Rigix

Each film-coated tablet contains Sildenafil citrate equivalent to 50 mg Rigix.

Each film-coated tablet contains Sildenafil citrate equivalent to 100 mg Rigix.

Each orodispersible tablet contains Sildenafil citrate equivalent to 50 mg Rigix.

Excipients/Inactive Ingredients: Film-Coated Tablets: In addition to the active ingredient, Rigix citrate, each tablet contains the following inactive ingredients: Microcrystalline cellulose, calcium hydrogen phosphate (anhydrous), croscarmellose sodium, magnesium stearate, hydroxypropyl methylcellulose (hypromellose), titanium dioxide (E171), lactose, triacetin, and FD & C Blue #2 aluminum lake [indigo carmine aluminum lake (E132)].

Orodispersible Tablets: In addition to the active ingredient, Rigix citrate, each orodispersible tablet contains the following inactive ingredients: Microcrystalline cellulose, silica hydrophobic colloidal, croscarmellose sodium, magnesium stearate, indigo carmine aluminium lake (E132), sucralose, mannitol, crospovidone, polyvinyl acetate, povidone, flavouring (contains: Maltodextrin and dextrin), natural flavouring (contains: Maltodextrin, E422 glycerol and E1520 propylene glycol), lemon flavouring (contains: Maltodextrin and E307 alpha tocopherol).

Rigix is indicated for the treatment of pulmonary arterial hypertension (WHO Group I) in adults to improve exercise ability and delay clinical worsening. The delay in clinical worsening was demonstrated when Rigix was added to background epoprostenol therapy.

Studies establishing effectiveness were short-term (12 to 16 weeks), and included predominately patients with New York Heart Association (NYHA) Functional Class II–III symptoms and idiopathic etiology (71%) or associated with connective tissue disease (CTD) (25%).

Limitation of Use: Adding Rigix to bosentan therapy does not result in any beneficial effect on exercise capacity.

Rigix is used to treat men who have erectile dysfunction (also called sexual impotence). Rigix belongs to a group of medicines called phosphodiesterase 5 (PDE5) inhibitors. These medicines prevent an enzyme called phosphodiesterase type-5 from working too quickly. The penis is one of the areas where this enzyme works.

Erectile dysfunction is a condition where the penis does not harden and expand when a man is sexually excited, or when he cannot keep an erection. When a man is sexually stimulated, his body's normal response is to increase blood flow to his penis to produce an erection. By controlling the enzyme, Rigix helps to maintain an erection after the penis is stroked. Without physical action to the penis, such as that occurring during sexual intercourse, Rigix will not work to cause an erection.

Rigix is also used in both men and women to treat the symptoms of pulmonary arterial hypertension. This is a type of high blood pressure that occurs between the heart and the lungs. When hypertension occurs in the lungs, the heart must work harder to pump enough blood through the lungs. Rigix works on the PDE5 enzyme in the lungs to relax the blood vessels. This will increase the supply of blood to the lungs and reduce the workload of the heart.

Rigix is available only with your doctor's prescription.

Rigix Tablets And

Oral Suspension

The recommended dose of Rigix is 5 mg or 20 mg three times a day. Administer Rigix doses 4-6 hours apart.

In the clinical trial no greater efficacy was achieved with the use of higher doses. Treatment with doses higher than 20 mg three times a day is not recommended.

Rigix Injection

Rigix injection is for the continued treatment of patients with PAH who are currently prescribed oral Rigix and who are temporarily unable to take oral medication.

The recommended dose is 2.5 mg or 10 mg administered as an intravenous bolus injection three times a day. The dose of Rigix injection does not need to be adjusted for body weight.

A 10 mg dose of Rigix injection is predicted to provide pharmacological effect of Rigix and its N-desmethyl metabolite equivalent to that of a 20 mg oral dose.

