Lofepramine

The safety of lofepramine for use during pregnancy has not been established and there is evidence of harmful effects in pregnancy in animals when high doses are given. Lofepramine has been shown to cross the placenta. The administration of lofepramine in pregnancy is therefore not advised unless there are compelling medical reasons.

Adverse effects such as withdrawal symptoms, respiratory depression and agitation have been reported in neonates whose mothers have taken tricyclic antidepressants during the last trimester of pregnancy.

Lofepramine is excreted in breast milk. The administration of lofepramine during breast-feeding is not advised unless there are compelling medical reasons.

As with other antidepressants, the ability to drive a car and operate machinery may be affected, especially in conjunction with alcohol. Therefore caution is recommended initially until the individual reaction to treatment is known.

The adverse reactions reported with lofepramine are listed below by system organ class. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

Blood and lymphatic system disorders

Rarely: Bone marrow depression including isolated reports of: agranulocytosis, eosinophilia, granulocytopenia, leucopenia, pancytopenia, thrombocytopenia.

Endocrine disorders

Rarely: Inappropriate secretion of antidiuretic hormone leading to hyponatraemia

Psychiatric disorders

Sleep disturbances, agitation, confusion, nightmares, hallucinations, hypomania, mania, psychoses, delirium. Cases of suicidal ideation and suicidal behaviours have been reported during lofepramine therapy or early after discontinuation.

It should be remembered that severely depressed patients are at risk of suicide until there is a complete remission of symptomatology.

Nervous system disorders

Dizziness, headache, paraesthesia, tremor.

Rarely: Drowsiness, convulsions, impairment of the sense of taste

Very Rarely: Uncoordinated movement.

Eye disorders

Visual disturbances including blurred vision, mydriasis, disturbances of accommodation; induction of glaucoma

Ear and labyrinth disorders

Very Rarely: Tinnitus

Cardiac disorders

Tachycardia, cardiac conduction disorders, increase in cardiac insufficiency, QT-prolongation, arrhythmias (including ventricular arrhythmias or Torsades de Pointes.)

Vascular disorders

Hypotension

Gastrointestinal disorders

Gastrointestinal disturbances including nausea, vomiting, diarrhoea; constipation and dryness of mouth.

Hepatobiliary disorders

Raised liver enzyme levels, sometimes progressing to clinical hepatitis and jaundice, have been reported in some patients, usually occurring within the first 3 months of starting therapy

Skin and subcutaneous tissue disorders

Skin rash, allergic skin reactions and "photosensitivity reactions"

Rarely: Cutaneous bleeding, sweating.

Renal and urinary disorders

Urinary hesitancy, urinary retention.

Reproductive system and breast disorders

Interference with sexual function, testicular disorders (e.g. testicular pain), gynaecomastia, galactorrhoea.

General disorders and administration site conditions

Malaise, facial oedema.

Rarely: Inflammation of mucosal membranes

Investigations

Changes of blood sugar level

Anticholinergic

Some of the above mentioned adverse reactions may be due to the anticholinergic activity of lofepramine, these include:

• dryness of mouth, constipation, visual disturbances including e.g. blurred vision,
• mydriasis, disturbances of accommodation
• induction of glaucoma,
• urinary hesitancy, urinary retention,
• sweating, tachycardia, impairment of the sense of taste
• tremor, confusion, delirium,
• nightmares, hallucinations, psychoses, mania and hypomania

Class effects

Epidemiological studies, mainly in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRls and TCAs. The mechanism leading to this risk is unknown. The following adverse effects have been encountered in patients under treatment with tricyclic antidepressants and should therefore be considered as theoretical hazards of lofepramine even in the absence of substantiation: psychotic manifestations, including mania and paranoid delusions may be exacerbated during treatment with tricyclic antidepressants; withdrawal symptoms may occur on abrupt cessation of therapy and include insomnia, irritability and excessive perspiration; adverse effects such as withdrawal symptoms, respiratory depression and agitation have been reported in neonates whose mothers have taken tricyclic antidepressants during the last trimester of pregnancy.