Ritonavir

Explanation

Praziquantel is rapidly metabolised by the cytochrome P450 enzyme system (CYP3A4) and undergoes first-pass effect; the praziquantel label explicitly states that "CYP450 inhibitors, for example cimetidine, ketoconazole, itraconazole, erythromycin and ritonavir, may increase praziquantel plasma concentrations". Raised levels potentiate the adverse effects (headache, dizziness, abdominal discomfort, nausea, urticaria and, in susceptible patients, seizures or arrhythmias — bradycardia, ventricular fibrillation and AV blocks have been observed). Monitor the patient during treatment (usually 1 day of therapy) and consider a lower dose in patients with liver disease, where exposure is already increased.

Explanation

Dexamethasone is metabolised by CYP3A4, and ritonavir is a potent inhibitor of this enzyme: the combination raises corticosteroid exposure, with a risk of corticosteroid excess — Cushing syndrome, adrenal suppression, hyperglycaemia, sodium and fluid retention, potassium loss and immunosuppression (the dexamethasone label lists potassium loss, hypokalaemic alkalosis and adrenal axis suppression among the adverse reactions). The combination occurs mainly in HIV patients needing corticosteroids; use the lowest effective dose, watch for signs of corticosteroid excess and adrenal function, and consider reducing the dexamethasone dose. Note: dexamethasone also induces CYP3A4 — in ritonavir-boosted regimens, evaluate the impact on the protease inhibitors.

Explanation

Levocetirizine is predominantly eliminated renally (without significant hepatic metabolism), so the pharmacokinetic interaction with ritonavir is limited; the clinical risk is additive sedation — the levocetirizine label warns about drowsiness and the increased effect with alcohol, sedatives and tranquillisers, and ritonavir also causes fatigue and CNS symptoms. In patients with renal or hepatic impairment (in whom levocetirizine accumulates and the dose should be reduced) and in the elderly, the combination requires vigilance: monitor drowsiness, dizziness and driving ability, and use the lowest effective levocetirizine dose.

Explanation

Cetirizine is predominantly eliminated renally, with minimal hepatic metabolism, so the pharmacokinetic interaction with ritonavir is limited; the clinical risk is additive sedation — the cetirizine label warns about drowsiness and the increased effect with alcohol, sedatives and tranquillisers, and ritonavir also causes fatigue and CNS symptoms. In patients with renal or hepatic impairment (in whom cetirizine accumulates and the dose should be reduced — the label recommends asking a doctor) and in the elderly, the combination requires vigilance: monitor drowsiness, dizziness and driving ability, and use the lowest effective cetirizine dose.

Explanation

Explanation

Sildenafil is metabolised by CYP3A4, and ritonavir (a potent inhibitor) markedly raises its concentrations: the ritonavir label recommends for erectile dysfunction "sildenafil 25 mg every 48 hours" and contraindicates sildenafil (Revatio) in pulmonary hypertension; the label lists the sildenafil-associated adverse events — visual abnormalities, hypotension, prolonged erection and syncope. Raised sildenafil levels potentiate the risk of hypotension, headache, flushing, dyspepsia, priapism and visual disturbances. For erectile dysfunction, never exceed 25 mg every 48 hours; for pulmonary hypertension, the combination is contraindicated — seek an alternative.

Explanation

Explanation

Ritonavir (a protease inhibitor, often used as a pharmacokinetic booster) is a potent CYP3A4 inhibitor, and co-administration with atorvastatin raises statin concentrations and the risk of myopathy/rhabdomyolysis. The atorvastatin label specifies: with saquinavir+ritonavir, darunavir+ritonavir or fosamprenavir(+ritonavir), do not exceed 20 mg of atorvastatin per day; with tipranavir+ritonavir the combination is not recommended; with lopinavir+ritonavir consider the risk/benefit. In practice (HIV on antiretroviral therapy), use the lowest appropriate dose and titrate slowly with monitoring of lipids, muscle symptoms and CK; alternatively, consider a statin less dependent on CYP3A4. Instruct the patient about myopathy signs.

Explanation

Explanation

Ritonavir has a complex pharmacokinetic profile: it is a potent inhibitor of CYP3A4 and CYP2D6, but also an inducer of other enzymes and transporters. The net effect on warfarin is variable and unpredictable between patients — most reports show an INR increase, but cases of reduction exist. When ritonavir is used at low boosting doses (with other antiretrovirals), the effect is equally variable. The INR should be monitored frequently at initiation, during and after ritonavir discontinuation, adjusting the warfarin dose according to the result and alerting for bleeding and thrombosis signs.