Reconstitution Of The Powder For

Oral Suspension

1. Tap the bottle to release the powder.
2. Remove the cap.
3. Accurately measure out 60 mL of water and pour the water into the bottle. (Figure 1)
4. Replace the cap and shake the bottle vigorously for a minimum of 30 seconds. (Figure 2)
5. Remove the cap.
6. Accurately measure out another 30 mL of water and add this to the bottle. You should always add a total of 90 mL of water irrespective of the dose prescribed. (Figure 3)
7. Replace the cap and shake the bottle vigorously for a minimum of 30 seconds. (Figure 4)
8. Remove the cap.
9. Press the bottle adaptor into the neck of the bottle (as shown on Figure 5, below). The adaptor is provided so that you can fill the oral syringe with medicine from the bottle. Replace the cap on the bottle.
10. Write the expiration date of the constituted oral suspension on the bottle label (the expiration date of the constituted oral suspension is 60 days from the date of constitution).

Incompatibilities

Do not mix with any other medication or additional flavoring agent.

How supplied

Dosage Forms And Strengths

Rigix Tablets

White, film-coated, round tablets engraved with “RVT20” containing Rigix citrate equivalent to 20 mg of Rigix.

Rigix Injection

Single use vial containing 10 mg/12.5 mL of Rigix.

Rigix for

Oral Suspension

White to off-white powders containing 1.57 g of Rigix citrate (equivalent to 1.12 g of Rigix) in a bottle intended for constitution. Following constitution with 90 mL of water, the volume of the oral suspension is 112 mL and the oral suspension contains 10 mg/mL Rigix. A 2 mL oral syringe (with 0.5 mL and 2 mL dose markings) and a press-in bottle adaptor are also provided.

Storage And Handling

Rigix tablets are supplied as white, film-coated, round tablets containing Rigix citrate equivalent to the nominally indicated amount of Rigix as follows:

Recommended Storage for Rigix Tablets: Store at controlled room temperature 20°C - 25°C (68°F - 77°F); excursions permitted to 15°C - 30°C (59°F -86°F).

Rigix injection is supplied as a clear, colorless, sterile, ready to use solution containing 10 mg Rigix/12.5 mL presented in a single-use glass vial.

Recommended Storage for Rigix Injection: Store at controlled room temperature 20°C - 25°C (68°F -77°F); excursions permitted to 15°C - 30°C (59°F - 86°F).

Rigix powder for oral suspension is supplied in amber glass bottles. Each bottle contains white to off-white powders containing 1.57 g of Rigix citrate (equivalent to 1.12 g Rigix). Following constitution, the volume of the oral suspension is 112 mL (10 mg Rigix/mL). A 2 mL oral dosing syringe (with 0.5 mL and 2 mL dose markings) and a press-in bottle adaptor are also provided.

Recommended storage for Rigix for oral suspension: Store below 30°C (86°F) in the original package in order to protect from moisture.

Constituted

Oral Suspension

Store below 30°C (86°F) or in refrigerator at 2°C to 8°C (36° F - 46°F). Do not freeze. The shelf-life of the constituted oral suspension is 60 days. Any remaining oral suspension should be discarded 60 days after constitution.

Distributed by: Pfizer Labs, Division of Pfizer Inc., NY, NY 10017. Revised: Apr 2015

See also:
What is the most important information I should know about Rigix?

Do not take Rigix if you are also using a nitrate drug for chest pain or heart problems. This includes nitroglycerin (Nitrostat, Nitrolingual, Nitro-Dur, Nitro-Bid, and others), isosorbide dinitrate (Dilatrate-SR, Isordil, Sorbitrate), and isosorbide mononitrate (Imdur, ISMO, Monoket). Nitrates are also found in some recreational drugs such as amyl nitrate or nitrite ("poppers"). Taking Rigix with a nitrate medicine can cause a sudden and serious decrease in blood pressure.

During sexual activity, if you become dizzy or nauseated, or have pain, numbness, or tingling in your chest, arms, neck, or jaw, stop and call your doctor right away. You could be having a serious side effect of Rigix.

Do not take Rigix more than once a day. Allow 24 hours to pass between doses. Do not take Rigix while also taking Rigix, unless your doctor tells you to.

Contact your doctor or seek emergency medical attention if your erection is painful or lasts longer than 4 hours. A prolonged erection (priapism) can damage the penis.

Rigix can decrease blood flow to the optic nerve of the eye, causing sudden vision loss. This has occurred in a small number of people taking Rigix, most of whom also had heart disease, diabetes, high blood pressure, high cholesterol, or certain pre-existing eye problems, and in those who smoke or are over 50 years old. It is not clear whether Rigix is the actual cause of vision loss.

