绥美凯的注意事项有哪些？

GlaxoSmithKline (GSK) recently announced that its joint venture ViiV Healthcare’s single-tablet compound preparation Inbec (chemical name: dolutegravir) for the treatment of HIV, which is based on the new generation of integrase inhibitor Tevicai (chemical name: dolutegravir), has officially been launched in mainland China. This is the first single-pill compound preparation with a complete treatment plan in the field of HIV treatment in mainland China. As an innovative single-tablet compound preparation with obvious clinical therapeutic advantages, Dolutegra Abalamid Tablets can provide great convenience for the treatment of HIV-infected patients. In addition, what are the precautions?

Precautions for Dote Abalamid Tablets:

Spreading 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.

Body weight and metabolic parameters (lipids and blood glucose)

During antiretroviral therapy, weight gain and elevated blood lipid and blood glucose levels may occur. These changes may be related in part to disease control and lifestyle. In some cases, there is evidence of treatment effects on lipids, but there is no clear evidence that weight gain is associated with any particular treatment. Monitoring of lipids and blood glucose should refer to established HIV treatment guidelines. Dyslipidemia should be treated appropriately based on the clinical situation.

Liver disease

The safety and effectiveness of Trimax have not been established in patients with pre-existing severe liver disease. Suimeikan is not recommended for patients with moderate to severe liver damage.

Patients with pre-existing hepatic dysfunction, including those with chronic active hepatitis, develop hepatic dysfunction with increased frequency during combined antiretroviral therapy and should be monitored according to standard protocols. If in these patients there is evidence of worsening liver disease, withholding or discontinuing treatment should be considered.

Patients with chronic hepatitis B or hepatitis C

Patients with chronic hepatitis B or hepatitis C who receive combination antiretroviral therapy are at increased risk for serious and potentially fatal hepatic adverse effects. If you are also taking antiviral treatment for hepatitis B or hepatitis C, please refer to the relevant product information for these medicines.

Suimeikai contains lamivudine, which is effective against hepatitis B. Abacavir and dolutegravir lack such effects. It is generally believed that lamivudine monotherapy is not an adequate treatment for hepatitis B because of the high risk of developing hepatitis B virus resistance. Therefore, if Trimax is used to treat patients co-infected with hepatitis B, another antiviral drug is generally required. Treatment guidelines should be consulted.

If patients co-infected with hepatitis B virus discontinue Trimax, regular monitoring of liver function and HBV replication markers is recommended, as discontinuation of lamivudine may lead to acute exacerbation of hepatitis.

myocardial infarction

Observational studies have demonstrated an association between myocardial infarction and abacavir use. The patients participating in the study were mainly those who had received antiretroviral therapy. Clinical trial data show a limited number of myocardial infarctions and a small increase in risk cannot be ruled out. Overall, there are some inconsistencies between observational cohort data and randomized trial data, so a causal relationship between abacavir treatment and the risk of myocardial infarction cannot be confirmed or denied. To date, there is no precise biological mechanism to explain the possible increased risk. While using Trimax, steps should be taken to minimize all modifiable risk factors (such as smoking, hypertension, and hyperlipidemia).

osteonecrosis

Although the etiology is thought to be multifactorial (including use of corticosteroids, bisphosphonates, alcohol consumption, severe immunosuppression, and high body mass index), cases of osteonecrosis have been reported, particularly in patients with advanced HIV disease and/or long-term exposure to CART. Patients should be advised to seek medical attention if they experience joint pain, joint stiffness, or difficulty moving.

Opportunistic infections

Patients should be informed that HIV infection cannot be cured by Trimax or any other antiretroviral treatment and that they may still develop opportunistic infections and other complications of HIV infection. Therefore, patients should be under close clinical observation by physicians experienced in treating HIV-related diseases.

Resistance

Because the recommended dose of dolutegravir in patients who are resistant to integrase inhibitors is 50 mg twice daily, Trimeq is not recommended for patients who are resistant to integrase inhibitors.

drug interactions

When administered concomitantly with etravirine (without potentiating protease inhibitors), efavirenz, nevirapine, rifampicin, tipranavir/ritonavir, carbamazepine, phenytoin, phenobarbital, and St. John's wort, the recommended dose of dolutegravir is 50 mg twice daily, so TRIUMEQ is not recommended in patients taking these medications.

TRIUMEQ should not be administered concurrently with antacids containing polyvalent cations. It is recommended to take TRIUMEQ 2 hours before or 6 hours after these medications.

It is recommended to take TRIUMEQ 2 hours before or 6 hours after dosing calcium or iron supplements.

Dolutegravir may increase metformin concentrations. If dolutegravir is administered concurrently with metformin, the metformin dose may require adjustment when therapy is initiated and discontinued to maintain glycemic control (see Drug Interactions). Metformin is eliminated by the kidneys, so renal function must be monitored when coadministered with dolutegravir. Concurrent administration may increase the risk of lactic acidosis in patients with moderate renal impairment (stage 3a, creatinine clearance [CrCl] 45-59 mL/min), and a conservative approach is recommended. Metformin dose reduction is strongly recommended.

Coadministration of lamivudine with cladribine is not recommended.

TRIUMEQ should not be taken with other medicines containing dolutegravir, abacavir, lamivudine, or emtricitabine.

Effects on ability to drive and operate machinery

Patients should be informed that dizziness has been reported during treatment with dolutegravir. The patient's clinical status and adverse effect profile should be kept in mind when considering a patient's ability to drive or operate machinery.