Lofepramine (brand name: Lomont (UK) Emdalen (ZA), Gamanil (IE, UK (discontinued)) & Tymelyt (discontinued)) is a third generation tricyclic antidepressant which was introduced in 1983 for the treatment of depressive disorders. Lofepramine is less sedating than, for instance, amitriptyline, and is safer in overdose than older tricyclics.
§Indications
In the United Kingdom, Lofepramine is licensed for the treatment of depression which is its primary use in medicine.
§Side effects
- Common
- Constipation
- Dry Mouth
- Blurred Vision
- Sleepiness
- Uncommon
- Rare
- Constipation (leading to paralytic ileus, particularly in the elderly)
- Skin Rashes
- Very Rare
- Blurred Vision (precipitation of angle-closure glaucoma)
§Other side effects
Delusions, nightmares, facial oedema, general feeling of being unwell, bleeding from skin, inflammation of mucous membranes, loss of taste, psychiatric problems such as self-harm, pins and needles, sweating, dizziness. Can cause behavioural disturbance in the young. May produce weight gain or cause changes in the levels of blood sugar. Some patients report muscular discomfort, particularly in the shoulders.
§Interactions
Lofepramine is known to interact with
- Alcohol. Increased sedative effect
- Antiepileptics. Possibly antagonise the anticonvulsant effect of antiepileptics by lowering the convulsive threshold
- Antihistamines. Possible increase of antimuscarinic and sedative effects
- Antimuscarinics. Possible increase of antimuscarinic side-effects
- Anxiolytics and Hypnotics. Increased sedative effect
- Apraclonidine. Avoidance advised by manufacturer of apraclonidine
- Brimonidine. Avoidance advised by manufacturer of brimonidine
- Diazoxide. Enhanced hypotensive effect
- Hydralazine. Enhanced hypotensive effect
- Monoamine oxidase inhibitors (MAOIs). Do not start until 2 weeks after stopping MAOIs, also MAOIs should not be started until at least 1â€"2 weeks after stopping tricyclic-related antidepressants
- Moclobemide. do not start moclobemide for at least 1 week after stopping tricyclic-related antidepressants
- Nitrates. Possibly reduce effects of sublingual tablets of nitrates (failure to dissolve under tongue owing to dry mouth)
- Sodium Nitroprusside. Enhanced hypotensive effect
§Contraindications
- In the immediate recovery period after myocardial infarction
- In arrhythmias (particularly heart block)
- In the manic phase of bipolar disorder
- In acute porphyria
- With Amiodarone
- With Terfenadine
- In severe liver and/or severe renal impairment
§Mechanism of action
Lofepramine is a strong inhibitor of norepinephrine reuptake (Ki=5.4 nM) and a moderate inhibitor of serotonin reuptake (Ki=70 nM). It is a weak-intermediate level antagonist of the muscarinic acetylcholine receptors (Ki values of 67 nM, 330 nM, 130 nM, 340 nM, 460 nM for M1, M2, M3, M4 & M5 respectively).
The measured affinity [Kd (nM)] of Lofepramine at different receptor or transporter binding sites are listed below:
§Pharmacokinetics
It is partially converted to its active metabolite desipramine in vivo. However, it is unlikely this property plays a substantial role in its overall effects as lofepramine exhibits lower toxicity and anticholinergic side effects relative to desipramine while retaining equivalent antidepressant efficacy.
§Warnings
To be used with caution for epileptic patients or those with glaucoma or psychosis. Lofepramine should not be given to people who have suffered liver failure or heart disease. Not advisable for use in pregnant women.
§Availability
In the United Kingdom, lofepramine is marketed (as the hydrochloride salt) in the form of 70Â mg tablets and 5ml oral suspension as the generic Lomont.