Explanation

Tadalafil is predominantly metabolized by CYP3A4. Ritonavir, an inhibitor of CYP3A4 (and also of CYP2C9, CYP2C19 and CYP2D6), increases tadalafil exposure in a dose-dependent manner: with ritonavir 500–600 mg twice daily AUC increased by 32% (with a 30% reduction in Cmax), and with ritonavir 200 mg twice daily AUC increased by 124%. This increase potentiates the hypotensive effect of tadalafil and the risk of headache and flushing. The label recommends dose adjustment: for as-needed use, do not exceed 10 mg every 72 hours; for once-daily use, do not exceed 2.5 mg. The combination should be monitored, especially in patients with cardiovascular disease or on antihypertensive therapy.

Explanation

Dutasteride is extensively metabolized in humans by the CYP3A4 and CYP3A5 isoenzymes. The label recommends caution when prescribing to patients taking potent CYP3A4 inhibitors on a chronic basis, such as ritonavir, since inhibition of these enzymes may reduce dutasteride clearance and increase its plasma concentrations. No specific studies of this combination were conducted, but the potential for a drug-drug interaction justifies the caution. During prolonged treatment, the emergence of dutasteride adverse effects such as gynecomastia, decreased libido or erectile dysfunction should be monitored, and the need for the drug should be reassessed in patients on long-term antiretroviral therapy.

Explanation

Ritonavir, a potent CYP450 inhibitor, may interfere with cyclophosphamide metabolism, which is activated by hepatic hydroxylation (CYP2A6, 2B6, 3A, 2C9, 2C19) — the FDA label documents that protease inhibitors "may increase the concentration of cytotoxic metabolites and may enhance the toxicities of cyclophosphamide, including higher incidence of infections, neutropenia, and mucositis". The practical consequence is an increased risk of haematological and infectious toxicity in the oncology patient. In patients with HIV or receiving ritonavir as a pharmacokinetic booster, monitor the blood count and signs of infection, and consider cyclophosphamide dose adjustment. This is not a clinically trivial interaction — it requires active vigilance throughout the cycle.

Explanation

Explanation

Carbamazepine is a potent inducer of CYP3A4, CYP1A2, and UGT. Ritonavir is metabolised by CYP3A4 and is itself a CYP3A4 inhibitor. Co-administration reduces ritonavir levels by 50-90%, compromising antiretroviral efficacy. Carbamazepine may also induce P-glycoprotein, accelerating ritonavir elimination. This combination is CONTRAINDICATED by EACS/BHIVA guidelines. Alternatives: switch carbamazepine to valproate (non-inducer) or lamotrigine (weak inducer). If carbamazepine is essential, use a ritonavir-free ARV regimen (e.g. dolutegravir + tenofovir + lamotrigine).

Explanation

Escitalopram is metabolised by CYP2C19 and CYP3A4. Ritonavir inhibits CYP3A4 and CYP2C19. Co-administration may increase escitalopram levels 1.5-2-fold. The risk of serotonin syndrome is moderate. Monitor for serotonergic signs (agitation, tremor, diaphoresis). Reduce escitalopram dose by 50% if necessary. Alternative: citalopram (metabolised by CYP3A4, less susceptible to ritonavir).

Explanation

Venlafaxine is metabolised by CYP2D6 (active desvenlafaxine) and CYP3A4. Ritonavir inhibits CYP3A4. Co-administration may increase venlafaxine levels 1.5-2-fold. Additional risk: venlafaxine may cause dose-dependent hypertension (>150 mg/day), and elevated levels increase this risk. Monitor blood pressure and serotonergic signs. Reduce venlafaxine dose if necessary.

Explanation

Ritonavir inhibits CYP3A4, the main metabolic pathway for diazepam. Levels may increase significantly, prolonging sedation. Monitor sedation and respiratory function. Reduce diazepam dose by 50%. Consider switching to lorazepam (not metabolised by CYP) or midazolam (short-acting).

Explanation

Sertraline is metabolised by CYP2B6, CYP2C19, CYP2C9, and CYP3A4. Ritonavir inhibits CYP3A4 and CYP2C19. Co-administration may increase sertraline levels 1.5-2-fold. The risk of serotonin syndrome is moderate. Monitor for serotonergic signs. Reduce sertraline dose by 50% if necessary. Sertraline is generally well tolerated in HIV patients, but requires vigilance.

Explanation

Oxcarbazepine (MHD) moderately induces CYP3A4, while ritonavir potently inhibits CYP3A4. The outcome depends on dose and timing — generally ritonavir's inhibitory effect predominates. However, oxcarbazepine may compromise pre-exposure prophylaxis (PrEP) or integrase inhibitor-based ARV regimens. Consider switching oxcarbazepine to levetiracetam (does not induce CYP) in HIV patients.