Maraviroc: Difference between revisions

(Created page with "Maraviroc is a CCR5 co-receptor antagonist (entry inhibitor) used in combination with other antiretrovirals for '''CCR5-tropic HIV-1 only'''. It is unique among antiretrovirals in targeting a host cell receptor rather than a viral enzyme. A tropism assay is required before use.<ref name="SelzentryPI">Selzentry (maraviroc) [prescribing information]. Research Triangle Park, NC: ViiV Healthcare; 2020.</ref> ==Administration== *Type: CCR5 co-receptor a...")
 
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Maraviroc is a CCR5 co-receptor antagonist (entry inhibitor) used in combination with other antiretrovirals for '''CCR5-tropic HIV-1 only'''. It is unique among antiretrovirals in targeting a host cell receptor rather than a viral enzyme. A [[HIV - AIDS (main)|tropism assay]] is required before use.<ref name="SelzentryPI">Selzentry (maraviroc) [prescribing information]. Research Triangle Park, NC: ViiV Healthcare; 2020.</ref>
Maraviroc is a CCR5 co-receptor antagonist (entry inhibitor) used in combination with other antiretrovirals for CCR5-tropic HIV-1 only. It is unique among antiretrovirals in targeting a host cell receptor rather than a viral enzyme. A [[HIV - AIDS (main)|tropism assay]] is required before use.<ref name="SelzentryPI">Selzentry (maraviroc) [prescribing information]. Research Triangle Park, NC: ViiV Healthcare; 2020.</ref>


==Administration==
==Administration==
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==Adult Dosing==
==Adult Dosing==
Dose depends entirely on concomitant CYP3A medications:<ref name="SelzentryPI"/>
Dose depends entirely on concomitant CYP3A medications:<ref name="SelzentryPI"/>
*'''With strong CYP3A inhibitors''' (e.g., ritonavir-boosted PIs, ketoconazole): '''150 mg PO BID'''
*With strong CYP3A inhibitors (e.g., ritonavir-boosted PIs, ketoconazole): 150 mg PO BID
*'''With strong CYP3A inducers''' (e.g., rifampin, carbamazepine, phenytoin, efavirenz): '''600 mg PO BID'''
*With strong CYP3A inducers (e.g., rifampin, carbamazepine, phenytoin, efavirenz): 600 mg PO BID
*'''Without strong CYP3A inhibitors or inducers''' (e.g., tipranavir/ritonavir, raltegravir, NRTIs): '''300 mg PO BID'''
*Without strong CYP3A inhibitors or inducers (e.g., tipranavir/ritonavir, raltegravir, NRTIs): 300 mg PO BID
*May take with or without food
*May take with or without food


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*Adult:<ref name="SelzentryPI"/>
*Adult:<ref name="SelzentryPI"/>
**Mild to moderate (Child-Pugh A or B): No dose adjustment; monitor closely if moderate impairment + CYP3A inhibitor
**Mild to moderate (Child-Pugh A or B): No dose adjustment; monitor closely if moderate impairment + CYP3A inhibitor
**Severe (Child-Pugh C): Not studied; '''not recommended'''
**Severe (Child-Pugh C): Not studied; not recommended
*Pediatric: Not studied
*Pediatric: Not studied


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==Pharmacology==
==Pharmacology==
*Half-life: ~14–18 hours<ref name="Abel2009">Abel S, et al. Maraviroc: pharmacokinetics and drug interactions. ''Antivir Ther''. 2009;14(5):607-618.</ref>
*Half-life: ~14–18 hours<ref name="Abel2009">Abel S, et al. Maraviroc: pharmacokinetics and drug interactions. ''Antivir Ther''. 2009;14(5):607-618.</ref>
*Metabolism: CYP3A4 (primary); also a P-gp substrate. Does '''not''' inhibit major CYP450 enzymes at therapeutic doses<ref name="Abel2009"/>
*Metabolism: CYP3A4 (primary); also a P-gp substrate. Does not inhibit major CYP450 enzymes at therapeutic doses<ref name="Abel2009"/>
*Excretion: ~76% feces, ~20% urine<ref name="Abel2009"/>
*Excretion: ~76% feces, ~20% urine<ref name="Abel2009"/>


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==Comments==
==Comments==
*Not a first-line ARV; used in treatment-experienced patients with confirmed R5-tropic virus
*Not a first-line ARV; used in treatment-experienced patients with confirmed R5-tropic virus
*'''ED hepatotoxicity recognition:''' New rash + eosinophilia + liver enzyme elevation → suspect DILI, hold drug, check hepatic panel, consult [[HIV - AIDS (main)|HIV/ID]]<ref name="LiverTox"/>
*ED hepatotoxicity recognition: New rash + eosinophilia + liver enzyme elevation → suspect DILI, hold drug, check hepatic panel, consult [[HIV - AIDS (main)|HIV/ID]]<ref name="LiverTox"/>
*'''Postural hypotension''' may be symptomatic in renal impairment or on CYP3A inhibitors — manage with IV fluids and supine positioning
*Postural hypotension may be symptomatic in renal impairment or on CYP3A inhibitors — manage with IV fluids and supine positioning
*Maraviroc does not significantly affect levels of other drugs, making it lower risk for interactions when prescribing in the ED<ref name="Abel2009"/>
*Maraviroc does not significantly affect levels of other drugs, making it lower risk for interactions when prescribing in the ED<ref name="Abel2009"/>
*Overdose: Supportive care; no specific antidote; unlikely removed by dialysis<ref name="SelzentryPI"/>
*Overdose: Supportive care; no specific antidote; unlikely removed by dialysis<ref name="SelzentryPI"/>

