Delavirdine (Rescriptor) is an NNRT (non-nucleoside reverse transcriptase) inhibitor that is used in combination with other antiretroviral drugs for the treatment of HIV infection.
Delavirdine Uses:
- Used in the treatment of HIV-1 infection combined with at least two additional antiretroviral agents
Delavirdine (Rescriptor) Dose in Adults:
Delavirdine (Rescriptor) Dose in the treatment of HIV-1 infection (part of a combination therapy):
- Oral: 400 mg three times a day.
Delavirdine (Rescriptor) Dose in Children:
Refer to adults dosing.
Pregnancy Risk Category: C
- Although the risk of preterm birth may increase with antiretroviral treatment (ART), there are conflicting information.
- This is due to the variability in maternal factors such as disease severity and gestational age at therapy's start.
- Some studies have found an increase in stillbirths, low birth weights, and infants of small gestational age, but not all.
- Because of the obvious benefits, maternal ART should never be withheld.
- All infants who have been exposed to antiretroviral medication should be referred for long-term monitoring.
- Children with mitochondrial dysfunction or other organ system abnormalities should be evaluated, especially the heart and CNS.
- NNRTI therapy is more common for women who have hypersensitivity reactions, including hepatic toxicities and rash.
- Information regarding pregnancy risk is not available.
- Health and Human Services (HHS), Perinatal HIV Guidelines, have not made any recommendations regarding the use delavirdine during pregnancy.
- Females who are pregnant with delavirdine should switch to a recommended regimen.
- All pregnant women with HIV should be treated to prevent the virus from reaching the limit of detection.
- This will reduce the chance of perinatal transmission. Females who are pregnant with HIV are monitored more often than those who have not.
- HIV-positive women should continue ART after giving birth. The therapy may need to be modified after delivery.
- Health care providers should be encouraged to enroll pregnant females exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-2584263 or http://www.APRegistry.com).
- The National Perinatal HIV Hotline (888-448-8765) offers a clinical consultation for health care professionals who are dealing with HIV-infected women and infants.
Use during breastfeeding:
- It is not known if Delavirdine is present in breast milk.
- Postnatal HIV transmission can still be prevented by using maternal or infant antiretroviral treatment.
- A multiclass-resistant virus was also detected in breastfed infants despite the mother's use of ART.
- To reduce the risk of HIV transmission, avoid breastfeeding in US where the formula is affordable, accessible, safe, and durable.
Dose in Kidney Disease:
Dosage adjustments have not been provided in the manufacturer’s labeling (has not been studied). As per guidelines, dosage adjustment is not necessary for renal impairment.
Dose in Liver disease:
Dosage adjustments have not been provided in the manufacturer’s labeling (has not been studied). However, use cautiously as delavirdine primarily undergoes hepatic metabolism.
Side effects of Delavirdine (Rescriptor):
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
- Depression
- Anxiety
- Cognitive Dysfunction
- Confusion
- Emotional Lability
- Hallucination
- Paralysis
- Vertigo
- Dermatologic:
- Skin Rash
- Desquamation
- Erythema Multiforme
- Fungal Dermatitis
- Stevens-Johnson Syndrome
- Endocrine & Metabolic:
- Increased Serum Transaminases
- Increased Amylase
- Increased Serum Bilirubin
- Hyperglycemia
- Hyperkalemia
- Hypertriglyceridemia
- Hyperuricemia
- Hypocalcemia
- Hyponatremia
- Hypophosphatemia
- Increased Gamma-Glutamyl Transferase
- Menstrual Disease
- Redistribution Of Body Fat
- Gastrointestinal:
- Nausea
- Vomiting
- Abdominal Pain
- 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
- Prolonged Prothrombin Time
- Adenopathy
- Bruise
- Eosinophilia
- Granulocytosis
- Leukopenia
- Pancytopenia
- Purpura
- Spleen Disease
- Thrombocytopenia
- Hepatic:
- Hepatomegaly
- Increased Serum Alkaline Phosphatase
- Jaundice
- Hypersensitivity:
- Angioedema
- Hypersensitivity Reaction
- Infection:
- Abscess
- Candidiasis
- Infection
- Neuromuscular & Skeletal:
- Ostealgia
- Tetany
- Ophthalmic:
- Conjunctivitis
- Renal:
- Increased Serum Creatinine
- Nephrolithiasis
- Renal Pain
- Respiratory:
- Bronchitis
- Chest Congestion
- Dyspnea
- Pneumonia
- Miscellaneous:
- Fever
Contraindication to Delavirdine (Rescriptor):
- Hypersensitivity (to delavirdine or any component of the formulation)
- Concomitant use of the following drugs:
- alprazolam
- astemizole
- cisapride
- ergot alkaloids
- midazolam
- pimozide
- rifampin
- terfenadine
- triazolam
Warnings and Precautions
- Fat redistribution
- Redistribution may occur (e.g., buffalo hump; peripheral wasting with an increased abdominal girth; cushingoid appearance).
