Nelfinavir

Dosage Forms & Strengths

oral powder for suspension

• 50mg/1g scoopful

tablet

• 250mg
• 625mg

HIV Infection

750 mg PO q8hr, OR

1250 mg PO q12hr

Dosage Modifications

Renal impairment: Dose adjustment not necessary

Hepatic impairment

• Mild impairment (Child-Pugh class A): Dose adjustment not necessary
• Severe impairment (Child-Pugh Class B or C): Not recommended

Multiple Myeloma (Orphan)

Orphan designation for treatment of multiple myeloma

Sponsor

• Swiss Group for Clinical Cancer Research (SAKK); Effingerstrasse 33; Bern, Switzerland

Dosage Forms & Strengths

oral powder for suspension

• 50mg/1g scoopful

tablet

• 250mg
• 625mg

HIV Infection

<2 years: Safety and efficacy not established

2-13 years: 45-55 mg/kg PO q12hr, OR 25-35 mg/kg PO q8hr 

Not to exceed adult dose of 2,500 mg/day (q12hr dosing) or 1,875 mg/day (q8hr dosing)

Adolescents: 1,250 mg PO q12hr, OR 750 mg PO q8hr

Also see Administration

>10%

Diarrhea (14-20%)

1-10%

Nausea (3-7%)

Flatulence (1-5%)

Abdominal pain (1%)

Anemia (1%)

Allergic reaction (1%)

Impaired concentration (1%)

Lipodystrophy (1%)

Metabolic acidosis (1%)

Rash (1-3%)

Leukopenia (1%)

Thrombocytopenia (1%)

Weakness (1%)

<1%

QTc prolongation

Torsades de pointes

Diabetes mellitus, new onset and exacerbation

Hyperglycemia

Contraindications

Hypersensitivity

Coadministration with major CYP3A4 substrates and/or inducers

Drugs that are contraindicated with nelfinavir include alpha1-adrenoreptor agonists (eg, alfuzosin), antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, quinidine), rifampin, voriconazole, ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), cisapride, St. John’s wort, lovastatin, simvastatin, lurasidone, pimozide, sildenafil (when used for PAH), midazolam, and triazolam

Cautions

Risk to pregnant/ pediatric pts: EMS (ethyl methanesulfonate) impurity shown to be teratogenic, mutagenic & carcinogenic in animal studies

Oral powder contains 11.2 mg of phenylalanine per gram of powder

Risk of immune reconstitution syndrome if used in combination with other antiretroviral drugs

Caution in patients with hemophilia A or B (risk of bleeding); increased bleeding, including spontaneous skin hematomas and hemarthrosis reported with protease inhibitors; in more than half of cases, administration of protease inhibitors was continued or reintroduced

Increased risks of fat redistribution, hemolytic anemia, hyperbilirubinemia if used in combination with other antiretroviral drugs

Increases risk of developing new onset diabetes mellitus; exacerbation of DM & hyperglycemia

Not for use in patients with moderate to- evere hepatic impairment

In pediatrics, drug exposure is highly variable

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of nelfinavir there are no specific foods that you must exclude from your diet when receiving this medication.
 

• Keep nelfinavir and all other medicines out of the reach of children.
• Keep bottle closed and store at room temperature (between 59°F and 86°F) away from sources of moisture such as a sink or other damp place. Heat and moisture may reduce the effectiveness of nelfinavir.
• Do not keep medicine that is out of date or that you no longer need. Be sure that if you throw any medicine away, it is out of the reach of children.
• Store in original container.

Nelfinavir is an antiviral medicine that prevents human immunodeficiency virus (HIV) from multiplying in your body.

Nelfinavir is used to treat HIV, the virus that can cause acquired immunodeficiency syndrome (AIDS). Nelfinavir is not a cure for HIV or AIDS.

Nelfinavir may also be used for purposes not listed in this medication guide.

You should not use nelfinavir if you have moderate to severe liver disease.

