Fosamprenavir Tablets

• Tell all of your health care providers that you take this medicine (fosamprenavir tablets). This includes your doctors, nurses, pharmacists, and dentists.
• This medicine interacts with many other drugs. The chance of this medicine's side effects may be raised or how well this medicine (fosamprenavir tablets) works may be lowered. The chance of the other drugs' side effects may also be raised. This may include very bad, life-threatening, or deadly side effects. Check with your doctor and pharmacist to make sure that it is safe for you to take this medicine with all of your other drugs (prescription or OTC, natural products, vitamins).
• If you have high blood sugar (diabetes), talk with your doctor. This medicine may raise blood sugar.
• Some people with hemophilia have had times of more bleeding when taking drugs like this one. If you have hemophilia, talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine is not a cure for HIV. Stay under the care of your doctor.
• Talk with your doctor before you drink alcohol.
• This medicine does not stop the spread of diseases like HIV or hepatitis that are passed through blood or having sex. Do not have any kind of sex without using a latex or polyurethane condom. Do not share needles or other things like toothbrushes or razors. Talk with your doctor.
• Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking this medicine (fosamprenavir tablets).
• Use with care in children. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Do not breast-feed if you have HIV disease unless your doctor tells you to.

Use this medicine (fosamprenavir tablets) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• It is important that you do not miss or skip a dose of this medicine (fosamprenavir tablets) during treatment.
• Take with or without food.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.
• If you are not sure what to do if you miss a dose, call your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Chest pain or pressure.
• Very upset stomach or throwing up.
• Pain in side.
• More trips to the bathroom, more thirst, or weight loss.
• Pain when passing urine.
• Back pain, belly pain, or blood in the urine. May be signs of a kidney stone.
• Numbness or tingling in the mouth.
• Very bad dizziness or passing out.
• Shortness of breath.
• Sweating a lot.
• Feeling very tired or weak.
• Change in body fat.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
• This medicine may help the immune system work. If you have an infection that you did not know you had, it may show up when you take this medicine. Tell your doctor right away if you notice any signs of infection like fever, sore throat, weakness, cough, or shortness of breath after you start this medicine (fosamprenavir tablets).

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

See also Contraindications (4), Clinical Pharmacology (12.3).

If fosamprenavir is used in combination with ritonavir, see full prescribing information for ritonavir for additional information on drug interactions.

 Cytochrome P450 Inhibitors and Inducers

Amprenavir, the active metabolite of fosamprenavir, is an inhibitor of CYP3A4 metabolism and therefore should not be administered concurrently with medications with narrow therapeutic windows that are substrates of CYP3A4. Data also suggest that amprenavir induces CYP3A4.

Amprenavir is metabolized by CYP3A4. Coadministration of fosamprenavir and drugs that induce CYP3A4, such as rifampin, may decrease amprenavir concentrations and reduce its therapeutic effect. Coadministration of fosamprenavir and drugs that inhibit CYP3A4 may increase amprenavir concentrations and increase the incidence of adverse effects.

The potential for drug interactions with fosamprenavir changes when fosamprenavir is coadministered with the potent CYP3A4 inhibitor ritonavir. The magnitude of CYP3A4-mediated drug interactions (effect on amprenavir or effect on coadministered drug) may change when fosamprenavir is coadministered with ritonavir. Because ritonavir is a CYP2D6 inhibitor, clinically significant interactions with drugs metabolized by CYP2D6 are possible when coadministered with fosamprenavir plus ritonavir.

There are other agents that may result in serious and/or life-threatening drug interactions [see Contraindications (4)].

 Drugs that Should Not Be Coadministered with Fosamprenavir

See Contraindications (4).

 Established and Other Potentially Significant Drug Interactions

Table 7 provides a listing of established or potentially clinically significant drug interactions. Information in the table applies to fosamprenavir with or without ritonavir, unless otherwise indicated.

