Side Effects of ritonavir: A Synthesis of Findings from 21 Studies

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Original Abstract of the Article

Major Research Findings

Ritonavir is a protease inhibitor widely used in HIV treatment and has recently gained attention as a COVID-19 treatment. Ritonavir enhances drug efficacy by inhibiting an enzyme called CYP3A, which slows down drug metabolism in the body. However, CYP3A is involved in the metabolism of various drugs, so there is a potential for side effects due to interactions with ritonavir. 19

This study summarizes the side effects of ritonavir-based therapy based on data from multiple papers.

Reasons for Side Effects

Ritonavir inhibits CYP3A, which can slow down the metabolism of other drugs, potentially raising their blood concentrations. This can lead to side effects due to interactions with other medications. 19

Common Side Effects

Gastrointestinal Side Effects

Ritonavir is known to cause gastrointestinal side effects. This is because ritonavir inhibits CYP3A in the gastrointestinal tract, affecting digestive function. Reported gastrointestinal side effects include nausea, vomiting, and diarrhea. 3

Neurological Side Effects

Ritonavir can cause neurological side effects. This is because ritonavir inhibits CYP3A in the nervous system, impacting nervous system function. Reported neurological side effects include headaches, dizziness, and drowsiness. 7

Metabolic Disorders

Ritonavir can cause metabolic disorders. This is because ritonavir inhibits CYP3A in the liver, affecting lipid metabolism. Reported metabolic disorders include high cholesterol, high triglycerides, and others. 6

Skin Reactions

Ritonavir can cause skin reactions. This is because ritonavir inhibits CYP3A in the skin, affecting skin function. Reported skin reactions include rash, itching, and eczema. 17

Kidney Dysfunction

Ritonavir can cause kidney dysfunction. This is because ritonavir inhibits CYP3A in the kidneys, affecting kidney function. Reported kidney dysfunction includes kidney failure.

Other

In addition to the above, ritonavir can cause various side effects. Therefore, it is essential to follow your doctor's instructions carefully when taking ritonavir. 10

Side Effect Management

Gastrointestinal Side Effects

Taking ritonavir with meals or in small doses is recommended to reduce gastrointestinal side effects. If you experience severe nausea or vomiting, consult your doctor. 3

Neurological Side Effects

Avoid driving or hazardous activities when taking ritonavir to reduce neurological side effects. If you experience severe headaches or dizziness, consult your doctor. 7

Metabolic Disorders

Dietary and exercise therapy are essential for preventing metabolic disorders. Regular blood tests are recommended to check your cholesterol and triglyceride levels. 6

Skin Reactions

Consult your doctor if you experience skin reactions. Proper treatment can help alleviate the symptoms. 17

Kidney Dysfunction

Regular blood tests are recommended to check your kidney function to prevent kidney dysfunction. Ensure adequate hydration when taking ritonavir.

Comparison Between Studies

Similarities in Studies

Multiple studies have shown that ritonavir can cause a range of side effects. In particular, gastrointestinal side effects, neurological side effects, and metabolic disorders have been reported.

Differences in Studies

The types and frequencies of side effects caused by ritonavir vary between studies. This is likely due to differences in study participants and ritonavir administration methods.

Points to Note for Application in Real Life

Understanding the risk of side effects is crucial when taking ritonavir. Consult your doctor about the risks of side effects, especially when combining ritonavir with other medications.

Limitations of Current Research

Research on ritonavir is still insufficient. There are still many unknowns, particularly regarding long-term side effects. It is hoped that future research will enhance our understanding of the safety of ritonavir.

Future Research Directions

It is crucial to conduct further research to elucidate the specific side effects caused by ritonavir and develop methods to mitigate these effects. Additional research is also needed to understand the interactions between ritonavir and other medications.

Conclusion

Ritonavir is an effective drug for HIV treatment, but it can cause various side effects. When taking ritonavir, understand the risks of side effects and follow your doctor's instructions. If you have concerns about side effects, consult your doctor.

Literature analysis of 21 papers
Positive Content
19
Neutral Content
0
Negative Content
2
Article Type
1
0
0
4
17
2.

Side effects and tolerability of post-exposure prophylaxis with zidovudine, lamivudine, and lopinavir/ritonavir: a comparative study with HIV/AIDS patients.

Author: CaiJuan, XiaoJiang, ZhangQiang

HIV prevention

This study looked at the safety and tolerability of a combination of three antiretroviral drugs (zidovudine, lamivudine, and lopinavir/ritonavir) in healthcare workers who were exposed to HIV. The study found that the combination was well tolerated and safe.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Scutellaria baicalensis and a constituent flavonoid, baicalein, attenuate ritonavir-induced gastrointestinal side-effects.