Serious drug interactions can occur when certain medicines are used together with nelfinavir. Tell each of your healthcare providers about all medicines you use now, and any medicine you start or stop using.

Take nelfinavir exactly as directed by your doctor. Do not take it more often, and do not take it for a longer time than your doctor ordered. Also, do not stop taking nelfinavir without first checking with your doctor. Keep taking nelfinavir for the full time of treatment, even if you begin to feel better.

It is important to take nelfinavir together with other medicines for HIV. Be sure to take all of the medicines your doctor ordered, and to take them at the right times.

nelfinavir comes with a patient information leaflet. Read and follow these instructions carefully before starting treatment and each time you refill your prescription. Ask your doctor if you have any questions.

Nelfinavir works best if it is taken with food.

If you are also using didanosine (Videx®), take it 1 hour before or at least 2 hours after taking nelfinavir.

If you cannot swallow the tablet whole, you may dissolve it in a small amount of water. Be sure to drink or swallow the entire mixture right away. Then refill the glass with water and drink it so none of the medicine is left on the sides of the glass.

Measure the powder carefully using the measuring scoop provided with the medicine. Mix the powder with a small amount of water, milk, soy milk, baby formula, or a dietary supplement drink. Do not use apple juice, grapefruit juice, orange juice, or apple sauce. After mixing your medicine with a liquid, use the mixture right away. Be sure to drink or swallow all of the mixture. If not used right away, you may store this mixture in the refrigerator for up to 6 hours.

nelfinavir works best when there is a constant amount in the blood. To help keep the amount constant, do not miss any doses. Also, it is best to take the doses at evenly spaced times during the day. For example, if you are to take three doses each day, the doses should be spaced about 8 hours apart. If you need help in planning the best times to take your medicine, check with your doctor.

Dosing

The dose of nelfinavir will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of nelfinavir. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For treatment of HIV infection:
  • For oral dosage form (oral powder):
    • Children 2 to 13 years of age—Dose is based on body weight and must be determined by your doctor. The dose is usually 45 to 55 milligrams (mg) per kilogram (kg) of body weight two times a day or 25 to 35 mg per kg of body weight three times a day.
    • Children younger than 2 years of age—Use and dose must be determined by your doctor.
  • For oral dosage form (tablets):
    • Adults and children 13 years and older—1250 mg (five 250 mg tablets or two 625 mg tablets) two times a day or 750 milligrams (mg) (three 250 mg tablets) three times a day.
    • Children 2 to 13 years of age—Dose is based on body weight and must be determined by your doctor. The dose is usually 45 to 55 milligrams (mg) per kilogram (kg) of body weight two times a day or 25 to 35 mg per kg of body weight three times a day.
    • Children younger than 2 years of age—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of nelfinavir, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep the bottle tightly closed. Keep the medicine in the original bottle that you were given at the pharmacy.

If you will be taking nelfinavir for a long time, it is very important that your doctor check the progress of you or your child at regular visits to make sure nelfinavir is working properly. Blood tests may be needed to check for unwanted effects.

Do not use nelfinavir if you are also using alfuzosin (Uroxatral®), amiodarone Cordarone®), lovastatin (Advicor®, Altocor®, Mevacor®), lurasidone (Latuda®), oral midazolam (Versed®), pimozide (Orap®), quinidine (Quinaglute®), rifampin (Rifadin®), sildenafil (Revatio®), simvastatin (Simcor®, Vytorin®, Zocor®), triazolam (Halcion®), or ergot medicines (eg, dihydroergotamine, ergotamine, methylergonovine, DHE 45®, Ergomar®),

Do not take other medicines unless they have been discussed with your doctor. This includes prescription and nonprescription (over-the-counter [OTC]) medicines, and herbal (eg, St. John's wort) or vitamin supplements.

