Philcort-16 Drug Interactions

Methylprednisolone is a cytochrome P450 enzyme (CYP) substrate and is metabolised mainly by the CYP3A4 enzyme. CYP3A4 is the dominant enzyme of the most abundant CYP subfamily in the liver of adult humans. It catalyzses 6β-hydroxylation of steroids, the essential Phase I metabolic step for both endogenous and synthetic corticosteroids. Many other compounds are also substrates of CYP3A4, some of which (as well as other medicines) have been shown to alter glucocorticoid metabolism by induction (upregulation) or inhibition of the CYP3A4 enzyme.
CYP3A4 Inhibitors: Drugs that inhibit CYP3A4 activity generally decrease hepatic clearance, resulting in increased plasma concentration of methylprednisolone. Coadministration of CYP3A4 inhibitors may require titration of methylprednisolone dosage to reduce the risk of adverse effects and avoid steroid toxicity.
CYP3A4 Inhibitors include: Antifungals such as ketoconazole and itraconazole.
Antiemetics such as aprepitant and fosaprepitant.
Immunosuppressants such as ciclosporin. Mutual inhibition of metabolism occurs with concurrent use of ciclosporin and methylprednisolone, which may increase the plasma concentrations of either or both drugs. Therefore, it is possible that adverse events associated with the use of either drug alone may be more likely to occur upon coadministration. Convulsions have been reported with concurrent use of methylprednisolone and ciclosporin.
Macrolide antibacterials such as clarithromycin, erythromycin and troleandomycin.
HIV-Protease inhibitors such as indinavir and ritonavir, may increase plasma concentrations of corticosteroids. Corticosteroids may induce the metabolism of HIV-protease inhibitors, resulting in reduced plasma concentrations.
Calcium channel blockers such as diltiazem.
Isoniazid may increase the plasma concentration of methylprednisolone. In addition, there is a potential effect of methylprednisolone to increase the acetylation rate and clearance of isoniazid.
Oral contraceptives such as ethinylestradiol and norethisterone, retard the metabolism of corticosteroids due to increased binding to globulin, resulting in increased plasma levels of corticosteroids and potentiating their biological effect. The dose of corticosteroids may need to be adjusted when commencing or stopping oral contraceptive therapy.
Grapefruit juice.
CYP3A4 Inducers: Drugs that induce CYP3A4 activity generally increases hepatic clearance, resulting in decreased plasma concentrations of methylprednisolone. Coadministration of these substances may require an increase in methylprednisolone dosage to achieve the desired result.
CYP3A4 Inducers include: Anticonvulsants such as phenobarbital, phenytoin, carbamazepine and primidone.
Bactericidal antibiotics such as rifampicin and rifabutin.
CYP3A4 Substrates: In the presence of another CYP3A4 substrate, the hepatic clearance of methylprednisolone may be affected, with corresponding dosage adjustments required. It is possible that adverse events associated with the use of either drug alone may be more likely to occur with coadministration. Most CYP3A4 inhibitors are also CYP3A4 substrates.
Immunosuppressants such as cyclophosphamide and tacrolimus.
Other Interactions: Other interactions and effects that occur with methylprednisolone are described as follows.
Antacids: Concurrent use may decrease absorption of corticosteroids. Efficacy may be reduced sufficiently to require dosage adjustments in patients receiving small doses of corticosteroids.
Antidiabetic Agents: Corticosteroids may increase blood glucose levels. Dose adjustments of antidiabetic therapy may be required with concurrent therapy.
Anticholinergics: Corticosteroids may influence the effect of anticholinergics.
Acute myopathy has been reported with the concomitant use of high doses of corticosteroids and anticholinergics, such as neuromuscular blocking drugs.
Antagonism of the neuromuscular blocking effects of pancuronium and vecuronium has been reported in patients taking corticosteroids. This interaction may be expected with all competitive neuromuscular blockers.
Anticholinesterases: Steroids may reduce the effects of anticholinesterases in myasthenia gravis.
Anticoagulants (Oral): The effect of methylprednisolone on oral anticoagulants is variable. There are reports of enhances as well as diminished effects of anticoagulants when given concurrently with corticosteroids. Therefore, coagulation indices (such as INR or prothrombin time) should be monitored to maintain the desired anticoagulant effects.
Aromatase Inhibitors: Aminoglutethimide-induced adrenal suppression may exacerbate endocrine changes caused by prolonged glucocorticoid treatment.
Cardiac Glycosides: There is a risk of toxicity if hypokalaemia occurs due to corticosteroid treatment.
Diuretics and Other Potassium Depleting Agents: Excessive potassium loss maybe experienced with concurrent use of corticosteroids and potassium depleting diuretics (such as furosemide and thiazides) or carbonic anhydrase inhibitors (such as acetazolamide). Patients should be observed closely for development of hypokalaemia. There is also an increased risk of hypokalaemia with concurrent use of corticosteroids with amphotericin B, xanthines, or beta2 agonists.
Mifepristone: The effect of corticosteroids may be reduced for 3-4 days after taking mifepristone.
NSAIDs: Concomitant administration may increase the risk of gastrointestinal bleeding and ulceration. Methylprednisolone may increase the renal clearance of high-dose aspirin, which can lead to decreased salicylate serum levels. Discontinuation of methylprednisolone treatment can lead to raised salicylate serum levels, which could lead to an increased risk of salicylate toxicity.
Somatropin: Concomitant administration may inhibit the growth promoting effects of somatropin.
Sympathomimetics: There is an increased risk of hypokalaemia with concurrent high doses of corticosteroids and sympathomimetics such as salbutamol, salmeterol, terbutaline or formoterol.
Vaccines: Live vaccines should not be given to individuals with impaired immune responsiveness. The antibody response to other vaccines may be diminished.