maraviroc

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: ccr5 co.receptor antagonists

REMS

CCR5-tropic HIV-1 infection (in combination with other antiretrovirals).

Blocks a specific receptor on CD-4 and T-cell surfaces, which prevents CCR5-tropic HIV-1 from entering.

Therapeutic effects:

Decreased invasion of CD-4 and T-cells by CCR5-tropic HIV-1 resulting in viral replication.

Absorption: 2–33% absorbed following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Mostly metabolized by the liver by the CYP3A isoenzyme; 8% renal excretion as unchanged drug.

Half-Life: 14–18 hr.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	0.5–4 hr	1–2 hr

Contraindicated in:

Dual/mixed or CXCR4-tropic HIV-1;
Severe renal impairment or end-stage renal disease in patients who are taking potent CYP3A inhibitors or inducers;
Lactation: Breastfeeding not recommended for mothers infected with HIV.

Use Cautiously in:

Pre-existing liver disease including hepatitis B or C (may ↑ risk of hepatotoxicity);
Cardiovascular disease or risk factors (↑ risk of cardiovascular events);
Orthostatic hypotension;
Patients with severe renal impairment or end-stage renal disease who are not taking potent CYP3A inhibitors or inducers (↓ dose if symptoms of orthostatic hypotension occur);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk; not recommended for pregnant females with HIV who are antiretroviral naive;
Pedi: Children weighing 2 kg (safety and effectiveness not established);
Geri: Consider age-related in renal/hepatic function, concurrent drug therapy and concomitant disease in older adults.

CV: myocardial ischemia/infarction, orthostatic hypotension

Derm: DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS

GI: abdominal pain, appetite disorder, HEPATOTOXICITY

MS: musculoskeletal pain

Neuro: dizziness

Resp: cough, upper respiratory tract infection

Misc: fever, ↑risk of infection, hypersensitivity reactions (including lip swelling and facial edema), immune reconstitution syndrome

Drug-drug:

CYP3A inhibitors, including protease inhibitors (excluding tipranavir/ritonavir), elvitegravir/ritonavir, ketoconazole, itraconazole, clarithromycin, nefazodone, lopinavir/ritonavir, and atazanavir, may ↑ levels and the risk of toxicity; ↓ maraviroc dose.
CYP3A inducers, including efavirenz, rifampin, etravirine, carbamazepine, phenytoin, and phenobarbital, may ↓ levels and effectiveness; ↑ maraviroc dose.
Antihypertensives may ↑ risk of orthostatic hypotension.

Drug-Natural Products:

St. John's wort may ↓ levels; concurrent use not recommended.

