly for seizures and sensori-motor dysfunction.

• Assess CBC, lipid panel, uric acid level, and HIV-specific tests.

• Watch for secondary infections, particularly fungal and EENT infections.

Be aware that immune reconstitution syndrome may occur in patients receiving combination anti-retroviral therapy. During initial phase of therapy, patient whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium complex, cytomegalovirus, Pneumocystis jiroveci pneumonia, and tuberculosis), which may necessitate further evaluation and treatment.

Patient teaching

• Advise patient to take with a meal or snack. Inform him that he may mix oral powder with nonacidic fluids.

• Tell patient he may take missed dose up to 1 hour before next scheduled dose.

Instruct patient to report depression or suicidal thoughts.

• Tell patient that drug may predispose him to other infections, especially fungal and EENT infections. Advise him to avoid crowds and to wash hands often and thoroughly.

• Tell patient with phenylketonuria (or caregiver) that powder contains phenylalanine.

Tell patient to immediately report new or worsening signs or symptoms.

Advise patient not to use St. John's wort while taking this drug.

• Advise female patient to use reliable barrier contraception.

• Advise female patient not to breastfeed, because breast milk may transfer HIV to infant.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, vision, strength, and alertness.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.