1 Name of Medicine
Venlafaxine (as hydrochloride).
2 Qualitative and Quantitative Composition
Venlafaxine XR-WGR capsules are available containing 37.5 mg, 75 mg, 150 mg or 225 mg of venlafaxine (as hydrochloride).
List of excipient with known effect. Phenylalanine, sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
Modified release capsules.
Venlafaxine XR-WGR capsules are a modified release formulation, which release the active constituent, venlafaxine hydrochloride, from mini-tablets within the capsule. Drug release is controlled by diffusion through the coating on the mini-tablets and is not pH dependent.
Venlafaxine XR-WGR venlafaxine (as hydrochloride) modified release capsules are available as:
37.5 mg, light grey opaque cap/peach opaque body size "3" hard capsule with thick and thin radial circular bands on both the cap and body in red ink.
75 mg, peach opaque cap/peach opaque body size "1" hard capsule with thick and thin radial circular bands on both the cap and body in red ink.
150 mg, dark orange opaque cap/dark orange opaque body size "0" hard capsule with thick and thin radial circular bands on both the cap and body in white ink.
225 mg, pink opaque cap/pink opaque body size '00' hard capsule with thick and thin radial circular bands on both the cap and body in blue ink.
4 Clinical Particulars
4.9 Overdose
In managing overdosage, consider the possibility of multiple medication involvement. (See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Signs and symptoms. During pre-marketing trials, most patients who have overdosed with venlafaxine were asymptomatic. Of the remainder, somnolence was the most commonly reported symptom. Mild sinus tachycardia and mydriasis have also been reported. There were no reports of seizures, respiratory distress, significant cardiac disturbances, or significant laboratory test result abnormalities among any of the cases reported to date. However, seizures and respiratory distress occurred in one patient in an on-going study who ingested an estimated 2.75 g of venlafaxine with naproxen and thyroxine. Generalised convulsions and coma resulted and emergency resuscitation was required. Recovery was good without sequelae.
In post-marketing experience, overdose with venlafaxine was reported predominantly in combination with alcohol and/or other drugs. The most commonly reported events in overdose include tachycardia, changes in level of consciousness (ranging from somnolence to coma), mydriasis, vomiting and seizures. Other events reported included electrocardiogram changes (e.g. prolongation of QT interval, bundle branch block, QRS prolongation), ventricular fibrillation, ventricular tachycardia (including torsade de pointes), bradycardia, hypotension, vertigo, and death. Serotonin toxicity has been reported in association with venlafaxine overdose.
Fatal overdoses. Published retrospective analyses from the United Kingdom (UK) report the rate of antidepressant overdose deaths per million prescriptions. In these analyses, the rate for venlafaxine is higher than that for SSRIs, but lower than that for tricyclic antidepressants. These analyses did not adjust for suicide risk factors.
Epidemiological studies have shown that venlafaxine is prescribed to patients with a higher pre-existing burden of suicide risk factors than patients prescribed SSRIs. The extent to which the finding of an increased risk of fatal outcomes can be attributed to the toxicity of venlafaxine in overdosage as opposed to some characteristics of venlafaxine-treated patients is not clear, Prescriptions of venlafaxine should be written for the smallest quantity of drug consistent with good patient management, in order to reduce the risk of overdose (see Section 4.4 Special Warnings and Precautions for Use, Clinical worsening and suicide risk).
Management of overdosage. Severe poisoning may require complex emergency treatment and monitoring. Therefore, in event of suspected overdose involving venlafaxine, prompt contact with Poisons Information Centre on 13 11 26 (Australia) is recommended.
General supportive and symptomatic measures are recommended. Ensure an adequate airway, oxygenation and ventilation. Cardiac rhythm and vital signs must be monitored. Administration of activated charcoal may also limit drug absorption. Where there is a risk of aspiration, induction of emesis is not recommended. No specific antidotes for venlafaxine are known. Forced diuresis, dialysis, haemoperfusion and exchange transfusion are unlikely to be of benefit. Venlafaxine and ODV are not considered dialyzable because haemodialysis clearance of both compounds is low.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
5 Pharmacological Properties
5.3 Preclinical Safety Data
Genotoxicity. There was no evidence of gene mutation or chromosomal change in a series of genotoxicity assays using venlafaxine and the main human metabolite ODV.
Carcinogenicity. Venlafaxine was given by oral gavage to mice and rats for 18 months and 24 months respectively, at dosages up to 120 mg/kg/day. There were no clear drug-related oncogenic effects in either species. In these studies, animal exposure to the main human metabolite ODV was less, and exposure to venlafaxine was more than would be expected in humans taking the recommended therapeutic and maximum doses.
6 Pharmaceutical Particulars
6.7 Physicochemical Properties
Venlafaxine hydrochloride is a white to off-white crystalline solid with a solubility of 572 mg/mL in water (adjusted to ionic strength of 0.2 M with sodium chloride).
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSVENLEN.gif Its molecular weight is 313.9 and its molecular formula is C17H27NO2.HCl.
The full chemical name for venlafaxine hydrochloride is 1-[(R/S)-2-(2-dimethylamino)-1- (4-methoxyphenyl)ethyl]cyclohexanol hydrochloride.
CAS number. 99300-78-4.
7 Medicine Schedule (Poisons Standard)
S4, Prescription Only Medicine.
Summary Table of Changes
https://stagingapi.mims.com/au/public/v2/images/fulltablegif/VNXRGRST.gif
