Description
Duloxetine Pharmacodynamics
Duloxetine is an antidepressant, serotonin and noradrenaline reuptake inhibitor, weakly inhibits dopamine reuptake, with no significant affinity for histaminergic, dopaminergic, cholinergic and adrenergic receptors. The mechanism of action of duloxetine in the treatment of depression is to inhibit serotonin and noradrenaline reuptake, resulting in increased serotonergic and noradrenergic neurotransmission in the CNS.
Duloxetine has a central mechanism of pain syndrome suppression, which is primarily manifested by an increase in the threshold of pain sensitivity in pain syndrome of neuropathic etiology.
Indications
Depression;
Painful form of peripheral diabetic neuropathy;
Generalized anxiety disorder;
Chronic musculoskeletal pain syndrome (including that caused by fibromyalgia, chronic pain syndrome in the lower back and osteoarthritis of the knee).
Contraindications
Hypersensitivity to any of the ingredients of the drug;
Concomitant use with monoamine oxidase inhibitors (MAOIs);
Uncompensated closed-angle glaucoma;
Under 18 years of age (there is no clinical experience of duloxetine administration in patients in this age group);
Sucrose/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption;
Liver diseases accompanied by hepatic insufficiency;
Concomitant use of potent CYP1A2 isoenzyme inhibitors (fluvoxamine, ciprofloxacin, enoxacin);
Severe CKD (creatinine clearance (CK) less than 30 ml/min);
Uncontrolled arterial hypertension.
Dosage and administration method
- Orally. The capsules should be swallowed in whole without chewing or crushing. Do not add the drug to food or mix it with liquids, because it may damage the enteric coating of the pellets.
- The recommended starting dose of the drug is 60 mg once daily regardless of meals.
In some patients, it is necessary to increase the dose from 60 mg 1 time per day to a maximum dose of 120 mg per day in two doses to achieve good results. No systematic evaluation of doses above 120 mg has been performed. - In patients with renal impairment: the initial dose should be 30 mg 1 time per day in patients with severe renal impairment (terminal stage of CKD, creatinine clearance < 30 ml/min).
- In patients with impaired liver function: the initial dose of the drug should be reduced or the frequency of administration should be reduced in patients with cirrhosis.
- Abrupt withdrawal of therapy should be avoided. If duloxetine treatment is discontinued, the dose should be gradually reduced over one to two weeks to reduce the risk of withdrawal. If significant withdrawal symptoms occur after reducing the dose or discontinuing treatment, continuation of the previously prescribed dose may be considered. Subsequently, the physician may continue the dose reduction, but even more gradually.
