Co-treatment with thyroid hormones may also increase the potential for adverse reactions. Pharmacology
Doxepin is a tricyclic antidepressant (TCA). It acts as a serotonin–norepinephrine reuptake inhibitor (SNRI) (a reuptake inhibitor of serotonin and norepinephrine), with additional antiadrenergic, antihistamine, antiserotonergic, and anticholinergic activities. Pharmacodynamics
Doxepin is a reuptake inhibitor of serotonin and norepinephrine, or a serotonin–norepinephrine reuptake inhibitor (SNRI), and has additional antiadrenergic, antihistamine, antiserotonergic, and anticholinergic activities. It is specifically an antagonist of the histamine H1 and H2 receptors, the serotonin 5-HT2A and 5-HT2C receptors, the α1-adrenergic receptor, and the muscarinic acetylcholine receptors (M1–M5). Similarly to other tricyclic antidepressants, doxepin is often prescribed as an effective alternative to SSRI medications. Doxepin is also a potent blocker of voltage-gated sodium channels, and this action is thought to be involved in both its lethality in overdose and its effectiveness as an analgesic (including in the treatment of neuropathic pain, and as a local anesthetic). The potencies of doxepin in terms of its receptor antagonism specifically are as follows:
Extremely strong: Histamine H1 receptor
Strong: α1-adrenergic receptor, 5-HT2A and muscarinic acetylcholine receptors
Moderate: 5-HT2C and 5-HT1A receptors
Weak: α2-adrenergic and D2 receptorsBased on its IC50 values for monoamine reuptake inhibition, doxepin is relatively selective for the inhibition of norepinephrine reuptake,  with a much weaker effect on the serotonin transporter. Although there is a significant effect that takes place at one of the specific serotonergic binding sites, the 5-HT2A serotonin receptor subtype.
Contraindications
Hypersensitivity against diclofenac
History of allergic reactions (bronchospasm, shock, rhinitis, urticaria) following the use of other NSAIDs such as aspirin
Third-trimester pregnancy
Active stomach and/or duodenal ulceration or gastrointestinal bleeding
Inflammatory bowel disease such as Crohns disease or ulcerative colitis
Severe congestive heart failure (NYHA III/IV)
Pain management in the setting of coronary artery bypass graft (CABG) surgery
Severe liver insufficiency (Child-Pugh Class C)
Severe chronic kidney disease (creatinine clearance <30 ml/min)
Caution in patients with pre-existing hepatic porphyria, as diclofenac may trigger attacks
Caution in patients with severe, active bleeding such as cerebral hemorrhage
NSAIDs in general should be avoided during dengue fever, as it induces (often severe) capillary leakage and subsequent heart failure. Caution in patients with fluid retention or heart failure
Can lead to onset of new hypertension or worsening of pre-existing hypertension
Can cause serious skin adverse events such as exfoliative dermatitis, Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal

Adverse effects
Diclofenac consumption has been associated with significantly increased vascular and coronary risk in a study including coxib, diclofenac, ibuprofen and naproxen. Upper gastrointestinal complications were also reported. Major adverse cardiovascular events (MACE) were increased by about a third by diclofenac, chiefly due to an increase in major coronary events. Compared with placebo, of 1000 patients allocated to diclofenac for a year, three more had major vascular events, one of which was fatal.