ritonavir and Adrenal-Insufficiency

Highly effective antiretroviral treatment has improved the life expectancy of human immunodeficiency virus (HIV) infected patients, but has led to an increase in the comorbidities related to aging, such as the chronic obstructive pulmonary disease (COPD). All this implies the need for a greater number of drugs and an increasing risk of drugs interactions with antiretroviral treatment, particularly protease inhibitors.. We report a case of iatrogenic adrenal insufficiency interaction secondary to ritonavir and inhaled fluticasone in an HIV-infected patient with COPD. A review was made of the cases reported in adults in the medical literature (Medline) up to December 2012.. A total of 34 cases were reported. The mean age was 4 years. The mean dose of ritonavir was 187 mg/day, while the fluticasone dose was 866 μg/day. The average time of the interaction between ritonavir and fluticasone was 8 months. In 85% of cases fluticasone was discontinued at the time of diagnosis of adrenal insufficiency/Cushing syndrome. Almost all (90%) patients had a complete resolution of the symptoms after changing the treatment.. HIV-infected patients on antiretroviral therapy with protease inhibitor boosted with ritonavir which requires the use of inhaled corticosteroids, beclomethasone would be the best treatment option.

Topics: Administration, Inhalation; Adrenal Insufficiency; Aged; Bronchodilator Agents; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Protease Inhibitors; Humans; Iatrogenic Disease; Male; Ritonavir

Antiretroviral therapies for HIV may cause systemic toxicities when coadministered with corticosteroids. Potential drug-drug interactions may occur, leading to iatrogenic Cushing syndrome or adrenal insufficiency. This article highlights the drug-drug interactions of antiretroviral therapies with corticosteroids. Practice implications are discussed.

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Drug Interactions; HIV Infections; Humans; Ritonavir

Topics: Adrenal Insufficiency; Adult; Aged; Comorbidity; Cushing Syndrome; Drug Interactions; Female; Fluticasone; HIV Infections; Humans; Iatrogenic Disease; Male; Middle Aged; Ritonavir; Steroids; Triamcinolone; Young Adult

This case report describes a woman living with HIV on treatment including ritonavir-boosted darunavir, who suffered complete secondary adrenal insufficiency after a single intra-articular injection of the corticosteroid triamcinolone. There is a known pharmacological interaction between ritonavir and those corticosteroids which are metabolised by the CYP3A4 pathway. This interaction may lead to complete adrenal insufficiency, which is a life-threatening condition. Adrenal insufficiency must be promptly diagnosed and hydrocortisone replacement started. People living with HIV should be on lifelong antiretroviral treatment, and corticosteroids are common in the treatment of many different conditions seen by various specialists. This case highlights that not only physicians engaged in HIV treatment need to be aware of this important interaction.

Topics: Adrenal Insufficiency; Anti-Retroviral Agents; Female; Glucocorticoids; HIV Infections; Humans; Injections, Intra-Articular; Middle Aged; Ritonavir; Sjogren's Syndrome; Triamcinolone

We present the case of a 58-year-old HIV-infected patient with adrenal insufficiency after local injection of triamcinolone, most likely due to drug-drug interaction with his ritonavir-boosted antiretroviral therapy (ART). This is the first case of adrenal insufficiency occurring without prior symptoms of Cushing's syndrome in a patient on a booster-containing ART. We want to draw attention to this seemingly rare, but potentially life-threatening medical condition that can occur even in short-term use of glucocorticoids in low doses in patients on booster-containing ART and summarize some considerations for management.

Topics: Adrenal Insufficiency; Antiretroviral Therapy, Highly Active; Drug Interactions; Glucocorticoids; HIV Infections; Humans; Low Back Pain; Male; Middle Aged; Ritonavir; Triamcinolone

Topics: Administration, Inhalation; Adrenal Insufficiency; Aged; Asthma; Bronchodilator Agents; Budesonide; HIV Infections; HIV Protease Inhibitors; Humans; Male; Ritonavir; Withholding Treatment

Ritonavir is a powerful inhibitor of the cytochrome P450 3A4 (CYP3A4) isoenzyme. It is used as a pharmaceutical enhancer in the management of HIV-positive patients. However, when co-administered with other drugs that are metabolised via the CYP3A4 pathway, ritonavir can potentially cause serious drug-drug interactions. Inhaled fluticasone propionate, which is used to treat asthma and chronic obstructive airway disease, is particularly prone to such interactions due to its physiological attributes. We report a HIV-positive 48-year-old male patient who presented to Al Nahdha Hospital, Muscat, Oman, in 2012 with weight loss, generalised weakness and fatigue and diagnosed with secondary adrenal insufficiency as a result of concomitant ritonavir and inhaled fluticasone.

