Invirase and Kaletra Oral Solution

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Talk to your doctor before using saquinavir together with lopinavir. Combining these medications can increase the risk of an irregular heart rhythm that may be serious. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, or irregular heartbeat during treatment with these drugs, whether together or alone. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

MONITOR CLOSELY: Both saquinavir and lopinavir have been associated with prolongation of the QT interval when coadministered with ritonavir as a pharmacokinetic booster. Theoretically, combining these medications may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In a study of 59 healthy volunteers aged 18 to 55 years who were administered saquinavir/ritonavir at a therapeutic dosage of 1000 mg/100 mg twice daily and a supratherapeutic dosage of 1500 mg/100 mg twice daily, the maximum mean QT prolongation (QTcS; study-specific QT interval correction) on treatment day 3 was 18.9 msec for the lower dosage and 30.2 msec for the supratherapeutic dosage, compared to 12.2 msec for the active control (moxifloxacin 400 mg). The majority of subjects (89% and 80% in the therapeutic and supratherapeutic groups, respectively) had a QTcS less than 450 msec, and none had a QTc interval exceeding the potentially clinically relevant threshold of 500 msec. In a study of 39 healthy adults who were administered lopinavir-ritonavir at a therapeutic dosage of 400 mg-100 mg twice daily and a supratherapeutic dosage of 800 mg-200 mg twice daily, the maximum mean time-matched difference in QTcF interval from placebo (after baseline correction) was 5.3 msec for the lower dosage and 15.2 msec for the supratherapeutic dosage in the 12 hours postdose on treatment day 3 when exposures were approximately 1.5 and 3-fold higher, respectively, than those observed with recommended once-daily or twice-daily dosages of lopinavir-ritonavir at steady state. No subject experienced an increase in QTcF greater than 60 msec from baseline or a QTcF interval greater than 500 msec. There have been cases of QT interval prolongation and torsade de pointes arrhythmia during postmarketing use of lopinavir-ritonavir, although causality could not be established. Limited clinical data have been published regarding the effects of saquinavir in combination with lopinavir and ritonavir on the QT interval. Two cases of QT prolongation were observed in a group of 26 pediatric patients who received lopinavir/ritonavir at higher than recommended dosages (400 mg/100 mg/m2 without concomitant NNRTI and 480 mg/120 mg/m2 with concomitant NNRTI) with saquinavir mesylate added at week 4. However, both subjects had additional predisposing conditions such as electrolyte abnormalities, concomitant medications, or preexisting cardiac abnormalities.

MONITOR CLOSELY: Both saquinavir and lopinavir have been associated with prolongation of the PR interval when coadministered with ritonavir as a pharmacokinetic booster. Theoretically, combining these medications may result in additive effects and increased risk of bradycardia and heart block. In a study of 59 healthy volunteers aged 18 to 55 years, PR interval prolongation greater than 200 msec (first-degree atrioventricular block) was observed on treatment day 3 in 40% and 47% of subjects during administration of saquinavir/ritonavir at a therapeutic dosage of 1000 mg/100 mg twice daily and a supratherapeutic dosage of 1500 mg/100 mg twice daily, respectively, compared to 3% of subjects during administration of the active control (moxifloxacin) and 5% of subjects during administration of placebo. The maximum mean PR interval changes relative to the predose baseline value were 25 msec and 34 msec for the saquinavir/ritonavir therapeutic and supratherapeutic regimens, respectively, while almost no change occurred during the moxifloxacin and placebo arms. In a study of 39 healthy adults who were administered lopinavir-ritonavir at a therapeutic dosage of 400 mg-100 mg twice daily and a supratherapeutic dosage of 800 mg-200 mg twice daily, mean changes from baseline in the PR interval ranged from 11.6 to 24.4 msec in the 12 hours postdose on treatment day 3 when exposures were approximately 1.5 and 3-fold higher, respectively, than those observed with recommended once-daily or twice-daily dosages of lopinavir-ritonavir at steady state. After baseline correction, the maximum mean difference from placebo in the PR interval was 24.9 msec for the lower dosage and 31.9 msec for the supratherapeutic dosage. Maximum PR interval observed was 286 msec, and no second- or third-degree heart block occurred. There have been postmarketing reports of asymptomatic prolongation of the PR interval in some patients receiving combination antiretroviral therapy containing lopinavir-ritonavir. Second- and third-degree atrioventricular block have occurred rarely in patients with underlying structural heart disease or preexisting conduction system abnormalities and in patients receiving lopinavir-ritonavir with other drugs known to prolong the PR interval.

MANAGEMENT: The product labeling for saquinavir and lopinavir-ritonavir both recommend that these medications not be used with other agents that can prolong the QT interval. Whether they should be used with each other is unknown, but coadministration may increase the risk of QT and PR prolongation and should preferably be avoided if possible. If concomitant use is necessary, the recommended dosages are saquinavir 1000 mg twice daily and lopinavir-ritonavir 400 mg-100 mg twice daily. Once-daily dosing of lopinavir-ritonavir has not been studied for use in combination with saquinavir. Patients should be advised to notify their physician if they experience dizziness, lightheadedness, fainting, palpitations, syncope, and/or irregular heartbeat.

Invirase

Generic Name: saquinavir

Brand name: Invirase, Fortovase

Synonyms: n.a.

What is Invirase?

Kaletra Oral Solution

Generic Name: lopinavir / ritonavir

Brand name: Kaletra

Synonyms: Kaletra

What is Kaletra Oral Solution?