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Apretude is a brand name for Cabotegravir. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Apretude is indicated in combination with safer sex practices for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in high-risk adults and adolescents, weighing at least 35 kg (see sections 4.2, 4.4 and 5.1).
Verbatim from this product's EMA label. Tap a section to expand.
Apretude should be prescribed by a healthcare professional experienced in the management of HIV PrEP. Each injection should be administered by a healthcare professional. 3). A combined antigen/antibody test as well as an HIV-RNA-based test should both be negative.
Prescribers are advised to perform both tests, even if the result of the HIV- RNA-based test will become available after cabotegravir injection. If a combined testing strategy including both tests is not available, testing should follow local guidelines.
Prior to starting Apretude, individuals should be carefully selected to agree to the required dosing schedule and counselled about the importance of adherence to scheduled dosing visits to help reduce the risk of acquiring HIV-1 infection.
The healthcare provider and individual may decide to use cabotegravir tablets as an oral lead-in prior to the initiation of Apretude injection to assess tolerability or may proceed directly to Apretude injections (see Table 1 and Table 2 for dosing recommendations).
Posology Oral lead-in Refer to the oral Apretude tablet SmPC for oral lead-in information. 3 Injection Initiation injections The recommended initial dose is a single 600 mg intramuscular injection. If oral lead-in has been used, the first injection should be planned for the last day of oral lead-in or within 3 days thereafter.
One month later, a second 600 mg intramuscular injection should be administered. Individuals may be given the second 600 mg initiation injection up to 7 days before or after the scheduled dosing date. Continuation injections – 2 months apart After the second initiation injection, the recommended continuation injection dose in adults is a single 600 mg intramuscular injection administered every 2 months.
Individuals may be given injections up to 7 days before or after the date of the scheduled injection date. Table 1 Recommended intramuscular dosing schedule Initiation injections (one month apart) Continuation injections (two months apart) Medicinal product Direct to injection: months 1 and 2 or Following oral lead-in: months 2 and 3 Two months after final initiation injection and every 2 months onwards Cabotegravir 600 mg 600 mg Missed doses Individuals who miss a scheduled injection visit should be reassessed to ensure resumption of PrEP remains appropriate.
Summary of the safety profile The most frequently reported adverse reactions in HPTN 083 were: Injection site reactions (82%), headache (17%) and diarrhoea (14%).
The most frequently reported adverse reactions in HPTN 084 were:
Injection site reactions (38%), headache (23%) and transaminase increased (19%). 4). Tabulated list of adverse reactions Adverse reactions for cabotegravir were identified from the Phase III clinical studies; HPTN 083 and HPTN 084; and post-marketing data.
In HPTN 083, the median time on blinded study product was 65 weeks and 2 days (1 day to 156 weeks and 1 day), with a total exposure on cabotegravir of 3270 person years. In HPTN 084, the median time on blinded study product was 64 weeks and 1 day (1 day to 153 weeks and 1 day), with a total exposure on cabotegravir of 1920 person years.
The adverse reactions considered at least possibly related to cabotegravir in adults and adolescents are listed in Table 4 by system organ class and frequency. Frequencies are defined as very common ( 1/10), common ( 1/100 to < 1/10), uncommon ( 1/1 000 to < 1/100), rare ( 1/10 000 to < 1/1 000), very rare (< 1/10 000).
Table 4 Tabulated list of adverse reactions1 MedDRA System organ class (SOC) Frequency category Adverse reactions 10 Immune system disorders Uncommon Hypersensitivity* Psychiatric disorders Common Abnormal dreams Insomnia Depression Anxiety Uncommon Suicide attempt; Suicidal ideation (particularly in individuals with a pre-existing psychiatric illness) Nervous system disorders Very common Headache Common Dizziness Uncommon Somnolence Vasovagal reactions (in response to injections) Gastrointestinal disorders Very common Diarrhoea Common Nausea Abdominal pain2 Flatulence Vomiting Hepatobiliary Disorders Uncommon Hepatotoxicity Skin and subcutaneous tissue disorders Common Rash3 Uncommon Urticaria* Angioedema* Very rare Stevens-Johnson syndrome*, toxic epidermal necrolysis* Musculoskeletal and connective tissue disorders Common Myalgia General disorders and administrative site conditions Very common Pyrexia5 Injection site reactions4 (pain6 and tenderness, nodule, induration) Common Injection site reaction4 (swelling, bruising, erythema, warmth, pruritus, anaesthesia) Fatigue Malaise Uncommon Injection site reactions4 (haematoma, discolouration, abscess) Investigations Very common Transaminase increased Uncommon Weight increased Blood bilirubin increased 1 The frequency of the identified adverse reactions are based on all reported occurrences of the adverse reactions and are not limited to those considered at least possibly related by the investigator.
