Dosage Form: tablet, film coated: oral suspension
FULL PRESCRIBING INFORMATION
Indications and Usage for Lexiva
Lexiva® is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection.
The following points should be considered when initiating therapy with Lexiva plus ritonavir in protease inhibitor-experienced patients:
- The protease inhibitor-experienced patient study was not large enough to reach a definitive conclusion that Lexiva plus ritonavir and lopinavir plus ritonavir are clinically equivalent [see Clinical Studies (14.2)].
- Once-daily administration of Lexiva plus ritonavir is not recommended for adult protease inhibitor-experienced patients or any pediatric patients.
Lexiva Dosage and Administration
Lexiva Tablets may be taken with or without food.
Adults should take Lexiva Oral Suspension without food. Pediatric patients should take Lexiva Oral Suspension with food [see Clinical Pharmacology (12.3)]. If emesis occurs within 30 minutes after dosing, re-dosing of Lexiva Oral Suspension should occur.
Higher-than-approved dose combinations of Lexiva plus ritonavir are not recommended due to an increased risk of transaminase elevations [see Overdosage (10)].
When Lexiva is used in combination with ritonavir, prescribers should consult the full prescribing information for ritonavir.
Adults
Therapy-Naive Adults
- Lexiva 1,400 mg twice daily (without ritonavir).
- Lexiva 1,400 mg once daily plus ritonavir 200 mg once daily.
- Lexiva 1,400 mg once daily plus ritonavir 100 mg once daily.
Dosing of Lexiva 1,400 mg once daily plus ritonavir 100 mg once daily is supported by pharmacokinetic data [see Clinical Pharmacology (12.3)].
- Lexiva 700 mg twice daily plus ritonavir 100 mg twice daily.
- Dosing of Lexiva 700 mg twice daily plus 100 mg ritonavir twice daily is supported by pharmacokinetic and safety data [see Clinical Pharmacology (12.3)].
Protease Inhibitor-Experienced Adults
- Lexiva 700 mg twice daily plus ritonavir 100 mg twice daily
Pediatric Patients (Aged 2 to 18 Years)
The recommended dosage of Lexiva in patients aged greater than or equal to 2 years should be calculated based on body weight (kg) and should not exceed the recommended adult dose. The data are insufficient to recommend: (1) once-daily dosing of Lexiva alone or in combination with ritonavir, and (2) any dosing of Lexiva in therapy-experienced patients aged 2 to 5 years.
Therapy-Naive Aged 2 to 5 Years
- Lexiva Oral Suspension 30 mg/kg twice daily, not to exceed the adult dose of Lexiva 1,400 mg twice daily.
Therapy-Naive Aged Greater Than or Equal to 6 Years
- Either Lexiva Oral Suspension 30 mg/kg twice daily not to exceed the adult dose of Lexiva 1,400 mg twice daily or Lexiva Oral Suspension 18 mg/kg plus ritonavir 3 mg/kg twice daily not to exceed the adult dose of Lexiva 700 mg plus ritonavir 100 mg twice daily.
Therapy-Experienced Aged Greater Than or Equal to 6 Years
- Lexiva Oral Suspension 18 mg/kg plus ritonavir 3 mg/kg administered twice daily not to exceed the adult dose of Lexiva 700 mg twice daily plus ritonavir 100 mg twice daily.
Other Dosing Considerations
- When administered without ritonavir, the adult regimen of Lexiva Tablets 1,400 mg twice daily may be used for pediatric patients weighing at least 47 kg.
- When administered in combination with ritonavir, Lexiva Tablets may be used for pediatric patients weighing at least 39 kg; ritonavir capsules may be used for pediatric patients weighing at least 33 kg.
Patients With Hepatic Impairment
See Clinical Pharmacology (12.3).Mild Hepatic Impairment (Child-Pugh Score Ranging From 5 to 6): Lexiva should be used with caution at a reduced dosage of 700 mg twice daily without ritonavir (therapy-naive) or 700 mg twice daily plus ritonavir 100 mg once daily (therapy-naive or protease inhibitor-experienced).
