Maraviroc (Selzentry) is an orally available antiretroviral drug that acts as a CCR5 receptor antagonist. It is used in the treatment of HIV-1 infection in combination with other antiviral drugs.

Maraviroc (Selzentry) Uses:

• HIV-1 infection:

  • Treatment of only CCR5-tropic HIV-1 infection in patients 2 years and older and weighing ≥10 kg, in combination with other antiretroviral agents.

Maraviroc (Selzentry) use in COVID-19 infection:

Since no effective drugs have been found to treat patients with COVID-19 infection. Many drugs have been hypothesized to be effective. Maraviroc is thought to act as an antiviral molecule targeting SARS-CoV-2 Mpro [Ref].

Maraviroc (Selzentry) Dose in Adults:

Maraviroc (Selzentry) Dose in the treatment of HIV-1 infection:

• Oral:
  • 300 mg BD;
  • The dose recommended when maraviroc administered concomitantly with other medications that are not potent CYP3A inhibitors or inducers, including tipranavir/ritonavir, nevirapine, raltegravir, all NRTIs, and enfuvirtide.

• ---

  Dosage adjustment for concomitant CYP3A inhibitors/inducers:

  • CYP3A inhibitors (with or without a potent CYP3A inducer):

    • 150 mg BD;
    • The dose recommended when maraviroc administered concomitantly with potent CYP3A inhibitors including (but not limited to) protease inhibitors (excluding tipranavir/ritonavir), delavirdine, elvitegravir/ritonavir, ketoconazole, itraconazole, clarithromycin, nefazodone, telithromycin, and boceprevir.

  • CYP3A inducers (without a potent CYP3A inhibitor):

    • 600 mg BD;
    • The dose recommended when maraviroc administered concomitantly with potent CYP3A inducers including (but not limited to) efavirenz, etravirine, rifampin, carbamazepine, phenobarbital, and phenytoin

Maraviroc (Selzentry) Dose in Children:

• Use in combination with other antiretroviral agents.

Maraviroc (Selzentry) Dose in the treatment of HIV-1 infection:

• Administration without potent CYP3A inhibitors or inducers:

  • Children ≥2 years and Adolescents:

    • Weight <30 kg: Not recommended
    • Weight ≥30 kg: Oral: 300 mg BD

• Administration with potent CYP3A inhibitors or inducers:

  • Children ≥2 years (weighing ≥10 kg) and Adolescents:
    • See dosage adjustment for concomitant therapy

Dosing adjustment for concomitant CYP3A4 inhibitors/inducers:

• Children ≥2 years and Adolescents:

  • CYP3A inhibitors (with or without a CYP3A4 inducer):

    • The dose recommended when maraviroc administered concomitantly with strong CYP3A inhibitors including (but not limited to):
      • Protease inhibitors (excluding tipranavir/ritonavir), boceprevir, delavirdine, elvitegravir/ritonavir, ketoconazole, itraconazole, clarithromycin, nefazodone, and telithromycin
    • 10 to <20 kg: Oral: 50 mg BD
    • 20 to <30 kg: Oral: 75 mg BD (tablets) or 80 mg BD (oral solution)
    • 30 to <40 kg: Oral: 100 mg BD
    • ≥40 kg: Oral: 150 mg BD

  • CYP3A inducers (without a strong CYP3A4 inhibitor):

    • In pediatric patients, maraviroc not recommended
    • In adults, dosage adjustment recommended when maraviroc administered concomitantly with CYP3A inducers including (but not limited to):
      • Efavirenz, etravirine, rifampin, carbamazepine, phenobarbital, and phenytoin

