Accutane (Isotretinoin) and Tadalafil Interaction: What Patients and Prescribers Need to Know

Is there a direct interaction between isotretinoin and tadalafil?

The Accutane label's drug interactions section covers vitamin A, tetracyclines, micro-dosed progesterone contraception, a norethindrone/ethinyl estradiol study, St. John's wort, phenytoin and systemic corticosteroids [1]. The Absorica label likewise notes that isotretinoin did not cause clinically significant changes in norethindrone and ethinyl estradiol [3]. The Cialis label's interactions section covers nitrates, alpha-blockers, antihypertensives, alcohol, CYP3A4 inhibitors and inducers, and several drugs tadalafil does not affect [2]. Neither the Accutane nor the Cialis label names the other product [1][2].

The labels do not point to a shared enzyme pathway. Isotretinoin is metabolized in vitro by CYP2C8, CYP2C9, CYP3A4 and CYP2B6 [1]. Tadalafil is mainly metabolized by CYP3A4, and the Cialis label says tadalafil does not inhibit or induce CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6 or CYP2E1 [2]. Neither label states a dose adjustment for the pair [1][2].

What does the tadalafil label say about blood pressure?

Tadalafil is a PDE5 inhibitor and a mild systemic vasodilator [2]. The tadalafil numbers and warnings here are from the Cialis label, which covers tadalafil tablets for ED and BPH; Adcirca is a different tadalafil product and dose for pulmonary arterial hypertension [2][4]. In a clinical pharmacology study, tadalafil 20 mg produced a mean maximal decrease in supine blood pressure, relative to placebo, of 1.6/0.8 mm Hg in healthy subjects [2]. The same label says patients with severely impaired autonomic control of blood pressure may be particularly sensitive to vasodilators, and that ED treatments should not be used in men for whom sexual activity is inadvisable because of cardiovascular status [2].

Tadalafil is contraindicated with any form of organic nitrate and with guanylate cyclase stimulators such as riociguat [2]. The Cialis label also says tadalafil can add to the blood-pressure-lowering effects of alpha-blockers, antihypertensives and substantial alcohol (5 units or more) [2].

Does isotretinoin lower or raise blood pressure?

The adverse reaction lists in the Accutane and Absorica labels do not include low blood pressure [3][1]. The Absorica list does include dizziness, syncope, palpitations and tachycardia, and its warnings include intracranial hypertension [3]. The Accutane label describes early signs of pseudotumor cerebri as papilledema, headache, nausea and vomiting, and visual disturbances [1].

What lipid and liver monitoring does isotretinoin require?

The Accutane label reports marked elevations of serum triglycerides in approximately 25% of patients receiving the drug in clinical trials, a decrease in high-density lipoprotein in about 15%, and an increase in cholesterol in about 7%; the effects on triglycerides, HDL and cholesterol were reversible when the drug was stopped [1]. The label also lists acute pancreatitis, including rare fatal hemorrhagic pancreatitis [1].

The Accutane label says blood lipid determinations should be done before treatment and then at intervals until the lipid response is established, which usually occurs within 4 weeks; it recommends more frequent checks for patients with diabetes, obesity, increased alcohol intake, lipid metabolism disorder or a family history of lipid disorder [1]. The Absorica label says to complete a fasting lipid profile and liver function tests in all patients before treatment, lists lipid abnormalities and hepatotoxicity among its warnings, and says to monitor lipid levels at regular intervals and stop if hypertriglyceridemia cannot be controlled [3].

What symptoms do the labels flag?

The Cialis label says to seek emergency treatment if an erection lasts more than 4 hours, whether painful or not, because priapism can permanently damage erectile tissue. It also says to stop tadalafil and seek medical care for sudden loss of vision in one or both eyes, which could be non-arteritic anterior ischemic optic neuropathy, and for sudden decrease or loss of hearing [2].

The Accutane label says patients with early signs of pseudotumor cerebri should be screened for papilledema and, if papilledema is present, told to discontinue isotretinoin and be referred to a neurologist [1]. The Absorica label lists psychiatric disorders, including depression, psychosis and rarely suicidal ideation, suicide attempts, and aggressive or violent behavior, among its warnings [3]. Its adverse reaction list also includes sexual dysfunction, including erectile dysfunction and decreased libido, that may continue after treatment stops [3].

Does iPLEDGE change anything for a patient also taking tadalafil?

Isotretinoin is available only through the iPLEDGE REMS because of embryo-fetal toxicity [3]. Every patient is enrolled; patients who can get pregnant must follow pregnancy testing and prevention rules, and patients who cannot get pregnant must not share the drug or donate blood [3]. Tadalafil is prescription-only and is not part of that program [5].