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Drug Interactions between Hivid and Lipitor

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

zalcitabine atorvastatin

Applies to: Hivid (zalcitabine) and Lipitor (atorvastatin)

GENERALLY AVOID: Zalcitabine can cause peripheral neuropathy in up to one-third of patients with advanced HIV disease, and concurrent use of other agents that are also associated with this adverse effect can potentiate the risk and/or severity of nerve damage. Zalcitabine-related peripheral neuropathy is a sensorimotor neuropathy characterized initially by numbness and burning dysesthesia involving the distal extremities. These symptoms may be followed by sharp shooting pains or severe continuous burning pain if the drug is not withdrawn, and progress to severe pain requiring narcotic analgesics. The neuropathy is potentially irreversible. However, with prompt discontinuation of zalcitabine, it is usually slowly reversible, although symptoms may initially progress following discontinuation.

MANAGEMENT: Use of zalcitabine with other drugs that have the potential to cause peripheral neuropathy should be avoided whenever possible. Otherwise, careful monitoring is recommended for symptoms of neuropathy such as burning, tingling, pain, numbness, or weakness in the extremities, particularly in patients with a low CD4 cell count or diabetes. Since the development of peripheral neuropathy appears to be dose-related, the recommended dosage of zalcitabine should not be exceeded. Patients should be advised to promptly discontinue zalcitabine therapy and contact their physician if neuropathy develops. Therapy may be reinstituted following resolution of neuropathy symptoms, but dosage should be reduced to one-half the initially recommended dosage. Zalcitabine should be permanently discontinued in patients who develop severe peripheral neuropathy during treatment.

References

  1. "Product Information. HIVID (zalcitabine)." Roche Laboratories PROD (2001):
  2. Argov Z, Mastaglia FL "Drug-induced peripheral neuropathies." Br Med J 1 (1979): 663-6

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Drug and food interactions

Moderate

atorvastatin food

Applies to: Lipitor (atorvastatin)

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of atorvastatin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. When a single 40 mg dose of atorvastatin was coadministered with 240 mL of grapefruit juice, atorvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 16% and 37%, respectively. Greater increases in Cmax (up to 71%) and/or AUC (up to 2.5 fold) have been reported with excessive consumption of grapefruit juice (>=750 mL to 1.2 liters per day). Clinically, high levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

ADJUST DOSING INTERVAL: Fibres such as oat bran and pectin may diminish the pharmacologic effects of HMG-CoA reductase inhibitors by interfering with their absorption from the gastrointestinal tract.

MANAGEMENT: Patients receiving therapy with atorvastatin should limit their consumption of grapefruit juice to no more than 1 liter per day. Patients should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed. In addition, patients should either refrain from the use of oat bran and pectin or, if concurrent use cannot be avoided, to separate the administration times by at least 2 to 4 hours.

References

  1. Richter WO, Jacob BG, Schwandt P "Interaction between fibre and lovastatin." Lancet 338 (1991): 706
  2. McMillan K "Considerations in the formulary selection of hydroxymethylglutaryl coenzyme a reductase inhibitors." Am J Health Syst Pharm 53 (1996): 2206-14
  3. "Product Information. Lipitor (atorvastatin)." Parke-Davis PROD (2001):
  4. Boberg M, Angerbauer R, Fey P, Kanhai WK, Karl W, Kern A, Ploschke J, Radtke M "Metabolism of cerivastatin by human liver microsomes in vitro. Characterization of primary metabolic pathways and of cytochrome P45 isozymes involved." Drug Metab Dispos 25 (1997): 321-31
  5. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  6. Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther 66 (1999): 118-27
  7. Neuvonen PJ, Backman JT, Niemi M "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet 47 (2008): 463-74
View all 7 references

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Minor

zalcitabine food

Applies to: Hivid (zalcitabine)

Zalcitabine bioavailability may be decreased by 14% if taken with meals. The mechanism and clinical significance are unknown.

References

  1. "Product Information. HIVID (zalcitabine)." Roche Laboratories PROD (2001):

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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