Product Information
Registration Status: ActiveAPO-DOXEPIN CAPSULE 25mg is approved to be sold in Singapore with effective from 1997-01-13. It is marketed by PHARMAFORTE SINGAPORE PTE LTD, with the registration number of SIN09120P.
This product contains Doxepin 25mg in the form of CAPSULE. It is approved for ORAL use.
This product is manufactured by APOTEX INC in CANADA.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Doxepin is a dibenzoxepin-derivative tricyclic antidepressant (TCA). Structurally similar to phenothiazines, TCAs contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, doxepin does not affect mood or arousal, but may cause sedation. In depressed individuals, doxepin exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as doxepin and amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. Doxepin has less sedative and anticholinergic effects than amitriptyline. See toxicity section below for a complete listing of side effects. When orally administered, doxepin may be used to treat depression and insomnia. Unlabeled indications of oral doxepin also include chronic and neuropathic pain, and anxiety. Doxepin may also be used as a second line agent to treat idiopathic urticaria. As a topical agent, doxepin may be used relieve itching in patients with certain types of eczema. It may be used for the management of moderate pruritus in adult patients with atopic dermatitis or lichen simplex chronicus.
Indication
**Oral: ** - Indicated for the treatment of depression and/or anxiety [FDA Label]. - Indicated for the treatment of depression and/or anxiety associated with different conditions, including alcoholism, organic disease and manic-depressive disorders [FDA Label]. - Indicated for the treatment of insomnia characterized by difficulties with sleep maintenance [L1347]. Topical: - Indicated for the short-term (up to 8 days) management of moderate pruritus in adult patients with atopic dermatitis or lichen simplex chronicus [L1344].
Mechanism of Action
The mechanism of action of doxepin is not completely understood. It is thought that like amitriptyline, doxepin enhances the actions of norepinephrine and serotonin by blocking their reuptake at the neuronal membrane. However, doxepin weakly inhibits the reuptake of dopamine. Doxepin may also act on histamine H1-receptors, resulting in sedative effects, and β-adrenergic receptors. It is also an antagonist of 5-hydroxytryptamine (serotonin) receptors, alpha-1 adrenergic receptor, and muscarinic cholinergic receptors.
Pharmacokinetics
- Absorption
- Doxepin is reported to be well-absorbed from the GI tract. Peak plasma concentrations (Cmax) occur within 1-2 hours of oral administration [A1945]. The AUC and Cmax are expected to increase when administered with a high fat meal [L1347]. Doxepin is also a lipophillic drug and may be capable of crossing the blood-brain-barrier.
- Distribution
- Doxepin is widely distributed throughout the body tissues. The mean apparent volume of distribution following a single 6 mg oral dose of Silenor to healthy subjects was 11,930 L [L1347].
- Metabolism
- Extensively metabolized in the liver via the same pathways as other TCAs. Following oral administration, doxepin undergoes extensive oxidation and demethylation. In vitro studies have shown that CYP2C19 and CYP2D6 are the major enzymes involved in doxepin metabolism, and that CYP1A2 and CYP2C9 are involved to a lesser extent [L1347]. N-demethylation produces a primary active metabolite, N-desmethyldoxepin (nordoxepin). The primary metabolite undergoes further biotransformation to glucuronide conjugates [L1347].
- Elimination
Clearance
The mean total apparent plasma clearance of a single oral dose of 50 mg doxepin in healthy individuals was 0.93 l/hr/kg [A1945].
Toxicity
Oral LD50 values in mouse and rat are 180 mg/kg and 147 mg/kg, respectively [MSDS]. Cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. No evidence of carcinogenic potential was observed in mice studies. Doxepin was negative in in vitro (bacterial reverse mutation, chromosomal aberration in human lymphocytes) and in vivo (rat micronucleus) assays, indicating it is unlikely to be mutagenic compound [L1347]. The effects of doxepin on fertility were investigated in male and female rats. Adverse effects on fertility (increased copulatory interval and decreased corpora lutea, implantation, viable embryos and litter size) and sperm parameters (increased percentages of abnormal sperm and decreased sperm motility) were observed [L1347]. However the AUC for doxepin and nordoxepin at the no-effect dose for adverse effects on reproductive performance and fertility in rats (10 mg/kg/day) are less than those in humans at the maximum recommended human dose of 6 mg/day [L1347].
Active Ingredient/Synonyms
Cidoxepin | Doxepin | Doxepin |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.