Moderate Hepatic Impairment (Child-Pugh Score Ranging From 7 to 9): Lexiva should be used with caution at a reduced dosage of 700 mg twice daily without ritonavir (therapy-naive), or 450 mg twice daily plus ritonavir 100 mg once daily (therapy-naive or protease inhibitor-experienced).
Severe Hepatic Impairment (Child-Pugh Score Ranging From 10 to 15): Lexiva should be used with caution at a reduced dosage of 350 mg twice daily without ritonavir (therapy-naive) or 300 mg twice daily plus ritonavir 100 mg once daily (therapy-naive or protease inhibitor-experienced).
Dosage Forms and Strengths
Lexiva Tablets, 700 mg, are pink, film-coated, capsule-shaped, biconvex tablets with “GX LL7” debossed on one face.
Lexiva Oral Suspension, 50 mg/mL, is a white to off-white suspension that has a characteristic grape-bubblegum-peppermint flavor.
Contraindications
Lexiva is contraindicated:
- in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome) to any of the components of this product or to amprenavir.
- when coadministered with drugs that are highly dependent on CYP3A4 for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (Table 1).
| Drug Class/Drug Name | Clinical Comment |
Alpha 1-adrenoreceptor antagonist: Alfuzosin | Potentially increased alfuzosin concentrations can result in hypotension. |
Antiarrhythmics: Flecainide, propafenone | POTENTIAL for serious and/or life-threatening reactions such as cardiac arrhythmias secondary to increases in plasma concentrations of antiarrhythmics if Lexiva is co-prescribed with ritonavir. |
Antimycobacterials: Rifampina | May lead to loss of virologic response and possible resistance to Lexiva or to the class of protease inhibitors. |
Ergot derivatives: Dihydroergotamine, ergonovine, ergotamine, methylergonovine | POTENTIAL for serious and/or life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. |
GI motility agents: Cisapride | POTENTIAL for serious and/or life-threatening reactions such as cardiac arrhythmias. |
Herbal products: St. John’s wort (hypericum perforatum) | May lead to loss of virologic response and possible resistance to Lexiva or to the class of protease inhibitors. |
HMG co-reductase inhibitors: Lovastatin, simvastatin | POTENTIAL for serious reactions such as risk of myopathy including rhabdomyolysis. |
Neuroleptic: Pimozide | POTENTIAL for serious and/or life-threatening reactions such as cardiac arrhythmias. |
Non-nucleoside reverse transcriptase inhibitor: Delavirdinea | May lead to loss of virologic response and possible resistance to delavirdine. |
PDE5 inhibitor: Sildenafil (REVATIO®) (for treatment of pulmonary arterial hypertension) | A safe and effective dose has not been established when used with Lexiva. There is increased potential for sildenafil-associated adverse events (which include visual disturbances, hypotension, prolonged erection, and syncope). |
Sedative/hypnotics: Midazolam, triazolam | POTENTIAL for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression. |
a See Clinical Pharmacology (12.3) Tables 10, 11, 12, or 13 for magnitude of interaction.
- when coadministered with ritonavir in patients receiving the antiarrhythmic agents flecainide and propafenone. If Lexiva is coadministered with ritonavir, reference should be made to the full prescribing information for ritonavir for additional contraindications.
Warnings and Precautions
Drug Interactions
See Table 1 for listings of drugs that are contraindicated due to potentially life-threatening adverse events, significant drug interactions, or due to loss of virologic activity [see Contraindications (4), Drug Interactions (7.2)]. See Table 6 for a listing of established and other potentially significant drug interactions [see Drug Interactions (7.3)].
Skin Reactions
Severe and life-threatening skin reactions, including 1 case of Stevens-Johnson syndrome among 700 patients treated with Lexiva in clinical studies. Treatment with Lexiva should be discontinued for severe or life-threatening rashes and for moderate rashes accompanied by systemic symptoms [see Adverse Reactions (6)].