PO (Adults ): Concurrent potent CYP3A inhibitors (with or without potent CYP3A inducers), including protease inhibitors (except tipranavir/ritonavir), elvitegravir/ritonavir, ketoconazole, itraconazole, clarithromycin, and other potent CYP3A inhibitors: 150 mg twice daily; Concurrent potent CYP3A inducers (without a potent CYP3A inhibitor), including efavirenz, rifampin, etravirine, carbamazepine, phenytoin, and phenobarbital: 600 mg twice daily; Noninteracting concomitant medications, including NRTIs, tipranavir/ritonavir, nevirapine, raltegravir, enfuvirtide, and other medications that not potent CYP3A inhibitors/inducers: 300 mg twice daily.
PO (Children ≥40 kg): Concurrent potent CYP3A inhibitors (with or without a CYP3A inducer), including clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, and protease inhibitors (except tipranavir/ritonavir), : 150 mg twice daily (as tablets [if ≥2 yr] or oral solution); Concurrent potent and moderate CYP3A inducers (without a potent CYP3A inhibitor), including carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin: Not recommended; Noninteracting concomitant medications that are not potent CYP3A inhibitors/inducers, including dolutegravir, enfuvirtide, nevirapine, all NRTIs, raltegravir, and tipranavir/ritonavir: 300 mg twice daily (as tablets [if ≥2 yr] or oral solution).
PO (Children 30–<40 kg): Concurrent potent CYP3A inhibitors (with or without a CYP3A inducer), including clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, and protease inhibitors (except tipranavir/ritonavir): 100 mg twice daily (as tablets [if ≥2 yr] or oral solution); Concurrent potent and moderate CYP3A inducers (without a potent CYP3A inhibitor), including carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin: Not recommended; Noninteracting concomitant medications that are not potent CYP3A inhibitors/inducers, including dolutegravir, enfuvirtide, nevirapine, all NRTIs, raltegravir, and tipranavir/ritonavir: 300 mg twice daily (as tablets [if ≥2 yr] or oral solution).
PO (Children 20–<30 kg): Concurrent potent CYP3A inhibitors (with or without a CYP3A inducer), including clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, and protease inhibitors (except tipranavir/ritonavir): 75 mg twice daily (as tablets [if ≥2 yr] or oral solution); Concurrent potent and moderate CYP3A inducers (without a potent CYP3A inhibitor), including carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin: Not recommended; Noninteracting concomitant medications that are not potent CYP3A inhibitors/inducers, including dolutegravir, enfuvirtide, nevirapine, all NRTIs, raltegravir, and tipranavir/ritonavir: 200 mg twice daily (as tablets [if ≥2 yr] or oral solution).
PO (Children 14–<20 kg): Concurrent potent CYP3A inhibitors (with or without a CYP3A inducer), including clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, and protease inhibitors (except tipranavir/ritonavir): 50 mg twice daily (as tablets [if ≥2 yr] or oral solution); Concurrent potent and moderate CYP3A inducers (without a potent CYP3A inhibitor), including carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin: Not recommended; Noninteracting concomitant medications that are not potent CYP3A inhibitors/inducers, including dolutegravir, enfuvirtide, nevirapine, all NRTIs, raltegravir, and tipranavir/ritonavir: 200 mg twice daily (as tablets [if ≥2 yr] or oral solution).
PO (Children 10–<14 kg): Concurrent potent CYP3A inhibitors (with or without a CYP3A inducer), including clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, and protease inhibitors (except tipranavir/ritonavir): 50 mg twice daily (as tablets [if ≥2 yr] or oral solution); Concurrent potent and moderate CYP3A inducers (without a potent CYP3A inhibitor), including carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin: Not recommended; Noninteracting concomitant medications that are not potent CYP3A inhibitors/inducers, including dolutegravir, enfuvirtide, nevirapine, all NRTIs, raltegravir, and tipranavir/ritonavir: 150 mg twice daily (as tablets [if ≥2 yr] or oral solution).
PO (Children 6–<10 kg): Concurrent potent CYP3A inhibitors (with or without a CYP3A inducer), including clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, and protease inhibitors (except tipranavir/ritonavir): Not recommended; Concurrent potent and moderate CYP3A inducers (without a potent CYP3A inhibitor), including carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin: Not recommended; Noninteracting concomitant medications that are not potent CYP3A inhibitors/inducers, including dolutegravir, enfuvirtide, nevirapine, all NRTIs, raltegravir, and tipranavir/ritonavir: 100 mg twice daily (as oral solution).
PO (Children 4–<6 kg): Concurrent potent CYP3A inhibitors (with or without a CYP3A inducer), including clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, and protease inhibitors (except tipranavir/ritonavir): Not recommended; Concurrent potent and moderate CYP3A inducers (without a potent CYP3A inhibitor), including carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin: Not recommended; Noninteracting concomitant medications that are not potent CYP3A inhibitors/inducers, including dolutegravir, enfuvirtide, nevirapine, all NRTIs, raltegravir, and tipranavir/ritonavir: 40 mg twice daily (as oral solution).
PO (Children 2–<4 kg): Concurrent potent CYP3A inhibitors (with or without a CYP3A inducer), including clarithromycin, cobicistat, elvitegravir/ritonavir, itraconazole, ketoconazole, nefazodone, and protease inhibitors (except tipranavir/ritonavir): Not recommended; Concurrent potent and moderate CYP3A inducers (without a potent CYP3A inhibitor), including carbamazepine, efavirenz, etravirine, phenobarbital, phenytoin, and rifampin: Not recommended; Noninteracting concomitant medications that are not potent CYP3A inhibitors/inducers, including dolutegravir, enfuvirtide, nevirapine, all NRTIs, raltegravir, and tipranavir/ritonavir: 30 mg twice daily (as oral solution).