1). 2) are achieved and maintained within hours after initiation of oral lead-in and within 7 days from the first injection (without oral lead-in). The exact time from initiation of Apretude for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown.
g. knowledge of HIV-1 status, regular testing for other sexually transmitted infections, condom use). 3). Individuals should be re-confirmed to be HIV negative at each subsequent injection of Apretude. A combined antigen/antibody test as well as an HIV-RNA-based test should both be negative.
Prescribers are advised to perform both tests, even if the result of the HIV-RNA-based test will become available after cabotegravir injection. If a combined testing strategy including both tests is not available, testing should follow local guidelines while taking Apretude.
If clinical symptoms consistent with acute viral infection are present and recent (< 1 month) exposures to HIV-1 are suspected, HIV-1 status should be reconfirmed. Potential risk of resistance There is a potential risk of developing resistance to cabotegravir if an individual acquires HIV-1 either before or while taking Apretude, or following discontinuation of Apretude (see Long- acting properties of Apretude injection).
To minimise this risk, it is essential to confirm HIV-1 negative status at each subsequent injection of Apretude. A combined antigen/antibody test as well as an HIV- RNA-based test should both be negative. Prescribers are advised to perform both tests, even if the result of the HIV-RNA-based test will become available after cabotegravir injection.
If a combined testing strategy including both tests is not available, testing should follow local guidelines. Individuals who are diagnosed with HIV-1 should immediately begin anti-retroviral therapy (ART). Apretude alone does not constitute a complete regimen for the treatment of HIV-1 and HIV-1 resistance mutations have emerged in some individuals with undetected HIV-1 infection who were only taking Apretude.
1. 4). 5). 5
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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If a delay of more than 7 days from a scheduled injection date cannot be avoided, it will be a missed dose, therefore, cabotegravir 30 mg tablets may be used once daily, for a duration of up to two months, to replace one scheduled injection visit.
The first dose of oral cabotegravir (or an alternative oral PrEP therapy) should be taken approximately two months (+/- 7 days) after the last injection of cabotegravir. For oral PrEP durations greater than two months, an alternative PrEP regimen to oral cabotegravir is recommended.
Injection dosing should be resumed on the day oral cabotegravir dosing completes or within 3 days, thereafter, as recommended in Table 2. Table 2 Injection dosing recommendations after missed injections or following oral cabotegravir (PrEP) to replace an injection Missed Doses Time since last injection Recommendation If second injection is missed and time since first injection is: ≤ 2 months Administer one 600 mg injection as soon as possible and continue with the every 2 month injection dosing schedule.
> 2 months Restart the individual on one 600 mg initiation injection, followed by a second 600 mg initiation injection one month later. Then follow the every two month injection dosing schedule. 4 If 3rd or subsequent injection is missed and time since prior injection is: ≤ 3 months Administer one 600 mg injection as soon as possible and continue with the every 2 month injection dosing schedule.
> 3 months Restart the individual on one 600 mg initiation injection, followed by a second 600 mg initiation injection one month later. Then follow the every two month injection dosing schedule. Special populations Elderly No dose adjustment is required in elderly individuals.
2). Hepatic impairment No dose adjustment is required in individuals with mild or moderate hepatic impairment (Child-Pugh score A or B). 2]). If administered in an individual with severe hepatic impairment, cabotegravir should be used with caution.