Birth control pills that contain estrogen may not work as well while you are using nelfinavir. To keep from getting pregnant, use another form of birth control together with your pills. Other forms include condoms, diaphragms, or contraceptive foams or jellies.

nelfinavir may increase blood sugar levels. Check with your doctor if you or your child notice a change in the results of your blood or urine sugar tests.

nelfinavir may cause you to have excess body fat. Tell your doctor if you or your child notice changes in your body shape, such as an increased amount of fat in the upper back and neck, or around the chest and stomach area. You might also lose fat from the legs, arms, and face.

When you start taking HIV medicines, your immune system may get stronger. If you or your child have certain infections, such as pneumonia or tuberculosis, you may notice new symptoms when your body tries to fight them. If this occurs, be sure to tell your doctor.

nelfinavir will not keep you from giving HIV to your partner during sex. Make sure you understand this and practice safe sex, even if your partner also has HIV, by using a latex condom or other barrier method. nelfinavir will not keep you from giving HIV to other people if they are exposed to your blood. Do not re-use or share needles with anyone.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Confusion
• dehydration
• dry or itchy skin
• fruity mouth odor
• increased hunger
• increased thirst
• increased urination
• nausea
• unusual tiredness or weakness
• vomiting
• weight loss

• Abdominal or stomach pain
• chills
• clay-colored stools
• cough
• dark urine
• difficulty with breathing
• dizziness
• drowsiness
• fever
• headache
• irregular heartbeat
• loss of appetite
• muscle tremors
• noisy breathing
• rapid, deep breathing
• recurrent fainting
• restlessness
• skin rash
• stomach cramps
• tightness in the chest
• unpleasant breath odor
• vomiting of blood
• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Diarrhea

• Intestinal gas
• redistribution or accumulation of body fat

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Viracept: 250 mg, 625 mg

• Viracept

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, since <2% excreted in urine a dosage reduction would not be expected. Guidelines suggest that no dosage adjustment is necessary (HHS [adult] 2015).

>10%: Gastrointestinal: Diarrhea (adults: 14% to 20%; children: 39% to 47%)

1% to 10%:

Central nervous system: Anxiety (<2%), depression (<2%), dizziness (<2%), drowsiness (<2%), emotional lability (<2%), headache (<2%), insomnia (<2%), malaise (<2%), migraine (<2%), myasthenia (<2%), pain (<2%), paresthesia (<2%), seizure (<2%), sleep disorder (<2%), suicidal ideation (<2%)

Dermatologic: Skin rash (adults: 1% to 3%), dermatitis (<2%), diaphoresis (<2%), folliculitis (<2%), fungal dermatitis (<2%), maculopapular rash (<2%), pruritus (<2%), urticaria (<2%)

Endocrine & metabolic: Dehydration (<2%), hyperglycemia (<2%), hyperlipidemia (<2%), hyperuricemia (<2%), hypoglycemia (<2%), increased amylase (<2%), increased gamma-glutamyl transferase (<2%), increased lactate dehydrogenase (<2%), lipodystrophy (<2%), redistribution of body fat (<2%)

Gastrointestinal: Nausea (adults: 3% to 7%), flatulence (adults: 1% to 5%), abdominal pain (<2%), anorexia (<2%), dyspepsia (<2%), epigastric pain (<2%), gastrointestinal hemorrhage (<2%), oral mucosa ulcer (<2%), pancreatitis (<2%), vomiting (<2%)

Genitourinary: Sexual disorder (<2%), urine abnormality (<2%)

Hematologic & oncologic: Lymphocytopenia (adults: 1% to 6%), decreased neutrophils (adults: 1% to 5%), anemia (<2%), leukopenia (<2%), thrombocytopenia (<2%)

Hepatic: Abnormal hepatic function tests (<2%), hepatitis (<2%), increased serum alkaline phosphatase (<2%), increased serum transaminases (<2%)

Hypersensitivity: Hypersensitivity reaction (<2%; including bronchospasm, edema, and skin rash)

