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Delavirdine

Pronunciation

(de la VIR deen)

Index Terms

  • DLV
  • U-90152S

Dosage Forms

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

Tablet, Oral, as mesylate:

Rescriptor: 100 mg, 200 mg

Brand Names: U.S.

  • Rescriptor

Pharmacologic Category

  • Antiretroviral, Reverse Transcriptase Inhibitor, Non-nucleoside (Anti-HIV)

Pharmacology

Delavirdine binds directly to reverse transcriptase, blocking RNA-dependent and DNA-dependent DNA polymerase activities

Absorption

Rapid

Distribution

Low concentration in saliva and semen; CSF 0.4% concurrent plasma concentration

Metabolism

Hepatic via CYP3A4 and 2D6 (Note: May reduce CYP3A activity and inhibit its own metabolism.)

Excretion

Urine (51%, <5% as unchanged drug); feces (44%); nonlinear kinetics exhibited

Time to Peak

Plasma: 1 hour

Half-Life Elimination

5.8 hours (range: 2-11 hours)

Protein Binding

~98%, primarily to albumin

Use: Labeled Indications

Treatment of HIV-1 infection in combination with at least two additional antiretroviral agents

Contraindications

Hypersensitivity to delavirdine or any component of the formulation; concurrent use of alprazolam, astemizole, cisapride, ergot alkaloids, midazolam, pimozide, rifampin, terfenadine, or triazolam

Dosing: Adult

HIV-1 infection (part of combination): Oral: 400 mg 3 times/day

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

HIV-1 infection (part of combination): Adolescents ≥16 years: Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer’s labeling (has not been studied). Guidelines state that no dosage adjustment is necessary in renal impairment (HHS [adult] 2015).

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling (has not been studied). However, delavirdine is primarily metabolized by the liver, use with caution.

Extemporaneously Prepared

A dispersion of delavirdine may be made with tablets. Add four 100 mg tablets to at least 3 oz of water; allow to stand for a few minutes and stir until uniform dispersion. Administer immediately. To ensure full dose is administered, rinse glass and drink liquid; also rinse mouth and swallow following ingestion.

Administration

Patients with achlorhydria should take the drug with an acidic beverage; antacids and delavirdine should be separated by 1 hour. A dispersion of delavirdine may be prepared by adding four 100 mg tablets to at least 3 oz of water. Allow to stand for a few minutes and stir until uniform dispersion. Drink immediately. Rinse glass and mouth, then swallow the rinse to ensure total dose administered. The 200 mg tablets should be taken intact.

Dietary Considerations

May be taken without regard to meals.

Storage

Store at 20°C to 25°C (68°F to 77°F). Protect from humidity.

Drug Interactions

Alitretinoin (Systemic): CYP2C9 Inhibitors (Strong) may increase the serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with strong CYP2C9 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a strong CYP2C9 inhibitor. Consider therapy modification

Antacids: May decrease the serum concentration of Delavirdine. Management: Separate doses of delavirdine and antacids by at least 1 hour. Monitor for decreased delavirdine therapeutic effects with this combination. Consider therapy modification

ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

Astemizole: Delavirdine may enhance the arrhythmogenic effect of Astemizole. Delavirdine may increase the serum concentration of Astemizole. Avoid combination

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Bosentan: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy

Cannabis: May increase the serum concentration of CYP2C9 Inhibitors (Strong). More specifically, tetrahydrocannabinol serum concentrations may be increased. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Delavirdine. Avoid combination

Carvedilol: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Monitor therapy

Cilostazol: CYP2C19 Inhibitors may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in patients who are also receiving inhibitors of CYP2C19. Consider therapy modification

Citalopram: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with a strong CYP2C19 inhibitor. Patients using this combination should be monitored closely for evidence of citalopram toxicity (e.g., serotonin syndrome, QT prolongation, etc.). Consider therapy modification

Clopidogrel: CYP2C19 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to a risk for impaired clopidogrel effectiveness with such a combination, carefully consider the need for a strong CYP2C19 inhibitor in patients receiving clopidogrel. Monitor patients closely for evidence of a diminished response to clopidogrel. Consider therapy modification

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Monitor therapy

CYP2C19 Substrates: CYP2C19 Inhibitors (Strong) may decrease the metabolism of CYP2C19 Substrates. Consider therapy modification

CYP2C9 Substrates: CYP2C9 Inhibitors (Strong) may decrease the metabolism of CYP2C9 Substrates. Consider therapy modification

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

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. 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. Monitor therapy

