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Maraviroc

Medically reviewed by Drugs.com. Last updated on Mar 21, 2020.

Pronunciation

(mah RAV er rock)

Index Terms

  • UK-427,857

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Oral:

Selzentry: 20 mg/mL (230 mL) [contains sodium benzoate; strawberry flavor]

Tablet, Oral:

Selzentry: 25 mg, 75 mg, 150 mg, 300 mg [contains fd&c blue #2 aluminum lake, soybean lecithin]

Brand Names: U.S.

  • Selzentry

Pharmacologic Category

  • Antiretroviral, CCR5 Antagonist (Anti-HIV)

Pharmacology

Maraviroc, a CCR5 antagonist, selectively and reversibly binds to the chemokine (C-C motif receptor 5 [CCR5]) coreceptors located on human CD4 cells. CCR5 antagonism prevents interaction between the human CCR5 coreceptor and the gp120 subunit of the viral envelope glycoprotein, thereby inhibiting gp120 conformational change required for CCR5-tropic HIV-1 fusion with the CD4 cell and subsequent cell entry.

Distribution

Vd: ~194 L

Metabolism

Hepatic, via CYP3A to inactive metabolites

Excretion

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

Time to Peak

Plasma: 0.5 to 4 hours

Half-Life Elimination

14 to 18 hours

Protein Binding

~76%

Special Populations: Renal Function Impairment

In a single 300 mg dose study in patients with severe renal impairment (CrCl <30 mL/minute) and ESRD, Cmax and AUC were 2.4- and 3.2-fold higher, respectively, for patients with severe renal impairment, and 1.7- and 2-fold higher, respectively, for ESRD patients.

Use: Labeled Indications

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

Contraindications

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

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to maraviroc or any component of the formulation

Dosing: Adult

HIV-1 infection, treatment: Oral: 300 mg twice daily; 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 therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Pediatric

HIV-1 infection, treatment: Note: Only recommended for patients with CCR5-tropic HIV-1; prior to therapy, conduct tropism assay to exclude presence of CXCR4-tropic or mixed/dual tropic HIV (maraviroc should not be used). Gene mutation and antiretroviral resistance patterns should be evaluated (refer to https://www.iasusa.org/ for more information) when necessary.

Administration without potent CYP3A inhibitors or inducers:

Children ≥2 years and Adolescents:

Weight <30 kg: Not recommended.

Weight ≥30 kg: Oral: Tablets, oral solution: 300 mg twice daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Administration

Oral: Administer without regards to meals. Stable immunologic parameters and virologic suppression have been reported following administration of crushed tablets (Fulco 2019). However, an oral solution is commercially available.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Discard any unused oral solution 60 days after opening.

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600mg twice/day, but only in the absence of a concurrent strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Do not use in patients with CrCl less than 30 mL/min. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Maraviroc. Management: Reduce maraviroc to 150mg twice/day in adult and pediatric patients weighing 40kg or more. See full interaction monograph or maraviroc labeling for dose adjustments in pediatric patients less than 40kg. Do not use in patients with CrCl less than 30mL/min. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Delavirdine: May increase the serum concentration of Maraviroc. Monitor therapy

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Efavirenz: May decrease the serum concentration of Maraviroc. Of note, this effect only applies in the absence of a strong CYP3A4 inhibitor Management: Increase maraviroc adult dose to 600mg twice/day, but only in the absence of a concurrent strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Do not use in patients with CrCl less than 30 mL/min. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Etravirine: May decrease the serum concentration of Maraviroc. Of note, this effect only applies in the absence of a strong CYP3A4 inhibitor Management: Increase maraviroc adult dose to 600mg twice/day, but only in the absence of a concurrent strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Do not use in patients with CrCl less than 30 mL/min. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

St John's Wort: May decrease the serum concentration of Maraviroc. Avoid combination

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Adverse Reactions

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

>10%:

Dermatologic: Skin rash (11%)

Gastrointestinal: Vomiting (children and adolescents: 12%; may be more common with oral solution)

Infection: Infection (55%)

Respiratory: Upper respiratory tract infection (23% to 32%), cough (14%)

Miscellaneous: Fever (13%)

1% to 10%:

Cardiovascular: Hypertension (3%), cardiac failure (<2%), cerebrovascular accident (<2%), coronary artery disease (<2%), coronary occlusion (<2%), endocarditis (<2%), myocardial infarction (<2%), portal vein thrombosis (<2%), septic shock (<2%), unstable angina pectoris (<2%)

Central nervous system: Dizziness (9%; children and adolescents: 3%; including postural dizziness), insomnia (8%), paresthesia (≤5%), dysesthesia (≤5%), anxiety (4%), impaired consciousness (4%), depression (4%), peripheral neuropathy (4%), malaise (≤4%), pain (≤4%), sensory disturbance (3% to 4%; includes body temperature perception disorder), memory impairment (3%), epilepsy (<2%), loss of consciousness (<2%), meningitis (<2%; includes viral), facial paralysis (<2%), seizure (<2%)

