he SmPC of the co-administered protease inhibitor. Based on interaction studies with the ritonavir boosted protease inhibitors (lopinavir/ritonavir, atazanavir), concurrent administration of omeprazole or ranitidine does not significantly modify ritonavir efficacy as a pharmacokinetic enhancer despite a slight change of exposure (about 6 - 18%).
4.6 Pregnancy and lactation
A limited number (> 800) of pregnant women were exposed to ritonavir during pregnancy; a very limited number (< 300) were exposed during the first trimester. These data largely refer to exposures where ritonavir was used in combination therapy and not at therapeutic ritonavir doses but at lower doses as a pharmacokinetic enhancer for other PIs. These limited data indicate no increase in the rate of birth defects compared to rates observed in population-based birth defect surveillance systems. Animal data have shown reproductive toxicity (see 5.3). The use of Norvir may be considered in pregnancy only when the benefits outweigh the risk to the foetus.
Ritonavir adversely interacts with oral contraceptives (OCs). Therefore, an alternative, effective and safe method of contraception should be used during treatment.
It is not known whether this medicine is excreted in human milk. Milk excretion has not been measured in the animal studies, however a study in rats showed some effects on offspring development during lactation which are compatible with excretion of ritonavir in milk in that species. HIV infected women should not breast-feed their infants under any circumstances to avoid transmission of HIV.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed. As somnolence and dizziness are known undesirable effects, this should be taken into account when driving or using machinery.
Norvir oral solution contains alcohol (43%).
4.8 Undesirable effects
Ritonavir dosed as a pharmacokinetic enhancer
Adverse reactions associated with the use of ritonavir as a pharmacokinetic enhancer are dependent on the specific co-administered PI. For information on adverse reactions refer to the SPC of the specific co-administered PI.
Ritonavir dosed as an antiretroviral agent
In the original clinical studies (Phase II/III), adverse reactions with possible, probable or unknown relationship to ritonavir were reported in 2% of 1033 patients.
The following adverse reactions of moderate to severe intensity with possible or probable relationship to ritonavir have been reported. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness: very common (> 1/10); common (> 1/100 to < 1/10); uncommon (> 1/1000 to < 1/100); rare(> 1/10,000 to < 1/1,000): not known (cannot be estimated from the available data).
Events noted as having a frequency not known were identified via post-marketing surveillance
Undesirable effects in clinical studies and post-marketing in adult patients
Blood and lymphatic system disorders
Common
Decreased WBC, decreased haemoglobin, decreased neutrophils, increased eosinophils
Uncommon
Increased WBC, increased neutrophils and increased prothrombin time
Not known
Thrombocytopenia
Immune system disorders
Common
Allergic reactions including urticaria, mild skin eruptions, bronch |