Sulfa Allergy
Lexiva should be used with caution in patients with a known sulfonamide allergy. Fosamprenavir contains a sulfonamide moiety. The potential for cross-sensitivity between drugs in the sulfonamide class and fosamprenavir is unknown. In a clinical study of Lexiva used as the sole protease inhibitor, rash occurred in 2 of 10 patients (20%) with a history of sulfonamide allergy compared with 42 of 126 patients (33%) with no history of sulfonamide allergy. In 2 clinical studies of Lexiva plus low-dose ritonavir, rash occurred in 8 of 50 patients (16%) with a history of sulfonamide allergy compared with 50 of 412 patients (12%) with no history of sulfonamide allergy.
Hepatic Toxicity
Use of Lexiva with ritonavir at higher-than-recommended dosages may result in transaminase elevations and should not be used [see Dosage and Administration (2), Overdosage (10)]. Patients with underlying hepatitis B or C or marked elevations in transaminases prior to treatment may be at increased risk for developing or worsening of transaminase elevations. Appropriate laboratory testing should be conducted prior to initiating therapy with Lexiva and patients should be monitored closely during treatment.
Diabetes/Hyperglycemia
New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, and hyperglycemia have been reported during postmarketing surveillance in HIV-infected patients receiving protease inhibitor therapy. Some patients required either initiation or dose adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, diabetic ketoacidosis has occurred. In those patients who discontinued protease inhibitor therapy, hyperglycemia persisted in some cases. Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made and causal relationships between protease inhibitor therapy and these events have not been established.
Immune Reconstitution Syndrome
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Lexiva. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
Fat Redistribution
Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance,” have been observed in patients receiving antiretroviral therapy, including Lexiva. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.
Lipid Elevations
Treatment with Lexiva plus ritonavir has resulted in increases in the concentration of triglycerides and cholesterol [see Adverse Reactions (6)]. Triglyceride and cholesterol testing should be performed prior to initiating therapy with Lexiva and at periodic intervals during therapy. Lipid disorders should be managed as clinically appropriate [see Drug Interactions (7)].
Hemolytic Anemia
Acute hemolytic anemia has been reported in a patient treated with amprenavir.
Patients With Hemophilia
There have been reports of spontaneous bleeding in patients with hemophilia A and B treated with protease inhibitors. In some patients, additional factor VIII was required. In many of the reported cases, treatment with protease inhibitors was continued or restarted. A causal relationship between protease inhibitor therapy and these episodes has not been established.
Nephrolithiasis
Cases of nephrolithiasis were reported during postmarketing surveillance in HIV-infected patients receiving Lexiva.Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made. If signs or symptoms of nephrolithiasis occur, temporary interruption or discontinuation of therapy may be considered.
Resistance/Cross-Resistance
Because the potential for HIV cross-resistance among protease inhibitors has not been fully explored, it is unknown what effect therapy with Lexiva will have on the activity of subsequently administered protease inhibitors. Lexiva has been studied in patients who have experienced treatment failure with protease inhibitors [see Clinical Studies (14.2)].
Adverse Reactions
- Severe or life-threatening skin reactions have been reported with the use of Lexiva [see Warnings and Precautions (5.2)].
- The most common moderate to severe adverse reactions in clinical studies of Lexiva were diarrhea, rash, nausea, vomiting, and headache.
- Treatment discontinuation due to adverse events occurred in 6.4% of patients receiving Lexiva and in 5.9% of patients receiving comparator treatments. The most common adverse reactions leading to discontinuation of Lexiva (incidence less than or equal to 1% of patients) included diarrhea, nausea, vomiting, AST increased, ALT increased, and rash.
Clinical Trials
Adults
The data for the 3 active-controlled clinical trials described below reflect exposure of 700 HIV-1 infected patients to Lexiva Tablets, including 599 patients exposed to Lexiva for greater than 24 weeks, and 409 patients exposed for greater than 48 weeks. The population age ranged from 17 to 72 years. Of these patients, 26% were female, 51% Caucasian, 31% black, 16% American Hispanic, and 70% were antiretroviral-naive. Sixty-one percent received Lexiva 1,400 mg once daily plus ritonavir 200 mg once daily, 24% received Lexiva 1,400 mg twice daily, and 15% received Lexiva 700 mg twice daily plus ritonavir 100 mg twice daily.
