Doravirine ('''PIFELTRO'''), a non-nucleoside reverse transcriptase inhibitor ([[NNRTI]]) used together with other [[HIV-1]] medicines to treat [[Human Immunodeficiency Virus]]-1 (HIV-1) infection.
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[[File:Doravirine.svg|thumb|right|Chemical structure of Doravirine]]
'''Doravirine''' is a [[non-nucleoside reverse transcriptase inhibitor]] (NNRTI) used in the treatment of [[HIV/AIDS]]. It is marketed under the brand name '''Pifeltro''' and is used in combination with other antiretroviral agents for the treatment of [[HIV-1]] infection in adults. Doravirine is known for its efficacy in suppressing the viral load and its favorable side effect profile compared to other NNRTIs.
This medicine is used together with other [[HIV-1]] medicines to treat Human Immunodeficiency Virus-1 (HIV-1) infection in adults:
== Mechanism of Action ==
* who have not received HIV-1 medicines in the past, or
* to replace their current HIV-1 medicines for people whose healthcare provider determines that they meet certain requirements.
== '''How does this medicine work?''' ==
Doravirine works by inhibiting the activity of the [[reverse transcriptase]] enzyme, which is crucial for the replication of [[HIV]]. By binding to the reverse transcriptase enzyme, doravirine prevents the conversion of viral RNA into DNA, thereby blocking the replication of the virus within the host cell.
* Doravirine is an [[antiretroviral]] drug.
== Pharmacokinetics ==
* Doravirine is a '''pyridinone non-nucleoside reverse transcriptase inhibitor''' of HIV-1 and '''inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase (RT)'''.
* Doravirine '''does not inhibit the human cellular DNA polymerases α, β, and mitochondrial DNA polymerase γ'''.
== '''Who Should Not Use this medicine ?''' ==
Doravirine is administered orally and is well absorbed in the gastrointestinal tract. It has a half-life of approximately 15 hours, allowing for once-daily dosing. The drug is metabolized primarily by the [[cytochrome P450]] enzyme CYP3A4, and it is excreted in both urine and feces.
This medicine cannot be used in patients who use:
== Clinical Use ==
* the [[anticonvulsants]] [[carbamazepine]], [[oxcarbazepine]], [[phenobarbital]], [[phenytoin]]
* the [[androgen receptor]] inhibitor [[enzalutamide]]
* the antimycobacterials [[rifampin]], [[rifapentine]]
* the cytotoxic agent [[mitotane]]
* St. John's wort ([[Hypericum perforatum]])
Doravirine is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults who have no prior antiretroviral treatment history. It is also used in patients who are virologically suppressed on a stable antiretroviral regimen for at least six months.
== '''What drug interactions can this medicine cause?''' ==
== Side Effects ==
* Co-administration of PIFELTRO with a CYP3A inducer decreases doravirine plasma concentrations, which may reduce PIFELTRO efficacy.
Common side effects of doravirine include nausea, dizziness, headache, fatigue, and diarrhea. It is generally well-tolerated, and serious side effects are rare. Patients should be monitored for potential drug interactions, especially with other medications that are metabolized by CYP3A4.
* Co-administration of PIFELTRO is contraindicated with enzalutamide.
* Co-administration of PIFELTRO is contraindicated with Anticonvulsants carbamazepine,oxcarbazepine,phenobarbital,phenytoin.
* Co-administration of PIFELTRO is contraindicated with rifampin or rifapentine.
* Co-administration of PIFELTRO is contraindicated with mitotane.
* Co-administration of PIFELTRO is contraindicated with St. John's wort.
== '''Is this medicine FDA approved?''' ==
== Drug Interactions ==
* It was approved for use in the United States in 2018.
Doravirine can interact with other drugs that induce or inhibit CYP3A4. Caution should be exercised when co-administering doravirine with drugs such as [[rifampin]], [[carbamazepine]], and [[St. John's Wort]], as these can decrease the effectiveness of doravirine by increasing its metabolism.
== '''How should this medicine be used?''' ==
== Related Pages ==
'''Recommended Dosage '''
* [[HIV/AIDS]]
* The recommended dosage regimen of PIFELTRO in adults is '''one 100 mg tablet taken orally once daily''' with or without food.
* One tablet taken twice daily (approximately 12 hours apart).
[[Category:HIV/AIDS]]
'''Administration'''
* Take PIFELTRO every day exactly as your doctor tells you to take it.
* Take PIFELTRO 1 time each day, at about the same time every day.
* If you take the medicine rifabutin during treatment with PIFELTRO, take PIFELTRO 2 times each day, about 12 hours apart, as prescribed by your doctor. You may not have enough doravirine in your blood if you take rifabutin during treatment with PIFELTRO.
