Drug Interactions between budesonide and nevirapine

You should avoid the regular consumption of large amounts of grapefruits and grapefruit juice while taking budesonide. Grapefruit can raise the levels of budesonide in your body and lead to increased side effects. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.

Nevirapine can cause severe, life-threatening skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions characterized by rash, constitutional findings, and organ dysfunction including hepatic failure. Fatalities in association with these reactions have been reported. The first 6 weeks of therapy is the period of greatest risk, and intense monitoring is recommended during the first 18 weeks. In controlled clinical trials, Grade 3 and 4 rashes were reported during the first 6 weeks in 1.5 % of nevirapine-treated patients compared to 0.1% of placebo subjects. Patients who develop signs or symptoms of severe skin reactions or hypersensitivity reactions possibly related to nevirapine at any time during therapy must discontinue the drug and seek medical attention immediately. Because nevirapine-induced hepatitis and hepatic failure may be associated with hypersensitivity reactions, liver function tests should be performed in these patients as well as all patients who develop a rash within the first 18 weeks of treatment. Nevirapine should be permanently discontinued if clinical hepatitis or transaminase elevations combined with rash or other systemic symptoms occur, and should not be restarted after recovery. Nevirapine therapy should also not be restarted following severe skin or hypersensitivity reactions or a rash that is accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, eosinophilia, granulocytopenia, lymphadenopathy, or renal dysfunction. During the initial 2-week lead-in period of 200 mg/day (4 mg/kg/day in pediatric patients), the dosage of nevirapine should not be increased if any rash occurs. Dose escalation should only be attempted after the rash resolves.

The use of nevirapine has been associated with severe, life-threatening, and fatal hepatotoxicity, particularly in the first 18 weeks of therapy. Fulminant and cholestatic hepatitis, hepatic necrosis, and hepatic failure have been reported. Nevirapine-induced hepatitis and hepatic failure may be associated with signs of hypersensitivity, which can include severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, eosinophilia, granulocytopenia, lymphadenopathy, or renal dysfunction. In controlled clinical trials, symptomatic hepatic events regardless of severity occurred on average in 4% (range 0% to 11%) of patients who received nevirapine and 1.2% of patients in control groups. The risk was greatest in the first 6 weeks of therapy and continued to be greater in the nevirapine groups compared to controls through 18 weeks of treatment. In general, the patients at greatest risk of hepatic events are women with high CD4 counts. During the first 6 weeks of treatment, women have a 3-fold higher risk than men for symptomatic, often rash-associated, hepatic events (5.8% vs. 2.2%). In a retrospective review, women with CD4 counts greater than 250 cells/mm3 had a 12-fold higher risk of symptomatic hepatic events compared to women with lower CD4 counts (11% vs. 0.9%). A 5-fold increased risk was observed in men with CD4 counts greater than 400 cells/mm3 compared to men with lower CD4 counts (6.3% vs. 1.2%). Additionally, coinfection with hepatitis B or C and/or increased liver function tests at the start of therapy are associated with a greater risk of later symptomatic events (6 weeks or more after starting nevirapine) and asymptomatic increases in AST or ALT. Therapy with nevirapine should be administered cautiously in patients with preexisting liver disease or liver function test abnormalities. Due to the risk of drug accumulation, nevirapine should not be administered to patients with severe hepatic impairment. All patients treated with nevirapine should undergo intensive clinical and laboratory monitoring (i.e., once a month or more) during the first 18 weeks of therapy, and regular monitoring thereafter. Liver function tests should be performed at baseline, prior to dose escalation, and at two weeks post-dose escalation. Patients should be instructed to discontinue nevirapine and seek medical attention promptly if signs and symptoms of hepatic injury or hypersensitivity develop such as fever, pruritus, rash, facial edema, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. Nevirapine should be permanently discontinued if clinical hepatitis or transaminase elevations combined with rash or other systemic symptoms occur, and should not be restarted after recovery. In some cases, hepatic injury progresses despite discontinuation of treatment.

