Both CYP1A2 and CYP2D6 are responsible for Duloxetine metabolism Inhibitors of CYP1A2 and CYP2D6 Concomittant use of drugs that inhibit CYP1A2 metabolism include- Cimetidine, Quinolones antimicrobials such as Ciprofloxacin and Enoxacin and drugs that inhibit CY2D6 along with Duloxetine would be expected to result in higher concentrations of Duloxetine Drugs Highly Bound to Plasma Protein- Because Duloxetine is highly bound to plasma proteins administration of Duloxetine to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug potentially resulting in adverse events.

Discontinuating Duloxetine Symptoms associated with discontinuation of duloxetine and other SSRIs andSNRIs have been reported. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessatin is recommended whenever possible.

Diabetic Peripheral Neuropathic pain

Serotin and Norephinephrine reuptake inhibitors - include Duloxetine and Desvenlafaxine Refer - Duloxetine

Transcient nausea of mild to moderate intensity was the most commonly reported adverse effect.

Though use of Duloxetine was associated with significant increase inheart rate, there was no sustained elevation in the blood pressure and it did not prolong corrected QT interval Most common ADR is dose related.

It is mild to moderate severity and tends to resolve within 1-4 weeks. Other ADR reported- Dry mouth, Insomnia, Fatigue, Constipation, Dizziness, Headache, Somnolence Increased sweating, Vomiting, Diarrhea, Anorexia, and tremor. Serious adverse events are rare in Duloxetine Therapy.

Known hypersensitivity to Duloxetine or any of the inactive ingredients In patients taking monoamine oxidase inhibitors (MAOIs) In patients with uncontrolled narrow angle glaucoma In patients with liver disease resulting in hepatic impairment Pregnancy and lactation In combinations with CYP1A2 inhibitors, like Fluvoxamine, Ciprofloxacin, or Enoxacine, since the combination results in elevated plasma concentrations of Duloxetine Precautions- Hepatoxicity- Duloxetine increases therisk of elevation of serum transaminase lrevels. Duloxetine should ordinarily not be prescribed to patients with substantial alcohol use.

Effect on Blood Pressure- Duloxetine treatment is associated with mean increases in blood pressure compared to placebo. Blood pressure should be measured prior to initiating treatment and periodically measured throughout treatment.

Activation of Mania/Hypomania- Activation of mania/hypomania has been reported in small proportions. Duloxetine should be used cautiously in patients with a history of mania

Diabetic Peripheral Neuropathic pain Dosage recommended 60mg mg per day Consider starting at lower dose in patients with renal impairment or tolerability concerns

Serotin and Norephinephrine reuptake inhibitors - include Duloxetine and Desvenlafaxine Refer - Duloxetine

Pharmacokinetics-

Orally administered Duloxetine iswell absorbed. The time to reach Cmx and tmax is in the range of 4-6 hrs in healthy volunteers Duloxetine ishugly bound (> 90% ) to proteins in human plasma .

Duloxetine bioavailbility (AUC) appears to be reduced by about one-third in smokers. Dosage modifications are not recommended for smokers

Pregnancy In animal reproduction studies Duloxetine has been shown to have advese effects on embrryo/fetal and postnatal development. Labor/Delivery Duloxetine should be used during labor and delivery only if the potential benefits justifies the risk to the fetus. Nursing mothers- Duloxetine and/or its metabolites are excreted into the milk of lactating rats. It is not known whether or not Duloxetine and/ or its metabolites are excreted into human milk.

Duloxetine not recommended.

Pediatric Use- Safety and efficay in pediatric patients have not been established

Geriatric use- No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other clinical experience has not identified differences in responses between the two groups. However, greater sensitivity of some older individuals cannot be ruled out.