Maraviroc Pregnancy Risk Category: B

• Maraviroc shows moderate transfer to the human placenta.
• The data from the antiretroviral pregnancy registry do not provide sufficient information to assess human teratogenic risks.
• Although maternal antiretroviral treatment (ART) may increase preterm births, the information available is inconsistent due to variability in maternal factors (disease severity and gestational age at the initiation of therapy),
• Some studies have shown an increased risk of stillbirth and low birth weight in infants under gestational age. However, not all studies have confirmed this.
• Maternal ART is an important treatment option that has clear benefits.
• Avoid delay if you are concerned about adverse neonatal outcomes.
• All infants who have been exposed to antiretroviral medication should be followed up for a long time
• Potential mitochondrial dysfunction should be considered for children who have significant organ abnormalities of unknown origin (especially the heart or CNS).
• Due to insufficient data, the Health and Human Services (HHS), Perinatal HIV Guidelines don't recommend maraviroc for HIV-infected pregnant women who are antiretroviral naive.
• Maraviroc is not recommended for pregnant women who have received ART therapy in the previous but are starting again, or who need a new regimen due to poor tolerance of poor virologic response.
• If the viral suppression is effective and the regimen is well tolerated, females who are pregnant while taking maraviroc might continue to take it.
• Pregnancy does not require dosage adjustments.
• To keep HIV-positive pregnant women under the control and to reduce the chance of perinatal transmission, it is generally recommended that ART be performed.
• Monitoring during pregnancy is more common than monitoring in adults who are not pregnant.
• All HIV-positive women should continue ART after giving birth. ART can also be modified once the baby is born.

Maraviroc use during breastfeeding:

• It is unknown if maraviroc can be found in breast milk.
• Postnatal HIV transmission is not completely eliminated by infant or maternal antiretroviral treatment.
• A multiclass-resistant virus was also detected in breastfed infants, despite maternal therapy.
• To reduce the possibility of HIV transmission, women with HIV should not breastfeed in the US. The formula is affordable, safe and easily accessible.

Maraviroc (Selzentry) Dose in Kidney Disease:

• CrCl ≥30 mL/minute:

  • No dosage adjustment necessary

• CrCl <30 mL/minute:

  • Concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer) or concomitant potent CYP3A inducer (without a potent CYP3A inhibitor):
    • Use is contraindicated
  • Other concomitant medications (eg, tipranavir/ritonavir, nevirapine, raltegravir, all NRTIs, enfuvirtide, and other medications that are not potent CYP3A inhibitors or inducers):
    • No dosage adjustment necessary, unless postural hypotension occurs; then, reduce dose to 150 mg BD

• ESRD requiring intermittent hemodialysis (IHD):

Note: Hemodialysis has minimal effect on clearance

• Concomitant potent CYP3A inhibitors (with or without a potent CYP3A inducer) or concomitant potent CYP3A inducer (without a potent CYP3A inhibitor):
  • Use is contraindicated
• Other concomitant medications (eg, tipranavir/ritonavir, nevirapine, raltegravir, all NRTIs, enfuvirtide, and other medications that are not potent CYP3A inhibitors or inducers):
  • No dosage adjustment necessary, unless postural hypotension occurs; then, reduce dose to 150 mg BD.

Maraviroc (Selzentry) Dose in Liver disease:

• Mild to moderate impairment:
  • There are no dosage adjustments provided in the manufacturer's labeling
  • However, maraviroc concentrations are increased in mild to moderate impairment
  • Use cautiously.
• Moderate impairment (with concomitant potent CYP3A inhibitor):
  • There are no dosage adjustments provided in the manufacturer's labeling
  • However, maraviroc concentrations are increased moderate impairment
  • Use cautiously and monitor closely for adverse events.
• Severe impairment:
  • There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

• Includes data from both treatment-naive and treatment-experienced patients.
• Unless otherwise noted, the frequency of adverse events is as reported in adults receiving combination antiretroviral therapy.

Common Side Effects of Maraviroc (Selzentry):

• Dermatologic:

  • Skin rash

• Gastrointestinal:

  • Vomiting

• Infection:

  • Infection

• Respiratory:

  • Upper respiratory tract infection
  • Cough

• Miscellaneous:

  • Fever

Less Common Side Effects of Maraviroc (Selzentry):

• Cardiovascular:

  • Hypertension
  • Cardiac Failure
  • Cerebrovascular Accident
  • Coronary Artery Disease
  • Coronary Occlusion
  • Endocarditis
  • Myocardial Infarction
  • Portal Vein Thrombosis
  • Septic Shock
  • Unstable Angina Pectoris

• Central Nervous System:

  • Dizziness
  • Insomnia
  • Paresthesia
  • Dysesthesia
  • Anxiety
  • Impaired Consciousness
  • Depression
  • Peripheral Neuropathy
  • Malaise
  • Pain
  • Sensory Disturbance
  • Memory Impairment
  • Epilepsy
  • Loss Of Consciousness
  • Meningitis
  • Facial Paralysis
  • Seizure

