Usage
- Maraviroc is prescribed for the treatment of CCR5-tropic HIV-1 infection in adults and children aged 2 years and older. It is crucial to confirm CCR5-tropism before initiating therapy. It is always used in combination with other antiretroviral medications.
- Pharmacological Classification: CCR5 antagonist, antiretroviral.
- Mechanism of Action: Maraviroc works by selectively and reversibly binding to the CCR5 co-receptor on the surface of CD4+ T-cells. This action blocks the HIV-1 virus from entering the host cell, thus inhibiting viral replication. It is effective only against HIV-1 strains that use the CCR5 co-receptor for cell entry (CCR5-tropic).
Alternate Names
- International Nonproprietary Name (INN): Maraviroc.
- Brand Names: Selzentry, Celsentri.
How It Works
- Pharmacodynamics: Maraviroc prevents HIV-1 entry into CD4+ T-cells by allosterically blocking the CCR5 co-receptor. This inhibits the gp120 viral envelope protein from interacting with the co-receptor, preventing fusion and entry of the virus into the host cell.
- Pharmacokinetics:
- Absorption: Maraviroc is absorbed orally with a bioavailability of approximately 23% for the tablet and 33% for the oral solution. Food does not significantly affect absorption.
- Metabolism: Primarily metabolized in the liver, mainly by CYP3A4.
- Elimination: Excreted primarily in feces, with a smaller amount in urine. The half-life is approximately 14 hours.
- Mode of Action: Maraviroc binds allosterically to the CCR5 receptor, inducing a conformational change that prevents interaction with the viral gp120 protein.
- Receptor Binding: Specifically targets the CCR5 co-receptor on CD4+ T-cells.
- Elimination Pathways: Primarily hepatic metabolism (CYP3A4) followed by fecal excretion; a smaller amount is excreted in urine.
Dosage
Standard Dosage
Adults:
- The standard adult dose varies depending on concomitant medications due to drug interactions. It is usually 300 mg twice daily. Dose adjustments are needed depending on the co-administered antiretrovirals, especially CYP3A inhibitors and inducers.
Children:
- Children (2 years and older): Dosage is based on body weight and concomitant medications. Oral solution and tablet formulations are available. Dose adjustments are made based on weight and co-administered drugs, particularly CYP3A inhibitors and inducers.
Special Cases:
- Elderly Patients: No specific dose adjustments are recommended based on age alone, but consider renal and hepatic function.
- Patients with Renal Impairment: Contraindicated in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease (ESRD) when administered with potent CYP3A inhibitors or inducers. Dosage modifications are required for lesser degrees of impairment.
- Patients with Hepatic Dysfunction: No specific dose adjustments are recommended, but monitor closely for hepatotoxicity.
- Patients with Comorbid Conditions: Caution is advised for patients with cardiovascular disease.
Clinical Use Cases
Maraviroc is not indicated for use in clinical scenarios such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is specifically indicated for the treatment of CCR5-tropic HIV-1 infection in combination with other antiretrovirals.
Dosage Adjustments
Dose adjustments are needed based on drug interactions, especially involving CYP3A4 inhibitors and inducers, and renal function.
Side Effects
Common Side Effects
- Cough, fever, upper respiratory tract infections, rash, dizziness, diarrhea, abdominal pain, nausea, fatigue, headache.
Rare but Serious Side Effects
- Hepatotoxicity (including life-threatening liver failure), severe skin reactions, allergic reactions, cardiovascular events.
Long-Term Effects
- Increased risk of certain infections and malignancies associated with HIV infection itself, metabolic changes (e.g., dyslipidemia, insulin resistance).
Adverse Drug Reactions (ADR)
- Hepatotoxicity, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis.
Contraindications
- Hypersensitivity to maraviroc.
- Severe renal impairment (CrCl <30 mL/min) or ESRD in patients taking potent CYP3A4 inhibitors or inducers.
Drug Interactions
- CYP3A4 Inhibitors: Reduce maraviroc dose (e.g., protease inhibitors, azole antifungals, some macrolides).
- CYP3A4 Inducers: Increase maraviroc dose (e.g., rifampin, efavirenz, carbamazepine).
- Many other drug interactions exist; refer to a comprehensive drug interaction resource for detailed information.
- Interactions with food (e.g., grapefruit juice) and lifestyle factors (e.g., smoking) are not clinically significant.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Insufficient human data to establish safety; however, animal data do not indicate developmental toxicity. Maraviroc levels may be decreased during pregnancy.
- Breastfeeding: Maraviroc should not be used during breastfeeding due to the risk of infant exposure and potential HIV transmission through breast milk. Women with HIV should not breastfeed.
Drug Profile Summary
- Mechanism of Action: CCR5 antagonist, blocks HIV-1 entry into CD4+ cells.
- Side Effects: Cough, fever, rash, dizziness, hepatotoxicity, severe skin reactions.
- Contraindications: Hypersensitivity, severe renal impairment with CYP3A modulators.
- Drug Interactions: Numerous, especially with CYP3A4 inhibitors/inducers.
- Pregnancy & Breastfeeding: Insufficient data, not recommended.
- Dosage: Adult: 300 mg BID (adjusted based on drug interactions); Pediatric: weight-based.
- Monitoring Parameters: Liver function tests, HIV viral load, CD4+ cell count, renal function, signs of hypersensitivity reactions.
Popular Combinations
Maraviroc is combined with other antiretroviral agents based on individual patient characteristics, including resistance testing and potential drug interactions. No specific combinations are universally “popular.”
Precautions
- Assess for CCR5-tropism before starting therapy.
- Monitor liver function, renal function, and watch for signs of hypersensitivity reactions.
- Avoid in pregnancy and breastfeeding.
- Caution in patients with cardiovascular disease.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Maraviroc?
A: The adult dose is typically 300 mg twice daily but is adjusted based on concomitant medications. Pediatric dosing is weight-based.
Q2: How is Maraviroc administered?
A: Orally, as tablets or oral solution, with or without food.
Q3: What are the most serious side effects of Maraviroc?
A: Hepatotoxicity (liver damage), severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), allergic reactions.
Q4: Can Maraviroc cure HIV?
A: No, Maraviroc does not cure HIV. It helps to control viral replication but does not eradicate the virus.
Q5: Who should not take Maraviroc?
A: Patients with hypersensitivity to maraviroc and those with severe renal impairment or ESRD taking potent CYP3A inhibitors/inducers.
Q6: What are the key drug interactions with Maraviroc?
A: Many drugs interact, especially CYP3A4 inhibitors and inducers. Check a drug interaction resource for detailed information.
Q7: Can Maraviroc be used during pregnancy?
A: Insufficient data are available to determine safety in pregnancy. It is generally avoided unless the potential benefit outweighs the risk.
Q8: How does Maraviroc work differently from other HIV medications?
A: It specifically targets the CCR5 co-receptor, a unique mechanism compared to other antiretroviral drug classes.
Q9: Why is tropism testing necessary before starting Maraviroc?
A: Maraviroc is only effective against CCR5-tropic HIV-1. Tropism testing ensures the drug will be active against the patient’s viral strain.
Q10: What should be monitored in patients taking Maraviroc?
A: Liver function tests, HIV viral load, CD4+ cell count, renal function, and clinical signs of hypersensitivity.