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 clinical practice.
Selected adverse reactions reported during the clinical efficacy studies of Lexiva are shown in Tables 2 and 3. Each table presents adverse reactions of moderate or severe intensity in patients treated with combination therapy for up to 48 weeks.
| Adverse Reaction | APV30001a | APV30002a | ||
Lexiva 1,400 mg b.i.d. (n = 166) | Nelfinavir 1,250 mg b.i.d. (n = 83) | Lexiva 1,400 mg q.d./ Ritonavir 200 mg q.d. (n = 322) | Nelfinavir 1,250 mg b.i.d. (n = 327) | |
| Gastrointestinal | ||||
| Diarrhea | 5% | 18% | 10% | 18% |
| Nausea | 7% | 4% | 7% | 5% |
| Vomiting | 2% | 4% | 6% | 4% |
| Abdominal pain | 1% | 0% | 2% | 2% |
| Skin | ||||
| Rash | 8% | 2% | 3% | 2% |
| General disorders | ||||
| Fatigue | 2% | 1% | 4% | 2% |
| Nervous system | ||||
| Headache | 2% | 4% | 3% | 3% |
aAll patients also received abacavir and lamivudine twice daily.
| Adverse Reaction | Lexiva 700 mg b.i.d./ Ritonavir 100 mg b.i.d.a (n = 106) | Lopinavir 400 mg b.i.d./ Ritonavir 100 mg b.i.d.a (n = 103) |
| Gastrointestinal | ||
| Diarrhea | 13% | 11% |
| Nausea | 3% | 9% |
| Vomiting | 3% | 5% |
| Abdominal pain | <1% | 2% |
| Skin | ||
| Rash | 3% | 0% |
| Nervous system | ||
| Headache | 4% | 2% |
aAll patients also received 2 reverse transcriptase inhibitors.
Skin rash (without regard to causality) occurred in approximately 19% of patients treated with Lexiva in the pivotal efficacy studies. Rashes were usually maculopapular and of mild or moderate intensity, some with pruritus. Rash had a median onset of 11 days after initiation of Lexiva and had a median duration of 13 days. Skin rash led to discontinuation of Lexiva in less than 1% of patients. In some patients with mild or moderate rash, dosing with Lexiva was often continued without interruption; if interrupted, reintroduction of Lexiva generally did not result in rash recurrence.
The percentages of patients with Grade 3 or 4 laboratory abnormalities in the clinical efficacy studies of Lexiva are presented in Tables 4 and 5.
| Laboratory Abnormality | APV30001a | APV30002a | ||
Lexiva 1,400 mg b.i.d. (n = 166) | Nelfinavir 1,250 mg b.i.d. (n = 83) | Lexiva 1,400 mg q.d./ Ritonavir 200 mg q.d. (n = 322) | Nelfinavir 1,250 mg b.i.d. (n = 327) | |
| ALT (>5 x ULN) | 6% | 5% | 8% | 8% |
| AST (>5 x ULN) | 6% | 6% | 6% | 7% |
| Serum lipase (>2 x ULN) | 8% | 4% | 6% | 4% |
| Triglyceridesb (>750 mg/dL) | 0% | 1% | 6% | 2% |
| Neutrophil count, absolute (<750 cells/mm3) | 3% | 6% | 3% | 4% |
aAll patients also received abacavir and lamivudine twice daily.
bFasting specimens.
ULN = Upper limit of normal.
The incidence of Grade 3 or 4 hyperglycemia in antiretroviral-naive patients who received Lexiva in the pivotal studies was less than 1%.
| Laboratory Abnormality | Lexiva 700 mg b.i.d./ Ritonavir 100 mg b.i.d.a (n = 104) | Lopinavir 400 mg b.i.d./ Ritonavir 100 mg b.i.d.a (n = 103) |
| Triglyceridesb (>750 mg/dL) | 11%c | 6%c |
| Serum lipase (>2 x ULN) | 5% | 12% |
| ALT (>5 x ULN) | 4% | 4% |
| AST (>5 x ULN) | 4% | 2% |
| Glucose (>251 mg/dL) | 2%c | 2%c |
aAll patients also received 2 reverse transcriptase inhibitors.
bFasting specimens.
cn = 100 for Lexiva plus ritonavir, n = 98 for lopinavir plus ritonavir.
