Product Information
Registration Status: ActiveACUGESIC CAPSULE 50mg is approved to be sold in Singapore with effective from 1996-02-10. It is marketed by DUOPHARMA (SINGAPORE) PTE LTD, with the registration number of SIN08953P.
This product contains Tramadol 50mg in the form of CAPSULE. It is approved for ORAL use.
This product is manufactured by DUOPHARMA (M) SDN BHD in MALAYSIA.
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
A narcotic analgesic proposed for moderate to severe pain. It may be habituating. Tramadol is also prepared as a variable release capsules, marketed under the brand name ConZip. For example, a 150 mg capsule will contain 37.5 mg of the immediate release form and 112.5 mg of the extended release form.
Indication
Indicated in the treatment of moderate to severe pain. Consider for those prone to constipation or respiratory depression. Tramadol is used to treat postoperative, dental, cancer, and acute musculosketetal pain and as an adjuvant to NSAID therapy in patients with osteoarthritis.
Mechanism of Action
Tramadol and its O-desmethyl metabolite (M1) are selective, weak OP3-receptor agonists. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. The analgesic properties of Tramadol can be attributed to norepinephrine and serotonin reuptake blockade in the CNS, which inhibits pain transmission in the spinal cord. The (+) enantiomer has higher affinity for the OP3 receptor and preferentially inhibits serotonin uptake and enhances serotonin release. The (-) enantiomer preferentially inhibits norepinephrine reuptake by stimulating alpha(2)-adrenergic receptors.
Pharmacokinetics
- Absorption
- Racemic tramadol is rapidly and almost completely absorbed after oral administration. The mean absolute bioavailability of a 100 mg oral dose is approximately 75%. The mean peak plasma concentration of racemic tramadol and M1 occurs at two and three hours, respectively, after administration in healthy adults.
- Distribution
- * 2.6 L/kg [male, 100 mg intravenous dose] * 2.9 L/kg [female, 100 mg intravenous dose]
- Metabolism
- Hepatic. The major metabolic pathways appear to be N- and O- demethylation and glucuronidation or sulfation in the liver. One metabolite (O-desmethyltramadol, denoted M1) is pharmacologically active in animal models. CYP3A4 and CYP2B6 facilitates the biotransformation of tramadol to N-desmethyl-tramadol. CYP2D6 facilitates the biotransformation of tramadol to O-desmethyl-tramadol.
- Elimination
Clearance
* 5.9 mL/min/Kg [Healthy Adults, 100 mg qid, MD p.o] * 8.5 mL/min/Kg [Healthy Adults, 100 mg SD p.o] * 6.89 mL/min/Kg [Geriatric, (<75 yr), 50 mg SD p.o.] * 4.23 mL/min/Kg [Hepatic Impaired, 50 mg SD p.o.] * 4.23 mL/min/Kg [Renal Impaired, Clcr10-3mL/min, 100 mg SD i.v.] * 3.73 mL/min/Kg [Renal Impaired, CLcr<5 mL/min, 100 mg SD i.v.] * 6.4 mL/min/Kg [Male following a 100 mg IV dose] * 5.7 mL/min/Kg [Female following a 100 mg IV dose]
Toxicity
LD50=350mg/kg (orally in mice)
Active Ingredient/Synonyms
(+)-Tramadol | (+)-trans-2-(Dimethylaminomethyl)-1-(m-methoxyphenyl)cyclohexanol | Tramadol |
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.