Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Accord-UK Ltd (Trading style: Accord), Whiddon Valley, Barnstaple, Devon, EX32 8NS
Terbinafine tablets are not recommended for patients with chronic or active hepatic disease. Before prescribing Terbinafine tablets, liver function test should be performed. Hepatotoxicity may occur in patients with and without pre-existing hepatic disease therefore periodic monitoring (after 4-6 weeks of treatment) of liver function test is recommended. Terbinafine tablets should be immediately discontinued in case of elevation of liver function test. Very rare cases of serious hepatic failure (some with a fatal outcome, or requiring hepatic transplant) have been reported in patients treated with Terbinafine tablets. In the majority of hepatic failure cases the patients had serious underlying systemic conditions and a causal association with the intake of Terbinafine tablets was uncertain. (see section 4.8 Undesirable effects).
Patients prescribed Terbinafine tablets should be warned to report immediately any signs and symptoms of unexplained persistent nausea, decreased appetite, fatigue, vomiting, right upper abdominal pain, or jaundice, dark urine or pale faeces. Patients with these symptoms should discontinue taking oral Terbinafine tablets and the patient’s hepatic function should be immediately evaluated.
Patients on Terbinafine tablets who develop a high fever or sore throat should be examined concerning possible haematological reactions
Terbinafine tablets should be used with caution in patients with pre-existing psoriasis or lupus erythematosus as very rare cases of lupus erythematosus have been reported.
Terbinafine tablets are a potent inhibitor of the isoenzyme CYP2D6, which should be considered if Terbinafine tablets are combined with medicinal products metabolised by this isoenzyme that are titrated individually (see section 4.5). Dose adjustments may be necessary.
Serious skin reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis) have been very rarely reported in patients taking Terbinafine tablets. If progressive skin rash occurs, Terbinafine tablets treatment should be discontinued.
Very rare cases of blood disorders (neutropenia, agranulocytosis, thrombocytopenia, pancytopenia) have been reported in patients treated with Terbinafine tablets. Aetiology of any blood disorders that occur in patients treated with Terbinafine tablets should be evaluated and consideration should be given for a possible change in medication regimen, including discontinuation of treatment with Terbinafine tablets.
In patients with renal impairment (creatinine clearance less than 50 mL/min or serum creatinine of more than 300 micro mol/L) the use of Terbinafine tablets has not been adequately studied, and therefore, is not recommended (see section 5.2 Pharmacokinetic properties).
The plasma clearance of Terbinafine tablets may be accelerated by drugs which induce metabolism (such as rifampicin) and may be inhibited by drugs which inhibit cytochrome P450 (such as cimetidine). Where co-administration of such drugs is required, it may be necessary to adjust the dose of Terbinafine tablets accordingly.
Cimetidine decreased the clearance of Terbinafine tablets by 33%.
Fluconazole increased the Cmax and AUC of Terbinafine tablets by 52% and 69% respectively, due to inhibition of both CYP2C9 and CYP3A4 enzymes. Similar increase in exposure may occur when other drugs which inhibit both CYP2C9 and CYP3A4 such as ketoconazole and amiodarone are concomitantly administered with Terbinafine tablets.
Rifampicin increased the clearance of Terbinafine tablets by 100%.
According to the results from studies undertaken in vitro and in healthy volunteers, Terbinafine tablets shows negligible potential for inhibiting or enhancing the clearance of most drugs that are metabolised via the cytochrome P450 system (e.g. terfenadine, triazolam, tolbutamide or oral contraceptives) with exception of those metabolised through CYP2D6 (see below).
Terbinafine tablets do not interfere with the clearance of antipyrine or digoxin.
Some cases of irregular menstruation have been reported in patients taking Terbinafine tablets concomitantly with oral contraceptives, although the incidence of these disorders remains within the background incidence of patients taking oral contraceptives alone.
Terbinafine tablets decreased the clearance of caffeine administered intravenously by 19%.
In vitro and in vivo studies have shown that Terbinafine tablets inhibits the CYP2D6-mediated metabolism. This finding may be of clinical relevance for compounds predominantly metabolised by CYP2D6, e.g. certain members of the following drug classes, tricyclic antidepressants (TCAs), beta-blockers, selective serotonine reuptake inhibitors (SSRIs), antiarrhythmics (including class 1A, 1B and 1C) and monoamine oxidase inhibitors (MAO-Is) Type B, especially if they also have a narrow therapeutic window (see 4.4. Special warnings and precautions for use).
Terbinafine tablets decreased the clearance of desipramine by 82%.
Terbinafine tablets increased the clearance of ciclosporin by 15%.
Foetal toxicity and fertility studies in animals suggest no adverse effects. Since clinical experience in pregnant women is very limited, Terbinafine tablets should not be used during pregnancy unless clinical condition of the woman requires treatment with oral Terbinafine tablets and the potential benefits for the mother outweigh any potential risks for the foetus.
Terbinafine tablets are excreted in breast milk; mothers receiving oral treatment with terbinafine tablets should therefore not breast-feed.
Foetal toxicity and fertility studies in animals suggest no adverse effects.
No studies on the effects of Terbinafine tablets treatment on the ability to drive and use machines have been performed. Patients who experience dizziness as an undesirable effect should avoid driving vehicles or using machines.
The following adverse reactions have been observed in the clinical trials or during post marketing experience.
Adverse reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data)
Table 1:
Very rare: Neutropenia, agranulocytosis, thrombocytopenia, pancytopenia
Not known: Anaemia.
Very rare: Anaphylactoid reaction, angioedema, cutaneous and systemic lupus erythematosus
Not known: Anaphylactic reactions, serum sickness-like reaction
Very common: Decreased appetite
Not known: Anxiety, depression*
Common: Headache
Uncommon: Hypogeusia**, ageusia**
Rare: Malaise
Very rare: Dizziness, paraesthesia and hypoaesthesia
Not known: Anosmia
Not known: Hypoacusis, hearing impaired, tinnitus
Not known: Vasculitis
Very common: Abdominal distension, dyspepsia, nausea, abdominal pain, diarrhoea.
Not known: Pancreatitis
Rare: Hepatic failure, hepatic enzymes increased
Not known: hepatitis, jaundice, cholestasis
Very common: Rash, urticaria
Very rare: Erythema multiforme ,Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis (AGEP)). Psoriasiform eruptions or exacerbation of psoriasis. Alopecia.
Not known: Photosensitivity reaction, photodermatosis, photosensitivity allergic reaction and polymorphic light eruption
Very common: Arthralgia, myalgia
Not known: Rhabdomyolysis
Very rare: Fatigue
Not known: Influenza like illness, pyrexia
Not known: Blood creatinine phosphokinase increased, weight decreased***
* Anxiety and depressive symptoms secondary to dysgeusia.
** Hypogeusia, including ageusia, which usually recover within several weeks after discontinuation of the drug. Isolated cases of prolonged hypogeusia have been reported.
*** Weight decreased secondary to hypogeusia.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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