Table 7. Established and Other Potentially Significant Drug Interactions

* See Clinical Pharmacology (12.3)Tables 10, 11, 12, or 13 for magnitude of interaction.
Concomitant Drug Class: Drug Name	Effect on Concentration of Amprenavir or Concomitant Drug	Clinical Comment
HCV/HIV-Antiviral Agents
HCV protease inhibitor: Boceprevir	Fosamprenavir: ↓Amprenavir (predicted) ↔ or ↓Boceprevir (predicted)   Fosamprenavir/ ritonavir: ↓Amprenavir (predicted) ↓Boceprevir (predicted)	Coadministration of fosamprenavir or fosamprenavir/ritonavir and boceprevir is not recommended.
HCV protease inhibitor: Simeprevir	Fosamprenavir: ↔Amprenavir (predicted) ↑ or ↓Simeprevir (predicted) Fosamprenavir/ ritonavir: ↔Amprenavir (predicted) ↑Simeprevir (predicted)	Coadministration of fosamprenavir or fosamprenavir/ritonavir and simeprevir is not recommended.
HCV protease inhibitor: Paritaprevir (coformulated with ritonavir and ombitasvir and coadministered with dasabuvir)	Fosamprenavir: ↑Amprenavir (predicted) ↑ or ↔Paritaprevir (predicted) Fosamprenavir/ ritonavir: ↑ or ↔Amprenavir (predicted) ↑Paritaprevir (predicted)	Appropriate doses of the combinations with respect to safety and efficacy have not been established.   Fosamprenavir 1,400 mg once daily may be considered when coadministered with paritaprevir/ritonavir/ombitasvir/dasabuvir.   Coadministration of fosamprenavir/ritonavir and paritaprevir/ritonavir/ombitasvir/ dasabuvir is not recommended.
Non-nucleoside reverse transcriptase inhibitor: Efavirenz*	Fosamprenavir: ↓Amprenavir	Appropriate doses of the combinations with respect to safety and efficacy have not been established.
	Fosamprenavir/ ritonavir: ↓Amprenavir	An additional 100 mg/day (300 mg total) of ritonavir is recommended when efavirenz is administered with fosamprenavir/ritonavir once daily. No change in the ritonavir dose is required when efavirenz is administered with fosamprenavir plus ritonavir twice daily.
Non-nucleoside reverse transcriptase inhibitor: Nevirapine*	Fosamprenavir: ↓Amprenavir ↑Nevirapine	Coadministration of nevirapine and fosamprenavir without ritonavir is not recommended.
	Fosamprenavir/ ritonavir: ↓Amprenavir ↑Nevirapine	No dosage adjustment required when nevirapine is administered with fosamprenavir/ritonavir twice daily.   The combination of nevirapine administered with fosamprenavir/ritonavir once-daily regimen has not been studied.
HIV protease inhibitor: Atazanavir*	Fosamprenavir: Interaction has not been evaluated.   Fosamprenavir/ ritonavir: ↓Atazanavir ↔Amprenavir	Appropriate doses of the combinations with respect to safety and efficacy have not been established.
HIV protease inhibitors: Indinavir*, nelfinavir*	Fosamprenavir: ↑Amprenavir   Effect on indinavir and nelfinavir is not well established.   Fosamprenavir/ ritonavir: Interaction has not been evaluated.	Appropriate doses of the combinations with respect to safety and efficacy have not been established.
HIV protease inhibitors: Lopinavir/ritonavir*	↓Amprenavir ↓Lopinavir	An increased rate of adverse events has been observed. Appropriate doses of the combinations with respect to safety and efficacy have not been established.
HIV protease inhibitor: Saquinavir*	Fosamprenavir: ↓Amprenavir   Effect on saquinavir is not well established.   Fosamprenavir/ ritonavir: Interaction has not been evaluated.	Appropriate doses of the combination with respect to safety and efficacy have not been established.
HIV integrase inhibitor: Raltegravir*	Fosamprenavir: ↓Amprenavir ↓Raltegravir   Fosamprenavir/ ritonavir: ↓Amprenavir ↓Raltegravir	Appropriate doses of the combination with respect to safety and efficacy have not been established.
HIV integrase inhibitor: Dolutegravir*	Fosamprenavir/ ritonavir: ↓Dolutegravir	The recommended dose of dolutegravir is 50 mg twice daily when coadministered with fosamprenavir/ritonavir.   Use an alternative combination where possible in patients with known or suspected integrase inhibitor resistance.
HIV CCR5 co-receptor antagonist: Maraviroc*	Fosamprenavir/ ritonavir: ↓Amprenavir ↑Maraviroc	No dosage adjustment required for fosamprenavir/ritonavir. The recommended dose of maraviroc is 150 mg twice daily when coadministered with fosamprenavir/ritonavir. Fosamprenavir should be given with ritonavir when coadministered with maraviroc.
Other Agents
Antiarrhythmics: Amiodarone, lidocaine (systemic), and quinidine	↑Antiarrhythmics	Use with caution. Increased exposure may be associated with life-threatening reactions such as cardiac arrhythmias. Therapeutic concentration monitoring, if available, is recommended for antiarrhythmics.
Anticoagulant: Warfarin		Concentrations of warfarin may be affected. It is recommended that INR (international normalized ratio) be monitored.
Anticonvulsants: Carbamazepine, phenobarbital, phenytoin	Fosamprenavir: ↓Amprenavir	Use with caution. Fosamprenavir may be less effective due to decreased amprenavir plasma concentrations in patients taking these agents concomitantly.
Phenytoin*	Fosamprenavir/ ritonavir: ↑Amprenavir ↓Phenytoin	Plasma phenytoin concentrations should be monitored and phenytoin dose should be increased as appropriate. No change in fosamprenavir/ritonavir dose is recommended.
Antidepressant: Paroxetine, trazodone	↓Paroxetine	Any paroxetine dose adjustment should be guided by clinical effect (tolerability and efficacy).
	↑Trazodone	Adverse events of nausea, dizziness, hypotension, and syncope have been observed following coadministration of trazodone and ritonavir. If trazodone is used with a CYP3A4 inhibitor such as fosamprenavir, the combination should be used with caution and a lower dose of trazodone should be considered.
Antifungals: Ketoconazole*, itraconazole	↑Ketoconazole ↑Itraconazole	Increase monitoring for adverse events.   Fosamprenavir: Dose reduction of ketoconazole or itraconazole may be needed for patients receiving more than 400 mg ketoconazole or itraconazole per day.   Fosamprenavir/ritonavir: High doses of ketoconazole or itraconazole (greater than 200 mg/day) are not recommended.
Anti-gout: Colchicine	↑Colchicine	Patients with renal or hepatic impairment should not be given colchicine with fosamprenavir/ritonavir.   Fosamprenavir/ritonavir and coadministration of colchicine:   Treatment of gout flares: 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (half tablet) 1 hour later. Dose to be repeated no earlier than 3 days.   Prophylaxis of gout flares: If the original regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day. If the original regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day.   Treatment of familial Mediterranean fever (FMF): Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day).   Fosamprenavir and coadministration of colchicine:   Treatment of gout flares: 1.2 mg (2 tablets) x 1 dose. Dose to be repeated no earlier than 3 days.   Prophylaxis of gout flares: If the original regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg twice a day or 0.6 mg once a day.   If the original regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once a day.   Treatment of FMF: Maximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day).
