Drug interactions

Because it inhibits the P450 liver enzymes, ritonavir (Norvir) interacts with a large number of other medicines.1 Some of these drug interactions may be life-threatening.

It is extremely important for patients taking ritonavir to check with their doctor before taking any other medications whatsoever. Abbott, ritonavir’s manufacturer, has produced a card listing all the drug’s possible interactions.

Patients taking ritonavir should not take the following drugs:

  • Alfuzosin
  • Amiodarone (Cordarone X)
  • Astemizole
  • Bepidril
  • Chlorazepate (Tranxene), due to a risk of sedation and breathing difficulties
  • Cisapride
  • Colchicine in patients with renal or hepatic impairment
  • Diazepam, due to a risk of sedation and breathing difficulties
  • Ergotamine tartrate (Cafergot / Migril), due to a risk of blood vessel constriction
  • Estazolam, due to a risk of sedation and breathing difficulties
  • Flecainide acetate (Tambocor)
  • Flurazepam (Dalmane), due to a risk of sedation and breathing difficulties
  • Halofantrine
  • Hypericin (St John’s wort)
  • Lovastatin
  • Lumefantrine
  • Midazolam (Hypnovel), due to a risk of sedation and breathing difficulties
  • Pethidine hydrochloride (Pamergan P100)2
  • Pimozide (Orap)
  • Piroxicam (Feldene / Brexidol)
  • Propafenone (Arythmol)
  • Quinidine sulphate (Kinidin Dureles)
  • Simvastatin (Zocor)
  • Terfenadine
  • Triazolam, due to a risk of sedation and breathing difficulties3
  • Vardenafil (Levitra)
  • Voriconazole (Vfend).

Co-administration of ritonavir with efavirenz (Sustiva) can increase the likelihood of side-effects such as dizziness, nausea and unusual skin sensations, as well as elevated liver enzymes.

Other drugs that should be used cautiously by people taking ritonavir include the following:

  • Amitriptyline (Tryptizol, Elavil, Lentizol) levels may be increased by ritonavir.
  • Atorvastatin (Lipitor) levels are increased by ritonavir.
  • Atovaquone (Wellvone) levels may be reduced by ritonavir.
  • Clomipramine (Anafranil) levels may be increased by ritonavir.
  • Codeine phosphate levels may be reduced by ritonavir.
  • Desipramine (Pertrofan) levels may be increased by ritonavir.
  • Fluoxetine (Prozac) levels may be increased by ritonavir.
  • Fluticasone propionate (Flixotide) levels are increased by ritonavir. This can cause symptoms of Cushing’s syndrome and suppression of the adrenal glands, including weight gain, weakening of the skin, sweating, facial hair growth and psychological disturbances.4 5
  • Imipramine (Tofranil) levels may be increased by ritonavir.
  • Ketoconazole (Nizoral) levels are increased by ritonavir, increasing the incidence of side-effects.
  • Ketoprofen (Orudis / Oruvail) levels may be reduced by ritonavir.
  • Lorazepam levels may be reduced by ritonavir.
  • Maprotiline (Ludiomil) levels may be increased by ritonavir.
  • Methadone hydrochloride (Methadose) concentrations are reduced by ritonavir, requiring dose escalation to avoid the risk of withdrawal symptoms developing.
  • Morphine (Oramorph / Sevredol / Morcap SR / Morphegesic SR / MST Continus / MXL / Zomorph) levels may be reduced by ritonavir.
  • Naproxen (Naprosyn / Synflex) levels may be reduced by ritonavir.
  • Nefazodone (Dutonin) levels may be increased by ritonavir.
  • Nortryptiline (Allegron) levels may be increased by ritonavir.
  • Oxazepam levels may be reduced by ritonavir.
  • Paroxetine (Seroxat) levels may be increased by ritonavir.
  • Prednisolone levels are increased by ritonavir.6
  • Propofol (Diprivan) levels may be reduced by ritonavir.
  • Rifabutin (Mycobutin): levels are increased by ritonavir, so it should be taken at the lower dose of 150mg two to three times a week.7
  • Sertraline (Lustral) levels may be increased by ritonavir.
  • Sildenafil (Viagra) levels are increased eleven-fold by ritonavir, increasing the incidence of dangerous side-effects.8 The dose of sildenafil should be reduced to less than 25mg every 48 hours. Sildenafil is contraindicated if used for treatment of pulmonary arterial hypertension (due to dose required).
  • Tadalafil (Cialis) levels are increased by ritonavir, so it should be taken at a reduced dose.
  • Temazepam levels may be reduced by ritonavir.
  • Trazadone (Molipaxin) levels may be increased by ritonavir.
  • Venlafaxine (Effexor) levels may be increased by ritonavir.

Ritonavir decreases the blood concentrations of the oral contraceptive ethinylestradiol, so alternative forms of contraception should be used.

One case of reduced levels of valproic acid (Depakote) has also been reported in a patient taking ritonavir, resulting in re-emergence of symptoms of bipolar disorder.9 However, further data are required to confirm this link.

Ritonavir capsules and oral solution contain alcohol. They should therefore not be taken with the alcoholism treatment drug disulfiram (Antabuse) or medicines with similar modes of action, including the antibiotic metronidazole (Flagyl / Flagyl S / Metrolyl).

References

  1. Kempf D et al. Coadministration with ritonavir enhances the plasma levels of HIV protease inhibitors by inhibition of cytochrome P450. Third Conference on Retroviruses and Opportunistic Infections, Washington, abstract 143, 1996
  2. Piscitelli S et al. The effect of ritonavir on the pharmacokinetics of meperidine and normeperidine. Pharmacother 20: 549-553, 2000
  3. Greenblatt DJ et al. Differential impairment of triazolam and zolpidem clearance by ritonavir. J Acquir Immune Defic Syndr 24: 129-136, 2000
  4. Samaras K et al. Iatrogenic Cushing’s syndrome with osteoporosis and secondary adrenal failure in human immunodeficiency virus-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors: six cases. J Clin Endocrinol 90: 4394-4398, 2005
  5. Gillett MJ et al. Iatrogenic Cushing's syndrome in an HIV-infected patient treated with ritonavir and inhaled fluticasone. AIDS 19: 740-741, 2005
  6. Penzak SR et al. Prednisolone pharmacokinetics in the presence and absence of ritonavir after oral predisone administration to healthy volunteers. J Acquir Immune Defic Syndr 40: 573-580, 2005
  7. Gallicano K et al. A pharmacokinetic study of intermittent rifabutin dosing with a combination of ritonavir and saquinavir in patients infected with human immunodeficiency virus. Clin Pharmacol Ther 70: 149-158, 2001
  8. Muirhead GJ et al. Pharmacokinetic interactions between sildenafil and saquinavir / ritonavir. Br J Clin Pharmacol 50: 99-107, 2000
  9. Sheehan NL et al. Possible interaction between lopinavir / ritonavir and valproic acid exacerbates bipolar disorder. Ann Pharmacother 40: 147-150, 2006
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
close

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.