Synthivan belongs to anti-viral medication which is includes atazanavir & ritonavir as an active moiety. Ritonavir is also a protease enzyme inhibitor, which is a peptidomimetic agent for both HIV-1 & HIV-2 type infections. Synthivan tablets are fixed dose combination, which is categorized as protease inhibitor. Atazanavir is a chemically classified as azapeptide, which is containing bis-aryl substituent on hydrazine moiety exhibits anti-retroviral activity against wild type & mutant forms of HIV protease.
Atazanavir & Ritonavir
300mg & 100mg
Synthivan tablet includes active molecules are classified as protease inhibitor, which is contain in the treatment of HIV-1 infections.
Mechanism of Synthivan
HIV protease enzymes which is includes in division of auxiliary and multiplicative proteins that may deliver from significant HIV qualities, similar to choke and pol. This action of protein ought to be diminished because of repressing the protease chemical by ritonavir, a functioning substance of Ritomune tablets. Gal: cover the proteins confused in center and nucleocapsid. Pol: cover the turnaround transcriptase, ribonuclease H, integrase and protease. The division of lady buddy polyprotein ought to be counteracted by ritonavir which prompts generation of youthful and non-irresistible viral particles.
Atazanavir specifically restrains the infection particular preparing of viral Gag and Gag-Pol polyproteins in HIV-1 contaminated cells by official to the dynamic site of HIV-1 protease, hence keeping the arrangement of develop virions. Atazanavir isn't dynamic against HIV-2.
Atazanavir is administering with food will leads to increase the bioavailability and decreases the pharmacokinetics variability.The mean oral bioavailability of atazanavir is 60 to 68%. The absorption of atazanavir is occurs very quickly; with Tmax value is 2.5 hours. After administration of ritonavir, the maximum plasma concentration is reaches within 2 hours & 4 hours in both fasted & non fasted condition.
Ritonavir is highly binds to human plasma protein by 98 to 99%. Atazanavir is binds to serum proteins by 86%.
Ritonavir has major metabolite such as Isopropylthiazole oxidation. The major isoenzyme used for the metabolism of ritonavir is CYP3A. Atazanavir is highly metabolized, in liver. The biotransformation of atazanavir majorly occurs by undergoing Monooxygenation & Dioxygenation.
The elimination process of ritonavir is majorly via feces & urine. The mean terminal half life period of ritonavir is 3 to 5 hours. The mean terminal half life period of atazanavir is relatively 7 hours.
Dosage and administration of Synthivan
Atazanavir should not used alone; it should be combined with ritonavir which is majorly prescribed for therapy experienced adult patients with preceding virologic failure. The higher dose of ritonavir will cause reducing the safety profile of atazanavir.
Before starting the treatment with atazanavir
Patients who are going to receiving the atazanavir should be performed with renal function test periodically for both prior and during the therapy. Serum creatinine, creatinine clearance, urine analysis should be checked frequently. Hepatic function test is also performed before starting & during the treatment.
The prescribed dose of Synthivan is one tablet should be administered as a single dose by combining with any of the following drugs like;Tenofovir, H2 receptor antagonist: Proton pump inhibitors
In therapy experienced patients (adults)
The recommended dose is one tablet of Synthivan should be administered as a single dose.
H2 receptor antagonist: The gastric regulator drug should not be exceeding a dose equal to famotidine 20mg as two times a day. Synthivan tablets should be concurrently administered with & or at least 10 hours after the dose of H2 receptor antagonist. If patient taking H2 receptor antagonist, Synthivan tablets should be taken with food. If patients administered tenofovir & H2 receptor antagonist concurrently, then Synthivan tablets should not be recommend. In therapy experienced patients who are getting Synthivan tablets, proton pump inhibitor should not be recommended. Synthivan tablets should not be administered with efavirenz, because of reducing atazanavir exposure.
In pregnant women
The recommended dose of Synthivan is; In both new commenced or already treated patients: The prescribed dose is one Synthivan tablet should be administered as a single dose. In case of combination of H2RA or tenofovir DF, the recommended dose is 400mg of atazanavir & 100mg of ritonavir should be recommended as a single dose. In therapy experienced pregnant patients during 2nd or 3rd trimester, atazanavir should not be suggested. In severe condition, Synthivan tablets should not be used. Synthivan tablets should be administered with food. Synthivan tablets are fixed dose combination; it should not be breaking, chew or crush.
The major adverse effects of Synthivan tablets are
Cardiac conduction abnormalities Rash Increased bilirubin levels Chronic kidney disease Nephrolithiasis Cholelithiasis
The common side effects
Increased AST, ALT, Increased lipase, Increased creatine kinase, Neutropenia, Increased glucose, Increased triglycerides, Decreased platelets
Post marketing reports
Edema, Pancreatitis, Liver function abnormalities, Diabetes mellitus, Arthralgia, Alopecia, Maculopapular rash, Angioedema, Pruritus
Some adverse effects may occur during therapy using with Synthivan tablets
Cardiac conduction abnormalities
This is due to prolonged elevation of PR intervals by atazanavir. Monitor with ECG frequently for reducing the adverse effects.
During the Synthivan treatment patient should be monitored with renal function test.
Nephrolithiasis & cholelithiasis
To overcome the problem, patient must be provided with additional management. Temporary postponement or discontinuation of therapy is occurring. Adverse effects may occur due to drug interactions, like; Synthivan with drugs are metabolized by CYP3A or CYP3A causes increased concentration of these drugs.
Rash is the one of the most important effect occurred on skin. Atazanavir should be stopped during rashes present.
Severe bleeding occurs, discontinue the protease inhibitor therapy.
Symptomatic elevation of bilirubin occurs by prohibits the UDP glucuronosyl transferase. Dose reduction is not possible, once the level of bilirubin is elevates stop the treatment.
Check the blood glucose level periodically Patient must be prescribed with dose adjustment insulin or oral hypoglycemic agents. Diabetes ketoacidosis should be occurred after discontinue the treatment.
Immune reconstitution syndrome
Stop the Synthivan therapy. Redistribution of fat occurred in the body leads to cause obesity. To overcome the problem in severe condition, discontinue the treatment.