Dermatologic: Nail disease (6%; nail and nail bed disorder [excluding infection and infestation]), sweat gland disease (5%; apocrine and eccrine gland disorders), folliculitis (4%), pruritus (4%), tinea (4%), acne vulgaris (3%), alopecia (2%), erythema (2%), condyloma acuminatum (2%)

Endocrine & metabolic: Lipodystrophy (3% to 4%)

Gastrointestinal: Abdominal distension (≤10%), bloating (≤10%), flatulence (≤10%), decreased gastrointestinal motility (9%), change in appetite (8%), constipation (6%; may be more common with oral solution), abdominal pain (children and adolescents: 4%; may be more common with oral solution), diarrhea (children and adolescents: 4%; may be more common with oral solution), nausea (children and adolescents: 4%; may be more common with oral solution), carcinoma in situ of esophagus (<2%), colitis (Clostridioides [formerly Clostridium] difficile-associated: <2%)

Genitourinary: Genitourinary complaint (urinary tract/bladder symptoms, 3% to 5%), ejaculatory disorder (≤3%), erectile dysfunction (≤3%)

Hematologic & oncologic: Anemia (8%), neutropenia (4% to 6%), benign skin neoplasm (3%), basal cell carcinoma (<2%), bone marrow depression (<2%), Bowen disease (<2%), carcinoma (nasopharyngeal: <2%), hypoplastic anemia (<2%), liver metastases (<2%), malignant lymphoma (including diffuse large B-cell and anaplastic large cell lymphomas T- and null-cell types), malignant neoplasm (anal: <2%), malignant neoplasm of bile duct (cholangiocarcinoma; <2%), malignant neoplasm of tongue (<2%; malignant stage unspecified), neoplasm (<2%; includes abdominal and unspecified malignant endocrine neoplasm), squamous cell carcinoma (<2%), squamous cell carcinoma of skin (<2%)

Hepatic: Increased serum AST (>5 x ULN: 5%), cholestatic jaundice (<2%), hepatic cirrhosis (<2%), hepatic failure (<2%), jaundice (<2%)

Infection: Herpes virus infection (7% to 8%), bacterial infection (6%), herpes zoster (≤5%), varicella zoster infection (≤5%), meningococcal infection (3%) viral infection (3%), influenza (2%), bacterial infection (treponema <2%)

Neuromuscular & skeletal: Arthropathy (6% to 7%), myalgia (3%), increased creatine phosphokinase (<2%), myositis (<2%; may be infective), osteonecrosis (<2%), rhabdomyolysis (<2%), tremor (<2%; excluding congenital)

Ophthalmic: Conjunctivitis (2%), eye disease (2%; includes infection and inflammation), hemianopia (<2%), visual field defect (<2%)

Otic: Otitis media (2%)

Respiratory: Bronchitis (7% to 13%), upper respiratory complaint (6% to 9%), sinusitis (7%), irregular breathing (4%), nasal congestion (≤4%), rhinitis (≤4%), lower respiratory tract infection (≤3%), pulmonary infection (≤3%), paranasal sinus disease (3%), pneumonia (<2%)

Frequency not defined:

Hepatic: Hepatitis, hepatotoxicity

Immunologic: Immune reconstitution syndrome

<1%, postmarketing, and/or case reports: DRESS syndrome, ischemic heart disease, Stevens-Johnson syndrome, toxic epidermal necrolysis

ALERT: U.S. Boxed Warning

Hepatotoxicity:

Hepatotoxicity has been reported with use of maraviroc. Severe rash or evidence of a systemic allergic reaction (eg, eosinophilia, elevated immunoglobulin E [IgE], fever) prior to the development of hepatotoxicity may occur. Patients with signs or symptoms of hepatitis or allergic reaction following use of maraviroc should be immediately evaluated.

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: May cause dizziness. If this occurs, patients should avoid driving or operating machinery.

• Hepatotoxicity: [US Boxed Warning]: Possible drug-induced hepatotoxicity with allergic type features has been reported; hepatotoxicity may be preceded by severe rash or other signs of systemic allergic reactions (eg, pruritic rash, eosinophilia, fever, increased IgE) and/or hepatic adverse events (transaminase increases or signs/symptoms of hepatitis); some cases have been life-threatening; immediately evaluate patients with signs and symptoms of allergic reaction or hepatitis (with or without allergy symptoms). Use with caution in patients with pre-existing hepatic dysfunction or coinfection with HBV and/or HCV, however symptoms have occurred in the absence of pre-existing hepatic conditions. Monitor hepatic function at baseline and as clinically indicated during treatment. Consider discontinuation in any patient with possible hepatitis or with elevated transaminases combined with systemic allergic events. Rechallenge with maraviroc is not recommended (HHS [pediatric] 2019).

• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.

• Infections: Monitor closely for signs/symptoms of developing infections; use associated with a small increase of certain upper respiratory tract infections and herpes virus infections during clinical trials.