ULN = Upper limit of normal.
Pediatric Patients: Lexiva with and without ritonavir was studied in 144 pediatric patients aged 2 to 18 years in 2 open-label studies. Safety information from 75 pediatric patients receiving Lexiva twice daily with or without ritonavir follows.
All adverse events regardless of causality, all drug-related adverse events, and all laboratory events occurred with similar frequency in pediatrics compared with adults, with the exception of vomiting. Vomiting, regardless of causality, occurred more frequently among pediatric patients receiving Lexiva twice daily with ritonavir ([30%] all aged between 2 and 18 years) and without ritonavir ([56%] all aged between 2 and 5 years) compared with adults receiving Lexiva twice daily with ritonavir (10%) and without ritonavir (16%). The median duration of drug-related vomiting episodes was 1 day (range: 1 to 62 days). Vomiting required temporary dose interruptions in 4 pediatric patients and was treatment-limiting in 1 pediatric patient, all of whom were receiving Lexiva twice daily with ritonavir.
Postmarketing Experience
In addition to adverse reactions reported from clinical trials, the following reactions have been identified during post-approval use of Lexiva. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Lexiva.
Cardiac Disorders
Myocardial infarction.
Metabolism and Nutrition Disorders
Hypercholesterolemia.
Nervous System Disorders
Oral paresthesia.
Skin and Subcutaneous Tissue Disorders
Angioedema.
Urogenital
Nephrolithiasis.
Drug Interactions
See also Contraindications (4), Clinical Pharmacology (12.3).
If Lexiva is used in combination with ritonavir, see full prescribing information for ritonavir for additional information on drug interactions.
CYP Inhibitors and Inducers
Amprenavir, the active metabolite of fosamprenavir, is an inhibitor of cytochrome P450 3A4 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 Lexiva and drugs that induce CYP3A4, such as rifampin, may decrease amprenavir concentrations and reduce its therapeutic effect. Coadministration of Lexiva and drugs that inhibit CYP3A4 may increase amprenavir concentrations and increase the incidence of adverse effects.
The potential for drug interactions with Lexiva changes when Lexiva 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 Lexiva is coadministered with ritonavir. Because ritonavir is a CYP2D6 inhibitor, clinically significant interactions with drugs metabolized by CYP2D6 are possible when coadministered with Lexiva 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 Lexiva
See Contraindications (4).
Established and Other Potentially Significant Drug Interactions
Table 6 provides a listing of established or potentially clinically significant drug interactions. Information in the table applies to Lexiva with or without ritonavir, unless otherwise indicated.
Table 6. Established and Other Potentially Significant Drug Interactions
| Concomitant Drug Class: Drug Name | Effect on Concentration of Amprenavir or Concomitant Drug | Clinical Comment |
| HIV-Antiviral Agents | ||
Non-nucleoside reverse transcriptase inhibitor: Efavirenza | Lexiva: ↓Amprenavir Lexiva/ritonavir: ↓Amprenavir | Appropriate doses of the combinations with respect to safety and efficacy have not been established. An additional 100 mg/day (300 mg total) of ritonavir is recommended when efavirenz is administered with Lexiva/ritonavir once daily. No change in the ritonavir dose is required when efavirenz is administered with Lexiva plus ritonavir twice daily. |
Non-nucleoside reverse transcriptase inhibitor: Nevirapinea | Lexiva: ↓Amprenavir ↑Nevirapine Lexiva/ritonavir: ↓Amprenavir ↑Nevirapine | Coadministration of nevirapine and Lexiva without ritonavir is not recommended. No dosage adjustment required when nevirapine is administered with Lexiva/ritonavir twice daily. The combination of nevirapine administered with Lexiva/ritonavir once-daily regimen has not been studied. |
HIV protease inhibitor: Atazanavira | Lexiva: Interaction has not been evaluated. Lexiva/ritonavir: ↓Atazanavir ↔Amprenavir | Appropriate doses of the combinations with respect to safety and efficacy have not been established. |