Antimycobacterial: Rifabutin*	↑Rifabutin and rifabutin metabolite	A complete blood count should be performed weekly and as clinically indicated to monitor for neutropenia.   Fosamprenavir: A dosage reduction of rifabutin by at least half the recommended dose is required.   Fosamprenavir/ritonavir: Dosage reduction of rifabutin by at least 75% of the usual dose of 300 mg/day is recommended (a maximum dose of 150 mg every other day or 3 times per week).
Antipsychotics: Quetiapine	Fosamprenavir/ ritonavir: ↑Quetiapine	Initiation of fosamprenavir with ritonavir in patients taking quetiapine: Consider alternative antiretroviral therapy to avoid increases in quetiapine drug exposures. If coadministration is necessary, reduce the quetiapine dose to 1/6 of the current dose and monitor for quetiapine-associated adverse reactions. Refer to the quetiapine prescribing information for recommendations on adverse reaction monitoring.   Initiation of quetiapine in patients taking fosamprenavir with ritonavir: Refer to the quetiapine prescribing information for initial dosing and titration of quetiapine.
Lurasidone	↑Lurasidone	Fosamprenavir: If coadministration is necessary, reduce the lurasidone dose. Refer to the lurasidone prescribing information for concomitant use with moderate CYP3A4 inhibitors.   Fosamprenavir/ritonavir: Use of lurasidone is contraindicated.
Benzodiazepines: Alprazolam, clorazepate, diazepam, flurazepam	↑Benzodiazepines	Clinical significance is unknown. A decrease in benzodiazepine dose may be needed.
Calcium channel blockers: Diltiazem, felodipine, nifedipine, nicardipine, nimodipine, verapamil, amlodipine, nisoldipine, isradipine	↑Calcium channel blockers	Use with caution. Clinical monitoring of patients is recommended.
Corticosteroid: Dexamethasone	↓Amprenavir	Use with caution. Fosamprenavir may be less effective due to decreased amprenavir plasma concentrations.
Endothelin-receptor antagonists: Bosentan	↑Bosentan	Coadministration of bosentan in patients on fosamprenavir:In patients who have been receiving fosamprenavir for at least 10 days, start bosentan at 62.5 mg once daily or every other day based upon individual tolerability.   Coadministration of fosamprenavir in patients on bosentan:Discontinue use of bosentan at least 36 hours prior to initiation of fosamprenavir.   After at least 10 days following the initiation of fosamprenavir, resume bosentan at 62.5 mg once daily or every other day based upon individual tolerability.
Histamine H2-receptor antagonists: Cimetidine, famotidine, nizatidine, ranitidine*	Fosamprenavir: ↓Amprenavir   Fosamprenavir/ ritonavir: Interaction not evaluated	Use with caution. Fosamprenavir may be less effective due to decreased amprenavir plasma concentrations.
HMG-CoA reductase inhibitors: Atorvastatin*	↑Atorvastatin	Titrate atorvastatin dose carefully and use the lowest necessary dose; do not exceed atorvastatin 20 mg/day.
Immunosuppressants: Cyclosporine, tacrolimus, sirolimus	↑Immunosuppressants	Therapeutic concentration monitoring is recommended for immunosuppressant agents.
Inhaled beta-agonist: Salmeterol	↑Salmeterol	Concurrent administration of salmeterol with fosamprenavir is not recommended. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia.
Inhaled/nasal steroid: Fluticasone	Fosamprenavir: ↑Fluticasone Fosamprenavir/ ritonavir: ↑Fluticasone	Use with caution. Consider alternatives to fluticasone, particularly for long-term use.   May result in significantly reduced serum cortisol concentrations. Systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression have been reported during postmarketing use in patients receiving ritonavir and inhaled or intranasally administered fluticasone. Coadministration of fluticasone and fosamprenavir/ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.
Narcotic analgesic: Methadone	↓Methadone	Data suggest that the interaction is not clinically relevant; however, patients should be monitored for opiate withdrawal symptoms.
Oral contraceptives: Ethinyl estradiol/norethindrone*		Alternative methods of non-hormonal contraception are recommended.
	Fosamprenavir: ↓Amprenavir ↓Ethinyl estradiol	May lead to loss of virologic response.*
	Fosamprenavir/ ritonavir: ↓Ethinyl estradiol	Increased risk of transaminase elevations. No data are available on the use of fosamprenavir/ritonavir with other hormonal therapies, such as hormone replacement therapy (HRT) for postmenopausal women.
PDE5 inhibitors: Sildenafil, tadalafil, vardenafil	↑Sildenafil ↑Tadalafil ↑Vardenafil	May result in an increase in PDE5 inhibitor-associated adverse events, including hypotension, syncope, visual disturbances, and priapism.   Use of PDE5 inhibitors for pulmonary arterial hypertension (PAH): • Use of sildenafil (REVATIO) is contraindicated when used for the treatment of PAH [see Contraindications (4)]. • The following dose adjustments are recommended for use of tadalafil (ADCIRCA®) with fosamprenavir:   Coadministration of ADCIRCA in patients on fosamprenavir: In patients receiving fosamprenavir for at least 1 week, start ADCIRCA at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability.   Coadministration of fosamprenavir in patients on ADCIRCA: Avoid use of ADCIRCA during the initiation of fosamprenavir. Stop ADCIRCA at least 24 hours prior to starting fosamprenavir. After at least 1 week following the initiation of fosamprenavir, resume ADCIRCA at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability.   Use of PDE5 inhibitors for erectile dysfunction: Fosamprenavir: • Sildenafil: 25 mg every 48 hours. • Tadalafil: no more than 10 mg every 72 hours. • Vardenafil: no more than 2.5 mg every 24 hours.   Fosamprenavir/ritonavir: • Sildenafil: 25 mg every 48 hours. • Tadalafil: no more than 10 mg every 72 hours. • Vardenafil: no more than 2.5 mg every 72 hours.   Use with increased monitoring for adverse events.
Proton pump inhibitors: Esomeprazole* , lansoprazole, omeprazole, pantoprazole, rabeprazole	Fosamprenavir: ↔Amprenavir ↑Esomeprazole   Fosamprenavir/ ritonavir: ↔Amprenavir ↔Esomeprazole	Proton pump inhibitors can be administered at the same time as a dose of fosamprenavir with no change in plasma amprenavir concentrations.
Tricyclic antidepressants: Amitriptyline, imipramine	↑Tricyclics	Therapeutic concentration monitoring is recommended for tricyclic antidepressants.