Diclofenac (Systemic): CYP2C9 Inhibitors (Strong) may increase the serum concentration of Diclofenac (Systemic). Management: Consider using a lower dose of diclofenac when used together with a strong CYP2C9 inhibitor. Arthrotec (diclofenac and misoprostol) labeling specifically recommends limiting the total daily dose to a maximum of 50 mg twice/day. Consider therapy modification

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy

Dronabinol: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Dronabinol. Monitor therapy

Efavirenz: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Efavirenz. Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Efavirenz. Avoid combination

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. 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

Ergonovine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Ergonovine. Specifically, this would be most likely with delavrdine, while other Non-Nucleoside Reverse Transcriptase Inhibitors may be more likely to decrease the concentration of Ergonovine. Avoid combination

Etravirine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Etravirine. This has been observed with the NNRTIs efavirenz and nevirapine. Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Etravirine. This has been observed with delavirdine. Avoid combination

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

Flibanserin: CYP2C19 Inhibitors (Strong) may increase the serum concentration of Flibanserin. Monitor therapy

Fosamprenavir: May decrease the serum concentration of Delavirdine. The active metabolite amprenavir is likely responsible for this effect. Delavirdine may increase the serum concentration of Fosamprenavir. Specifically, delavirdine may increase concentrations of the active metabolite amprenavir. Avoid combination

Fosphenytoin: May decrease the serum concentration of Delavirdine. Delavirdine may increase the serum concentration of Fosphenytoin. Avoid combination

H2-Antagonists: May decrease the serum concentration of Delavirdine. Management: Chronic therapy with H2-antagonists should be avoided in patients who are being treated with delavirdine. The clinical significance of short-term H2-antagonist therapy with delavirdine is uncertain, but such therapy should be undertaken with caution. Avoid combination

HYDROcodone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of HYDROcodone. Monitor therapy

Lacosamide: Delavirdine may increase the serum concentration of Lacosamide. Management: Lacosamide prescribing information cautions that a lacosamide dose reduction may be warranted in patients with renal dysfunction or mild-moderate hepatic impairment who are also using a strong inhibitor of CYP2C9 and CYP3A4, such as delavirdine. Consider therapy modification

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification

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

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy

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

Ospemifene: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Ospemifene. Monitor therapy

Parecoxib: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Parecoxib. Monitor therapy

Phenytoin: May decrease the serum concentration of Delavirdine. Delavirdine may increase the serum concentration of Phenytoin. Avoid combination

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination

Protease Inhibitors: May decrease the serum concentration of Delavirdine. Delavirdine may increase the serum concentration of Protease Inhibitors. Consider therapy modification

Proton Pump Inhibitors: May decrease the serum concentration of Delavirdine. Management: Chronic therapy with proton pump inhibitors (PPIs) should be avoided in patients treated with delavirdine. The clinical significance of short-term PPI therapy with delavirdine is uncertain, but such therapy should be undertaken with caution. Avoid combination

Ramelteon: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Ramelteon. Monitor therapy

Rifamycin Derivatives: May increase the metabolism of Delavirdine. Delavirdine may increase the serum concentration of Rifamycin Derivatives. Specifically, Rifabutin serum concentration may be increased. Avoid combination

Rilpivirine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Rilpivirine. This mechanism applies to coadministration of delavirdine. Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Rilpivirine. This mechanism applies to coadministration of efavirenz, etravirine, and nevirapine. Avoid combination

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: Delavirdine may increase the serum concentration of Simeprevir. Avoid combination

St John's Wort: May decrease the serum concentration of Reverse Transcriptase Inhibitors (Non-Nucleoside). Specifically, St. Johns Wort may increase the metabolism of Reverse Transcriptase Inhibitors (Non-Nucleoside). Avoid combination

Terfenadine: Delavirdine may enhance the arrhythmogenic effect of Terfenadine. Delavirdine may increase the serum concentration of Terfenadine. Avoid combination

Tetrahydrocannabinol: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Adverse Reactions

Frequency not always defined. Frequency of adverse reactions reported from occurrence in clinical trials with delavirdine when used as part of combination antiretroviral therapy.

