Vocabria Injection

/ GSK

Cabotegravir tablets can be started as oral therapy before starting cabotegravir injection to assess tolerability of cabotegravir, or proceed directly to cabotegravir injection.
Oral lead-in
When used for oral lead-in, oral cabotegravir together with oral rilpivirine should be taken for approximately one month (at least 28 days) to assess tolerability to cabotegravir and rilpivirine (see section 4.4). One cabotegravir 30 mg tablet should be taken with one rilpivirine 25 mg tablet, once daily. When administered with rilpivirine, cabotegravir tablets should be taken with a meal.
Following discontinuation of cabotegravir and rilpivirine injection, it is essential to adopt an alternative, fully suppressive antiretroviral regimen no later than one month after the final injection when dosed monthly and no later than two months after the final injection when dosed every 2 months.
Monthly dosing
Initiation injection (600 mg corresponding to 3 mL dose)
On the final day of current antiretroviral therapy or oral lead-in therapy, the recommended initial dose in adults is a single 600 mg intramuscular injection. Cabotegravir injection and rilpivirine injection should be administered at separate gluteal injection sites at the same visit.
Continuation injection (400 mg corresponding to 2 mL dose)
After the initiation injection, the continuation injection dose in adults is a single 400 mg monthly intramuscular injection. Cabotegravir injection and rilpivirine injection should be administered at separate gluteal injection sites at the same visit. Patients may be given injections up to 7 days before or after the date of the monthly 400 mg injection schedule.
Every 2 Month Dosing
Initiation Injections – one month apart (600 mg)
On the final day of current antiretroviral therapy or oral lead-in therapy, the recommended initial dose in adults is a single 600 mg intramuscular injection.
One month later, a second cabotegravir 600 mg intramuscular injection should be administered. Patients may be given the second 600 mg initiation injection up to 7 days before or after the scheduled dosing date.
Cabotegravir injection and rilpivirine injection should be administered at separate gluteal injection sites at the same visit.
Continuation Injections – 2 months apart (600 mg)
After the initiation injections, the recommended continuation dose in adults is a single 600 mg intramuscular injection administered every 2 months. Cabotegravir injection and rilpivirine injection should be administered at separate gluteal injection sites at the same visit. Patients may be given injections up to 7 days before or after the date of every 2 month, 600 mg injection schedule.
See prescribing information for full details.

Treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen without present or past evidence of viral resistance to, and no prior virological failure with agents of the non-nucleoside reverse transcriptase inhibitor (NNRTI) and integrase inhibitor (INI) class. In combination with rilpivirine injection.

* Hypersensitivity to the active substance or to any of the excipients
* Concomitant use with rifampicin, rifapentine, carbamazepine, oxcarbazepine, phenytoin or phenobarbital