• Dermatologic:

  • Nail Disease
  • Sweat Gland Disease
  • Folliculitis
  • Pruritus
  • Tinea
  • Acne Vulgaris
  • Alopecia
  • Erythema
  • Condyloma Acuminatum

• Endocrine & Metabolic:

  • Lipodystrophy

• Gastrointestinal:

  • Abdominal Distension
  • Bloating
  • Flatulence
  • Decreased Gastrointestinal Motility
  • Change In Appetite
  • Constipation
  • Abdominal Pain
  • Diarrhea
  • Nausea
  • Carcinoma In Situ Of Esophagus
  • Colitis

• Genitourinary:

  • Genitourinary Complaint
  • Ejaculatory Disorder
  • Erectile Dysfunction

• Hematologic & Oncologic:

  • Anemia
  • Neutropenia
  • Benign Skin Neoplasm
  • Basal Cell Carcinoma
  • Bone Marrow Depression
  • Bowen Disease
  • Carcinoma
  • Hypoplastic Anemia
  • Liver Metastases
  • Malignant Lymphoma
  • Malignant Neoplasm
  • Malignant Neoplasm Of Bile Duct
  • Malignant Neoplasm Of Tongue
  • Neoplasm
  • Squamous Cell Carcinoma
  • Squamous Cell Carcinoma Of Skin

• Hepatic:

  • Increased Serum AST
  • Cholestatic Jaundice
  • Hepatic Cirrhosis
  • Hepatic Failure
  • Jaundice

• Infection:

  • Herpes Virus Infection
  • Bacterial Infection
  • Herpes Zoster
  • Varicella Zoster Infection
  • Meningococcal Infection Viral Infection
  • Influenza
  • Bacterial Infection

• Neuromuscular & Skeletal:

  • Arthropathy
  • Myalgia
  • Increased Creatine Phosphokinase
  • Myositis
  • Osteonecrosis
  • Rhabdomyolysis
  • Tremor

• Ophthalmic:

  • Conjunctivitis
  • Eye Disease
  • Hemianopia
  • Visual Field Defect

• Otic:

  • Otitis Media

• Respiratory:

  • Bronchitis
  • Upper Respiratory Complaint
  • Sinusitis
  • Irregular Breathing
  • Nasal Congestion
  • Rhinitis
  • Lower Respiratory Tract Infection
  • Pulmonary Infection
  • Paranasal Sinus Disease
  • Pneumonia

Rare side effects of Maraviroc (Selzentry):

• Hepatic:

  • Hepatitis
  • Hepatotoxicity

• Immunologic:

  • Immune Reconstitution Syndrome

Contraindications to Maraviroc (Selzentry):

Patients with severe renal impairment (CrCl 30 mL/minute), or end-stage kidney disease (ESRD), who are also taking potent CYP3A inducers or inhibitors.

Canadian labeling: Additional contraindications not in US labeling

• Hypersensitivity to maraviroc and any component of the formulation

Warnings and precautions

• CNS effects

  • May cause dizziness.
  • CNS symptoms can cause patients to avoid driving and operating machinery.

• Hepatotoxicity: [US Boxed Warning]

  • Reports have suggested that drug-induced liver toxicities could be caused by allergic-type symptoms.
  • Severe rash and other symptoms may precede hepatotoxicity.
  • Patients with pre-existing HBV/HCV infection or hepatic dysfunction should be cautious. However, symptoms can occur even if there are no pre-existing conditions.
  • Monitor your liver function at baseline, and as indicated by your doctor during treatment.
  • Patients with hepatitis, elevated transaminases or systemic allergic reactions should be considered for discontinuation.
  • It is not recommended to engage in a battle with maraviroc.

• Immune reconstitution syndrome:

  • The immune reconstitution syndrome may occur in patients who have received HIV treatment.
  • This can lead to an inflammatory response to an indolent, residual opportunistic virus.
  • Additional evaluation and treatment may still be necessary.

• Infections

  • Pay attention to any signs or symptoms that indicate the possibility of developing infection.
  • Clinical trials have shown that there was a slight increase in certain upper respiratory tract infections as well as herpes virus infection.