Prolonged use of corticosteroids may cause posterior subcapsular cataracts and elevated intraocular pressure, the latter of which may lead to glaucoma and/or damage to the optic nerves. Therapy with corticosteroids should be administered cautiously nonetheless in patients with a history of cataracts, glaucoma, or increased intraocular pressure. Although adverse effects of corticosteroids may be minimized by local rather than systemic administration, the risks are not entirely abolished. Inhaled and nasally applied drug may be absorbed into the circulation, especially when large doses are used. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used.

Prolonged use of corticosteroids may cause posterior subcapsular cataracts and elevated intraocular pressure, the latter of which may lead to glaucoma and/or damage to the optic nerves. Therapy with corticosteroids should be administered cautiously nonetheless in patients with a history of cataracts, glaucoma, or increased intraocular pressure. Although adverse effects of corticosteroids may be minimized by local rather than systemic administration, the risks are not entirely abolished. Inhaled and nasally applied drug may be absorbed into the circulation, especially when large doses are used. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used.

Nevirapine is partially removed by hemodialysis. In a pharmacokinetic study of nevirapine in patients with renal impairment, six subjects requiring hemodialysis exhibited a 44% reduction in nevirapine systemic exposure (AUC) over a one-week period. There was also evidence of accumulation of nevirapine hydroxy-metabolites in plasma in these patients; however, the clinical significance is unknown. A supplemental dose following each dialysis session is indicated for patients undergoing chronic hemodialysis.

The use of corticosteroids may rarely precipitate or aggravate conditions of hyperadrenocorticism. Although adverse effects of corticosteroids may be minimized by local rather than systemic administration, the risks are not entirely abolished. Inhaled and nasally applied drug may be absorbed into the circulation, especially when large doses are used. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used. The development of symptoms such as menstrual irregularities, acneiform lesions, cataracts and cushingoid features during inhaled or nasal corticosteroid therapy may indicate excessive use.

The immunosuppressant and anti-inflammatory effects of corticosteroids, particularly in higher dosages, may decrease host resistance to infectious agents, decrease the ability to localize infections, and mask the symptoms of infection. Secondary infections may be more likely to develop. Therapy with corticosteroids should be administered cautiously in patients with an infection, particularly active or quiescent tuberculosis or in hepatitis B carriers. Monitor patients for any new or worsening infection and use with caution in these patients. A serious or even fatal course of chickenpox and measles can occur in susceptible patients. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used.

Some inhaled corticosteroid formulations contain lactose and may cause adverse reactions including cough, wheezing and bronchospasm in patients with severe milk protein allergy or intolerance. Caution is advised.

Corticosteroids are predominantly cleared by hepatic metabolism and impairment of the liver function may lead to their accumulation. Patients with hepatic disease should be closely monitored.

Pharmacologic dosages of corticosteroids may increase the risk of corneal perforation in patients with ocular herpes simplex. Therapy with inhaled and nasal corticosteroids should be administered cautiously in such patients.

Prolonged use of inhaled corticosteroids may be associated with a reduction in bone density. This effect appears to be dose-related and has been reported primarily with high dosages (800 mcg/day or more of beclomethasone or equivalent for 1 year or greater). Reduced levels of total body calcium have also been demonstrated in patients receiving lower dosages. Long-term therapy with inhaled and nasal corticosteroids should be administered cautiously in patients with osteoporosis. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used.

Nevirapine metabolites are primarily eliminated by the kidney. The clinical significance of possible reduced metabolite clearance in renal impairment is uncertain. Therapy with nevirapine should be administered cautiously in patients with renal impairment.

The immunosuppressant and anti-inflammatory effects of corticosteroids, particularly in higher dosages, may decrease host resistance to infectious agents, decrease the ability to localize infections, and mask the symptoms of infection. Secondary infections may be more likely to develop. Therapy with corticosteroids should be administered cautiously in patients with an infection, particularly active or quiescent tuberculosis or in hepatitis B carriers. Monitor patients for any new or worsening infection and use with caution in these patients. A serious or even fatal course of chickenpox and measles can occur in susceptible patients. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used.