or hepatitis B or C, please refer to the relevant product information for these medicinal products.
Patients with pre-existing liver dysfunction including chronic active hepatitis have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
Renal disease: Since the renal clearance of ritonavir is negligible, the decrease in the total body clearance is not expected in patients with renal impairment. For specific dosing information in patients with renal impairment, refer to the Summary of Product Characteristics (SPC) of the co-administered protease inhibitor. See also section 4.2.
Ritonavir oral solution contains castor oil polyoxyl which may cause stomach upset and diarrhoea. Ritonavir oral solution also contains the azo-colouring agent sunset yellow (E110) which may cause allergic reactions.
Ritonavir oral solution contains alcohol (43% v/v), ie up to 258 mg per maximum dose of 600 mg, equivalent to 65 ml beer, 27 ml wine per dose. Each 100 mg dose contains up to 43 mg alcohol and each 200 mg dose contains 86 mg alcohol. Therefore concomitant administration of Norvir with disulfiram or medicines with disulfiram-like reactions (eg metronidazole) should be avoided. Also to be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease or epilepsy.
Osteonecrosis: Although the etiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported in patients with advanced HIV-disease and/or long-term exposure to combination antiretroviral therapy (CART). Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
PR interval prolongation: ritonavir has been shown to cause modest asymptomatic prolongation of the PR interval in some healthy adult subjects. Rare reports of 2nd or 3rd degree atrioventricular block in patients with underlying structural heart disease and pre-existing conduction system abnormalities or in patients receiving medicinal products known to prolong the PR interval (such as verapamil or atazanavir) have been reported in patients receiving ritonavir. Norvir should be used with caution in such patients (see section 5.1).
Interactions with other medicinal products
Ritonavir dosed as an antiretroviral agent
The following Warnings and Precautions should be considered when ritonavir is used as an antiretroviral agent. When ritonavir is used as a pharmacokinetic enhancer at the 100 mg and 200 mg level it cannot be assumed that the following warnings and precautions will also apply. When ritonavir is used as a pharmacokinetic enhancer, full details on the warnings and precautions relevant to that particular PI must be considered, therefore the Summary of Product Characteristics, section 4.4, for the particular PI must be consulted to determine if the information below is applicable.
PDE5 inhibitors: Particular caution should be used when prescribing sildenafil, tadalafil or vardenafil for the treatment of erectile dysfunction in patients receiving ritonavir. Co-administration of ritonavir with these medicinal products is expec |
