pms-Dexamethasone Drug Interactions

Prior to the use of Dexamethasone in combination with any other medicinal product, reference should be made to the Summary of Product Characteristics of that product.
Pharmacodynamic interactions: NSAIDs and salicylates: Patients taking NSAIDs should be monitored, as NSAIDs may increase the incidence and/or severity of gastric ulcers. Acetylsalicylic acid should be used carefully in combination with corticosteroids in hypoprothrombinaemia.
The renal clearance of salicylates is increased by corticosteroids. Therefore, the dosage of salicylates may be reduced once the steroids are discontinued. Steroid withdrawal may result in salicylate intoxication due to the increase of salicylate concentration in the serum.
Antidiabetic agents: Corticosteroids reduce the effect of antidiabetic agents such as insulin, sulfonylurea, and metformin. Hyperglycaemia and diabetic ketoacidosis may occur occasionally. Therefore, at the beginning of treatment, diabetics should have more frequent blood and urine tests.
Diuretics, amphotericin B, tetracosactide, laxatives, cardiac glycosides: The hypokalemic effect of acetazolamide, loop diuretics, thiazide diuretics, kaliuretics, amphotericin B injections (glucomineral)-corticosteroids, tetracosactide and laxatives will increase. Hypokalemia promotes cardiac arrhythmias, especially torsade de pointes, and increases the toxicity of cardiac glycosides. Before the start of corticosteroid treatment, hypokalemia should be corrected and patients should be monitored clinically, for electrolytes and by electrocardiography. Furthermore, there are case reports in which the simultaneous use of amphotericin B and hydrocortisone led to an enlarged heart and heart failure.
Antiulcer drugs: Carbenoxolone increases the risk of hypokalemia.
Chloroquine, hydroxychloroquine and mefloquine: Increased risk of myopathies and cardiomyopathies.
Antihypertensive agents: Concomitant administration of ACE inhibitors creates an increased risk of blood disorders.
The blood pressure-lowering effects of antihypertensive drugs may be affected by corticosteroids. The dose of the anti-hypertensive treatment may have to be adjusted during the treatment with dexamethasone.
Thalidomide: Great care should be taken during co-administration with thalidomide, a there have been reported cases of toxic epidermal necrolysis.
Vaccines: The effect of vaccinations may be reduced during treatment with dexamethasone.
Vaccination with live vaccines during treatment with large therapeutic doses of dexamethasone (and other corticosteroids) is contraindicated due to the possibility of viral infection. In this case, vaccination should be postponed for at least 3 months after the completion of treatment with corticosteroids. Other types of immunisation during treatment with large therapeutic doses of corticosteroids are dangerous due to the risk of neurological complications and decreased or absent increase in the antibody titers (in comparison with expected values) and therefore a smaller protective effect. However, patients who have received corticosteroids locally (parenteral) or for a short period of time (less than 2 weeks), in smaller doses may be immunised.
Cholinesterase inhibitors: Concomitant use of cholinesterase inhibitors and corticosteroids may cause serious muscle weakness in patients with myasthenia gravis. If possible, cholinesterase inhibitors should be discontinued at least 24 hours before the start of corticosteroid therapy.
Fluoroquinolones: The risk of tendinitis and tendon rupture is increased in patients treated concomitantly with glucocorticoids and fluoroquinolones.
CYP3A inhibitors: Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.
Pharmacokinetic interactions: Effects of other medicinal products on dexamethasone: CYP3A4 inducers: Dexamethasone is metabolized via the cytochrome P450 3A4 (CYP3A4).
The administration of dexamethasone with inducers of CYP3A4, such as ephedrine, barbiturates, rifabutin, rifampicin, phenytoin, and carbamazepine can lead to reduced plasma concentrations of dexamethasone, so the dose must be increased.
Aminoglutethimide: Aminoglutethimide can accelerate the reduction of dexamethasone and reduce its efficacy. If necessary, the dexamethasone dosage should be adjusted.
Bile acid resins: Bile acid resins, such as cholestyramine, may decrease the absorption of dexamethasone.
Topically applied gastrointestinal drugs, antacids, activated charcoal: Decreased glucocorticoid resorption has been described during co-administration of prednisolone and dexamethasone. Therefore, the administration of glucocorticoids and topically applied gastrointestinal drugs, antacids, activated charcoal should be postponed (with an interval of at least two hours).
CYP3A4 inhibitors: The administration of dexamethasone with inhibitors of CYP3A4, such as azole antifungals (e.g. ketoconazole, itraconazole), HIV protease inhibitors (e.g. ritonavir) and macrolide antibiotics (e.g. erythromycin) may lead to increased plasma concentrations and reduced clearance of dexamethasone. If required, the dexamethasone dose should be reduced.
Ketoconazole may not only increase the plasma concentration of dexamethasone by inhibition of CYP3A4, but also suppress adrenal corticosteroid synthesis and cause adrenal insufficiency upon discontinuation of corticosteroid treatment.
Estrogens and oral contraceptives: Estrogens, including oral contraceptives, may inhibit the metabolism of certain corticosteroids and thus enhance their effect.
Effects of dexamethasone on other medicinal products: CYP3A4 substrates: Dexamethasone is a moderate inducer of CYP3A4. The administration of dexamethasone with substances metabolized by CYP3A4 can lead to increased clearance and decreased plasma concentrations of these substances.
Tuberculostatics: A reduction of isoniazid plasma concentrations was observed during concurrent use of prednisolone. Patients taking isoniazid should be monitored closely.
Cyclosporine: Concomitant administration of cyclosporine and corticosteroids may lead to an increased effect of both substances. There is an increased risk of cerebral seizures.
Praziquantel: Reduced praziquantel plasma concentrations create a risk of treatment failure due to the increased hepatic metabolism of dexamethasone.
Oral anticoagulants (coumarin): Concomitant corticosteroid therapy may either potentiate or lead to a weakening of the effect of oral anticoagulants. In case of high doses or of treatment lasting over 10 days there is a risk of bleeding specific to corticosteroid therapies (gastrointestinal mucosa, vascular fragility). Patients who use corticosteroids combined with oral anticoagulants should be closely monitored (controls on day 8, then every two weeks during and after treatment).
Atropine and other anticholinergics: Intraocular pressure increases may be noted during co-administration with dexamethasone.
Non-depolarizing muscle relaxants: the muscle relaxing effect may last longer.
Somatotropin: the effect of the growth hormone can be reduced.
Protirelin: Reduced increase in TSH may be noted during administration of protirelin.