HIV protease inhibitors: Indinavira, nelfinavira | Lexiva: ↑Amprenavir Effect on indinavir and nelfinavir is not well established. Lexiva/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/ritonavira | ↓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: Saquinavira | Lexiva: ↓Amprenavir Effect on saquinavir is not well established. Lexiva/ritonavir: Interaction has not been evaluated. | Appropriate doses of the combination with respect to safety and efficacy have not been established. |
HIV integrase inhibitor: Raltegravira | Lexiva: ↓Amprenavir ↓Raltegravir Lexiva/ritonavir: ↓Amprenavir ↓Raltegravir | Appropriate doses of the combination with respect to safety and efficacy have not been established [see Clinical Pharmacology (12.3)]. |
| Other Agents | ||
Antiarrhythmics: Amiodarone, bepridil, 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 Phenytoina | Lexiva: ↓Amprenavir Lexiva/ritonavir: ↑Amprenavir ↓Phenytoin | Use with caution. Lexiva may be less effective due to decreased amprenavir plasma concentrations in patients taking these agents concomitantly. Plasma phenytoin concentrations should be monitored and phenytoin dose should be increased as appropriate. No change in Lexiva/ritonavir dose is recommended. |
Antidepressant: Paroxetine, trazodone | ↓Paroxetine ↑Trazodone | Coadministration of paroxetine with Lexiva/ritonavir significantly decreased plasma levels of paroxetine. Any paroxetine dose adjustment should be guided by clinical effect (tolerability and efficacy). Concomitant use of trazodone and Lexiva with or without ritonavir may increase plasma concentrations of 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 Lexiva, the combination should be used with caution and a lower dose of trazodone should be considered. |
Antifungals: Ketoconazolea, itraconazole | ↑Ketoconazole ↑Itraconazole | Increase monitoring for adverse events. Lexiva: Dose reduction of ketoconazole or itraconazole may be needed for patients receiving more than 400 mg ketoconazole or itraconazole per day. Lexiva/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 Lexiva/ritonavir. Lexiva/ritonavirand 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. Treatment of familial Mediterranean fever (FMF): Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day). Lexivaand 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. Treatment of FMF: Maximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day). |
Antimycobacterial: Rifabutina | ↑Rifabutin and rifabutin metabolite | A complete blood count should be performed weekly and as clinically indicated to monitor for neutropenia. Lexiva: A dosage reduction of rifabutin by at least half the recommended dose is required. Lexiva/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). |
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. Lexiva may be less effective due to decreased amprenavir plasma concentrations. |
Endothelin receptor antagonists: Bosentan | ↑Bosentan | Coadministration of bosentan in patients on Lexiva: In patients who have been receiving Lexiva for at least 10 days, start bosentan at 62.5 mg once daily or every other day based upon individual tolerability. Coadministration of Lexiva in patients on bosentan: Discontinue use of bosentan at least 36 hours prior to initiation of Lexiva. After at least 10 days following the initiation of Lexiva, resume bosentan at 62.5 mg once daily or every other day based upon individual tolerability. |
Histamine H2-receptor antagonists: Cimetidine, famotidine, nizatidine, ranitidinea | Lexiva: ↓Amprenavir Lexiva/ritonavir: Interaction not evaluated | Use with caution. Lexiva may be less effective due to decreased amprenavir plasma concentrations. |
HMG-CoA reductase inhibitors: Atorvastatina, rosuvastatin | ↑Atorvastatin ↑Rosuvastatin | Use the lowest possible dose of atorvastatin or rosuvastatin with careful monitoring, or consider other HMG-CoA reductase inhibitors such as fluvastatin or pravastatin. |
Immunosuppressants: Cyclosporine, tacrolimus, rapamycin | ↑Immunosuppressants | Therapeutic concentration monitoring is recommended for immunosuppressant agents. |
Inhaled beta agonist: Salmeterol | ↑Salmeterol | Concurrent administration of salmeterol with Lexiva 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 | Lexiva: ↑Fluticasone Lexiva/ritonavir: ↑Fluticasone | |
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