Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral, as mesylate:
Rescriptor: 100 mg [DSC], 200 mg
Pharmacology
Mechanism of Action
Delavirdine binds directly to reverse transcriptase, blocking RNA-dependent and DNA-dependent DNA polymerase activities
Pharmacokinetics/Pharmacodynamics
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 to 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
Dosage and Administration
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.
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
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 (High risk with Inducers). Monitor therapy
CarBAMazepine: May decrease the serum concentration of Delavirdine. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). 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 (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
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. 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 (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
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
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
Histamine H2 Receptor 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
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. 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
Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification
Maraviroc: Delavirdine may increase the serum concentration of Maraviroc. Monitor therapy
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
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy
Orlistat: May decrease the serum concentration of Antiretroviral Agents. 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
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
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: 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
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant weak CYP3A4 inhibitors. Consider therapy modification
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (if needed) of ubrogepant should be limited to 50 mg. Consider therapy modification
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%, postmarketing and/or case reports: 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
Pregnancy Considerations
Outcome information specific to delavirdine use in pregnancy is no longer being reviewed and updated in the Health and Humans Services (HHS) perinatal guidelines. 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. Hypersensitivity reactions (including hepatic toxicity and rash) are more common in women on non-nucleoside reverse transcriptase inhibitor therapy; it is not known if pregnancy increases this risk.
Based on the HHS perinatal HIV guidelines, delavirdine is not one of the recommended antiretroviral agents for use during 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 (888-448-8765) for clinical consultation (HHS [perinatal] 2019).
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 yellow skin), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), burning or numbness feeling, unable to pass urine, change in amount of urine passed, confusion, change in balance, abnormal heartbeat, sensing things that seem real but are not, trouble with memory, 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; vomiting blood; involuntary eye movements; muscle pain; joint pain; 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.