 Therapy-Naive Adult Trials

APV30001

A randomized, open-label trial evaluated treatment with fosamprenavir calcium tablets (1,400 mg twice daily) versus nelfinavir (1,250 mg twice daily) in 249 antiretroviral treatment-naive subjects. Both groups of subjects also received abacavir (300 mg twice daily) and lamivudine (150 mg twice daily).

The mean age of the subjects in this trial was 37 years (range: 17 to 70 years); 69% of the subjects were male, 20% were CDC Class C (AIDS), 24% were white, 32% were black, and 44% were Hispanic. At baseline, the median CD4+ cell count was 212 cells per mm3 (range: 2 to 1,136 cells per mm3; 18% of subjects had a CD4+ cell count of less than 50 cells per mm3 and 30% were in the range of 50 to less than 200 cells per mm3). Baseline median HIV-1 RNA was 4.83 log10 copies per mL (range: 1.69 to 7.41 log10 copies per mL; 45% of subjects had greater than 100,000 copies per mL).

The outcomes of randomized treatment are provided in Table 15.

Table 15. Outcomes of Randomized Treatment through Week 48 (APV30001)

* Subjects achieved and maintained confirmed HIV-1 RNA less than 400 copies per mL (less than 50 copies per mL) through Week 48 (Roche AMPLICOR HIV-1 MONITOR Assay Version 1.5). † Includes consent withdrawn, lost to follow up, protocol violations, those with missing data, and other reasons.
Outcome (Rebound or discontinuation = failure)	Fosamprenavir 1,400 mg b.i.d. (n = 166)	Nelfinavir 1,250 mg b.i.d. (n = 83)
Responder*	66% (57%)	52% (42%)
Virologic failure	19%	32%
Rebound	16%	19%
Never suppressed through Week 48	3%	13%
Clinical progression	1%	1%
Death	0%	1%
Discontinued due to adverse reactions	4%	2%
Discontinued due to other reasons†	10%	10%

Treatment response by viral load strata is shown in Table 16.