• Malignancy: May affect immune surveillance and lead to an increased risk of malignancy due to pharmacologic mechanism of action. No increase in malignancy has been observed. Long term follow up needed to assess this risk.

• Postural hypotension: Symptomatic postural hypotension has occurred; use caution in patients at risk due to concomitant medication or history of condition. An increased risk of postural hypotension may occur in patients with severe renal insufficiency or in those with ESRD. Patients with severe renal dysfunction or ESRD who experience postural hypotension should have dose reduced.

• Skin and hypersensitivity reactions: Severe and life-threatening skin and hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis and drug rash with eosinophilia with systemic symptoms (DRESS), have been reported with use, predominately in patients also receiving concomitant agents associated with these reactions. Rash and constitutional findings (eg, fever, muscle aches, conjunctivitis, oral lesions), with or without organ dysfunction (including hepatic failure), have also accompanied these reports. Discontinue maraviroc and any other suspected agent immediately if symptoms or signs of hypersensitivity occur. Monitor liver function tests and clinical status as appropriate.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease, or in patients with a history of or current cardiac risk factors for postural hypotension, or receiving concomitant medication known to lower blood pressure. Patients who have cardiovascular comorbidities could be at risk for cardiac adverse events prompted by postural hypotension. During trials, a small increase in cardiovascular events (myocardial ischemia and/or infarction) occurred in treated patients compared to placebo, although a contributory relationship relative to therapy is unknown. Of note, patients experiencing events generally had cardiac disease/risk factors prior to therapy.

• Hepatic impairment: Use caution in patients with HBV and/or HCV coinfection or with mild-to-moderate hepatic impairment; maraviroc concentrations are increased. Maraviroc concentrations are further increased in patients with moderate hepatic impairment receiving concomitant potent CYP3A inhibitors; monitor closely for adverse events. Use in patients with severe hepatic impairment has not been studied.

• Renal impairment: Renal impairment may increase maraviroc concentrations. Use with caution in patients with mild-to-moderate renal impairment. An increased risk of postural hypotension may occur in patients with severe renal impairment or in those with ESRD. Patients with severe renal dysfunction or ESRD who experience postural hypotension should have dose reduced. Use in patients with severe renal impairment or ESRD who are receiving potent CYP3A inhibitors or inducers is contraindicated.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol and/or sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggest that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol and/or benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.

Other warnings/precautions:

• Appropriate use: Prior to therapy, coreceptor tropism testing should be performed for presence of CCR5-tropic only virus HIV-1 infection. Therapy not recommended for use in patients with CXCR4- or dual/mixed tropic HIV-1 infection; efficacy not demonstrated in this population. In studies with treatment-naive patients, virologic failure and emergent lamivudine resistance was more common in maraviroc-treated patients compared to patients receiving efavirenz.

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)

Reproductive Considerations

The Health and Human Services perinatal HIV guidelines do not recommend maraviroc (except in special circumstances) for females living with HIV who are not yet pregnant but are trying to conceive.

For males and females living with HIV and planning a pregnancy, maximum viral suppression below the limits of detection with antiretroviral therapy (ART), modification of therapy (if needed), optimization of the woman’s health, and a discussion of the potential risks and benefits of ART therapy during pregnancy is recommended prior to conception (HHS [perinatal] 2019).

Pregnancy Considerations

Maraviroc has moderate transfer across the human placenta.

Data collected by the antiretroviral pregnancy registry are insufficient to evaluate human teratogenic risk. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm delivery, stillbirth, low birth weight, and small for gestational age infants. Actual risks may be influenced by maternal factors, such as disease severity, gestational age at initiation of therapy, and specific ART regimen; therefore, close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children without HIV but who were exposed to ART in utero and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.

The Health and Human Services perinatal HIV guidelines do not recommend maraviroc for pregnant females living with HIV who are antiretroviral naive; maraviroc is not recommended (except in special circumstances) in pregnant females who have had ART therapy in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). Females who become pregnant while taking maraviroc may continue if viral suppression is effective and the regimen is well tolerated. Dose adjustments are not needed due to pregnancy.

In general, ART is recommended for all pregnant females living with HIV to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Monitoring of pregnant females is more frequent than in nonpregnant adults. ART should be continued postpartum for all females living with HIV and can be modified after delivery.

Health care providers are encouraged to enroll pregnant females exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com). Health care providers caring for pregnant females living with HIV and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2019).

Patient Education

What is this drug used for?

• It is used to treat HIV infection.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Constipation

• Diarrhea

• Common cold symptoms

• Heartburn

• Bloating

• Abdominal pain

• Passing gas

• Trouble sleeping

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Infection

• Severe dizziness

• Passing out

• Burning or numbness feeling

• Chest pain

• Unable to pass urine

• Change in amount of urine passed

• Joint pain

• Muscle pain

• Severe loss of strength and energy

• Swollen glands

• Depression

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.