Drug profile of Daruvir 600mg
Daruvir 600mg tablets are containing an active substance known as Darunavir which expels anti-retroviral activity.
Due to the appearance of anti-viral medicine resistance which occurred during single use of Daruvir, it is administered by combining with other anti-retroviral drugs.
Daruvir is pharmacologically classified as HIV protease inhibitor, involved in the treatemtn of AIDS & HIV infections.
Brand name: Daruvir
Active ingredients: Darunavir
Pack: 60 tablets in a container
Classified as: Anti-retroviral drug
Prescribing information of Daruvir 600mg
The prescribing information of Daruvir in adults is;
Daruvir should be combined with ritonavir & also with other anti-retroviral drugs which is involved in the therapy of HIV-1 infections.
The uses of Daruvir is depends on;
Analysis of plasma HIV-1 RNA levels
CD4+ cells counts
Both are taking into consideration, after 48 weeks duration of time in anti-retroviral thapy for both new commenced or already treated patients in phase 3 trials.
The prescribing information of Daruvir in pediatric patients is;
The safety of Daruvir is effective only in pediatric patient with the age of 3 years.
Daruvir should be combined with ritonavir & also with other anti-retroviral drugs.
The use of darunavir in both adult & pediatric patients who are already experienced should be based on history of therapy.
Mechanism of Daruvir 600mg
Darunavir is expels an anti-retroviral effect by inhibiting the protease enzyme which is responsible for HIV viral proliferation, Dimerization and catalytic effect of HIV-1 protease also forbidden.
In virus infected cells, darunavir involved in inhibits the separation of HIV encoded Gag-pol polyproteins, thus the inhibition which forbids the production of mature infectious virus particle.
Darunavir has molecular flexibility, so it can easily adapts for changing shape of protease enzymes.
The co administration of Daruvir with 100mg of ritonavir as two times a day, the Tmax value reaches between 2.5 to 4 hours.
The mean bioavailability of both Daruvir & ritonavir is occurs by 37% & 82% respectively.
The effect of food, while taking Daruvir with ritonavir with food causes increases Cmax & AUC of darunavir compared to fasted state.
Combination of Daruvir with ritonavir must be taken with food.
Daruvir should be bind with human plasma protein nearly by 95%
The metabolism of Daruvir is undergoing by oxidation.
The metabolism is intensively occurred with the help of CYP enzymes, formerly by CYP3A.
Darunavir is highly eliminated via feces & urine at range of 41.2% & 7.7%.
The mean terminal half life period of Daruvir is almost 15 hours.
The creatinine clearance of both Daruvir alone or in combination, is 32.8L/hr & 5.9L/hr respectively.
When to take the Daruvir 600mg
Daruvir should be administered with food.
Dosage regimens of Daruvir 600mg
The Daruvir tablets should be combined with ritonavir for exerting good therapeutic effect.
In new commencement patients: for adults
The prescribed dose of Daruvir is 800mg should be administered with food as a single dose by combining with 100mg of ritonavir.
In therapy experienced patients:
The prescribed dose is 600mg of Daruvir with 100mg of ritonavir as a two times a day.
Pediatric age of 3 to less than 18 years:
In pediatric patients, Daruvir should not be used as single dosing for daily.
Dose recommendation should be based on weighing at least 10kg but less than 15 kg;
Greater or equal to 10kg to less tan 11kg: The prescribed dose is 200mg of Daruvir with 32mg of ritonavir
Greater or equal to 11kg to less than 12 kg: The prescribed dose is 220mg of Daruvir with 32mg of ritonavir
Greater or equal to 12kg to less than 13kg: The prescribed dose is 240mg of Daruvir with 40mg of ritonavir
Greater or equal to 13kg to less than 14kg: The prescribed dose is 260mg of Daruvir with 40mg of ritonavir
Greater or equal to 14kg to less than 15kg: The prescribed dose is 280mg of Daruvir with 48mg of ritonavir.
Dose recommendation for weighing at least 15kg;
≥ 15kg to <30kg: 375mg of Daruvir with 50mg ritonavir
≥30kg to <40kg: 450mg of Daruvir with 60mg of ritonavir
≥40kg: 600mg of Daruvir with 100mg of ritonavir
For liver impairment:
In mild to moderate hepatic impairment patients, dosage adjustment should not be suggested.
In severe hepatic impairment patients, the use of Daruvir should not be allowed.