Table 16. Proportions of Responders through Week 48 by Screening Viral Load (APV30001)

Screening Viral Load HIV-1 RNA (copies/mL)	Fosamprenavir 1,400 mg b.i.d.		Nelfinavir 1,250 mg b.i.d.
	< 400 copies/mL	n	< 400 copies/mL	n
≤ 100,000	65%	93	65%	46
> 100,000	67%	73	36%	37

Through 48 weeks of therapy, the median increases from baseline in CD4+ cell counts were 201 cells per mm3 in the group receiving fosamprenavir and 216 cells per mm3 in the nelfinavir group.

APV30002

A randomized, open-label trial evaluated treatment with fosamprenavir calcium tablets (1,400 mg once daily) plus ritonavir (200 mg once daily) versus nelfinavir (1,250 mg twice daily) in 649 treatment-naive subjects. Both treatment groups also received abacavir (300 mg twice daily) and lamivudine (150 mg twice daily).

The mean age of the subjects in this trial was 37 years (range: 18 to 69 years); 73% of the subjects were male, 22% were CDC Class C, 53% were white, 36% were black, and 8% were Hispanic. At baseline, the median CD4+ cell count was 170 cells per mm3 (range: 1 to 1,055 cells per mm3; 20% of subjects had a CD4+ cell count of less than 50 cells per mm3 and 35% were in the range of 50 to less than 200 cells per mm3). Baseline median HIV-1 RNA was 4.81 log10 copies per mL (range: 2.65 to 7.29 log10 copies per mL; 43% of subjects had greater than 100,000 copies per mL).

The outcomes of randomized treatment are provided in Table 17.

Table 17. Outcomes of Randomized Treatment through Week 48 (APV30002)

* Subjects achieved and maintained confirmed HIV-1 RNA less than 400 copies per mL (less than 50 copies per mL) through Week 48 (Roche AMPLICOR HIV-1 MONITOR Assay Version 1.5). † Includes consent withdrawn, lost to follow up, protocol violations, those with missing data, and other reasons.
Outcome (Rebound or discontinuation = failure)	Fosamprenavir 1,400 mg q.d./ Ritonavir 200 mg q.d. (n = 322)	Nelfinavir 1,250 mg b.i.d. (n = 327)
Responder*	69% (58%)	68% (55%)
Virologic failure	6%	16%
Rebound	5%	8%
Never suppressed through Week 48	1%	8%
Death	1%	0%
Discontinued due to adverse reactions	9%	6%
Discontinued due to other reasons†	15%	10%

Treatment response by viral load strata is shown in Table 18.

Table 18. Proportions of Responders through Week 48 by Screening Viral Load (APV30002)

Screening Viral Load HIV-1 RNA (copies/mL)	Fosamprenavir 1,400 mg q.d./ Ritonavir 200 mg q.d.		Nelfinavir 1,250 mg b.i.d.
	< 400 copies/mL	n	< 400 copies/mL	n
≤ 100,000	72%	197	73%	194
> 100,000	66%	125	64%	133

Through 48 weeks of therapy, the median increases from baseline in CD4+ cell counts were 203 cells per mm3 in the group receiving fosamprenavir and 207 cells per mm3 in the nelfinavir group.

 Protease Inhibitor-Experienced Adult Trials

APV30003

A randomized, open-label, multicenter trial evaluated 2 different regimens of fosamprenavir plus ritonavir (fosamprenavir calcium tablets 700 mg twice daily plus ritonavir 100 mg twice daily or fosamprenavir calcium tablets 1,400 mg once daily plus ritonavir 200 mg once daily) versus lopinavir/ritonavir (400 mg/100 mg twice daily) in 315 subjects who had experienced virologic failure to 1 or 2 prior protease inhibitor-containing regimens.

The mean age of the subjects in this trial was 42 years (range: 24 to 72 years); 85% were male, 33% were CDC Class C, 67% were white, 24% were black, and 9% were Hispanic. The median CD4+ cell count at baseline was 263 cells per mm3 (range: 2 to 1,171 cells per mm3). Baseline median plasma HIV-1 RNA level was 4.14 log10 copies per mL (range: 1.69 to 6.41 log10 copies per mL).

The median durations of prior exposure to NRTIs were 257 weeks for subjects receiving fosamprenavir/ritonavir twice daily (79% had greater than or equal to 3 prior NRTIs) and 210 weeks for subjects receiving lopinavir/ritonavir (64% had greater than or equal to 3 prior NRTIs). The median durations of prior exposure to protease inhibitors were 149 weeks for subjects receiving fosamprenavir/ritonavir twice daily (49% received greater than or equal to 2 prior protease inhibitors) and 130 weeks for subjects receiving lopinavir/ritonavir (40% received greater than or equal to 2 prior protease inhibitors).

The time-averaged changes in plasma HIV-1 RNA from baseline (AAUCMB) at 48 weeks (the endpoint on which the trial was powered) were -1.4 log10 copies per mL for twice-daily fosamprenavir/ritonavir and -1.67 log10 copies per mL for the lopinavir/ritonavir group.