Author: MehendaleSangeeta, AungHan, WangChong-Zhi, TongRobin, FooAdela, XieJing-Tian, YuanChun-Su

Reduce GI dysfunction

Ritonavir, a protease inhibitor used in AIDS therapy, can cause gastrointestinal side effects such as nausea and vomiting. Scutellaria baicalensis and its active constituent, baicalein, were found to attenuate these gastrointestinal effects in rats.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

4.

Indinavir/low-dose ritonavir containing HAART in HIV-1 infected children has potent antiretroviral activity, but is associated with side effects and frequent discontinuation of treatment.

Author: FraaijP L A, VerweelG, van RossumA M C, HartwigN G, BurgerD M, de GrootR

HIV-1 treatment
Side effects
Therapy discontinuation

Indinavir plus low-dose ritonavir and two nucleoside reverse transcriptase inhibitors (NRTIs) were effective in controlling HIV-1 infection in children. However, this regimen was associated with side effects and therapy discontinuation.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

Interaction of ritonavir-boosted tipranavir with loperamide does not result in loperamide-associated neurologic side effects in healthy volunteers.

Author: MukwayaGeoffrey, MacGregorThomas, HoelscherDavid, HemingThomas, LeggDaniel, KavanaughKelli, JohnsonPhillip, SaboJohn P, McCallisterScott

Diarrhea treatment
Respiratory depression

This study examined the safety of loperamide when used with protease inhibitors, which are known to increase loperamide levels in the brain. Tipranavir reduced loperamide levels, while ritonavir increased them. Despite these pharmacokinetic changes, loperamide did not cause respiratory depression or pupil constriction in any of the study participants.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

6.

Lopinavir/ritonavir vs. indinavir/ritonavir in antiretroviral naive HIV-infected patients: immunovirological outcome and side effects.

Author: BongiovanniMarco, BiniTeresa, ChiesaElisabetta, CicconiPaola, AdorniFulvio, Monforte d'ArminioAntonella

Improved immunovirological outcomes
Drug discontinuation
Increased total cholesterol

This study compared the effectiveness and toxicity of two antiretroviral treatments, LPV/r and IDV/r, in HIV-1 patients. Both treatments achieved viral suppression, but IDV/r was less effective and had a higher risk of discontinuation due to toxicity.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

7.

The relationship between ritonavir plasma levels and side-effects: implications for therapeutic drug monitoring.

Author: GattiG, Di BiagioA, CasazzaR, De PascalisC, BassettiM, CrucianiM, VellaS, BassettiD

Gastrointestinal side effects
Neurological side effects

Higher ritonavir concentrations are associated with an increased risk of neurological or gastrointestinal side effects. Dosage adjustments guided by plasma level monitoring may improve tolerance without compromising treatment effectiveness.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform.

Author: ErnstAlexander, PiragyteIndre, MpAyisha Marwa, LeNgoc Dung, GrandgirardDenis, LeibStephen L, OatesAndrew, MercaderNadia

Counteracted inflammatory response
Embryo activity effects
Reduced body size
Reduced heart functionality

This study investigated the effects of 162 marketed drugs on cardiovascular development in zebrafish embryos. It was found that Remdesivir reduced body size and heart functionality at clinically relevant doses, while Ritonavir and Baricitinib showed reduced heart functionality. Molnupiravir and Baricitinib also showed effects on embryo activity. Sabizabulin was highly toxic at concentrations only 5 times higher than the maximum concentration reached in the blood after administration, and led to a mean mortality of 20% at that maximum concentration. The study also found that zebrafish can be used as a model to study the inflammatory response to SARS-CoV-2 spike protein treatment, and that Remdesivir, Ritonavir, Molnupiravir, Baricitinib, and Sabizabulin counteracted the inflammatory response related gene expression upon spike protein treatment. These findings highlight the need to rule out potential side effects of drugs on embryogenesis, and demonstrate the usefulness of zebrafish in studying the immune-modulating properties of COVID-19 compounds.

ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

A case report of severe hyponatremia secondary to Paxlovid-induced SIADH.

Author: MohamedSarah, Reda MostafaMostafa, Magdi EidMohamed, AbdelQadirYossef Hassan, AbdelghafarYomna Ali, SwedSarya, JahshanBishara, El-RadiWaddah Abd

COVID-19 treatment
Reduced viral load
Hyponatremia
SIADH

This article describes a case of a patient who developed severe hyponatremia after receiving nirmatrelvir-ritonavir (Paxlovid) for mild COVID-19 infection. The authors suggest that the hyponatremia may be secondary to Paxlovid.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

13.

Monitoring tacrolimus toxicity following Paxlovid administration in a liver transplant patient.

Author: MaynardRobert D, BatesPhillip, Korpi-SteinerNichole

Mitigated transplant rejection
Prevented side effects
Drug interactions
Tacrolimus toxicity

This case report describes a liver transplant patient who experienced tacrolimus toxicity after receiving Paxlovid. The case highlights the importance of therapeutic drug monitoring and the need for a higher clinical reportable range for tacrolimus testing to better manage drug toxicity.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

14.