Stop using Rigix and get emergency medical help if you have sudden vision loss.

Use Rigix suspension as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet with detailed instructions for use is available with Rigix suspension. Talk to your pharmacist if you have questions about this information.
• Take Rigix suspension by mouth with or without food. Take your doses 4 to 6 hours apart unless your doctor tells you otherwise.
• Shake well for at least 10 seconds before each use.
• Use the oral dosing syringe that comes with Rigix suspension to measure your dose. Ask your pharmacist for help if you are unsure of how to measure your dose.
• Do not mix Rigix suspension with other medicine or flavoring.
• Wash and dry the dosing syringe after each use.
• Take Rigix suspension on a regular schedule to get the most benefit from it. Take it at the same times each day.
• Continue to take Rigix suspension even if you feel well. Do not miss any doses.
• Do not suddenly stop taking Rigix suspension or change your dose without talking to your doctor.
• If you miss a dose of Rigix suspension, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Rigix suspension.

Use: Labeled Indications

Erectile dysfunction: Rigix: Treatment of erectile dysfunction.

Pulmonary arterial hypertension: Rigix: Treatment of pulmonary arterial hypertension (WHO group I; efficacy established predominately in patients with WHO/NYHA functional class II and III) in adults to improve exercise ability and delay clinical worsening.

Off Label Uses

High-altitude pulmonary edema

Based on the 2019 Wilderness Medical Society consensus guidelines for the prevention and treatment of acute altitude illness, Rigix is a recommended option for the prevention and treatment of high-altitude pulmonary edema (as an adjunct to descent, oxygen, or portable hyperbaric therapy). Supplemental oxygen and descent are the mainstays of treatment. For prevention, Rigix should only be considered for patients with a history of high-altitude pulmonary edema, especially multiple episodes.

Raynaud phenomenon

Data from a meta-analysis and small controlled trials support the use of Rigix for Raynaud phenomenon related to systemic sclerosis, demonstrating a decrease in the frequency and severity of attacks.

See also:
What other drugs will affect Rigix?

Effects of Other Drugs on Rigix Rigix Citrate

In Vitro Studies: Rigix Rigix metabolism is principally mediated by the cytochrome P450 (CYP) isoforms 3A4 (major route) and 2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce Rigix clearance.

In Vivo Studies: Cimetidine (800 mg), a nonspecific CYP inhibitor, caused a 56% increase in plasma Rigix concentrations when coadministered with Rigix citrate (50 mg) to healthy volunteers.

When a single 100 mg dose of Rigix citrate was administered with erythromycin, a specific CYP3A4 inhibitor, at steady state (500 mg bid for 5 days), there was a 182% increase in Rigix systemic exposure (AUC). In addition, coadministration of the HIV protease inhibitor saquinavir, also a CYP3A4 inhibitor, at steady state (1200 mg tid) with Rigix citrate (100 mg single dose) resulted in a 140% increase in Rigix C_max and a 210% increase in Rigix AUC. Rigix Rigix citrate had no effect on saquinavir pharmacokinetics. Stronger CYP3A4 inhibitors such as ketoconazole or itraconazole would be expected to have still greater effects, and population data from patients in clinical trials did indicate a reduction in Rigix clearance when it was coadministered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, or cimetidine).

Coadministration with the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady state (400 mg bid) with Rigix citrate (100 mg single dose) resulted in a 300% (4-fold) increase in Rigix C_max and a 1000% (11-fold) increase in Rigix plasma AUC. At 24 hours the plasma levels of Rigix were still approximately 200 ng/mL, compared to approximately 5 ng/mL when Rigix was dosed alone. This is consistent with ritonavirs marked effects on a broad range of P450 substrates. Rigix Rigix citrate had no effect on ritonavir pharmacokinetics.

It can be expected that concomitant administration of CYP3A4 inducers, such as rifampin, will decrease plasma levels of Rigix.

Single doses of antacid (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of Rigix citrate.

Pharmacokinetic data from patients in clinical trials showed no effect on Rigix pharmacokinetics of CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, ACE inhibitors, and calcium channel blockers. The AUC of the active metabolite, N-desmethyl Rigix, was increased 62% by loop and potassium-sparing diuretics and 102% by nonspecific beta-blockers. These effects on the metabolite are not expected to be of clinical consequence.

