Rukobia
Rukobia Uses, Dosage, Side Effects, Food Interaction and all others data.
Rukobia is the phosphonooxymethyl prodrug of temsavir, a novel HIV-1 attachment inhibitor. It binds to and inhibits the activity of gp120, a subunit within the HIV-1 gp160 envelope glycoprotein that facilitates the attachment of HIV-1 to host cell CD4 receptors - in doing so, temsavir prevents the first step in the HIV-1 viral lifecycle. The discovery of gp120 as a potential target of interest in the treatment of HIV-1 infection is relatively recent, and was born out of a desire to find alternative target proteins (i.e. mechanistically orthogonal therapies) for the treatment of HIV-1 patients with resistant infections. Fostemavir is the first attachment inhibitor to receive FDA approval, granted in July 2020 for use in combination with other antiretrovirals in highly treatment-experienced patients with multidrug-resistant HIV-1 infection whom are failing their current therapy. Targeting gp120 subunits is a new and novel therapeutic approach to HIV-1 infection, and the addition of attachment inhibitors, like temsavir, to the armament of therapies targeted against HIV-1 fills a necessary niche for therapeutic options in patients left with few, if any, viable treatments.
Temsavir inhibits the first stage in the HIV-1 viral lifecycle: attachment. It has a moderate duration of action necessitating twice-daily dosing. Rukobia, administered at roughly 4x the recommended human dose, has been observed to significantly prolong the QTc-interval. Patients with a history of QTc-prolongation, those receiving other QTc-prolonging medications, and/or those with pre-existing cardiac disease should use fostemsavir with caution, and should be monitored at baseline and throughout therapy for signs or symptoms suggestive of QTc-prolongation. Rukobia should also be used with caution in patients with hepatitis B or C co-infection as elevations in hepatic transaminases were observed in greater proportions in these populations in clinical trials.
| Trade Name | Rukobia |
| Availability | Prescription only |
| Generic | Fostemsavir |
| Fostemsavir Other Names | Fostemsavir |
| Related Drugs | Biktarvy, Truvada, tenofovir, ritonavir, Complera, Atripla, Stribild |
| Weight | 600mg, |
| Type | Oral tablet, extended release |
| Formula | C25H26N7O8P |
| Weight | Average: 583.498 Monoisotopic: 583.158047823 |
| Protein binding | Temsavir is approximately 88.4% protein-bound in plasma, primarily to serum albumin. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Rukobia is an antiretroviral HIV-1 attachment inhibitor targeted against the gp120 subunit within the HIV-1 gp160 envelope glycoprotein.
Rukobia is indicated, in combination with other antiretrovirals, for the treatment of multidrug-resistant HIV-1 infection in heavily treatment-experienced adults failing their current antiretroviral therapy due to resistance, intolerance, or safety concerns.
Rukobia is also used to associated treatment for these conditions: Human Immunodeficiency Virus Type 1 (HIV-1) Infection
How Rukobia works
The gp120 subunit within the gp160 envelope glycoprotein of HIV-1 is a new and novel target in the treatment of HIV-1 infection. These subunits are responsible for facilitating the first step in the viral life cycle, attachment, by mediating the interaction between the virus and host cell CD4 receptors. Following attachment, HIV-1 undergoes assembly, budding, and maturation within the host cell, after which mature viral particles are released to continue the viral life cycle.
Rukobia's active metabolite, temsavir, is an HIV-1 attachment inhibitor. It binds directly to the gp120 subunit to inhibit viral interaction with host CD4 receptors, thereby preventing the initial attachment required for viral replication. It has also been shown to inhibit other gp120-dependent post-attachment steps required for viral entry.
Toxicity
Data regarding fostemsavir overdose are unavailable. Symptoms of overdose are likely to be consistent with fostemsavir's adverse effect profile and may therefore involve significant GI disturbance and prolongation of the QT interval. In the event of overdose, patients should be monitored closely, including the use of ECG, and treated symptomatically as clinically indicated. As fostemsavir is highly protein-bound, dialysis is unlikely to be of benefit in the event of an overdose.
Food Interaction
- Avoid St. John's Wort. The use of strong inducers of CYP3A enzymes, including St. John's Wort, is contraindicated in patients receiving fostemsavir.
- Take with or without food. Co-administration with food slightly alters pharmacokinetics, but not to a clinically significant extent.
Rukobia Drug Interaction
Moderate: dolutegravir / rilpivirine, emtricitabine / tenofovirUnknown: alpha-lipoic acid, testosterone, flax, multivitamin with minerals, acetylcysteine, dabigatran, bifidobacterium infantis / lactobacillus acidophilus, ubiquinone, levothyroxine, dolutegravir, ibalizumab, cholecalciferol
Rukobia Disease Interaction
Volume of Distribution
The steady-state volume of distribution of temsavir following intravenous administration is approximately 29.5 L.
Elimination Route
The absorption of temsavir is significantly limited by suboptimal dissolution and solubility following oral administration. Rukobia, a phosphonooxymethyl prodrug of temsavir, has improved aqueous solubility and stability under acidic conditions as compared to its parent drug - following oral administration of fostemsavir, the absolute bioavailability is approximately 26.9%. The Cmax and AUCtau following oral administration of fostemsavir 600mg twice daily was 1770 ng/mL and 12,900 ng.h/L, respectively, with a Tmax of approximately 2 hours.
Co-administration of fostemsavir with a standard meal increases its AUC by approximately 10%, while co-administration with a high-fat meal increases its AUC by approximately 81%.
Half Life
The half-life of temsavir is approximately 11 hours. Rukobia is generally undetectable in plasma following oral administration.
Clearance
The mean clearance and apparent clearance of temsavir, the active metabolite of fostemsavir, are 17.9 L/h and 66.4 L/h, respectively.
Elimination Route
Temsavir is highly metabolized, after which it is excreted in the urine and feces as inactive metabolites. Approximately 51% of a given dose is excreted in the urine, with 5
Innovators Monograph
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