* If virologic failure is suspected, an alternative regimen should be adopted as soon as possible.
Long acting properties
Residual concentrations of cabotegravir may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer).
Baseline factors associated with virological failure
Before starting the regimen, it should be taken into account that multivariable analyses indicate that a combination of at least 2 of the following baseline factors may be associated with an increased risk of virological failure: archived rilpivirine resistance mutations, HIV-1 subtype A6/A1, or BMI >30 kg/m2. Available data suggest that virologic failure occurs more often when these patients are treated according to the every 2 month dosing regimen as compared to the monthly dosing regimen. In patients with an incomplete or uncertain treatment history without pre-treatment resistance analyses, caution is warranted in the presence of either BMI >30 kg/m2 or HIV-1 A6/A1 subtype.
Severe cutaneous adverse reactions (SCARs)
The severe cutaneous adverse reactions, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported very rarely in association with cabotegravir treatment.
Hypersensitivity reactions
Hypersensitivity reactions have been reported in association with integrase inhibitors including cabotegravir. These reactions were characterised by rash, constitutional findings and sometimes organ dysfunction, including liver injury. This medical product and other suspected medicinal products should be discontinued immediately, should signs or symptoms of hypersensitivity develop (including, but not limited to, severe rash, or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial oedema, hepatitis, eosinophilia or angioedema). Clinical status, including liver aminotransferases should be monitored and appropriate therapy initiated.
Hepatoxicity
Hepatotoxicity has been reported in a limited number of patients receiving cabotegravir with or without known pre-existing hepatic disease. Administration of cabotegravir oral lead-in was used in clinical studies to help identify patients who may be at risk of hepatotoxicity.
Monitoring of liver chemistries is recommended and treatment should be discontinued if hepatotoxicity is suspected.
HBV/HCV co-infection
It is not recommended to initiate cabotegravir in patients with hepatitis B co-infection. Patients with hepatitis B co-infection were excluded from studies with cabotegravir. Limited data is available in patients with hepatitis C co-infection. Monitoring of liver function is recommended in patients with hepatitis C co-infection.
Immune reactivation syndrome
In HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, such reactions have been observed within the first few weeks or months of initiation of CART. Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, and Pneumocystis jirovecii pneumonia. Any inflammatory symptoms should be evaluated and treatment instituted when necessary. Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution, however, the reported time to onset is more variable and these events can occur many months after initiation of treatment.
Opportunistic infections
Patients should be advised that cabotegravir or any other antiretroviral therapy does not cure HIV infection and that they may still develop opportunistic infections and other complications of HIV infection. Therefore, patients should remain under close clinical observation by physicians experienced in the treatment of these associated HIV diseases.
See prescribing information for full details.

Common: Depression, Anxiety, Abnormal dreams, Insomnia, Dizziness, Nausea
Vomiting, Abdominal pain, Flatulence, Diarrhoea, Rash, Myalgia, Injection site reactions (swelling, erythema, pruritus, bruising, warmth, haematoma), Fatigue
Asthenia, Malaise, Weight increased.
Very common: Headache, Injection site reactions (pain4 and discomfort, nodule, induration), Pyrexia.
See prescribing information for full details.

Effect of other medicinal products on the pharmacokinetics of cabotegravir
Cabotegravir is primarily metabolised by uridine diphosphate glucuronosyl transferase (UGT) 1A1 and to a lesser extent by UGT1A9. Medicinal products which are strong inducers of UGT1A1 or UGT1A9 are expected to decrease cabotegravir plasma concentrations leading to lack of efficacy. In poor metabolizers of UGT1A1, representing a maximum clinical UGT1A1 inhibition, the mean AUC, Cmax and Ctau of oral cabotegravir increased by up to 1.5-fold. The impact of an UGT1A1 inhibitor may be slightly more pronounced, however, considering the safety margins of cabotegravir, this increase is not expected to be clinically relevant. No dosing adjustments are recommended
Cabotegravir is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), however, because of its high permeability, no alteration in absorption is expected when co-administered with either P-gp or BCRP inhibitors.
Effect of cabotegravir on the pharmacokinetics of other medicinal products
In vivo, cabotegravir did not have an effect on midazolam, a cytochrome P450 (CYP) 3A4 probe. In vitro, cabotegravir did not induce CYP1A2, CYP2B6, or CYP3A4.
In vitro cabotegravir inhibited organic anion transporters OAT1 and OAT3. Therefore, caution is advised when co-dosing with narrow therapeutic index OAT1/3 substrate drugs (e.g. methotrexate).
See prescribing information for full details.

Pregnancy: There are a limited amount of data from the use of cabotegravir in pregnant women. The effect of cabotegravir on human pregnancy is unknown. Cabotegravir injection is not recommended during pregnancy unless the expected benefit justifies the potential risk to the foetus.
Cabotegravir has been detected in systemic circulation for up to 12 months or longer after an injection.
Lactation: It is recommended that women living with HIV do not breast-feed their infants in order to avoid transmission of HIV.
See prescribing information for full details.

There is no specific treatment for cabotegravir overdose. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary.
Cabotegravir is known to be highly protein bound in plasma; therefore, dialysis is unlikely to be helpful in removal of medicinal product from the body. Management of overdose should take into consideration the prolonged exposure to the medicine following an injection.

Patients should be informed that dizziness, fatigue and somnolence has been reported during treatment.