Drug Interactions between moxifloxacin / triamcinolone and saquinavir

MONITOR CLOSELY: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of triamcinolone. No pharmacokinetic data are available. However, there have been numerous published case reports of Cushing's syndrome and adrenal suppression associated with concomitant use of triamcinolone with various ritonavir-containing antiretroviral regimens and one case report with nefazodone.

MANAGEMENT: The possibility of increased corticosteroid effects should be considered when triamcinolone is used with potent CYP450 3A4 inhibitors. Some authorities advise against concomitant use unless the potential benefit outweighs the risk. If coadministration is necessary, a lower dosage of triamcinolone may be appropriate. Patients should be monitored for signs and symptoms of hypercorticism such as acne, striae, thinning of the skin, easy bruising, moon facies, dorsocervical "buffalo" hump, truncal obesity, increased appetite, acute weight gain, edema, hypertension, hirsutism, hyperhidrosis, proximal muscle wasting and weakness, glucose intolerance, exacerbation of preexisting diabetes, depression, and menstrual disorders. Other systemic glucocorticoid effects may include adrenal suppression, immunosuppression, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents. Following extensive use with a potent CYP450 3A4 inhibitor, a progressive dosage reduction may be required over a longer period if triamcinolone is to be withdrawn from therapy, as there may be a significant risk of adrenal suppression. Signs and symptoms of adrenal insufficiency include anorexia, hypoglycemia, nausea, vomiting, weight loss, muscle wasting, fatigue, weakness, dizziness, postural hypotension, depression, and adrenal crisis manifested as inability to respond to stress (e.g., illness, infection, surgery, trauma).

MONITOR CLOSELY: Concomitant administration of corticosteroids may potentiate the risk of tendinitis and tendon rupture associated with fluoroquinolone treatment. The mechanism is unknown. Tendinitis and tendon rupture have most frequently involved the Achilles tendon, although cases involving the rotator cuff (the shoulder), the hand, the biceps, and the thumb have also been reported. Some have required surgical repair or resulted in prolonged disability. Tendon rupture can occur during or up to several months after completion of fluoroquinolone therapy.

MANAGEMENT: Caution is recommended if fluoroquinolones are prescribed in combination with corticosteroids, particularly in patients with other concomitant risk factors (e.g., age over 60 years; recipient of kidney, heart, and/or lung transplant). Patients should be advised to stop taking the fluoroquinolone, avoid exercise and use of the affected area, and promptly contact their physician if they experience pain, swelling, or inflammation of a tendon. In general, fluoroquinolones should only be used to treat conditions that are proven or strongly suspected to be caused by bacteria and only if the benefits outweigh the risks.

CONTRAINDICATED: Saquinavir in combination with ritonavir may cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval 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 general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Coadministration of ritonavir-boosted saquinavir with other drugs that can prolong the QT interval is considered contraindicated.