- Immune reconstitution syndrome:
- An immune reconstitution syndrome is an inflammation response to an indolent, residual opportunistic HIV infection.
- This may also occur later in treatment. It may be necessary for further evaluation.
- Rash:
- It is common for rash to occur, which can lead to therapy being stopped.
- This usually happens within 1-3 weeks. The effect lasts approximately 2 weeks. Most patients can resume therapy after a brief interruption of treatment.
- Hepatic impairment
- Be careful.
- HIV:
- Use it in a proper way: This should not be used alone or as part of an initial antiretroviral treatment regimen, as resistance is rapidly emerging. Cross-resistance to NNRTI (non nucleoside reverse transcriptase inhibitors) may occur, but there is low risk of cross-resistance with protease inhibitions.
- Renal impairment
- Be careful.
Delavirdine: Drug Interactions
Note: Drug Interaction Categories:
- Risk Factor C: Monitor When Using Combination
- Risk Factor D: Consider Treatment Modification
- Risk Factor X: Avoid Concomitant Use
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Risk Factor C (Monitor therapy). |
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The serum concentrations of ARIPiprazole and CYP3A4 (Weak) can be increased by inhibiting CYP3A4 (Weak). Management: Increased aripiprazole pharmacologic effect should be monitored. Aripiprazole dose adjustment may be necessary depending on the indication and concomitant therapy. |
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High risk of Inducers may cause a decrease in serum concentrations of CYP3A4 substrates. |
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Moderate CYP3A4 Inducers |
High risk of Inducers may cause a decrease in serum concentrations of CYP3A4 substrates. |
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High risk of Inducers may cause a decrease in serum concentrations of CYP3A4 substrates. |
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Dofetilide is increased by the inhibition of CYP3A4 |
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High risk of Inducers may cause a decrease in serum concentrations of CYP3A4 substrates. |
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Flibanserin |
Flibanserin serum concentration increased by inhibition of CYP3A4 |
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High risk of Inducers may cause a decrease in serum concentrations of CYP3A4 substrates. |
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Maraviroc serum concentration may be increased |
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Increases the serum NiMODipine concentration by inhibiting CYP3A4 ("Weak") |
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Orlistat |
It is possible for the serum concentration of Antiretroviral agents to be reduced. |
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Sarilumab |
High risk of Inducers may cause a decrease in serum concentrations of CYP3A4 substrates. |
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High risk of Inducers may cause a decrease in serum concentrations of CYP3A4 substrates. |
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High risk of Inducers may cause a decrease in serum concentrations of CYP3A4 substrates. |
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Risk Factor D (Consider therapy modifications) |
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Antacids |
It is possible for the serum concentration of Delavirdine to be reduced. Management: Delavirdine and anti-acids should not be taken together for more than an hour. This combination should be monitored for any decrease in delavirdine therapeutic effect. |
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Strong CYP3A4 Inducers |
High risk of Inducers may cause an increase in metabolism of CYP3A4 substrates. Management: A substitute should be considered when one of the interacting drugs is not available. Some combinations may have a contraindication. See appropriate manufacturer labeling. |
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Dabrafenib |
It is possible to decrease serum levels of CYP3A4 Substrates High Risk with Inducers. Management: It is important to seek alternatives to the CYP3A4 substrat. In cases where concomitant therapy is impossible, closely monitor the clinical effects of any substrate. |
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It is possible to decrease serum concentrations of CYP3A4 substrates (high risk with inducers). Management: It is important to avoid concurrent use of enzalutamide and CYP3A4 Substrates with a narrow therapeutic index. Take care when using enzalutamide or any other CYP3A4 sub-substance. |
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Lomitapide |
Increases serum Lomitapide concentration by inhibiting CYP3A4 ("Weak") Management: Patients taking lomitapide 5mg per 24 hours can continue to take the dose, but patients who are taking lomitapide 10mg per 24 hours or more should reduce their dose by half. Dosage of titrate should not exceed 30 mg per day for adults. |
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Lorlatinib |
It is possible to decrease the serum concentrations of CYP3A4 substrates (High Risk with Inducers). Management: It is important to avoid concurrent use of lorlatinib and any CYP3A4 Substrates. This can lead to therapeutic failure or serious clinical consequences. |
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Low serum concentrations of CYP3A4 Substrates may be reduced. Treatment: Patients receiving mitotane may require substantial adjustments to the dosage of CYP3A4 Substrates. |
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It is possible to decrease serum concentrations of CYP3A4 substrates (High Risk with Inducers). Management: Do not combine pitolisant and a CYP3A4 substrat with a low therapeutic index. Pay attention to the use of pitolisant with other CYP3A4 substrats. |