* Take PIFELTRO with or without food.
* Do not change your dose or stop taking PIFELTRO without talking to your doctor. Stay under a doctor's care when taking PIFELTRO.
* It is important that you do not miss or skip doses of PIFELTRO.
* If you miss a dose of PIFELTRO, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the next dose at your regular time. Do not take 2 doses of PIFELTRO at the same time.
* If you have any questions, call your doctor or pharmacist.
* When your PIFELTRO supply starts to run low, get more from your doctor or pharmacy. This is very important because the amount of virus in your blood may increase if the medicine is stopped for even a short time. The virus may develop resistance to PIFELTRO and become harder to treat.
== '''What are the dosage forms and brand names of this medicine?''' ==
This medicine is available in fallowing doasage form:
* '''As Tablets:''' 100 mg doravirine
This medicine is available in fallowing brand namesː
*'''PIFELTRO'''
=='''What side effects can this medication cause?'''==
The most common side effects of this medicine include:
* nausea
* dizziness
* headache
* tiredness
* diarrhea
* stomach (abdominal) pain
* abnormal dreams
PIFELTRO can cause serious side effects, including:
* Changes in your immune system (Immune Reconstitution Syndrome)
==''' What special precautions should I follow?''' ==
* [[Immune reconstitution syndrome]] has been reported in patients treated with combination antiretroviral therapy.
* [[Autoimmune disorder|Autoimmune disorders]] (such as [[Graves' disease]], [[polymyositis]], [[Guillain-Barré syndrome]], and [[autoimmune hepatitis]]) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable and can occur many months after initiation of treatment.
== '''What to do in case of emergency/overdose?''' ==
* {{overdose}}
== '''Can this medicine be used in pregnancy?''' ==
* No adequate human data are available to establish whether or not PIFELTRO poses a risk to pregnancy outcomes.
* There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to PIFELTRO during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.
=='''Can this medicine be used in children?'''==
* Safety and efficacy of PIFELTRO have not been established in pediatric patients less than 18 years of age.
== '''What are the active and inactive ingredients in this medicine?''' ==
* '''Active ingredient:''' doravirine.
* '''Inactive ingredients: '''colloidal silicon dioxide, croscarmellose sodium, hypromellose acetate succinate, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. The tablet film coating contains hypromellose, lactose monohydrate, titanium dioxide and triacetin. The coated tablets are polished with carnauba wax.
== '''Who manufactures and distributes this medicine?''' ==
* '''Manufactured for:''' Merck Sharp & Dohme Corp., a subsidiary of
* MERCK & CO., INC., Whitehouse Station, NJ 08889, USA
== '''What should I know about storage and disposal of this medication?''' ==
* Store PIFELTRO tablets at room temperature between 68°F to 77°F (20°C to 25°C).
* Keep PIFELTRO in the original bottle.
* Do not take the tablets out of the bottle to store in another container, such as a pill box.
* Keep the bottle tightly closed to protect PIFELTRO from moisture.
* The PIFELTRO bottle contains a desiccant to help keep your medicine dry (protect it from moisture). Keep the desiccant in the bottle. Do not eat the desiccant.
* Keep PIFELTRO and all medicines out of the reach of children.
Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of HIV/AIDS. It is marketed under the brand name Pifeltro and is used in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. Doravirine is known for its efficacy in suppressing the viral load and its favorable side effect profile compared to other NNRTIs.
Doravirine works by inhibiting the activity of the reverse transcriptase enzyme, which is crucial for the replication of HIV. By binding to the reverse transcriptase enzyme, doravirine prevents the conversion of viral RNA into DNA, thereby blocking the replication of the virus within the host cell.
Doravirine is administered orally and is well absorbed in the gastrointestinal tract. It has a half-life of approximately 15 hours, allowing for once-daily dosing. The drug is metabolized primarily by the cytochrome P450 enzyme CYP3A4, and it is excreted in both urine and feces.
Doravirine is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults who have no prior antiretroviral treatment history. It is also used in patients who are virologically suppressed on a stable antiretroviral regimen for at least six months.
Common side effects of doravirine include nausea, dizziness, headache, fatigue, and diarrhea. It is generally well-tolerated, and serious side effects are rare. Patients should be monitored for potential drug interactions, especially with other medications that are metabolized by CYP3A4.
Doravirine can interact with other drugs that induce or inhibit CYP3A4. Caution should be exercised when co-administering doravirine with drugs such as rifampin, carbamazepine, and St. John's Wort, as these can decrease the effectiveness of doravirine by increasing its metabolism.