The proportions of subjects who achieved and maintained confirmed HIV-1 RNA less than 400 copies per mL (secondary efficacy endpoint) were 58% with twice-daily fosamprenavir/ritonavir and 61% with lopinavir/ritonavir (95% CI for the difference: -16.6, 10.1). The proportions of subjects with HIV-1 RNA less than 50 copies per mL with twice-daily fosamprenavir/ritonavir and with lopinavir/ritonavir were 46% and 50%, respectively (95% CI for the difference: -18.3, 8.9). The proportions of subjects who were virologic failures were 29% with twice-daily fosamprenavir/ritonavir and 27% with lopinavir/ritonavir.

The frequency of discontinuations due to adverse events and other reasons, and deaths were similar between treatment arms.

Through 48 weeks of therapy, the median increases from baseline in CD4+ cell counts were 81 cells per mm3 with twice-daily fosamprenavir/ritonavir and 91 cells per mm3 with lopinavir/ritonavir.

This trial was not large enough to reach a definitive conclusion that fosamprenavir/ritonavir and lopinavir/ritonavir are clinically equivalent.

Once-daily administration of fosamprenavir plus ritonavir is not recommended for protease inhibitor-experienced patients. Through Week 48, 50% and 37% of subjects receiving fosamprenavir 1,400 mg plus ritonavir 200 mg once daily had plasma HIV-1 RNA less than 400 copies per mL and less than 50 copies per mL, respectively.

 Pediatric Trials

Three open-label trials in pediatric subjects aged at least 4 weeks to 18 years were conducted. In 1 trial (APV29005), twice-daily dosing regimens (fosamprenavir with or without ritonavir) were evaluated in combination with other antiretroviral agents in pediatric subjects aged 2 to 18 years. In a second trial (APV20002), twice-daily dosing regimens (fosamprenavir with ritonavir) were evaluated in combination with other antiretroviral agents in pediatric subjects aged at least 4 weeks to younger than 2 years. A third trial (APV20003) evaluated once-daily dosing of fosamprenavir with ritonavir; the pharmacokinetic data from this trial did not support a once-daily dosing regimen in any pediatric patient population.

APV29005

Fosamprenavir

Twenty (18 therapy-naive and 2 therapy-experienced) pediatric subjects received fosamprenavir calcium oral suspension without ritonavir twice daily. At Week 24, 65% (13 of 20) achieved HIV-1 RNA less than 400 copies per mL, and the median increase from baseline in CD4+ cell count was 350 cells per mm3.

Fosamprenavir Plus Ritonavir

Forty-nine protease inhibitor-naive and 40 protease inhibitor-experienced pediatric subjects received fosamprenavir calcium oral suspension or tablets with ritonavir twice daily. At Week 24, 71% of protease inhibitor-naive (35 of 49) and 55% of protease inhibitor-experienced (22 of 40) subjects achieved HIV-1 RNA less than 400 copies per mL; median increases from baseline in CD4+ cell counts were 184 cells per mm3 and 150 cells per mm3 in protease inhibitor-naive and experienced subjects, respectively.

APV20002

Fifty-four pediatric subjects (49 protease inhibitor-naive and 5 protease inhibitor-experienced) received fosamprenavir calcium oral suspension with ritonavir twice daily. At Week 24, 72% of subjects achieved HIV-1 RNA less than 400 copies per mL. The median increases from baseline in CD4+ cell counts were 400 cells per mm3 in subjects aged at least 4 weeks to younger than 6 months and 278 cells per mm3 in subjects aged 6 months to 2 years.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Drug Interactions: A statement to patients and healthcare providers is included on the product’s bottle label: ALERT: Find out about medicines that should NOT be taken with Fosamprenavir Calcium Tablets.

Fosamprenavir calcium tablets may interact with many drugs; therefore, advise patients to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products, particularly St. John’s wort.

Advise patients receiving PDE5 inhibitors that they may be at an increased risk of PDE5 inhibitor-associated adverse events, including hypotension, visual changes, and priapism, and should promptly report any symptoms to their healthcare provider.

Instruct patients receiving hormonal contraceptives to use alternate contraceptive measures during therapy with fosamprenavir calcium tablets because hormonal levels may be altered, and if used in combination with fosamprenavir calcium tablets and ritonavir, liver enzyme elevations may occur.

Sulfa Allergy: Advise patients to inform their healthcare provider if they have a sulfa allergy. The potential for cross-sensitivity between drugs in the sulfonamide class and fosamprenavir is unknown.

Redistribution/Accumulation of Body Fat: Inform patients that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy, including fosamprenavir calcium tablets, and that the cause and long-term health effects of these conditions are not known at this time.

Information about HIV-1 Infection: Fosamprenavir calcium tablets are not a cure for HIV-1 infection and patients may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. Patients must remain on continuous HIV therapy to control HIV-1 infection and decrease HIV-1-related illness. Patients should be told that sustained decreases in plasma HIV-1 RNA have been associated with a reduced risk of progression to AIDS and death.

Advise patients to remain under the care of a physician when using fosamprenavir calcium tablets.

Advise patients to take all HIV medications exactly as prescribed.

Advise patients to avoid doing things that can spread HIV-1 infection to others.