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Inhibitors of Protease |
The serum concentrations of Protease Inhibitors and Delavirdine could be reduced or increased. |
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Risk Factor X (Avoid Combination) |
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Astemizole |
Astemizole's arrhythmogenic effects may be increased. It is possible to increase the serum Astemizole concentration. |
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It is possible for the serum concentration of Delavirdine to be reduced. |
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Reverse Transcriptase inhibitors (Non Nucleoside) may increase the serum concentration of Efavirenz. Reverse Transcriptase inhibitors (Non Nucleoside) may decrease the serum concentration of Efavirenz. |
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Reverse Transcriptase inhibitors (Non Nucleoside) may increase the serum Ergonovine concentration. This would be more common with delavirdine. However, it is less likely to occur with non-Nucleoside Reverse Transcriptase Inhibitors. |
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Reverse Transcriptase inhibitors (Non Nucleoside) may decrease the serum level of Etravirine. This was observed with NNRTIs nevirapine and efavirenz. Reverse Transcriptase inhibitors (Non-Nucleoside) may increase the serum level of Etravirine. This was observed with delavirdine. |
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It is possible that the serum level of Delavirdine could be reduced. This is most likely due to the active metabolite amprenavir. Delavirdine may increase the serum concentrations of Fosamprenavir. Delavirdine, in particular, causes an increase in the active metabolite amprenavir. |
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It is possible for the serum concentration of Delavirdine to be reduced. Delavirdine may increase the serum concentration of Fosphenytoin. |
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Histamine H2 Receptor Antagonists |
It is possible for the serum concentration of Delavirdine to be lower. Patients receiving delavirdine should not be given chronic H2-antagonist therapy. Although the clinical significance of delavirdine-based H2-antagonist therapy for short periods is unknown, caution should be exercised. |
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It is possible that the serum concentration of Delavirdine could be reduced. The serum concentration of Phenytoin may be increased by Delavirdine. |
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Increases the serum level of Pimozide by inhibiting CYP3A4 |
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Inhibitors of the proton pump |
It is possible for the serum concentration of Delavirdine to be lower. Treatment: Patients treated with Delavirdine should not be given prolonged proton pump inhibitors. Although the clinical significance of PPI therapy with Delavirdine for short-term is unknown, caution should be exercised when using such therapy. |
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Rifamycin Derivatives |
It is possible to increase the metabolism of Delavirdine. Delavirdine may increase the serum concentration of Rifamycin Derivatives. This will affect Rifabutin's serum concentration. |
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Reverse Transcriptase inhibitors (Non Nucleoside) may increase the serum Rilpivirine concentration. This mechanism can be used to co-administration delavirdine. Reverse Transcriptase inhibitors (Non Nucleoside) may decrease the serum Rilpivirine concentration. This is possible when nevirapine, etravirine and efavirenz are co-administered. |
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Delavirdine may increase the serum Simeprevir concentration. |
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St John's Wort |
It is possible to decrease the serum concentration of Reverse Transcriptase Inhibitors NonNucleoside. St. John's Wort may increase the metabolism of Reverse Transcriptase Inhibitors Non-Nucleoside. |
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Terfenadine |
Terfenadine's arrhythmogenic effects may be enhanced by Delavirdine. Delavirdine can increase Terfenadine's serum concentration. |
Monitoring parameters:
- Liver function tests (if given with saquinavir)
How to administer Delavirdine (Rescriptor)?
- The drug should be given with an acidic beverage in patients with achlorhydria; separate antacids and delavirdine by 1 hour.
- May prepare a dispersion of delavirdine by adding 4 tablets 100 mg each to at least 3 oz of water.
- It should be allowed to stand for a few minutes and stirred until uniform dispersion. Should be drunk immediately.
- The glass and the moth should be rinsed then the rinse should be swallowed to ensure that the total dose is administered. Tale the 200 mg tablets in intact form.
Mechanism of action of Delavirdine (Rescriptor):
Delavirdine binds directly to reverse transcriptase, causing blockade in the RNA-dependent or DNA-dependent DNA polymerase activities
Absorption:
- Rapidly absorbable
Distribution:
- Saliva and Semen (in low concentration); CSF 0.4% concurrent Plasma concentration
Protein binding:
- Highly bound to proteins (98%, mainly albumin).
Metabolism
- CYP3A4 & 2D6 are found in the liver. (Note: This may cause a decrease in CYP3A activity or inhibit its own metabolism.
Bioavailability
- Tablet: 85% when taken in tablet form, and almost 100% when taken as an oral slurry
Half-life elimination:
- 5.8 Hours (range: 2-11hrs)
Plasma peak time:
- 60 minutes
Excretion:
- 51% through urine (less that 5% as an unchanged drug)
- 44 % via feces
International Brand Names of Delavirdine:
- Rescriptor
Delavirdine Brand Names in Pakistan:
No Brands available in Pakistan.