Neuromuscular & skeletal: Arthralgia (<2%), arthritis (<2%), back pain (<2%), hyperkinesia (<2%), increased creatine phosphokinase (<2%), lipoatrophy (<2%), lipotrophy (<2%), muscle cramps (<2%), myalgia (<2%), myopathy (<2%), weakness (<2%)

Ophthalmic: Acute iritis (<2%), eye disease (<2%)

Renal: Nephrolithiasis (<2%)

Respiratory: Dyspnea (<2%), pharyngitis (<2%), rhinitis (<2%), sinusitis (<2%)

Miscellaneous: Fever (<2%)

<1% (Limited to important or life-threatening): Hyperbilirubinemia, immune reconstitution syndrome, jaundice, metabolic acidosis, prolonged Q-T interval on ECG, torsades de pointes

Adverse events were not observed in animal reproduction studies. Nelfinavir has a minimal to low level of transfer across the human placenta. No increased risk of overall birth defects has been observed following first trimester exposure according to data collected by the antiretroviral pregnancy registry. A small increased risk of preterm birth has been associated with maternal use of protease inhibitor-based combination antiretroviral therapy during pregnancy; however, the benefits of use generally outweigh this risk and protease inhibitors (PIs) should not be withheld if otherwise recommended. Information related to stillbirth, low birth weight, and small for gestational age infants is limited. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children who develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction. Hyperglycemia, new onset of diabetes mellitus, or diabetic ketoacidosis have been reported with PIs; it is not clear if pregnancy increases this risk.

Combination antiretroviral therapy (cART) therapy is recommended for all HIV-infected pregnant women to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. When HIV is diagnosed during pregnancy in a woman who has never received antiretroviral therapy, cART should begin as soon as possible after diagnosis. The Health and Humans Services (HHS) Perinatal HIV Guidelines do not recommended nelfinavir for initial therapy in antiretroviral-naive pregnant women due to lower viral suppression when compared to other regimens. A standard dose of 1,250 mg twice daily has been shown to provide adequate plasma concentrations although lower and variable levels may occur late in pregnancy; the standard 750 mg 3 times daily dosing is not recommended in pregnant women. In general, women who become pregnant on a stable cART regimen may continue that regimen if viral suppression is effective, appropriate drug exposure can be achieved, contraindications for use in pregnancy are not present, and the regimen is well tolerated. Monitoring during pregnancy is more frequent than in non-pregnant adults; cART should be continued postpartum.

For HIV-infected couples planning a pregnancy, maximum viral suppression with cART is recommended prior to conception for the HIV-infected partner(s) and expert consultation is recommended; modification of therapy (if needed) and optimization of the woman’s health should be done prior to conception. HIV-infected women not planning a pregnancy may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. In addition, consistent use of condoms is also recommended (even during pregnancy) to prevent transmission of HIV or other sexually transmitted diseases.

Health care providers are encouraged to enroll pregnant women exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Health care providers caring for HIV-infected women and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2016).

Applies to nelfinavir: oral powder for reconstitution, oral tablet

General

Most side effects were of mild severity. The most common side effect was diarrhea, which was usually of mild to moderate severity.[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (up to 20%)
Common (1% to 10%): Nausea, flatulence
Frequency not reported: Abdominal pain, dyspepsia, epigastric pain, gastrointestinal bleeding, increased amylase, mouth ulceration, pancreatitis, vomiting[Ref]

Hematologic

Common (1% to 10%): Decreased lymphocytes, decreased neutrophils, decreased hemoglobin
Frequency not reported: Anemia, leukopenia, thrombocytopenia

HIV protease inhibitor therapy:
-Frequency not reported: Increased bleeding (including spontaneous skin hematomas, hemarthrosis) in hemophiliacs[Ref]

Increased bleeding (including spontaneous skin hematomas and hemarthrosis) in patients with hemophilia type A and B has been associated with protease inhibitors. In many of the reported cases, treatment with protease inhibitors was continued or restarted and some patients required additional factor VIII. A causal relationship between protease inhibitor therapy and these episodes has not been established.[Ref]