Advise patients not to re-use or share needles or other injection equipment.

Advise patients not to share personal items that can have blood or body fluids on them, like toothbrushes and razor blades.

Always practice safer sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.

Female patients should be advised not to breastfeed because it is not known if fosamprenavir can be passed to your baby in your breast milk and whether it could harm your baby. Mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in the breast milk.

Fosamprenavir calcium tablets must always be used in combination with other antiretroviral drugs. Inform patients not to alter the dose or discontinue therapy without consulting their physician. Physicians should instruct their patients that if they miss a dose, they should take it as soon as possible and then return to their normal schedule. Patients should not double their next dose or take more than the prescribed dose.

Fosamprenavir Calcium Tablets
(fos″ am pren′ a vir kal′ see um)

Important: Fosamprenavir calcium tablets can interact with other medicines and cause serious side effects. It is important to know the medicines that should not be taken with fosamprenavir calcium tablets. See the section “Who should not take fosamprenavir calcium tablets?”

Read this Patient Information before you start taking fosamprenavir calcium tablets and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment.

What are fosamprenavir calcium tablets?

Fosamprenavir calcium tablets are a prescription anti-HIV medicine used with other anti-HIV medicines to treat human immunodeficiency (HIV-1) infections in adults and children 4 weeks of age and older. Fosamprenavir calcium tablets are a type of anti-HIV medicine called a protease inhibitor. HIV-1 is the virus that causes AIDS (Acquired Immune Deficiency Syndrome).

When used with other anti-HIV medicines, fosamprenavir calcium tablets may help:

1. Reduce the amount of HIV-1 in your blood. This is called “viral load”. 2. Increase the number of white blood cells called CD4 (T) cells, which help fight off other infections. Reducing the amount of HIV-1 and increasing the CD4 (T) cell count may improve your immune system. This may reduce your risk of death or infections that can happen when your immune system is weak (opportunistic infections).

It is not known if fosamprenavir is safe and effective in children younger than 4 weeks of age.

Fosamprenavir calcium tablets do not cure HIV-1 infection or AIDS. People taking fosamprenavir calcium tablets may develop infections or other conditions associated with HIV-1 infection, including opportunistic infections (for example, pneumonia and herpes virus infections).

You should remain under the care of your healthcare provider when using fosamprenavir calcium tablets.

Avoid doing things that can spread HIV-1 infection to others.

• Do not re-use or share needles or other injection equipment. • Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades. • Do not have any kind of sex without protection. Always practice safer sex by using a latex or polyurethane condom to lower the chance of sexual contact with any body fluids such as semen, vaginal secretions, or blood.

Ask your healthcare provider if you have any questions on how to prevent passing HIV to other people.

Who should not take fosamprenavir calcium tablets?

Do not take fosamprenavir calcium tablets if you take any of the following medicines:

• alfuzosin (UROXATRAL®) • flecainide • propafenone (RYTHMOL SR®) • rifampin (RIFADIN®, RIFAMATE®, RIFATER®, RIMACTANE®) • ergot including: • dihydroergotamine mesylate (D.H.E. 45®, MIGRANAL®) • ergotamine tartrate (CAFERGOT®, MIGERGOT®, ERGOMAR®, MEDIHALER ERGOTAMINE®) • methylergonovine (METHERGINE®) • St. John’s wort (Hypericum perforatum) • lovastatin (ADVICOR®, ALTOPREV®) • simvastatin (ZOCOR®, VYTORIN®, SIMCOR®) • pimozide (ORAP®) • delavirdine mesylate (RESCRIPTOR®) • sildenafil (REVATIO®), for treatment of pulmonary arterial hypertension • triazolam (HALCION®) • lurasidone (LATUDA®)

Serious problems can happen if you or your child take any of the medicines listed above with fosamprenavir calcium tablets.

Do not take fosamprenavir calcium tablets if you are allergic to AGENERASE® (amprenavir), fosamprenavir calcium, or any of the ingredients in fosamprenavir calcium tablets. See the end of this leaflet for a complete list of ingredients in fosamprenavir calcium tablets.

What should I tell my healthcare provider before taking fosamprenavir calcium tablets?

Before taking fosamprenavir calcium tablets, tell your healthcare provider if you:

• are allergic to medicines that contain sulfa • have liver problems, including hepatitis B or C • have kidney problems • have high blood sugar (diabetes) • have hemophilia • have any other medical condition • are pregnant or plan to become pregnant. It is not known if fosamprenavir will harm your unborn baby.   Pregnancy Registry. There is a pregnancy registry for women who take antiviral medicines during pregnancy. The purpose of the registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry. • Do not breastfeed. We do not know if fosamprenavir can be passed to your baby in your breast milk and whether it could harm your baby. Also, mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in the breast milk.

Tell your healthcare provider about all prescription and over-the-counter medicines you take. Also tell your healthcare provider about any vitamins, herbal supplements, and dietary supplements you are taking.