• Malignancy

  • The pharmacologic mechanism may cause an increase in malignancy and affect immune surveillance.
  • There has not been an increase in malignancy.
  • This risk requires long-term monitoring.

• Postural hypotension:

  • Hypotension symptoms have been diagnosed.
  • Patients at high risk for the condition should be treated with caution if they are taking medication or have a history of it.
  • Patients with severe renal impairment or ESRD may be at greater risk for postural hypotension.
  • Patients suffering from severe renal dysfunction or ESRD should be given a lower dose.

• Hypersensitivity and skin reactions

  • Patients who have received concomitant medications with these reactions have reported severe and life-threatening skin reactions and hypersensitivity reactions.
  • These reports have been accompanied by rash and other constitutional findings (eg, fevers, muscle aches, conjunctivitis or oral lesions), as well as organ dysfunction (including hepatic impairment).
  • If hypersensitivity symptoms develop, discontinue use of maraviroc or any other suspected agent.
  • As appropriate, monitor hepatic function.

• Cardiovascular disease

  • Patients with heart disease or patients who have a history or are currently at risk for postural hypotension or those taking concomitant medications that lower blood pressure should be cautious.
  • Postural hypotension can lead to cardiac adverse events in patients with cardiovascular comorbidities.
  • Trials revealed that there was a slight increase in the number of cardiovascular events in patients treated with therapy (myocardial infarction and/or myocardial ischemia) compared to placebo.
  • However, it is not known if this relationship is related to therapy.
  • Not to be overlooked, most patients who experience cardiac events had previously experienced risk factors or cardiac disease.

• Hepatic impairment

  • Patients with HBV/or HCV coinfection, mild-to-moderate liver impairment or HCV coinfection should be cautious. Maraviroc concentrations may increase.
  • Patients with mild hepatic impairment receive concomitant potent CYP3A inhibits.
  • Maraviroc concentrations may be increased further. Monitor closely for any adverse reactions.
  • It has not been tested in patients with severe liver impairment.

• Renal impairment

  • Maraviroc concentrations may be affected by renal impairment.
  • Patients with moderate-to-severe renal impairment should be cautious.
  • Patients with severe renal impairment and those with ESRD may be at greater risk for postural hypotension.
  • Patients with severe renal disease or ESRD should be given a lower dose.
  • Patients with severe renal impairment or ESRD are not recommended to use this drug.

Maraviroc: Drug Interaction

Monitoring parameters:

• Viral load, CD4 count, transaminases and bilirubin (prior to initiation and periodically during treatment)
• Signs/symptoms of infection, rash, severe skin reactions, hepatitis and/or allergic reaction
• Postural hypotension
• Tropism testing (prior to initiation)

How to administer Maraviroc (Selzentry)?

• Oral:
  • Administer without regard to meals.
  • Stable immunologic parameters and virologic suppression have been reported following the administration of crushed tablets.
  • However, an oral solution is commercially available.

Mechanism of action of Maraviroc (Selzentry):

• Maraviroc, an antagonist of CCR5, selectively and reversibly binds the chemokine C-C motif receptor 5, [CCR5]) coreceptors on human CD4 cells.
• CCR5 antagonism is a block in interaction between the human CCR5 cortexor and the gp120 unit of the viral envelope glycoprotein.
• This inhibits gp120 conformational changes required for CCR5tropic HIV-1 fusion to the CD4 cells and subsequent cell entry.

Notification:

• • Pediatric patients with Maraviroc were >=30kg and received non-interacting concomitant medication.
  • These parameters were comparable to those in adults.

Protein binding:

• ~76%

Metabolism:

• Hepatic, via CYP3A to inactive metabolites

Bioavailability:

• 23% to 33% (maraviroc is a substrate for the efflux transporter P-gp)

Half-life elimination:

• 14 to 18 hours

Time to peak, plasma:

• 0.5 to 4 hours

Excretion:

• Urine (~20%, 8% as unchanged drug)
• feces (76%, 25% as unchanged drug)

International Brands of Maraviroc:

• Selzentry
• Celsentri

Maraviroc Brand Names in Pakistan:

No Brands Available in Pakistan.