Neurological side effects and drug interactions of antiviral compounds against SARS-CoV-2.

Author: AkhvledianiTamar, Bernard-ValnetRaphael, DiasSara P, EikelandRandi, PfauslerBettina, SellnerJohann,

Antiviral treatment

This article summarizes the available knowledge about antiviral drugs against SARS-CoV-2 from a neurologist's perspective.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

15.

Interactions of the Anti-SARS-CoV-2 Agents Molnupiravir and Nirmatrelvir/Paxlovid with Human Drug Transporters.

Author: BakosÉva, Temesszentandrási-AmbrusCsilla, Özvegy-LaczkaCsilla, GáborikZsuzsanna, SarkadiBalázs, TelbiszÁgnes

Antiviral treatment
Drug interactions

Molnupiravir and Nirmatrelvir, two antiviral agents used to treat COVID-19, can interact with various human transporters, potentially leading to drug-drug interactions. Molnupiravir inhibited CNT1,2 and ENT1,2 nucleoside transporters, while Nirmatrelvir inhibited OATPs and ABCB1.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

17.

Nirmatrelvir-ritonivir, COVID-19, and possible adverse cutaneous reactions.

Author: AlbrechtJ Mark, CooperBenjamin R, WallerJacquelyn D, PresleyColby L, PulsipherKayd J, RundleChandler W, DellavalleRobert P

COVID-19 treatment
Skin reactions

This review discusses the cutaneous side effects of nirmatrelvir-ritonivir (Paxlovid), a medication used to treat COVID-19, and compares them to common skin manifestations of COVID-19. The review also discusses potential drug interactions between Paxlovid and commonly used dermatological medications.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

18.

Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?

Author: HashemianSeyed Mohammad Reza, SheidaAmirhossein, TaghizadiehMohammad, MemarMohammad Yousef, HamblinMichael R, Bannazadeh BaghiHossein, Sadri NahandJavid, AsemiZatollah, MirzaeiHamed

Antiviral activity
Side effects

Nirmatrelvir is an antiviral drug that inhibits the SARS-CoV-2 main protease (Mpro), preventing viral replication. Paxlovid is a combination of nirmatrelvir and ritonavir, an HIV protease inhibitor that acts as a pharmacological enhancer for nirmatrelvir. This review summarizes the current literature on nirmatrelvir and ritonavir efficacy in treating SARS-CoV-2 infection, as well as their safety and possible side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

19.

The inhibitory and inducing effects of ritonavir on hepatic and intestinal CYP3A and other drug-handling proteins.

Author: LoosNancy H C, BeijnenJos H, SchinkelAlfred H

Reduced side effects

This review examines the use of ritonavir as a booster in HIV pharmacotherapy and COVID-19 treatment. It explores the possibility of using lower ritonavir doses, potentially reducing side effects without compromising efficacy. The review also discusses the duration of CYP3A inhibition after ritonavir discontinuation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

20.

Case Series of Patients with Coronavirus Disease 2019 Pneumonia Treated with Hydroxychloroquine.

Author: TanakaTomohiro, OkamotoMasaki, MatsuoNorikazu, Naitou-NishidaYoshiko, NounoTakashi, KojimaTakashi, NishiiYuuya, UchiyashikiYoshihiro, TakeokaHiroaki, NagasakiYoji

COVID-19 treatment
Improved condition
Cardiac events
Diarrhea
Liver enzyme elevation

Hydroxychloroquine (HCQ) therapy for COVID-19 has been widely debated. This case series shows that HCQ was well-tolerated in 27 patients with COVID-19, with manageable side effects. Although HCQ has not been endorsed as a standard treatment for COVID-19, this study provides evidence of its tolerability in some patients.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

21.

Triple Combination Therapy With 2 Antivirals and Monoclonal Antibodies for Persistent or Relapsed Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Patients.

Author: MikulskaMalgorzata, SepulcriChiara, DentoneChiara, MagneFederica, BallettoElisa, BaldiFederico, LabateLaura, RussoChiara, MirabellaMichele, MagnascoLaura, Di GraziaCarmen, GhiggiChiara, RaiolaAnna Maria, GiacobbeDaniele Roberto, VenaAntonio, BeltraminiSabrina, BruzzoneBianca, LemoliRoberto M, AngelucciEmanuele, BassettiMatteo

COVID-19 response
Side effects

Combination therapy with two antivirals (mainly remdesivir and nirmatrelvir/ritonavir) and anti-spike monoclonal antibodies (mAbs) demonstrated high rates of virological and clinical response in severely immunocompromised patients with prolonged or relapsed COVID-19. In a study of 22 patients, 75% achieved virological response at day 14, and 73% had clinical and virological response at day 30. Including mAbs in the combination therapy was significantly associated with better response rates.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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