Renal Impairment

(Adults ): CCr <30 mL/min or on hemodialysis (not receiving potent CYP3A inhibitors or potent or moderate CYP3A inducers): 300 mg twice daily; ↓ dose to 150 mg twice daily if symptoms of orthostatic hypotension occur; CCr <30 mL/min or on hemodialysis (receiving potent CYP3A inhibitors or potent or moderate CYP3A inducers): Contraindicated.

Renal Impairment

(Children ≥2 kg): CCr <30 mL/min or on hemodialysis (receiving potent CYP3A inhibitors or potent or moderate CYP3A inducers): Contraindicated.

(Generic available)

Tablets: 150 mg; 300 mg
Oral solutionstrawberry flavor: 20 mg/mL

Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
Assess for signs or symptoms of hepatitis or allergic reaction (pruritic rash, jaundice, dark urine, vomiting, abdominal pain, fever, eosinophilia, elevated IgE). If symptoms occur, discontinue maraviroc immediately.
Assess for rash periodically during therapy. May cause SJS. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, facial swelling) associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.

Lab Test Considerations:

Testing for CCR5-tropic HIV-1 should be obtained prior to initiating therapy.
- Monitor viral load and CD4 cell count regularly during therapy.
- Monitor AST, ALT, and serum bilirubin prior to and periodically during therapy. May cause ↑ AST, ALT, total bilirubin, amylase, and lipase.
- May cause ↓ absolute neutrophil count.

PO: May be administered without regard to food.
- Administer oral solution using included press-in bottle adapter and appropriate oral dosing syringe: for doses ≤2.5 mL, use the 3-mL syringe; for doses >2.5 mL, use 10-mL syringe. Use care when measuring neonate doses due to the small volumes of oral solution required. Solution is clear and colorless. Store at room temperature. Discard unused solution 60 days after first opening bottle.

Explain purpose and side effects of medication to patient. Advise patient to readPatient Information before starting therapy and with each Rx refill in case of changes. Take as directed at the same time each day. Instruct patient not to share medication with others. Emphasize the importance of regular follow-up exams and blood counts to determine progress.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort; may decrease effectiveness.
Maraviroc must always be used in combination with other antiretroviral drugs. Do not take more than prescribed amount, and do not stop taking without consulting health care professional. Take missed doses as soon as remembered; then return to regular dose schedule. If it is within 6 hr of next dose, omit dose and take next dose at regular time. Do not double doses.
Inform patient that maraviroc does not cure HIV or prevent associated or opportunistic infections. May reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and to avoid sharing needles or donating blood to prevent spreading HIV to others. If new symptoms of infection develop after starting maraviroc, notify health care professional.
Advise patient to discontinue maraviroc and notify health care professional if chest pain, signs of hepatotoxicity (itchy rash, yellow-colored skin or eyes, dark urine, vomiting, abdominal pain) or signs of immune reconstitution syndrome (signs and symptoms of an infection—
Mycobacterium avium
complex infection, cytomegalovirus,
Pneumocystis jirovecii
pneumonia, tuberculosis, reactivation of herpes simplex and herpes zoster) occur.
May cause dizziness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
Advise patient to make position changes slowly to minimize postural hypotension.
Rep: May cause fetal harm. Advise females of reproductive potential taking oral contraceptives to use a nonhormonal method of birth control during therapy. Instruct patient to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding. Inform pregnant women of the pregnancy exposure registry that monitors pregnancy outcomes in women exposed to maraviroc during pregnancy. To enroll in the Antiviral Pregnancy Registry call 1-800-258-4263.

Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
Decrease in viral load and increase in CD4 cell counts.

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