多替阿巴拉米片中文版说明书

Chinese version manual

Generic name: Doptabalamid tablets

Product name: Suimeikai

All names: Trimeq, Docetabalamid, TRIUMEQ, Inbec

It is suitable for the treatment of adults and adolescents over 12 years old (with a weight of at least 40kg) infected with human immunodeficiency virus (HIV).

Usage and dosage:

dose

Adults and teenagers (weighing at least 40kg)

For adults and adolescents, the recommended dose of Trimax is one tablet once daily.

Adults or adolescents whose body weight is less than 40 kg should not be given Trimax because Trimax is a fixed-dose tablet and the dose cannot be reduced.

Trimax is a fixed-dose tablet and should not be used in patients who require dose adjustments. If one of the active ingredients needs to be discontinued or a dose adjustment is required, separate formulations of dolutegravir, abacavir, or lamivudine may be used. In these cases, physicians should refer to the respective product information for these medicines.

Miss a dose

If the patient misses a dose of Suimei Kai and there are more than 4 hours before the next dose, Sui Meikai should be taken as soon as possible. If the next dose is less than 4 hours away, patients should not take the missed dose and simply resume their usual dosing schedule.

elderly patients

There are limited data on the use of dolutegravir, abacavir, and lamivudine in patients aged ≥65 years, and there is no evidence that older patients require different doses than younger adults. Taking into account age-related changes, such as decreased renal function and changes in hematological parameters, special caution is recommended when administering the drug in this age group.

kidney damage

Patients whose creatinine clearance rate is less than 50mL/min are not recommended to take Suimeikai.

liver damage

Abacavir is primarily metabolized by the liver. There are no clinical data in patients with moderate or severe hepatic impairment, therefore, use of Trimax is not recommended unless deemed necessary. For patients with mild hepatic impairment, close monitoring is required, including monitoring of abacavir plasma levels if feasible

Adverse reactions:

Clinical data on Trimax are limited, and the most commonly reported adverse reactions that are possibly or probably related to dolutegravir and abacalongvir/lamivudine are nausea (12%), insomnia (7%), dizziness (6%), and headache (6%).

Adverse reactions (nausea, vomiting, diarrhea, pyrexia, drowsiness, rash) occur frequently in patients with abacavir hypersensitivity reactions. Therefore, patients who develop these symptoms should be carefully evaluated for the presence of this hypersensitivity reaction. Very rarely, erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis have been reported and abacavir hypersensitivity cannot be excluded. In such cases, abacavir-containing medicinal products should be discontinued.

In individual patients, the most serious adverse events that may be associated with dolutegravir and abacavir/lamivudine are hypersensitivity reactions, including rash and severe hepatic effects.

An analysis of pooled data from Phase IIb to IIIb clinical trials found that the adverse reactions observed with the combination of dolutegravir + abacavir/lamivudine were generally consistent with the adverse reaction profiles of the single ingredients dolutegravir, abacavir, and lamivudine.

There was no difference in the severity of adverse reactions observed between the combination and the single ingredients.

Taboo:

Contraindicated in patients with known hypersensitivity to dolutegravir, abacavir, and lamivudine or any excipients.

Concomitant use with dofetilide and pisicanide is prohibited.

Things to note:

Spread HIV

Although viral suppression with antiretroviral therapy has been shown to significantly reduce the risk of sexual transmission, residual risks cannot be excluded. Precautions should be taken to prevent transmission in accordance with national guidance.

hypersensitivity reaction

Both abacavir and dolutegravir carry the risk of triggering a hypersensitivity reaction (HSR) and share some common characteristics, such as fever and/or rash and other symptoms indicating involvement of multiple organs. It is clinically impossible to determine whether abacavir or dolutegravir is responsible for a hypersensitivity reaction that occurs with Trimeq. Hypersensitivity reactions have been observed to occur more commonly with abacavir, some of which can be life-threatening and, in rare cases, fatal if not managed appropriately. Patients who test positive for the HLA-B*5701 allele are at higher risk of developing abacavir hypersensitivity reactions. However, abacavir hypersensitivity reactions are reported less frequently in patients who do not carry this allele.

Therefore, the following measures should be followed:

Before starting treatment, HLA-B*5701 status must be confirmed.

Patients with a positive HLA-B5701 status, or patients with a negative HLA-B5701 status who had a suspected abacavir hypersensitivity reaction when previously receiving an abacavir-containing treatment regimen, should not be treated with Trimax.

If a hypersensitivity reaction is suspected, Trimax should be discontinued without delay, even if the HLA-B*5701 allele is not present. If a hypersensitivity reaction occurs and treatment with Trimax is not discontinued immediately, a life-threatening reaction may result. Clinical status, including hepatic aminotransferases and bilirubin, should be monitored.

After discontinuing Trimax due to suspected hypersensitivity reaction, Trimax or any other medicine containing abacavir or dolutegravir should never be restarted.

After a suspected hypersensitivity reaction to abacavir, symptoms may return within hours if abacavir-containing medicines are restarted. Relapses are generally more severe than the initial episode and may include life-threatening hypotension and death.

To avoid re-dosing abacavir and dolutegravir, patients with suspected hypersensitivity reactions should be instructed to discard remaining Trimax tablets.

Clinical description of hypersensitivity reactions

In clinical studies, <1% of patients treated with dolutegravir reported hypersensitivity reactions, manifesting as rash, systemic symptoms, and sometimes organ dysfunction, including severe hepatic reactions.

Hypersensitivity reactions to abacavir have been well characterized during clinical studies and post-marketing surveillance. Symptoms generally occur within the first six weeks after starting abacavir treatment (median time to onset is 11 days), but these reactions may occur at any time during treatment.

Nearly all hypersensitivity reactions to abacavir include fever and/or rash. Other signs and symptoms observed as part of abacavir hypersensitivity reactions include respiratory and gastrointestinal symptoms. Importantly, these symptoms may lead to misdiagnosis of a hypersensitivity reaction as a respiratory illness (pneumonia, bronchitis, pharyngitis) or gastroenteritis. Continuing treatment can worsen symptoms associated with hypersensitivity reactions and may be life-threatening. These symptoms generally resolve after discontinuation of abacavir.

Rarely, life-threatening reactions may occur within hours of restarting abacavir in patients who have discontinued abacavir for reasons other than symptoms of a hypersensitivity reaction. In such patients, abacavir therapy must be restarted in an environment where immediate medical attention is available.

Mechanism of action:

Dolutegravir: Can inhibit HIV integrase by binding to the active site of integrase and blocking the strand transfer step of reverse transcription deoxyribonucleic acid (DNA) integration (a key step in the HIV replication cycle).

Abacavir: Abacavir is a carbocyclic synthetic nucleoside analog. Abacavir is converted into the active metabolite carbavir triphosphate (CBV-TP) under the action of intracellular enzymes, which is a deoxyguanosine-5'-triphosphate (dGTP) analog. CBV-TP inhibits the activity of HIV-1 reverse transcriptase (RT) by competing with the natural substrate dGTP and inserting into viral DNA.

Lamivudine: Lamivudine is a synthetic nucleoside analogue. Lamivudine is phosphorylated in cells to generate the active 5-triphosphate metabolite, lamivudine triphosphate (3TC-TP). The main mode of action of 3T-CTP is to terminate DNA chain synthesis by inserting nucleotide analogs, thereby inhibiting RT activity.

Storage:

Seal and store below 30℃.

Tablets should be stored in their original packaging to avoid moisture absorption. Seal the vial tightly and do not remove the desiccant.