Topics: Administration, Inhalation; Adrenal Insufficiency; Asthma; Bronchodilator Agents; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Male; Middle Aged; Oman; Ritonavir

Topics: Adrenal Insufficiency; Adult; Androstadienes; Anti-Inflammatory Agents; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Female; Fluticasone; HIV Protease Inhibitors; Humans; Iatrogenic Disease; Ritonavir

Topics: Adrenal Insufficiency; Adult; Anti-HIV Agents; Drug Combinations; Female; HIV Infections; HIV Protease Inhibitors; Humans; Infant, Newborn; Lopinavir; Pregnancy; Pregnancy Complications, Infectious; Ritonavir

Ritonavir is a protease inhibitor (PI) frequently prescribed with highly active antiretroviral therapy. It functions to boost the effectiveness of other PIs as a result of blocking their breakdown by the cytochrome P450 (3A4) pathway. Through this same mechanism, ritonavir has been shown to cause iatrogenic Cushing's syndrome (ICS) in patients using inhaled fluticasone. In addition, a small number of recent cases suggest that ritonavir may also cause this disorder by prolonging the duration of injected corticosteroids, such as triamcinolone. This case report presents a human immunodeficiency virus (HIV) patient taking ritonavir with ICS and secondary adrenal insufficiency, presumably due to systemic absorption and decreased metabolism of an epidural triamcinolone injection. To the authors knowledge, there have only been 4 previously reported cases describing ritonavir-potentiating ICS after receiving a corticosteroid epidural. This provides further proof that caution should be taken with nonparenteral use of triamcinolone in HIV patients on PIs.

Topics: Adrenal Insufficiency; Antiretroviral Therapy, Highly Active; Cushing Syndrome; Drug Interactions; Female; Glucocorticoids; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Injections, Epidural; Middle Aged; Pennsylvania; Ritonavir; Treatment Outcome; Triamcinolone

A 52-year-old man with well-controlled HIV infection taking ritonavir and increasing doses of inhaled fluticasone for chronic bronchitis developed thrush. Within days of discontinuing fluticasone and initiating fluconazole, he presented with fatigue, malaise, lower-extremity oedema and orthostasis. Testing confirmed exogenous Cushing's syndrome and secondary adrenal insufficiency. Although ritonavir-fluticasone interactions have been previously reported as a cause for adrenal insufficiency, we propose that fluconazole increased the rapidity of onset and severity of symptoms through synergistic inhibition of the adrenal axis.

Topics: Adrenal Insufficiency; Androstadienes; Anti-HIV Agents; Anti-Inflammatory Agents; Bronchitis; Drug Interactions; Fluconazole; Fluticasone; HIV Infections; Humans; Male; Middle Aged; Ritonavir

Lopinavir-ritonavir is a human immunodeficiency virus 1 (HIV-1) protease inhibitor boosted by ritonavir, a cytochrome p450 inhibitor. A warning about its tolerance in premature newborns was recently released, and transient elevation of 17-hydroxyprogesterone (17OHP) was noted in 2 newborns treated with lopinavir-ritonavir in France.. To evaluate adrenal function in newborns postnatally treated with lopinavir-ritonavir.. Retrospective cross-sectional analysis of the database from the national screening for congenital adrenal hyperplasia (CAH) and the French Perinatal Cohort. Comparison of HIV-1-uninfected newborns postnatally treated with lopinavir-ritonavir and controls treated with standard zidovudine.. Plasma 17OHP and dehydroepiandrosterone-sulfate (DHEA-S) concentrations during the first week of treatment. Clinical and biological symptoms compatible with adrenal deficiency.. Of 50 HIV-1-uninfected newborns who received lopinavir-ritonavir at birth for a median of 30 days (interquartile range [IQR], 25-33), 7 (14%) had elevated 17OHP levels greater than 16.5 ng/mL for term infants (>23.1 ng/mL for preterm) on days 1 to 6 vs 0 of 108 controls having elevated levels. The median 17OHP concentration for 42 term newborns treated with lopinavir-ritonavir was 9.9 ng/mL (IQR, 3.9-14.1 ng/mL) vs 3.7 ng/mL (IQR, 2.6-5.3 ng/mL) for 93 term controls (P < .001). The difference observed in median 17OHP values between treated newborns and controls was higher in children also exposed in utero (11.5 ng/mL vs 3.7 ng/mL; P < .001) than not exposed in utero (6.9 ng/mL vs 3.3 ng/mL; P = .03). The median DHEA-S concentration among 18 term newborns treated with lopinavir-ritonavir was 9242 ng/mL (IQR, 1347-25,986 ng/mL) compared with 484 ng/mL (IQR, 218-1308 ng/mL) among 17 term controls (P < .001). The 17OHP and DHEA-S concentrations were positively correlated (r = 0.53; P = .001). All term newborns treated with lopinavir-ritonavir were asymptomatic, although 3 premature newborns experienced life-threatening symptoms compatible with adrenal insufficiency, including hyponatremia and hyperkalemia with, in 1 case, cardiogenic shock. All symptoms resolved following completion of the lopinavir-ritonavir treatment.. Among newborn children of HIV-1-infected mothers exposed in utero to lopinavir-ritonavir, postnatal treatment with a lopinavir-ritonavir-based regimen, compared with a zidovudine-based regimen, was associated with transient adrenal dysfunction.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Insufficiency; Case-Control Studies; Cross-Sectional Studies; Dehydroepiandrosterone Sulfate; Female; France; HIV Infections; HIV-1; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Lopinavir; Male; Pregnancy; Pregnancy Complications, Infectious; Pyrimidinones; Retrospective Studies; Ritonavir; Zidovudine