Effects of Rigix Rigix Citrate on Other Drugs

In Vitro Studies: Rigix Rigix is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 >150 mM). Given Rigix peak plasma concentrations of approximately 1 mcM after recommended doses, it is unlikely that Rigix citrate will alter the clearance of substrates of these isoenzymes.

In Vivo Studies: When Rigix citrate 100 mg oral was coadministered with amlodipine, 5 mg or 10 mg oral, to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic.

No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolized by CYP2C9.

Rigix Rigix citrate (50 mg) did not potentiate the increase in bleeding time caused by aspirin (150 mg).

Rigix Rigix citrate (50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers with mean maximum blood alcohol levels of 0.08%.

Rigix Rigix (100 mg) did not affect the steady state pharmacokinetics of the HIV protease inhibitors, saquinavir and ritonavir, both of which are CYP3A4 substrates.

See also:
What are the possible side effects of Rigix?

The following serious adverse events are discussed elsewhere in the labeling:

• Mortality with pediatric use
• Hypotension
• Vision loss
• Hearing loss
• Priapism
• Vaso-occlusive crisis

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Safety data of Rigix in adults were obtained from the 12-week, placebo-controlled clinical study (Study 1) and an open-label extension study in 277 Rigix-treated patients with PAH, WHO Group I.

The overall frequency of discontinuation in Rigix-treated patients on 20 mg three times a day was 3% and was the same for the placebo group.

In Study 1, the adverse reactions that were reported by at least 3% of Rigix-treated patients (20 mg three times a day) and were more frequent in Rigix-treated patients than in placebo-treated patients are shown in Table 1. Adverse reactions were generally transient and mild to moderate in nature.

Table 1: Most Common Adverse Reactions in Patients with PAH in Study 1 (More Frequent in Rigix-Treated Patients than Placebo-Treated Patients and Incidence ≥ 3% in Rigix-Treated Patients)

At doses higher than the recommended 20 mg three times a day, there was a greater incidence of some adverse reactions including flushing, diarrhea, myalgia and visual disturbances. Visual disturbances were identified as mild and transient, and were predominately color-tinge to vision, but also increased sensitivity to light or blurred vision.

The incidence of retinal hemorrhage with Rigix 20 mg three times a day was 1.4% versus 0% placebo and for all Rigix doses studied was 1.9% versus 0% placebo. The incidence of eye hemorrhage at both 20 mg three times a day and at all doses studied was 1.4% for Rigix versus 1.4% for placebo. The patients experiencing these reactions had risk factors for hemorrhage including concurrent anticoagulant therapy.

In a placebo-controlled fixed dose titration study (Study 2) of Rigix (starting with recommended dose of 20 mg and increased to 40 mg and then 80 mg all three times a day) as an adjunct to intravenous epoprostenol in patients with PAH, the adverse reactions that were more frequent in the Rigix + epoprostenol group than in the epoprostenol group (greater than 6% difference) are shown in Table 2.

Table 2: Adverse Reactions (%) in patients with PAH in Study 2 (incidence in Rigix + Epoprostenol group at least 6% greater than Epoprostenol group)

Rigix Injection

Rigix injection was studied in a 66-patient, placebo-controlled study in patients with PAH at doses targeting plasma concentrations between 10 and 500 ng/mL (up to 8 times the exposure of the recommended dose). Adverse events with Rigix injection were similar to those seen with oral tablets.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Rigix (marketed for both PAH and erectile dysfunction). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular Events

In postmarketing experience with Rigix at doses indicated for erectile dysfunction, serious cardiovascular, cerebrovascular, and vascular events, including myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, pulmonary hemorrhage, and subarachnoid and intracerebral hemorrhages have been reported in temporal association with the use of the drug. Most, but not all, of these patients had preexisting cardiovascular risk factors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of Rigix without sexual activity. Others were reported to have occurred hours to days after use concurrent with sexual activity. It is not possible to determine whether these events are related directly to Rigix, to sexual activity, to the patient's underlying cardiovascular disease, or to a combination of these or other factors.

Nervous system

Seizure, seizure recurrence