Taking fosamprenavir calcium tablets with certain other medicines may cause serious side effects. Fosamprenavir calcium tablets may affect the way other medicines work, and other medicines may affect how fosamprenavir calcium tablets work.

Especially tell your healthcare provider if you take:

• quetiapine (SEROQUEL®) • estrogen-based contraceptives (birth control pills). Fosamprenavir calcium tablets may reduce effectiveness of estrogen-based contraceptives. During treatment with fosamprenavir calcium tablets, you should use a different contraceptive method. • medicines to treat liver problems, including hepatitis C infection.

Know all the medicines that you take. Keep a list of them with you to show healthcare providers and pharmacists when you get a new medicine.

How should I take fosamprenavir calcium tablets?

• Stay under the care of a healthcare provider while taking fosamprenavir calcium tablets. • Take fosamprenavir calcium tablets exactly as prescribed by your healthcare provider. • Do not change your dose or stop taking fosamprenavir calcium tablets without talking with your healthcare provider. • If your child is taking fosamprenavir, your child’s healthcare provider will decide the right dose based on your child’s weight. • You can take fosamprenavir calcium tablets with or without food. • If you miss a dose of fosamprenavir calcium tablets, take the next dose as soon as possible and then take your next dose at the regular time. Do not double the next dose. If you take too many fosamprenavir calcium tablets, call your healthcare provider or go to the nearest hospital emergency room right away.

What are the possible side effects of fosamprenavir calcium tablets?

Fosamprenavir calcium tablets may cause serious side effects including:

• Severe skin rash. Fosamprenavir calcium tablets may cause severe or life-threatening skin reactions or rash.
 
If you get a rash with any of the following symptoms, stop taking fosamprenavir calcium tablets and call your healthcare provider or get medical help right away: • hives or sores in your mouth, or your skin blisters and peels • trouble swallowing or breathing • swelling of your face, eyes, lips, tongue, or throat • Liver problems. Your healthcare provider should do blood tests before and during your treatment with fosamprenavir calcium tablets to check your liver function. Some people with liver problems, including hepatitis B or C, may have an increased risk of developing worsening liver problem during treatment with fosamprenavir calcium tablets. • Diabetes and high blood sugar (hyperglycemia). Some people who take protease inhibitors, including fosamprenavir calcium tablets, can get high blood sugar, develop diabetes, or your diabetes can get worse. Tell your healthcare provider if you notice an increase in thirst or urinate often while taking fosamprenavir calcium tablets. • Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Call your healthcare provider right away if you start having new symptoms after starting your HIV medicine. • Changes in body fat. These changes can happen in people who take antiretroviral therapy. The changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the back, chest, and stomach area. Loss of fat from the legs, arms, and face may also happen. The exact cause and long-term health effects of these conditions are not known. • Changes in blood tests. Some people have changes in blood tests while taking fosamprenavir calcium tablets. These include increases seen in liver function tests, blood fat levels, and decreases in white blood cells. Your healthcare provider should do regular blood tests before and during your treatment with fosamprenavir calcium tablets. • Increased bleeding problems in some people with hemophilia. Some people with hemophilia have increased bleeding with protease inhibitors, including fosamprenavir calcium tablets. • Kidney stones. Some people have developed kidney stones while taking fosamprenavir calcium tablets. Tell your healthcare provider right away if you develop signs or symptoms of kidney stones: • pain in your side • blood in your urine • pain when you urinate

The most common side effects of fosamprenavir calcium tablets in adults include:

• nausea • vomiting • diarrhea • headache

Vomiting is the most common side effect in children when taking fosamprenavir calcium tablets.

Tell your healthcare provider about any side effect that bothers you or that does not go away.

These are not all the possible side effects of fosamprenavir calcium tablets. For more information, ask your healthcare provider or pharmacist.

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

How should I store fosamprenavir calcium tablets?

• Store fosamprenavir calcium tablets at room temperature between 20° to 25°C (68° to 77°F). • Keep the bottle of fosamprenavir calcium tablets tightly closed.

Keep fosamprenavir calcium tablets and all medicines out of the reach of children.

General information about fosamprenavir calcium tablets

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use fosamprenavir calcium tablets for a condition for which they were not prescribed. Do not give fosamprenavir calcium tablets to other people, even if they have the same symptoms you have. They may harm them.

This leaflet summarizes the most important information about fosamprenavir calcium tablets. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about fosamprenavir calcium tablets that is written for health professionals.

For more information, call Mylan Pharmaceuticals Inc. at 1-877-446-3679 (1-877-4-INFO-RX).

What are the ingredients in fosamprenavir calcium tablets?

Active ingredient: fosamprenavir calcium

Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, povidone, red iron oxide, silicified microcrystalline cellulose, titanium dioxide and triacetin.

This Patient Information has been approved by the U.S. Food and Drug Administration.

The brand names listed are trademarks of their respective owners.

Manufactured for:
Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.

Manufactured by:
Mylan Laboratories Limited
Hyderabad 500 034, India
Code No.: MH/DRUGS/25/NKD/89

75056335

Revised: 1/2017
MX:FOSM:R5