Latest revision as of 09:12, 22 March 2026

Maraviroc is a CCR5 co-receptor antagonist (entry inhibitor) used in combination with other antiretrovirals for CCR5-tropic HIV-1 only. It is unique among antiretrovirals in targeting a host cell receptor rather than a viral enzyme. A tropism assay is required before use.[1]

Administration

  • Type: CCR5 co-receptor antagonist (entry inhibitor)
  • Dosage Forms: 25 mg, 75 mg, 150 mg, 300 mg tablets; 20 mg/mL oral solution
  • Routes of Administration: Oral
  • Common Trade Names: Selzentry (US), Celsentri (EU)

Adult Dosing

Dose depends entirely on concomitant CYP3A medications:[1]

  • With strong CYP3A inhibitors (e.g., ritonavir-boosted PIs, ketoconazole): 150 mg PO BID
  • With strong CYP3A inducers (e.g., rifampin, carbamazepine, phenytoin, efavirenz): 600 mg PO BID
  • Without strong CYP3A inhibitors or inducers (e.g., tipranavir/ritonavir, raltegravir, NRTIs): 300 mg PO BID
  • May take with or without food

Pediatric Dosing

  • Approved for patients ≥2 kg; weight-based dosing adjusted for CYP3A interactions[1]
  • Consult pediatric ID or prescribing information for weight-based tables

Special Populations

Pregnancy Rating

  • Formerly Category B; no adequate controlled studies in pregnant women[1]
  • Animal studies showed no teratogenicity; standard dose appears appropriate in pregnancy[2]

Lactation risk

  • Secreted into rat milk; unknown in human milk. Women with HIV should not breastfeed (risk of HIV transmission)[1]

Renal Dosing

  • Adult:[1]
    • CrCl ≥30 mL/min: No adjustment needed
    • CrCl <30 mL/min or ESRD: Contraindicated if on potent CYP3A inhibitors or inducers; otherwise no adjustment but reduce to 150 mg BID if postural hypotension occurs
    • Hemodialysis has minimal effect on clearance
  • Pediatric: Insufficient data

Hepatic Dosing

  • Adult:[1]
    • Mild to moderate (Child-Pugh A or B): No dose adjustment; monitor closely if moderate impairment + CYP3A inhibitor
    • Severe (Child-Pugh C): Not studied; not recommended
  • Pediatric: Not studied

Contraindications

  • Allergy to class/drug
  • CXCR4-tropic or dual/mixed-tropic HIV-1 (ineffective)[1]
  • Severe renal impairment (CrCl <30 mL/min) or ESRD when coadministered with potent CYP3A inhibitors or inducers[1]

Adverse Reactions

Serious

Common

  • Upper respiratory tract infections, cough
  • Fever, rash, dizziness
  • Abdominal pain, nausea, diarrhea
  • Transaminase elevations (~10%, usually mild and asymptomatic)[3]

Pharmacology

  • Half-life: ~14–18 hours[4]
  • Metabolism: CYP3A4 (primary); also a P-gp substrate. Does not inhibit major CYP450 enzymes at therapeutic doses[4]
  • Excretion: ~76% feces, ~20% urine[4]

Mechanism of Action

Maraviroc is a selective allosteric antagonist of CCR5, a chemokine co-receptor on CD4+ T cells required for entry of R5-tropic HIV-1. It binds within the transmembrane domain of CCR5, altering the extracellular conformation so that viral gp120 cannot recognize the receptor, blocking viral-host membrane fusion and cell entry.[5] It has no activity against CXCR4-tropic virus. Resistance occurs primarily through outgrowth of pre-existing CXCR4-using viral populations or gp120 V3 loop mutations.[1]

Comments

  • Not a first-line ARV; used in treatment-experienced patients with confirmed R5-tropic virus
  • ED hepatotoxicity recognition: New rash + eosinophilia + liver enzyme elevation → suspect DILI, hold drug, check hepatic panel, consult HIV/ID[3]
  • Postural hypotension may be symptomatic in renal impairment or on CYP3A inhibitors — manage with IV fluids and supine positioning
  • Maraviroc does not significantly affect levels of other drugs, making it lower risk for interactions when prescribing in the ED[4]
  • Overdose: Supportive care; no specific antidote; unlikely removed by dialysis[1]
  • Avoid St. John's wort (decreases maraviroc levels)[1]

See Also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Selzentry (maraviroc) [prescribing information]. Research Triangle Park, NC: ViiV Healthcare; 2020.
  2. ↑ Colbers A, et al. Maraviroc pharmacokinetics in HIV-1-infected pregnant women. Clin Infect Dis. 2015;61(10):1582-1589.
  3. ↑ 3.0 3.1 3.2 Maraviroc. LiverTox. NCBI Bookshelf. Updated 2019.
  4. ↑ 4.0 4.1 4.2 4.3 Abel S, et al. Maraviroc: pharmacokinetics and drug interactions. Antivir Ther. 2009;14(5):607-618.
  5. ↑ Dorr P, et al. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5. Antimicrob Agents Chemother. 2005;49(11):4721-4732.
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