Topics: Adenine; Adrenal Insufficiency; Adult; Atazanavir Sulfate; Cushing Syndrome; Cytochrome P-450 Enzyme Inhibitors; Female; HIV Protease Inhibitors; HIV Seropositivity; Humans; Iatrogenic Disease; Injections, Intramuscular; Lamivudine; Oligopeptides; Organophosphonates; Pruritus; Pyridines; Ritonavir; Tenofovir; Triamcinolone Acetonide

Topics: Adrenal Insufficiency; Bronchiolitis Obliterans; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cushing Syndrome; Drug Interactions; Female; HIV Infections; HIV Protease Inhibitors; Humans; Male; Pulmonary Disease, Chronic Obstructive; Rhinitis, Allergic, Perennial; Ritonavir

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenal Insufficiency; Adult; Aged; Anti-Asthmatic Agents; Asthma; Child; Cushing Syndrome; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Diltiazem; Dose-Response Relationship, Drug; Drug Interactions; Female; HIV Protease Inhibitors; Humans; Incidence; Itraconazole; Male; Middle Aged; Retrospective Studies; Ritonavir; Verapamil

The development of an iatrogenic Cushing's syndrome (ICS) followed by secondary adrenal failure remains an exceptional event after a single dose administration of a synthetic glucocorticoid. Medical attention has been drawn recently on the possible impact of ritonavir-based antiretroviral regimens on the systemic deleterious effects of a chronic administration of corticosteroids in HIV-infected patients. Three HIV-infected patients treated by a ritonavir-boosted protease inhibitor (PI) regimen received a single intra-articular injection of 40 mg triamcinolone acetonide in our university hospital. The three patients rapidly developed signs and symptoms of ICS followed by secondary adrenal insufficiency. Special attention must be paid when a single administration of corticosteroids has to be given in HIV-positive patients under ritonavir-boosted antiretroviral treatment, as these patients are at risk of developing early cushingoid features and a prolonged suppression of their hypothalamic-pituitary-adrenal axis.

Topics: Adrenal Insufficiency; Cushing Syndrome; Female; Glucocorticoids; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Injections, Intra-Articular; Male; Middle Aged; Ritonavir; Triamcinolone Acetonide

A 14-year-old female with perinatally acquired HIV on boosted protease inhibitor (PI) therapy with atazanavir and ritonavir rapidly developed cushingoid features with excessive weight gain and moon facies within 2 weeks of receiving inhaled fluticasone/salmeterol for asthma treatment. Soon after discontinuing PIs and inhaled steroid, she required hospitalization for dyspnea, headache, muscle weakness, and extreme fatigue requiring hydrocortisone replacement therapy for presumed adrenal insufficiency. Cushing syndrome and adrenal suppression were very likely caused by elevated steroid systemic concentrations resulting from the cytochrome p450 interaction between the protease inhibitors and fluticasone. The Naranjo probability scale score of 5 suggests that the event was probably drug related. This is the first case report of fluticasone and PI-induced Cushing syndrome and adrenal suppression in a pediatric patient without a history of recent or concomitant treatment with systemic steroid therapy. Additionally, this case is unique as it is the most rapid (<2 weeks) presentation documented, thus far. Health care professionals should be conscious of this important drug-drug interaction in HIV-infected children and adolescents and be aware that rapid onset of hypercortisolism and adrenal suppression are possible.

Topics: Adolescent; Adrenal Insufficiency; Albuterol; Androstadienes; Anti-HIV Agents; Anti-Inflammatory Agents; Atazanavir Sulfate; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Female; Fluticasone; HIV Infections; Humans; Hydrocortisone; Oligopeptides; Pyridines; Ritonavir; Salmeterol Xinafoate

Topics: Administration, Inhalation; Adrenal Insufficiency; Androstadienes; Asthma; Bronchodilator Agents; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Ritonavir

We present 2 cases of Cushing syndrome with secondary adrenal insufficiency from concomitant use of ritonavir and inhaled corticosteroids in children with human immunodeficiency virus infection. These cases highlight the need for special consideration when treatment with an inhaled/intranasal corticosteroid is indicated in children receiving antiretroviral therapy.

Topics: Administration, Inhalation; Adolescent; Adrenal Insufficiency; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Cushing Syndrome; Drug Interactions; Drug Therapy, Combination; Female; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Ritonavir; Salmeterol Xinafoate

Ritonavir, a protease inhibitor (PI), is a potent inhibitor of cytochrome P450 3A4. This pharmacological effect, even at low doses (

Topics: Administration, Inhalation; Adrenal Insufficiency; Adult; Androstadienes; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Protease Inhibitors; Humans; Male; Middle Aged; Osteoporosis; Ritonavir