Hepatic

Common (1% to 10%): Elevated AST, elevated ALT
Frequency not reported: Elevated GGT, abnormal liver function tests, hepatitis
Postmarketing reports: Jaundice, bilirubinemia[Ref]

Musculoskeletal

Common (1% to 10%): Elevated creatine kinase
Frequency not reported: Arthralgia, arthritis, back pain, cramps, increased creatine phosphokinase, myalgia, myasthenia, myopathy[Ref]

Dermatologic

Common (1% to 10%): Rash
Frequency not reported: Dermatitis, folliculitis, fungal dermatitis, maculopapular rash, pruritus, sweating, urticaria[Ref]

Nervous system

Frequency not reported: Dizziness, headache, hyperkinesia, migraine, paresthesia, seizures, somnolence[Ref]

Other

Frequency not reported: Accidental injury, asthenia, fever, malaise, pain[Ref]

Respiratory

Frequency not reported: Dyspnea, pharyngitis, rhinitis, sinusitis[Ref]

Cardiovascular

Postmarketing reports: QTc prolongation, torsades de pointes[Ref]

Metabolic

Frequency not reported: Anorexia, increased alkaline phosphatase, increased LDH, hyperlipidemia, hyperuricemia, hyperglycemia, hypoglycemia, dehydration, redistribution/accumulation of body fat
Postmarketing reports: Metabolic acidosis

Combination antiretroviral therapy:
-Frequency not reported: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance")

HIV protease inhibitor therapy:
-Postmarketing reports: New onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, hyperglycemia, ketoacidosis[Ref]

Psychiatric

Frequency not reported: Anxiety, depression, emotional lability, insomnia, sleep disorder, suicidal ideation[Ref]

Hypersensitivity

Frequency not reported: Allergic reaction
Postmarketing reports: Hypersensitivity reactions (including bronchospasm, moderate to severe rash, fever, edema)[Ref]

Renal

Frequency not reported: Kidney calculus[Ref]

Genitourinary

Frequency not reported: Sexual dysfunction, urine abnormality[Ref]

Immunologic

Frequency not reported: Immune reconstitution/reactivation syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome)

Ocular

Frequency not reported: Acute iritis, eye disorder[Ref]

Some side effects of nelfinavir may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Administration advice:
-Administer all doses with a meal (for optimal absorption).
-For patients unable to swallow the tablets: Place tablet(s) in small amount of water; once dissolved, mix the cloudy liquid well, then consume immediately; rinse the glass with water and swallow the rinse to ensure the entire dose is consumed.
-Mix the measured dose of the oral powder with a small amount of water, milk, formula, soy formula, soy milk, or dietary supplements; once mixed, consume the entire contents in order to obtain the full dose; if the mixture is not consumed immediately, it must be stored under refrigeration, but storage must not exceed 6 hours.
-Consult the manufacturer product information regarding missed doses.

Storage requirements:
-Store at 15C to 30C (59F to 86F).
-Store in original bottle and keep tightly closed.

Reconstitution/preparation techniques:
-Acidic foods or juices (e.g., orange juice, apple juice, apple sauce) should not be mixed with the oral powder as a bitter taste may result.
-The oral powder should not be reconstituted with water in its original container.

General:
-The oral powder contains 50 mg (as nelfinavir free base) in each level scoopful (1 g).
-If a teaspoon is used to measure the oral powder, 1 level teaspoon contains 200 mg of nelfinavir (4 level scoops equals 1 level teaspoon).

Monitoring:
-Hematologic: Bleeding in hemophiliacs

Substance Name

Nelfinavir

CAS Registry Number

159989-64-7

Drug Class

Antiinfective Agents

Anti-HIV Agents

Antiviral Agents

Anti-Retroviral Agents

HIV Protease Inhibitors