2]). Cabotegravir has not been studied in individuals with end-stage renal disease on renal replacement therapy. As cabotegravir is greater than 99% protein bound, dialysis is not expected to alter exposures of cabotegravir. If administered in an individual on renal replacement therapy, cabotegravir should be used with caution.
Paediatric population The safety and efficacy of cabotegravir in children and adolescents weighing less than 35 kg have not been established. No data are available. Method of administration For intramuscular use. Injections must be administered to the ventrogluteal (recommended as it is located away from major nerves and blood vessels) or the dorsogluteal sites.
Care should be taken to avoid inadvertent injection into a blood vessel. Once the suspension has been drawn into the syringe, the injection should be administered as soon as possible, but may remain in the syringe for up to 2 hours.
If the medicinal product remains in the syringe for more than 2 hours, the filled syringe and needle must be discarded. When administering […]
2Abdominal pain includes the following grouped MedDRA preferred terms: upper abdominal pain and abdominal pain. 3Rash includes the following grouped MedDRA preferred terms: rash, rash erythematous, rash macular, rash maculo-papular, rash morbilliform, rash papular, rash pruritic.
4ISRs listed in the table have been seen in 2 participants or more. 5Pyrexia includes the following grouped MedDRA preferred terms: pyrexia and feeling hot. The majority of pyrexia adverse reactions were reported within one week of injections.
6May rarely result in temporary gait disturbance. 4. Description of selected adverse reactions Local injection site reactions (ISRs) In HPTN 083, 2% of participants discontinued cabotegravir because of ISRs. Out of 20286 injections, 8900 ISRs were reported.
A total of 2117 participants received at least one injection. Of the 1740 (82%) participants who experienced at least one ISR, the maximum severity of ISRs reported was mild (Grade 1, 34% of participants), moderate (Grade 2, 46% of participants) or severe (Grade 3, 3% of participants).
The median duration of overall ISR adverse reactions was 4 days. The proportion of participants reporting ISRs at each visit and the severity of the ISRs decreased over time. In HPTN 084, no participants discontinued cabotegravir because of ISRs.
Out of 13068 injections, 1171 ISRs were reported. A total of 1519 participants received at least one injection. Of the 578 (38%) participants who experienced at last one ISR, the maximum severity of ISRs reported was mild (Grade 1, 25% of participants), moderate (Grade 2, 13% of participants) or severe (Grade 3, < 1% of participants).
The median duration of overall ISR adverse reactions was 8 days. The proportion of participants reporting ISRs at each visit and the severity of the ISRs generally decreased over time. 0 n=598) in weight from baseline, respectively. 0 n=218) in weight from baseline, respectively.
Changes in laboratory chemistries In both HPTN 083 and HPTN 084, a similar proportion of participants in the cabotegravir and TDF/FTC groups were observed to have elevated hepatic transaminases (ALT/AST) levels and maximum post baseline increases were mostly Grades 1 and 2.
In HPTN 083, the number of participants in the cabotegravir vs TDF/FTC groups who experienced maximum post baseline Grade 3 or 4 ALT levels were 40 (2%) vs 44 (2%) and Grade 3 or 4 AST levels were 68 (3%) vs 79 (3%), respectively. In HPTN 084, the number of […]
Importance of adherence Individuals should be counselled periodically to strictly adhere to the recommended oral lead-in and injection dosing schedule in order to reduce the risk of HIV-1 infection and the potential development of resistance.
2). 6). 6 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 administration.
At the time of prescription, patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, cabotegravir should be withdrawn immediately and an alternative form of PrEP considered (as appropriate).
If the patient has developed a serious reaction such as SJS or TEN with the use of cabotegravir, treatment with cabotegravir must not be restarted in this patient at any time. 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. Apretude 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).
8). 8). Administration of cabotegravir oral lead- in was used in clinical studies to help identify individuals who may be at risk of hepatotoxicity. Clinical and laboratory monitoring are recommended and Apretude should be discontinued if hepatotoxicity is confirmed, and individuals managed as clinically indicated (see Long-acting properties of Apretude injection).
8). Although clinical studies did not show an increased incidence of psychiatric illness in adolescents compared to adult subjects, given the vulnerability of the adolescent population, adolescents should be counselled before prescribing, and periodically while […]