Daruvir 600mg caused side effects
Stevens Johnson syndrome
Elevation of AST/ALT
Increasing alkaline phosphatase
Elevation of blood glucose level
Elevation of pancreatic lipase & amylase
Redistribution of fat
Acute generalized exanthematous pustulosis
Drug- drug interaction
Daruvir with ritonavir combined with drugs metabolized by CYP3A & CYP2D6, causes elevation of plasma concentration of these drugs which leads to cause extended therapeutic effect.
Both Daruvir & ritonavir are metabolized by CYP3A, drug which promote the CYP3A effect leads to elevate the clearance of darunavir & ritonavir which concluded as diminishing the plasma concentration of darunavir & ritonavir.
Daruvir & ritonavir combine with drugs which inhibits the CYP3A may leads to cause depleting the clearance of darunavir & ritonavir results as elevation of concentration of darunavir & ritonavir.
Daruvir tablet should be combined with Didanosine, affect the exposure of Didanosine. To overcome the problem Didanosine should be administered one hour earlier or two hours after the dose of Daruvir.
Daruvir concomitant with indinavir, causes increasing the effect of concentration of both darunavir & indinavir.
Daruvir with Lopinavir & ritonavir combination leads to cause decreasing the effect of concentration of darunavir
Daruvir combined with anti-arrhythmia agents causes increasing concentration of anti-arrhythmia.
Daruvir with warfarin an anti-coagulant, causes decreasing concentration of warfarin
Daruvir with carbamazepine an anti-convulsants, causes increasing the concentration of carbamazepine; with phenytoin or Phenobarbital causes decreasing the concentration of these drugs.
Daruvir combined with any anti-depressant agents, may leads to cause increasing the effect of concentration of these drugs.
Daruvir combined with anti-infective, anti-fungal or anti-gout cause’s elevation of effect of concentration of these drugs.
Daruvir combined with beta blocker, benzodiazepines, or calcium channel blocker, causes increasing its concentration.
Daruvir with dexamethasone causes decreasing the concentration of darunavir
Daruvir with lipid lowering agents, causes increasing the effect of concentration of these drugs.
Daruvir with immunosuppressant causes increasing the concentration of immuno suppressants.
Food drug interaction
Presence of food will leads to elevates the level of darunavir in the body.
Food will lead the absorption of darunavir.
Some drugs may contraindicate to darunavir ritonavir combination;
Alfuzosin, ergot derivatives, Cisapride, pimozide, Midazolam, st. Johns wort, lovastatin, simvastatin, rifampin, sildenafil
Hypersensitive reactions are produced due to patients are contraindicate to the component present in the Daruvir tablets.
For general consideration, Daruvir should be combined with ritonavir and should be taken with food for better anti-viral activity.
Drug induced hepatitis should be occurs, to avoid this problem, patient should be monitored with hepatic function test.
Darunavir is a sulfonamide moiety, use with cautiously if patients are allergy to sulfonamide.
Some drug – drug interaction may causes severe life threatening conditions. Avoid the combinational therapy.
Increasing blood glucose level during the Daruvir therapy is a major adverse effect.
Monitor the patient’s glucose level during the treatment periodically.
Redistribution of fat:
The major adverse risk of this condition is obesity. This may generally occurs in anti-retroviral treatments.
Immune reconstitution syndrome:
This may occurs in Daruvir therapy; to overcome the problem therapy should be discontinued.
In protease inhibitor therapies, there is a chance of getting increased bleeding condition leads to skin hematomas & hemarthrosis in patients suffered with hemophilia type A or B.
Pregnancy and lactation
Pregnancy category C
Darunavir should not be used in pregnancy & lactating period.
Mild to moderate: No dosage adjustment
Severe: not recommended
Based on creatinine clearance value, dosage management should be considered.
Storage and handling
Daruvir container should be stored at 25oC
Do not store the container in heat, moisture & light
If missed dose occurs, must consult with medical practitioner and follow the instructions.
Regular dosing schedule should be maintained.
In case of over dosage, there is no special anti-dote is present for treating the over dosage of darunavir.
Provide general supportive measures
Gastric lavage or emesis should be suggested to remove the unabsorbed content from the body.
Activated charcoal is also indicated to eliminate the unabsorbed content.
Hemodialysis is also not beneficial, because darunavir is highly bound to human plasma protein.