Cardiovascular: Cardiac arrhythmia, cardiac insufficiency, cardiac rate disturbance, cardiomyopathy, hypersensitivity angiitis, hypertension, orthostatic hypotension, peripheral vascular disease

Central nervous system: Headache (19% to 20%), depression (10% to 15%), anxiety (6% to 8%), cognitive dysfunction, confusion, emotional lability, hallucination, paralysis, vertigo

Dermatologic: Skin rash (16% to 32%), desquamation, erythema multiforme, fungal dermatitis, Stevens-Johnson syndrome

Endocrine & metabolic: Increased serum transaminases (2% to 5%), increased amylase (3%), increased serum bilirubin (2%), hyperglycemia, hyperkalemia, hypertriglyceridemia, hyperuricemia, hypocalcemia, hyponatremia, hypophosphatemia, increased gamma-glutamyl transferase, menstrual disease, redistribution of body fat

Gastrointestinal: Nausea (20% to 25%), vomiting (3% to 11%), abdominal pain (4% to 6%), anorexia, bloody stools, colitis, diarrhea, diverticulitis, fecal incontinence, gastroenteritis, gastrointestinal hemorrhage, gingival hemorrhage, increased serum lipase, pancreatitis, vomiting

Genitourinary: Hematuria, urinary tract infection

Hematologic & oncologic: Decreased hemoglobin (1% to 3%), prolonged prothrombin time (2%), adenopathy, bruise, eosinophilia, granulocytosis, leukopenia, pancytopenia, purpura, spleen disease, thrombocytopenia

Hepatic: Hepatomegaly, increased serum alkaline phosphatase, jaundice

Hypersensitivity: Angioedema, hypersensitivity reaction

Infection: Abscess, candidiasis (oral/vaginal), infection

Neuromuscular & skeletal: Ostealgia, tetany

Ophthalmic: Conjunctivitis

Renal: Increased serum creatinine, nephrolithiasis, renal pain

Respiratory: Bronchitis (6% to 8%), chest congestion, dyspnea, pneumonia

Miscellaneous: Fever (4% to 12%)

<1% (Limited to important or life-threatening): Acute renal failure, hemolytic anemia, hepatic failure, immune reconstitution syndrome, rhabdomyolysis

Warnings/Precautions

Concerns related to adverse effects:

• Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).

• 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.

• Rash: Occurs frequently, may require discontinuation of therapy; usually occurs within 1-3 weeks and lasts <2 weeks. Most patients may resume therapy following a treatment interruption.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• HIV: Appropriate use: Due to rapid emergence of resistance, delavirdine should not be used as monotherapy or as a component of an initial antiretroviral regimen; cross-resistance may be conferred to other non-nucleoside reverse transcriptase inhibitors, although potential for cross-resistance with protease inhibitors is low.

• Renal impairment: Use with caution in patients with renal impairment.

Concurrent drug therapy issues:

• High potential for interactions: Use with caution in patients taking strong CYP3A4 inhibitors, moderate or strong CYP3A4 inducers and major CYP3A4 substrates (see Drug Interactions); consider alternative agents that avoid or lessen the potential for CYP-mediated interactions.

Special populations:

• Pediatric: Safety and efficacy have not been established in children.

Other warnings/precautions:

• Long-term effects: The long-term effects of delavirdine are not known.

Monitoring Parameters

Liver function tests if administered with saquinavir

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies. Hypersensitivity reactions (including hepatic toxicity and rash) are more common in women on NNRTI therapy; it is not known if pregnancy increases this risk.

Combination antiretroviral therapy (cART) therapy is recommended for all HIV-infected pregnant women. The goal of therapy is to keep the viral load below the limit of detection and prevent perinatal transmission. Therapy must be individualized. In general, women who become pregnant on a stable cART regimen may continue that regimen if viral suppression is effective, contraindications for use in pregnancy are not present, and the regimen is well tolerated. For HIV infected couples planning a pregnancy, maximum viral suppression with cART is recommended prior to conception for the HIV-infected partner(s). When HIV is diagnosed during pregnancy in a woman who has never received antiretroviral therapy, cART should be considered as soon as possible after diagnosis to reduce the risk of perinatal transmission. If antiretroviral drug-resistance testing is done, treatment may be started prior to obtaining results, then adjusted accordingly. Monitoring during pregnancy is more frequent than in non-pregnant adults. If cART must be interrupted for <24 hours, stop then restart all medications simultaneously in order to decrease the chance of developing resistance. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children who develop significant organ system abnormalities (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.

HIV infected women not planning a pregnancy may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. In addition, consistent use of condoms is also recommended (even during pregnancy) to prevent transmission of HIV or other sexually transmitted diseases.

Health care providers are encouraged to enroll pregnant women exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Health care providers caring for HIV-infected women and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2016).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea or vomiting. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), burning or numbness feeling, urinary retention, change in amount of urine passed, confusion, change in balance, abnormal heartbeat, hallucinations, memory impairment, mood changes, severe dizziness, passing out, severe headache, shortness of breath, excessive weight gain, swelling of arms or legs, pale skin, bruising, bleeding, severe loss of strength and energy, vision changes, eye pain, severe eye irritation, change in body fat, severe diarrhea; black, tarry, or bloody stools; involuntary eye movements; or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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